Exercise-based cardiac rehabilitation for coronary heart disease (Review)

Background Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise‐based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016. Objectives To assess the clinical effectiveness and cost‐effectiveness of exercise‐based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health‐related quality of life (HRQoL) in people with CHD. Search methods We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021. Selection criteria We included randomised controlled trials (RCTs) of exercise‐based interventions with at least six months’ follow‐up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease. Data collection and analysis We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta‐analysis by duration of follow‐up: short‐term (6 to 12 months); medium‐term (> 12 to 36 months); and long‐term ( > 3 years), and used meta‐regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow‐up time point). Main results This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post‐MI and post‐revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty‐one of the included trials were performed in low‐ and middle‐income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow‐up time was 12 months (range 6 months to 19 years). At short‐term follow‐up (6 to 12 months), exercise‐based CR likely results in a slight reduction in all‐cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all‐cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials; NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise‐based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow‐up. We are uncertain about the effects of exercise‐based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I2 = 53%), and of small study bias for all‐cause hospitalisation, but not for all other outcomes. At medium‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all‐cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise‐based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta‐regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow‐up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise‐based CR may slightly increase HRQoL across several subscales (SF‐36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow‐up; however, these may not be clinically important differences. The eight trial‐based economic evaluation studies showed exercise‐based CR to be a potentially cost‐effective use of resources in terms of gain in quality‐adjusted life years (QALYs). Authors' conclusions This updated Cochrane Review supports the conclusions of the previous version, that exercise‐based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all‐cause mortality, and a large reduction in all‐cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow‐up. Over longer‐term follow‐up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well‐designed, adequately‐reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer‐term follow‐up, and assess costs and cost‐effectiveness

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

“Having diabetes shouldn’t stop them”: healthcare professionals’ perceptions of physical activity in children with Type 1 diabetes

Background Healthcare professionals (HCP) working with children who have Type 1 Diabetes Mellitus (T1DM) have an important role in advising about and supporting the control of blood glucose level in relation to physical activity. Regular physical activity has known benefits for children with T1DM, but children with chronic conditions may face barriers to participation. The perceptions of HCPs were explored in an effort to understand what influences physical activity in children with T1DM and to inform the practice of those working with children who have T1DM. Methods Semi-structured interviews with 11 HCPs involved in the care of children with T1DM in the UK were conducted. Interviews were recorded, transcribed verbatim and data were analysed using thematic analysis. Results The factors perceived to influence participation in physical activity are presented as five major themes and eleven sub-themes. Themes included the positive influence of social support, the child’s motivation to be active, the potential for formal organisations such as school and diabetes clinic to support physical activity, the challenges faced by those who have T1DM and the perceived barriers to HCPs fulfilling their role of promoting physical activity. Conclusions Healthcare professionals recognised their role in helping children with T1DM and their parents to incorporate physical activity into diabetes management and everyday life, but perceived barriers to the successful fulfilment of this role. The findings highlight the potential for clinical and non-clinical supportive systems to be sensitive to these challenges and facilitate children’s regular participation in physical activity

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

A physical activity intervention for children with type 1 diabetes- steps to active kids with diabetes (STAK-D): a feasibility study

Background This study describes the development and feasibility evaluation of a physical activity intervention for children with type 1 diabetes called ‘Steps to Active Kids with Diabetes’ (STAK-D). It aims to explore the feasibility and acceptability of the intervention and study design. Methods Thirteen children aged 9-11 years and their parents were recruited from one paediatric diabetes clinic. A process evaluation was conducted alongside a two-arm randomised feasibility trial, including assessment of rate of recruitment, adherence, retention, data completion and burden, implementation fidelity and adverse events. Qualitative interviews with children (n=9), parents (n=8), healthcare professionals (n=3) and STAK-D volunteers (n=8) explored intervention acceptability. Interviews were analysed thematically. Results Rate of recruitment was 25%, with 77% retention at 3-month follow-up. Study burden was low, data completion was high and the intervention was delivered as per protocol. No serious adverse event was reported. Engagement with intervention materials was generally good, but attendance at group activity sessions was low due to logistical barriers. Interview analysis identified preferred methods of recruitment, motivations for recruitment, barriers and facilitators to adherence, the experience of data collection, experience of the STAK-D programme and its perceived benefits. Conclusions STAK-D was feasible and acceptable to children, their parents and healthcare professionals, but group sessions may present logistical issues. Recruitment and retention may be improved with a clinic-wide approach to recruitment. Trial registration This trial was registered on ClinicalTrials.gov: NCT02144337 (16/01/2014). Keywords Children, feasibility study, intervention, paediatric diabetes, physical activity, process evaluation, self-efficacy, type 1 diabete

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Graded structure in sexual definitions: categorizations of having “had sex” and virginity loss among homosexual and heterosexual men and women

Definitions of sexual behavior display a robust hierarchy of agreement regarding whether or not acts should be classed as, for example, sex or virginity loss. The current research offers a theoretical explanation for this hierarchy, proposing that sexual definitions display graded categorical structure, arising from goodness of membership judgments. Moderation of this graded structure is also predicted, with the focus here on how sexual orientation identity affects sexual definitions. A total of 300 18- to 30-year-old participants completed an online survey, rating 18 behaviors for how far each constitutes having “had sex” and virginity loss. Participants fell into one of four groups: heterosexual male or female, gay male or lesbian. The predicted ratings hierarchy emerged, in which bidirectional genital acts were rated significantly higher than unidirectional or nonpenetrative contact, which was in turn rated significantly higher than acts involving no genital contact. Moderation of graded structure was also in line with predictions. Compared to the other groups, the lesbian group significantly upgraded ratings of genital contact that was either unidirectional or nonpenetrative. There was also evidence of upgrading by the gay male sample of anal intercourse ratings. These effects are theorized to reflect group-level variation in experience, contextual perspective, and identity-management. The implications of the findings in relation to previous research are discussed. It is suggested that a graded structure approach can greatly benefit future research into sexual definitions, by permitting variable definitions to be predicted and explained, rather than merely identified

CO I Barcoding Reveals New Clades and Radiation Patterns of Indo-Pacific Sponges of the Family Irciniidae (Demospongiae: Dictyoceratida)

DNA barcoding is a promising tool to facilitate a rapid and unambiguous identification of sponge species. Demosponges of the order Dictyoceratida are particularly challenging to identify, but are of ecological as well as biochemical importance.Here we apply DNA barcoding with the standard CO1-barcoding marker on selected Indo-Pacific specimens of two genera, Ircinia and Psammocinia of the family Irciniidae. We show that the CO1 marker identifies several species new to science, reveals separate radiation patterns of deep-sea Ircinia sponges and indicates dispersal patterns of Psammocinia species. However, some species cannot be unambiguously barcoded by solely this marker due to low evolutionary rates.We support previous suggestions for a combination of the standard CO1 fragment with an additional fragment for sponge DNA barcoding