A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient's physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.

Methods: This international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic.

The NITRATE-OCT study-inorganic nitrate reduces in-stent restenosis in patients with stable coronary artery disease: a double-blind, randomised controlled trial.

Background: Coronary angioplasty and stent insertion is a first line treatment for patients with coronary artery disease, however it is complicated in the long-term by in-stent restenosis (ISR) in a proportion of patients with an associated morbidity. Despite this, currently there are no effective treatments available for the prevention of ISR. Repeat percutaneous revascularisation carries increased risks of major adverse cardiovascular events and a higher incidence of stent failure.

Characterization of dynamic changes in cardiac microstructure after reperfused ST-elevation myocardial infarction by biphasic diffusion tensor cardiovascular magnetic resonance.

Background And Aims: Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling.

Predictors of the efficacy of His bundle pacing in patients with a prolonged PR interval: A stratified analysis of the HOPE-HF randomized controlled trial.

Aims: The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VOmax) but there was significant improvement in heart failure specific quality of life.

A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol.

Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g.

Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation: a prospective, randomized, multi-centre, open label trial.

Aims: There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF.

Decision support system to evaluate ventilation in the acute respiratory distress syndrome (DeVENT study)-trial protocol.

Background: The acute respiratory distress syndrome (ARDS) occurs in response to a variety of insults, and mechanical ventilation is life-saving in this setting, but ventilator-induced lung injury can also contribute to the morbidity and mortality in the condition. The Beacon Caresystem is a model-based bedside decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean, in particular ARDS.

Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.

Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids.

Background & Aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).

Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 10 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV.

Ablation versus Anti-Arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent Atrial Fibrillation (AVATAR-AF): Design and rationale.

Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment.

Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure.

Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki.

Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy.

Implantable cardiodefibrillators (ICDs) have proven benefit in preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk stratification essential. Data on the predictive accuracy on the European Society of Cardiology (ESC) risk scoring system have been conflicting. We independently evaluated the ESC risk scoring system in our cohort of patients with HC from a large tertiary center and compared this with previous guidance by the American College of Cardiology Foundation and Heart Association (ACCF/AHA).

A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus.

Introduction: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum.

Are valved holding chambers (VHCs) interchangeable? An in vitro evaluation of VHC equivalence.

Introduction: The European Medicines Agency (EMA) requires that a specific valved holding chamber (VHC) is designated for use with a given pressurised metered dose inhaler (pMDI). No other regulatory authorities impose similar requirements, implying that VHCs are interchangeable. This in vitro study, employing EMA assessment criteria, assessed the equivalence of four anti-static VHCs (aVHCs) versus the non-conducting VHC most widely referenced in pMDI monographs, the AeroChamber Plus™ (AC+) VHC.

Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease.

Background And Purpose: Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort.

Methods: A total of 1185 participants (age, 68.

Multicentre observational study of surgical system failures in aortic procedures and their effect on patient outcomes.

Background: Vascular surgical care has changed dramatically in recent years with little knowledge of the impact of system failures on patient safety. The primary aim of this multicentre observational study was to define the landscape of surgical system failures, errors and inefficiency (collectively termed failures) in aortic surgery. Secondary aims were to investigate determinants of these failures and their relationship with patient outcomes.

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK).

Background: Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases.

Objectives: (1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters.

Design: A three-arm, multicentre, single-blind, randomised placebo-controlled trial.

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK).

Aims: The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering.

Methods And Results: A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged ≥55 years with AAA diameter 3.

No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.

Background: Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality.

Methods: Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.

Hypertension management in England: a serial cross-sectional study from 1994 to 2011.

Background: Hypertension is the leading risk factor contributing to the global burden of disease. We aimed to assess the change in blood pressure management between 1994 and 2011 in England with a series of annual surveys.

Methods: We did a serial cross-sectional study of five Health Survey for England surveys based on nationally representative samples of non-institutionalised adults (aged ≥16 years).