Metacognitive therapy home-based self-help for anxiety and depression in cardiovascular disease patients in the UK: A single-blind randomised controlled trial.

BACKGROUND: Anxiety and depression in cardiac rehabilitation (CR) are associated with greater morbidity, mortality, and increased healthcare costs. Current psychological interventions within CR have small effects based on low-quality studies of clinic-based interventions with limited access to home-based psychological support. We tested the effectiveness of adding self-help metacognitive therapy (Home-MCT) to CR in reducing anxiety and depression in a randomised controlled trial (RCT). METHODS AND FINDINGS: We ran a single-blind, multi-centre, two-arm RCT. A total of 240 CR patients were recruited from 5 NHS-Trusts across North West England between April 20, 2017 and April 6, 2020. Patients were randomly allocated to Home-MCT+CR (n = 118, 49.2%) or usual CR alone (n = 122, 50.8%). Randomisation was 1:1 via randomised blocks within hospital site, balancing arms on sex and baseline Hospital Anxiety and Depression Scale (HADS) scores. The primary outcome was the HADS total score at posttreatment (4-month follow-up). Follow-up data collection occurred between August 7, 2017 and July 20, 2020. Analysis was by intention to treat. The 4-month outcome favoured the MCT intervention group demonstrating significantly lower end of treatment scores (HADS total: adjusted mean difference = -2.64 [-4.49 to -0.78], p = 0.005, standardised mean difference (SMD) = 0.38). Sensitivity analysis using multiple imputation (MI) of missing values supported these findings. Most secondary outcomes also favoured Home-MCT+CR, especially in reduction of post-traumatic stress symptoms (SMD = 0.51). There were 23 participants (19%) lost to follow-up in Home-MCT+CR and 4 participants (3%) lost to follow-up in CR alone. No serious adverse events were reported. The main limitation is the absence of longer term (e.g., 12-month) follow-up data. CONCLUSION: Self-help home-based MCT was effective in reducing total anxiety/depression in patients undergoing CR. Improvement occurred across most psychological measures. Home-MCT was a promising addition to cardiac rehabilitation and may offer improved access to effective psychological treatment in cardiovascular disease (CVD) patients. TRIAL REGISTRATION: NCT03999359.

Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: PATHWAY-A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy.

BACKGROUND: Depression and anxiety in cardiovascular disease are significant, contributing to poor prognosis. Unfortunately, current psychological treatments offer mixed, usually small improvements in these symptoms. The present trial tested for the first time the effects of group metacognitive therapy (MCT; 6 sessions) on anxiety and depressive symptoms when delivered alongside cardiac rehabilitation (CR). METHODS: A total of 332 CR patients recruited from 5 National Health Service Trusts across the North-West of England were randomly allocated to MCT+CR (n=163, 49.1%) or usual CR alone (n=169, 50.9%). Randomization was 1:1 via minimization balancing arms on sex and Hospital Anxiety and Depression Scale scores within hospital site. The primary outcome was Hospital Anxiety and Depression Scale total after treatment (4-month follow-up). Secondary outcomes were individual Hospital Anxiety and Depression Scales, traumatic stress symptoms, and psychological mechanisms including metacognitive beliefs and repetitive negative thinking. Analysis was intention to treat. RESULTS: The adjusted group difference on the primary outcome, Hospital Anxiety and Depression Scale total score at 4 months, significantly favored the MCT+CR arm (-3.24 [95% CI, -4.67 to -1.81], P<0.001; standardized effect size, 0.52 [95% CI, 0.291 to 0.750]). The significant difference was maintained at 12 months (-2.19 [95% CI, -3.72 to -0.66], P=0.005; standardized effect size, 0.33 [95% CI, 0.101 to 0.568]). The intervention improved outcomes significantly for both depression and anxiety symptoms when assessed separately compared with usual care. Sensitivity analysis using multiple imputation of missing values supported these findings. Most secondary outcomes favored MCT+CR, with medium to high effect sizes for psychological mechanisms of metacognitive beliefs and repetitive negative thinking. No adverse treatment-related events were reported. CONCLUSIONS: Group MCT+CR significantly improved depression and anxiety compared with usual care and led to greater reductions in unhelpful metacognitions and repetitive negative thinking. Most gains remained significant at 12 months. Study strengths include a large sample, a theory-based intervention, use of longer-term follow-up, broad inclusion criteria, and involvement of a trials unit. Limitations include no control for additional contact as part of MCT to estimate nonspecific effects, and the trial was not intended to assess cardiac outcomes. Nonetheless, results demonstrated that addition of the MCT intervention had broad and significant beneficial effects on mental health symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ISRCTN74643496.

Levels of depressive symptoms in cardiac patients attending cardiac rehabilitation with a history of depression: pre Covid-19 and Covid-19 period comparison.

BACKGROUND: The large-scale changes in cardiac rehabilitation (CR) programme delivery in response to COVID-19 has led to diminished provision. The influence of these service changes on the depression symptoms of patients in CR programmes is unknown. Our study investigated the extent of depressive symptoms prior to and during the COVID-19 periods in patients with a previous history of depression at the start of CR. METHODS: Use of Registry routine practice data, National Audit of Cardiac Rehabilitation (NACR), from COVID-19 period Feb 2020 and Jan 2021, as well as pre COVID-19 period Feb 2019 and Jan 2020, was extracted. Depressive symptoms were defined according to Hospital Anxiety and Depression Score ≥ 8. Chi-square tests and independent samples t-tests were used to investigate baseline characteristics. Additionally, a binary logistic regression to examine the factors associated with high levels of depressive symptoms. RESULTS: In total 3661 patients with a history of depression were included in the analysis. Patients attending CR during COVID-19 were found to be 11% more likely to have high levels of acute depressive symptoms compared to patients attending CR prior to COVID-19. Physical inactivity, increased anxiety, a higher total number of comorbidities, increased weight, and living in the most deprived areas were statistically significant factors associated with high levels of acute depressive symptoms at the start of CR following multivariate adjustments. CONCLUSION: Our research suggests that following a cardiac event patients with prior history of depression have high levels of acute depressive symptoms at CR baseline assessment. This finding exists in both the pre Covid-19 and Covid-19 periods in patients with a history of depression.

Benefits of cardiac rehabilitation following acute coronary syndrome for patients with and without diabetes: a systematic review and meta-analysis.

AIM: The benefits of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) are well established. However, the relative benefit of CR in those with comorbidities, including diabetes, is not well understood. This systematic review and meta-analysis examined the benefit of CR on exercise capacity and secondary outcomes in ACS patients with a co-diagnosis of diabetes compared to those without. METHODS: Five databases were searched in May 2021 for randomised controlled trials (RCTs) and observational studies reporting CR outcomes in ACS patients with and without diabetes. The primary outcome of this study was exercise capacity expressed as metabolic equivalents (METs) at the end of CR and ≥ 12-month follow-up. Secondary outcomes included health-related quality of life, cardiovascular- and diabetes-related outcomes, lifestyle-related outcomes, psychological wellbeing, and return to work. If relevant/possible, studies were pooled using random-effects meta-analysis. RESULTS: A total of 28 studies were included, of which 20 reported exercise capacity and 18 reported secondary outcomes. Overall, the studies were judged to have a high risk of bias. Meta-analysis of exercise capacity was undertaken based on 18 studies (no RCTs) including 15,288 patients, of whom 3369 had diabetes. This analysis showed a statistically significant smaller difference in the change in METs in ACS patients with diabetes (standardised mean difference (SMD) from baseline to end of CR: - 0.15 (95% CI: - 0.24 to - 0.06); SMD at the ≥ 12-month follow-up: - 0.16 (95% CI: - 0.23 to - 0.10, four studies)). CONCLUSION: The benefit of CR on exercise capacity in ACS patients was lower in those with diabetes than in those without diabetes. Given the small magnitude of this difference and the substantial heterogeneity in the results of the study caused by diverse study designs and methodologies, further research is needed to confirm our findings. Future work should seek to eliminate bias in observational studies and evaluate CR based on comprehensive outcomes.

A pragmatic effectiveness-implementation study comparing trial evidence with routinely collected outcome data for patients receiving the REACH-HF home-based cardiac rehabilitation programme.

BACKGROUND: Cardiac rehabilitation for heart failure continues to be greatly underused worldwide despite being a Class I recommendation in international clinical guidelines and uptake is low in women and patients with mental health comorbidities. METHODS: Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) programme was implemented in four UK National Health Service early adopter sites ('Beacon Sites') between June 2019 and June 2020. Implementation and patient-reported outcome data were collected across sites as part of the National Audit of Cardiac Rehabilitation. The change in key outcomes before and after the supervised period of REACH-HF intervention across the Beacon Sites was assessed and compared to those of the intervention arm of the REACH-HF multicentre trial. RESULTS: Compared to the REACH-HF multicentre trial, patients treated at the Beacon Site were more likely to be female (33.8% vs 22.9%), older (75.6 vs 70.1), had a more severe classification of heart failure (26.5% vs 17.7%), had poorer baseline health-related quality of life (MLHFQ score 36.1 vs 31.4), were more depressed (HADS score 6.4 vs 4.1) and anxious (HADS score 7.2 vs 4.7), and had lower exercise capacity (ISWT distance 190 m vs 274.7 m). There appeared to be a substantial heterogeneity in the implementation process across the four Beacon Sites as evidenced by the variation in levels of patient recruitment, operationalisation of the REACH-HF intervention and patient outcomes. Overall lower improvements in patient-reported outcomes at the Beacon Sites compared to the trial may reflect differences in the population studied (having higher morbidity at baseline) as well as the marked challenges in intervention delivery during the COVID-19 pandemic. CONCLUSION: The results of this study illustrate the challenges in consistently implementing an intervention (shown to be clinically effective and cost-effective in a multicentre trial) into real-world practice, especially in the midst of a global pandemic. Further research is needed to establish the real-world effectiveness of the REACH-HF intervention in different populations.

Effectiveness of Mobile Health Augmented Cardiac Rehabilitation (MCard) on health-related quality of life among post-acute coronary syndrome patients: A randomized controlled trial.

Objectives: To determine the effectiveness of Mobile health augmented Cardiac rehabilitation (MCard) on health-related quality of life (HRQoL) among post-acute coronary syndrome (post-ACS) patients. Methods: At the Armed Forces Institute of Cardiology (AFIC), a tertiary care hospital in Rawalpindi, Pakistan, a two-arm randomised controlled trial was conducted in which mobile health augmented cardiac rehabilitation (MCard) was developed and implemented on post-ACS patients from January 2019 until March 2021. The trial conforms to the CONSORT statement 2010. The post-ACS patients were randomly allocated (1:1) to an intervention group (received MCard; counselling, empowering with self-monitoring devices, short text messages, in addition to standard post-ACS care) or control group (standard post-ACS care). HRQoL was assessed by generic Short Form-12 and MacNew quality of life myocardial infarction (QLMI) tools. Participants were followed for 24 weeks with data collection and analysis at three time points (baseline, 12 weeks and 24 weeks). Results: At baseline, 160 patients (80 in each group; mean age 52.66±8.46 years; 126 male, 78.75%) were recruited, of which 121(75.62%) continued and were analysed at 12-weeks and 119(74.37%) at 24-weeks. The mean SF-12 physical component score significantly improved in the MCard group at 12 weeks follow-up (48.93 vs control 43.87, p<.001) and 24 weeks (53.52 vs 46.82 p<.001). The mean SF-12 mental component scores also improved significantly in the MCard group at 12 weeks follow-up (44.84 vs control 41.40, p<.001) and 24 weeks follow-up (48.95 vs 40.12, p<.001). At 12-and 24-week follow-up, all domains of MacNew QLMI (social, emotional, physical and global) were also statistically significant (p<.001) improved in the MCard group, unlike the control group. Conclusion: MCard is an effective and acceptable intervention at improving all domains of HRQoL. There was an improvement in physical, mental, social, emotional and global domains among the MCard group in comparison to the control group. The addition of MCard programs to post-ACS standard care may improve patient outcomes and reduce the burden on the health care setting.

The development of a theory and evidence-based intervention to aid implementation of exercise into the prostate cancer care pathway with a focus on healthcare professional behaviour, the STAMINA trial.

BACKGROUND: Twice-weekly supervised aerobic and resistance exercise for 12 weeks reduces fatigue and improves quality of life in men on Androgen Deprivation Therapy for prostate cancer. Despite the National Institute for Health and Care Excellence (NICE) proposing this as standard of care, it does not routinely take place in practice. Healthcare professionals are in a prime position to deliver and integrate these recommendations. A change in the behaviour of clinical teams is therefore required. In this paper, we describe the development of a training package for healthcare professionals using theory and evidence to promote delivery of such recommendations as standard care. METHODS: The intervention development process was guided by the Medical Research Council guidance for complex interventions and the Behaviour Change Wheel. Target behaviours were identified from the literature and thirty-five prostate cancer care healthcare professionals (including oncologists, consultant urologists, clinical nurse specialists, physiotherapists, general practitioners and commissioners) were interviewed to understand influences on these behaviours. The Theoretical Domains Framework was used to identify theoretical constructs for change. Behaviour change techniques were selected based on theory and evidence and were translated into intervention content. The intervention was refined with the input of stakeholders including healthcare professionals, patients, and exercise professionals in the form of rehearsal deliveries, focus groups and a workshop. RESULTS: Seven modifiable healthcare professional target behaviours were identified to support the delivery of the NICE recommendations including identifying eligible patients suitable for exercise, recommending exercise, providing information, exercise referral, providing support and interpret and feedback on progress. Ten domains from the Theoretical Domain's Framework were identified as necessary for change, including improving knowledge and skills, addressing beliefs about consequences, and targeting social influences. These were targeted through twenty-two behaviour change techniques delivered in a half-day, interactive training package. Based on initial feedback from stakeholders, the intervention was refined in preparation for evaluation. CONCLUSIONS: We designed an intervention based on theory, evidence, and stakeholder feedback to promote and support the delivery of NICE recommendations. Future work will aim to test this training package in a multi-centre randomised trial. If proven effective, the development and training package will provide a template for replication in other clinical populations, where exercise has proven efficacy but is insufficiently implemented.

Analysis of a Web-Based Dashboard to Support the Use of National Audit Data in Quality Improvement: Realist Evaluation.

BACKGROUND: Dashboards can support data-driven quality improvements in health care. They visualize data in ways intended to ease cognitive load and support data comprehension, but how they are best integrated into working practices needs further investigation. OBJECTIVE: This paper reports the findings of a realist evaluation of a web-based quality dashboard (QualDash) developed to support the use of national audit data in quality improvement. METHODS: QualDash was co-designed with data users and installed in 8 clinical services (3 pediatric intensive care units and 5 cardiology services) across 5 health care organizations (sites A-E) in England between July and December 2019. Champions were identified to support adoption. Data to evaluate QualDash were collected between July 2019 and August 2021 and consisted of 148.5 hours of observations including hospital wards and clinical governance meetings, log files that captured the extent of use of QualDash over 12 months, and a questionnaire designed to assess the dashboard's perceived usefulness and ease of use. Guided by the principles of realist evaluation, data were analyzed to understand how, why, and in what circumstances QualDash supported the use of national audit data in quality improvement. RESULTS: The observations revealed that variation across sites in the amount and type of resources available to support data use, alongside staff interactions with QualDash, shaped its use and impact. Sites resourced with skilled audit support staff and established reporting systems (sites A and C) continued to use existing processes to report data. A number of constraints influenced use of QualDash in these sites including that some dashboard metrics were not configured in line with user expectations and staff were not fully aware how QualDash could be used to facilitate their work. In less well-resourced services, QualDash automated parts of their reporting process, streamlining the work of audit support staff (site B), and, in some cases, highlighted issues with data completeness that the service worked to address (site E). Questionnaire responses received from 23 participants indicated that QualDash was perceived as useful and easy to use despite its variable use in practice. CONCLUSIONS: Web-based dashboards have the potential to support data-driven improvement, providing access to visualizations that can help users address key questions about care quality. Findings from this study point to ways in which dashboard design might be improved to optimize use and impact in different contexts; this includes using data meaningful to stakeholders in the co-design process and actively engaging staff knowledgeable about current data use and routines in the scrutiny of the dashboard metrics and functions. In addition, consideration should be given to the processes of data collection and upload that underpin the quality of the data visualized and consequently its potential to stimulate quality improvement. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-033208.

Mobile Health Augmented Cardiac Rehabilitation (MCard) in Post-Acute Coronary Syndrome Patients: A randomised controlled trial protocol.

OBJECTIVES: To determine the effectiveness of mobile health augmented cardiac rehabilitation (MCard) on health-related quality of life (HRQoL), clinical and behavioural outcomes in post-ACS. METHODS: A single-centre, single-blinded, two-arm randomised controlled trial is planned at Armed Forces Institute of Cardiology (AFIC), Pakistan. The duration was two years, that is from January 2019 till December 2020. A total of 160 participants were recruited and randomly allocated to the control group or the intervention group. Intervention is a mobile health augmented cardiac rehabilitation (MCard), a medically supervised cardiac rehabilitation program for 23-24 weeks. The phase one includes individual counselling during the hospital stay and in phase two includes communication of standardised messages related to healthy lifestyle modification through a specifically designed software. RESULTS: This clinical trial results will give insight into the impact of MCard in improving the health outcomes (HRQoL, clinical and behavioural) of participants. If proven to be effective, this technology can be scaled up and implemented in other cardiac centres in the country. It utilises fewer human resources and can be delivered at a lower cost. CONCLUSION: The study protocol will be giving evidence either MCard can contribute to improving the HRQoL, clinical and behavioural outcomes of post-ACS patients following hospital discharge. Considering the COVID-9 situation, this is the perfect time to implement and evaluate the effectiveness of MCard on health outcomes among post-ACS patients.

Exercise-induced myocardial dysfunction detected by cardiopulmonary exercise testing is associated with increased risk of mortality in major oncological colorectal surgery.

BACKGROUND: Cardiopulmonary exercise testing (CPET) identifies high-risk patients before major surgery. In addition to using oxygen uptake and ventilatory efficiency to assess functional capacity, CPET can be used to identify underlying myocardial dysfunction through the assessment of the oxygen uptake to heart rate response (oxygen pulse response). We examined the relationship of oxygen pulse response, in combination with other CPET variables and known cardiac risk factors, with mortality after colorectal cancer surgery. METHODS: This work focused on a retrospective cohort study of patients who had CPET and underwent colorectal cancer surgery. The primary outcome was a composite of in-hospital and 30-day mortality. Ventilatory inefficiency (Ve/Vco2>34) and exercise-induced myocardial dysfunction (abnormal oxygen pulse response) were investigated for an association with mortality using bivariable analysis and multivariable Cox regression. RESULTS: A total of 1214 patients who underwent colorectal cancer surgery were included, and the primary outcome occurred in 26 patients (2.1%). Multivariable Cox regression showed abnormal oxygen pulse response was independently associated with the primary outcome (odds ratio [OR]=2.75; 95% confidence interval [CI], 1.17-6.47). Bivariable analysis showed that Ve/Vco2 >34 was associated with the primary outcome (OR=3.43; 95% CI, 1.47-8.01). Combining Ve/Vco2 >34 and abnormal oxygen pulse response conferred an increased risk for the primary outcome (OR=4.47; 95% CI, 1.62-12.34), compared with Ve/Vco2 >34 and normal oxygen pulse response. CONCLUSION: Ventilatory inefficiency and an abnormal oxygen pulse response were independently associated with short- (30-day) and long-term (2-yr) mortality. Oxygen pulse response may provide additional information when considering perioperative risk stratification.

Exploring variation in the use of feedback from national clinical audits: a realist investigation.

BACKGROUND: National Clinical Audits (NCAs) are a well-established quality improvement strategy used in healthcare settings. Significant resources, including clinicians' time, are invested in participating in NCAs, yet there is variation in the extent to which the resulting feedback stimulates quality improvement. The aim of this study was to explore the reasons behind this variation. METHODS: We used realist evaluation to interrogate how context shapes the mechanisms through which NCAs work (or not) to stimulate quality improvement. Fifty-four interviews were conducted with doctors, nurses, audit clerks and other staff working with NCAs across five healthcare providers in England. In line with realist principles we scrutinised the data to identify how and why providers responded to NCA feedback (mechanisms), the circumstances that supported or constrained provider responses (context), and what happened as a result of the interactions between mechanisms and context (outcomes). We summarised our findings as Context+Mechanism = Outcome configurations. RESULTS: We identified five mechanisms that explained provider interactions with NCA feedback: reputation, professionalism, competition, incentives, and professional development. Professionalism and incentives underpinned most frequent interaction with feedback, providing opportunities to stimulate quality improvement. Feedback was used routinely in these ways where it was generated from data stored in local databases before upload to NCA suppliers. Local databases enabled staff to access data easily, customise feedback and, importantly, the data were trusted as accurate, due to the skills and experience of staff supporting audit participation. Feedback produced by NCA suppliers, which included national comparator data, was used in a more limited capacity across providers. Challenges accessing supplier data in a timely way and concerns about the quality of data submitted across providers were reported to constrain use of this mode of feedback. CONCLUSION: The findings suggest that there are a number of mechanisms that underpin healthcare providers' interactions with NCA feedback. However, there is variation in the mode, frequency and impact of these interactions. Feedback was used most routinely, providing opportunities to stimulate quality improvement, within clinical services resourced to collect accurate data and to maintain local databases from which feedback could be customised for the needs of the service.

Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies.

Among the many signalling lipids, endocannabinoids are increasingly recognized for their important roles in neuronal and glial development. Recent experimental evidence suggests that, during neuronal differentiation, endocannabinoid signalling undergoes a fundamental switch from the prenatal determination of cell fate to the homeostatic regulation of synaptic neurotransmission and bioenergetics in the mature nervous system. These studies also offer novel insights into neuropsychiatric disease mechanisms and contribute to the public debate about the benefits and the risks of cannabis use during pregnancy and in adolescence.

To what extent is multi-morbidity associated with new onset depression in patients attending cardiac rehabilitation?

BACKGROUND: Depression is associated with increased mortality and poor prognosis in patients with cardiovascular disease (CVD). However, little is known about the patient characteristics associated with new onset post heart event depressive symptoms, specifically medical comorbidities, among cardiac rehabilitation (CR) participants. Therefore, this paper examines the comorbidity profile and characteristics associated with new onset depressive symptoms in patients attending CR. METHODS: An observational study using the routine practice data of British Heart Foundation National Audit of Cardiac Rehabilitation (NACR) from the last six years between April 2012 and March 2018. Patients with new onset post heart event depression and no previous documented history of depression were selected as the study population. An independent samples t-test and chi square tests were used to compare the association between new onset depressive symptoms and patient variables including demographics, clinical measures and comorbidities. A binary logistic regression was conducted to investigate the predictors of new onset depressive symptoms employing log-likelihood ratio statistic. RESULTS: The analyses included 109,055 CR patients with new onset depression measured by Hospital Anxiety and Depression Scale (HADS). At baseline assessment, comorbidity measures associated with new onset depressive symptoms were increased total number of comorbidities and a range of comorbidities - including diabetes, angina, arthritis, chronic back problems, asthma, stroke, anxiety, rheumatism, claudication, osteoporosis, chronic bronchitis and emphysema. After multivariate adjustments were done, at the start of CR, the significant predictors of new onset depressive symptoms were physical inactivity, high HADS anxiety score measurement, increased weight, total number of comorbidities, diabetes, stroke, chronic back problems, being from areas with higher levels of social deprivation, being single, and male. CONCLUSION: The research findings establish new insights into the association between patient demographic and clinical variables across a range of comorbidities in patients with new onset post heart event depressive symptoms. At the start of CR, patients with new onset depressive symptoms need to be assessed skilfully as they tend to have a complex multi-morbid presentation linked to psychosocial risk factors known to hinder CR engagement.

Association between heart rate variability and haemodynamic response to exercise in chronic heart failure.

OBJECTIVES: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output. DESIGN: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure. RESULTS: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043). CONCLUSIONS: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure.

To what extent is the variation in cardiac rehabilitation quality associated with patient characteristics?

BACKGROUND: Huge variability in quality of service delivery of cardiac rehabilitation (CR) in the UK. This study aimed to ascertain whether the variation in quality of CR delivery is associated with participants' characteristics. METHODS: Individual patient data from 1 April 2013 to 31 March 2014 were collected electronically from the UK's National Audit of Cardiac Rehabilitation database. Quality of CR delivery is categorised as low, middle, and high based on six service-level criteria. The study included a range of patient variables: patient demographics, cardiovascular risk factors, comorbidities, physical and psychosocial health measures, and index of multiple deprivation. RESULTS: The chance that a CR patient with more comorbidities attended a high-quality programme was 2.13 and 1.85 times higher than the chance that the same patient attended a low- or middle-quality programme, respectively. Patients who participated in high-quality CR programmes tended to be at high risk (e.g. increased waist size and high blood pressure); high BMI, low physical activity levels and high Hospital Anxiety and Depression Scale scores; and were more likely to be smokers, and be in more socially deprived groups than patients in low-quality programmes. CONCLUSIONS: These findings show that the quality of CR delivery can be improved and meet national standards by serving a more multi-morbid population which is important for patients, health providers and commissioners of healthcare. In order for low-quality programmes to meet clinical standards, CR services need to be more inclusive in respect of patients' characteristics identified in the study. Evaluation and dissemination of information about the populations served by CR programmes may help low-quality programmes to be more inclusive.

"Struggling with practices" - a qualitative study of factors influencing the implementation of clinical quality registries for cardiac rehabilitation in England and Denmark.

BACKGROUND: The use of clinical quality registries as means for data driven improvement in healthcare seem promising. However, their use has been shown to be challenged by a number of aspects, and we suggest some may be related to poor implementation. There is a paucity of literature regarding barriers and facilitators for registry implementation, in particular aspects related to data collection and entry. We aimed to illuminate this by exploring how staff perceive the implementation process related to the registries within the field of cardiac rehabilitation in England and Denmark. METHODS: A qualitative, interview-based study with staff involved in collecting and/or entering data into the two case registries (England N = 12, Denmark N = 12). Interviews were analysed using content analysis. The Consolidated Framework for Implementation Research was used to guide interviews and the interpretation of results. RESULTS: The analysis identified both similarities and differences within and between the studied registries, and resulted in clarification of staffs´ experiences in an overarching theme: ´Struggling with practices´ and five categories; the data entry process, registry quality, resources and management support, quality improvement and the wider healthcare context. Overall, implementation received little focused attention. There was a lack of active support from management, and staff may experience a struggle of fitting use of a registry into a busy and complex everyday practice. CONCLUSION: The study highlights factors that may be important to consider when planning and implementing a new clinical quality registry within the field of cardiac rehabilitation, and is possibly transferrable to other fields. The results may thus be useful for policy makers, administrators and managers within the field and beyond. Targeting barriers and utilizing knowledge of facilitating factors is vital in order to improve the process of registry implementation, hence helping to achieve the intended improvement of care processes and outcomes.

Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure: A preliminary stakeholder consensus event.

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders (n = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme. The tasks were completed anonymously and related to clinical rehabilitation programmes and associated research. Health-related quality of life, exercise capacity and symptom evaluation were voted as the most important categories to assess for clinical purposes (median rank: 1, 2 and 3 accordingly) and research purposes (median rank; 1, 3 and 4.5 accordingly) within combined exercise rehabilitation. All stakeholders agreed that profiling symptoms at baseline were 'moderately', 'very' or 'extremely' important to assess for clinical and research purposes in combined rehabilitation. Profiling of frailty was ranked of the same importance for clinical purposes in combined rehabilitation. Stakeholders identified a suite of multidisciplinary measures that may be important to assess in a combined COPD and CHF exercise rehabilitation programme.

Factors associated with acute depressive symptoms in patients with comorbid depression attending cardiac rehabilitation.

BACKGROUND: The literature suggests that comorbid depression, defined in this paper as a history of depression prior to a cardiovascular event, has an impact on later onset depression as well as constituting increased risk of mortality and adverse cardiac events. However, which factors are associated with depression, specifically in patients with comorbid depression, is unclear. Therefore, this paper investigates the factors associated with depression in patients with comorbid depression attending cardiac rehabilitation (CR). METHODS: This observational study used routinely collected data from the British Heart Foundation National Audit of Cardiac Rehabilitation for the time period between April 2012 and March 2017. CR participants with comorbid depression were selected as the study population. An independent t-test and chi-square test were used to compare the association between acute depression symptoms and baseline characteristics in this population. RESULTS: A total of 2715 CR patients with comorbid depression were analysed. Characteristics associated with acute depressive symptoms in patients with comorbid depression were found to be: young age (MD: 2.71, 95% CI 1.91, 3.50), increased number of comorbidities (MD: -0.50, 95% CI -0.66, - 0.34), increased weight (MD: -1.94, 95% CI -3.35, - 0.52), high BMI (MD: -1.94, 95% CI -3.35, - 0.52), HADS anxiety (MD: -5.17, 95% CI -5.47, - 4.87), comorbid anxiety (52.4%, p <  0.001), physical inactivity (150 min moderate physical activity a week and 75 min vigorous exercise a week; 27.5%, p <  0.001; 5.6%, p <  0.001 respectively), smoking (12.7%, p <  0.001), and being less likely to be partnered (63.6%, p <  0.001). CONCLUSION: The study demonstrated the association between a variety of clinical and socio-demographic factors and depression. The findings of the research indicated that, at CR baseline assessment, caution must be taken with patients with comorbid depression, specifically those with higher level depressive symptoms at the start of rehabilitation. Furthermore, their multi-comorbid condition must also be taken into account. Patients with higher depression symptoms and comorbid depression scored five points higher on the HADS anxiety scale in comparison to patients with lower level depression symptoms at the start of CR, which demonstrated that anxiety and depression are interrelated and present together.

Proteomic response to linoleic acid hydroperoxide in Saccharomyces cerevisiae.

Yeast AP-1 transcription factor (Yap1p) and the enigmatic oxidoreductases Oye2p and Oye3p are involved in counteracting lipid oxidants and their unsaturated breakdown products. In order to uncover the response to linoleic acid hydroperoxide (LoaOOH) and the roles of Oye2p, Oye3p and Yap1p, we carried out proteomic analysis of the homozygous deletion mutants oye3Δ, oye2Δ and yap1Δ alongside the diploid parent strain BY4743. The findings demonstrate that deletion of YAP1 narrowed the response to LoaOOH, as the number of proteins differentially expressed in yap1Δ was 70% of that observed in BY4743. The role of Yap1p in regulating the major yeast peroxiredoxin Tsa1p was demonstrated by the decreased expression of Tsa1p in yap1Δ. The levels of Ahp1p and Hsp31p, previously shown to be regulated by Yap1p, were increased in LoaOOH-treated yap1Δ, indicating their expression is also regulated by another transcription factor(s). Relative to BY4743, protein expression differed in oye3Δ and oye2Δ under LoaOOH, underscored by superoxide dismutase (Sod1p), multiple heat shock proteins (Hsp60p, Ssa1p, and Sse1p), the flavodoxin-like protein Pst2p and the actin stabiliser tropomyosin (Tpm1p). Proteins associated with glycolysis were increased in all strains following treatment with LoaOOH. Together, the dataset reveals, for the first time, the yeast proteomic response to LoaOOH, highlighting the significance of carbohydrate metabolism, as well as distinction between the roles of Oye3p, Oye2p and Yap1p.

Regulated endosomal trafficking of Diacylglycerol lipase alpha (DAGLα) generates distinct cellular pools; implications for endocannabinoid signaling.

Diacylglycerol lipase alpha (DAGLα) generates the endocannabinoid (eCB) 2-arachidonylglycerol (2-AG) that regulates the proliferation and differentiation of neural stem cells and serves as a retrograde signaling lipid at synapses. Nothing is known about the dynamics of DAGLα expression in cells and this is important as it will govern where 2-AG can be made and released. We have developed a new construct to label DAGLα at the surface of live cells and follow its trafficking. In hippocampal neurons a cell surface pool of DAGLα co-localizes with Homer, a postsynaptic density marker. This surface pool of DAGLα is dynamic, undergoing endocytosis and recycling back to the postsynaptic membrane. A similar cycling is seen in COS-7 cells with the internalized DAGLα initially transported to EEA1 and Rab5-positive early endosomes via a clathrin-independent pathway before being transported back to the cell surface. The internalized DAGLα is present on reticular structures that co-localize with microtubules. Importantly, DAGLα cycling is a regulated process as inhibiting PKC results in a significant reduction in endocytosis. This is the first description of DAGLα cycling between the cell surface and an intracellular endosomal compartment in a manner that can regulate the level of the enzyme at the cell surface.