Adherence to smoking cessation medications: investigating relevant factors and developing strategies to improve smoking cessation and medication adherence

BACKGROUND: Tobacco smoking accounts for 11.5% of deaths globally. The Australian Burden of Disease study estimated that tobacco smoking accounts for one in every eight deaths. Tobacco control is an integral part of the sustainable development goal (SDG-3), a goal for strengthening the implementation of the WHO FCTC around the globe. Smoking cessation is one of the most important and cost-effective preventive health measures to reduce the risk of mortality and morbidity. Smoking cessation can be achieved through a variety of methods, but the most widely accepted approach involves seeking behavioural support from a health professional, with or without pharmacological therapy. Tobacco treatment guidelines and professional societies around the globe recommend the use of smoking cessation medications (SCMs) for tobacco treatment. SCMs reduce the extent of withdrawal symptoms and work by reducing the occurrence and strength of urges to smoke or cravings. There are three pharmacotherapies currently licensed widely throughout the globe for smoking cessation: Nicotine replacement therapy (NRT), bupropion, and varenicline. However, there are inconsistent findings across studies regarding the effectiveness of SCMs. The variations in the effectiveness could be partially explained by the inconsistent use of the SCMs. AIMS: This thesis aims to answer the following key research questions, in a systematic way, using three phases: Phase 1: What is the level of adherence to SCMs and its impact on smoking cessation? Aims: I. To synthesis studies describing adherence to SCMs and produce a pooled estimate of the level of adherence and its effect on the success of quit attempts. (Chapter 2) II. To explore the level and impact of adherence and other relevant factors on successful quitting among smokers and ex-smokers in Australia. (Chapters 4, 5) Phase 2: What are the barriers and facilitators of adherence to SCMs? Aims: I. To synthesis and summarise studies that explored factors associated with adherence to SCMs by using a predefined behavioural model (COM-B model). (Chapter 3) II. To explore the barriers and facilitators to adherence to SCMs among smokers and ex-smokers in Australia. (Chapter 4) III. To explore the attitude, practice, and perceived barriers to adherence support provision among health care providers (HCP) in Australia. (Chapter 6) Phase 3: How can we improve adherence to SCMs? Aims: I. To determine modes of intervention delivery strategies to improve the rate of successful smoking cessation. (Chapter 7) II. To co-design an intervention directed to improve adherence to SCMs and successful quitting in Australia. (Chapter 8). METHODS: This thesis used multiple methodologies to address the research objectives. Seven studies were conducted in three phases. I began this program of work by conducting a systematic review and meta-analysis to evaluate the rate and impact of adherence to NRT using studies conducted in various countries. This was followed by a systematic review to evaluate the barriers and facilitators of adherence to NRT using a theoretical framework, the Capability, Opportunity, Motivation, and Behaviour (COM-B) Model. Based on the findings from the reviews, cross-sectional studies were conducted in Australia to evaluate the contemporary level of adherence, the factors associated with adherent SCM use, and the effect of adherence on smoking cessation. To evaluate adherence, participants’ self-reported duration and weekly consumption pattern of SCMs were used. Participants were considered adherent if they utilised SCMs for a minimum of 4 weeks and, on average, for 5 or more days per week. A further descriptive study was conducted to evaluate the attitudes and practices of HCPs towards adherence to SCMs in Australia. Finally, a systematic stepped approach using the BCW guide and modified consensus-based Delphi study among expert panels was conducted to design interventions targeted to improve adherence to SCMs. To investigate the mode of intervention for the proposed interventions, an umbrella review was used in addition to the HCP survey and consultation with expert panels in the modified Delphi study. KEY FINDINGS: 1. The level of adherence to SCMs was found to be low and significantly associated with successful smoking cessation. I. Only one in four participants were found to be adherent to SCMs in a meta-analysis as well as a national cross-sectional study in Australia. II. Adherence to SCMs was found to be associated with a two-fold increase in successful smoking cessation. 2. A range of factors were associated with adherence to SCMs. I. A multitude of factors related to the person making a quit attempt such as forgetfulness and attitude towards the medications were found to be associated with adherence to SCMs. II. Various perceived barriers to providing adherence services by HCPs were reported such as lack of skill, lack of knowledge, and lack of resources. 3. Improving adherence to smoking cessation medications is a complex issue that requires a comprehensive approach using multiple intervention delivery modes. I. Superior effectiveness in smoking cessation was achieved when face-to-face approaches were blended with web and/or mobile-based modes of intervention. Participating HCPs in Australia considered face-to-face, mobile phone-based, and web-based interventions as acceptable and effective modes to deliver adherence support. II. Improving adherence to SCMs requires a multi-level and comprehensive adherence approach. An adherence support wheel was designed to guide implementation strategies and programmes to improve adherence and enhance the effectiveness of SCMs. The adherence wheel incorporated 13 strategies including providing detailed instruction on how to use SCMs; establishing a realistic expectation about SCMs; and providing training for HCPs regarding comprehensive smoking cessation care with specifics on the provision of adherence support. DISCUSSION AND CONCLUSION: This thesis provides robust evidence regarding relevant factors and strategies to improve adherence to SCM and smoking cessation. Improving adherence to SCMs is a complex issue that requires a comprehensive approach and interventions rather than focusing on a single intervention strategy. The designed adherence support wheel can potentially be used to inform future smoking cessation trials and programmes. Further research is required to test the effectiveness and to identify opportunities for further enhancing the suitability of the proposed adherence support strategies elicited using the adherence support wheel. The findings from this thesis can be used to inform current clinical practice and relevant policies targeted to curb the burden of smoking through improving the effectiveness of SCMs, adherence, and smoking cessation. This thesis can contribute a new strategy to improve the effectiveness of smoking cessation medications and provide a valuable input for Australia’s national goal to reduce the rate of smoking below 10% in 2025

Koori Quit Pack mailout smoking cessation support for Aboriginal and Torres Strait Islander people who smoke: a feasibility study protocol

Introduction: Smoking remains the leading preventable cause of death for Aboriginal and Torres Strait Islander people in Australia. Aboriginal and Torres Strait Islander people who smoke are more likely to make a quit attempt than their non-Aboriginal counterparts but less likely to sustain the quit attempt. There is little available evidence specifically for and by Indigenous peoples to inform best practice smoking cessation care. The provision of a free Koori Quit Pack with optional nicotine replacement therapy sent by mail may be a feasible, acceptable and effective way to access stop smoking support for Aboriginal and Torres Strait Islander peoples. Methods and analysis: An Aboriginal-led, multisite non-randomised single-group, pre-post feasibility study across three states in Australia will be conducted. Participants will be recruited via service-targeted social media advertising and during usual care at their Aboriginal Community Controlled Health Services. Through a process of self-referral, Aboriginal and Torres Strait Islander people who smoke daily will complete a survey and receive mailout smoking cessation support. Data will be collected over the phone by an Aboriginal Research Assistant. This pilot study will inform the development of a larger, powered trial. Ethics and dissemination: Ethics approval has been obtained from the Aboriginal Health & Medical Research Council Ethics Committee of New South Wales (NSW) (#1894/21) and the University of Newcastle (#H-2022-0174). Findings will be reported through peer-reviewed journals and presentations at relevant local, national and international conferences. The findings will be shared with the NSW and Victoria Quitline, Aboriginal Health and Medical Research Council and Victorian Aboriginal Community Controlled Organisation and the National Heart Foundation. </p

Which way? Group-based smoking and vaping cessation support for Aboriginal and Torres Strait Islander women: protocol for a non-randomised type 1 hybrid implementation study.

INTRODUCTION: Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%-130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities. METHODS AND ANALYSIS: The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness. ETHICS AND DISSEMINATION: Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments. TRIAL REGISTRATION NUMBER: ACTRN12625001050448

The burden and trend of diseases and their risk factors in Australia, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

The burden and trend of diseases and their risk factors in Australia, 1990–2019: a systematic analysis for the Global Burden of Disease Study 201

Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990–2019: results from the Global Burden of Disease Study 2019

Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990–2019: results from the Global Burden of Disease Study 201

Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 201

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990–2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990–2019, for 204 countries and territories: the Global Burden of Diseases Study 201

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 201

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background: Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings: In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation: Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

BackgroundRegularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels.MethodsWe applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level.FindingsIn 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]).InterpretationThe annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.FundingBill & Melinda Gates Foundation