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AnteayerBMJ Open

Investigating the ability to adhere to cardiometabolic medications with different properties: a retrospective cohort study of >500 000 patients in the USA

Por: Lauffenburger · J. C. · Tesfaye · H. · Solomon · D. H. · Antman · E. M. · Glynn · R. J. · Lee · S. B. · Tong · A. · Choudhry · N. K.
Objective

Poor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been evaluated objectively. We sought to determine the extent to which oral medication properties thought to be influential translate into lower objectively-measured adherence.

Design

Retrospective cohort study.

Setting

US nationwide commercial claims database, 2016–2019.

Participants

Among patients initiating first-line hypertension, diabetes or hyperlipidaemia treatment based on clinical guidelines, we measured pill size, shape, colour and flavouring, number of pills/day and fixed-dose combination status as properties.

Outcome measures

Outcomes included discontinuation after the first fill (ie, never filling again over a minimum of 1-year follow-up) and long-term non-adherence (1-year proportion of days covered

Results

Across 604 323 patients, 14.6% discontinued after filling once (ie, were non-persistent), and 54.0% were non-adherent over 1-year follow-up. Large pill size was associated with non-adherence, except for thiazides (eg, metformin adjusted OR (aOR): 1.12, 95% CI: 1.06 to 1.18). Greater pill burden was associated with a higher risk of non-adherence across all classes (eg, metformin aOR: 1.58, 95% CI: 1.53 to 1.64 for two pills/day). Taking less than one pill/day was also associated with higher risk of non-adherence and non-persistence (eg, non-persistence statin aOR: 1.29, 95% CI: 1.20 to 1.38). Pill shape, colour, flavouring and combination status were associated with mixed effects across classes.

Conclusions

Pill burden and pill size are key properties affecting adherence for almost all classes; others, like size and combination, could modestly affect medication adherence. Clinical interventions could screen patients for potential intolerance to medication and potentially implement more convenient dosing schedules.

Infographic summaries for clinical practice guidelines: results from user testing of the BMJ Rapid Recommendations in primary care

Por: Van Bostraeten · P. · Aertgeerts · B. · Bekkering · G. E. · Delvaux · N. · Dijckmans · C. · Ostyn · E. · Soontjens · W. · Matthysen · W. · Haers · A. · Vanheeswyck · M. · Vandekendelaere · A. · Van der Auwera · N. · Schenk · N. · Stahl-Timmins · W. · Agoritsas · T. · Vermandere · M.
Objectives

Infographics have the potential to enhance knowledge translation and implementation of clinical practice guidelines at the point of care. They can provide a synoptic view of recommendations, their rationale and supporting evidence. They should be understandable and easy to use. Little evaluation of these infographics regarding user experience has taken place. We explored general practitioners’ experiences with five selected BMJ Rapid Recommendation infographics suited for primary care.

Methods

An iterative, qualitative user testing design was applied on two consecutive groups of 10 general practitioners for five selected infographics. The physicians used the infographics before clinical encounters and we performed hybrid think-aloud interviews afterwards. 20 interviews were analysed using the Qualitative Analysis Guide of Leuven.

Results

Many clinicians reported that the infographics were simple and rewarding to use, time-efficient and easy to understand. They were perceived as innovative and their knowledge basis as trustworthy and supportive for decision-making. The interactive, expandable format was preferred over a static version as general practitioners focused mainly on the core message. Rapid access through the electronic health record was highly desirable. The main issues were about the use of complex scales and terminology. Understanding terminology related to evidence appraisal as well as the interpretation of statistics and unfamiliar scales remained difficult, despite the infographics.

Conclusions

General practitioners perceive infographics as useful tools for guideline translation and implementation in primary care. They offer information in an enjoyable and user friendly format and are used mainly for rapid, tailored and just in time information retrieval. We recommend future infographic producers to provide information as concise as possible, carefully define the core message and explore ways to enhance the understandability of statistics and difficult concepts related to evidence appraisal.

Trial registration number

MP011977.

What are effective vaccine distribution approaches for equity-deserving and high-risk populations during COVID-19? Exploring best practices and recommendations in Canada: protocol for a mixed-methods multiple case codesign study

Por: Aggarwal · M. · Katz · A. · Kokorelias · K. M. · Wong · S. T. · Aghajafari · F. · Ivers · N. M. · Martin-Misener · R. · Aubrey-Bassler · K. · Breton · M. · Upshur · R. E. G. · Kwong · J. C.
Introduction

The WHO has stated that vaccine hesitancy is a serious threat to overcoming COVID-19. Vaccine hesitancy among underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution. In Canada, governments of each province or territory manage their own healthcare system, providing an opportunity to compare and contrast distribution strategies. The overarching objective of this study is to identify effective vaccine distribution approaches and advance knowledge on how to design and implement various strategies to meet the different needs of underserved communities.

Methods and analysis

Multiple case studies in seven Canadian provinces will be conducted using a mixed-methods design. The study will be informed by Experience-Based CoDesign techniques and theoretically guided by the Socio-Ecological Model and the Vaccine Hesitancy Matrix frameworks. Phase 1 will involve a policy document review to systematically explore the vaccine distribution strategy over time in each jurisdiction. This will inform the second phase, which will involve (2a) semistructured, in-depth interviews with policymakers, public health officials, researchers, providers, groups representing patients, researchers and stakeholders and (2b) an analysis of population-based administrative health data of vaccine administration. Integration of qualitative and quantitative data will inform the identification of effective vaccine distribution approaches for various populations. Informed by this evidence, phase 3 of the study will involve conducting focus groups with multiple stakeholders to codesign recommendations for the design and implementation of effective vaccine delivery strategies for equity-deserving and at-risk populations.

Ethics and dissemination

This study is approved by the University of Toronto’s Health Sciences Research Ethics Board (#42643), University of British Columbia Behavioural Research Ethics Board (#H22-01750-A002), Research Ethics Board of the Nova Scotia Health Authority (#48272), Newfoundland and Labrador Health Research Ethics Board (#2022.126), Conjoint Health Research Ethics Board, University of Calgary (REB22-0207), and University of Manitoba Health Research Board (H2022-239). The outcome of this study will be to produce a series of recommendations for implementing future vaccine distribution approaches from the perspective of various stakeholders, including equity-deserving and at-risk populations.

Promoting REproductive Planning And REadiness in Diabetes (PREPARED) Study protocol: a clinic-randomised controlled trial testing a technology-based strategy to promote preconception care for women with type 2 diabetes

Por: Bailey · S. C. · Pack · A. P. · Wismer · G. · Calderon · N. · Velazquez · E. · Batio · S. · Ekong · A. · Eggleston · A. · Wallia · A. · Wolf · M. S. · Schauer · J. M. · Tenfelde · S. · Liebovitz · D. M. · Grobman · W. A.
Introduction

Women with type 2 diabetes (T2DM) are more likely to experience adverse reproductive outcomes, yet preconception care can significantly reduce these risks. For women with T2DM, preconception care includes reproductive planning and patient education on: (1) the importance of achieving glycaemic control before pregnancy, (2) using effective contraception until pregnancy is desired, (3) discontinuing teratogenic medications if pregnancy could occur, (4) taking folic acid, and (5) managing cardiovascular and other risks. Despite its importance, few women with T2DM receive recommended preconception care.

Methods and analysis

We are conducting a two-arm, clinic-randomised trial at 51 primary care practices in Chicago, Illinois to evaluate a technology-based strategy to ‘hardwire’ preconception care for women of reproductive age with T2DM (the PREPARED (Promoting REproductive Planning And REadiness in Diabetes) strategy) versus usual care. PREPARED leverages electronic health record (EHR) technology before and during primary care visits to: (1) promote medication safety, (2) prompt preconception counselling and reproductive planning, and (3) deliver patient-friendly educational tools to reinforce counselling. Post-visit, text messaging is used to: (4) encourage healthy lifestyle behaviours. English and Spanish-speaking women, aged 18–44 years, with T2DM will be enrolled (N=840; n=420 per arm) and will receive either PREPARED or usual care based on their clinic’s assignment. Data will be collected from patient interviews and the EHR. Outcomes include haemoglobin A1c (primary), reproductive knowledge and self-management behaviours. We will use generalised linear mixed-effects models (GLMMs) to evaluate the impact of PREPARED on these outcomes. GLMMs will include a fixed effect for treatment assignment (PREPARED vs usual care) and random clinic effects.

Ethics and dissemination

This study was approved by the Northwestern University Institutional Review Board (STU00214604). Study results will be published in journals with summaries shared online and with participants upon request.

Trial registration number

ClinicalTrials.gov Registry (NCT04976881).

Systematic review of seroprevalence of SARS-CoV-2 antibodies and appraisal of evidence, prior to the widespread introduction of vaccine programmes in the WHO European Region, January-December 2020

Por: Vaughan · A. · Duffell · E. · Freidl · G. S. · Lemos · D. S. · Nardone · A. · Valenciano · M. · Subissi · L. · Bergeri · I. · K Broberg · E. · Penttinen · P. · Pebody · R. · Keramarou · M.
Objectives

Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.

Design

A systematic review of the literature.

Data sources

We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO ‘COVID-19 Global literature on coronavirus disease’ database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control.

Eligibility criteria

Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels.

Data extraction and synthesis

At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies.

Results

In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7–5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%–12%); n=101), with the highest estimates in areas following widespread local transmission.

Conclusions

The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study

Por: Joeris · A. · Sprague · S. · Blauth · M. · Gosch · M. · Wattanapanom · P. · Jarayabhand · R. · Poeze · M. · Wong · M. K. · Kwek · E. B. K. · Hegeman · J. H. · Perez-Uribarri · C. · Guerado · E. · Revak · T. J. · Zohner · S. · Joseph · D. · Phillips · M. R.
Introduction

Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres.

Methods

The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore.

Results

GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (–$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (–$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year).

Conclusions

This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings.

Level of evidence

Economic, level 2.

Trial registration number

NCT02297581.

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case-control study

Por: Helin · T. A. · Raatikainen · P. · Lehto · M. · Haukka · J. · Lassila · R.
Objectives

We studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin.

Design

This was a retrospective nested case–control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up.

Setting

National FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007–31 December 2011.

Participants

A total of 54 568 warfarin-anticoagulated patients.

Results

The number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111–141 g/L vs 123–147 g/L, p

Conclusions

The deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.

Cohort profile: recruitment and retention in a prospective cohort of Canadian healthcare workers during the COVID-19 pandemic

Por: Cherry · N. · Adisesh · A. · Burstyn · I. · Durand-Moreau · Q. · Galarneau · J.-M. · Labreche · F. · Ruzycki · S. M. · Zadunayski · T.
Purpose

Healthcare workers were recruited early in 2020 to chart effects on their health as the COVID-19 pandemic evolved. The aim was to identify modifiable workplace risk factors for infection and mental ill health.

Participants

Participants were recruited from four Canadian provinces, physicians (medical doctors, MDs) in Alberta, British Columbia, Ontario and Quebec, registered nurses (RNs), licensed practical nurses (LPNs) and healthcare aides (HCAs) in Alberta and personal support workers (PSWs) in Ontario. Volunteers gave blood for serology testing before and after vaccination. Cases with COVID-19 were matched with up to four referents in a nested case-referent study.

Findings to date

Overall, 4964/5130 (97%) of those recruited joined the longitudinal cohort: 1442 MDs, 3136 RNs, 71 LPNs, 235 PSWs, 80 HCAs. Overall, 3812 (77%) were from Alberta. Prepandemic risk factors for mental ill health and respiratory illness differed markedly by occupation. Participants completed questionnaires at recruitment, fall 2020, spring 2021, spring 2022. By 2022, 4837 remained in the cohort (127 had retired, moved away or died), for a response rate of 89% (4299/4837). 4567/4964 (92%) received at least one vaccine shot: 2752/4567 (60%) gave postvaccine blood samples. Ease of accessing blood collection sites was a strong determinant of participation. Among 533 cases and 1697 referents recruited to the nested case-referent study, risk of infection at work decreased with widespread vaccination.

Future plans

Serology results (concentration of IgG) together with demographic data will be entered into the publicly accessible database compiled by the Canadian Immunology Task Force. Linkage with provincial administrative health databases will permit case validation, investigation of longer-term sequelae of infection and comparison with community controls. Analysis of the existing dataset will concentrate on effects on IgG of medical condition, medications and stage of pregnancy, and the role of occupational exposures and supports on mental health during the pandemic.

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