Update of Current Status in on Tobacco Harm Reduction GNF 2019

HIROYA KUMAMARU, MD, PHD AOI UNIVERSAL HOSPITAL GLOBAL NICOTINE FORUM 2019 Number of deaths due to in JAPAN 2

（ ） x1000 121 120 117 121+36=151,000/ in 2015 108 Male 128,000/ in 2007 Female 100 100 85

80 71 No. of death of No. 59 60 47 37 36 40 31 32 32 26 23 27 18 20 13 8.0 4.1 0 '50 '55 '60 '65 '70 '75 '80 '85 '90 '95 '00 '05 ‘10 (year）

Peto, R. et al.：MORTALITY FROM SMOKING IN DEVELOPED COUNTRIES 1950−2020 JAPAN CTSU：265, 2015 より作図 http://gas.ctsu.ox.ac.uk/tobacco/C3160.pdf Economical loss : ￥4.3 trillion due to smoking in Japan

Economic Loss due to Smoking

Loss of labor force due to smoking related diseases 23,596 billion yen Positive Economic Impact Cleaning expense due to smoking 39 billion yen

Fire safety expense due to smoking 1,879 billion yen

Medical expenditure of bystanders affected by 1,431 billion yen Medical expenditure of smokers 16,249 billion yen

2.8 trillion yen 4.3 trillion yen Source: Health Economics Research Group, 2005 statistics Heat-not-burn products

 IQOS：Phillip Morris International

 Glo : British American Tobacco

 Ploom-Tech : were launched since 2014 in Japan Overall tobacco consumptions keeps decreasing, while are replaced quickly by smoke-free products (Japan)

21% reduction (15% year before)

Source: Tobacco Institute of Japan IMS and PMJ Estimate/smokefree products ＋ includes competitive smoke-free products IMS Youth Initiation of HNB - MOH Grant Research

• Prof. Y Osaki of Tottori Unversity, Medical School • A study of drinking behavior, smoking behavior, sleep disruption, and excessive internet use • Among approximately 64,000 Japanese middle and high school students • Surveys were conducted in schools between December 2017 and February 2018. Within smoking behavior, the authors looked at patterns of smoking, heated tobacco product use, and e-cigarette use. Specifically, they asked participants to report ever, monthly, and daily use of these products. Results are summarized in the table below:

Source: Yoneatsu Osaki, Chief investigator, Professor, Division of Environmental and Preventive Medicine, Faculty of Medicine, Tottori University. https://mhlw-grants.niph.go.jp/niph/search/NIDD00.do?resrchNum=201709021A

6 New versions of IQOS

IQOS 3 \10,980(4,980) IQOS 3 Multi \8,980 New versions of glo

glo series 2 \2,980

glo series 2 mini \3,980 New Color Variation & Version of Ploom-TECH

Ploom-TECH \2,980

Ploom-TECH+ \4,980 Latest version & color variation of Ploom S

Ploom S \7,980

JT has changed strategy to use tobacco leaves not like former versions Smoking Restrictions in Japan (2017-18)

National Level

Outdoor No national restrictions

Indoor Health Promotion Law Facility manager efforts to prevent passive smoking in public places Industrial Safety and Health Law Employers efforts to prevent passive smoking in the workplace

Local Level

Outdoor Outdoor smoking restrictions in around 220/800 municipalities Of these, approx. half have exempted HNB from restrictions

Indoor Two Prefectures (Hyogo / Kanagawa) have indoor smoking restrictions Metropolitan Government passed an ordinance to prevent passive smoking to be implemented by 2020. e-cigarettes expectation and launch

Summary

 3 HnB products have been still successful to reduce cigarette smoking in Japan so far.  HnBs are not causing “Gateway phenomenon” in younger generation in Japan.  Movement of smoke-free environment is on-going by the Japanese government towards Tokyo Olympic in 2020.  From the viewpoint of physician, Vapor products are even more favorable than HnBs for nicotine-dependent people and are expected to be launched shortly (I ASAP).  Pharmacological efficacy of nicotine for dementia/MCI, other neuro- psychological impairment is very interesting. Thank you for your attention !! Health and Labour Sciences Research Grant (Comprehensive research project on cardiovascular diseases, diabetes mellitus, and other lifestyle-related diseases) Annual Report of MHLW Research Committee

Field survey on drinking and smoking and the development of effective alcohol reduction intervention approaches for the prevention of lifestyle-related diseases

Yoneatsu Osaki Chief investigator Professor, Division of Environmental and Preventive Medicine, Faculty of Medicine, Tottori University

Project summary The investigators conducted a nationwide survey in 2017 to find out about the alcohol drinking and smoking behaviors of middle- and high-school students in Japan. Frequency of drinking and that of smoking among the youth of middle- and high-school age were lower than the results of our previous survey. The frequency of drinking per week and the frequency of smoking per month and per day were extremely low. Other prominent findings included the following: certain percentages of drinkers were heavy drinkers and binge drinkers (i.e. drinkers consuming large quantities of alcohol in a single session); many of the drinkers and smokers were able to purchase alcohol and cigarettes by themselves; the use of non-alcoholic “beers” and cocktail drinks was on the rise; middle- and high-school students were victims of “alcohol harassment (i.e. the act of forcing others to drink as an abuse of authority)”; the frequency of using cigarette alternatives was nearly as high as that of conventional cigarettes; higher prices, age verification, and restrictions on the use of vending machines appeared to make it difficult to obtain cigarettes; their exposure to secondhand smoke was still high and the frequency of passive smoking outside home showed no decrease; the frequency of sleeping disturbance remained high; and excessive Internet use was on the rise. A review of literature on the health effect of alcohol use was conducted, and a substantial number of articles with high levels of evidence were collected. Data on evidence-based brief intervention were collected to be used for an alcohol reduction program scheduled to be launched in FY 2018, and these data have been used as basic data for the development of intervention programs that reflect the reality in Japan.

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know-how on the method. The nationwide study Project investigators conducted in FY 2017 shed light on the smoking

and drinking behaviors of Japan's middle- and Yoshitaka Kaneita (Professor, Nihon University high-school students, and this has made it possible School of Medicine) to evaluate our progress towards the targets and Hideyuki Kanda (Professor, Shimane University identify what our challenges are at this point. In Faculty of Medicine) the meantime, there are also targets for adult Susumu Higuchi (President, National Hospital drinking (i.e. percentage of adults who consume Organization Kurihama Medical and Addiction) alcohol at a level that increases a risk of Osamu Itani (Associate Professor, Nihon developing lifestyle-related diseases). Again, University School of Medicine) evaluation of the progress toward these targets is Hisashi Yoshimoto (Associate Professor, possible only based on the type of survey that is University of Tsukuba Faculty of Medicine) similar to the nationwide survey our group Hitoshi Maesato (Director, National Hospital conducted on adult drinking behaviors, in 2003, Organization Kurihama Medical and Addiction) 2008, and 2013 (Osaki Y, 2016). The 2018 Aya Kinjo (Lecturer, Tottori University Faculty nationwide survey has helped us understand the of Medicine) drinking behaviors of adults, evaluate the measures Maki Jike (Assistant Professor, Nihon that have been taken so far, and identify the University School of Medicine) challenges we have. Yuichiro Otsuka (Assistant Professor, Nihon As a result of the development of master plan University School of Medicine) under the Basic Act on Measures against Ruriko Minobe (Physician, National Hospital Alcohol-related Health Harm, it is now required Organization Kurihama Medical and Addiction) that screening be performed to identify problem Yuki Kuwabara (Assisstant Professor, Tottori drinkers, and support to reduce drinking (brief University Faculty of Medicine) intervention) be provided. Under the Specific Health Guidance, brief intervention (BI) is to be A. Objectives provided based on the Alcohol Use Disorders Healthy Japan 21 (2nd term) aims for zero Identification Test (AUDIT) since FY 2013. underage smoking and drinking. Evaluating the Whether or not it is actually provided in real life results of the efforts requires that the levels be settings is not clear, however, and our group aims monitored using the same method used in the study to find out how AUDIT is performed, followed by that produced the baseline levels for the evaluation. BI, in the Specific Health Checkups and Specific Our group has conducted a nationwide survey in Health Guidance settings, and look into any 1996, 2000, 2004, 2007, 2008, 2010, 2012 and obstacles in performing the test and providing the 2014 (Osaki Y, 2008, 2009), and has accumulated intervention. In the West, multiple randomized

2 controlled studies have demonstrated BI's effects review; and (3) to gather evidence on brief in helping people cut down on alcohol interventions in Japan and overseas that aim to consumption in the primary care settings reduce excessive alcohol consumption, and (Cochrane Database, 2007). In Japan, meanwhile, develop brief intervention programs that reflect the evidence of the effects of BI has yet to be reality in Japan. established even as the policy has already been launched, which raises an issue. In this project, our B. Research approaches group conducts a literature review to collect data 1) Nationwide survey on the smoking and drinking on BI programs whose evidence has been behaviors of middle- and high-school students: established, reviews Japan's BI, and develop a Survey objects were determined, and simplified version that can be readily adopted by questionnaires were created. Candidate schools busy healthcare providers in real life. Between FY were selected randomly from among middle and 2018 and 2019, we will conduct a randomized high schools around Japan. A request for survey controlled study to demonstrate the effects of was made to the principals of the candidate schools, intervention, both in its standard and simplified and an anonymous survey was conducted in all versions, in the primary care setting. We will also students enrolled at the schools which agreed to attempt to demonstrate the effects of the simplified participate in the survey. Questionnaire forms were BI, based on Japan Health Insurance Association's collected, and data input and data cleaning were post-checkup follow-up guidance in medium- and performed before basic tabulation was performed. small-size businesses, and propose methods of The survey objects included the use of electronic intervention that can be adopted in the health cigarettes, which poses a new set of challenges, checkup and health guidance settings. and non-alcoholic beverages, among other things. Our research objectives for FY 2017 were as 2) Literature review on health effects of alcohol: follows: (1) to conduct a nationwide survey on the Searches of Japanese and international papers on smoking and alcohol drinking behaviors of middle- the health effects of alcohol were performed, and and high-school students in Japan, for the purpose the selected papers were reviewed in group reading of finding out about today's underage smoking and sessions. Evidence tables were created, to tabulate drinking, for which Health Japan 21 (2nd term) the results on subjects by sex, age group, amount sets targets, and investigate lifestyles that have of alcohol intake, type of alcohol, and how they health-related implications that are considered to drink, etc., for different major diseases. be common among middle- and high-school 3) Review on brief interventions (BI) aimed at students, including sleep disturbance and excessive reducing alcohol consumption: Searches and Internet use; (2) to correct Japanese and collection of Japanese and international literature international papers on alcohol and health with on BI, or alcohol reduction support, were high levels of evidence, and conduct a systematic conducted, to obtain summaries of studies with

3 high levels of evidence, and understand the 103 schools in total (56%). The number of intervention methods whose evidence has been questionnaires returned was 64,417 in total, established, in terms of how they are done and including 22,275 from the middle schools and what is done. Descriptions on measures to be taken 42,142 from the high schools. Of these, 64,329 to address an abnormal or emergency situation were subject for analysis, after excluding those were also noted. Shortcomings of Japan's BI respondents who left all questions unanswered, and manuals were identified. two who did not indicate either their grade or age. The survey was conducted after the ethical review (Ethical considerations) by Faculty of Medicine, Tottori University. The nationwide survey we conducted on smoking (1) Drinking behaviors and drinking among middle- and high-school The survey conducted in 2017 found declines in students is an anonymous survey where no private the proportions of students who had ever information was collected. Results for individual consumed alcohol, the proportions of students who schools are not made public. The survey was had consumed alcohol in the preceding month, and conducted only at schools whose principals the proportions of students who consumed alcohol consented to participating in the survey. The study at least once every week compared to the previous protocol has been reviewed and approved by the survey (2014), for both male and female students, Tottori University Faculty of Medicine ethical and for all school grades. The proportion of review board. students who had ever consumed alcohol was 16.2% (male: 17.1%; female: 15.3%) for the C. Study results middle-school students, and 29.4% (male: 30.3%; 1) Nationwide survey on the smoking and drinking female: 28.5%) for the high-school students. The behaviors of middle- and high-school students proportion of students who had consumed alcohol This survey employed a cross-sectional, sample in the preceding month was 2.8% (male: 3.2%; survey design. Ninety-eight middle schools and 86 female: 2.4%) for the middle-school students, and high schools were selected for the survey, from 7.0% (male: 7.7%; female: 6.3%) for the among the 10,325 and 4,907 schools across the high-school students. The proportion of students country, respectively. The survey took place who consumed alcohol at least once every week between December 2017 and February 2018. The was 0.4% (male: 0.5%; female: 0.4%) for the schools were selected by one-stage cluster middle-school students, and 1.7% (male: 2.0%; sampling with probabilities proportional to size. female: 1.3%) for the high-school students. By sex, Survey subjects were all of the students enrolled in the frequency was higher among male students, all of the schools selected. Consent to participate in although the male-female difference was smaller the study was obtained from 48 middle schools compared to that for smoking. (response rate: 49%) and 55 high schools (64%), or (2) Smoking behaviors

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Starting this time, our survey asked questions (male: 2.9%; female: 1.4%) for the high-school about smoking for different types of tobacco students. The proportion of students who had products: namely, conventional cigarettes, smoked in the preceding month was 0.5% (male: heat-not-burn tobacco products, and electronic 0.6%; female: 0.4%) for the middle-school cigarettes. The frequency of using conventional students, and 0.9% (male: 1.2%; female: 0.6%) for cigarettes was compared to those in the past the high-school students. The proportion of surveys. The proportion of students who had ever students who smoked every day was 0.1% (male: smoked conventional cigarettes were higher with 0.1%; female: 0.1%) the middle-school students, older students, with the proportion higher in and 0.1% (male: 0.1%; female: 0.0%) for the female students than in their male counterparts. high-school students. The proportion of proportion Compared to the results of previous surveys, the of students who had ever smoked electronic proportion of proportion of students who had ever cigarettes was 2.1% (male: 2.4%; female: 1.7%) smoked was on the decline. With respect to the for the middle-school students, and 3.5% (male: frequency of smoking by three types of tobacco 4.9%; female: 2.1%) for the high-school students. products, the proportion of students who had ever The proportion of students who had smoked in the smoked conventional cigarettes was 2.6% (male: preceding month was 0.7% (male: 0.8%; female: 3.1%; female: 2.1%) for the middle-school 0.5%) for the middle-school students, and 1.0% students, and 5.1% (male: 6.9%; female: 3.3%) for (male: 1.5%; female: 0.5%) for the high-school the high-school students. The proportion of students. The proportion of students who smoked students who had smoked in the preceding month every day was 0.1% (male: 0.1%; female: 0.1%) was 0.6% (male: 0.7%; female: 0.5%) for the for the middle-school students, and 0.1% (male: middle-school students, and 1.5% (male: 2.0%; 0.1%; female: 0.1%) for the high-school students. female: 0.9%) for the high-school students. The (3) Sleep disturbance proportion of students who smoked every day was The results of subjects' self-rating of the quality 0.1% (male: 0.2%; female: 0.1%) for the of sleep for the preceding 30 days showed that the middle-school students, and 0.5% (male: 0.7%; answer of “Fairly good” was the most common, female: 0.2%) for the high-school students. followed by “Fairly poor” both among the male Compared to the results from when we conducted and female students. The proportion of students our first survey, the proportions of students who who rated it as being “Fairly poor” was slightly had smoked in the preceding month and those of higher among the female students, and the rate students who smoked every day decreased were higher among older students, although the significantly. The proportion of proportion of proportion was lower in the 12th graders than in students who had ever smoked heat-not-burn the 11th graders. The average hours of sleep for the tobacco products was 1.1% (male: 1.3%; female: preceding 30 days was “6 hours or more and less 0.9%) for the middle-school students, and 2.2% than 7 hours” for the largest portion of the students,

5 both male and female, followed by “Less than 5 screening for pathological Internet users were hours” for the male students and “5–6 hours” for compared to those of a survey conducted in 2012 the female students. The trend of short sleep was using the same screening test. The results of the more pronounced among older students. As for the comparison revealed marked increases in the frequency of having difficulties in getting to sleep proportions of students rated as being maladaptive for the preceding 30 days, “Sometimes” was the users (YDQ score 3-4) and pathological users most common answer among both the male and (YDQ score 5 or higher) in FY 2017, both for the female students, and the rates were higher among middle- and high-school students, as well as for older students. The results on the frequency of both sexes, with the proportions higher among the waking up during the night for the preceding 30 female students. days found that “Never” was the most common, The proportion of students in 2017 who were followed by “Sometimes.” The proportion of rated as being pathological users (YDQ score 5 or students who chose “Sometimes” was higher in the higher) was 12.4% (male: 10.6%; female: 14.3%) high-school students than in the middle-school for the middle-school students, and 16.0% (male: students, and more common in the female students 13.2%; female: 18.9%) for the high-school than in the male students. The results on the students in 2017. When the results from the 2012 frequency of being awake early in the morning for survey were adjusted with the number of students the preceding 30 days, meanwhile, found “Never” in each grade, the proportion was 6.0% (male: to be the most common answer, although a little 4.4%; female: 7.7%) for the middle-school over 10% of the students chose “Sometimes.” It students, and 9.4% (male: 7.6%; female: 11.2%) was also slightly more common in the high-school for the high-school students. The figure had students than in the middle-school students. doubled for the middle-school students. The (4) Excessive Internet use proportion of students in 2017 who were rated as The time spent online on weekdays for the being maladaptive users (YDQ score 3–4) was preceding 30 days was most commonly less than 2 21.8% (male: 20.8%; female: 22.9%) for the hours (from 1-2 hours) both in the male and female middle-school students, and 27.1% (male: 24.3%; students, although more spent 4-5 hours online female: 29.9%) for the high-school students. The among the high-school students, with a sizeable proportion in 2012 was 12.6% (male: 10.9%; portion of them spending 5 hours or longer. Female female: 14.4%) and 18.5% (male: 15.9%; female: students tended to spend longer hours online. As 21.1%), respectively, again showing significant for the time spent online on weekends, 4-5 hours increases. In other words, the proportions of was the most common, followed by 5 hours or adaptive users with YDQ score of 2 or less had longer. Very few stayed off-line, while many of the reduced significantly. middle- and high-school students used the Internet for long hours. The results of an 8-question 2) Literature review on health effects of alcohol

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As the world sees tighter regulations on alcohol consume more than 14 drinks (for men) or 7 drinks consumption and use, Japan enacted the Basic Act (for women) per week, as suggested by NIAAA, on Measures against Alcohol-related Health Harm, those whose levels of drinking is considered to and has since promoted measures against excessive pose a risk of developing lifestyle-related diseases drinking. Among the areas of focus recognized is (40 g 100% ethanol/day for men, and 20 g 100% “to ensure the complete dissemination of ethanol/day for women) as defined in Health Japan knowledge on risks associated with alcohol 21, and those whose AUDIT score exceeds 8–10. consumption,” which requires the provision of the Screenings used included the AUDIT-C, which is a latest and best findings on risks associated with simplified version of the AUDIT, in which the drinking, backed by evidence-based medicine. cut-off score for alcohol use disorders is 5 for men In recent years, systematic reviews, or SRs, have and 4 for women. In another occasion, NIAAA been conducted on the health effects of alcohol used a question asking people if they had had 5 or consumption, in which researchers take a more drinks (for men) or 4 or more drinks (for systematic look at previous studies, synthesize women) at a time during the preceding one-year them both quantitatively and qualitatively, and period for screening. Modes of intervention ranged propose strong evidence based on them. In this widely, from interviews and brochures to IT project, our group conducted an overview of SRs devices. It was shown that the effects in reducing to compile and analyze evidence. Searches in drinking were greater as well as longer-lasting with PubMed found 523 SRs, and after they were multiple interventions than with a single checked for eligibility for inclusion in our review, intervention. In terms of time, while BI was shown 118 SRs have ultimately been selected. We plan to to be more effective if given in five minutes or evaluate the quality of the individual studies longer, longer counseling sessions that lasted over covered by the SRs selected, then analyze the 20 minutes showed no difference to shorter BI in validity of the evidence they offer. their effectiveness. Other than standard BI, Ultra-BI, a further simplified version that is given 3) Review on brief interventions aimed at reducing in less than ten minutes, was also proposed for the alcohol consumption primary care settings, including emergency rooms, As a measure against alcohol-related issues, brief where reduced alcohol consumption or binge intervention (BI) has been widely used around the drinking were reported. BI guidelines proposed world as an evidence-backed technique. In this included the following: (i) NIAAA guideline: collaborative research project, we collected interventions based on an intervention algorithm representative reviews and literatures on the effects using motivational interview technique, and of BI, to amass findings including factors establishing goals, developing plans, and providing concerning the effects of BI and guidelines on BI. educational materials to help people cut back on Target populations of BI included people who alcohol consumption down to 5 drinks or less for

7 men and 4 drinks or less for women; (ii) NICE who consumed alcohol at least once every week, guideline: 12 weekly sessions of 60 minutes' the proportion of students who had smoked in the duration using cognitive and behavioral therapies; preceding month, and the proportion of students (iii) HAPPY Program: a program developed by who smoked every day had become fairly low, Hizen Psychiatric Center that combines health apparently having bottomed out. Whatever the case education, provision of information, and may be, this is a desirable trend as we forecast the interventions for heavy drinkers who are in a phase health issues faced by future generations of adults of indifference, with a greater focus on . compared to other BI approaches; and (iv) alcohol Our prominent findings included the following: reduction support under Specific Health Guidance: certain percentages of drinkers were heavy guidance on reducing alcohol consumption for drinkers and binge drinkers (i.e. drinkers people subject to Specific Health Guidance whose consuming large quantities of alcohol in a single AUDIT score is 8-14, with a focus on the session); many of the drinkers and smokers were FRAMES model, targets in alcohol consumption, able to purchase alcohol and cigarettes by and a diary of alcohol use. Taking into themselves; the use of non-alcoholic “beers” and consideration the insights obtained through our cocktail drinks was on the rise; middle- and review, we intend to develop and test multiple BI high-school students were victims of “alcohol models that can be adapted in the community and harassment (i.e. the act of forcing others to drink as general healthcare settings. an abuse of authority)”; the frequency of using cigarette alternatives was nearly as high as that of D. Discussion conventional cigarettes; higher prices, age For the first time since 2014, our group conducted verification, and restrictions on the use of vending a nationwide survey to find out about the smoking machines appeared to make it difficult to obtain and drinking behaviors, sleep disturbance, and cigarettes; their exposure to secondhand smoke excessive Internet use among middle- and was still high and the frequency of passive high-school students. The results found major smoking outside home showed no decrease; the changes from those of the past surveys. frequency of sleeping disturbance remained high; The frequency of drinking and that of smoking and excessive Internet use was on the rise. among middle- and high-school students showed The medical and epidemiological insights into the steady decreases. While the proportion of students health effects of alcohol use we gain have rapidly who had ever consumed alcohol, the proportion of become deeper in the recent years, with a number students who had consumed alcohol in the of reports offering insights with a point of view preceding month, and the proportion of students that is different from conventional ones. It will be who had ever smoked continued on the existing essential to further refine our reviews, identify trend of linear decreases, the proportion of students what parts of existing knowledge need to be

8 modified, and create user-friendly tools to provide cross-sectional study of adolescents in Japan. J information. The brief intervention approaches and Epidemiol. 27(3):107-111, 2017. what they should incorporate have now been mostly established. They should now be broken 2. Presentation at conferences down into forms that can be applied to use in 1) Osaki Y, Kinjo A, Kuwahara Y, Imamoto A, Japan's healthcare, health checkup, and health Maesato H, Minobe R. Drinking and health topics guidance settings, to provide a basis for the and their epidemiological evidence: Recent development of intervention tools for future epidemiological findings on health hazards of intervention studies. alcohol. Japanese Journal of Studies on Alcohol and Drug Dependence, 52(4):229,2017 (Japanese E. Conclusion Medical Society of Alcohol and Addiction Studies The frequency of smoking and that of drinking symposium) were on a steady decline. There were some 2) Osaki Y, Kinjo A, Oida T, Kuwahara Y. Topics findings that raised concerns, however, including in the fields of adolescent public health - Message the increase in the frequency of non-alcoholic for the future from the forefront of research: Latest “beers” and cocktail drinks, the use of electronic trends in underage drinking and smoking behaviors. cigarettes and heat-not-burn tobacco products, and Japanese Journal of Public Health, the excessive Internet use. 64(10):244,2017 (Japanese Society of Public Regular monitoring will remain critical. Health symposium)

F. Health crisis and risk information H. Intellectual property application / registration N/A 1. Patent application N/A G. Publication of research findings 2. Utility model registration 1. Publication of papers N/A 1) Kinjo A, Imamoto A, Ikeda M, Itani O, Ohida T, 3. Other Kaneita Y, Kanda H, Tanihata T, Higuchi S, Osaki Y. The Association Between Alcohol-Flavoured Non-Alcoholic Beverages and Alcohol Use in Japanese Adolescents. Alcohol Alcohol. 52(3);351-357,2017. 2) Morioka H, Itani O, Osaki Y, Higuchi S, Jike M, Kaneita Y, Kanda H, Nakagome S, Ohida T. The association between alcohol use and problematic internet use: A large-scale nationwide

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