Disproportionate Rates of COVID-19 Among Black Canadian Communities: Lessons from a Cross-Sectional Study in the First Year of the Pandemic.

BACKGROUND: Racialized communities, including Black Canadians, have disproportionately higher COVID-19 cases. We examined the extent to which SARS-CoV-2 infection has affected the Black Canadian community and the factors associated with the infection. METHODS: We conducted a cross-sectional survey in an area of Ontario (northwest Toronto/Peel Region) with a high proportion of Black residents along with 2 areas that have lower proportions of Black residents (Oakville and London, Ontario). SARS-CoV-2 IgG antibodies were determined using the EUROIMMUN assay. The study was conducted between August 15, 2020, and December 15, 2020. RESULTS: Among 387 evaluable subjects, the majority, 273 (70.5%), were enrolled from northwest Toronto and adjoining suburban areas of Peel, Ontario. The seropositivity values for Oakville and London were comparable (3.3% (2/60; 95% CI 0.4-11.5) and 3.9% (2/51; 95% CI 0.5-13.5), respectively). Relative to these areas, the seropositivity was higher for the northwest Toronto/Peel area at 12.1% (33/273), relative risk (RR) 3.35 (1.22-9.25). Persons 19 years of age or less had the highest seropositivity (10/50; 20.0%, 95% CI 10.3-33.7%), RR 2.27 (1.23-3.59). There was a trend for an interaction effect between race and location of residence as this relates to the relative risk of seropositivity. INTERPRETATION: During the early phases of the pandemic, the seropositivity within a COVID-19 high-prevalence zone was threefold greater than lower prevalence areas of Ontario. Black individuals were among those with the highest seroprevalence of SARS-CoV-2.

Dual-energy x-ray absorptiometry assessment of bone health in Australian men with prostate cancer commencing androgen deprivation therapy.

OBJECTIVE: To determine the prevalence in Australia of bone health assessment of men with prostate cancer by dual-energy x-ray absorptiometry (DXA), from six months before to twelve months after initiation of androgen deprivation therapy (ADT). DESIGN, SETTING: Cross-sectional national study; linkage of de-identified Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data. PARTICIPANTS: Men (18 years or older) first dispensed PBS-subsidised ADT during 1 May 2017 - 31 July 2020. MAIN OUTCOME MEASURES: Prevalence of MBS-subsidised DXA assessments undertaken from six months before to twelve months after first ADT prescription. RESULTS: Of 33 836 men with prostate cancer commencing ADT therapy during 2017-20, 6683 (19.8%) underwent DXA bone heath assessments between six months before and twelve months after commencing ADT; the mean time from first ADT dispensing to DXA scanning was +90 days (standard deviation, 134 days). The proportion of men aged 54 years or younger who had scans (66 of 639, 10%) was smaller than that of men aged 70-84 years (4528 of 19 378, 23.4%; adjusted odds ratio, 0.36; 95% CI, 0.28-0.47). CONCLUSIONS: For about 80% of men with prostate cancer commencing ADT in Australia, therapy initiation was not accompanied by DXA assessment of bone health. Given the excellent long term prognosis for men with prostate cancer and the availability of bone protective therapy, bone health monitoring should be a routine component of prostate cancer care for men receiving ADT.

The disproportionately large contribution of the Maori and Pacific Islander community to the healthcare burden of gout in Western Sydney.

BACKGROUND: Gout is a common chronic inflammatory disorder due to monosodium urate deposition, which results in severe inflammatory arthritis. It is particularly common in those of Maori or Pacific Islander heritage. There is a significant number of this at-risk ethnic group in western Sydney. AIMS: To determine the healthcare burden of gout in Western Sydney. METHODS: We characterised patients managed in the emergency departments (EDs) of the four Western Sydney Local Health District (WSLHD) hospitals and those admitted for gout as the primary or secondary diagnosis from 1 January 2017 to 31 December 2018. RESULTS: There were 472 patients managed in ED on 552 occasions at a direct cost to the LHD of A$367 835. Those of Maori or Pacific Islander ethnicity comprised 25.2% (n = 119/472), while half (n = 39/80) of those managed in ED for gout on two or more occasions were of Maori or Pacific Islander ethnicity. Overall, 310 patients were admitted with gout as the principal diagnosis on 413 occasions at a cost of A$1.73 million. Seventy-five (24.2%) of the 310 patients were of Maori or Pacific Islander heritage. A total of 584 WSLHD inpatients had gout as a secondary diagnosis. This was associated with 714 admissions. CONCLUSIONS: The disproportionately large healthcare burden of gout in Western Sydney from the relatively small Maori and Pacific Islander population needs attention. Urgent culturally appropriate interventions to address gout are required to address this inequality.

Bone health assessment with dual energy X-ray absorptiometry in men with high-risk prostate carcinoma commencing adjuvant androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is a key component of therapy for patients with high-risk prostate carcinoma, but it may be deleterious for bone health. We sought to determine the frequency of dual energy x-ray absorptiometry (DXA) scanning in patients commencing adjuvant ADT for treatment of high-risk prostate cancer at a large integrated regional cancer centre. Material and methods: The electronic medical records (EMR) of all patients with high-risk prostate carcinoma commenced on adjuvant ADT between January 1, 2016 and December 31, 2017 at the Mid-North Coast Cancer Institute, Coffs Harbour, Australia were reviewed. Patients commenced on neoadjuvant ADT and long-term suppressive ADT for metastatic disease were excluded. The following data were obtained: socio-demographic information, prostate cancer data, ADT details and DXA results. Results: 188 men (mean age ± SD, 75.4 ± 7 years) were commenced on adjuvant ADT for a total duration (mean ± SD) of 23.4 ± 7 months. Most (n = 155/188, 82%) were commenced on leuprorelin acetate. While only 26/188 (14%) had a DXA scan performed prior to ADT, another 133 (71%) had a DXA scan at a median of 20 days (interquartile range 7-98), later. Of the 159 men with DXA readings, 76 (48%) were osteopaenic and 38 (24%) were osteoporotic by DXA criteria. Conclusion: A high level (85%) of DXA scanning in men commencing ADT for prostate cancer can be achieved at a regional centre. The high prevalence (72%) of low bone mass in our unselected cohort underscores the importance of routine DXA scanning to guide bone health management during ADT.

An enquiry into the crippling gout affecting Pacific Islander and Maori men in Western Sydney.

AIM: Despite the effectiveness and availability of urate-lowering therapies (ULT), we continue to see a number of advanced cases of tophaceous gout in the Pacific Islander and Maori population in Western Sydney. Although the high prevalence and increased severity of gout in this cohort has been well documented, there has been little qualitative research undertaken in Australia into the lived experience of this group of people. It is this gap in the research that our study aimed to address. METHODS: Participants were recruited from the rheumatology clinics at Westmead and Blacktown Hospitals. Those eligible to participate were Pacific Islander and Maori patients with tophaceous gout currently living in the Western Sydney Local Health District (WSLHD). Data collection took the form of 10 semi-structured interviews, which were subsequently transcribed verbatim. A thematic analysis of the data was then performed. RESULTS: Thematic analysis identified 6 key themes: lack of understanding of the disease and its potential effects; missed opportunities for intervention and disjointed care; chronic reliance upon corticosteroids; trivialization of gout as a nuisance illness; the substantial financial impact of chronic illness; and the all-consuming nature of severe gout. CONCLUSION: The human cost of severe tophaceous gout in this cohort is immense. All 10 participants exemplified the disease's devastating social effects. We propose 4 key recommendations: improved education regarding diagnosis and management; immediate prescription of ULT at first presentation; a lower threshold for out-of-hospital rheumatologist referral; and improved follow-up through a nurse- and pharmacist-led collaborative gout management program.

Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients.

Endothelial dysfunction has been implicated in atherosclerosis, ischemic heart disease, and stroke. Endothelial progenitor cells (EPCs), found in the bone marrow and peripheral blood as rare cell population, demonstrated a high proliferation and differentiation capacity. Understanding how such diseases influence the quantity and functionality of EPCs is essential for the development of novel therapies. This study aims to investigate the factors that affect the quantity and functionality of circulating EPCs in stroke patients and healthy controls. Blood samples were collected once from healthy donors (n = 30) and up to 3 times (within 7 days (baseline), 3 and 12 months post-stroke) from stroke patients (n = 207). EPC subpopulations were isolated with flow cytometry for characterization. The Matrigel tubular formation assay was performed as a measure of functionality. An increased amount of circulating EPCs was observed in stroke patients over 45 years when compared to age-matched healthy individuals. EPCs showed a rising trend in stroke patients over the 12-month post-stroke period, reaching statistical significance at 12 months post-stroke. Isolated CD34+KDR+ cells from stroke patients showed impairment in tubular formation capability when compared to cells from healthy donors. The quantity and vasculogenic function of circulating EPCs in peripheral blood have been effectively evaluated in stroke patients and healthy control donors in this study. Age and stroke are found to be 2 influencing factors on the angiogenic capacity. It is suggested that the increase in EPC number is triggered by the recovery response following ischemic stroke. Graphical abstract.

Total Breastfeeding Duration and Household Food Insecurity in Healthy Urban Children.

OBJECTIVE: Health care policy positions breastfeeding as an important part of the solution to household food insecurity; however, there are critical gaps in our knowledge of the relationship between breastfeeding duration (exposure variable) and household food insecurity (outcome variable). Our objective was to examine this relationship. METHODS: A cross-sectional study was conducted from 2008 to 2016 of healthy urban children (N = 3838) who were 0 to 3 years old and recruited from The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Total breastfeeding duration was collected from parent-reported questionnaires. Household food insecurity was measured using 1-item and 2-item food insecurity screens. Multivariable regression analysis was performed adjusting for prespecified covariates. RESULTS: The median total breastfeeding duration was 10.5 months (interquartile range, 6.0-14.0), and 14.7% of households were food insecure. After adjusting for child characteristics (age, sex), maternal characteristics (age, ethnicity, education, employment), and family characteristics (number of children, single parent family, neighborhood equity score), there was no significant association between total breastfeeding duration and household food insecurity (odds ratio, 0.99; 95% confidence interval, 0.98-1.01). Although low-income families had an increased odds of being household food insecure (P ≤ .001), we found no significant association between total breastfeeding duration and household food insecurity at varying income levels. CONCLUSIONS: We found no association between breastfeeding duration and household food insecurity, regardless of family income. Although breastfeeding is associated with improved child health outcomes and considered to be part of the solution to household food insecurity, interventions focused on social determinants may provide more promising targets for the prevention of household food insecurity.

Perceptions of Doppler ultrasound for rheumatoid arthritis disease activity assessment and education.

AIM: The aim of this qualitative study was to report the findings of the Defining rheumatoid arthritis progression using Doppler Ultrasound in Clinical practice (DEDUCE) Medical Practice Activity, which was developed to facilitate the utilization of Doppler ultrasound (DUS) by Australian rheumatologists in the treatment of patients with rheumatoid arthritis (RA). METHOD: Twenty-one rheumatologists recruited a total of 80 patients with RA in Disease Activity Score of 28 joints (DAS28) remission for DUS assessment and completed a pre- and post-activity questionnaire assessing their experience with DUS, as well as a 6-month follow-up questionnaire. Rheumatologists discussed DUS results with patients using visual aids. Patients completed a pre- and post-DUS assessment questionnaire. Data were summarized using descriptive statistics. RESULTS: Following completion of the activity, 95% of rheumatologists (20/21) believed DUS was a useful assessment tool for patients with RA. The majority found the DUS results useful and more than half thought the DUS assessment fit well into their consultation. A majority of rheumatologists indicated they would use DUS imaging in patients with low disease activity and remission, and for disease activity assessment to inform in therapeutic decision-making. All patients who responded found the visual aids useful and most felt that discussing DUS results improved understanding of their disease and would help with medication adherence. CONCLUSION: Incorporation of DUS imaging into routine clinical practice is feasible, encourages rheumatologists to utilize and expand their clinical application of DUS imaging in patients with RA, and may improve patient understanding of their disease and adherence to medication.

Constrained Optimization Methods in Health Services Research-An Introduction: Report 1 of the ISPOR Optimization Methods Emerging Good Practices Task Force.

Providing health services with the greatest possible value to patients and society given the constraints imposed by patient characteristics, health care system characteristics, budgets, and so forth relies heavily on the design of structures and processes. Such problems are complex and require a rigorous and systematic approach to identify the best solution. Constrained optimization is a set of methods designed to identify efficiently and systematically the best solution (the optimal solution) to a problem characterized by a number of potential solutions in the presence of identified constraints. This report identifies 1) key concepts and the main steps in building an optimization model; 2) the types of problems for which optimal solutions can be determined in real-world health applications; and 3) the appropriate optimization methods for these problems. We first present a simple graphical model based on the treatment of "regular" and "severe" patients, which maximizes the overall health benefit subject to time and budget constraints. We then relate it back to how optimization is relevant in health services research for addressing present day challenges. We also explain how these mathematical optimization methods relate to simulation methods, to standard health economic analysis techniques, and to the emergent fields of analytics and machine learning.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

INTRODUCTION: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. METHODS AND ANALYSIS: This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. ETHICS AND DISSEMINATION: Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. TRIAL REGISTRATION NUMBER: ACTRN12614000418673, Pre-results.

Transforming Healthcare Delivery: Integrating Dynamic Simulation Modelling and Big Data in Health Economics and Outcomes Research.

In the era of the Information Age and personalized medicine, healthcare delivery systems need to be efficient and patient-centred. The health system must be responsive to individual patient choices and preferences about their care, while considering the system consequences. While dynamic simulation modelling (DSM) and big data share characteristics, they present distinct and complementary value in healthcare. Big data and DSM are synergistic-big data offer support to enhance the application of dynamic models, but DSM also can greatly enhance the value conferred by big data. Big data can inform patient-centred care with its high velocity, volume, and variety (the three Vs) over traditional data analytics; however, big data are not sufficient to extract meaningful insights to inform approaches to improve healthcare delivery. DSM can serve as a natural bridge between the wealth of evidence offered by big data and informed decision making as a means of faster, deeper, more consistent learning from that evidence. We discuss the synergies between big data and DSM, practical considerations and challenges, and how integrating big data and DSM can be useful to decision makers to address complex, systemic health economics and outcomes questions and to transform healthcare delivery.

Pilot study assessing the novel use of musculoskeletal ultrasound in patients with rheumatoid arthritis to improve patient attitudes and adherence to medication.

OBJECTIVE: To determine if showing patients with rheumatoid arthritis (RA) ultrasound (US) images of their inflamed joints: (i) increased belief in the necessity of medication; (ii) encouraged patient activation, that is, confidence and understanding in managing their health; and (iii) facilitated medication adherence. METHOD: Eighteen patients aged ≥ 18 years old with active RA (DAS28 [Disease Activity Score of 28 joints] > 2.6) requiring increased immunosuppression were included. The following questionnaires were administered at baseline (T1), 3 days post-US (T2) and 10 days post-US (T3): (i) Beliefs about Medicines Questionnaire (BMQ) to measure the cost-benefit analysis made by patients regarding the necessity versus concern of medication; (ii) Patient Activation Measure (PAM-13) to assess patient activation; (iii) Compliance Questionnaire-Rheumatology (CQR) to measure medication adherence; and (iv) Routine Assessment of Patient Index-3 (RAPID3) to assess physical function, pain and global status. US of ≥ 1 clinically affected joints was performed on one occasion with an explanation of findings. RESULTS: Patient cost-benefit decisions shifted positively following US, that is, favored belief in the necessity of medication with a mean ± SD cost-benefit ratio (possible range - 20 to + 20) at T1 of 1.17 ± 6.10 which increased to 2.54 ± 5.38 at T2 and 4.06 ± 5.76 at T3, P = 0.043 by analysis of variance (anova). PAM-13, CQR and RAPID3 scores remained stable (all P > 0.05 by anova). CONCLUSION: Showing patients with RA 'real-time' US images of clinically inflamed joints resulted in a more favorable cost-benefit analysis, that is, increased patient belief in the necessity of medication versus concern about taking medication. There was no change in patient activation, medication adherence or disease severity.

Applying dynamic simulation modeling methods in health care delivery research-the SIMULATE checklist: report of the ISPOR simulation modeling emerging good practices task force.

Health care delivery systems are inherently complex, consisting of multiple tiers of interdependent subsystems and processes that are adaptive to changes in the environment and behave in a nonlinear fashion. Traditional health technology assessment and modeling methods often neglect the wider health system impacts that can be critical for achieving desired health system goals and are often of limited usefulness when applied to complex health systems. Researchers and health care decision makers can either underestimate or fail to consider the interactions among the people, processes, technology, and facility designs. Health care delivery system interventions need to incorporate the dynamics and complexities of the health care system context in which the intervention is delivered. This report provides an overview of common dynamic simulation modeling methods and examples of health care system interventions in which such methods could be useful. Three dynamic simulation modeling methods are presented to evaluate system interventions for health care delivery: system dynamics, discrete event simulation, and agent-based modeling. In contrast to conventional evaluations, a dynamic systems approach incorporates the complexity of the system and anticipates the upstream and downstream consequences of changes in complex health care delivery systems. This report assists researchers and decision makers in deciding whether these simulation methods are appropriate to address specific health system problems through an eight-point checklist referred to as the SIMULATE (System, Interactions, Multilevel, Understanding, Loops, Agents, Time, Emergence) tool. It is a primer for researchers and decision makers working in health care delivery and implementation sciences who face complex challenges in delivering effective and efficient care that can be addressed with system interventions. On reviewing this report, the readers should be able to identify whether these simulation modeling methods are appropriate to answer the problem they are addressing and to recognize the differences of these methods from other modeling approaches used typically in health technology assessment applications.

How well do patients understand written instructions?: health literacy assessment in rural and urban rheumatology outpatients.

The aim of this study was to assess health literacy (word recognition and comprehension) in patients at a rural rheumatology practice and to compare this to health literacy levels in patients from an urban rheumatology practice.Inclusion criteria for this cross-sectional study were as follows: ≥18-year-old patients at a rural rheumatology practice (Mid-North Coast Arthritis Clinic, Coffs Harbour, Australia) and an urban Sydney rheumatology practice (Combined Rheumatology Practice, Kogarah, Australia). Exclusion criteria were as follows: ill-health precluding participation; poor vision/hearing, non-English primary language. Word recognition was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM). Comprehension was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Practical comprehension and numeracy were assessed by asking patients to follow prescribing instructions for 5 common rheumatology medications.At the rural practice (Mid-North Coast Arthritis Clinic), 124/160 patients agreed to participate (F:M 83:41, mean age 60.3 ±â€Š12.2) whereas the corresponding number at the urban practice (Combined Rheumatology Practice) was 99/119 (F:M 69:30, mean age 60.7 ±â€Š17.5). Urban patients were more likely to be born overseas, speak another language at home, and be employed. There was no difference in REALM or TOFHLA scores between the 2 sites, and so data were pooled. REALM scores indicated 15% (33/223) of patients had a reading level ≤Grade 8 whereas 8% (18/223) had marginal or inadequate functional health literacy as assessed by the TOFHLA. Dosing instructions for ibuprofen and methotrexate were incorrectly understood by 32% (72/223) and 21% (46/223) of patients, respectively.Up to 15% of rural and urban patients had low health literacy and <1/3 of patients incorrectly followed dosing instructions for common rheumatology drugs.There was no significant difference in word recognition, functional health literacy, and numeracy between rural and urban rheumatology patients.

NICE recommendations for the assessment of stable chest pain: assessing the early economic and service impact in the rapid-access chest pain service.

BACKGROUND: In 2010, guidelines published by the National Institute for Clinical Excellence (NICE) suggested a change in the way patients with stable chest pain of suspected cardiac origin were investigated. These guidelines removed exercise treadmill testing from routine use and introduced cardiac CT to regular use. OBJECTIVE: To investigate whether these guidelines had improved our service provision by reducing the number of further investigations required to make a diagnosis, and to see if our costs had increased now that the less expensive exercise treadmill tests were not recommended. METHODS: Clinic letters were used to assess patients pretest likelihood of coronary artery disease for two six-month cohorts of consecutive patients seen in the rapid access chest pain clinic (January-June 2010 and July-December 2011) using NICE published methodology, and to ascertain which investigations patients had. Using NICE modelled costs, we generated comparative hypothetical costs for each cohort and an average cost per patient. RESULTS: In the January-June 2010 cohort, 435 patients with chest pain were seen, and in July-December 2011, 334 patients were seen. In the pre-NICE guidelines cohort, 23% of patients required two investigations as compared with 11.4% in the post-NICE guidelines cohort, with no patient requiring three investigations as compared with 3% in the original cohort. There was no significant increase in costs per patient in the post-NICE guidance group. CONCLUSIONS: Implementing NICE guidance reduced the number of investigations needed per patient, and did not prove more expensive for our department in the short term.

pKa of acetate in water: a computational study.

Several computational methods including the conductor-like polarizable continuum model, CPCM with both UAKS and UAHF cavities, Cramer and Truhlar's generalized Born solvation model, SM5.4(AM1), SM5.4(PM3), and SM5.43R(mPW1PW91/6-31+G(d)), and mixed QM/MM-Ewald simulations were used to calculate the pK(a) values of acetate and bicarbonate anions in aqueous solution. This work provided a critical and comprehensive assessment of the quality of these theoretical models in the calculation of aqueous solvation free energies for the singly charged acetate and bicarbonate ions, as well as the doubly charged acetate dianion and carbonate dianion. It was shown that QM/MM-Ewald simulations could give an accurate and consistent evaluation of the pK(a) values of acetate and bicarbonate based on both the relative and absolute pK(a) formulas, while other methods could yield satisfactory results only for certain calculations. However, this does not mean that the current QM/MM-Ewald protocol is superior to other methods. The useful information obtained in this investigation is that both the absolute and relative pK(a) formulas should better be tested in accurate calculations of pK(a) values based on any methods.