Bleeding risk in patients prescribed dual antiplatelet therapy and triple therapy after coronary interventions: the ADAPTT retrospective population-based cohort studies.

Background: Bleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified. Objectives: The objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy. Design: The study was designed as three retrospective population-based cohort studies emulating target randomised controlled trials. Setting: The study was set in primary and secondary care in England from 2010 to 2017. Participants: Participants were patients aged ≥ 18 years undergoing coronary artery bypass grafting or emergency percutaneous coronary intervention (for acute coronary syndrome), or conservatively managed patients with acute coronary syndrome. Data sources: Data were sourced from linked Clinical Practice Research Datalink and Hospital Episode Statistics. Interventions: Coronary artery bypass grafting and conservatively managed acute coronary syndrome: aspirin (reference) compared with aspirin and clopidogrel. Percutaneous coronary intervention: aspirin and clopidogrel (reference) compared with aspirin and prasugrel (ST elevation myocardial infarction only) or aspirin and ticagrelor. Main outcome measures: Primary outcome: any bleeding events up to 12 months after the index event. Secondary outcomes: major or minor bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular events. Results: The incidence of any bleeding was 5% among coronary artery bypass graft patients, 10% among conservatively managed acute coronary syndrome patients and 9% among emergency percutaneous coronary intervention patients, compared with 18% among patients prescribed triple therapy. Among coronary artery bypass grafting and conservatively managed acute coronary syndrome patients, dual antiplatelet therapy, compared with aspirin, increased the hazards of any bleeding (coronary artery bypass grafting: hazard ratio 1.43, 95% confidence interval 1.21 to 1.69; conservatively-managed acute coronary syndrome: hazard ratio 1.72, 95% confidence interval 1.15 to 2.57) and major adverse cardiovascular events (coronary artery bypass grafting: hazard ratio 2.06, 95% confidence interval 1.23 to 3.46; conservatively-managed acute coronary syndrome: hazard ratio 1.57, 95% confidence interval 1.38 to 1.78). Among emergency percutaneous coronary intervention patients, dual antiplatelet therapy with ticagrelor, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.06, 95% confidence interval 0.89 to 1.27). Among ST elevation myocardial infarction percutaneous coronary intervention patients, dual antiplatelet therapy with prasugrel, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.48, 95% confidence interval 1.02 to 2.12), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.10, 95% confidence interval 0.80 to 1.51). Health-care costs in the first year did not differ between dual antiplatelet therapy with clopidogrel and aspirin monotherapy among either coronary artery bypass grafting patients (mean difference £94, 95% confidence interval -£155 to £763) or conservatively managed acute coronary syndrome patients (mean difference £610, 95% confidence interval -£626 to £1516), but among emergency percutaneous coronary intervention patients were higher for those receiving dual antiplatelet therapy with ticagrelor than for those receiving dual antiplatelet therapy with clopidogrel, although for only patients on concurrent proton pump inhibitors (mean difference £1145, 95% confidence interval £269 to £2195). Conclusions: This study suggests that more potent dual antiplatelet therapy may increase the risk of bleeding without reducing the incidence of major adverse cardiovascular events. These results should be carefully considered by clinicians and decision-makers alongside randomised controlled trial evidence when making recommendations about dual antiplatelet therapy. Limitations: The estimates for bleeding and major adverse cardiovascular events may be biased from unmeasured confounding and the exclusion of an eligible subgroup of patients who could not be assigned an intervention. Because of these limitations, a formal cost-effectiveness analysis could not be conducted. Future work: Future work should explore the feasibility of using other UK data sets of routinely collected data, less susceptible to bias, to estimate the benefit and harm of antiplatelet interventions. Trial registration: This trial is registered as ISRCTN76607611. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 8. See the NIHR Journals Library website for further project information.

People who have a heart attack are treated with a stent to open up the blocked artery that caused the heart attack, with surgery to bypass the blocked artery or with medication only. Whatever the treatment, they are prescribed one or more antiplatelet drugs, either aspirin only or aspirin and an additional antiplatelet (clopidogrel, prasugrel or ticagrelor), for 12 months after the heart attack. Antiplatelets are given to prevent another heart attack, but increase the risk of bleeding. We used a large general practice database and a database describing patients' attendances and admissions to hospital to determine how many people bleed with different antiplatelet combinations. We found that, overall, up to 1 in 10 people taking antiplatelets (rising to 2 in 10 if also taking an anticoagulant such as warfarin or dabigatran) reported a bleed. Among patients treated with surgery or medication only, we compared aspirin only (which is a less potent therapy) with aspirin and clopidogrel (a more potent therapy). Among patients treated with stents, we compared aspirin and clopidogrel (less potent therapy) with aspirin and prasugrel or ticagrelor (more potent therapy). In all three populations, the more potent therapy increased the risk of bleeding by about one and a half times, but this was not offset by a reduced risk of having a subsequent heart attack. This may be explained by low adherence to the medication: between one-third and almost half of all patients did not adhere to their regimen, and non-adherence was generally higher among patients taking a more potent therapy. It may also be explained by bias inherent in the study, for example if the groups prescribed different antiplatelet regimens had different risks of having another heart attack. Nevertheless, the results show that doctors should be cautious about prescribing more potent antiplatelet therapy because it may increase serious bleeds without necessarily reducing the number of heart attacks.

The experience of conducting collaborative and intensive pragmatic qualitative (CLIP-Q) research to support rapid public health and healthcare innovation.

A key challenge for qualitative methods in applied health research is the fast pace that can characterize the public health and health and care service landscape, where there is a need for research informed by immediate pragmatic questions and relevant findings are required quickly to inform decision-making. The COVID-19 pandemic accelerated the pace at which evidence was needed to inform urgent public health and healthcare decision-making. This required qualitative researchers to step up to the challenge of conducting research at speed whilst maintaining rigor and ensuring the findings are credible. This article illustrates how working with multidisciplinary, collaborative teams and the tailoring of qualitative methods to be more pragmatic and efficient can provide timely and credible results. Using time-limited case studies of applied qualitative health research drawn from the work of the Behavioral and Qualitative Science Team from the National Institute for Health and Care Research Applied Research Collaboration West (NIHR ARC West), we illustrate our collaborative and intensive pragmatic qualitative (CLIP-Q) approach. CLIP-Q involves (i) collaboration at all stages of the design, conduct and implementation of projects and, where possible, co-production with people with lived experience, (ii) an intensive team-based approach to data collection and analysis at pace, and (iii) pragmatic study design and efficient strategies at each stage of the research process. The case studies include projects conducted pre COVID-19 and during the first wave of the pandemic, where urgent evidence was required in weeks rather than months to inform rapid public health and healthcare decision making.

Confounders and co-interventions identified in non-randomized studies of interventions.

OBJECTIVES: To identify potential confounders and co-interventions systematically to optimise control of confounding for three non-randomized studies of interventions (NRSI) designed to quantify bleeding in populations exposed to different dual antiplatelet therapy (DAPT). STUDY DESIGN AND SETTING: Systematic review, interviews, and surveys with clinicians. We searched Ovid Medline, Ovid Embase, and the Cochrane Library to identify randomized-controlled trials and cohort studies of DAPT interventions. Two researchers independently screened citations, identified eligible studies and extracted data. We conducted individual semi-structured interviews with six cardiologists and six cardiac surgeons to elicit factors clinicians consider when they prescribe DAPT. We administered two online surveys for members of professional cardiology and cardiac surgery organisations. RESULTS: We screened 2,544 records, identified 322 eligible studies, and extracted data from 47. We identified 10 co-interventions and 70 potential confounders: review 31 (91%); interviews 19 (56%); surveys 31 (91%). 16/34 (47%) were identified by all three methods while, 3/34 (9%) were picked up by one method only. CONCLUSION: The review identified the majority of factors, but the interviews identified hard-to-measure factors such as perceived patient adherence and local prescribing culture. The methods could, in principle, be widely applied when designing or reviewing non-randomized studies of interventions (NRSI).

Patient perspectives of nuisance bleeding and adherence to dual antiplatelet therapy: a qualitative study.

OBJECTIVE: To understand the experiences of patients with dual antiplatelet therapy (DAPT) and nuisance bleeding, and their perspectives of the impact of nuisance bleeding on medication adherence and information seeking. METHODS: We conducted focus groups with patients who had undergone percutaneous coronary intervention, coronary artery bypass graft and conservatively managed acute coronary syndrome patients. Two focus groups were with patients at the early stages of treatment (0-3 months), and two with patients coming to the end of treatment (9-12 months). Group discussions were audio recorded, and recordings were transcribed verbatim, anonymised and analysed using framework analysis. FINDINGS: Nine patients taking DAPT for up to 3 months, and 12 taking DAPT between 9 and 12 months participated in the focus groups. We found that: (1) participants adhered to treatment when they believed DAPT was important to health outcomes; (2) those who experienced nuisance bleeding reported symptoms to be mild and manageable; (3) participants' and their family's understanding of DAPT risks and benefits, and their ability to manage symptoms, influenced perspectives of and experiences with adherence. Factors influencing DAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from hospital. CONCLUSIONS: Positive attitudes towards adherence were facilitated by knowledge and understanding of DAPT and confidence in dealing with symptoms caused by DAPT, but hindered by lack of opportunities to access relevant, timely and appropriate medication counselling. Education interventions should aim to support medication literacy through family-centred approaches and involve patients and families at all stages of intervention design and evaluation.

Implementing a Digital Tool to Support Shared Care Planning in Community-Based Mental Health Services: Qualitative Evaluation.

BACKGROUND: Mental health services aim to provide recovery-focused care and facilitate coproduced care planning. In practice, mental health providers can find supporting individualized coproduced care with service users difficult while balancing administrative and performance demands. To help meet this aim and using principles of coproduction, an innovative mobile digital care pathway tool (CPT) was developed to be used on a tablet computer and piloted in the West of England. OBJECTIVE: The aim of this study was to examine mental health care providers' views of and experiences with the CPT during the pilot implementation phase and identify factors influencing its implementation. METHODS: A total of 20 in-depth telephone interviews were conducted with providers participating in the pilot and managers in the host organization. Interviews were audio recorded, transcribed, anonymized, and thematically analyzed guided by the Consolidated Framework for Implementation Research. RESULTS: The tool was thought to facilitate coproduced recovery-focused care planning, a policy and organizational as well as professional priority. Internet connectivity issues, system interoperability, and access to service users' health records affected use of the tool during mobile working. The organization's resources, such as information technology (IT) infrastructure and staff time and IT culture, influenced implementation. Participants' levels of use of the tool were dependent on knowledge of the tool and self-efficacy; perceived service-user needs and characteristics; and perceptions of impact on the therapeutic relationship. Training and preparation time influenced participants' confidence in using the tool. CONCLUSIONS: Findings highlight the importance of congruence between staff, organization, and external policy priorities and digital technologies in aiding intervention engagement, and the need for ongoing training and support of those intended to use the technology during and after the end of implementation interventions.

Re-thinking health literacy: using a capabilities approach perspective towards realising social justice goals.

Health literacy has gained popularity as a useful concept to promote and protect health. Even though health literacy research has been prolific it has also been fragmented, facing challenges in achieving its empowerment and social justice-related aims. Crucial limitations make the application of its principles to the health of vulnerable and underrepresented groups problematic, even though these groups are disproportionately affected by ill health. Efforts to refine and make the concept more relevant have tended to expand health literacy models and situate health literacy 'in context' to reflect environmental and social factors shaping health literacy. Context-related factors however, have not been consistently embedded in operationalisation and measurement efforts.This paper argues for health literacy to be re-conceptualised through a capabilities approach lens. It proposes that the capabilities approach can uniquely address the conceptual and methodological criticisms applied to health literacy, whilst encompassing its critical conceptual understandings of health. The advantage of this approach over and above other developments in health literacy theory and practice is its focus on both people's opportunities or freedoms to achieve desired health-related aims, and their ability to do so. It enables shifting the focus away from health literacy as individual skills and competencies and towards the enabling or inhibiting factors shaping health literacy. A participatory approach is seen as essential for realising this conceptual shift.

Pilot implementation of co-designed software for co-production in mental health care planning: a qualitative evaluation of staff perspectives.

Background: Mental health policies advocate service user participation in care planning. However, service users often feel they're not fully involved and direct access to users' own electronic care plans in the community can be an obstacle. To address this, an electronic care pathway tool (CPT) was co-designed by service users, staff and software developers, to facilitate co-production of care and crisis plans. Aims: To investigate the feasibility and acceptability of the pilot implementation of the CPT in professionals' practice to co-produce care plans and enable efficient working. Method: Qualitative interviews with fifteen mental health practitioners, and five service development/management staff. Normalisation process theory, which outlines the social processes involved in implementing technology, and co-production theory, informed interviews and data analysis. Results: Multiple factors influenced CPT usage, including people's views of technology, practitioners' relationships with service users, service users' mental health needs, and their capacity for reflective thinking. The CPT's visual and interactive features could enable co-production of care plans. The CPT supported practitioners' efficiency, but its features did not easily streamline with electronic patient records. Conclusions: CPT interactive touchpoints supported service users' therapeutic reflection and facilitated care planning involvement. Information technology system interoperability was an obstacle.

Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT) in the UK: study protocol for three population-based cohort studies emulating 'target trials' (the ADAPTT Study).

INTRODUCTION: 'Real world' bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified. METHODS AND ANALYSIS: We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three 'target trials' in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study's main limitation-that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD. ETHICS AND DISSEMINATION: This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders. TRIAL REGISTRATION NUMBER: 76607611; Pre-results.

A systematic review of training interventions addressing sexual violence against marginalized at-risk groups of women.

Women from marginalized groups working in occupations such as domestic work are at increased risk for sexual violence. Scarce evidence exists about training interventions targeting such groups. The article aims to identify community and workplace-based training interventions aiming to increase capacity among marginalized at-risk women to deal with sexual violence. A systematic review was applied. Inclusion criteria were English language published between 2003 and 2013; reporting on delivery and/or evaluation; focusing on any form of sexual violence; delivered to professionals, affected or at-risk women; targeting migrant, at-risk women or domestic workers. Data were extracted on the setting, content, evaluation process and target population. Four studies which focused on prevention or responding to sexual violence were included. One study provided sexual violence training to vulnerable female and one provided a HIV prevention intervention to marginalized women. Learning objectives included increasing knowledge around issues of sexual violence and/or gender and human rights, prevention and response strategies. Two studies aimed to train trainers. All studies conducted an outcome evaluation and two a process evaluation. It seems there is a gap on participatory empowerment training for marginalized women. Community train-the-trainer interventions are imperative to protect themselves and deal with the risk of sexual violence.

Identifying outcomes of clinical genetic services: qualitative evidence and methodological considerations.

Extensive research into the tangible and intangible implications of Clinical Genetic Services (CGSs) has confirmed the relevance of a multidimensional outcome of benefit conceptually linked to perceived control. This paper aims to report qualitative findings from one small study aiming to add to the evidence pool confirming the relevance of such an outcome to participants from one UK clinical genetics center. Data were collected using focus groups and individual interviews with 22 service users from the following conditions: Hereditary Breast and Ovarian Cancer (HBOC), von Hippel Lindau disorder (VHL), Duchenne and Becker muscular dystrophy (DBMD), cystic fibrosis (CF) and tuberous sclerosis (TS). Transcripts were analyzed using thematic analysis and four dimensions of benefit were identified relating to cognitive, behavioral, social and emotional consequences. These dimensions related to an overarching conceptual outcome described as Perceived Familial Control. Findings are discussed to illustrate the inter-generational and intra-generational familial dimensions of CGSs and reinforce the significance of a familial focus to any genetics-specific outcome measure. The prospect and methodological considerations of a familial composite outcome measure for measuring overall benefit of CGSs is discussed based on current and past findings.