Increased difficulty accessing food and income change during the COVID-19 pandemic among youth living in the eThekwini district, South Africa.

OBJECTIVE: To estimate the effect of income change on difficulty accessing food since the COVID-19 pandemic for South African youth and evaluate whether this effect was modified by receiving social grants. DESIGN: A cross-sectional, online survey was conducted between December 2021 and May 2022. Primary outcome was increased difficulty accessing food since the COVID-19 pandemic. Income change was categorised as 'Decreased a lot', 'Decreased slightly' and 'Unchanged or increased'. Multivariable logistic regressions were used, with an interaction term between social grant receipt and income change. SETTING: eThekwini district, South Africa. PARTICIPANTS: Youth aged 16-24 years. RESULTS: Among 1,620 participants, median age was 22 years (IQR 19-24); 861 (53 %) were women; 476 (29 %) reported increased difficulty accessing food; 297 (18 %) reported that income decreased a lot, of whom 149 (50 %) did not receive social grants. Experiencing a large income decrease was highly associated with increased difficulty accessing food during the COVID-19 pandemic (adjusted OR [aOR] 3·63, 95 % CI 2·70, 4·88). The aOR for the effect of a large income decrease on difficulty accessing food, compared to no income change, were 1·49 (95 % CI 0·98, 2·28) among participants receiving social grants, and 6·63 (95 % CI 4·39, 9·99) among participants not receiving social grants. CONCLUSIONS: While social grant support made a great difference in lowering the effect of income decrease on difficulty accessing food, it was insufficient to fully protect youth from those difficulties. In post-pandemic recovery efforts, there is a critical need to support youth through economic empowerment programming and food schemes.

Experiential Aspects of Participation in Employment and Mobility for Adults With Physical Disabilities: Testing Cross-Sectional Models of Contextual Influences and Well-Being Outcomes.

OBJECTIVE: To use structural equation modeling to test research- and theory-informed models of potential predictors and outcomes of subjective experiences of employment and mobility participation in a national sample of people with physical disabilities. DESIGN: Cross-sectional survey. SETTING: Canada. PARTICIPANTS: English or French-speaking adults with a physical impairment affecting mobility and restricting activities or participation, and who participated in employment (n=457) or mobility (n=711) life domains. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Participants completed standardized measures of perceived health, and employment-specific and/or mobility-specific measures of perceived abilities, social support, accessibility and policies (predictor variables); the Measure of Experiential Aspects of Participation (MeEAP) in employment and/or mobility; and standardized measures of emotional well-being, social well-being and life satisfaction (outcome variables). RESULTS: Analyses using structural equation modeling showed that in both employment and mobility domains, perceived health, abilities, social support, and accessibility were positively related to experiential aspects of participation. Participation experiences were positively related to social well-being, emotional well-being, and life satisfaction. CONCLUSIONS: Results support and extend current theorizing on participation experiences among adults with physical disabilities. Intrapersonal and environmental factors may play a role in optimizing participation experiences in employment and mobility which, in turn, may lead to better well-being and life satisfaction. These results emphasize the importance of conceptualizing participation from an experiential perspective and provide a basis for advancing theory and practice to understand and improve the participation experiences and well-being of adults living with physical disabilities.

Examining gender and sexual orientation differences in physical intimate partner violence experienced and perpetrated by youth living in eThekwini district South Africa during the COVID-19 pandemic.

BACKGROUND: Young women and Lesbian, Gay, Bisexual, Trans, Non-binary/no gender, or Questioning (LGBTQ+) youth in South Africa face some of the highest global levels of intimate partner violence (IPV). Given limited evidence in the wake of the COVID-19 pandemic, which has fuelled IPV globally, we aimed to describe and compare experiences and perpetration of IPV of youth aged 16-24 by sexual orientation and gender identity (SOGI). METHODS: During the study period (December 2021-May 2022), youth aged 16-24 from eThekwini district, South Africa completed an online survey to understand multilevel impacts of the pandemic on youth. Participants were asked about experiences and perpetration of physical IPV since the start of the COVID-19 pandemic (March 2020). Descriptive statistics and adjusted logistic regressions compared the likelihood of experiencing and/or perpetrating physical IPV between cisgender and transgender inclusive heterosexual men; heterosexual women; gay, bisexual, or questioning men [GBQM]; lesbian, gay, bisexual, or questioning women [LGBQW]; or gender/sexual non-conforming youth [non-conforming]. RESULTS: Of 1,588 youth (mean age = 21.7 [SD = 2.3]; 71.7% Black) with non-missing SOGI and physical IPV data, 238 (15.0%) were LGBTQ+ (40.3% LGBQW and 36.1% non-conforming). Overall, 14.6% of respondents experienced physical IPV and 9.8% perpetrated physical IPV since the start of the pandemic, which differed by SOGI (12.3% of heterosexual men, 13.9% of heterosexual women, 22.0% of GBQM, 18.2% of LGBQW, and 25.0% of non-conforming youth experienced and 10.3% of heterosexual men; 7.7% of heterosexual women; 10.0% of GBQM; 18.2% of LGBQW; and 16.7% of non-conforming youth perpetrated). In adjusted models, compared to heterosexual women, non-conforming youth had increased odds of experiencing (adjusted odds ratio [aOR] = 2.36; 95%CI, 1.26-4.39) physical IPV and compared to heterosexual men, non-conforming youth had greater odds of perpetrating physical IPV (aOR = 2.19; 95%CI, 1.07-4.48) during the pandemic. CONCLUSION: Over one in six youth in our study experienced and one in ten perpetrated physical IPV since the onset of the COVID-19 pandemic, with gender and sexual non-conforming youth experiencing and perpetrating IPV at significantly greater rates than cisgender/heterosexual peers. Our findings highlight the need for gender transformative efforts that move beyond the gender binary to support healthy relationships and IPV prevention for LGBTQ + youth in South Africa and globally.

Economic hardship and perpetration of intimate partner violence by young men in South Africa during the COVID-19 pandemic (2021-2022): a cross-sectional study.

BACKGROUND: Economic hardship is a potential trigger for intimate partner violence (IPV) perpetration. While higher IPV rates have been reported in low-income regions, few African studies have focused on IPV being triggered by economic hardship among young men during the COVID-19 pandemic. We therefore estimated economic hardship's effect on IPV perpetration by young men in eThekwini District, South Africa, during the COVID-19 pandemic. METHODS: A cross-sectional survey of COVID-19 pandemic experiences was conducted among youth aged 16-24 years through an anonymous self-administered questionnaire, including questions about economic hardship (increased difficulty accessing food or decreased income) and IPV perpetration. A prespecified statistical analysis plan with a directed acyclic graph of assumed exposure, outcome, and confounder relationships guided our analyses. We measured association of economic hardship and IPV perpetration through odds ratios (ORs) computed from a multivariable logistic regressions adjusted for measured confounders. Secondary outcomes of physical and sexual IPV perpetration were analyzed separately using the same specifications. Propensity score matching weights (PS-MW) were used in sensitivity analyses. Analysis code repository: https://github.com/CAndrewBasham/Economic_Hardship_IPV_perpetration/ RESULTS: Among 592 participants, 12.5% reported perpetrating IPV, 67.6% of whom reported economic hardship, compared with 45.6% of those not reporting IPV perpetration (crude OR = 2.49). Median age was 22 years (interquartile range 20-24). Most (80%) were in a relationship and living together. Three quarters identified as Black, 92.1% were heterosexual, and half had monthly household income < R1600. We estimated an effect of economic hardship on the odds of perpetrating IPV as OR = 1.83 (CI 0.98-3.47) for IPV perpetration overall, OR = 6.99 (CI 1.85-36.59) for sexual IPV perpetration, and OR = 1.34 (CI 0.69-2.63) for physical IPV perpetration. PS-MW-weighted ORs for IPV perpetration by economic hardship were 1.57 (overall), 4.45 (sexual), and 1.26 (physical). CONCLUSION: We estimated 83% higher odds of self-reported IPV perpetration by self-reported economic hardship among young South African men during the COVID-19 pandemic. The odds of sexual IPV perpetration were The seven-times higher by economic hardship, although with limited precision. Among young men in South Africa, economic hardship during COVID-19 was associated with IPV perpetration by men. Our findings warrant culturally relevant and youth-oriented interventions among young men to reduce the likelihood of IPV perpetration should they experience economic hardship. Further research into possible causal mechanisms between economic hardship and IPV perpetration could inform public health measures in future pandemic emergencies.

Multimorbidity prevalence and chronic disease patterns among tuberculosis survivors in a high-income setting.

OBJECTIVES: Multimorbidity is the presence of two or more chronic health conditions. Tuberculosis (TB) survivors are known to have higher prevalence of multimorbidity, although prevalence estimates from high-income low-TB incidence jurisdictions are not available and potential differences in the patterns of chronic disease among TB survivors with multimorbidity are poorly understood. In this study, we aimed to (1) compare the prevalence of multimorbidity among TB survivors with matched non-TB controls in a high-income setting; (2) assess the robustness of aim 1 analyses to different modelling strategies, unmeasured confounding, and misclassification bias; and (3) among people with multimorbidity, elucidate chronic disease patterns specific to TB survivors. METHODS: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015, using health administrative data. Participants were divided into two groups: people diagnosed with TB (TB survivors) and people not diagnosed with TB (non-TB controls) in British Columbia. Coarsened exact matching (CEM) balanced demographic, immigration, and socioeconomic covariates between TB survivors and matched non-TB controls. Our primary outcome was multimorbidity, defined as ≥2 chronic diseases from the Elixhauser comorbidity index. RESULTS: In the CEM-matched sample (n=1962 TB survivors; n=1962 non-TB controls), we estimated that 21.2% of TB survivors (n=416), compared with 12% of non-TB controls (n=236), had multimorbidity. In our primary analysis, we found a double-adjusted prevalence ratio of 1.74 (95% CI: 1.49-2.05) between TB survivors and matched non-TB controls for multimorbidity. Among people with multimorbidity, differences were observed in chronic disease frequencies between TB survivors and matched controls. CONCLUSION: TB survivors had a 74% higher prevalence of multimorbidity compared with CEM-matched non-TB controls. TB-specific multimorbidity patterns were observed through differences in chronic disease frequencies between the matched samples. These findings suggest a need for TB-specific multimorbidity interventions in high-income settings such as Canada. We suggest TB survivorship as a framework for developing person-centred interventions for multimorbidity among TB survivors.

RéSUMé: OBJECTIFS: La multimorbidité est la présence de deux affections chroniques ou plus. On sait que la prévalence de la multimorbidité est plus élevée chez les survivants de la tuberculose, mais il n'y a pas d'estimations de prévalence disponibles dans les entités administratives à revenu élevé et à faible incidence de tuberculose, et les différences potentielles dans les structures de la morbidité chronique chez les survivants de la tuberculose atteints de multimorbidité sont mal comprises. Dans cette étude, nous avons voulu 1) comparer la prévalence de la multimorbidité chez des survivants de la tuberculose appariés à des témoins sans tuberculose dans un milieu à revenu élevé; 2) évaluer la robustesse des analyses du 1er objectif par rapport à différentes stratégies de modélisation, à la confusion non mesurée et au biais d'erreur de classification; et 3) élucider, chez les personnes atteintes de multimorbidité, les structures de la morbidité chronique propres aux survivants de la tuberculose. MéTHODE: Nous avons mené à l'aide de données administratives sur la santé une étude de cohorte populationnelle des personnes ayant immigré en Colombie-Britannique (Canada) entre 1985 et 2015. Les participants ont été divisés en deux groupes : les personnes ayant un diagnostic de tuberculose (« survivants de la tuberculose ¼) et les personnes n'ayant pas de diagnostic de tuberculose (« témoins sans tuberculose ¼) en Colombie-Britannique. Un appariement exact avec groupement (coarsened exact matching [CEM]) a permis d'équilibrer les covariables démographiques, socioéconomiques et d'immigration entre les survivants de la tuberculose et les témoins sans tuberculose appariés. Notre principal résultat a été la multimorbidité, définie comme étant la présence de ≥ 2 affections chroniques selon l'indice de comorbidité d'Elixhauser. RéSULTATS: Dans l'échantillon CEM (n = 1 962 survivants de la tuberculose; n = 1 962 témoins sans tuberculose), nous avons estimé que 21,2 % des survivants de la tuberculose (n = 416), contre 12 % des témoins sans tuberculose (n = 236), étaient atteints de multimorbidité. Dans notre analyse primaire, nous avons obtenu un ratio de prévalence doublement ajusté de 1,74 (IC de 95 % : 1,49-2,05) entre les survivants de la tuberculose et les témoins sans tuberculose appariés pour ce qui est de la multimorbidité. Chez les personnes atteintes de multimorbidité, des différences ont été observées dans la fréquence des maladies chroniques entre les survivants de la tuberculose et les témoins appariés. CONCLUSION: Les survivants de la tuberculose avaient une prévalence de multimorbidité supérieure de 74 % à celle des témoins sans tuberculose appariés selon la méthode CEM. Les structures de multimorbidité propres à la tuberculose ont été observées selon les différences dans la fréquence des maladies chroniques entre les échantillons appariés. Ces constatations indiquent qu'il faudrait mener des interventions sur la multimorbidité propres à la tuberculose dans des milieux à revenu élevé comme le Canada. Nous suggérons d'utiliser la survie à la tuberculose comme cadre d'élaboration d'interventions centrées sur la personne pour lutter contre la multimorbidité chez les survivants de la tuberculose.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

BACKGROUND: Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. METHODS: We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. FINDINGS: From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. INTERPRETATION: No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. TRIAL REGISTRATION: Registration: PROSPERO (CRD42022309818).

An E-value analysis of potential unmeasured or residual confounding in systematic reviews of post-tuberculosis mortality, respiratory disease, and cardiovascular disease.

INTRODUCTION: Unmeasured confounding poses a serious threat to observational studies of post-TB health outcomes. E-values have been recently proposed as a method to assess the magnitude of unmeasured confounding necessary to nullify, or to render non-significant, relative effect estimates from observational studies. METHODS: We calculated E-values for both the risk ratio (RR) point estimates and their lower 95% confidence limits (LCL) from studies of post-TB mortality, respiratory disease, and cardiovascular disease (CVD) included in published systematic reviews within and across post-TB outcome domains. We also employed a meta-analytic E-value approach to estimate the proportion of unconfounded study RRs greater than 1.1 at different levels of unmeasured confounding. RESULTS: Across post-TB health outcome domains, we observed a median E-value of 5.59 (IQR = 3.19-7.35) for RRs, and 2.95 (IQR = 1.71-4.61) for LCLs. Post-TB mortality studies had higher median E-values (E-valueRR = 6.90 and E-valueLCL = 4.54) than studies of respiratory disease (E-valueRR = 5.59, E-valueLCL = 2.94) or CVD (E-valueRR = 3.90, E-valueLCL = 1.81). The E-value at which the estimated proportion of studies with unconfounded RRs greater than 1.1 would remain over 0.7 was 3.45 for post-TB mortality, 3.96 for post-TB respiratory disease, and 1.71 for post-TB CVD meta-analyses. CONCLUSIONS: Unmeasured confounding with an association of 2.95 or greater with both the exposure (TB) and outcome, on the risk ratio scale, could render most post-TB health studies' findings statistically non-significant. Post-TB mortality and respiratory disease studies had higher E-values than TB-CVD studies, indicating that either (a) TB-CVD studies may be more susceptible to unmeasured confounding bias, or (b) the true effect of TB on CVD is lower.

Post-tuberculosis airway disease: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015.

BACKGROUND: Current epidemiological evidence of post-TB airway disease is largely cross-sectional and derived from high-TB-incidence settings. We present the first cohort study of post-TB airway disease in a low-TB-incidence setting. AIMS: (1) analyze the risk of airway disease by respiratory TB, (2) assess potential unmeasured confounding between TB and airway disease, and (3) investigate TB effect measure modification. METHODS: A population-based cohort study using healthcare claims data for immigrants to British Columbia (BC), Canada, 1985-2015. Airway disease included chronic airway obstruction, asthma, bronchitis, bronchiolitis, and emphysema. Respiratory TB was defined from TB registry data. Cox proportional hazards (PH) regressions were used to analyze time-to-airway disease by respiratory TB. Sensitivity analyses included varying definitions of TB and airway disease. Potential unmeasured confounding by smoking was evaluated by E-value and hybrid least absolute shrinkage and selection operator (LASSO)-high-dimensional propensity score (hdPS). FINDINGS: In our cohort (N = 1 005 328; nTB=1141) there were 116 840 incident cases of airway disease during our 30-year study period (10.43 per 1,000 person-years of follow-up), with cumulative incidence of 42·5% among respiratory TB patients compared with 11·6% among non-TB controls. The covariate-adjusted hazard ratio (aHR) for airway disease by respiratory TB was 2·08 (95% CI: 1·91-2·28) with E-value=3·58. The LASSO-hdPS analysis produced aHR=2·26 (95% CI: 2·07-2·47). INTERPRETATION: A twofold higher risk of airway disease was observed among immigrants diagnosed with respiratory TB, compared with non-TB controls, in a low-TB-incidence setting. Unmeasured confounding is unlikely to explain this relationship. Models of post-TB care are needed. FUNDING: Canadian Institutes of Health Research.

Tuberculosis-associated depression: a population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015.

PURPOSE: To estimate the risk of tuberculosis (TB)-associated depression. A second aim was to estimate the extent to which any increased risk of depression among TB patients may be mediated by the length of hospital length stay (LOS) METHODS: Retrospective cohort study of linked healthcare claims and public health surveillance data. Our primary outcome, time-to-depression, was analyzed using Cox proportional hazards (PH) regressions. Causal mediation analysis was used to estimate the natural direct and indirect effect of TB mediated by hospital LOS. RESULTS: Among 755,836 participants (52.2% female, median age=35 years, median follow-up=8.75 years), 2295 were diagnosed with TB (exposure), and 128,963 were diagnosed with depression (outcome). We observed a covariate-adjusted hazard ratio (aHR) of 1.24 (95% CI, 1.14-1.34) for depression by TB. The total effect of TB on depression was decomposed into a natural direct effect of TB of aHR=1.11 (95% CI, 1.02-1.21) and an indirect effect through hospital LOS of aHR=1.11 (95% CI, 1.10-1.12), indicating that TB's total effect was mediated by 50% (95% CI, 35-82%) through hospital LOS. CONCLUSIONS: TB patients had a 24% higher risk of developing depression. TB's effect was mediated substantially by hospital LOS, requiring further study. Depression screening among TB patients is warranted.

Post-tuberculosis mortality risk among immigrants to British Columbia, Canada, 1985-2015: a time-dependent Cox regression analysis of linked immigration, public health, and vital statistics data.

OBJECTIVE: To compare non-tuberculosis (non-TB)-cause mortality risk overall and cause-specific mortality risks within the immigrant population of British Columbia (BC) with and without TB diagnosis through time-dependent Cox regressions. METHODS: All people immigrating to BC during 1985-2015 (N = 1,030,873) were included with n = 2435 TB patients, and the remaining as non-TB controls. Outcomes were time-to-mortality for all non-TB causes, respiratory diseases, cardiovascular diseases, cancers, and injuries/poisonings, and were ascertained using ICD-coded vital statistics data. Cox regressions were used, with a time-varying exposure variable for TB diagnosis. RESULTS: The non-TB-cause mortality hazard ratio (HR) was 4.01 (95% CI 3.57-4.51) with covariate-adjusted HR of 1.69 (95% CI 1.50-1.91). Cause-specific covariate-adjusted mortality risk was elevated for respiratory diseases (aHR = 2.96; 95% CI 2.18-4.00), cardiovascular diseases (aHR = 1.63; 95% CI 1.32-2.02), cancers (aHR = 1.40; 95% CI 1.13-1.75), and injuries/poisonings (aHR = 1.85; 95% CI 1.25-2.72). CONCLUSIONS: In any given year, if an immigrant to BC was diagnosed with TB, their risk of non-TB mortality was 69% higher than if they were not diagnosed with TB. Healthcare providers should consider multiple potential threats to the long-term health of TB patients during and after TB treatment. TB guidelines in high-income settings should address TB survivor health.

RéSUMé: OBJECTIF: Au moyen de régressions de Cox avec une covariable temporalisée, comparer le risque global de mortalité non due à la tuberculose et les risques de mortalité par cause au sein de la population immigrante de la Colombie-Britannique (C.-B.) avec et sans diagnostic de tuberculose. MéTHODE: Toutes les personnes ayant immigré en C.-B. entre 1985 et 2015 (N = 1 030 873) ont été incluses, dont n = 2 435 patients tuberculeux, le reste étant des témoins non tuberculeux. Nos résultats incluaient le temps jusqu'à la mortalité de toute cause autre que la tuberculose, soit les maladies respiratoires, les maladies cardiovasculaires, les cancers et les blessures/empoisonnements, déterminé à l'aide des statistiques de l'état civil codées selon la CIM. Nous avons utilisé des régressions de Cox avec une variable d'exposition temporalisée pour le diagnostic de tuberculose. RéSULTATS: Le coefficient de danger (CD) de mortalité non due à la tuberculose était de 4,01 (IC de 95 % : 3,57-4,51) avec un CD ajusté selon la covariable de 1,69 (IC de 95 % : 1,50-1,91). Le risque de mortalité par cause ajusté selon la covariable était élevé pour : les maladies respiratoires (CDa = 2,96; IC de 95 % : 2,18-4,00), les maladies cardiovasculaires (CDa = 1,63; IC de 95 % : 1,32-2,02), les cancers (CDa = 1,40; IC de 95 % : 1,13-1,75) et les blessures/empoisonnements (CDa = 1,85; IC de 95 % : 1,25-2,72). CONCLUSIONS: Chaque année, si une personne ayant immigré en C.-B. avait un diagnostic de tuberculose, son risque de mortalité non due à la tuberculose était supérieur de 69 % à celui d'une personne sans diagnostic de tuberculose. Les professionnels de santé devraient tenir compte des multiples menaces possibles à la santé à long terme de leurs patients tuberculeux pendant et après le traitement de la tuberculose. Les lignes directrices sur la tuberculose dans les milieux à revenu élevé devraient tenir compte de la santé des survivants de la tuberculose.

The contrasting role of nasopharyngeal angiotensin converting enzyme 2 (ACE2) transcription in SARS-CoV-2 infection: A cross-sectional study of people tested for COVID-19 in British Columbia, Canada.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of: (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. METHODS: A cross-sectional study of n = 424 "participants" aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. FINDINGS: Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0•092). Mean relative transcription of transmembrane (P = 0•00012) and soluble (P<0•0001) ACE2 isoforms, as well as TMPRSS2 (P<0•0001) was higher in COVID-19-negative participants than COVID--19 positive ones, yielding a negative correlation between targeted host gene expression and positive COVID-19 diagnosis. In bivariate analysis of COVID-19-positive participants, transcription of transmembrane ACE2 positively correlated with SARS-CoV-2 viral RNA load (B = 0•49, R2=0•14, P<0•0001), transcription of soluble ACE2 negatively correlated (B= -0•85, R2= 0•26, P<0•0001), and no correlation was found with TMPRSS2 transcription (B= -0•042, R2=<0•10, P = 0•69). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 transcription (Β= 0•89, 95%CI: [0•59 to 1•18]), while transcription of the soluble isoform appears to protect against high viral RNA load in the upper respiratory tract (Β= -0•099, 95%CI: [-0•18 to -0•022]). INTERPRETATION: Nasopharyngeal ACE2 transcription plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transcription of the transmembrane ACE2 isoform positively correlates, while transcription of the soluble isoform negatively correlates with viral RNA load after adjusting for age, biological sex, and transcription of TMPRSS2. FUNDING: This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Regional variation in multimorbidity prevalence in British Columbia, Canada: a cross-sectional analysis of Canadian Community Health Survey data, 2015/16. / Variations régionales de prévalence de la multimorbidité en Colombie-Britannique (Canada) : analyse transversale des données de l'Enquête sur la santé dans les collectivités canadiennes de 2015-2016.

INTRODUCTION: Multimorbidity represents a major concern for population health and service delivery planners. Information about the population prevalence (absolute numbers and proportions) of multimorbidity among regional health service delivery populations is needed for planning for multimorbidity care. In Canada, health region-specific estimates of multimorbidity prevalence are not routinely presented. The Canadian Community Health Survey (CCHS) is a potentially valuable source of data for these estimates. METHODS: Data from the 2015/16 cycle of the CCHS for British Columbia (BC) were used to estimate and compare multimorbidity prevalence (3+ chronic conditions) through survey-weighted analyses. Crude frequencies and proportions of multimorbidity prevalence were calculated by BC Health Service Delivery Area (HSDA). Logistic regression was used to estimate differences in multimorbidity prevalence by HSDA, adjusting for known confounders. Multiple imputation using chained equations was performed for missing covariate values as a sensitivity analysis. The definition of multimorbidity was also altered as an additional sensitivity analysis. RESULTS: A total of 681 921 people were estimated to have multimorbidity in BC (16.9% of the population) in 2015/16. Vancouver (adj-OR = 0.65; 95% CI: 0.44-0.97) and Richmond (adj-OR = 0.55; 95% CI: 0.37-0.82) had much lower prevalence of multimorbidity than Fraser South (reference HSDA). Missing data analysis and sensitivity analysis showed results consistent with the main analysis. CONCLUSION: Multimorbidity prevalence estimates varied across BC health regions, and were lowest in Vancouver and Richmond after controlling for multiple potential confounders. There is a need for provincial and regional multimorbidity care policy development and priority setting. In this context, the CCHS represents a valuable source of information for regional multimorbidity analyses in Canada.

Multimorbidity prevalence in Canada: a comparison of Northern Territories with Provinces, 2013/14.

Rapid social, economic, and environmental changes in the northern territories of Canada have raised concerns about potentially increasing levels of chronic disease. This concern prompted us to compare multimorbidity prevalence in Canada between the territories and provinces. We analyzed Canadian Community Health Survey data for 2013/14. We defined multimorbidity, the outcome, as having 3 or more chronic conditions and used survey-weighted multivariable logistic regression for comparisons between territories and provinces. We found a prevalence of multimorbidity in Canada of 14.0% (95% CI: 13.6, 14.3). We could not find significant difference in multimorbidity prevalence between the territories and provinces of Canada overall; however, the territories tended to have lower prevalence estimates than provinces for multimorbidity (adj-OR = 0.88; 95% CI: 0.74-1.04). Sensitivity analyses from propensity score analyses had similar conclusions. Effect modification analyses identified lower multimorbidity in territories versus provinces among households without a post-secondary graduate (adj-OR = 0.46; 95% CI: 0.34-0.61 for northern residence), males (adj-OR = 0.71; 95% CI: 0.54-0.93), and ages 12-29 years (adj-OR = 0.63; 95% CI: 0.39-0.99). Caution is needed in interpreting the results in light of representativeness of CCHS in northern populations of Canada.

Tuberculosis among northern Manitoba First Nations, 2008-2012: program performance on- and off-reserve.

OBJECTIVES: The objectives of this study were to: (1) report tuberculosis (TB) program performance for northern First Nations in the province of Manitoba; (2) present methods for TB program performance measurement using routinely collected surveillance data; and (3) advance dialogue on performance measurement of Canadian TB programs. METHODS: Data on a retrospective cohort of people diagnosed with TB in Manitoba between January 1, 2008 and December 31, 2010, and their contacts, were extracted from the Manitoba TB Registry. Performance measures based on US-CDC were analyzed. Adjusted probability ratios (aPR) and 95% confidence intervals (CIs) were reported with comparisons between on-/off-reserve First Nations, adjusted for age, sex, and treatment history. RESULTS: A cohort of n = 149 people diagnosed with TB and n = 3560 contacts were identified. Comparisons off-/on-reserve: Treatment completion (aPR = 1.03; 95% CI 0.995-1.07); early detection (aPR = 0.87; 95% CI 0.57-1.33); HIV testing and reporting (aPR = 0.42; 95% CI 0.21-0.83); pediatric TB (age < 15 years) (aPR = 1.20; 95% CI 0.47-3.06); retreatment for TB (aPR = 0.93; 95% CI 0.89-0.97); contact elicitation (aPR = 0.94; 95% CI 0.84-1.05); contact assessment (aPR = 0.69; 95% CI 0.50-0.94). Pediatric (ages < 15 years) TB incidence in northern Manitoba was 37.1 per 100,000/year. CONCLUSION: TB program performance varies depending on residence in a reserve or non-reserve community. Action is urgently needed to address TB program performance in terms of contact investigation and HIV testing/reporting for First Nations off-reserve and to address high rates of pediatric TB in northern Manitoba. First Nations collaboration and models of care should be considered both on- and off-reserve to improve TB program performance.

Long-term all-cause mortality in people treated for tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Accurate estimates of long-term mortality following tuberculosis treatment are scarce. This systematic review and meta-analysis aimed to estimate the post-treatment mortality among tuberculosis survivors, and examine differences in mortality risk by demographic and clinical characteristics. METHODS: We systematically searched Embase, MEDLINE, and the Cochrane Database of Systematic Reviews for cohort studies published in English between Jan 1, 1997, and May 31, 2018. We included research papers that used a cohort study design, included bacteriological or clinical confirmation of tuberculosis disease for all participants, and reported, or provided enough data to calculate, mortality estimates for people with tuberculosis and a valid control group representative of the general population. We excluded studies that reported duplicate data, had a study population of fewer than 50 people overall, had a follow-up period shorter than 12 months after treatment completion, or had a loss to follow-up of more than 30%. From eligible studies, we extracted standardised mortality ratios (SMRs), or calculated them when the data were sufficient, by dividing the sum of the observed deaths by the sum of the expected deaths. For studies that did not report SMR as their mortality estimate, either mortality hazard ratios or mortality rate ratios were extracted and pooled with SMRs. Random-effects meta-analysis was used to obtain pooled SMRs. Between-study heterogeneity was estimated with I2. This study was prospectively registered in PROSPERO (CRD42018092592). FINDINGS: Of the 7283 unique studies identified, data from ten studies, reporting on 40 781 individuals and 6922 deaths, were included. The pooled SMR for all-cause mortality among people with tuberculosis, compared with the control group, was 2·91 (95% CI 2·21-3·84; I2=99%, pheterogeneity<0·0001). When restricted to people with confirmed treatment completion or cure, the pooled SMR was 3·76 (95% CI 3·04-4·66; I2=95%). Effect estimates were similar when stratified by tuberculosis type, sex, age, and country income category. Causes of mortality were extracted for 4226 deaths that occurred post-treatment, with most deaths attributable to cardiovascular disease (20% [95% CI 15-26]; I2=92%). INTERPRETATION: People treated for tuberculosis have significantly increased mortality following treatment compared with the general population or matched controls. These findings support the need for further research to understand and address the biomedical and social factors that affect the long-term prognosis of this population. FUNDING: None.

Homicide mortality rates in Canada, 2000-2009: Youth at increased risk.

OBJECTIVES: To estimate and compare Canadian homicide mortality rates (HMRs) and trends in HMRs across age groups, with a focus on trends for youth. METHODS: Data for the period of 2000 to 2009 were collected from Statistics Canada's CANSIM (Canadian Statistical Information Management) Table 102-0540 with the following ICD-10-CA coded external causes of death: X85 to Y09 (assault) and Y87.1 (sequelae of assault). Annual population counts from 2000 to 2009 were obtained from Statistics Canada's CANSIM Table 051-0001. Both death and population counts were organized into five-year age groups. A random effects negative binomial regression analysis was conducted to estimate age group-specific rates, rate ratios, and trends in homicide mortality. RESULTS: There were 9,878 homicide deaths in Canada during the study period. The increase in the overall homicide mortality rate (HMR) of 0.3% per year was not statistically significant (95% CI: -1.1% to +1.8%). Canadians aged 15-19 years and 20-24 years had the highest HMRs during the study period, and experienced statistically significant annual increases in their HMRs of 3% and 4% respectively (p < 0.05). A general, though not statistically significant, decrease in the HMR was observed for all age groups 50+ years. A fixed effects negative binomial regression model showed that the HMR for males was higher than for females over the study period [RRfemale/male = 0.473 (95% CI: 0.361, 0.621)], but no significant difference in sex-specific trends in the HMR was found. CONCLUSION: An increasing risk of homicide mortality was identified among Canadian youth, ages 15-24, over the 10-year study period. Research that seeks to understand the reasons for the increased homicide risk facing Canada's youth, and public policy responses to reduce this risk, are warranted.