Objective
To review and synthesise the global evidence regarding the health effects of electronic cigarettes (e‐cigarettes, vapes).
Study design
Umbrella review (based on major independent reviews, ...including the 2018 United States National Academies of Sciences, Engineering, and Medicine NASEM report) and top‐up systematic review of published, peer‐reviewed studies in humans examining the relationship of e‐cigarette use to health outcomes published since the NASEM report.
Data sources
Umbrella review: eight major independent reviews published 2017–2021. Systematic review: PubMed, MEDLINE, Scopus, Web of Science, the Cochrane Library, and PsycINFO (articles published July 2017 – July 2020 and not included in NASEM review).
Data synthesis
Four hundred eligible publications were included in our synthesis: 112 from the NASEM review, 189 from our top‐up review search, and 99 further publications cited by other reviews. There is conclusive evidence linking e‐cigarette use with poisoning, immediate inhalation toxicity (including seizures), and e‐cigarette or vaping product use‐associated lung injury (EVALI; largely but not exclusively for e‐liquids containing tetrahydrocannabinol and vitamin E acetate), as well as for malfunctioning devices causing injuries and burns. Environmental effects include waste, fires, and generation of indoor airborne particulate matter (substantial to conclusive evidence). There is substantial evidence that nicotine e‐cigarettes can cause dependence or addiction in non‐smokers, and strong evidence that young non‐smokers who use e‐cigarettes are more likely than non‐users to initiate smoking and to become regular smokers. There is limited evidence that freebase nicotine e‐cigarettes used with clinical support are efficacious aids for smoking cessation. Evidence regarding effects on other clinical outcomes, including cardiovascular disease, cancer, development, and mental and reproductive health, is insufficient or unavailable.
Conclusion
E‐cigarettes can be harmful to health, particularly for non‐smokers and children, adolescents, and young adults. Their effects on many important health outcomes are uncertain. E‐cigarettes may be beneficial for smokers who use them to completely and promptly quit smoking, but they are not currently approved smoking cessation aids. Better quality evidence is needed regarding the health impact of e‐cigarette use, their safety and efficacy for smoking cessation, and effective regulation.
Registration
Systematic review: PROSPERO, CRD42020200673 (prospective).
Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is ...limited.
A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated.
During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking.
Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.
Improved survival means that cancer is increasingly becoming a chronic disease. Understanding and improving functional outcomes are critical to optimising survivorship. We quantified physical and ...mental health-related outcomes in people with versus without cancer, according to cancer type.
Questionnaire data from an Australian population-based cohort study (45 and Up Study (n = 267,153)) were linked to cancer registration data to ascertain cancer diagnoses up to enrolment. Modified Poisson regression estimated age- and sex-adjusted prevalence ratios (PRs) for adverse person-centred outcomes-severe physical functional limitations (disability), moderate/high psychological distress and fair/poor quality of life (QoL)-in participants with versus without cancer, for 13 cancer types.
Compared to participants without cancer (n = 244,000), cancer survivors (n = 22,505) had greater disability (20.6% versus 12.6%, respectively, PR = 1.28, 95%CI = (1.25-1.32)), psychological (22.2% versus 23.5%, 1.05 (1.02-1.08)) and poor/fair QoL (15.2% versus 10.2%; 1.28 (1.24-1.32)). The outcomes varied by cancer type, being worse for multiple myeloma (PRs versus participants without cancer for disability 3.10, 2.56-3.77; distress 1.53, 1.20-1.96; poor/fair QoL 2.40, 1.87-3.07), lung cancer (disability 2.81, 2.50-3.15; distress 1.67, 1.46-1.92; poor/fair QoL 2.53, 2.21-2.91) and non-Hodgkin's lymphoma (disability 1.56, 1.37-1.78; distress 1.20, 1.05-1.36; poor/fair QoL 1.66, 1.44-1.92) and closer to those in people without cancer for breast cancer (disability 1.23, 1.16-1.32; distress 0.95, 0.90-1.01; poor/fair QoL 1.15, 1.05-1.25), prostate cancer (disability 1.11, 1.04-1.19; distress 1.09, 1.02-1.15; poor/fair QoL 1.15, 1.08-1.23) and melanoma (disability 1.02, 0.94-1.10; distress 0.96, 0.89-1.03; poor/fair QoL 0.92, 0.83-1.01). Outcomes were worse with recent diagnosis and treatment and advanced stage. Physical disability in cancer survivors was greater in all population subgroups examined and was a major contributor to adverse distress and QoL outcomes.
Physical disability, distress and reduced QoL are common after cancer and vary according to cancer type suggesting priority areas for research, and care and support.
Epidemiologic studies have observed association between short sleep duration and both cardiovascular disease (CVD) and type 2 diabetes, although these results may reflect confounding by pre-existing ...illness. This study aimed to determine whether short sleep duration predicts future CVD or type 2 diabetes after accounting for baseline health. Baseline data for 241,949 adults were collected through the 45 and Up Study, an Australian prospective cohort study, with health outcomes identified via electronic database linkage. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals. Compared to 7h sleep, <6h sleep was associated with incident CVD in participants reporting ill-health at baseline (HR=1.38 95% CI: 1.12-1.70), but not after excluding those with baseline illness and adjusting for baseline health status (1.03 0.88-1.21). In contrast, the risk of incident type 2 diabetes was significantly increased in those with <6h versus 7h sleep, even after excluding those with baseline illness and adjusting for baseline health (HR=1.29 1.08-1.53, P=0.004). This suggests the association is valid and does not simply reflect confounding or reverse causation. Meta-analysis of ten prospective studies including 447,124 participants also confirmed an association between short sleep and incident diabetes (1.33 1.20-1.48). Obtaining less than 6 hours of sleep each night (compared to 7 hours) may increase type 2 diabetes risk by approximately 30%.
Cancer care represents a substantial and rapidly rising healthcare cost in Australia. Our aim was to provide accurate population-based estimates of the health services cost of cancer care using ...large-scale linked patient-level data.
We analysed data for incident cancers diagnosed 2006-2010 and followed to 2014 among 266,793 eligible participants in the 45 and Up Study. Health system costs included Medicare and pharmaceutical claims, inpatient hospital episodes and emergency department presentations. Costs for cancer cases and matched cancer-free controls were compared, to estimate monthly/annual excess costs of cancer care by cancer type, before and after diagnosis and by phase of care (initial, continuing, terminal). Total costs incurred in 2013 were also estimated for all people diagnosed in Australia 2009-2013.
7624 participants diagnosed with cancer were matched with up to three controls. The mean excess cost of care per case was AUD$1,622 for the year before diagnosis, $33,944 for the first year post-diagnosis and $8,796 for the second year post-diagnosis, with considerable variation by cancer type. Mean annual cost after the initial treatment phase was $4,474/case and the mean cost for the last year of life was $49,733/case. In 2013 the cost for cancers among people in Australia diagnosed during 2009-2013 was ~$6.3billion (0.4% of Gross Domestic Product; $272 per capita), with the largest costs for colorectal cancer ($1.1billion), breast cancer ($0.8billion), lung cancer ($0.6billion) and prostate cancer ($0.5billion).
The cost of cancer care is substantial and varies by cancer type and time since diagnosis. These findings emphasise the economic importance of effective primary and secondary cancer prevention strategies.
In recent decades, there has been a shift to later childbearing in high-income countries. There is limited large-scale evidence of the relationship between maternal age and child outcomes beyond the ...perinatal period. The objective of this study is to quantify a child's risk of developmental vulnerability at age five, according to their mother's age at childbirth.
Linkage of population-level perinatal, hospital, and birth registration datasets to data from the Australian Early Development Census (AEDC) and school enrolments in Australia's most populous state, New South Wales (NSW), enabled us to follow a cohort of 99,530 children from birth to their first year of school in 2009 or 2012. The study outcome was teacher-reported child development on five domains measured by the AEDC, including physical health and well-being, emotional maturity, social competence, language and cognitive skills, and communication skills and general knowledge. Developmental vulnerability was defined as domain scores below the 2009 AEDC 10th percentile cut point. The mean maternal age at childbirth was 29.6 years (standard deviation SD, 5.7), with 4,382 children (4.4%) born to mothers aged <20 years and 20,026 children (20.1%) born to mothers aged ≥35 years. The proportion vulnerable on ≥1 domains was 21% overall and followed a reverse J-shaped distribution according to maternal age: it was highest in children born to mothers aged ≤15 years, at 40% (95% CI, 32-49), and was lowest in children born to mothers aged between 30 years and ≤35 years, at 17%-18%. For maternal ages 36 years to ≥45 years, the proportion vulnerable on ≥1 domains increased to 17%-24%. Adjustment for sociodemographic characteristics significantly attenuated vulnerability risk in children born to younger mothers, while adjustment for potentially modifiable factors, such as antenatal visits, had little additional impact across all ages. Although the multi-agency linkage yielded a broad range of sociodemographic, perinatal, health, and developmental variables at the child's birth and school entry, the study was necessarily limited to variables available in the source data, which were mostly recorded for administrative purposes.
Increasing maternal age was associated with a lesser risk of developmental vulnerability for children born to mothers aged 15 years to about 30 years. In contrast, increasing maternal age beyond 35 years was generally associated with increasing vulnerability, broadly equivalent to the risk for children born to mothers in their early twenties, which is highly relevant in the international context of later childbearing. That socioeconomic disadvantage explained approximately half of the increased risk of developmental vulnerability associated with younger motherhood suggests there may be scope to improve population-level child development through policies and programs that support disadvantaged mothers and children.
To quantify changes in anticoagulant use in Australia since the introduction of Non-vitamin K antagonist anticoagulants (NOACs) and to estimate government expenditure.
Interrupted-time-series ...analysis quantifying anticoagulant dispensing, before and after first Pharmaceutical Benefits Scheme (PBS) NOAC listing in August 2009 for venous thromboembolism prevention; and expanded listing for stroke prevention in non-valvular atrial fibrillation (AF) in August 2013, up to June 2016. Estimated government expenditure on PBS-listed anticoagulants.
PBS dispensing in 10% random sample of Australians, restricted to continuous concessional beneficiaries dispensed oral anticoagulants from July 2005 to June 2016. Total PBS anticoagulant expenditure was calculated using Medicare Australia statistics.
Monthly dispensing and initiation of oral anticoagulants (warfarin, rivaroxaban, dabigatran or apixaban). Annual PBS anticoagulant expenditure.
An estimated 149,180 concessional beneficiaries were dispensed anticoagulants (100% warfarin) during July 2005. This increased to 292,550 during June 2016, of whom 47.0%, 27.1%, 18.7% and 7.2% were dispensed warfarin, rivaroxaban, apixaban and dabigatran, respectively. Of 16,500 initiated on anticoagulants in June 2016, 24.3%, 38.2%, 30.0% and 7.5% were initiated on warfarin, rivaroxaban, apixaban, and dabigatran, respectively. Compared to July 2005-July 2013, from August 2013-June 2016, dispensings for all anticoagulants increased by 2,303 dispensings/month (p<0.001, 95%CI = 1,229 3,376); warfarin dispensing decreased by 1,803 dispensings/month (p<0.001, 95%CI = -2,606, -1,000). Total PBS anticoagulant expenditure was $19.5 million (97.0% concessional) in 2008/09, of which 100% was warfarin and $203.3 million (86.2% concessional) in 2015/16, of which 11.2% was warfarin.
The introduction of the NOACs led to substantial increases in anticoagulant use and expenditure in Australia.
Lysosomes help maintain cellular proteostasis, and defects in lysosomal positioning and function can cause disease, including neurodegenerative disorders. The spatiotemporal distribution of lysosomes ...is regulated by small GTPases including Rabs, which are activated by guanine nucleotide exchange factors (GEFs). DENN domain proteins are the largest family of Rab GEFs. Using a cell-based assay, we screened DENND6A, a member of the DENN domain protein family against all known Rabs and identified it as a potential GEF for 20 Rabs, including Rab34. Here, we demonstrate that DENND6A activates Rab34, which recruits a RILP/dynein complex to lysosomes, promoting lysosome retrograde transport. Further, we identify DENND6A as an effector of Arl8b, a major regulatory GTPase on lysosomes. We demonstrate that Arl8b recruits DENND6A to peripheral lysosomes to activate Rab34 and initiate retrograde transport, regulating nutrient-dependent lysosomal juxtanuclear repositioning. Loss of DENND6A impairs autophagic flux. Our findings support a model whereby Arl8b/DENND6A/Rab34-dependent lysosomal retrograde trafficking controls autophagy.
Smoking prevalence in Australia has decreased by 75% over the past 40 years. A major reduction in disease burden attributed to smoking has occurred in parallel, adjusted for the time lag between ...tobacco harms and disease occurrence. Yet, paradoxically, governments have seldom invested in tobacco control measures that require a financial outlay, such as social marketing, at required levels for optimal outcomes. The percentage of disease burden caused by smoking in Australia (9.3%) remains higher than that of any other preventable risk factor and the social costs are estimated at $136.9 billion annually. Tobacco control is rightly seen as an Australian public health success story. However, with up to two in three of Australia's 2.5 million current smokers at risk of dying prematurely from a smoking-related disease, much more needs to be done. In this paper, we explore a brief history of tobacco control in relation to policy reform and recent evidence, and outline the case for re-energising tobacco control at a time when public health has gained new political and social currency.
The World Health Organization's (WHO) 25X25 goal aims for a 25% relative reduction in premature death due to four non-communicable diseases (NCD4)-cancer, cardiovascular disease, chronic respiratory ...diseases and diabetes-by 2025 compared to 2010. This study aimed to quantify the premature mortality in the Australian population due to NCD4, quantify the variation in mortality rates by age and sex, predict the premature mortality due to NCD4 in 2025 and evaluate the progress towards the WHO 25X25 goal.
A population-based study using cause-specific mortality data of all deaths which occurred in Australia from 2010 to 2016 and registered up to 2017, for adults aged 30-69 years, was conducted. Age-specific and age-standardised mortality rates (ASMR) and probability of death for NCD4 were calculated for each year. ASMRs in 2016 were calculated for men and women. Deaths and the probability of death in 2025 were predicted using Poisson regression based on data from 2006 to 2016. To assess the progress against the WHO 25X25 goal, the relative reduction in the probability of death from NCD4 conditions in 2025 compared to 2010 was calculated.
ASMRs for NCD4 decreased from 2010 to 2016, except for diabetes which increased on average by 2.5% per year. Across sociodemographic factors, ASMRs were highest in males and increased with age. The projected probability of premature death in 2025 was 7.36%, equivalent to a relative reduction of 25.16% compared to 2010 levels.
Premature mortality due to cancer, cardiovascular disease, respiratory diseases and diabetes declined in Australia from 2010 to 2016. This trend is consistent across age groups and by sex, and higher mortality rates were observed in males and at older ages. Nationally, if the current trends continue, we estimate that Australia will achieve a 25.16% relative reduction in premature deaths due to NCD4 in 2025 compared to 2010, signifying substantial progress towards the WHO 25X25 goal. Concerted efforts will need to continue to meet the 25X25 goal, especially in the context of the COVID-19 pandemic.
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