Publications by authors named "Nicholls S"

Background: Instantaneous wave-free ratio (iFR) can reliably assess the physiological significance of coronary artery disease (CAD). Previous studies have demonstrated its interchangeability with other non-hyperaemic pressure ratios (NHPR), but there is no data exploring whether this association is maintained in patients with severe aortic stenosis (AS).

Methods: Forty-two patients (67 lesions) with severe AS were recruited and underwent invasive pressure-wire assessment.

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Background: The transfer of information is a key aspect of the transition of adolescent patients with inflammatory bowel disease (IBD) from pediatric to adult care. This is typically accomplished through the use of a consultation letter with a medical summary of the patient being transferred. To improve the quality and completeness of information included in a transfer letter, we developed a standardized medical summary template by integrating the feedback of adult and pediatric health care providers.

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Background And Aims: We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates.

Methods: We performed a pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque.

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In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis as one of the leading causes of global death, morbidity and economic burden, novel ways of analyzing and predicting its progression are needed. One such computational method is the use of fluid-structure interaction (FSI) to analyze the interaction between the blood flow and artery/plaque domains.

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Meta-research is the discipline of studying research itself. A core investigative tool in meta-research is the use of systematic or scoping reviews to study the characteristics, methods and reporting of primary research studies. In the context of identifying eligible publications for methodological reviews of randomized controlled trials (RCTs), a challenge is to efficiently distinguish the primary trial report - which reports results for the primary outcome - from other types of reports, including design papers and secondary or supplementary analyses, or what we collectively refer to as non-primary reports.

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Objective: To determine the association between prosthesis geometry with leaflet thrombosis (LT).

Background: Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) is a recognised entity. The association between prosthesis geometry with LT is unclear but maybe a potential modifiable factor in its prevention.

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Background: Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study.

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Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical protein kinase that controls protein synthesis in cells under stress. Although well studied in cancer, less is known about its roles in chronic inflammatory diseases. Here, we examined its regulation of macrophage cholesterol handling in the context of atherosclerosis.

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The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia.

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Over the last 3 decades there have been substantial improvements in treatments aimed at reducing cardiovascular (CV) events. As these treatments have been developed, there have been parallel improvements in coronary imaging modalities that can assess plaque volumes and composition, using both invasive and noninvasive techniques. Plaque progression can be seen to precede CV events, and therefore, many studies have longitudinally assessed changes in plaque characteristics in response to various treatments, aiming to demonstrate plaque regression and improvements in high-risk features, with the rationale being that this will reduce CV events.

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Objective: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute coronary syndromes (ACS).

Methods: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through August 23, 2020. Random-effects meta-analysis method was used to pool estimates.

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Objective: Plasma total HDL (high-density lipoprotein) is a heterogeneous mix of many protein-based subspecies whose functions and associations with coronary heart disease vary. We hypothesize that increasing HDL by CETP (cholesteryl ester transfer protein) inhibition failed to reduce cardiovascular disease risk, in part, because it increased dysfunctional subspecies associated with higher risk such as HDL that contains apoC3. Approach and Results: We studied participants in 2 randomized, double-blind, placebo-controlled trials of a CETP inhibitor on a background of atorvastatin treatment: ACCENTUATE (The Addition of Evacetrapib to Atorvastatin Compared to Placebo, High Intensity Atorvastatin, and Atorvastatin With Ezetimibe to Evaluate LDL-C Lowering in Patients With Primary Hyperlipidemia; 130 mg evacetrapib; n=126) and ILLUMINATE (Phase 3 Multi Center, Double Blind, Randomized, Parallel Group Evaluation of the Fixed Combination Torcetrapib/Atorvastatin, Administered Orally, Once Daily [Qd], Compared With Atorvastatin Alone, on the Occurrence of Major Cardiovascular Events in Subjects With Coronary Heart Disease or Risk Equivalents; 60 mg torcetrapib; n=80).

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Objectives: To describe prevalence of multiple primary outcomes, changes in primary outcomes and target sample sizes between protocols and final reports, and how issues of multiplicity are addressed in pragmatic trials.

Study Design And Setting: Individually randomized trials labeled as pragmatic, published 2014-2019 in MEDLINE and registered with ClinicalTrials.gov.

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Background: Hypo-attenuated leaflet thickening (HALT) may occur following transcatheter aortic valve replacement (TAVR), however, it remains unclear if HALT is a predictor of haemodynamic valve deterioration (HVD).

Aim: To determine the impact of HALT on the occurrence of HVD.

Methods: We prospectively evaluated 186 patients for the presence of HALT at a median of 6 weeks following TAVR (Interquartile-range [IQR] 4-12 weeks).

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Introduction: Elevated levels of low-density lipoprotein (LDL) cholesterol have been unequivocally demonstrated to play a causal role in atherosclerotic cardiovascular disease. The last thirty years have witnessed a generation of clinical trials that have demonstrated a reduction in cardiovascular risk with the use of increasing intensive lipid lowering regimens involving statin therapy in combination with other agents. However, many patients fail to achieve treatment mandated LDL cholesterol goals.

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Background And Aims: We need more pragmatic trials of interventions to improve care and outcomes for people living with Alzheimer's disease and related dementias. However, these trials present unique methodological challenges in their design, analysis, and reporting-often, due to the presence of one or more sources of clustering. Failure to account for clustering in the design and analysis can lead to increased risks of Type I and Type II errors.

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Aims: The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH).

Methods And Results: We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18-40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries.

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Objectives: To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent.

Methods: Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.

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Background: Core outcome sets (COS) are lists of consensus-determined outcomes to be measured and reported in all clinical research studies within a disease area. While including patients and families in COS development to improve their relevance and applicability to patient values is key, there is limited literature documenting practical barriers and facilitators to successful patient engagement in COS development. In this paper, as researchers and patient partners, we provide a resource for COS developers to meaningfully and effectively engage patients and families.

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The COVID-19 pandemic has highlighted the global imperative to address health inequities. Observational studies are a valuable source of evidence for real-world effects and impacts of implementing COVID-19 policies on the redistribution of inequities. We assembled a diverse global multi-disciplinary team to develop interim guidance for improving transparency in reporting health equity in COVID-19 observational studies.

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We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.

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