The Application of Serial Electrophysiological Testing in the Management of Patients With Ventricular Arrhythmias

The lethal potential of ventricular tachyarrhythmias is well recognised and because of the ineffectiveness of empirically prescribed therapy a directed approach to the treatment of these arrhythmias is mandated. The aim of the studies in this thesis was to further define the applicability of serial electrophysiological testing for the determination of effective antiarrhythmic therapy in patients with these arrhythmias. In Chapter 1, the potential mechanisms for the development of ventricular tachyarrhythmias and their relation to the use of programmed stimulation are discussed. The prognostic impact of ventricular arrhythmias is reviewed. The therapeutic options are described and the classification of antiarrhythmic drugs is explained. The different management strategies for the prescription of antiarrhythmic therapy are discussed. The historical development and rationale for electrophysiological testing is described. The methodology and equipment required for this approach is described in Chapter 2. In particular, the stimulation protocol employed in all studies in this thesis is explained. The induction of ventricular tachyarrhythmia in response to the stimulation protocol is dealt with in Chapter 3. The varying impact of different factors including the type of underlying heart disease in the patient population being studied and the different components of the stimulation protocol are described. The comparability of the results with those reported from other laboratories confirms the utility of the stimulation protocol. The controversial aspect of sensitivity, specificity and reproducibility of programmed stimulation is discussed. In Chapter 4, the techniques for tachycardia termination and the effectiveness of pacing modalities are described. The effect of cycle length and antiarrhythmic therapy on pacing termination are discussed. The concordance between the response to electrophysio-logical testing with both intravenous and oral formulations of procainamide is dealt with in Chapter 5. The advantages of testing intravenous therapy were offset by the observation that non indueibility with intravenous procainamide was not predictive of noninducibility with oral procainamide. The results from this study confirm that retesting on oral therapy is required even if the intravenous agent is shown to be effective. The use of serial electrophysiological drug testing to identify effective therapy in patients with ventricular tachyarrhythmias related to coronary artery disease is described in Chapter 6. Overall drug efficacy, efficacy of individual regimens and the effect of the type of induced arrhythmia on drug response are detailed. The long-term effectiveness of antiarrhythmic regimens identified as successful by electrophysiological testing is confirmed using both the accepted stimulation end-point of noninducibility and the more relaxed end-point of 15 or less repetitive responses. In Chapter 7, similar results confirming the predictive value of serial drug testing were obtained for patients with ventricular tachyarrhythmias related to cardiomyopathy. The effect of the combination of amiodarone plus the Type 1 agent procainamide on arrhythmia inducibility is discussed in Chapter 8. The main benefit of the addition of procainamide was on the haemodynamic impact of the induced arrhythmia which may provide a degree of protection from sudden death. Using multivariate statistical techniques the determinants of the response to serial electrophysiological drug testing were analysed in Chapter 9. Patients with poor left ventricular function were less likely to respond to medical therapy, and suppression of arrhythmia induction was more difficult in patients with induced sustained ventricular tachycardia than in patients with either ventricular fibrillation or nonsustained ventricular tachycardia. During follow up, if recurrence of arrhythmia occurred, it was more likely to be as sudden death if the patients had cardiac failure, and the induced arrhythmia in the discharge drug study was not symptomatically tolerated. The major independent variable which predicted recurrence of arrhythmia during follow-up was failure of serial electrophysiological drug testing to identify a successful therapy. In Chapter 10, the predictive value of the response to procainamide is discussed. Failure of procainamide to suppress arrhythmia inducibility predicts failure of other agents in patients with induced sustained ventricular tachycardia but not in patients with either ventricular fibrillation or nonsustained ventricular tachycardia. The implications of these observations in the evaluation of antiarrhythmic drug efficacy are discussed. In Chapter 11, the use of programmed stimulation to reveal the potential for drug related worsening of arrhythmias is described. The different proarrhythmic responses and their potential clinical value are discussed and the lack of predictability of these responses is investigated. Important unresolved problems in the clinical application of electrophysiological testing for the management of patients with ventricular tachyarrhythmias are discussed in Chapter 12

Improving Effective Interdisciplinary Team Work Using Team-Based Learning within the NH-ME LEND Curriculum: Comparing Years 1 – 3

This poster provided an update on an ongoing effort by faculty in the New Hampshire-Maine Leadership Education in Neurodevelopmental and Related Disabilities (NH-ME LEND) Program to implement Team-Based Learning (TBL). Three years of evaluation data was presented. Changes made to improve the process were identified as well as some of the unique obstacles to implementing TBL in a seminar that was conducted in two classrooms connected through video conferencing and had a high faculty-to-student ratio.https://digitalcommons.library.umaine.edu/ccids_posters/1008/thumbnail.jp

Engaging LEND Trainees in a Leadership and Policy Experience

This poster illustrated how faculty from the New Hampshire-Maine Leadership Education in Neurodevelopmental and Related Disabilities (NH-ME LEND) Program re-envisioned and implemented a comprehensive set of leadership, policy and advocacy experiences to further build upon the leadership potential of 23 LEND trainees by intentionally threading leadership skill development throughout the LEND curriculum.https://digitalcommons.library.umaine.edu/ccids_posters/1010/thumbnail.jp

Coaching LEND Faculty in Implementing Team-Based Learning Across Two States: Lessons Learned over Four Years

This poster describes the implementation of team-based learning (TBL) in the didactic seminar component of the NH-ME LEND program over four years. TBL has been found to be an effective instructional method, fostering communication, collaboration, and conflict negotiation among interdisciplinary teams. The process of coaching a large faculty across two states to implement TBL, faculty perceptions with TBL, lessons learned, and quality improvement strategies is described.https://digitalcommons.library.umaine.edu/ccids_posters/1028/thumbnail.jp

Assessing Trainee Understanding of Health Equity & Diversity

The NH-ME LEND Program engages in quality improvement efforts aimed at increasing trainee’s understanding of health equity and cultural competence. This poster 1) provided an overview of the curricular components related to health equity and diversity, 2) reported on six cohorts of trainees’ self-assessments in these areas, and 3) shared trainees’ personal reflections on their growth. Finally, ongoing program improvements efforts in these areas were discussed.https://digitalcommons.library.umaine.edu/ccids_posters/1011/thumbnail.jp

Utility of ambulatory electrocardiographic monitoring for predicting recurrence of sustained ventricular tachyarrhythmias in patients receiving amiodarone

The prognostic implications of changes in ventricular ectopic activity on serial 24 hour ambulatory electrocardiographic (Holter) recordings were prospectively evaluated in 107 patients with a history of sustained ventricular tachyarrhythmias treated with amiodarone for at least 30 days. Twenty-seven patients (25%) had insufficient ventricular ectopic activity < 10 ventricular premature complexes/h and no repetitive forms) on baseline Holter recordings for serial statistical analysis. In 53 (66%) of the remaining 80 patients, serial 24 hour Holter monitor recordings showed efficacy of treatment, defined as a 75% decrease in ventricular premature complexes, a 95% decrease in ventricular couplets and absence of ventricular tachycardia. During a mean followup period of 14.2 ± 9.9 months, 34 (32%) of the 107 patients had recurrence of a sustained ventricular tachyarrhythmia. Holter recording correctly predicted nine recurrences and correctly identified 37 patients who did not experience a recurrence. Holter efficacy failed to predict recurrence of a sustained ventricular tachyarrhythmia in 16 patients, and 18 patients remained free of recurrence despite failure to achieve Holter efficacy. The positive predictive value of Holter monitoring efficacy was 33% and the negative predictive value was 70%; however, these differences were not statistically significant by chi-square analysis. Similar results were obtained using Holter recordings performed relatively early in therapy (6 weeks and 4 months).Of the 27 patients without significant ventricular ectopic activity on the baseline Holter recording, 9 had an arrhythmia recurrence despite continued infrequent ventricular premature complexes and no repetitive forms on subsequent recordings. The recurrence rate in this group (33%) was similar to the overall recurrence rate.Therefore, among patients taking amiodarone for sustained ventricular tachyarrhythmias: 1) 25% will have insufficient ventricular ectopic activity on 24 hour Holter recordings for serial statistical analysis; and 2) in the remaining 75%, data obtained from serial Holter recordings are not predictive of arrhythmia recurrence

Atom-economic access to cationic magnesium complexes

Cationic alkaline-earth complexes attract interest for their enhanced Lewis acidity and reactivity compared with their neutral counterparts. Synthetic protocols to these complexes generally utilize expensive specialized reagents in reactions generating multiple by-products. We have studied a simple ligand transfer approach to these complexes using (NacNac)MgR and ER3 (NacNac = β-diketiminate anion; E = group 13 element; R = aryl/amido anion) which demonstrates high atom economy, opening up the ability to target these species in a more sustainable manner. The success of this methodology is dependent on the identity of the group 13 element with the heavier elements facilitating faster ligand exchange. Furthermore, while this reaction is successful with aromatic ligands such as phenyl and pyrrolyl, the secondary amide piperidide (pip) fails to transfer, which we attribute to the stronger 3-centre-4-electron dimerization interaction of Al2(pip)6

Codesigning a systemic discharge intervention for inpatient mental health settings (MINDS): a protocol for integrating realist evaluation and an engineering-based systems approach

© 2023 The Author(s). Published by BMJ. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: Transition following discharge from mental health hospital is high risk in terms of relapse, readmission and suicide. Discharge planning supports transition and reduces risk. It is a complex activity involving interacting systemic elements. The codesigning a systemic discharge intervention for inpatient mental health settings (MINDS) study aims to improve the process for people being discharged, their carers/supporters and staff who work in mental health services, by understanding, co-designing and evaluating implementation of a systemic approach to discharge planning. Methods and analysis: The MINDS study integrates realist research and an engineering-informed systems approach across three stages. Stage 1 applies realist review and evaluation using a systems approach to develop programme theories of discharge planning. Stage 2 uses an Engineering Better Care framework to codesign a novel systemic discharge intervention, which will be subjected to process and economic evaluation in stage 3. The programme theories and resulting care planning approach will be refined throughout the study ready for a future clinical trial. MINDS is co-led by an expert by experience, with researchers with lived experience co-leading each stage. Ethics and dissemination: MINDS stage 1 has received ethical approval from Yorkshire & The Humber—Bradford Leeds (Research Ethics Committee (22/YH/0122). Findings from MINDS will be disseminated via high-impact journal publications and conference presentations, including those with service user and mental health professional audiences. We will establish routes to engage with public and service user communities and National Health Service professionals including blogs, podcasts and short videos. Trial registration number: MINDS is funded by the National Institute of Health Research (NIHR 133013) https://fundingawards.nihr.ac.uk/award/NIHR133013. The realist review protocol is registered on PROSPERO. PROSPERO registration number: CRD42021293255.Peer reviewe

Invasive versus medical management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: a pilot randomized controlled trial

Background: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. Methods: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). Results: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years’ follow-up (median [interquartile range], 744 [570–853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. Conclusions: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751

Publication Records of Faculty Promoted to Professor: Evidence from the UK Accounting and Finance Academic Community

This study investigates the publication profiles of 140 accounting and finance faculty promoted to the senior rank of professor at UK and Irish universities during the period 1992 to 2007. On average, approximately 9 papers in Association of Business Schools (ABS) (2008)-listed journals, with 5 at the highest 3*/4* quality levels in a portfolio of 20 outputs are required for promotion to professor. Multivariate analysis provides evidence that publication requirements in terms of ABS ranked journal papers have increased over time, an effect attributed to the government research assessment exercise. There is no evidence that requirements differ for: internal versus external promotion, male versus female candidates; accounting versus finance professors, research intensity of institution peer group; or government research ranking of unit. There is also no evidence of a substitution effect in relation to increased recent publication history, quantity of non-ABS outputs or sole-authorship, all of which show a significant complementary effect. It is noted that there is very limited overlap in the UK and US publication journal sets, suggesting underlying geographically-based paradigm differences. The benchmarks provided in this study are informative in a range of decision settings: recruitment; those considering making an application for promotion to a chair and those involved in promotion panels; cross-disciplinary comparisons; and resource allocation. The evidence presented also contributes to the emerging policy debates concerning the aging demographic profile of accounting faculty, the management of academic labour and the Research Excellence Framework