Identification of circulating tumor cells captured by the FDA-cleared Parsortix® PC1 system from the peripheral blood of metastatic breast cancer patients using immunofluorescence and cytopathological evaluations.

Circulating Tumor Cells (CTCs) may serve as a non-invasive source of tumor material to investigate an individual's disease in real-time. The Parsortix® PC1 System, the first FDA-cleared medical device for the capture and harvest of CTCs from peripheral blood of metastatic breast cancer (MBC) patients for use in subsequent user-validated downstream analyses, enables the epitope-independent capture of CTCs with diverse phenotypes based on cell size and deformability. The aim of this study was to determine the proportion of MBC patients and self-declared female healthy volunteers (HVs) that had CTCs identified using immunofluorescence (IF) or Wright-Giemsa (WG) staining. Peripheral blood from 76 HVs and 76 MBC patients was processed on Parsortix® PC1 Systems. Harvested cells were cytospun onto a charged slide and immunofluorescently stained for identification of CTCs expressing epithelial markers. The IF slides were subsequently WG-stained and analyzed for CTC identification based on morphological features of malignant cells. All testing was performed by operators blinded to the clinical status of each subject. CTCs were identified on the IF slides in 45.3% (≥ 1) / 24.0% (≥ 5) of the MBC patients (range = 0 - 125, mean = 7) and in 6.9% (≥ 1) / 2.8% (≥ 5) of the HVs (range = 0 - 28, mean = 1). Among the MBC patients with ≥ 1 CTC, 70.6% had only CK + /EpCAM- CTCs, with none having EpCAM + /CK- CTCs. CTC clusters were identified in 56.0% of the CTC-positive patients. On the WG-stained slides, CTCs were identified in 42.9% (≥ 1) / 21.4% (≥ 5) of the MBC patients (range = 0 - 41, mean = 4) and 4.3% (≥ 1) / 2.9% (≥ 5) of the HVs (range = 0 - 14, mean = 0). This study demonstrated the ability of the Parsortix® PC1 System to capture and harvest CTCs from a significantly larger proportion of MBC patients compared to HVs when coupled with both IF and WG cytomorphological assessment. The presence of epithelial cells in subjects without diagnosed disease has been previously described, with their significance being unclear. Interestingly, a high proportion of the identified CTCs did not express EpCAM, highlighting the limitations of using EpCAM-based approaches.

Methylimidazolium ionic liquids - A new class of forever chemicals with endocrine disrupting potential.

A class of chemical with a potentially important perceived future contribution to the net zero carbon goal (as "green" solvents) is the methylimidazolium ionic liquids (MILs). These solvents are used in industrial processes such as biofuel production yet little is known about their environmental stability or toxicity in man although one MIL - 1-octyl-3-methylimidazolium (M8OI) - has been shown to activate the human estrogen receptor alpha (ERα). The stabilities of the chloride unsubstituted methylimidazolium (MI) and MILs possessing increasing alkyl chain lengths (2C, 1-ethyl-3-methylimidazolium (EMI); 4C, 1-butyl-3-methylimidazolium (BMI); 6C; 1-hexyl-3-methylimidazolium (HMI), 8C, M8OI; 10C, 1-decyl-3-methylimidazolium (DMI)) were examined in river water and a human liver model system. The MILs were also screened for their abilities to activate the human ERα in vitro and induce uterine growth in pre-pubertal rats in vivo. Short chain MILs (EMI, BMI and HMI) underwent negligible metabolism and mineralisation in river water; were not metabolised in a model of human liver metabolism; activated the human ERα in vitro and were estrogenic in vivo in rats. A structure-based computational approach predicted short chain MIL binding to both the estrogen binding site and an additional site on the human estrogen receptor alpha. Longer chain MILs (M8OI and DMI) were metabolised in river water and partially mineralised. Based on structure-activity considerations, some of these environmentally-derived metabolites may however, remain a hazard to the population. MILs therefore have the potential to become forever chemicals with adverse effects to both man, other animals and the environment in general.

Ionic Liquid 1-Octyl-3-Methylimidazolium (M8OI) Is Mono-Oxygenated by CYP3A4 and CYP3A5 in Adult Human Liver.

Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the alkyl chain in the human liver. The objective of this study was to examine the metabolism of M8OI in humans in more detail. In human hepatocytes, M8OI was mono-oxygenated to 1-(8-Hydroxyoctyl)-3-methyl-imidazolium (HO8IM) then further oxidised to 1-(7-carboxyheptyl)-3-methyl-1H-imidazol-3-ium (COOH7IM). The addition of ketoconazole-in contrast to a range of other cytochrome P450 inhibitors-blocked M8OI metabolism, suggesting primarily CYP3A-dependent mono-oxygenation of M8OI. Hepatocytes from one donor produced negligible and low levels of HO8IM and COOH7IM, respectively, on incubation with M8OI, when compared to hepatocytes from other donors. This donor had undetectable levels of CYP3A4 protein and low CYP3A enzyme activity. Transcript expression levels for other adult CYP3A isoforms-CYP3A5 and CYP3A43-suggest that a lack of CYP3A4 accounted primarily for this donor's low rate of M8OI oxidation. Insect cell (supersome) expression of various human CYPs identified CYP3A4 as the most active CYP mediating M8OI mono-oxygenation, followed by CYP3A5. HO8IM and COOH7IM were not toxic to human hepatocytes, in contrast to M8OI, and using a pooled preparation of human hepatocytes from five donors, ketoconazole potentiated M8OI toxicity. These data demonstrate that CYP3A initiates the mono-oxygenation and detoxification of M8OI in adult human livers and that CYP3A4 likely plays a major role in this process.

Estimating implicit and explicit racial and ethnic bias among community pharmacists in Canada.

Background: Bias, whether implicit (unconscious) or explicit (conscious), can lead to preferential treatment of specific social groups and antipathy towards others. When healthcare professionals (HCPs), including pharmacists, act on these biases, patient care and health outcomes can be adversely affected. This study aims to estimate implicit and explicit racial/ethnic bias towards Black and Arab people among community pharmacists in Ontario, Canada. Methods: Community pharmacists participated in a secure, web-based survey using a cross-sectional design that included Harvard's Race and Arab Implicit Association Tests (IATs) to examine bias towards Black and Arab people. Explicit (stated) preferences were measured by self-report. Data were analyzed using descriptive and inferential statistics. Results: The study surveyed 407 community pharmacists, 56.1 % of whom were women with an average age of 46.9. Implicit Association Test (IAT) results showed a statistically significant moderate preference for white people over both Black (mean IAT = 0.41) and Arab people (mean IAT = 0.35). However, most pharmacists explicitly stated that they had no racial/ethnic preference, with 75.7 % expressing a neutral preference between Black and white and 66.6 % neutral between Arab and white. However, a slight preference for white individuals was observed. Demographic factors such as age, place of birth, race/ethnicity, and experience significantly impacted IAT scores. For example, older, Canadian-born, white pharmacists with more experience displayed higher implicit bias scores. A mild correlation was found between implicit and explicit bias, indicating as implicit bias increases, explicit bias tends to become more negative. Conclusions: This study is the first to explore the issue of pharmacist bias in Canada and concentrate on anti-Arab bias. Our findings reveal that Ontario community pharmacists tend to have an unconscious inclination towards white people, which calls for further understanding of this matter. Additionally, we discovered a moderate degree of anti-Arab bias, indicating that studies on other HCPs should consider bias against this social group. Educational interventions are needed to address the implicit biases among community pharmacists in Ontario, Canada. These findings should aim to raise self-awareness of biases, educate about the potential implications of these biases on patient care, and provide strategies to reduce bias.

Contributions of listening effort and intelligibility to cortical tracking of speech in adverse listening conditions.

Cortical tracking of speech is vital for speech segmentation and is linked to speech intelligibility. However, there is no clear consensus as to whether reduced intelligibility leads to a decrease or an increase in cortical speech tracking, warranting further investigation of the factors influencing this relationship. One such factor is listening effort, defined as the cognitive resources necessary for speech comprehension, and reported to have a strong negative correlation with speech intelligibility. Yet, no studies have examined the relationship between speech intelligibility, listening effort, and cortical tracking of speech. The aim of the present study was thus to examine these factors in quiet and distinct adverse listening conditions. Forty-nine normal hearing adults listened to sentences produced casually, presented in quiet and two adverse listening conditions: cafeteria noise and reverberant speech. Electrophysiological responses were registered with electroencephalogram, and listening effort was estimated subjectively using self-reported scores and objectively using pupillometry. Results indicated varying impacts of adverse conditions on intelligibility, listening effort, and cortical tracking of speech, depending on the preservation of the speech temporal envelope. The more distorted envelope in the reverberant condition led to higher listening effort, as reflected in higher subjective scores, increased pupil diameter, and stronger cortical tracking of speech in the delta band. These findings suggest that using measures of listening effort in addition to those of intelligibility is useful for interpreting cortical tracking of speech results. Moreover, reading and phonological skills of participants were positively correlated with listening effort in the cafeteria condition, suggesting a special role of expert language skills in processing speech in this noisy condition. Implications for future research and theories linking atypical cortical tracking of speech and reading disorders are further discussed.

Temporal, spatial and space-time distribution of infections caused by five major enteric pathogens, Ontario, Canada, 2010-2017.

AIMS: In Canada, enteric diseases pose substantial health and economic burdens. The distribution of these diseases is uneven across both geography and time and understanding these patterns is therefore important for the prevention of future outbreaks. We evaluated temporal, spatial and space-time clustering of laboratory-confirmed cases of Campylobacter spp. (n = 28,728), non-typhoidal Salmonella spp. (n = 22,640), Shiga toxin-producing Escherichia coli (STEC; n = 1340), Yersinia spp. (n = 1674) and Listeria monocytogenes (n = 471) infections, reported between 2010 and 2017 inclusive in Ontario, the most populous province in Canada (population ~ 13,500,000 in 2016). METHODS AND RESULTS: For each enteric pathogen, we calculated the mean incidence rates (IRs) for Ontario's 35 public health unit (PHU) areas and visualized them using choropleth maps. We identified temporal, spatial and space-time high infection rate clusters using retrospective Poisson scan statistics. Campylobacter and Salmonella infections had the highest IRs, while Listeria infections had the lowest. Campylobacter, Salmonella, STEC and Listeria mostly clustered temporally in the spring/summer and sometimes extended into fall, while Yersinia showed a less clear seasonal pattern. The IR visualizations and spatial and space-time scan statistics showed geographic heterogeneity of infection rates with high infection rate clusters detected mainly in PHUs across the southwestern and central-western regions of Ontario for Campylobacter, Salmonella and STEC infections, and mainly in PHUs located in the central-eastern regions for Yersinia and Listeria. A high proportion of cases in some of the significant Salmonella, STEC and Listeria infection clusters were linked to disease outbreaks. CONCLUSIONS: Results from this study will inform heightened public health surveillance, and prevention and control programmes, in populations and regions of high infection rates. Further research is needed to determine the pathogen-specific socioeconomic, environmental and agricultural risk factors that may be related to the temporal and spatial disease patterns we observed in our study.

Predictors of non-adherence to cervical cancer screening among immigrant women in Ontario, Canada.

Cervical cancer is one of the most common types of cancer among women and is largely preventable with regular screening using Papanicolau (Pap) tests. In Canada, all provinces have regular screening programs, although with slightly differing recommendations. Previous research has found that immigrant women, who are a large proportion of the Canadian population, are at higher risk of being under-screened, or non-adherent to the recommended screening frequency. Using data from the 2017 Canadian Community Health Survey, this study examined: (1) the extent to which immigration status and time since immigration are associated with Pap test adherence in Ontario, and (2) predictors of Pap test adherence for immigrants and Canadian born populations in Ontario, Canada's most populous province, with a focus on the role of racial or ethnic identity among immigrants. Estimates of 3-year test adherence were 71.3 % (95 %CI: 66.9-75.7) among immigrant women and 75.4 % (95 %CI: 73.1-77.1) among non-immigrant women. Recent immigrants (6-10 years in Canada) had lower adherence (63.5 %, 95 %CI: 48.0-80.0). Logistic regression models found that immigrant women had lower adherence than Canadian-born women, controlling for age, household income, education, and having a primary care physician. Subgroup analysis found that South Asian immigrant women were least likely to be adherent. These results support targeted programming to increase screening adherence among recent immigrants and raise concerns regarding potential barriers to screening. Data that allow better disaggregation of racial and ethnic identities are important for better understanding the potential implications of these patterns for racial inequities in health.

The impact of speech type on listening effort and intelligibility for native and non-native listeners.

Listeners are routinely exposed to many different types of speech, including artificially-enhanced and synthetic speech, styles which deviate to a greater or lesser extent from naturally-spoken exemplars. While the impact of differing speech types on intelligibility is well-studied, it is less clear how such types affect cognitive processing demands, and in particular whether those speech forms with the greatest intelligibility in noise have a commensurately lower listening effort. The current study measured intelligibility, self-reported listening effort, and a pupillometry-based measure of cognitive load for four distinct types of speech: (i) plain i.e. natural unmodified speech; (ii) Lombard speech, a naturally-enhanced form which occurs when speaking in the presence of noise; (iii) artificially-enhanced speech which involves spectral shaping and dynamic range compression; and (iv) speech synthesized from text. In the first experiment a cohort of 26 native listeners responded to the four speech types in three levels of speech-shaped noise. In a second experiment, 31 non-native listeners underwent the same procedure at more favorable signal-to-noise ratios, chosen since second language listening in noise has a more detrimental effect on intelligibility than listening in a first language. For both native and non-native listeners, artificially-enhanced speech was the most intelligible and led to the lowest subjective effort ratings, while the reverse was true for synthetic speech. However, pupil data suggested that Lombard speech elicited the lowest processing demands overall. These outcomes indicate that the relationship between intelligibility and cognitive processing demands is not a simple inverse, but is mediated by speech type. The findings of the current study motivate the search for speech modification algorithms that are optimized for both intelligibility and listening effort.

Analytical performance of the FDA-cleared Parsortix® PC1 system.

Introduction: The Parsortix® PC1 system, Food and Drug Administration (FDA) cleared for use in metastatic breast cancer (MBC) patients, is an epitope-independent microfluidic device for the capture and harvest of circulating tumor cells from whole blood based on cell size and deformability. This report details the analytical characterization of linearity, detection limit, precision, and reproducibility for this device. Methods: System performance was determined using K2-EDTA blood samples collected from self-declared healthy female volunteers (HVs) and MBC patients spiked with prelabeled cultured breast cancer cell lines (SKBR3, MCF7, or Hs578T). Samples were processed on Parsortix® PC1 systems and captured cells were harvested and enumerated. Results: The system captured and harvested live SKBR3, MCF7, and Hs578T cells and fixed SKBR3 cells linearly between 2 and ~100 cells, with average harvest rates of 69%, 73%, 79%, and 90%, respectively. To harvest ≥1 cell ≥95% of the time, the system required 3, 5 or 4 live SKBR3, MCF7 or Hs578T cells, respectively. Average harvest rates from precision studies using 5, 10, and ~50 live cells spiked into blood for each cell line ranged from 63.5% to 76.2%, with repeatability and reproducibility percent coefficient of variation (%CV) estimates ranging from 12.3% to 32.4% and 13.3% to 34.1%, respectively. Average harvest rates using ~20 fixed SKBR3 cells spiked into HV and MBC patient blood samples were 75.0% ± 16.1% (%CV = 22.3%) and 68.4% ± 14.3% (%CV = 21.1%), respectively. Conclusions: These evaluations demonstrate the Parsortix® PC1 system linearly and reproducibly harvests tumor cells from blood over a range of 1 to ~100 cells.

Speaking in the presence of noise: Consistency of acoustic properties in clear-Lombard speech over time.

Individual speakers are often able to modify their speech to facilitate communication in challenging conditions, such as speaking in a noisy environment. Such vocal "enrichments" might include reductions in speech rate or increases in acoustic contrasts. However, it is unclear how consistently speakers enrich their speech over time. This study examined inter-speaker variability in the speech enrichment modifications applied by speakers. The study compared a baseline habitual speaking style to a clear-Lombard style and measured changes in acoustic differences between the two styles over sentence trials. Seventy-eight young adult participants read out sentences in the habitual and clear-Lombard speaking styles. Acoustic differences between speaking styles generally increased nonlinearly over trials, suggesting that speakers require practice before realizing their full speech enrichment potential when speaking clearly in noise with reduced auditory feedback. Using a recent objective intelligibility metric based on glimpses, the study also found that predicted intelligibility increased over trials, highlighting that communicative benefits of the clear-Lombard style are not static. These findings underline the dynamic nature of speaking styles.

Bioavailability of potentially toxic elements influences antibiotic resistance gene and mobile genetic element abundances in urban and rural soils.

Antibiotic resistance genes (ARGs) that can encode resistance traits in bacteria are found across the environment. While it is often difficult to discern their origin, their prevalence and diversity depends on many factors, one of which is their exposure to potentially toxic elements (PTE, i.e., metals and metalloids) in soils. Here, we investigated how ambient ARGs and mobile genetic elements (MGEs) relate to the relative bioavailability of different PTEs (total versus exchangeable and carbonate-bound PTE) in rural and urban soils in northeast England. The average relative abundances of ARGs in rural sites varied over a 3-log range (7.24 × 10-7 to 1.0 × 10-4 genes/16S rRNA), and relative ARG abundances in urban sites varied by four orders of magnitude (1.75 × 10-6 to 2.85 × 10-2 genes/16S rRNA). While beta-lactam and aminoglycoside resistance genes dominated rural and urban sites, respectively, non-specific ARGs, also called multidrug-resistance genes, were significantly more abundant in urban sites (p < 0.05). Urban sites also had higher concentrations of total and exchangeable forms of PTE than rural sites, whereas rural sites were higher in carbonate-bound forms. Significant positive Spearman correlations between PTEs, ARGs and MGEs were apparent, especially with bioavailable PTE fractions and at urban sites. This study found significant positive correlations between ARGs and beryllium (Be), which has not previously been reported. Overall, our results show that PTE bioavailability is important in explaining the relative selection of ARGs in soil settings and must be considered in future co-selection and ARG exposure studies.

Stepping up to the Canadian opioid crisis: a longitudinal analysis of the correlation between socioeconomic status and population rates of opioid-related mortality, hospitalization and emergency department visits (2000-2017). / Remédier à la crise des opioïdes au Canada : une analyse longitudinale de la corrélation entre le statut socioéconomique et les taux de décès, d'hospitalisations et de visites à l'urgence liés aux opioïdes dans la population (2000-2017).

INTRODUCTION: High levels of income inequality and increased opioid-related harm across Canada bring into question the role of socioeconomic status (SES) in the opioid epidemic. Only a few studies have examined this association, and most of those have analyzed this issue on a provincial level. This study examined the association between opioid-related health outcomes and SES, and investigated rate ratios over time. METHODS: Administrative databases were used to identify opioid-related mortality, hospitalization and emergency department visits between 2000 and 2017. Patient's postal code was linked to the quintile of median household income at the forward sortation area level. Crude rates and age- and sex-adjusted rates in each quintile were calculated, as well as the adjusted rate ratio of average annual rates between the lowest and highest quintiles. The significance of the time trend of rate ratios for all outcomes was examined using linear regression. RESULTS: A stepped gradient of opioid-related outcomes across all income quintiles emerged from these data. For mortality, hospitalization and emergency department visits, the average annual rate ratio between lowest quintile and highest quintile was 3.8, 4.3 and 4.9, respectively. These ratios were generally stable and consistent over the study period, albeit the opioid-related mortality SES gap decreased gradually (p < 0.01). CONCLUSION: Area income quintile was found to be highly associated with opioid outcomes. Psychosocial factors (stress, unemployment, housing insecurity) that are typically concentrated in low SES areas may play a significant role in the opioid epidemic. Health policies should address these factors in order to provide effective solutions.

The time course of adaptation to distorted speech.

When confronted with unfamiliar or novel forms of speech, listeners' word recognition performance is known to improve with exposure, but data are lacking on the fine-grained time course of adaptation. The current study aims to fill this gap by investigating the time course of adaptation to several different types of distorted speech. Keyword scores as a function of sentence position in a block of 30 sentences were measured in response to eight forms of distorted speech. Listeners recognised twice as many words in the final sentence compared to the initial sentence with around half of the gain appearing in the first three sentences, followed by gradual gains over the rest of the block. Rapid adaptation was apparent for most of the eight distortion types tested with differences mainly in the gradual phase. Adaptation to sine-wave speech improved if listeners had heard other types of distortion prior to exposure, but no similar facilitation occurred for the other types of distortion. Rapid adaptation is unlikely to be due to procedural learning since listeners had been familiarised with the task and sentence format through exposure to undistorted speech. The mechanisms that underlie rapid adaptation are currently unclear.

Incidence, Demographic, and Seasonal Risk Factors of Infections Caused by Five Major Enteric Pathogens, Ontario, Canada, 2010-2017.

In Canada, enteric infections cause significant health and economic burden. We evaluated the individual characteristics of laboratory-confirmed cases of Campylobacter spp. (n = 28,728), non-typhoidal Salmonella spp. (n = 22,640), Yersinia spp. (n = 1674), Verotoxin-producing Escherichia coli (VTEC; n = 1340), and Listeria monocytogenes (n = 471), reported between 2010 and 2017 inclusive, in Ontario, Canada (population ∼13,500,000). We calculated overall and pathogen-specific annual and mean incidence rates (IRs) for Ontario. We used multivariable Poisson and negative binomial regression models to estimate incidence rate ratios (IRRs) for years, seasons, age groups, and sexes, and we included two-way age and sex interaction terms in the models. Campylobacter and Salmonella infections had the highest IRs whereas Listeria infections had the lowest IRs. None of the infections showed long-term trends over the 8-year study period; however, rates of all five infections were elevated in the summer. More Salmonella, VTEC, and Listeria infections were linked to disease outbreaks than were Campylobacter and Yersinia infections. Overall, mean IRs of Campylobacter, Salmonella, Yersinia, and VTEC infections were highest in children 0-4 years old, whereas Listeria IRs peaked in adults 60 years and older. Higher mean IRs of Campylobacter were observed in males. No other differences by sex were statistically significant. The same mean rate was observed in both sexes for Listeria. Adjusting for all other factors, significant age- and sex-specific differences in IRs were observed in Campylobacter, Salmonella, and VTEC infection rates. No significant interactions of age and sex were found for Yersinia and Listeria infections. Future research should focus on the pathogen-specific socioeconomic, environmental, or agricultural risk factors that might be responsible for these infections.

How reliable are online speech intelligibility studies with known listener cohorts?

Although the use of nontraditional settings for speech perception experiments is growing, there have been few controlled comparisons of online and laboratory modalities in the context of speech intelligibility. The current study compares outcomes from three web-based replications of recent laboratory studies involving distorted, masked, filtered, and enhanced speech, amounting to 40 separate conditions. Rather than relying on unrestricted crowdsourcing, this study made use of participants from the population that would normally volunteer to take part physically in laboratory experiments. In sentence transcription tasks, the web cohort produced intelligibility scores 3-6 percentage points lower than their laboratory counterparts, and test modality interacted with experimental condition. These disparities and interactions largely disappeared after the exclusion of those web listeners who self-reported the use of low quality headphones, and the remaining listener cohort was also able to replicate key outcomes of each of the three laboratory studies. The laboratory and web modalities produced similar measures of experimental efficiency based on listener variability, response errors, and outlier counts. These findings suggest that the combination of known listener cohorts and moderate headphone quality provides a feasible alternative to traditional laboratory intelligibility studies.

National trends in population rates of opioid-related mortality, hospitalization and emergency department visits in Canada between 2000 and 2017. A population-based study.

BACKGROUND AND AIMS: Existing assessments of the time-trends of opioid-related mortality, hospitalization and emergency department visits in Canada have relied mainly on provincial databases, while national assessments generally do not provide information before 2016. We aimed to estimate Canadian national time trends in opioid-related mortality from 2000 to 2017 and opioid-related hospitalization and emergency department visits between 2000 and 2012. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents of all Canadian provinces and territories for which comparable data were available from 2000 to 2017. MEASUREMENTS: We identified opioid-related mortality, hospitalization and emergency department visits using validated algorithms using ICD codes from administrative databases. We calculated crude rates and sex- and age-adjusted rates per million. For hospitalizations, we calculated case-fatality, 90-day and 365-day all-cause mortality and opioid-related re-hospitalization rates. We used Poisson regression to examine the significance of the time trend. FINDINGS: From 2000 to 2017, the adjusted opioid mortality rate in Canada (outside Quebec) increased significantly by 592.9% (from 20.0 opioid deaths per million in 2000 to 118.3 in 2017). The highest year-to-year increases were from 2015 to 2016 (31.8%) and from 2016 to 2017 (52.2%). The adjusted hospitalizations doubled significantly during the study period (an increase of 103.7%, from 159.7 opioid hospitalizations per million Canadians in 2000 to 325.3 in 2012). The adjusted rate of emergency department visits increased significantly by 188.7% (from 280.6 per million in 2000 to 810.1 in 2012). Case-fatality was 2.3% overall and was mainly constant during the study period. Both 90- and 365-day all-cause mortality increased significantly between 2000 and 2011 (from 1.7 to 3.1% and 3.9 to 7.4%, respectively), while re-hospitalization for opioid-related diagnoses was reduced (from 7.8 to 6.4% and 14.2 to 12.9%, respectively). CONCLUSIONS: Opioid-related mortality, hospitalization and emergency department visits in Canada have been increasing gradually since 2000.

Area-Level Clustering of Shiga Toxin-Producing Escherichia coli Infections and Their Socioeconomic and Demographic Factors in Ontario, Canada: An Ecological Study.

Shiga toxin-producing Escherichia coli (STEC) infections are an important health burden for human populations in Ontario and worldwide. We assessed 452 STEC cases that were reported to Ontario's reportable disease surveillance system between 2015 and 2017. A retrospective scan statistic using a Poisson model was used to detect high-rate STEC clusters at the forward sortation area (FSA; the first three digits of a postal code) level. A significant spatial cluster in the southwest region of Ontario was identified. A case-case logistic regression analysis was applied to compare FSA-level socioeconomic and demographic characteristics among STEC cases included inside the spatial cluster with cases outside of the cluster. Cases included in the spatial cluster had higher odds of living in FSAs with a low median family income, low proportion of lone-parent families, and low proportion of the visible minority population. In addition, STEC cases inside the cluster had higher odds of coming from rural FSAs. Our study demonstrated that STEC cases were spatially clustered in Ontario and their clustering was associated with FSA-level socioeconomic and demographic determinants of cases.

Quantifying the contribution of modifiable risk factors to socio-economic inequities in cancer morbidity and mortality: a nationally representative population-based cohort study.

BACKGROUND: Compared with those with a higher socio-economic position (SEP), individuals with a lower SEP have higher cancer morbidity and mortality. However, the contribution of modifiable risk factors to these inequities is not known. This study aimed to quantify the mediating effects of modifiable risk factors to associations between SEP and cancer morbidity and mortality. METHODS: This study used a prospective observational cohort design. We combined eight cycles of the Canadian Community Health Survey (2000/2001-2011) as baseline data to identify a cohort of adults (≥35 years) without cancer at the time of survey administration (n = 309 800). The cohort was linked to the Discharge Abstract Database and the Canadian Mortality Database for cancer morbidity and mortality ascertainment. Individuals were followed from the date they completed the Canadian Community Health Survey until 31 March 2013. Dates of individual first hospitalizations for cancer and deaths due to cancer were captured during this time period. SEP was operationalized using a latent variable combining measures of education and household income. Self-reported modifiable risk factors, including smoking, excess alcohol consumption, low fruit-and-vegetable intake, physical inactivity and obesity, were considered as potential mediators. Generalized structural equation modelling was used to estimate the mediating effects of modifiable risk factors in associations between low SEP and cancer morbidity and mortality in the total population and stratified by sex. RESULTS: Modifiable risk factors together explained 45.6% of associations between low SEP and overall cancer morbidity and mortality. Smoking was the most important mediator in the total population and for males, accounting for 15.5% and 40.2% of the total effect, respectively. For females, obesity was the most important mediator. CONCLUSIONS: Modifiable risk factors are important mediators of socio-economic inequities in cancer morbidity and mortality. Nevertheless, more than half of the variance in these associations remained unexplained. Midstream interventions that target modifiable risk factors may help to alleviate inequities in cancer risk in the short term. However, ultimately, upstream interventions that target structural determinants of health are needed to reduce overall socio-economic inequities in cancer morbidity and mortality.

Adolescent Gender Identity, Sexual Orientation, and Cannabis Use: Potential Mediations by Internalizing Disorder Risk.

BACKGROUND/AIMS: Adolescents who identify as nonbinary gender or as not heterosexual report higher levels of mental illness than their counterparts. Cannabis use is a commonly employed strategy to cope with mental illness symptoms among adolescents; however, cannabis use can have many deleterious health consequences for youth. Within the frame of minority stress theory, this study investigates the relationships between gender identity and sexual orientation, internalizing disorder symptoms, and cannabis use among adolescents. METHOD: A national cross-sectional survey of a generalizable sample of high school students in Canada from the 2017 wave (N = 15,191) of the Cancer Risk Assessment in Youth Survey was analyzed in spring 2019. Mediation analyses were completed to examine risk of internalizing disorder symptoms as a potential mediator of the association between (1) gender identity and (2) sexual orientation, and cannabis use. RESULTS: Indirect effects in all models show significantly higher levels of reported internalizing disorder symptoms for female (OR = 3.44, 95% CI [2.84, 4.18]) and nonbinary gender (OR = 3.75, 95% CI [2.16, 6.51]) compared with male students. Sexual minority adolescents had higher odds of internalizing disorder risk relative to non-sexual minority adolescents (OR = 3.13, 95% CI [2.63, 3.74]). Students who reported higher rates of internalizing disorder symptoms were more likely to have ever used cannabis. Patterns of partial mediation are also present among all groups. DISCUSSION/CONCLUSIONS: Findings can be used to better inform mental health interventions for adolescents. Future study should explore specific mental health stressors of vulnerable adolescent groups with respect to cannabis use as a coping mechanism.