Correlation between country-level numbers of COVID-19 cases and mortalities, and country-level characteristics: A global study.

Background: Not much is known about correlations between country-level characteristics and country-level numbers of COVID-19 cases and mortalities. Methods: Using data from the World Health Organization and other international organisations, we summarised country-level COVID-19 case and mortality counts per 100,000 population, and COVID-19 case fatality rate from January 2020 to August 2021. We conducted adjusted linear regression analysis to assess relationships between these counts/rate and certain country-level characteristics. We reported adjusted regression coefficients, ß and associated 95% confidence intervals. Results: There was a positive correlation between the number of cases and country-level male/female ratio, and positive correlations between the numbers of cases and mortalities and country-level proportion of 60+-year-olds, universal health coverage index of service coverage (UHC) and tourism. Country economic status correlated negatively with the numbers of cases and mortalities. COVID-19 case fatality rate was highest in Peru, South American region (9.2%), and lowest in Singapore, Western Pacific region (0.1%). A negative correlation was observed between case fatality rate and country-level male/female ratio, population density and economic status. These observations remained mostly among mid-/low-income countries, particularly a positive correlation between the number of cases and male/female ratio and proportion of 60+-year-olds. Conclusions: Various country-level characteristics such as male/female ratio, proportion of older adults, country economic status, UHC and tourism appear to be correlated with the country-level number of COVID-19 cases and/or mortalities. Consideration of these characteristics may be necessary when designing country-level COVID-19 epidemiological studies and in comparing COVID-19 data between countries.

Implementing High-Quality Primary Care Through a Health Equity Lens.

The COVID-19 pandemic highlighted the importance of centering health equity in future health system and primary care reforms. Strengthening primary care will be needed to correct the longstanding history of mistreatment of First Nations/Indigenous and racialized people, exclusion of health care workers of color, and health care access and outcome inequities further magnified by the COVID-19 pandemic. The National Academies of Sciences, Engineering, and Medicine (NASEM) released a report on Implementing High-Quality Primary Care: Rebuilding the Foundation of Health Care, that provided a framework for defining high-quality primary care and proposed 5 recommendations for implementing that definition. Using the report's framework, we identified health equity challenges and opportunities with examples from primary care systems in the United States and Canada. We are poised to reinvigorate primary care because the recent pandemic and the attention to continued racialized police violence sparked renewed conversations and collaborations around equity, diversity, inclusion, and health equity that have been long overdue. The time to transition those conversations to actionable items to improve the health of patients, families, and communities is now.Appeared as Annals "Online First" article.

Integration of geriatric assessment into clinical oncology practice: A scoping review.

Sixty percent of newly diagnosed cancers occur in older adults and more complex planning is required to sustain quality care for older populations. Individualized care incorporating geriatric assessment can predict early mortality and treatment toxicity for older cancer patients. We mapped and summarized the available evidence on the integration of geriatric assessment into clinical oncology practice, and ascertained which domains have been implemented. We systematically searched bibliographic databases and trial registries for reports of clinical studies, clinical practice guidelines, systematic and non-systematic reviews, and grey literature published in English. We gathered data on study characteristics, geriatric domains and strategies evaluated, and relevant study objectives and findings. From a total of 10,124 identified citations, 38 articles met our eligibility criteria, 3 of which were clinical practice guidelines. Nearly half of these articles came from the United States. Domains of the geriatric assessment implemented in studies ranged from 1 to 12, with varied combinations. We identified 27 studies on strategies for implementing geriatric assessment and 24 studies on feasibility of implementing geriatric assessment, into clinical oncology practice. We also identified 3 main geriatric assessment models: 2 from the United States and 1 from Australia. Furthermore, we identified 2 reviews that reported varied components of geriatric assessment models. There is increasingly robust evidence to implement formal geriatric assessment in oncology practice. There remains a great deal of variation in the tools recommended to address each of the domains in a geriatric assessment, with only 1 guideline (American Society of Clinical Oncology guideline) settling on a specific best practice. Protocol registration: Open Science Framework osf.io/mec93.

Disease-Associated Costs in Children With Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: As a chronic noncurable disorder often diagnosed in childhood or adolescence, inflammatory bowel disease (IBD) confers a significant financial lifetime burden. The objective of this systematic review was to determine the disease-associated costs (both direct and indirect) associated with IBD in children and young adults. METHODS: We conducted a systematic review of the literature and included any study reporting direct health services-related costs or the indirect economic burden of IBD in persons aged ≤19 years (PROSPERO protocol number CRD2016036128). A technical panel of experts in pediatric gastroenterology and research methodology formulated the review questions, reviewed the search strategies and review methods, and provided input throughout the review process. RESULTS: Nine studies met criteria for inclusion, 6 of which examined direct costs, 1 of which examined both direct and indirect costs, 1 of which assessed indirect costs, and 1 of which assessed out-of-pocket (OOP) costs. Inflammatory bowel disease-associated costs were significantly higher compared with costs in non-IBD populations, with wide variations in cost estimates, which prevented us from conducting a meta-analysis. Costs in Crohn's disease were higher than in ulcerative colitis. Overall, direct costs shifted from inpatient hospitalization as a major source of direct costs to medications, mainly driven by anti-tumor necrosis factor agents, as the leading cause of direct costs. Predictors of high costs included uncontrolled disease, corticosteroid treatment in the previous year, and comorbidity burden. CONCLUSIONS: The pediatric literature examining IBD-attributable costs is limited, with widely variable cost estimates. There is a significant knowledge gap in the research surrounding indirect costs and OOP expenses.

Directly Acting Oral Anticoagulants for the Prevention of Stroke in Atrial Fibrillation in England and Wales: Cost-Effectiveness Model and Value of Information Analysis.

Objectives. Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. Methods. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2-3) with directly acting (or non-vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation. In addition to death, the 17-state Markov model included the events stroke, bleed, myocardial infarction, and intracranial hemorrhage. Input parameters were informed by systematic literature reviews and network meta-analysis. Expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were estimated to provide an upper bound on value of further research. Results. At willingness-to-pay threshold £20,000, all DOACs have positive expected incremental net benefit compared to warfarin, suggesting they are likely cost-effective. Apixaban has highest expected incremental net benefit (£7533), followed by dabigatran (£6365), rivaroxaban (£5279), and edoxaban (£5212). There was considerable uncertainty as to the optimal DOAC, with the probability apixaban has highest net benefit only 60%. Total estimated population EVPI was £17.94 million (17.85 million, 18.03 million), with relative effect between apixaban versus dabigatran making the largest contribution with EVPPI of £7.95 million (7.66 million, 8.24 million). Conclusions. At willingness-to-pay threshold £20,000, all DOACs have higher expected net benefit than warfarin but there is considerable uncertainty between the DOACs. Apixaban had the highest expected net benefit and greatest probability of having highest net benefit, but there is considerable uncertainty between DOACs. A head-to-head apixaban versus dabigatran trial may be of value.

Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis.

Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registration PROSPERO CRD 42013005324.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. OBJECTIVES: To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model. DESIGN: Systematic review, meta-analysis and cost-effectiveness analysis. SETTING: Primary care. PARTICIPANTS: Adults. INTERVENTION: Screening strategies, defined by screening test, age at initial and final screens, screening interval and format of screening {systematic opportunistic screening [individuals offered screening if they consult with their general practitioner (GP)] or systematic population screening (when all eligible individuals are invited to screening)}. MAIN OUTCOME MEASURES: Sensitivity, specificity and diagnostic odds ratios; the odds ratio of detecting new AF cases compared with no screening; and the mean incremental net benefit compared with no screening. REVIEW METHODS: Two reviewers screened the search results, extracted data and assessed the risk of bias. A DTA meta-analysis was perfomed, and a decision tree and Markov model was used to evaluate the cost-effectiveness of the screening strategies. RESULTS: Diagnostic test accuracy depended on the screening test and how it was interpreted. In general, the screening tests identified in our review had high sensitivity (> 0.9). Systematic population and systematic opportunistic screening strategies were found to be similarly effective, with an estimated 170 individuals needed to be screened to detect one additional AF case compared with no screening. Systematic opportunistic screening was more likely to be cost-effective than systematic population screening, as long as the uptake of opportunistic screening observed in randomised controlled trials translates to practice. Modified blood pressure monitors, photoplethysmography or nurse pulse palpation were more likely to be cost-effective than other screening tests. A screening strategy with an initial screening age of 65 years and repeated screens every 5 years until age 80 years was likely to be cost-effective, provided that compliance with treatment does not decline with increasing age. CONCLUSIONS: A national screening programme for AF is likely to represent a cost-effective use of resources. Systematic opportunistic screening is more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations. LIMITATIONS: Many inputs for the economic model relied on a single trial [the Screening for Atrial Fibrillation in the Elderly (SAFE) study] and DTA results were based on a few studies at high risk of bias/of low applicability. FUTURE WORK: Comparative studies measuring long-term outcomes of screening strategies and DTA studies for new, emerging technologies and to replicate the results for photoplethysmography and GP interpretation of 12-lead electrocardiography in a screening population. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013739. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. OBJECTIVE: To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. DESIGN: Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. SETTING: Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). PARTICIPANTS: Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). INTERVENTIONS: NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. MAIN OUTCOME MEASURES: Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. DATA SOURCES: MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. REVIEW METHODS: Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. RESULTS: Apixaban (Eliquis®, Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana®, Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. CONCLUSIONS: NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. LIMITATIONS: These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. FUTURE WORK: Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. FUNDING: The National Institute for Health Research Health Technology Assessment programme.