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AnteayerBMJ Open

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial

Por: Boczar · K. E. · Shin · S. · deKemp · R. A. · Dowlatshahi · D. · Tavoosi · A. · Wiefels · C. · Liu · P. · Lochnan · H. · MacPherson · P. A. · Chong · A. Y. · Torres · C. · Leung · E. · Tawakol · A. · Ahmadi · A. · Garrard · L. · Lefebvre · C. · Kelly · C. · MacPhee · P. · Tilokee · E. · Ragg
Background

Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy.

Objective

The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine’s effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes.

Methods and design

CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30–120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging.

Discussion

Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy.

Trial registration number

NCT04181996.

Very brief intervention for physical activity behaviour change in cardiac rehabilitation: protocol for the 'Measure It! effectiveness-implementation hybrid trial

Por: Freene · N. · McPhail · S. M. · Tyack · Z. · Kunstler · B. · Niyonsenga · T. · Keegan · R. · Gallagher · R. · Abhayaratna · W. · Verdicchio · C. · Davey · R.
Introduction

Physical inactivity is a risk factor for repeat cardiac events and all-cause mortality in coronary heart disease (CHD). Cardiac rehabilitation, a secondary prevention programme, aims to increase physical activity levels in this population from a reported low baseline. This trial will investigate the effectiveness and implementation of a very brief physical activity intervention, comparing different frequencies of physical activity measurement by cardiac rehabilitation clinicians. The Measure It! intervention (

Methods and analysis

This type 1 hybrid effectiveness–implementation study will use a two-arm multicentre assessor-blind randomised trial design. Insufficiently active (

Ethics and dissemination

The study has ethical approval (University of Canberra (ID 11836), Calvary Bruce Public Hospital (ID 14-2022) and the Greater Western Area (ID 2022/ETH01381) Human Research Ethics Committees). Results will be disseminated in multiple formats for consumer, public and clinical audiences.

Trial registration number

ACTRN12622001187730p.

Perception of and legal compliance with the law prohibiting cigarette sales to minors in Thailand following the raising of the minimum selling age to 20 years: a cross-sectional survey

Por: Phetphum · C. · Chomson · S. · Wangwonsin · A. · Prajongjeep · A. · Keeratisiroj · O.
Objectives

The minimum age for cigarette sales in Thailand was increased from 18 to 20 years, as stipulated in the Tobacco Products Control Act B.E. 2017. This study investigated tobacco retailers’ perceptions, cigarette sales behaviour and other factors relevant to selling cigarettes to people younger than 20 years in areas surrounding schools in Thailand.

Design

Cross-sectional survey.

Setting

Tobacco shops within a radius of 500 m of secondary schools across four regions of Thailand. Data collection took place between May and August 2019.

Participants

1440 tobacco retailers (grocery or convenience stores) were sampled via a stratified, two-stage cluster sampling method. 1021 retailers completed the self-administered questionnaire.

Outcome measures

Tobacco sales to people younger than 20 years.

Results

The prevalence of the retailers’ cigarette sales to youth younger than 20 years was 38.20% (95% CI 35.2% to 41.3%). Multivariable logistic regression analysis revealed associations with sale of single cigarettes (adjusted OR (AOR) 23.14, 95% CI 15.13 to 35.39), self-service sale of cigarettes (4.21, 2.59 to 6.86) and display of cigarettes at the point of sale (2.39, 1.47 to 3.89). Cigarette sales to underage youth were higher among retailers located in the northeast region (AOR 2.09, 95% CI 1.20 to 3.64) and among those who did not perceive the prosecution of violators in the past year (1.85, 1.16 to 2.96).

Conclusion

A large percentage of cigarette retailers violated the laws related to underage cigarette sales. Measures to minimise retailers’ legally non-compliant sales behaviours should be implemented along with improved legal enforcement.

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