Observational studies showed that circulating L-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation.

Interventions to promote positive parenting are often reported to offer good outcomes for children but they can consume substantial resources and they require rigorous appraisal.

Loss of muscle mass and strength with ageing is a major cause for falls, disability, and morbidity in older people. Previous studies have found that angiotensin-converting enzyme inhibitors (ACEi) may improve physical function in older people. It is unclear whether ACEi provide additional benefit when added to a standard exercise training program. We examined the effects of ACEi therapy on physical function in older people undergoing exercise training.

Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.

Caring for a child with intellectual disabilities can be a very rewarding but demanding experience. Research in this area has primarily focused on mothers, with relatively little attention given to the mental health of fathers.

Observational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively 'rule out' and 'rule in' acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible.

In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effects.

Background Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results A prespecified physiology substudy of the T-TIME trial. From 2016 to 2017, patients with ST-segment-elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double-blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2-4, and ≥4 hours) were prespecified. One hundred forty-four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0-55.0), coronary flow reserve(1.4 [1.1-2.0]), and resistive reserve ratio (1.7 [1.3-2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions In ST-segment-elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear.

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.

The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes.

Functional strength training in addition to conventional physical therapy could enhance upper limb recovery early after stroke more than movement performance therapy plus conventional physical therapy.

HelpMeDoIt! will test the feasibility of an innovative weight loss intervention using a smartphone app and website. Goal setting, self-monitoring and social support are three key facilitators of behaviour change. HelpMeDoIt! incorporates these features and encourages participants to invite 'helpers' from their social circle to help them achieve their goal(s).

Coronary angiography is performed to assess for obstructive coronary artery disease (CAD), but "nonobstructive CAD" is a common finding. Microvascular or vasospastic angina may be relevant, but routine confirmatory testing is not evidence based and thus rarely performed.

Access to Cognitive behavioural therapy (CBT) for depression is limited. One solution is CBT self-help books. Trial Objectives: To assess the impact of a guided self-help CBT book (GSH-CBT) on mood, compared to treatment as usual (TAU).

To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA).

Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA).

The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607 ). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and at 28-60 days post-discharge when multisystem imaging using chest computed tomography with pulmonary and coronary angiography and cardio-renal magnetic resonance imaging was also obtained. Longer-term clinical outcomes were assessed using electronic health records. Compared to controls (n = 29), at 28-60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was 'very likely' in 21 (13%) patients, 'probable' in 65 (41%) patients, 'unlikely' in 56 (35%) patients and 'not present' in 17 (11%) patients. At 28-60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain.