The socio-technical organisation of community pharmacies as a factor in the Electronic Prescription Service Release Two implementation: a qualitative study

Background The introduction of a new method of transmitting prescriptions from general practices to community pharmacies in England (Electronic Prescription Service Release 2 (EPS2)) has generated debate on how it will change work practice. As EPS2 will be a key technical element in dispensing, we reviewed the literature to find that there were no studies on how social and technical elements come together to form work practice in community pharmacies. This means the debate has little point of reference. Our aim therefore was to study the ways social and technical elements of a community pharmacy are used to achieve dispensing through the development of a conceptual model on pharmacy work practice, and to consider how a core technical element such the EPS2 could change work practice. Method We used ethnographic methods inclusive of case-study observations and interviews to collect qualitative data from 15 community pharmacies that were in the process of adopting or were soon to adopt EPS2. We analysed the case studies thematically and used rigorous multi-dimensional and multi-disciplinary interpretive validation techniques to cross analyse findings. Results In practice, dispensing procedures were not designed to take into account variations in human and technical integration, and assumed that repetitive and collective use of socio-technical elements were at a constant. Variables such as availability of social and technical resources, and technical know-how of staff were not taken into account in formalised procedures. Yet community pharmacies were found to adapt their dispensing in relation to the balance of social and technical elements available, and how much of the social and technical elements they were willing to integrate into dispensing. While some integrated as few technical elements as possible, some depended entirely on technical artefacts. This pattern also applied to the social elements of dispensing. Through the conceptual model development process, we identified three approaches community pharmacies used to appropriate procedures in practice. These were ‘technically oriented’, ‘improvising’ or ‘socially oriented’. Conclusion We offer a model of different work approaches community pharmacies use to dispense, which suggests that when adopting a core technical element such as the EPS2 system of dispensing there could be variations in its successful adoption. Technically oriented pharmacies might find it easiest to integrate a similar artefact into work practice although needs EPS2 to synchronise effectively with existing technologies. Pharmacies adopting an improvising-approach have the potential to improve how they organise dispensing through EPS2 although they will need to improve how they apply their operating procedures. Socially oriented pharmacies will need to dramatically adapt their approach to dispensing since they usually rely on few technical tools

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial

Background: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials. Aims: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients. Methods and analysis: RAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR. Ethics and dissemination: The trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion. Trial registration number: NCT03707314; Pre-results

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Self-help interventions for depressive disorders and depressive symptoms: a systematic review

<p>Abstract</p> <p>Background</p> <p>Research suggests that depressive disorders exist on a continuum, with subthreshold symptoms causing considerable population burden and increasing individual risk of developing major depressive disorder. An alternative strategy to professional treatment of subthreshold depression is population promotion of effective self-help interventions that can be easily applied by an individual without professional guidance. The evidence for self-help interventions for depressive symptoms is reviewed in the present work, with the aim of identifying promising interventions that could inform future health promotion campaigns or stimulate further research.</p> <p>Methods</p> <p>A literature search for randomised controlled trials investigating self-help interventions for depressive disorders or depressive symptoms was performed using PubMed, PsycINFO and the Cochrane Database of Systematic Reviews. Reference lists and citations of included studies were also checked. Studies were grouped into those involving participants with depressive disorders or a high level of depressive symptoms, or non-clinically depressed participants not selected for depression. A number of exclusion criteria were applied, including trials with small sample sizes and where the intervention was adjunctive to antidepressants or psychotherapy.</p> <p>Results</p> <p>The majority of interventions searched had no relevant evidence to review. Of the 38 interventions reviewed, the ones with the best evidence of efficacy in depressive disorders were S-adenosylmethionine, St John's wort, bibliotherapy, computerised interventions, distraction, relaxation training, exercise, pleasant activities, sleep deprivation, and light therapy. A number of other interventions showed promise but had received less research attention. Research in non-clinical samples indicated immediate beneficial effects on depressed mood for distraction, exercise, humour, music, negative air ionisation, and singing; while potential for helpful longer-term effects was found for autogenic training, light therapy, omega 3 fatty acids, pets, and prayer. Many of the trials were poor quality and may not generalise to self-help without professional guidance.</p> <p>Conclusion</p> <p>A number of self-help interventions have promising evidence for reducing subthreshold depressive symptoms. Other forms of evidence such as expert consensus may be more appropriate for interventions that are not feasible to evaluate in randomised controlled trials. There needs to be evaluation of whether promotion to the public of effective self-help strategies for subthreshold depressive symptoms could delay or prevent onset of depressive illness, reduce functional impairment, and prevent progression to other undesirable outcomes such as harmful use of substances.</p

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management

Aims: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. Methods and results: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case–control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P &lt; 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P &lt; 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P &lt;0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0–30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age &lt;75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score &gt;4 were associated with larger infarcts [&gt;10% left ventricular (LV) mass]. Conclusion: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation