Wednesday, 8 July 2020

Updated estimates of the burden of tobacco use

Yesterday the Canadian Centre on Substance Use and Addiction and the Canadian Institute for Substance Use Research released updated estimates of the economic and health burden that result from substance abuse. 

They provide the update in two useful versions: a report "Canadian Substance Use Costs and Harms 2015-2017"  and a data visualization tool.

Their study is a useful reminder that despite falling smoking rates, tobacco is the drug that is the biggest driver of health care costs and death.

Deaths from legal drugs eclipse those from illegal drugs.

This study estimates that in 2017, tobacco caused 6 in 10 deaths associated with substance abuse and alcohol caused an additional 1 in 4. Opioids were responsible for 1 in 15 substance-use related deaths. (Because illicit drugs tend to kill at a younger age, they were however associated with a greater number of potential yeras of productive life lost.)

Canadian Substance Use Costs and Harms 2015-2017 CCSA 

Legal drugs drive health care costs

Healthcare costs from substance use exceeded $13 billion in 2017 -- with about half caused by smoking. These costs included inpatient hospitalizations, day surgeries, emergency department visits, specialized treatment for SU disorders, physician time and prescription drugs (and were not able to include some costs for Quebec).

Canadian Substance Use Costs and Harms 2015-2017 CCSA 

There were no criminal justice costs associated with tobacco 

Those concerned that Canada's policing system is not actively engaged with trying to reduce contraband cigarette sales will not be comforted by this study's estimates that the criminal justice system spent no money policing offences related to tobacco. (Selling contraband tobacco has been a Criminal Code offence since 2014.)

Canadian Substance Use Costs and Harms 2015-2017 CCSA 

Tobacco control does not receive a proportionate share of prevention investments.

The study also included "other direct costs" associated with substance abuse. Among these were federal funding for research and prevention. obacco use may cause more than half the deaths and half the health-care costs, but it received less than one-quarter of federal investment in prevention and research.

Canadian Substance Use Costs and Harms 

Different methods - and different data sources - will produce different results

In this study, the authors based their calculations on smoking rates produced by the (now-defunct) Canadian Tobacco Alcohol and Drug Survey (13% in 2017). Had they used estimates produced by the Canadian Community Health Survey (16% in 2017), they would have included the costs related to an additional 1 million smokers.

Three years ago the Conference Board of Canada produced estimates of "The Costs of Tobacco Use in Canada" for 2012. They similarly found a $6 billion cost for direct health care costs, but their estimate for costs related to lost productivity were much higher ($9 billion vs. $6 billion).

Wednesday, 1 July 2020

A Canada Day holiday - and the start date for several tobacco control regulations.

Health Authorities have a tendency to use the first days of January and July as the moment when regulations come into force. And so it is that this week a number of changes to the tobacco and vaping regulations are taking effect.

Federal: Mandatory health warnings replace voluntary warnings on vaping packages

Last December, Health Canada published the final version of the Vaping Products Labelling and Packaging Regulations SOR/2019-353.  These regulations were made under the authority of two federal laws -- the Tobacco and Vaping Products Act and the Canadian Consumer Product Safety Act. 
The Regulations set out the requirements in two parts: labelling requirements pursuant to the TVPA, and labelling and child-resistant container requirements pursuant to the CCPSA. The labelling requirements include a list of ingredients and, for products containing nicotine, a health warning that nicotine is highly addictive, the concentration of nicotine, and warnings regarding the toxicity of nicotine when ingested. In addition, the Regulations set out expressions that may be used on the product or package to indicate when a vaping product is without nicotine. The Regulations also require refillable vaping products, including devices and their parts, to be child-resistant.
With these new regulations, vaping products are now required to carry warnings that cover 40% of the principal display panel and an even greater percentage on small packages. Only one warning on addiction is required, even though the companies had previously included voluntary warnings on general health effects. 

The impact of the new regulation and package redesign are on BAT's vaping brand is shown below. 

These new warnings may not be immediately visible to Canadian consumers. Health Canada is reported to have agreed to the request of convenience stores to delay enforcement of the regulations until January 1, 2021. 

Provincial:  Ontario moves flavoured and high-nicotine vaping products out of convenience stores.

In late February, the Ontario government announced that it would remove flavoured and high-nicotine vaping products from convenience stores and gas stations and permit their sale only in specialty vape shops. Ordinary stores would still be allowed to sell tobacco- and mint/menthol- flavoured vaping products, and vaping liquids that have less than 20 mg/ml concentratiaon of nicotine.

 The original implementation date of May 1st, however, was delayed by two months to July 1st in response to concerns of convenience retailers that this would increase the risk of COVID transmission.

The Ontario government resisted pressure to further delay implementation of this new rule, but it too has agreed to give the industry a 6 month grace period before taking any enforcement actions. The Convenience Industry Council claimed that implementation required  "a massive inventory change during the COVID crisis and the potential impacts on the health of our frontline workers". 

Provincial: Nova Scotia requires e-cigarette vendors to be licensed.

On Canada Day, Nova Scotia's new requirements for retail and wholesale vendor permits for e-cigarettes comes into force. The three-year permits cost $124, but require permit holders to provide some business information  that could be useful for public health monitoring.

Municipal: Edmonton's ban on shisha bars comes into force

When amending its smoking bylaw last year, Edmonton City Council accepted a one-year delay before imposing restrictions on Hookah bars/Shisha lounges. These regulations will come into force this July 1st. 

Some International measures: 

On July 1st, New York City ban on the sale of flavoured cigarettes comes into force. This city law was originally signed in December 2019. Because it was superseded by a similar law passed by the State legislature as part of its 2020 budget, which came into effect mid-May, the ban is already in effect.  Other NY state changes which come into force on July 1st include a ban on on-line sales, ads near schools and reporting requirements for manufacturers and distributors. (See page 191 and later of the Budget Bill S7506B). Quebec is the only Canadian jurisdiction to ban on-line sales. Health Canada intends to impose reporting requirements on vaping manufacturers, but has not yet indicated what they will be.

This week the Netherlands extends its ban on public smoking to e-cigarettes. Retail displays are also banned at supermarkets (the measure will affect other retailers, but not specialty tobacconists and kiosks at the end of the year). 
Regulatory round-up

The above are but a few of the many regulatory developments. To keep track of these, two information products have been updated:

Monday, 29 June 2020

BAT exploits PRIDE to sell e-cigarettes.

BAT has launched a new limited edition vaping device that is designed with a with a rainbow-like "vibrant spectrum of colours". 

The campaign to promote it comes on the heels of Pride Toronto's late June celebrations. 

The marketing slogan used in the promotional e-mails, Facebook and Instagram invites consumers to celebrate "Happy Pride."

Health Canada has recognized the health disparities experienced by this community with respect to tobacco use, and taken steps to ameliorate this inequity. Clamping down on this promotion would be something else they could take Pride in.

Thursday, 25 June 2020

Smoking rates have fallen -- but maybe not for the reason you think.

Last week Statistics Canada made available the Public Use Microdata from the Canadian Community Health Survey conducted in 2017 and 2018.  The gift of a 1000 variables!

The Canadian Community Health Survey (CCHS) is the doyen of Statistics Canada's health surveillance system. For 2 decades, government pollsters have used this survey to find explore the health and lifestyles of Canadians (aged 12 and up). To the benefit of all, data from this survey is made freely available to external researchers every two years in the form of a Public Use Micro File.

The methodological changes made to the survey in 2015 have not diminished its role as the most robust national measure of smoking rates in Canada, and the most reliable tool to look at progress. In this first of a series of posts using the new data, we look at progress between 2007-08 and 2017-2018.

Smoking is down -- but not because of quitting.

Smoking prevalence rates are the core indicator for monitoring tobacco control efforts. But the prevalence rate by itself does not tell us why changes are happening. It's too easy to think it is because smokers are quitting, when there may be other population factors at work. 

The change between 2007-08 and 2017-18 is a case in point. Over that decade, the number of smokers fell -- but the number of former smokers barely budged. It was the growth in never smokers (and the growth in population) that really made a difference. In that decade the population growth of 3.3 million people included an increase of 1.1 Canadians who say they have never smoked a whole cigarette.

More than 4 million Millenials and Gen Z are now on board, but 2 million from the heavy-smoking Silent Generation have been lost.

To take a closer look at population changes, we compared the smoking behaviour of separate population cohorts, those born in the decades ending with the survey year. For the survey's purposes, these can be seen as mostly aligned with the classic generations:  the Silent Generation (born before 1937 and between 1938 and 1947), older Boomers (1948 - 1957), younger boomers (1958 - 1967), Generation X (1968 to 1977), Xennials (1978 to 1987), Millenials (1988 to 1997) and Gen Z (after 1998). 

Each of these successive generations have different relationships to tobacco use, and received very different messages about tobacco in adolescence. As a result, smoking prevalence was much higher in some generations than in others.Three-quarters of Canadian men born before the mid 1950s (when smoking was widely accepted and advertised) tried smoking at least once, compared with only one-third of those born in the 1990s (who grew up surrounded by much less tobacco promotion or public smoking). 

Differences in these experiences, combined with differences in the proportion of the population that is in that generation can greatly affect the overall smoking prevalence rate. Over the past decade, many of the Silent Generation disappeared from the CCHS roster. An even larger number of Gen Z Canadians entered the pool of CCHS respondents. 

The number of Canadian smokers dropped by a million. It would have been almost double that had young people not been recruited to replace them.   

There were about 6 million smokers in 2007-08 and only 5 million in 2017-2018. Each generational cohort had a steady drop off in the number of smokers -- totalling 1.8 million fewer smokers among Canadians over 30 years of age in 2017-2018. 

Sadly, tobacco companies continued to recruit replacement smokers for those lost clients. Of Canada's 5 million smokers in 2017-2018, more than a million were born after 1998 -- three-quarters of them started smoking after 2008.  

Canada gained very few former smokers 

In 2007-2008, 7.1 million Canadians said they had smoked more than 100 cigarettes in their life, but didn't smoke any more. A decade later, that number had climbed to only 7.6 million. These were not the same Canadians, as more than 800,000 former smokers in the Silent Generation were no longer around to answer surveys at the end of the decade.

By the logic of the survey, there are two main ways a population of smokers can change status: they can become former smokers or they can disappear from the survey, likely because they have died.

This dark underside of falling smoking rates is exposed in the difference between the reduction in the number of smokers over a decade and the smaller growth in the number of former smokers. For example, among those who were in their 60s in 2017-2018 (i.e. born between 1948 and 1957), there were 342,600 fewer smokers after 10 years but only 135,700 more former smokers. 

Many more "never smokers" made a difference.

Statistics Canada provides two measures of people who can be considered to have never become a regular smoker. There are those who say they have never smoked a whole cigarette ("lifetime abstainers") and those who may have smoked one cigarette, but have never smoked more than 100 in their lifetime ("experimenters"). 

Both of categories have grown with succeeding generations. There were 3 million more lifetime abstainers in 2017-2018 than a decade previously, and three-quarters of a million more "experimenters".

In some presentations, former experimenters are lumped together with former smokers, inflating the apparent success of quitting efforts by blending together those who never became established smokers with those who did but managed to quit.

The takeaway? Smoking rates are falling, but quitting does not get the credit.
  • Canada's smoking rates dropped by almost 6 percentage points over a decade (from 22% to 16%), representing 1 million fewer smokers.
  • A main driver of change was the natural ageing of the population and the entry of younger cohorts who are less likely to have ever smoked. 
    • The prevalence of lifetime abstention from smoking increased by 6 percentage points over a decade (from 41% to 46%). 
    • The prevalence of never moving from experimental smoking to regular smoking increased by 2 percentage points (from 11% to 13%)
  •  A much less significant driver of change was smoking cessation. The prevalence of former smoking fell by 2 percentage points (from 26% to 24%). 
An Excel worksheet from which these tables have been built can be downloaded here

Wednesday, 17 June 2020

84% of Vape Stores fail Health Canada's inspections

Earlier this month, Health Canada made available its second Vaping Product Enforcement Report., continuing its regulatory innovation of making available the results of its inspections of vaping manufacturers, importers and sellers.

In the spring-summer of 2019, following numerous complaints about infractions of the federal Tobacco and Vaping Products Act (including ours!), Health Canada dramatically increased its inspections of retailers, festivals, web-sites and other locations where vaping products were marketed or promoted. 

By documenting and making public these enforcement efforts, Health Canada makes a significant contribution to our understanding of the challenges of regulating nicotine retailers and the importance of surveillance and oversight. 

The infractions

Between July and December 2019, departmental officials visited convenience stores on 2083 occasions, and visited specialty vaping shops 1080 times. A small number (14 Convenience stores and 90 vaping shops) were visited on two occasions. The inspectors were verifying compliance with both the Tobacco and Vaping Products Act and also the Canada Consumer Product Safety Act.

The enforcement reports do not describe what the inspectors were looking for, but they do give general information on what they found:
* One or more illegal activities were observed in 84% of vaping stores and in 13% of convenience stores
* illegal promotions were found in 60% of the vaping stores and 4% of the convenience stores
* prohibited flavour names in were found in 59% of vaping stores and 4% of convenience stores
* Non-child resistant packages were found in 1% of the vaping stores

The consequences

Health Canada also reports on the actions in took when problems were identified:
* none of the retailers were formally charged.
* there were no consequences recorded for 24% of the 993 occasions when non-compliance was observed.
* warning letters were issued on two occasions.
* seizure actions were taken in 73% of the occasions. It was not stated whether seized items remained on site or were removed.
* stop sale (voluntary actions by establishments to halt further distribution) were taken in 10% of occasions.

The seriousness with which Parliament saw the infractions of vaping law is reflected in the potential penalties: "Every person who contravenes [these sections] is guilty of an offence and liable on summary conviction to a fine not exceeding $500,000 or to imprisonment for a term not exceeding two years or to both." 

The reality, sadly, is that Canada's federal tobacco laws do not provide for administrative monetary penalties (although they are part of the Cannabis Act that was passed the same year). Meanwhile, imposing penalties on those who disregard tobacco laws requires the government to engage a complex, expensive and time-consuming court route. This rarely happens. 

The retailers involved

Health Canada's disclosure of the results of these compliance activities provides insight into the locations of retailers who were found to have failed to implement some provisions of the federal law. (The report does not identify those retailers who were found to be obeying it, although this is a practice in place with some health inspection systems. 

This data allows for a mapping of where the observations of non-compliance took place. Such maps are currently available for:

* British Columbia (87)
* Prairie Provinces (249)
* Greater Toronto  (299)
* Rest of Ontario (223)
Quebec (180)
* Atlantic Provinces ( 75 )

Only a small fraction of tobacco retail stores were inspected during this 6 month period - less than 1% of the 28,000 retailers reported by Imperial Tobacco to carry their products. The proportion of vaping specialty stores (for which we do not have an official count) which were inspected is likely higher, as these stores are less common. estimated that in June 2019 there were 1,100 brick and mortar specialty vape stores in Canada.

Sunday, 7 June 2020

Insights from the recent Canadian Tobacco and Nicotine Survey

Three months ago, Statistics Canada released some results from the Canadian Tobacco and Nicotine Survey (CTNS) This is a one-time survey conducted between the end of October and mid-December in 2019. The survey was taken by 8,600 Canadians, fewer than half of those who were asked to do so (a reponse rate of 44%).

Statistics Canada developed the survey with Health Canada, setting the survey goals to "fill important data gaps related to vaping, cannabis, and tobacco usage" and to "inform policy and provide a current snapshot of use across Canada."

The first results of the CNTS were released by Statistics Canada on March 5. These focused on:
* who was vaping (15% of youth and young adults, but less than 3% of adults);
* what they were vaping (nine times out of ten it was nicotine);
* why they were vaping (kids for fun, adults as a way to quit cigarettes); and
* what they thought about the harms of vaping (opinions varied).

Because this survey is not formally connected to other surveillance tools, drawing comparisons with previously estimated rates of smoking or vaping are problematic.  Nonetheless, as we wrote in March, it seems clear that the expansion of vaping marketing has had a more profound impact on youth and young adults than it has had on adult smokers. The number of young vapers has increased greatly, while the use of vaping products by adult smokers seems to have not changed measurably.

In late May, Statistics Canada generously provided us with the Public Use Microfile for this survey, allowing us to extract information on some key aspects of vaping behaviour among Canadians in 2019.

1.  One-fifth of Canadian vapers are teenagers who have never smoked a whole cigarette.

The survey results show that the number of Canadians who have never smoked cigarettes but who have used e-cigarettes in the past month exceed those who have once smoked but are now vaping instead. This is particularly true for teenagers, where three-quarters of vapers have never smoked a cigarette.

Last fall there were about 1.46 million Canadians who had vaped in the past month. Of these, one-quarter (364,800) were "former smokers." The remainder, in roughly equal quantity, were "never smokers"(535,900) or "current smokers" (559,700 dual users).

Smoking status of vapers, CNTS 2019
Past month vapers by age and smoking status
Statistics Canada.
Canadian Tobacco and Nicotine Survey, 2019

2. For every 100 people who tried vaping, 13 became daily users.
A great accomplishment for tobacco control has been establishing an environment where young people do not try smoking cigarettes -- even once. CTNS data reflects that progress: Four-fifths of young people (15 to 24 years of age) reply "no" to the question "Have you ever smoked a whole cigarette," compared with fewer than one-half of those in previous generations (over 25 years of age).

But among those who have ever smoked a cigarette, the proportion who became daily (likely addicted) smokers is the same at every age . Almost one in five (18%) of those who ever smoked a whole cigarette were smoking daily, regardless of their age group. This speaks to the addictive power of cigarettes and nicotine.

For vaping, more than one in eight (13%) of those who ever tried vaping were doing it every day last fall. In this case, however, the pattern is reversed in comparison with smoking. In this case, it is the younger generation who had much higher rates of experimentation than older Canadians. Fewer than one-fifth of adults (16%) had ever tried vaping, compared with more than two-fifths of youth and young adults (41%).

For cannabis, the rate of experimentation was essentially the same for all age groups, although young people were more likely to be daily users. Overall, the rate of daily use was about 9%, consistent with other estimates of rates of addiction to cannabis. 

Population prevalence of ever trying product and percentage of those who were daily users
Statistics Canada. 

Canadian Tobacco and Nicotine Survey, 2019

3. Almost half of smokers made a quit attempt over the past year. Few used a recommended cessation aid. 

Smokers and former smokers who said they had quit in the past year were asked how many times they had stopped smoking for at least one day as part of a quit attempt, and were also asked whether they had used any specific quit methods.

Almost one half (45%) identified making at least one quit attempt, with almost one-third (31%) trying more than twice.

When asked whether they had tried to quit using specific approaches, the majority (70%) said they had tried to quit on their own, and half (54%) said they had tried reducing the number of cigarettes. One-third (35%) said they had switched to vaping, one-quarter (25%) said they had used nicotine replacement and one-fifth (20%) said they had used an "other" method. (Because prescription medication was not identified on the questionnaire, treatments like varenicline may be included under "other"). So few people reported using Quitlines or internet programs that the number is unreportable.

The vast majority (88%) of these quit attempts were unsuccessful. Of the 1.75 million Canadians who tried to quit, only 201,000 were still not smoking at the time of the survey (12%). Differences in the outcomes for those using different cessation approaches were not tested for statistical significance, but are presented below. The largest number of successful quitters were those who identified as using no quit method.

The CTNS also asked current vapers whether they had tried quitting vaping, but is designed only to show how many tried but failed to quit. One-in-three vapers (35%) had tried at least once in the past year, but were still vaping at the time of the survey. This included 30% of those who vaped on a daily basis. 

Quitting methods used in past year, CTNS 2019
Methods used by those who tried to quit smoking in past year
Statistics Canada. 
Canadian Tobacco and Nicotine Survey, 2019

4. Tobacco-flavour is the only vaping flavour not attracting young people to vape.

Those who vaped in the past month were asked what their main reason for vaping was and also which flavours they usually chose. 

Four in ten vapers (39%) give recreational reasons for vaping, saying that the main reason they vape is out of curiosity or because they enjoy it. Tobacco flavours are almost never their usual flavours. The number who made this choice is too small to be reported according to Statistics Canada's guidelines. More than one-half of this group (56%) choose fruit, dessert or candy flavours, and about one-seventh (16%) say they prefer menthol or mint flavours. One-quarter (24%) do not have a usual flavour or have one different than those listed. 

Four in ten vapers (37%) give health-related reasons for vaping, saying the main reason they vape is to quit smoking, to cut down on the number of cigarettes they smoke or to avoid returning to smoking. Among this group, one-quarter (26%) used tobacco flavours. One-fifth (20%) choose mint or menthol flavours and twice as many (41%) choose fruit, desert or candy flavours. 

These differences were not tested for statistical significance, but are presented below. 

Flavour preferences by main reason for vaping
Statistics Canada. 

Canadian Tobacco and Nicotine Survey, 2019

This information is available on a downloadable fact sheet

Monday, 25 May 2020

Does vaping lead to smoking? Accumulating evidence of a gateway effect

Science marches on.
Four years ago, there was uncertain evidence that e-cigarette use by adolescents might lead to more smoking later on. Since then, a number of additional studies have been done. While the resutls vary, the evidence now consistently shows that early e-cigarette use is associated with subsequent uptake of smoking.

This post highlights four studies that show how evidence of a "gateway" effect has become progressively stronger over four years.

2016: Slower declines in youth smoking linked to e-cigarettes.

Jessica Barrington-Trimis and her colleagues analyzed data from grade 11 and 12 students, taken from a longitudinal study of children's health that was conducted in California in 1995, 1998, 2001, 2004 and 2014. Before e-cigarettes became available, smoking among California adolescents had been declining. Then in 2014, combined current e-cigarette use and cigarette use among Grade 12 students reached 13.7%. This was substantially greater than cigarette use in 2004 (9%) and only a little less than Grade 12 smoking prevalence in 2001 -- 14.7%.

These results suggested that e-cigarette use was occurring in adolescents who would not have otherwise used tobacco products.

2018: Young e-cigarette users much more likely to smoke cigarettes

The 2016 results were suggestive of an association between e-cigarette use and later smoking, but stronger evidence was needed. Dr. Barrington-Trimis and her colleagues pooled data from three similar prospective studies of high school students -- two in California and one in Connecticut. E-cigarette users were 4.6 times more like to become experimental cigarette smokers, 4.3 times more likely to become occasional cigarette smokers and 3.5 times more likely to become frequent cigarette users,

2017: E-cigarette users 4 times more likely to smoke.

While Dr. Barrington-Trimis were conducting their pooled analysis of data from three high school surveys, other researchers were conducting a meta-analysis.

(This type of pooled analysis treats the data from several sources as one larger data set. It is appropriate when the data sets are similar, as they were in the work of Dr. Barrington-Trimis and her colleagues -- data from three similarly-conducted prospective surveys of high school students. When data from different sources are more heterogeneous, meta-analysis is the preferred analytical procedure. Weighting procedures are used to adjust for differences among data sources.)

Dr Samir Soneji and his colleagues performed such a meta-analysis and published their results in 2017. Their results were similar to the results of the pooled analysis discussed above. Based on the combined results of nine studies they found that adolescents who had ever used e-cigarettes were 4.3 time more likely to become cigarette smokers.

2020: A bigger, more definitive meta-analysis provides more evidence for concern.

Science marches on and studies accumulate. By 2020, more studies on the relationship between vaping and youth smoking had been done and a larger meta-analysis was possible.

In March 2020, Jasmine Kouja and her colleagues published a meta-analysis of 17 studies of e-cigarette use and later smoking among youth, Their results were remarkably similar to earlier results from a pooled analysis and the previous meta-analysis.. E-cigarette users were 4.6 times more likely to become cigarette smokers later on. Results differed among the 17 studies in the meta-analysis, but all showed e-cigarette users more likely to become cigarette smokers, with findings ranging from 2.5 times more likely to 12.3 times more likely.

From less certain to more certain

In just four years, through repeated observations, we have moved from a tentative conclusion that e-cigarette use by adolescents might be associated with subsequent cigarette use to very strong evidence in support of a gateway effect. Seventeen studies from several different countries (including one from Canada) all found a relationship between e-cigarette use and subsequent uptake of smoking. 

While alternatives to this being a causal relationship still cannot be completely dismissed, it is now increasingly unlikely that the relationship is not one of cause and effect.

The studies cited above:

Barrington-Trimis, JL et al. E-cigarettes, Cigarettes, and the Prevalence of Adolescent Tobacco Use. Pediatrics August 2016, 138 (2) e20153983; DOI:

Barrington-Trimis, JL et al. E-cigarette Use and Subsequent Smoking Frequency Among Adolescents. November 2018 Pediatrics 142(6):e20180486

Soneji, S et al. Association Between Initial Use of e-Cigarettes and Subsequent Cigarette Smoking Among Adolescents and Young Adults. A Systematic Review and Meta-analysis. JAMA Pediatrics. 2017; 171 (8)

Khouja, JUN et al. Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis. Tobacco Control. March 2020.