Trusting relationships between patients with non-curative cancer and healthcare professionals create ethical obstacles for informed consent in clinical trials: a grounded theory study.

BACKGROUND: Clinical trial participation for patients with non-curative cancer is unlikely to present personal clinical benefit, which raises the bar for informed consent. Previous work demonstrates that decisions by patients in this setting are made within a 'trusting relationship' with healthcare professionals. The current study aimed to further illuminate the nuances of this relationship from both the patients' and healthcare professionals' perspectives. METHODS: Face-to-face interviews using a grounded theory approach were conducted at a regional Cancer Centre in the United Kingdom. Interviews were performed with 34 participants (patients with non-curative cancer, number (n) = 16; healthcare professionals involved in the consent process, n = 18). Data analysis was performed after each interview using open, selective, and theoretical coding. RESULTS: The 'Trusting relationship' with healthcare professionals underpinned patient motivation to participate, with many patients 'feeling lucky' and articulating an unrealistic hope that a clinical trial could provide a cure. Patients adopted the attitude of 'What the doctor thinks is best' and placed significant trust in healthcare professionals, focusing on mainly positive aspects of the information provided. Healthcare professionals recognised that trial information was not received neutrally by patients, with some expressing concerns that patients would consent to 'please' them. This raises the question: Within the trusting relationship between patients and healthcare professionals, 'Is it possible to provide balanced information?'. The theoretical model identified in this study is central to understanding how the trusting professional-patient relationship influences the decision-making process. CONCLUSION: The significant trust placed on healthcare professionals by patients presented an obstacle to delivering balanced trial information, with patients sometimes participating to please the 'experts'. In this high-stakes scenario, it may be pertinent to consider strategies, such as separation of the clinician-researcher roles and enabling patients to articulate their care priorities and preferences within the informed consent process. Further research is needed to expand on these ethical conundrums and ensure patient choice and autonomy in trial participation are prioritised, particularly when the patient's life is limited.

Exercise and Cardioprotection in Coronary Artery Disease: A Pilot Quasi-Experimental Study.

Sirtuin-1 is a protein that may orchestrate the cardioprotective effect of exercise by controlling cellular processes. This pilot study assessed the feasibility of performing a quasi-experimental study in this area. Patients with postacute myocardial infarction were recruited across four hospital sites in the United Kingdom. The participants were offered one weekly exercise session at Phase-III and Phase-IV cardiac rehabilitation (CR). Measurements were obtained pre-Phase-III CR (Week 1), post-Phase-III CR (Week 8), and post-Phase-IV CR (Week 22). Twenty-eight patients were recruited (79% male, 100% White, 60.2 ± 10.5 years old). The recruitment rate was not fulfilled (<70% eligible patients recruited; 0.9 participants recruited per week over 30 weeks). The success criteria for dropout rate, adherence rate, and collection of sirtuin-1 measures were satisfied. A large increase in sirtuin-1 (0.14 ± 0.03, d ≥ 0.8) was seen after Phase-III and Phase-IV CR. Collectively, a quasi-experimental study is feasible with a revised recruitment strategy.

Exercise and inflammation in coronary artery disease: A systematic review and meta-analysis of randomised trials.

Current evidence suggests that chronic inflammation contributes to the development of coronary artery disease (CAD). Interestingly, exercise may constitute a method of reducing inflammation in this patient population. As such, this systematic review and meta-analysis examined the evidence generated by randomised studies that investigated the effect of exercise on inflammatory biomarkers in CAD. Literature was sought from various sources. Outcomes were pooled in a random-effects model to calculate standardised mean differences (SMD) with 95% confidence intervals (CI). Twenty-five studies were reviewed; post-intervention C-reactive protein (SMD: -0.55 (95% CI: -0.93, -0.16), P = 0.005), fibrinogen (SMD: -0.52 (95% CI: -0.74, -0.29, P = <0.00001)), and von Willebrand factor (SMD: -1.57 (95% CI: -2.23, -0.92), P = <0.00001) values were significantly lower in exercise groups compared to controls. In addition, qualitative analyses identified evidence that supports a beneficial effect of exercise on these acute-phase reactants. However, the impact of exercise on anti-inflammatory cytokines, adhesion molecules, and chemokines is equivocal, which may be attributed to a paucity of research. Nevertheless, the findings of this review suggest that exercise induces an anti-inflammatory effect in CAD patients. Although, the quality of evidence needs to be improved by further randomised studies with high methodological qualities and large sample sizes.

The feasibility of delivering cardiac brief intervention to patients following ST-elevation myocardial infarction: Protocol for a pilot randomised controlled trial.

BACKGROUND: Patients experience emotional distress and hold cardiac misconceptions following ST-elevation myocardial infarction. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. The current study will establish a knowledge base for the feasibility of delivering this intervention to patients following ST-elevation myocardial infarction, with a preliminary exploration of impact on associated outcomes (ClinicalTrials.gov: NCT05848674). METHODS: A pilot randomised controlled trial incorporating a mixed-methods design will be conducted. Patients with ST-elevation myocardial infarction (number = 40) will be recruited from coronary care units at two hospital centres in Northern Ireland, with participants randomised (1:1) to the intervention or control group. Cardiac Brief Intervention constitutes a nurse-led, short (20 minutes) emotional and educational support discussion with a patient, with a leaflet that serves as a memory-aid. It will be delivered to the intervention group prior to discharge from a coronary care unit. The control group will receive standard care information. Data will be collected at baseline, post-intervention, 4 weeks from diagnosis, and 14 weeks from diagnosis. Feasibility measurements and process evaluation (quantitative and qualitative) will assess the viability of the research design and intervention delivery. Cardiac rehabilitation attendance data will be collected, and participants will complete questionnaires related to associated outcomes. Quantitative data will be reported with descriptive statistics and qualitative data will be analysed using framework analysis, with data integrated to achieve triangulation of findings. DISCUSSION: Educational and emotional difficulties following ST-elevation myocardial infarction may impede patient outcomes and cardiac rehabilitation participation. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. This study will evaluate the feasibility of delivering Cardiac Brief Intervention to patients. These results will inform large-scale definitive testing of the intervention, which may lead to adoption in clinical practice to improve cardiac rehabilitation uptake and patient outcomes.

"Why would you not listen? It is like being given the winning lottery numbers and deciding not to take them": semi-structured interviews with post-acute myocardial infarction patients and their significant others exploring factors that influence participation in cardiac rehabilitation and long-term exercise training.

PURPOSE: Despite the clinical benefits, coronary artery disease patient participation rates in cardiac rehabilitation (CR) and long-term exercise are poor. This study explored the factors related to participation in these interventions from the perspectives of post-acute myocardial infarction (AMI) patients and their significant others. METHODS: Semi-structured interviews were performed with post-AMI patients (number (n) = 10) and their significant others (n = 10) following phase-III and phase-IV CR. Reflexive thematic analysis with an inductive orientation was utilised to identify themes within the dataset (ClinicalTrials.gov identifier: NCT03907293). RESULTS: The overarching theme of the data was a perceived need to improve health, with the participants viewing health benefits as the principal motive for participating in CR and long-term exercise training. Three further themes were identified: motivation, extrinsic influences, and CR experience. These themes captured the underlying elements of the participants' decision to take part in CR and long-term exercise training for the purpose of health improvements. CONCLUSION: An AMI collectively impacts the attitudes and beliefs of patients and their significant others in relation to CR participation, long-term exercise, and health. The factors identified in this study may inform strategies to promote patient enrollment in CR and adherence to long-term exercise.IMPLICATIONS FOR REHABILITATIONPost-AMI patients and their significant others reported that health benefits were the primary motive for participating in CR and long-term exercise, with aspects related to motivation, extrinsic influences, and CR experience underpinning the decision.Healthcare professionals should supply information about health benefits during the CR referral process, with insights into the experiences of CR graduates potentially improving the strength of recommendation.CR facilitators may promote long-term exercise adherence by assisting patients with the identification of an enjoyable exercise modality.Healthcare professionals should include significant others in the CR referral process, which may enable these individuals to support the patients' decisions.

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes (SCORE-IT): a patient and healthcare professional consensus on a core outcome set for type 2 diabetes.

Objectives: Heterogeneity in outcomes measured across trials of glucose-lowering interventions for people with type 2 diabetes impacts on the ability to compare findings and may mean that the results have little importance to healthcare professionals and the patients that they care for. The SCORE-IT study (Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes) has addressed this issue by establishing consensus on the most important outcomes for non-surgical interventions for hyperglycemia in type 2 diabetes. Research design and methods: A comprehensive list of outcomes was developed from registered clinical trials, online patient resources, qualitative literature and long-term studies in the field. This list was then scored in a two-round online Delphi survey completed by healthcare professionals, people with type 2 diabetes, researchers in the field and healthcare policymakers. The results of this online Delphi were discussed and ratified at a face-to-face consensus meeting. Results: 173 people completed both rounds of the online survey (116 people with type 2 diabetes, 37 healthcare professionals, 14 researchers and 6 policymakers), 20 of these attended the consensus meeting (13 people with type 2 diabetes and 7 healthcare professionals). Consensus was reached on 18 core outcomes across five domains, which include outcomes related to diabetes care, quality of life and long-term diabetes-related complications. Conclusions: Implementation of the core outcome set in future trials will ensure that outcomes of importance to all stakeholders are measured and reported, enhancing the relevance of trial findings and facilitating the comparison of results across trials.

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 Diabetes (SCORE-IT): study protocol for the development of a core outcome set.

BACKGROUND: Type 2 diabetes is characterised by abnormal glucose metabolism, and treatment is aimed at normalising glycaemia. Outcomes measured in clinical trials should be meaningful to patients, health care professionals and researchers, yet there is heterogeneity in the outcomes used across trials of glucose-lowering interventions. This inconsistency affects the ability to compare findings and may mean that the results have little importance to health care professionals and the patients for whom they care. The SCORE-IT study aims to develop a core outcome set (COS) for use in all trials of glucose-lowering interventions for people with type 2 diabetes. METHODS/DESIGN: This study will involve three key stages in the development of a COS: (1) A list of outcomes will be identified from multiple sources, specifically registered clinical trials, online patient resources, the qualitative literature and landmark studies identified by a Study Steering Committee. (2) The list of outcomes will be scored by multiple stakeholder groups in a two-round online international Delphi survey. (3) The results of the online Delphi will be summarised and discussed at a face-to-face consensus meeting with representation from all stakeholder groups. DISCUSSION: The SCORE-IT study aims to develop an internationally relevant set of core outcomes for use in future trials of glucose-lowering interventions for type 2 diabetes. The use of a COS will improve the consistency of outcomes, allowing results of studies to be compared and combined and for new effective treatments to made available more quickly. TRIAL REGISTRATION: The COS study, of which this is a part, is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database, http://www.comet-initiative.org/studies/details/956 . Registered January 2017.

Multiple residues in the p-region and m2 of murine kir 2.1 regulate blockage by external ba.

We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on Ba(2+) blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary (CHO) cells and used the whole cell patch-clamp technique to record K(+) currents in the absence and presence of externally applied Ba(2+). Wild type Kir2.1 was blocked by externally applied Ba(2+) in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of Ba(2+) blockage. The estimated K(d)(0) was 108 microM for Kir2.1 wild type, 124 microM for a concatameric WT-Y145V dimer, 109 microM for a WT-Y145L dimer, and 267 microM for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for Ba(2+), also showing two components with very different time courses. Mutants D172K and D172R (lining the central, aqueous cavity of the channel) showed both a decreased affinity to Ba(2+) and a decrease in the on transition rate constant (k(on)). These results imply that residues stabilising the cytoplasmic end of the selectivity filter (T141, S165) and in the central cavity (D172) are major determinants of high affinity Ba(2+) blockage in Kir 2.1.