Inappropriate dosing of direct oral anticoagulants: findings from a clinical vignette study and physician survey.

Objective: Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods: DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers' dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results: In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years' experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions: Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial.

BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

Use of rapid cardiac magnetic resonance imaging to guide chelation therapy in patients with transfusion-dependent thalassaemia in India: UMIMI study.

AIMS: To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients. METHODS AND RESULTS: A prospective UK-India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P < 0.001) at follow-up. The baseline visit was attended by 103 patients (mean age 25 years) and 83% attended the second assessment. At baseline, 29% had a cardiac T2* < 20 ms, which represents significant iron loading, and 12% had left ventricular ejection fraction <60%, the accepted lower limit in this population. Only 3% were free of liver iron (T2* ≥ 17 ms). At 13 months, more patients were taking intensified dual chelation therapy (43% vs. 55%, P = 0.002). In those with cardiac siderosis (baseline T2* < 20 ms), there was an improvement in T2*-10.9 ± 5.9 to 13.5 ± 8.7 ms, P = 0.005-and fewer were classified as having clinically important cardiac iron loading (T2* < 20 ms, 24% vs. 16%, P < 0.001). This is the first illustration in an LMIC that incorporating CMR results into patient management plans can improve cardiac iron loading. CONCLUSION: For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

Physician-patient interactions and communication with conscious patients during simulated cath lab procedures: an exploratory study.

Background: This exploratory study investigates the feasibility for observing and evaluating intraoperative communication practices using simulation techniques. Complex procedures are increasingly performed on patients under local anaesthesia, where patients are fully conscious. Interventional cardiac procedures are one such example where patients have reported high levels of anxiety undergoing procedures. Although communication styles can serve to alleviate patient anxiety during interventions, leading to a better patient experience, there has been little observational research on communication, while patient perspectives in intraoperative contexts have been underexplored. Methods: In this mixed-methods study, observational analysis was conducted on 20 video-recorded simulated scenarios, featuring physician operators (of varied experience levels), communication and interactions with a simulated patient (trained actor), in a controlled and highly realistic catheter laboratory setting. Two independent raters and the simulated patient embedded in scenarios retrospectively rated physician communication styles and interactions with the patient via four key parameters. Patient perspectives of communication were further explored via a quantitative measure of anxiety and semistructured qualitative interviews. Results: While independent ratings of physician-patient communications demonstrated few discernible differences according to physicians' experience level, patient ratings were consistently higher for experienced physicians and lower for novice physicians for the four interaction styles. Furthermore, the patient's anxiety scores were differentiable according to operators' experience level. Thematic analysis provided further insights into how patient perspectives, including affective dimensions are characterised, and how physician interactions can amplify or attenuate feelings of anxiety through tone of voice, continuity in communication during the procedure, communicating while multitasking and connecting with the patient. Conclusions: Our findings indicate underlying patient assumptions about physicians' experience levels, intraoperative communication styles and impact on anxiety. While observational methods can be applied to simulated intraoperative clinical contexts, evaluation techniques such as observational rating tools need to incorporate patient perspectives about undergoing conscious surgery.

Overnight auto-adjusting continuous airway pressure + standard care compared with standard care alone in the prevention of morbidity in sickle cell disease phase II (POMS2b): study protocol for a randomised controlled trial.

BACKGROUND: In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life. METHODS/DESIGN: Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16-22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment. DISCUSSION: Altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events. TRIAL REGISTRATION: ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.

Sequential simulation used as a novel educational tool aimed at healthcare managers: a patient-centred approach.

Background: A new challenge for healthcare managers is to improve the patient experience. Simulation is often used for clinical assessment and rarely for those operating outside of direct clinical care. Sequential simulation (SqS) is a form of simulation that re-creates care pathways, widening its potential use. Local problem: Numbers, outcome measures and system profiling are used to inform healthcare decisions. However, none of these captures the personal subtleties of a patient's experience. Intervention: 56 students attended a teaching module using SqS and facilitated workshops as part of their induction week on an MSc International Health Management course. The workshop was voluntary and was offered as an opportunity for the students to gain an insight into the UK health system through the medium of simulation. Methods: An evaluation survey incorporating quantitative and qualitative student feedback was conducted. Descriptive statistics were generated from the quantitative data, and thematic analysis was undertaken for the qualitative data. Results: There was strong agreement for the acceptability of the workshop approach in relation to the aims and objectives. Likert scale (1--5) mean total=4.49. Participants responded enthusiastically (revealed through the qualitative data) with ideas related to perspectives sharing, understanding healthcare management and processes and the consideration of feasibility and practicalities. They also suggested other applications that SqS could be used for. Conclusion: The SqS approach has demonstrated that simulation has a wider potential than for clinical assessment alone. Further studies are required to determine its potential uses and affordances beyond its current format.

Distributed Simulation as a modelling tool for the development of a simulation-based training programme for cardiovascular specialties.

AIMS AND BACKGROUND: Distributed Simulation is the concept of portable, high-fidelity immersive simulation. Here, it is used for the development of a simulation-based training programme for cardiovascular specialities. We present an evidence base for how accessible, portable and self-contained simulated environments can be effectively utilised for the modelling, development and testing of a complex training framework and assessment methodology. Iterative user feedback through mixed-methods evaluation techniques resulted in the implementation of the training programme. APPROACH: Four phases were involved in the development of our immersive simulation-based training programme: (1) initial conceptual stage for mapping structural criteria and parameters of the simulation training framework and scenario development (n = 16), (2) training facility design using Distributed Simulation, (3) test cases with clinicians (n = 8) and collaborative design, where evaluation and user feedback involved a mixed-methods approach featuring (a) quantitative surveys to evaluate the realism and perceived educational relevance of the simulation format and framework for training and (b) qualitative semi-structured interviews to capture detailed feedback including changes and scope for development. Refinements were made iteratively to the simulation framework based on user feedback, resulting in (4) transition towards implementation of the simulation training framework, involving consistent quantitative evaluation techniques for clinicians (n = 62). For comparative purposes, clinicians' initial quantitative mean evaluation scores for realism of the simulation training framework, realism of the training facility and relevance for training (n = 8) are presented longitudinally, alongside feedback throughout the development stages from concept to delivery, including the implementation stage (n = 62). FINDINGS: Initially, mean evaluation scores fluctuated from low to average, rising incrementally. This corresponded with the qualitative component, which augmented the quantitative findings; trainees' user feedback was used to perform iterative refinements to the simulation design and components (collaborative design), resulting in higher mean evaluation scores leading up to the implementation phase. CONCLUSIONS: Through application of innovative Distributed Simulation techniques, collaborative design, and consistent evaluation techniques from conceptual, development, and implementation stages, fully immersive simulation techniques for cardiovascular specialities are achievable and have the potential to be implemented more broadly.

Magnetic Resonance-Augmented Cardiopulmonary Exercise Testing: Comprehensively Assessing Exercise Intolerance in Children With Cardiovascular Disease.

BACKGROUND: Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)-augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease. METHODS AND RESULTS: Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute; P=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute; P=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m2) and peak (5.3±1.2 L/min per m2) values compared with controls (resting 4.3±1.2 L/min per m2 and peak 6.6±1.2 L/min per m2) and PAH patients (resting 4.5±1.1 L/min per m2 and peak 5.9±1.1 L/min per m2). Both the PAH and tetralogy of Fallot patients had blunted exercise-induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL; P=0.005). CONCLUSIONS: MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference.

MR augmented cardiopulmonary exercise testing-a novel approach to assessing cardiovascular function.

The purposes of this study were: (1) to evaluate feasibility and acceptability of MRI augmented cardiopulmonary exercise testing (MR-CPET) in healthy adults and (2) to test whether peak values obtained at conventional and MR-CPET correlate and to demonstrate variation in peak oxygen consumption (VO2) relates to both peak cardiac output (CO) and peak oxygen extraction (ΔcO2). Seventeen healthy adults underwent CPET and MR-CPET using an MR compatible ergometer and CPET system customised for MR use. Continuous aortic flow measurement used a validated UNFOLD-SENSE spiral phase contrast magnetic resonance (PCMR) sequence.Fifteen of 17 volunteers completed exercise; exclusions were due to claustrophobia and inability to effectively master exercise technique. Measures of acceptability were lower but still satisfactory for MR-CPET.There were strong correlations between conventional and MR-CPET for peak VO2 (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001) and VE (r = 0.88, p < 0.001).Multiple linear regression analysis demonstrated peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (ß = 0.73 and 0.38 p < 0.0001) and conventional CPET (ß = 0.78, 0.28 p < 0.0001).MR-CPET is feasible, acceptable and demonstrates physiology not apparent with conventional CPET. MR-CPET allows differentiation of the contributions of CO and ΔcO2 to variation in peak VO2. We believe that this will be useful in understanding the origin of reduced exercise capacity in cardiac disease.

Safety and feasibility of intramyocardial versus intracoronary delivery of autologous cell therapy in advanced heart failure: the REGENERATE-IHD pilot study.

AIM: This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. METHODS & RESULTS: The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. CONCLUSION: Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.