Grace Shen-Tu’s research while affiliated with Alberta Health Services and other places

Purpose To characterize the association between metformin use and risk of total joint replacement in patients with diabetes using data from Alberta’s Tomorrow Project (ATP), a population-based cohort study of chronic diseases in Alberta, Canada. Methods The ATP participants with incidence of diabetes after enrollment were included and followed up to March 31, 2021. Metformin use, including daily doses, was measured by a time-varying approach during the follow-up. A multivariable Cox regression model was used to characterize the association between metformin use and risk of total joint replacement, after controlling for time-related variation in drug use, clinical status, BMI, lifestyles and concurrent medications. Results Among 3,001 incident cases of diabetes (52% females, age at diagnosis 61.3 ± 9.5 years, average follow-up of 7.3 ± 4.7 years), the rate of total joint replacement was 7.57 per 1,000 person-year (PY) for metformin users and 9.31 per 1,000 PY for non-metformin users, with rate ratio = 0.81 (95% CI = 0.59–1.11, p-value = 0.09). In multivariable Cox regression analysis, metformin use was not significantly associated with risk of total joint replacement, with hazard ratio of 0.74 (95% CI = 0.52–1.03, p-value = 0.07) for patients with metformin medication, HR = 0.75 (95% CI = 0.46–1.22) for 0–1.0 g/day metformin use, and HR = 0.73 (95% CI = 0.49–1.08) for 1.0 + g/day use (‘no metformin use’ as the reference group). Conclusions Although our findings are not statistically significant, our study suggests clinically a potential benefit of metformin use in reducing risk of total joint replacement in patients with diabetes.

Background. Hypertension affects over 1.28 billion adults worldwide, including a significant number of women. Although the gut microbiome is implicated in the onset and progression of hypertension, few studies have examined the relationship in middle-aged women. Methods. Within an established cohort, we investigated the relationship between gut microbiota and its metabolites in normotensive vs. hypertensive middle-aged women (n=108) matched for age (56.6+/-0.91 years) and body mass index (24.3+/-0.24 kg/m2). Fecal microbiota analysis was performed using 16S rRNA sequencing and serum metabolites were analyzed using LC-MS/QTOF. Associations between the microbiota, metabolomic alterations and systemic inflammatory cytokines were statistically examined to uncover their interrelationships and potential role in disease progression. Results. Women with hypertension had gut dysbiosis with an increased Firmicutes/Bacteroidetes ratio and higher abundances of inflammatory taxa including Anaerostipes and Collinsella. Untargeted serum metabolomics demonstrated that hypertensive participants had elevated levels of tryptophan, the pro-inflammatory metabolite kynurenine and lower levels of health-promoting indoles produced by the action of gut microbiota on tryptophan (p<0.05). These findings were confirmed in microbiota analysis showing a reduced abundance of indole-producing species (Alistipes shahii, Bacteroides faecichinchillae, Bacteroides stercoris)(p<0.05) suggesting a lower microbial activity of tryptophan-indole metabolism. Furthermore, hypertension increased inflammatory markers including an elevated IL12/IL10 ratio, interferon-? and tumor necrosis factor-?. The IL-12/IL-10 ratio demonstrated a positive correlation with kynurenine levels, emphasizing the involvement of cytokines and gut microbiota in driving systemic inflammation in hypertension. Conclusion. Imbalances in microbiota-regulated tryptophan metabolism contribute to systemic inflammation in hypertensive, middle-aged women, presenting a potentially modifiable target for intervention.

Background Effective mental healthcare coverage (EMHC) is an important health system performance indicator of a population’s mental healthcare needs. This study aims to assess the factors and healthcare costs associated with the receipt of EMHC for anxiety and depression. Methods This study draws on data from participants from Alberta’s Tomorrow Project with moderate or severe symptoms of anxiety and depression during the first wave of the COVID-19 pandemic (2020) with available medico-administrative and complete data [n = 720]. EMHC was assessed during the eighteen months as of March 1, 2020, and defined as adequate pharmacotherapy (i.e., antidepressant dispensed, with ≥ 80% proportion of days covered and 4 follow-up medical visits) and/or adequate psychotherapy (≥ 8 physician consultations for psychotherapy) depending on the severity of symptoms. Logistic regression analysis was used to study EMHC as a function of study variables. Regressions with augmented inverse probability weighting were used to estimate the total healthcare costs attributable to receipt of EMHC during the first 18-month period of the pandemic, controlling for confounders. Mean adjusted differences with 95% bias-corrected bootstrap confidence intervals (CIs) are presented. Results The proportion receiving EMHC was 26.7%. Individuals with worse self-rated mental health after the pandemic than before were less likely to receive EMHC. Those with a lifetime diagnosis of depression and anxiety were more likely to receive EMHC. The overall mean adjusted total healthcare costs attributable to receipt of EMHC during the pandemic was $2601 [ –$247, $5694]. The mean adjusted outpatient costs attributable to EMHC was significantly higher and reached$1613 [873, 2577]. Conclusion The study’s findings highlight the existence of health inequalities and potential unmet mental health needs in individuals with worsening mental health during the pandemic. The receipt of EMHC during the pandemic was not significantly associated with increased total healthcare costs. These findings underscore the need for mental health policies that are aimed at improving timely access to EMHC to address population unmet mental health service needs.

Objective: The objective is to characterize the impact of COVID-19 on major healthcare for diabetes, including hospitalization, emergency department (ED) visits and primary care visits in Alberta, Canada. Methods: Participants from Alberta’s Tomorrow Project (ATP) with pre-existing diabetes prior to 1 April 2018 were included and followed up to 31 March 2021. A time-segmented regression model was used to characterize the impact of COVID-19 on healthcare utilization after adjusting for seasonality, socio-demographic factors, lifestyle behaviors and comorbidity profile of patients. Results: Among 6099 participants (53.5% females, age at diagnosis 56.1 ± 9.9 y), the overall rate of hospitalization, ED visits and primary care visits was 151.5, 525.9 and 8826.9 per 1000 person-year during the COVID-19 pandemic (up to 31 March 2021), which means they reduced by 12% and 22% and increased by 6%, compared to pre-pandemic rates, respectively. Specifically, the first COVID-19 state of emergency (first wave of the outbreak) was associated with reduced rates of hospitalization, ED visits and primary care visits, by 79.4% (95% CI: 61.3–89.0%), 93.2% (95% CI: 74.6–98.2%) and 65.7% (95% CI: 47.3–77.7%), respectively. During the second state of emergency, healthcare utilization continued to decrease; however, a rebound (increase) of ED visits was observed during the period when the public health state of emergency was relaxed. Conclusion: The declared COVID-19 states of emergency had a negative impact on healthcare utilization for people with diabetes, especially for hospital and ED services, which suggests the importance of enhancing the capacity of these two healthcare sectors during future COVID-19-like public health emergencies.

Oral iron supplementation is the first-line treatment for addressing iron deficiency, a concern particularly relevant to women who are susceptible to sub-optimal iron levels. Nevertheless, the impact of iron supplementation on the gut microbiota of middle-aged women remains unclear. To investigate the association between iron supplementation and the gut microbiota, healthy females aged 40–65 years (n = 56, BMI = 23 ± 2.6 kg/m2) were retrospectively analyzed from the Alberta’s Tomorrow Project. Fecal samples along with various lifestyle, diet, and health questionnaires were obtained. The gut microbiota was assessed by 16S rRNA sequencing. Individuals were matched by age and BMI and classified as either taking no iron supplement, a low-dose iron supplement (6–10 mg iron/day), or high-dose iron (>100 mg/day). Compositional and functional analyses of microbiome data in relation to iron supplementation were investigated using various bioinformatics tools. Results revealed that iron supplementation had a dose-dependent effect on microbial communities. Elevated iron intake (>100 mg) was associated with an augmentation of Proteobacteria and a reduction in various taxa, including Akkermansia, Butyricicoccus, Verrucomicrobia, Ruminococcus, Alistipes, and Faecalibacterium. Metagenomic prediction further suggested the upregulation of iron acquisition and siderophore biosynthesis following high iron intake. In conclusion, adequate iron levels are essential for the overall health and wellbeing of women through their various life stages. Our findings offer insights into the complex relationships between iron supplementation and the gut microbiota in middle-aged women and underscore the significance of iron dosage in maintaining optimal gut health.

Human gut microbiota are recognized as critical players in both metabolic disease and drug metabolism. However, medication–microbiota interactions in cardiometabolic diseases are not well understood. To gain a comprehensive understanding of how medication intake impacts the gut microbiota, we investigated the association of microbial structure with the use of single or multiple medications in a cohort of 134 middle-aged adults diagnosed with cardiometabolic disease, recruited from Alberta’s Tomorrow Project. Predominant cardiometabolic prescription medication classes (12 total) were included in our analysis. Multivariate Association with Linear Model (MaAsLin2) was employed and results were corrected for age, BMI, sex, and diet to evaluate the relationship between microbial features and single- or multimedication use. Highly individualized microbiota profiles were observed across participants, and increasing medication use was negatively correlated with α-diversity. A total of 46 associations were identified between microbial composition and single medications, exemplified by the depletion of Akkermansia muciniphila by β-blockers and statins, and the enrichment of Escherichia/Shigella and depletion of Bacteroides xylanisolvens by metformin. Metagenomics prediction further indicated alterations in microbial functions associated with single medications such as the depletion of enzymes involved in energy metabolism encoded by Eggerthella lenta due to β-blocker use. Specific dual medication combinations also had profound impacts, including the depletion of Romboutsia and Butyricicoccus by statin plus metformin. Together, these results show reductions in bacterial diversity as well as species and microbial functional potential associated with both single- and multimedication use in cardiometabolic disease.

Background Scarce are the studies focusing on initiation of new mental health service use (MHSU) and distinguishing individuals who have sought services but have been unsuccessful in accessing these. Aims Assessing the factors associated with initiating new MHSU as compared to no MHSU due to self-reported no need, no MHSU due to health system and personal barriers and MHSU using resources already in place. Methods The sample included participants (n = 16,435) in the five established regional cohorts of the Canadian Partnership for Tomorrow’s Health (CanPath) who responded to the CanPath COVID-19 health surveys (May–December 2020 and January–June 2021). Multinomial regression analyses were carried out to study MHSU since the pandemic (March 2020) as a function of predisposing, enabling and need factors. Analyses were carried out in the overall sample and restricted to those with moderate and severe symptoms (MSS) of depression and/or anxiety (n = 2,237). Results In individuals with MSS of depression and/or anxiety, 14.4% reported initiating new MHSU, 22.0% had no MHSU due to barriers and personal reasons and 36.7% had no MHSU due to self-reported no need. Age, living alone, lower income, a decrease in income during the pandemic and health professional status were associated with MHSU. Younger adults were more likely to initiate MHSU during the pandemic than older adults who reported not being comfortable to seek mental health care or self-reported no need. Individuals living alone and with lower income were more likely to report not being able to find an appointment for mental health care. Conclusions Awareness campaigns focusing on older adults that explain the importance of seeking treatment is needed, as well as sensitising health professionals as to the importance of informing and aiding individuals at risk of social isolation and lower socio-economic status as to available mental health resources and facilitating access to care.

Aim To characterize the impact of the COVID‐19 pandemic on diabetes diagnosis using data from Alberta's Tomorrow Project (ATP), a population‐based cohort study of chronic diseases in Alberta, Canada. Materials and Methods The ATP participants who were free of diabetes on 1 April 2018 were included in the study. A time‐segmented regression model was used to compare incidence rates of diabetes before the COVID‐19 pandemic, during the first two COVID‐19 states of emergency, and in the period when the state of emergency was relaxed, after adjusting for seasonality, sociodemographic factors, socioeconomic status, and lifestyle behaviours. Results Among 43 705 ATP participants free of diabetes (65.5% females, age 60.4 ± 9.5 years in 2018), the rate of diabetes was 4.75 per 1000 person‐year (PY) during the COVID‐19 pandemic (up to 31 March 2021), which was 32% lower (95% confidence interval [CI] 21%, 42%; p < 0.001) than pre‐pandemic (6.98 per 1000 PY for the period 1 April 2018 to 16 March 2020). In multivariable regression analysis, the first COVID‐19 state of emergency (first wave) was associated with an 87.3% (95% CI −98.6%, 13.9%; p = 0.07) reduction in diabetes diagnosis; this decreasing trend was sustained to the second COVID‐19 state of emergency and no substantial rebound (increase) was observed when the COVID‐19 state of emergency was relaxed. Conclusions The COVID‐19 public health emergencies had a negative impact on diabetes diagnosis in Alberta. The reduction in diabetes diagnosis was likely due to province‐wide health service disruptions during the COVID‐19 pandemic. Systematic plans to close the post‐COVID‐19 diagnostic gap are required in diabetes to avoid substantial downstream sequelae of undiagnosed disease.

Objectives Few are the longitudinal studies on the changes in moderate or severe symptoms of anxiety or depression (MSS-ANXDEP) from before to during the COVID-19 pandemic in Canada. The aim was to study the change in MSS-ANXDEP and associated sociodemographic, economic, psychosocial, health behaviour and lifestyle, and clinical factors. Methods The current sample includes 59,997 adults aged ≥ 35 years participating in the 2018 and 2020 health surveys of the 5 established cohorts of the Canadian Partnership for Tomorrow’s Health (CanPath). MSS-ANXDEP was based on a cutoff score ≥ 10 on the 7-item Generalized Anxiety Disorder Scale and Patient Health Questionnaire (PHQ-8). Change in MSS-ANXDEP was categorized as follows: no MSS-ANXDEP, remitted, incident, and persistent. Multinomial regressions were used to study MSS-ANXDEP as a function of sociodemographic, economic, psychosocial, health behaviours and lifestyle, and clinical factors. Results Sociodemographic and economic (i.e. age, gender, cohort, race/ethnicity, lower income, decreased in income, work status, being an essential worker), lifestyle and health behaviours (i.e. smoking, cannabis and alcohol use, drinking more alcohol), psychosocial (i.e. provide help to others, information and instrumental support, and change in relationships with friends, family, and partner) and clinical factors (i.e. lifetime mental disorder and multimorbidity) were associated with remitted, incident, and persistent MSS-ANXDEP. Conclusion Health and socio-economic factors were associated with changes in symptoms of anxiety and depression during the pandemic, further increasing inequities in mental health needs. Public health campaigns on the importance of healthy behaviours should continue and health policies should reduce economic and social barriers to integrated substance use and mental health care.