Despite the Canadian healthcare system's commitment to equity, evidence for disparate access to primary care (PC) providers exists across individual social identities/positions. Intersectionality ...allows us to reflect the realities of how social power shapes healthcare experiences at an individual's interdependent and intersecting social identities/positions. The objectives of this study were to determine: (1) the extent to which intersections can be used classify those who had/did not have a PC provider; (2) the degree to which each social identity/position contributes to the ability to classify individuals as having a PC provider; and (3) predicted probabilities of having a PC provider for each intersection.
Using national cross-sectional data from 241,445 individuals in Canada aged ≥18, we constructed 320 intersections along the dimensions of gender, age, immigration status, race, and income to examine the outcome of whether one had a PC provider. Multilevel analysis of individual heterogeneity and discriminatory accuracy, a multi-level model using individual-level data, was employed to address intersectional objectives. An intra-class correlation coefficient (ICC) of 23% (95%CI: 21-26%) suggests that these intersections could, to a very good extent, explain individual variation in the outcome, with age playing the largest role. Not all between-intersection variance in this outcome could be explained by additive effects of dimensions (remaining ICC: 6%; 95%CI: 2-16%). The highest intersectional predicted probability existed for established immigrant, older South Asian women with high income. The lowest intersectional predicted probability existed for recently immigrated, young, Black men with low income.
Despite a "universal" healthcare system, our analysis demonstrated a substantial amount of inequity in primary care across intersections of gender, age, immigration status, race, and income.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Weight status and weight perception have a significant impact on life satisfaction. As overweight prevalence increases in Canada, it is important to understand how accuracy of ...weight perception (AWP) is associated with life satisfaction. This study explored the association between AWP and life satisfaction among Canadian adults with and without anxiety and/or mood disorders.
Methods
Using data from the 2015–2018 cycles of the Canadian Community Health Survey, an indicator of AWP was created to capture concordance between perceived weight and actual weight status. Univariate and multivariate Gaussian generalized linear models were assessed while stratifying by sex and presence of anxiety and/or mood disorders.
Results
Our sample included 88 814 males and 106 717 females. For both sexes, perceiving oneself as overweight or underweight, regardless of actual weight status, was associated with lower life satisfaction (β = −0.93 to −0.30), compared to those who accurately perceived their weight as ‘just about right’. Perceiving oneself as overweight or underweight was associated with more pronounced differences in life satisfaction scores in those with anxiety and/or mood disorders (β = −1.49 to −0.26) than in those without these disorders (β = −0.76 to −0.25).
Conclusion
Weight perception is more indicative of life satisfaction than actual weight status, especially in those with anxiety and/or mood disorders.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is ...poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.
Transposon mutagenesis with next-generation sequencing (TnSeq) is a powerful approach to annotate gene function in bacteria, but existing protocols for TnSeq require laborious preparation of every ...sample before sequencing. Thus, the existing protocols are not amenable to the throughput necessary to identify phenotypes and functions for the majority of genes in diverse bacteria. Here, we present a method, random bar code transposon-site sequencing (RB-TnSeq), which increases the throughput of mutant fitness profiling by incorporating random DNA bar codes into Tn5 and mariner transposons and by using bar code sequencing (BarSeq) to assay mutant fitness. RB-TnSeq can be used with any transposon, and TnSeq is performed once per organism instead of once per sample. Each BarSeq assay requires only a simple PCR, and 48 to 96 samples can be sequenced on one lane of an Illumina HiSeq system. We demonstrate the reproducibility and biological significance of RB-TnSeq with Escherichia coli, Phaeobacter inhibens, Pseudomonas stutzeri, Shewanella amazonensis, and Shewanella oneidensis. To demonstrate the increased throughput of RB-TnSeq, we performed 387 successful genome-wide mutant fitness assays representing 130 different bacterium-carbon source combinations and identified 5,196 genes with significant phenotypes across the five bacteria. In P. inhibens, we used our mutant fitness data to identify genes important for the utilization of diverse carbon substrates, including a putative d-mannose isomerase that is required for mannitol catabolism. RB-TnSeq will enable the cost-effective functional annotation of diverse bacteria using mutant fitness profiling.
A large challenge in microbiology is the functional assessment of the millions of uncharacterized genes identified by genome sequencing. Transposon mutagenesis coupled to next-generation sequencing (TnSeq) is a powerful approach to assign phenotypes and functions to genes. However, the current strategies for TnSeq are too laborious to be applied to hundreds of experimental conditions across multiple bacteria. Here, we describe an approach, random bar code transposon-site sequencing (RB-TnSeq), which greatly simplifies the measurement of gene fitness by using bar code sequencing (BarSeq) to monitor the abundance of mutants. We performed 387 genome-wide fitness assays across five bacteria and identified phenotypes for over 5,000 genes. RB-TnSeq can be applied to diverse bacteria and is a powerful tool to annotate uncharacterized genes using phenotype data.
Intraabdominal surgeries are frequently performed procedures that lead to a high volume of unplanned readmissions and postoperative complications. Patient sex may be a determinant of adverse outcomes ...in this population, possibly due to differences in biology or care delivery, but it is understudied. The authors hypothesized that there would be no association between patient sex and the risk of postoperative adverse outcomes in intraabdominal surgery.
This retrospective, population-based cohort study involved adult inpatients aged 18 yr or older who underwent intraabdominal surgeries in Ontario, Canada, between April 2009 and March 2016. The authors studied the association of patient sex on the primary composite outcome of all-cause death, hospital readmission, or major postoperative complications, all within 30 postoperative days. Inverse probability of exposure weighting based on propensity scores (computed using demographic characteristics such as rural residence status and median neighborhood income quintile, common comorbidities, and surgery- and hospital-specific characteristics) was used to estimate the adjusted association of sex on outcomes.
The cohort included 215,846 patients (52.3% female). The primary outcome was observed in 24,712 (21.9%) females and 25,486 (24.7%) males (unadjusted risk difference, 2.8% 95% CI, 2.5 to 3.2%; P < 0.001). After adjustment, the association between the male sex and the primary outcome was not statistically significant (adjusted risk difference, -0.2% 95% CI, -0.5 to 0.2%; P = 0.378).
In a large population of intraabdominal surgical patients, there was no differential risk between sexes in the composite outcome of all-cause death, hospital readmission, or major postoperative complications, all within 30 postoperative days.
Summary
Objective
: Internationally, primary care practice had to transform in response to the COVID pandemic. Informatics issues included access, privacy, and security, as well as patient concerns ...of equity, safety, quality, and trust. This paper describes progress and lessons learned.
Methods
: IMIA Primary Care Informatics Working Group members from Australia, Canada, United Kingdom and United States developed a standardised template for collection of information. The template guided a rapid literature review. We also included experiential learning from primary care and public health perspectives.
Results
: All countries responded rapidly. Common themes included rapid reductions then transformation to virtual visits, pausing of non-COVID related informatics projects, all against a background of non-standardized digital development and disparate territory or state regulations and guidance. Common barriers in these four and in less-resourced countries included disparities in internet access and availability including bandwidth limitations when internet access was available, initial lack of coding standards, and fears of primary care clinicians that patients were delaying care despite the availability of televisits.
Conclusions
: Primary care clinicians were able to respond to the COVID crisis through telehealth and electronic record enabled change. However, the lack of coordinated national strategies and regulation, assurance of financial viability, and working in silos remained limitations. The potential for primary care informatics to transform current practice was highlighted. More research is needed to confirm preliminary observations and trends noted.
Abstract Introduction Scientific evidence and recent large cohort studies indicate that many questions remain unanswered about relations between shift work (SW) and cardiovascular disease (CVD). ...Materials and Methods Large cohort studies and new clinical experimental research exploring the association of cardiovascular autonomic control, inflammation and sleep impairment with SW are revised. Wearable devices (WDs) and artificial intelligence (AI) techniques recently proposed to assess CVD biomarkers during working activity, sleeping and leisure time have also been explored. Results SW exposure intensity and new insights on age-dependent SW threshold require rigorous application in the workplace. Individual cardiovascular risk profile, including autonomic functioning, psychosocial and socio-economic conditions and incident CVD including hypertension, should be addressed to identify and manage hypersusceptible workers and to prevent post-retirement disability. It has been recently observed that shift work increases myocardial infarction reperfusion injury (EARLY-MYO-CMR registry). Gender differences in SW exposure, work-life balance and family-load remain poorly addressed. WDs and AI provide opportunities to identify circadian disruption, early signs of fatigue, low quality of sleep and sleep deprivation in SW. Finally, it is time to propose workplace intervention (SW duration and rotation, rest periods, facilities, and education) that may be individually tailored. Conclusions Though relations between SW and CVD including coronary heart disease have long been studied, the aforementioned gaps remain. Advanced technologies may furnish novel insights for workplace intervention aimed at reducing the effect of SW in CVD.
HER2-positive breast cancers exhibit high rates of innate and acquired resistance to trastuzumab (TZ), a HER2-directed antibody used as a first line treatment for this disease. TZ resistance may in ...part be mediated by frequent co-expression of EGFR and by sustained activation of the mammalian target of rapamycin (mTOR) pathway. Here, we assessed feasibility of combining the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus (RAD001) for treating HER2 overexpressing breast cancers with different sensitivity to TZ.
The gefitinib and RAD001 combination was broadly evaluated in TZ sensitive (SKBR3 and MCF7-HER2) and TZ resistant (JIMT-1) breast cancer models. The effects on cell growth were measured in cell based assays using the fixed molar ratio design and the median effect principle. In vivo studies were performed in Rag2M mice bearing established tumors. Analysis of cell cycle, changes in targeted signaling pathways and tumor characteristics were conducted to assess gefitinib and RAD001 interactions.
The gefitinib and RAD001 combination inhibited cell growth in vitro in a synergistic fashion as defined by the Chou and Talalay median effect principle and increased tumor xenograft growth delay. The improvement in therapeutic efficacy by the combination was associated in vitro with cell line dependent increases in cytotoxicity and cytostasis while treatment in vivo promoted cytostasis. The most striking and consistent therapeutic effect of the combination was increased inhibition of the mTOR pathway (in vitro and in vivo) and EGFR signaling in vivo relative to the single drugs.
The gefitinib and RAD001 combination provides effective control over growth of HER2 overexpressing cells and tumors irrespective of the TZ sensitivity status.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The onset of the COVID-19 pandemic necessitated a rapid shift in primary health care from predominantly in-person to high volumes of virtual care. The pandemic afforded the opportunity to conduct a ...deep regional examination of virtual care by family physicians in London and Middlesex County, Ontario, Canada that would inform the foundation for virtual care in our region post-pandemic.
(1) to determine volumes of in-person and virtual family physicians visits and characteristics of the family physicians and patients using them during the early COVID-19 pandemic; (2) to determine how virtual visit volumes changed over the pandemic, compared to in-person; and (3) to explore family physicians' experience in virtual visit adoption and implementation.
We conducted a concurrent mixed-methods study of family physicians from March to October 2020. The quantitative component examined mean weekly number of total, in-person and virtual visits using health administrative data. Differences in outcomes according to physician and practice characteristics for pandemic periods were compared to pre-pandemic. The qualitative study employed Constructivist Grounded Theory, conducting semi-structured family physicians interviews; analyzing data iteratively using constant comparative analysis. We mapped themes from the qualitative analysis to quantitative findings.
Initial volumes of patients decreased, driven by fewer in-person visits. Virtual visit volumes increased dramatically; family physicians described using telephone almost entirely. Rural family physicians reported video connectivity issues. By early second wave, total family physician visit volume returned to pre-pandemic volumes. In-person visits increased substantially; family physicians reported this happened because previously scarce personal protective equipment became available. Patients seen during the pandemic were older, sicker, and more materially deprived.
These results can inform the future of virtual family physician care including the importance of continued virtual care compensation, the need for equitable family physician payment models, and the need to attend to equity for vulnerable patients. Given the move to virtual care was primarily a move to telephone care, the modality of care delivery that is acceptable to both family physicians and their patients must be considered.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveDispersion, or variability in an individual’s performance across multiple tasks at a single assessment visit, has been associated with cognitive dysfunction (CD) in many neurodegenerative ...and neurodevelopmental disorders. We aimed to compute a dispersion score using neuropsychological battery (NB) tests and determine its association with CD in patients with SLE.MethodsCD was defined as a z-score of ≤−1.5 on ≥2 domains of the NB. To compute a type of dispersion score known as the intraindividual SD (ISD), the SD of age-adjusted and sex-adjusted z-scores was calculated for each visit in each patient. To estimate the association between ISD and cognitive status (CD and non-CD), we used multilevel logistic regression, adjusting for clinically important covariates.ResultsA total of 301 adult patients with SLE completed the NB at baseline, 187 of whom were reassessed at 6 months and 189 at 12 months. CD was observed in 35.2% of patients at baseline, 27.8% at 6 months and 28.0% at 12 months. Prior to covariate adjustment, the mean ISD for non-CD was 1.10±0.31 compared with 1.50±0.70 for CD. After adjusting for ethnicity, education, employment, socioeconomic status and anxiety/depression, there was a statistically significant association between ISD and CD (OR for one-unit increase in ISD: 13.56, 95% CI 4.80 to 38.31; OR for 1/10th-unit increase in ISD: 1.30, 95% CI 1.17 to 1.44). Findings were valid across multiple sensitivity analyses.ConclusionThis is the first study to show that patients with SLE who were classified as having CD by the NB had more variability across the NB tests (ie, higher ISD score) compared with those who were not classified as having CD.
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