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. Author manuscript; available in PMC: 2019 Apr 1.
Published in final edited form as: Addict Behav. 2017 Dec 21;79:195–200. doi: 10.1016/j.addbeh.2017.12.017

Age at Drinking Onset, Age at First Intoxication, and Delay to First Intoxication: Assessing the Concurrent Validity of Measures of Drinking Initiation with Alcohol Use and Related Problems

Meghan E Morean a,b,*, Alexa L’Insalata a, Ellyn R Butler a, Avalon McKee a, Suchitra Krishnan-Sarin b
PMCID: PMC5807182  NIHMSID: NIHMS932008  PMID: 29304425

Abstract

Introduction

Drinking at an early age (AO) and quickly progressing to drinking to intoxication (Delay = Age of Intoxication[AI]-AO) confer risk for alcohol use and alcohol-related problems. However, inconsistencies exist in the literature, which may reflect the use of different definitions of AO and AI. We evaluated whether 1) defining AO as age at first sip of alcohol (AO sip) versus age at which at least one standard drink was consumed (AO drink); and 2) defining AI as age at first “drunk” (AI drunk) versus age at first binge episode (≥5 standard drinks consumed; AI binge) resulted in different self-reported ages or differentially predicted drinking outcomes.

Methods

248 high school students (53.6% male; 16.50[1.19] years; 71.4% White) completed anonymous surveys assessing alcohol use.

Results

Participants reported a younger AO (sip) than AO (drink) and a younger AI (drunk) than AI (binge), resulting in significantly different Delay values for the four AO-AI pairings. Univariate general linear models indicated that AO-Delay pairings accounted for more variance in maximum drinks and alcohol-related problems than did the individual AO and AI variables. Pairings comprising AO (drink) and Delay (drink-binge) and AO (sip) and Delay (sip-binge), respectively, uniquely accounted for variance in both maximum drinks and problems.

Conclusions

Clearly defining AO and AI using objective definitions that reflect specific amounts of alcohol (e.g., first sip; first standard drink; first binge) appears to outperform subjective definitions of alcohol use (e.g., first drunk).

Keywords: age of onset, delay to intoxication, adolescents, alcohol, underage drinking

1.0 Introduction

Underage alcohol use poses serious public health problems at the level of the individual, the family, and society (SAMHSA, 2012). While rates of youth alcohol use have decreased over the past decade (Miech et al., 2015), continued efforts to curb underage drinking are warranted. Developing more effective prevention and intervention efforts inextricably is linked an improved understanding of alcohol-related risk factors among youth.

Age at drinking onset (AO) is an established risk factor for heavy alcohol use and alcohol-related problems, with most studies indicating that an earlier AO confers risk for heavier drinking and alcohol-related problems (e.g., Dawson et al., 2008; Hingson and Zha, 2009; Hingson et al., 2006). Research also indicates that drinking to intoxication at an early age (AI) confers similar risk (e.g., Hingson et al., 2006; Henry et al., 2011; Warner and White, 2003; Warner et al., 2007). Recent research suggests that deconstructing AI into its constituent components - AO and the lag time to first intoxication (i.e., Delay) – may be a more informative way of examining early intoxication; studying AO and Delay as joint alcohol-related risk factors accounts for additional variance in drinking outcomes relative to examining either AO or AI independently (Morean et al. 2012; Morean et al., 2014). Specifically, an earlier AO coupled with a shorter Delay predicts heavy drinking in high school students (Morean et al., 2014) and heavy drinking and alcohol-related problems in college students (Morean et al., 2012).

While the field is making strides in understanding the links between early drinking and negative alcohol-related consequences in youth, inconsistent research findings have been noted, especially with respect to the relationship between AO and negative alcohol outcomes. Several studies, including a systematic review of prospective cohort studies, have either found little to no evidence for associations between early drinking and negative drinking outcomes or have suggested that more complex, non-linear relationships exist (Afitska et al., 2008; Chou and Pickering, 1992; DeWit et al., 2000; Maimaris and McCambridge, 2014).

In an attempt to identify potential sources of the aforementioned inconsistencies across studies, we reviewed the AO literature. Of note, we found considerable variability in the types of questions that have been used to assess AO (for sample questions see Table 1). Some questions are non-specific with regard to the amount of alcohol consumed at the AO event (e.g., “How old were you when you started to drink alcohol?” [Eliasen et al., 2009]; “At what age did you start using alcohol?” [Pitkänen et al., 2005]) while others assess the onset of more regular drinking (e.g., “How old were you when you first started drinking? For example, having two or more drinks a week?” [Muthen, 2000]). Further complicating the research landscape, some questions refer to alcohol use occurring specifically outside of family or religious contexts (e.g., Warner et al., 2007), as drinking characterized by consuming more than just a few sips (e.g., Morean et al., 2014), or as drinking characterized by consuming a specific number of drinks (e.g., “a whole drink;” Kuperman, 2005). Of concern, in a number of cases, researchers have not reported explicitly what question they used to assess AO (e.g., Baltieri, 2014; Handley et al., 2013; Hayatbakhsh et al., 2014). Assessing AO using different questions may contribute to the inconsistencies in findings about the risk conferred by an early AO. Questions that assess specific quantities of alcohol consumed at AO (e.g., “How old were you when you drank at least one glass of alcohol for the first time [Monshouwer, 2003]) may produce more reliable results than questions that do not specify the amount of alcohol consumed (e.g., “At what age did you start using alcohol?” [Pitkänen, 2005]). The latter case may be associated with an earlier AO for some individuals who interpret the question to mean the first time they tried a sip of alcohol but may be associated with a later self-reported AO for individuals who interpreted the question to assess the onset of more regular alcohol use (e.g., monthly use). Differences in AO based on question type may translate to meaningful differences in study results. However, no study of which we are aware has evaluated this possibility.

Table 1.

A Sampling of Questions Used to Assess Age of Onset and Age of Intoxication

Age of Onset
First Author Year Country Question
Afistska 2008 UK When (if ever) did you first drink at least one glass of beer, wine, spirits?
Clark 2013 USA How old were you when you first had an alcoholic drink?”
Deutsch 2013a,b Australia How old were you the first time you had more than just a sip of beer, wine, or spirits?
DeWit 2000 Canada Not counting sips, how old were you the very first time you had a drink of beer, wine, or liquor?
Eliasen 2009 Denmark, Iceland, Norway, Sweden How old were you when you started to drink alcohol?
Grant 1997, 1998 USA Not counting sips, how old were you the very first time you had a drink of beer, wine, or liquor?
Grant 2001 USA How old were you when you first started drinking? For example, having two or more drinks a week?
Grant 2005 USA At what age did you begin drinking regularly (consuming alcohol at least once a month for ≥ 6 months?
Hingson 2000a,b 2002, 2006, 2008, 2009 USA About how old were you when you first started to drink, not counting small sips or tastes?
Kraus 2000 Germany At what age did you begin drinking regularly (consuming alcohol at least once a month)?
Kuperman 2005 USA How old were you when you had your very first whole drink?
Livingston 2008 Australia How old were you when you had your very first whole drink?
McGue 2001 USA How old were you the first time you used alcohol (on your own; more than your parents allowed you to)?
Monshouwer 2003 Netherlands How old were you when you drank at least one glass of alcohol for the first time?
Muthen 2000 USA How old were you when you first started drinking? For example, having two or more drinks a week?
Morean 2012 USA Not including drinking as part of religious ceremonies, at what age did you take your first drink on your own rather than just a sip from an adult’s glass?
Morean 2014 USA How old were you the first time you tried alcohol (more than just a few sips and not including drinking as part of religious activities)?
Nigg 2013 USA How old were you when you had your first drink of alcohol other than a few sips?
Pilatti 2014 Argentina How old were you the first time you drank a glass or more of any alcoholic beverage?
Pitkänen 2005a,b Finland At what age did you start using alcohol?
Prescott 1999 USA How old were you when you first had a drink, other than as part of a religious ceremony?
Schuckit 1983 USA At what age did you first take a drink on your own, rather than just a sip from an adult’s glass, not including religious ceremonies?
Stallings 1999 USA At what age did you first drink alcohol -- first time ever?
Ta 2010 USA How old were you when you had your first drink of alcohol other than a few sips?
Warner 2003, 2007 USA At what age did you try (more than a few sips) beer, wine, and hard liquor for the first time?
At what age did you first try each type of alcohol outside a family gathering?
York 2004 USA How old were you when you had your first drink of any beverage containing alcohol, other than a taste?
Zhang 2014 USA About how old were you when you began drinking alcoholic beverages, not counting small tastes?
Age of Intoxication
Adam 2011 Switzerland Have you ever been intoxicated due to alcohol? If so, at what age?
Afistska 2008 UK When (if ever) did you first get drunk on alcohol?
Deutsch 2013 Australia How old were you the first time you got drunk?
Ehlers 2006 USA What was the age the rst time you got drunk, that is, your speech was slurred or you were unsteady on your feet?
Fromme 1983 USA What was your age at the time of first intoxication?
Hingson 2003 USA How old were you when you first got drunk (unsteady, dizzy, or sick to your stomach)?
Hingson 2004 USA How old were you when you first got drunk?
Monshouwer 2003 Netherlands How old were you when you got drunk for the first time?
Morean 2012 USA How old were you when you first got drunk after drinking alcohol?
Morean 2014 USA How old were you the first time you got drunk?
Stallings 1999 USA At what age did you first become intoxicated?
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Given the diversity in the questions used to assess AO, we also reviewed the questions that have been used to assess AI. All studies conceptualized intoxication subjectively (e.g., feeling drunk; See Table 1). The subjectivity of the term “drunk” may result in widely varying responses. For example, some individuals may conceptualize the effects of drinking one or two drinks as constituting intoxication, especially during early drinking episodes, and subsequently report an AI corresponding to the first time they ever consumed one or two drinks. However, others may conceptualize intoxication as occurring at higher doses of alcohol, potentially resulting in an older self-reported AI. Thus, the field may benefit from assessing AI by specifying an objectively intoxicating amount of alcohol (i.e., a binge episode).

In the current study we evaluated the impact of defining AO as 1) the age at which an individual had his or her first sip of alcohol (AO sip) versus 2) the age at which an individual consumed at least one standard drink (AO drink). We also evaluated the impact of defining age of first intoxication as 1) the age at which an individual first experienced subjective intoxication (i.e., “got drunk”; AI drunk) versus 2) the age at which an individual first consumed at least five standard drinks on a single occasion (AI binge). We hypothesized that, on average, individuals would report an earlier AO (sip) than AO (drink) as well as an earlier AI (drunk) than AI (binge). We also examined whether the different operational definitions of AO and AI, considered independently and in concert with Delay, would relate differently to markers of problem drinking (i.e., maximum drinks consumed on a single occasion and the experience of alcohol-related problems). We anticipated that both the individual AO and AI variables and the AO-Delay pairings that were based on questions assessing a specific amount of alcohol (i.e., a sip, one standard drink, and/or five or more drinks [a binge episode]) would account for more variance in drinking outcomes than models containing subjectively defined “first drunk.”

2.0 Materials and Methods

2.1 Participants

Two hundred forty eight students from a high school in Connecticut completed a survey assessing alcohol use (53.6% male; mean age 16.50 [1.19] years; 17.5% 9th grade, 19.5% 10th grade, 38.2% 11th grade, 24.8% 12th grade; 71.4% White).

2.2 Procedures

The survey was approved by the Institutional Review Board of Yale University. During their lunch period, interested students completed a brief screener that was distributed by study staff. Students who responded “yes” to the question “Have you ever had a drink of alcohol?” were invited to complete the full survey in the library immediately after school. Prior to completing the survey, students were informed that participation was voluntary and anonymous, and that their data were confidential. Participants were compensated $5.

2.3 Measures

2.3.1 Demographic Information

Participants reported on their biological sex, race/ethnicity, age, and grade in school.

2.3.2 Age of Onset of Alcohol Use

Participants reported how old they were 1) “the very first time [they] had a sip of alcohol, counting even a very small sip” (i.e., AO sip) and 2) “the very first time [they] had at least 1 standard alcoholic drink [NOT counting small sips or small amounts consumed during religious activities]” (i.e., AO Drink). A standard drink was defined within the survey as a 12 ounce bottle or can of beer, a 5 ounce glass of wine, or a shot of hard liquor like vodka, rum, whiskey, or tequila, and pictures accompanied the description.

2.3.3 Age of First Intoxication

Participants reported how old they were 1) “the very first time [they] drank enough to feel drunk” (i.e., AI drunk) and 2) “the very first time [they] drank five or more drinks in one sitting” (i.e., AI binge).

2.3.4 Maximum Drinks

Participants reported on the maximum number of drinks they had ever consumed on a single occasion, which is an endophenotype related to alcohol dependence (Saccone et al., 2000).

2.3.5 Alcohol-Related Problems

(The Rutgers Alcohol Problem Index; RAPI; White & Labouvie, 1989). Using the response options “never, 1–2 times, 3–5 times, 6–10 times, >10 times,” participants rated how frequently over the past 3 months they experienced 23 negative consequences of alcohol use (e.g., neglected responsibilities; not able to study for a test).

2.4 Data Analytic Plan

We first examined mean scores for maximum drinks consumed on a single occasion and alcohol-related problems. We also calculated the four Delay variables: 1) Delay (sip-drunk); 2) Delay (sip-binge); 3) Delay (drink-drunk); and 4) Delay (drink-binge).

We then conducted paired-samples t-tests to evaluate whether AO (sip), AO (drink), AI (drunk), and AI (binge) differed significantly from one another. We similarly evaluated whether the four Delay variables differed significantly from one another.

Next, we ran four Univariate General Linear Models to evaluate whether AO (sip), AO (drink), AI (drunk), or AI (binge), respectively, predicted the maximum drinks and/or alcohol-related problems. Model covariates included sex, race, and grade in school (which allowed us to control for participant age and potential cohort effects within a grade simultaneously). The total number of drinks consumed in the past month also was included as a covariate in the models predicting alcohol-related problems. The four models were then rerun with each of the four pairings of AO and Delay included as the independent variables.

3.0 Results

On average, participants reported consuming a maximum of 9.12 [5.71] drinks on a single occasion (range 1–20). Given the scale of the RAPI (“never, 1–2 times, 3–5 times, 6–10 times, >10 times), it is difficult to interpret a mean score. For ease of interpretation, we report here a simple count of the number of alcohol-related problems experienced (8.80 [7.98] problems).

Paired samples t-tests indicated that self-reported AO (sip), AO (drink), AI (drunk), and AI (binge) all differed significantly from one another, p-values < .001, as did each of the Delay variables, p-values < .001 (See Table 2).

Table 2.

Age of Onset, Age of Intoxication, and Delay Variables differ significantly from one another based on question type

Variable Mean (years) Std. Dev.
Age at First Sip 11.32 3.28
Age at First Standard Drink 14.04 1.73
Age at First Drunk 14.53 1.35
Age at First Binge 14.85 1.36
Delay First Sip to First Drunk 3.32 2.99
Delay First Sip to First Binge 3.71 3.22
Delay First Drink to First Drunk 0.58 1.07
Delay First Drink to First Binge 0.85 1.22
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Note. All age of onset values differed from one another at p < .001. All delay variables differed from one another at p < .001.

The univariate GLM models indicated that starting to drink at an earlier age and drinking to intoxication at an earlier age, irrespective of operational definition, were associated with consuming a larger number of maximum drinks on a single occasion (see Table 3). Only binge drinking at an earlier age was associated with experiencing more alcohol-related problems (See Table 3).

Table 3.

Age of Onset and Age of Intoxication Variables Predict Maximum Number of Drinks Consumed (Lifetime) and Alcohol-Related Problems

Maximum # Drinks Alcohol-Related Problems
Variable df F ηp2 df F ηp2
Corrected Model (6, 228) 9.12 .20*** (7, 227) 9.76 .24***
Sex 1 32.86 .13*** 1 36.94 .14***
Grade 3 5.28 .07** 3 5.93 .08**
Race 1 0.32 .00 1 0.05 .00
Total Monthly Drinks -- -- -- 1 6.66 .03**
Age at First Sip 1 6.86 .03** 1 3.92 .01
Corrected Model (6, 228) 10.18 .22*** (7, 227) 8.83 .22***
Sex 1 24.88 .10*** 1 34.97 .14***
Grade 3 7.36 .09*** 3 4.74 .06*
Race 1 0.82 .00 1 0.15 .00
Total Monthly Drinks -- -- -- 1 5.69 .03*
Age at First Drink 1 11.41 .05** 1 0.43 .00
Corrected Model (6, 194) 7.78 .20*** (7, 193) 7.33 .22***
Sex 1 19.31 .09*** 1 26.98 .13***
Grade 3 4.85 .07** 3 3.23 .05*
Race 1 0.01 .00 1 0.42 .00
Total Monthly Drinks -- -- -- 1 3.69 .02*
Age at First Drunk 1 8.41 .04** 1 1.53 .01
Corrected Model (6, 185) 7.35 .20*** (7, 184) 8.24 .25***
Sex 1 14.75 .08*** 1 21.98 .11***
Grade 3 4.71 .07** 3 4.43 .07**
Race 1 0.18 .00 1 1.60 .01
Total Monthly Drinks -- -- -- 1 2.39 .01
Age at First Binge 1 11.71 .06** 1 4.85 .03*
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Note:

*

p < .05

**

p < .01

***

p < .001

-- denotes that total monthly drinks was not included as a model covariate.

Reference groups are females, 9th grade students, and non -Whites. Abbreviations are df (degrees of freedom); ηp2 (partial eta squared); Age at First Sip (age when participant consumed his/her first sip of alcohol); Age at First Drink (age when participant consumed his/her first standard drink); Age at First Drunk (age when participant first drank to the point of sub jective intoxication); Age at First Binge (age at when participant first engaged in a binge drinking episode)

With regard to the AO-Delay pairings, consuming a greater number of drinks was associated with an earlier AO and a shorter Delay across all models, with the exception of Delay (drink-drunk) which was not a significant predictor of maximum drinks when it was included alongside AO (drink) (see Table 4). Experiencing more alcohol-related problems was associated with an earlier AO only in the two models that also contained Delay to first binge (see Table 4). Experiencing more alcohol-related problems was associated with a shorter Delay across all models, with the exception of the model in which AO (drink) and Delay (drink-drunk) were entered together.

Table 4.

Different Pairings of Age of Onset and Delay to Intoxication Variables Predict Maximum Number of Drinks Consumed (Lifetime) and Alcohol-Related Problems

Maximum # Drinks Alcohol-Related Problems
Variable df F ηp2 df F ηp2
Corrected Model (7, 192) 6.55 .20*** (8, 191) 7.52 .25***
Sex 1 18.88 .09*** 1 24.53 .12***
Grade 3 4.50 .07** 3 3.01 .05*
Race 1 0.00 .00 1 0.11 .01
Total Monthly Drinks -- -- -- 1 2.97 .02
Age at First Sip 1 8.69 .05** 1 1.67 .01
Delay Sip to Drunk 1 5.73 .03* 1 4.83 .03*
Corrected Model (7, 182) 6.15 .20*** (8, 182) 8.50 .28***
Sex 1 14.19 .08*** 1 21.87 .11***
Grade 3 0.15 .00 3 4.14 .07**
Race 1 4.59 .07** 1 1.30 .01
Total Monthly Drinks -- -- -- 1 1.91 .01
Age at First Sip 1 12.36 .07*** 1 3.46 .02*
Delay Sip to Binge 1 9.28 .05** 1 7.65 .04**
Corrected Model (7, 188) 6.18 .19*** (8, 187) 6.41 .22***
Sex 1 20.62 .10*** 1 28.06 .14***
Grade 3 3.39 .05* 3 3.03 .05*
Race 1 0.19 .00 1 0.15 .00
Total Monthly Drinks -- -- -- 1 3.97 .02*
Age at First Drink 1 7.10 .04** 1 1.45 .01
Delay First Drink to First Drunk 1 2.63 .01 1 0.88 .01
Corrected Model (7, 184) 6.42 .20*** (8, 183) 7.12 .25***
Sex 1 14.75 .08*** 1 20.92 .11***
Grade 3 5.19 .08** 3 3.83 .06*
Race 1 0.27 .00 1 1.57 .01
Total Monthly Drinks -- -- -- 1 2.41 .01
Age at First Drink 1 12.78 .07*** 1 4.94 .03*
Delay First Drink to First Binge 1 5.70 .03* 1 5.55 .03*
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Note:

*

p < .05

**

p < .01

***

p < .001

-- denotes that total monthly drinks was not included as a model covariate.

Reference groups are females, 9th grade students, and non -Whites. Abbreviations are df (degrees of freedom); ηp2 (partial eta squared); Age at First Sip (age when participant consumed his/her first sip of alcohol); Age at First Drink (age when participant consumed his/her first standard drink); Delay to Drunk (delay between age of onset and first subjective experience of intoxication); Delay to Binge (delay between age of onset and first binge drinking episode)

4.0 Discussion

The current study expands our understanding of AO, AI, and Delay to first intoxication as risk factors for consuming a greater number of maximum drinks on a single occasion and the experience of alcohol-related problems in high school students. Of central importance, using different operational definitions of AO and AI translated to statistically significant differences in results, suggesting that the use of different operational definitions of these constructs may contribute, at least in part, to the discrepancies observed in prior research findings. As hypothesized, adolescents reported a younger AO (sip) relative to AO (drink) and a younger AI (drunk) relative to AI (binge). Further, when AO (sip), AO (drink), AI (drunk), and AI (binge) were examined as independent predictors of maximum drinks consumed on a single occasion, an earlier AO and an earlier AI were associated with drinking a larger number of maximum drinks irrespective of how these variables were defined. However, only an early AI (binge) was associated with experiencing more alcohol-related problems.

Consistent with prior research indicating that examining AO and Delay in concert represents a more informative way of conceptualizing early intoxication (Morean et al., 2012; Morean et al., 2014), each of the pairings of AO and Delay accounted for more variance in maximum drinks than did AO (sip), AO (drink), AI (drunk), and AI (binge), respectively. However, only the pairings comprising the clearly defined versions of AO (i.e., first sip and first drink) and Delay (drink-binge) accounted for significant variance in both maximum drinks and alcohol-related problems.

The novel study findings should be considered in light of several limitations. First, study results were based on participant self-report. In addition, the generalizability of the study results may be limited by the fact that data were collected within a single high school in Connecticut and by the fact that the analytic sample comprised high-risk adolescents who endorsed underage drinking. Furthermore, the study was cross-sectional. As such, it is not possible to state, for example, that an earlier AO and a shorter Delay cause heavy drinking or alcohol-related problems although prior longitudinal research has indicated such directionality (Morean et al., 2012). Of note, the current study did not test a truly ambiguous AO variable (e.g., when did you first start drinking), so the results are limited to the questions that were asked. In addition, the definition of binge drinking used in the current study (i.e., 5 or more drinks on a single occasion) may have resulted in a later AI (first binge) reported by females in the study than might have been the case if the standard definition of binge drinking was used (e.g., drinking 4 or more drinks in 2 hours for females or 5 or more drinks in two hours for males). Finally, although the current study suggests that different definitions of AO and AI are differentially associated with alcohol use outcomes, a meta-analysis comparing the predictive power of different AO and AI questions across studies would provide more definitive evidence. However, given the lack of consistency in the questions used to assess AO and AI in the extant literature and the variability in study samples (e.g., adults, adolescents, Americans, Europeans), conducting a meta-analysis was not possible. In the future, a meta-analysis should be conducted as additional research is conducted using standardized questions.

In spite of the limitations, the findings indicate that the way researchers and clinicians choose to operationalize age at drinking onset and first intoxication matters. Although additional research on this topic is warranted to determine the extent to which the current pattern of results can be replicated, asking participants or clients questions that clearly define the amount of alcohol consumed at AO (i.e., one sip or 1 standard drink) or AI (i.e., 5 or more standard drinks in a single occasion) appears to be a more informative approach for capturing risk associated with problematic drinking than asking questions that do not specify a specific amount of alcohol (e.g., first drunk).

Highlights.

  • Starting to drink at an early age confers risk for negative drinking consequences.

  • Quickly progressing to drinking to intoxication also confers alcohol-related risk.

  • Many different questions have been used to assess these constructs across studies.

  • Objectively defined age of onset and intoxication outperform subjective questions.

Acknowledgments

Role of Funding Source

This research was supported in part by P50AA12870 from the NIAAA (Center for Translational Neuroscience in Alcoholism). This sponsor had no role in the study design; collection, analysis or interpretation of the data; writing the manuscript; or the decision to submit the paper for publication.

Footnotes

Contributors

Drs. Morean and Krishnan-Sarin conceptualized the study and developed study hypotheses. Dr. Morean developed the self-report survey and managed the collection of the data. Dr. Morean, Ms. Butler, Ms. L’Insalata, and Ms. McKee ran the statistical analyses and collaborated on writing drafts of the manuscript. All authors contributed to the final manuscript and approved the submission.

Conflict of Interest

No conflicts declared

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