Levelling the playing field through the London Network of the UK clinical trials accelerator platform.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

Effect of message framing on support for a sugar-sweetened beverage tax in Australia: a cross-sectional survey analysis.

Sugar-sweetened beverage (SSB) taxes are present in many countries with evidence that they are effective in decreasing purchases of SSBs. However, in Australia where SSB consumption per capita is high, and calls for an SSB tax are frequent, there is no SSB tax and policymakers have stated their lack of support for such a tax. We examined whether political party voting preference and sociodemographic factors affect individuals' support for an SSB tax, and whether message framing affects this support. A nationally representative sample of 1519 Australian adults was recruited for an online experimental survey. Three persuasive frames and one control frame were randomly provided to participants and measures of agreement towards an SSB tax were assessed. Sociodemographic factors and political party preference were also captured. Message framing had minimal effect on the level of support for the tax. However, participants who received the 'supportive of food and drink companies frame' showed the highest positive feelings towards the tax, and participants in rural areas had higher levels of support for an SSB tax when receiving the 'protecting teenagers' frame. Participants who voted for conservative (right-leaning) parties and for Labour (a centre-left party) had similar levels of support towards the tax, which was considerably lower than Greens voters. Undecided voters had the lowest levels of support for the tax, and the frames had limited impact on them. These findings highlight the potential role of message framing in shaping public support for an SSB tax in Australia, particularly in the context of voting preference and sociodemographic factors.

Trajectories of Parental Warmth and the Role They Play in Explaining Adolescent Prosocial Behavior.

Adolescent prosocial behavior suggests social competence and it is associated with greater parental warmth yet the experience of warmth through child and adolescent development is not well understood as it relates to such prosocial behavior. A nationally representative dataset from the Longitudinal Study of Australian Children cohort was used. The analyses involved multiple waves beginning when children were aged 4-5. The main analyses used a sample of 2723 adolescents aged 16-17 years (Mean, S.D. = 16.45, 0.50; 49.2% female, 50.8% male). Parental warmth trajectories (from ages 4-5 through 16-17 years) were created and used to explore the accumulated effect of a lifecourse of parental warmth on adolescent prosocial behavior as measured when adolescents were aged 16-17 years. There were three trajectories described as, consistent (28.7%), slight decline (51.4%), and declining warmth (19.8%). These were associated with prosocial behavior; adolescents with a slight decline in warmth were 2.2 times less likely than those with consistent warmth to have the highest prosocial behavior. Consistent parental warmth likely provides greatest benefit for increased prosocial behavior in mid-adolescence.

What can death records tell us about multimorbidity?

BACKGROUND: Multimorbidity has been measured from many data sources which show that prevalence increases with age and is usually greater among women than men and in more recent periods. Analyses of multiple cause of death data have shown different patterns of multimorbidity associated with demographic and other characteristics. METHODS: Deaths in Australia among over 1.7 million decedents aged 55+ were stratified into three types: medically certified deaths, coroner-referred deaths with natural underlying causes and coroner-referred deaths with external underlying causes. Multimorbidity was measured by prevalence of ≥2 causes and analysed over three periods based on administrative changes: 2006-2012, 2013-2016 and 2017-2018. Poisson regression was used to examine the influence of gender, age and period. RESULTS: The prevalence of deaths with multimorbidity was 81.0% for medically certified deaths, 61.1% for coroner-referred deaths with natural underlying causes and 82.4% for coroner-referred deaths with external underlying causes. For medically certified deaths, multimorbidity increased with age: incidence rate ratio (IRR 1.070, 95% CI 1.068, 1.072) was lower for women than men (0.954, 95% CI 0.952, 0.956) and changed little over time. For coroner-referred deaths with natural underlying causes, multimorbidity showed the expected pattern increasing with age (1.066, 95% CI 1.062, 1.070) and being higher for women than men (1.025, 95% CI 1.015, 1.035) and in more recent periods. For coroner-referred deaths with external underlying causes, there were marked increases over time that differed by age group due to changes in coding processes. CONCLUSION: Death records can be used to examine multimorbidity in national populations but, like other data sources, how the data were collected and coded impacts the conclusions.

A new data driven method for summarising multiple cause of death data.

BACKGROUND: National mortality statistics are based on a single underlying cause of death. This practice does not adequately represent the impact of the range of conditions experienced in an ageing population in which multimorbidity is common. METHODS: We propose a new method for weighting the percentages of deaths attributed to different causes that takes account of the patterns of associations among underlying and contributing causes of death. It is driven by the data and unlike previously proposed methods does not rely on arbitrary choices of weights which can over-emphasise the contribution of some causes of death. The method is illustrated using Australian mortality data for people aged 60 years or more. RESULTS: Compared to the usual method based only on the underlying cause of death the new method attributes higher percentages of deaths to conditions like diabetes and dementia that are frequently mentioned as contributing causes of death, rather than underlying causes, and lower percentages to conditions to which they are closely related such as ischaemic heart disease and cerebrovascular disease. For some causes, notably cancers, which are usually recorded as underlying causes with few if any contributing causes the new method produces similar percentages to the usual method. These different patterns among groups of related conditions are not apparent if arbitrary weights are used. CONCLUSION: The new method could be used by national statistical agencies to produce additional mortality tables to complement the current tables based only on underlying causes of death.

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis.

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF. The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF. Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy.

STI and HIV testing: examining factors that influence uptake among domestic Australian-born, domestic overseas-born and international tertiary students studying in Australia.

OBJECTIVES: Sexual health knowledge among international students in Australia is lower than domestic students, however, little is known about what factors affect the uptake of STI testing, nor if there are differences for overseas-born domestic students. METHODS: We included sexually active respondents from a survey of university students in Australia (N = 3,075). Multivariate regression and mediation analyses investigated associations of STI and HIV testing with STI and HIV knowledge respectively, sexual risk behaviour and demographics, including comparisons among: domestic Australian-born, domestic overseas-born, and international students. RESULTS: STI and HIV knowledge was positively associated with STI and HIV testing respectively (STI OR = 1.13, 95% CI: 1.09, 1.16; HIV OR = 1.37, 95% CI: 1.27, 1.48). STI knowledge was significantly lower for international than domestic Australian-born students (10.8 vs. 12.2 out of 16), as was STI testing (32% vs. 38%); the difference in knowledge accounted for half the difference in STI testing rates between these two groups. International students from Southern Asia, and Eastern Asia reported the lowest STI testing rates. HIV testing was highest amongst international students from Africa and North America. Higher sexual risk behaviour, younger age, and identifying as gay or bisexual were positively associated with higher STI and HIV testing rates. CONCLUSIONS: Our study supports greater investment and commitment by universities for the provision of sexual health education that can promote access to testing to improve the health of their students.

The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma.

BACKGROUND: Encapsulated angioinvasive follicular thyroid carcinoma (EAFTC) is associated with an increased risk of distant metastasis and reduced survival compared to minimally invasive follicular thyroid carcinoma (MIFTC). There is controversy regarding the extent of surgery and adjuvant radioactive iodine therapy for angioinvasive follicular thyroid carcinoma when stratified by number of foci of angioinvasion. METHODS: All follicular thyroid carcinoma cases from 1990-2018 were identified from a thyroid cancer database. Primary outcomes were distant metastasis-free survival (DMFS) and disease-specific survival (DSS) with factors of interest being age, gender, tumour size, treatment, foci of angioinvasion and histological subtype. RESULTS: A total of 292 cases were identified; 139 MIFTC, 141 EAFTC and 12 widely invasive follicular thyroid carcinoma (WIFTC). Over a follow-up period of 6.25 years, DMFS was significantly reduced (p < 0.001) with 14.2% (EAFTC) and 50% of WIFTC developing metastasis. The risk of metastasis in EAFTC with ≥ 4 foci of angioinvasion was 31.7% (HR = 5.89, p = 0.004), 6.3% for EAFTC with < 4 foci of angioinvasion (HR = 1.74, p = 0.47), compared to 3.6% MIFTC. Age ≥ 50 years (HR = 4.24, p = 0.005) and tumour size (HR = 1.27, p = 0.014) were significantly associated with increased risk of distant metastasis. DSS was reduced significantly (p < 0.001), with 7.8% EAFTC patients dying of disease. For EAFTC patients, DSS was 96.8% for < 4 foci and 82.6% for ≥ 4 foci of angioinvasion (p = 0.003). CONCLUSION: EAFTC is at increased risk of distant metastasis related to the extent of angioinvasion. Tumours with < 4 foci of angioinvasion should be considered for a total thyroidectomy, particularly in older patients.

Competing public narratives in nutrition policy: insights into the ideational barriers of public support for regulatory nutrition measures.

BACKGROUND: Enacting evidence-based public health policy can be challenging. One factor contributing to this challenge is a lack of public support for specific policies, which may stem from limited interest or conviction by policy arguments. This can happen when messaging strategies regarding policy do not resonate with the target group and/or policy narratives compete in public discourse. To understand how policy messaging can better resonate with a target audience, we examined the frames and narratives used by the Australian public when discussing nutrition policies. METHODS: We conducted 76 street intercept interviews in urban and regional settings in Queensland, Australia. Quantitative data were analysed using mean agreement scores and t-tests, and the qualitative data were analysed using an adapted qualitative narrative policy framework (QNPF). The QNPF is used to illustrate how competing narratives vary in the way they define different elements. These elements often include setting, characters, plot, policy solution and belief systems. RESULTS: Level of support for all nutrition policies was generally moderate to high, although nutrition policies perceived to be most intrusive to personal freedoms were the least popular among the public. The value of fairness was consistently invoked when participants discussed their support for or opposition to policy. Using the QNPF, two distinct settings were evident in the narratives: concern for the community or concern for self. Villains were identified as either "other individuals, in particular parents" or "Big Food". Victims were identified as "children" or "the food industry, in particular farmers". Frequently used plots focused on individuals making poor choices because they were uneducated, versus Big Food being powerful and controlling people and the government. CONCLUSIONS: The study examined the frames and narratives used by the Australian public when discussing nutrition policies. By examining these frames and narratives, we gained insight into multiple strategies which may increase public support for certain nutrition policies in Australia.

The role of child diets in the association between pre-pregnancy diets and childhood behavioural problems: a mediation analysis.

OBJECTIVE: To quantify the mediating role of childhood diets in the relationship between maternal diets prior to pregnancy and childhood behavioural disorders. DESIGN: The Healthy Eating Index score was constructed using a semi-quantitative and validated 101-item FFQ. We assessed childhood behavioural disorders using the Strengths and Difficulties Questionnaire. Three dietary patterns were identified using principal component analysis to explore childhood dietary patterns (high fats and sugar; prudent diets; and diary). A causal inference framework for mediation analysis was used to quantify the mediating role of childhood diets in the association between pre-pregnancy diets and the risk of offspring behavioural problems. SETTING: This is a national representative population-based survey which covers all Australian citizens and permanent residents in Australia. PARTICIPANTS: We included 1448 mother-child pairs from the Australian Longitudinal Study on Women's Health and its sub-study mothers and their children's health. RESULTS: We found a 20 % of the total effect of the poor adherence to pre-pregnancy diet quality on the risk of offspring behavioural problems was mediated through childhood high consumptions of fats and sugar. No clear mediating effect through prudent and diary childhood diets was observed. CONCLUSION: This study suggests that childhood high fats and sugar consumption may contribute to the total effects of the pre-pregnancy diets on the risk of childhood behavioural problems.

Differing Methodologies Are Required to Estimate Prevalence of Dementia: Single Study Types Are No Longer Reliable.

Population-based surveys were used to estimate community prevalence of dementia, but have low response fractions due, among other things, to difficulties in obtaining informed consent from people with diminished capacity. Cohort studies of younger people are subject to recruitment bias and non-random drop-outs. Dementia registries can delineate sub-types of dementia but have limited population coverage and are costly to maintain. Administrative datasets have low costs but may be subject to selection bias and uncertain sensitivity. We propose that astute combination of methodologies, including assessment of coverage and validity of administrative datasets, is the most cost-effective process to estimate and monitor community prevalence.

Accuracy of death certifications of diabetes, dementia and cancer in Australia: a population-based cohort study.

BACKGROUND: National mortality statistics are only based on the underlying cause of death, which may considerably underestimate the effects of some chronic conditions. METHODS: The sensitivity, specificity, and positive and negative predictive values for diabetes (a common precursor to multimorbidity), dementia (a potential accelerant of death) and cancer (expected to be well-recorded) were calculated from death certificates for 9 056 women from the 1921-26 cohort of the Australian Longitudinal Study on Women's Health. Log binomial regression models were fitted to examine factors associated with the sensitivity of death certificates with these conditions as underlying or contributing causes of death. RESULTS: Among women who had a record of each of these conditions in their lifetime, the sensitivity was 12.3% (95% confidence interval, 11.0%, 13.7%), 25.2% (23.7%, 26.7%) and 57.7% (55.9%, 59.5%) for diabetes, dementia and cancer, respectively, as the underlying cause of death, and 40.9% (38.8%, 42.9%), 52.3% (50.6%, 54.0%) and 67.1% (65.4%, 68.7%), respectively, if contributing causes of death were also taken into account. In all cases specificity (> 97%) and positive predictive value (> 91%) were high, and negative predictive value ranged from 69.6% to 84.6%. Sensitivity varied with age (in different directions for different conditions) but not consistently with the other sociodemographic factors. CONCLUSIONS: Death rates associated with common conditions that occur in multimorbidity clusters in the elderly are underestimated in national mortality statistics, but would be improved if the multiple causes of death listed on a death certificate were taken into account in the statistics.

Designing an evidence-based Bayesian network for estimating the risk versus benefits of AstraZeneca COVID-19 vaccine.

Uncertainty surrounding the risk of developing and dying from Thrombosis and Thrombocytopenia Syndrome (TTS) associated with the AstraZeneca (AZ) COVID-19 vaccine may contribute to vaccine hesitancy. A model is urgently needed to combine and effectively communicate evidence on the risks versus benefits of the AZ vaccine. We developed a Bayesian network to consolidate evidence on risks and benefits of the AZ vaccine, and parameterised the model using data from a range of empirical studies, government reports, and expert advisory groups. Expert judgement was used to interpret the available evidence and determine the model structure, relevant variables, data for inclusion, and how these data were used to inform the model. The model can be used as a decision-support tool to generate scenarios based on age, sex, virus variant and community transmission rates, making it useful for individuals, clinicians, and researchers to assess the chances of different health outcomes. Model outputs include the risk of dying from TTS following the AZ COVID-19 vaccine, the risk of dying from COVID-19 or COVID-19-associated atypical severe blood clots under different scenarios. Although the model is focused on Australia, it can be adapted to international settings by re-parameterising it with local data. This paper provides detailed description of the model-building methodology, which can be used to expand the scope of the model to include other COVID-19 vaccines, booster doses, comorbidities and other health outcomes (e.g., long COVID) to ensure the model remains relevant in the face of constantly changing discussion on risks versus benefits of COVID-19 vaccination.

Association between reproductive lifespan and risk of incident type 2 diabetes and hypertension in postmenopausal women: Findings from a 20-year prospective study.

BACKGROUND: This study examined the association between reproductive lifespan and incident type 2 diabetes mellitus (T2DM) and hypertension in mid-age women. Also, the combined effect of reproductive lifespan and body mass index (BMI) on the risks of T2DM and hypertension were explored. METHODS: Reproductive lifespan was defined as the difference between age at menopause and age at menarche, and categorized as <35, 35-37, 38-40, and ≥41 years based on the quartile distribution. A multivariable Cox proportional hazard regression was used, adjusting for socio-demographic, lifestyle, and reproductive factors. RESULTS: Of 6357 postmenopausal women included (mean [SD] age at last follow-up, 66.3[3.3] years), a total of 655 developed incident T2DM (10.3%) and 1741 developed hypertension (30.0%) during 20 years of follow-up. The total sample had a mean (SD) reproductive lifespan of 37.9 (4.5). Compared with the women who had a reproductive lifespan of 38-40 years, those with a short reproductive lifespan (<35 years) had a 30% increased risk of T2DM and twice the risk of hypertension. Under the combined model, women who had a short reproductive lifespan (<35 years) and who had a BMI ≥30 kg/m2 at baseline showed a higher risk of T2DM (HR: 6.30, 95% CI: 4.41-8.99) and hypertension (HR: 6.06, 4.86-7.55) compared with women who had a reproductive lifespan of 38-40 years and a BMI < 25 kg/m2. CONCLUSIONS: A higher risk of both incident T2DM and hypertension at midlife was found among women experiencing a shorter reproductive lifespan, with pronounced risk for women experiencing both a short reproductive lifespan (<35 years) and a higher baseline BMI (≥30 kg/m2). Women with a short reproductive lifespan may benefit from maintaining healthy body weight in midlife.

Malaria Relapses Following Parasite-Free Blood Transfusions in the U.S. Army during the Korean War.

Latent Plasmodium vivax parasites in the liver known as hypnozoites activate causing malaria relapses months after the original infection. The putative initiation signal is unknown. Plasmodium falciparum infections appear to trigger P. vivax relapses and initiation of relapse may be triggered by hemolysis or fever. The U.S. Army hospital records from the Korean War (> 500,000 individual records) were used to determine whether there was an association between blood transfusion and vivax malaria relapse. Importantly, blood for transfusion was collected in the United States, so the risk of transmission of malaria parasites was minimal. Blood transfusion (largely for combat trauma) was a risk factor for subsequent vivax malaria (relative risk 2.54, 95% CI 2.15-2.99, P < 0.0001). As expected, blood transfusion was not a risk factor for subsequent dysentery, but transfusion was a risk factor for subsequent hepatitis. Blood transfusion causing an increased heme delivery to the liver and a subsequent redox signal within hepatocytes may partially explain hypnozoite activation leading to relapses of vivax malaria.

What Did We Miss? Analysis of Military Personnel Responses to an Open-Ended Question in a Post-Deployment Health Survey.

INTRODUCTION: Post-deployment health surveys completed by military personnel ask about a range of deployment experiences. These surveys are conducted to determine if there are links between experiences and poor health. Responses to open-ended questions in these surveys can identify experiences that might otherwise go unreported. These responses may increase knowledge about a particular deployment and inform future surveys. This study documented deployment experiences described by Australian Defence Force personnel who were deployed to the Middle East. MATERIALS AND METHODS: A survey completed by 14,032 personnel examined health outcomes and over 100 experiences relating to their Middle East deployment. Responses to two open-ended questions captured additional experiences. Descriptive statistics reveal the characteristics of those who did and did not describe additional experiences, and a content analysis details the nature and frequency of the experiences reported. The study was approved by an Institutional Review Board. RESULTS: Five percentage (n = 692) of personnel who completed the survey described additional deployment experiences. The most frequently reported experiences were specific Navy experiences; experiences of poor leadership; administrative or organizational issues; the anthrax vaccine; and traumatic events/potentially morally injurious experiences. CONCLUSIONS: The findings suggest that post-deployment health surveys should have questions about certain deployment experiences tailored by military service (i.e., Air Force, Army, and Navy). Researchers could consider including questions about personnel experiences of leadership for its impact on health and about potentially morally injurious experiences that may help explain adverse mental health. Clear wording of open-ended questions and participant instructions may improve response rates and reduce response biases.

Changes in dietary patterns from preconception to during pregnancy and its association with socio-demographic and lifestyle factors.

OBJECTIVE: To examine dietary patterns changes from preconception to during pregnancy and their associations with socio-demographic and lifestyle factors. DESIGN: This study used data from the Australian Longitudinal Study on Women's Health (ALSWH), a population-based prospective cohort study. Women's dietary patterns were assessed using Healthy Eating Index-2015 (HEI-2015) score and the four patterns were obtained from the factor analysis (Western diets, vegetable and grains, traditional vegetable and fruit patterns). Multi-variable linear regression and repeated measures mixed-effect models were used. SETTING: A national representative survey which covers all Australian citizens and permanent residents in Australia. PARTICIPANTS: 621 women were included from the ALSWH. RESULTS: Women's scores increased on the 'HEI-2015', 'traditional vegetable' and 'fruit' patterns while the 'vegetable and grains' decreased from preconception to during pregnancy. Women with higher education were more likely to increase their HEI-2015 score and fruit consumption from preconception to during pregnancy, respectively (ß = 2·31, (95 % CI 0·02, 4·60)) and (ß = 23·78, (95 % CI 4·58, 42·97)), than those with lower educational status. Single women were more likely to increase the consumption of vegetables and grains compared to married women (ß = 76·08, (95 % CI 20·83, 131·32)). Women with higher income had a greater increase in the HEI-2015 score than those with lower income (ß = 3·02, (95 % CI 0·21, 5·83)). CONCLUSION: The findings indicate that there have been marked dietary changes from preconception to during pregnancy. Changes in healthy dietary patterns were influenced by education, marital status and income.

Epidemiological studies of the association between reproductive lifespan characteristics and risk of Type 2 diabetes and hypertension: A systematic review.

Some reproductive factors are found to be associated with metabolic outcomes in women; however, little is known about reproductive lifespan characteristics and the mutual effect of age at menarche and age at menopause on cardiovascular risk. This systematic review evaluated reproductive lifespan characteristics and describes the mutual effect of age at menarche and age at menopause on the risk of type 2 diabetes (T2DM) and hypertension at midlife. PubMed, EMBASE, and Web of Science were screened for studies published up to September 1, 2020. The individual effect estimates were reviewed and synthesized without meta-analysis due to methodological and clinical or conceptual diversity in reported studies. Of the 3033 identified studies, 20 were included in the final synthesis: 6 reported reproductive life span; 12 reported age at menarche, and 7 reported age at menopause. Synthesis of two cohorts, with a median follow-up of 9-11 years, showed that a shorter reproductive lifespan was positively associated with T2DM, yielding 6-15% higher risk of T2DM for a one-year decrease in reproductive lifespan. A few studies also demonstrated that women who experienced early menarche (four of six studies) and early menopause (two of five studies) were positively associated with risk of T2DM. The association between reproductive lifespan and hypertension was unclear due to the limited availability of studies. Our findings suggest that a shorter reproductive lifespan is associated with T2DM risk in postmenopausal women, especially those with early menarche and early menopause. Large cohort studies are needed to assess the association between reproductive lifespan and incident hypertension in midlife.

Risk-benefit analysis of the AstraZeneca COVID-19 vaccine in Australia using a Bayesian network modelling framework.

Thrombosis and Thrombocytopenia Syndrome (TTS) has been associated with the AstraZencea (AZ) COVID-19 vaccine (Vaxzevria). Australia has reported low TTS incidence of < 3/100,000 after the first dose, with case fatality rate (CFR) of 5-6%. Risk-benefit analysis of vaccination has been challenging because of rapidly evolving data, changing levels of transmission, and variation in rates of TTS, COVID-19, and CFR between age groups. We aim to optimise risk-benefit analysis by developing a model that enables inputs to be updated rapidly as evidence evolves. A Bayesian network was used to integrate local and international data, government reports, published literature and expert opinion. The model estimates probabilities of outcomes under different scenarios of age, sex, low/medium/high transmission (0.05%/0.45%/5.76% of population infected over 6 months), SARS-CoV-2 variant, vaccine doses, and vaccine effectiveness. We used the model to compare estimated deaths from AZ vaccine-associated TTS with i) COVID-19 deaths prevented under different scenarios, and ii) deaths from COVID-19 related atypical severe blood clots (cerebral venous sinus thrombosis & portal vein thrombosis). For a million people aged ≥ 70 years where 70% received first dose and 35% received two doses, our model estimated < 1 death from TTS, 25 deaths prevented under low transmission, and > 3000 deaths prevented under high transmission. Risks versus benefits varied significantly between age groups and transmission levels. Under high transmission, deaths prevented by AZ vaccine far exceed deaths from TTS (by 8 to > 4500 times depending on age). Probability of dying from COVID-related atypical severe blood clots was 58-126 times higher (depending on age and sex) than dying from TTS. To our knowledge, this is the first example of the use of Bayesian networks for risk-benefit analysis for a COVID-19 vaccine. The model can be rapidly updated to incorporate new data, adapted for other countries, extended to other outcomes (e.g., severe disease), or used for other vaccines.