Association between Self-perceptions of Periodontal Health and Electronic Cigarette use in Young Adults
Abstract
Background:
The present study aimed to determine the association between self-perceptions of periodontal health and electronic cigarette use.
Material and Methods:
The study used an observational, analytical and cross-sectional design. 189 young adults aged 18 to 29 from the Metropolitan area of Lima, Peru, were recruited. In order to evaluate self-reported periodontal health, a questionnaire conceived by Quiroz et al. (2017) was used. This includes 13 questions divided into two dimensions (habits and self-perceived periodontal health). Poisson regression with robust variance was used to examine associations between qualitative variables and calculate raw and adjusted prevalence ratios.
Results:
59.46% of participants using electronic cigarettes were found to have a poor perception of gum health. Statistically significant associations were produced between poor perceptions of gum health and vaping, regarding both raw data (PR=0.81; 95% CI: 0.69-0.95; p=0.011) and data adjusted to consider covariates (PR=0.82; 95% CI: 0.69-0.97; p=0.021). No associations were observed for the dimensions of bleeding during brushing, reddish, and/or swollen gums.
Conclusion:
A relationship was found between poor perceptions of gum health and electronic cigarette use.
1. INTRODUCTION
According to the American Academy of Periodontology and the European Federation of Periodontology, good periodontal status is defined as: “The absence of inflammation of the gums and bleeding as well as the presence of a periodontium with normal or stable support without active bone resorption with physiological immunity” [1]. According to the 2016 Global Burden of Disease Study [2], periodontal disease was the eleventh most prevalent condition in the world. Likewise, 50% of adolescents and 44% of adults have calcified dental plaque, which could be a risk factor for developing gingivitis and/ or periodontitis.
Periodontal disease can be assessed clinically or through self-report questionnaires. These instruments have become valid and important tools for determining the prevalence of this condition in large populations. Additionally, self-report is often used as a screening method to detect certain diseases in individuals without signs or symptoms of the disease. Gum self-assessment and individual awareness of periodontal disease are the main issues when identifying periodontal disease [3-5].
Many habits can damage periodontal status. For example, it has been shown that exposure to electronic cigarette smoke can damage or induce apoptosis of epithelial cells which form the first line of defense. Damage can also occur to fibroblasts in the periodontal ligament, inducing increased oxidative activity within cells, which could damage DNA and harm oral health [6]. The electronic cigarette or vape is a device that contains a liquid that is first heated, then vaporized and, finally, inhaled by the user [7]. Nicotine is one of the components of electronic cigarettes. This is highly addictive and has been shown to alter the cytoskeleton and induce remodeling of the extracellular matrix in the gingival fibroblast [8, 9]. Further, it may contain flavorings and the base or additive propylene glycol is oxidized by the increase in temperature to form large concentrations of formaldehyde that irritate the periodontal tissue.
A study carried out in the United States concluded that young adults use electronic cigarettes more than other age groups, with men also being more likely to have tried electronic cigarettes on at least one occasion [10]. Currently, one in five young adults use electronic cigarettes and current consumption is projected to more than double by 2025 [11]. In Peru, the prevalence of electronic cigarette use in young adults is 12.6%, with trends also showing a constant increase [12].
Some research links vape use with the presence of periodontal disease. In 2019, an investigation using data from the Korean National Health and Nutrition Examination Survey (KHANES) gathered from 13.551 individuals concluded e-cigarette users were more likely to have periodontal disease [13].
However, an experimental in vitro study reported that flavorless e-cigarette aerosols are less harmful to the survival and growth of oral bacteria compared to conventional cigarette smoke, given that fewer colony-forming units are formed and biofilm formation is lower [14]. Thus, it is possible that e-cigarettes are not related to the presence of periodontal disease [6]. Controversy currently abounds due to the lack of scientific articles to have conducted in-depth evaluations. Given that discussed above, the aim of the present study was to determine the association between self-perceived periodontal health and electronic cigarette use in young adults from the Metropolitan area of Lima, Peru.
2. MATERIALS AND METHODS
2.1. Study Design
An observational, analytical and cross-sectional study design was used. The study was carried out among young adults from Metropolitan Lima in 2021.
2.2. Participants
In order to calculate sample size, proportions were compared within data gathered from a pilot test, with data pertaining to the perception of dimensions corresponding to reddish and/or swollen gums and electronic cigarette use. 17.65% of non-vaping participants stated that they never had reddish or swollen gums, whereas 42.86% of vapers reported sometimes presenting this alteration. Statistical analysis was carried out using the Epidat® version 4.2 program with a confidence level of 95%, power of 80% and a ratio of 1. The minimum required sample corresponded to 144 individuals. The final sample comprised 189 young adults aged 18 to 29. Participants were recruited via convenience sampling.
2.3. Inclusion and Exclusion Criteria
Young men and women aged between 18 and 29 years old who resided in Metropolitan Lima were recruited for the present study. Participants were required to be regular electronic cigarette users for at least 12 months prior to starting the research. Participants who stopped smoking during the execution of the investigation were excluded from the study. Participants had to report smoking at least one cigarette a month to be included in the study.
2.4. Ethical Considerations
The research project was approved by a research ethics subcommittee at Universidad Peruana de Ciencias Aplicadas, Lima, Peru (PI440-20). Participation was voluntary, with informed consent being provided by all participants.
2.5. Evaluation of the Periodontal Self-report Questionnaire
Self-perception of periodontal health was evaluated using the questionnaire conceived by Quiroz, et al. [15]. A Cronbach’s alpha of 0.76 has been reported for this instrument, with this suggesting that it is acceptably reliable. Questions are divided into two dimensions (habits and periodontal health perceptions). Items pertaining to questions are either dichotomous or polytomous.
2.6. Evaluation of Electronic Cigarette use and Frequency
In order to identify electronic cigarette users, the following question was posed: “Do you use electronic cigarettes?” Yes or no responses were possible. In the case of an affirmative response, participants were posed the question: “How many times do you use an electronic cigarette each moth?”. Response options were: every day, some days and never.
2.7. Covariate Evaluation
Covariates, including age, sex, place of residence, educational level, occupation, income and alcohol consumption, were recorded in line with previous research [13, 16-18].
2.8. Internal Validation of the Questionnaire
Internal validation of the questionnaire was carried out by an expert panel made up of five dentists from different specialties, all with at least 5 years of experience. (Appendix 2). Inter-rater agreement between the experts was calculated using Aiken’s V statistic, obtaining a value of 0.99. This suggests that the questionnaire has acceptable validity.
A pilot test was carried out with 20 young adults from Metropolitan Lima to confirm that the questionnaire was easy to understand, as already suggested by the expert panel. A Cronbach’s alpha of 0.68 was produced for the self-reporting of periodontal health and 0.73 for the question pertaining to “electronic cigarette use”. This suggests the good reliability of the instrument. Likewise, a “test-retest” technique was performed by calculating a Cohen’s Kappa statistic for both self-reported periodontal health and cigarette use, producing values of 0.79 and 0.70, respectively. This indicates good agreement between questionnaire responses in both cases.
With regards to the selection of participants, the survey was published on different Facebook® groups open to electronic cigarette users and participants could access a link to the questionnaire using Google Forms®.
2.9. Data Analysis
Data were recorded in a Microsoft Excel®, version 2021, spreadsheet, with collected information being examined and verified. For data analysis, the statistical program Stata®. Version 16.00 was used. Descriptive measures were calculated, specifically, absolute and relative frequencies for all qualitative study variables and median and interquartile range for all quantitative variables, given that the latter were not normally distributed. In order to determine associations between qualitative variables and electronic cigarette consumption, the Chi-square test and Fisher’s Exact test were conducted, where relevant. For multivariate analysis, Poisson regression with robust variance was performed for qualitative self-reported periodontal health variables, calculating prevalence ratios (PR) for crude and adjusted data (95% CI).
3. RESULTS
The present study aimed to determine the association between self-perceived periodontal health and electronic cigarette use in young adults from Metropolitan Lima in 2021. 189 individuals who met previously established inclusion and exclusion criteria were evaluated. A statistically significant association was found between electronic cigarette use and perceptions of gum health (p=0.005).
Table 1 presents the general characteristics, oral health habits and self-perceptions of periodontal health reported by participants. Regarding the overall sample, median age was 22 (24-21) years and 59.79% were male. 74 respondents of those surveyed reported electronic cigarette use (39.15%), whilst 115 reported no such use (60.85%). The majority of participants had higher education or held university degrees. With regards to habits, all respondents reported brushing their teeth and using toothpaste for oral hygiene, however, 36.92% had not visited the dentist in recent years. On the other hand, 93.3% of those surveyed had a good perception of tooth brushing. With regards to self-reported periodontal health, 80.42% of those surveyed were found to have good or very good perceptions of the state of health of their gums. 91.53% of participants stated that they “never or sometimes” presented bleeding during brushing and only 6.36% reported that their gums appeared reddish and/or swollen.
Variable | n | % |
---|---|---|
Age* | 22 | (24-21) |
Gender | - | - |
Male | 113 | (59.79) |
Female | 76 | (40.21) |
Residence | - | - |
South Lima | 35 | (18.52) |
Downtown lima | 127 | (67.20) |
North Lima | 14 | (7.41) |
East Lima | 13 | (6.88) |
Education level | - | - |
High school | 19 | (10.05) |
Undergraduate | 26 | (13.76) |
University | 135 | (71.43) |
Postgraduate | 9 | (4.76) |
Monthly income* | 7750 | (13000-3000) |
Alcohol status | - | - |
Never | 3 | (1.59) |
Ever | 186 | (98.41) |
Occupation | - | - |
Employer | 9 | (4.76) |
Independent worker | 52 | (27.41) |
Employee | 36 | (19.05) |
Others Ψ | 92 | (48.68) |
Electronic cigarette use | - | - |
Use | - | - |
Yes | 74 | (39.15) |
No | 115 | (60.85) |
Frequency | - | - |
Non-use | 115 | (60.85) |
Some days | 55 | (29.10) |
Everyday | 19 | (10.05) |
Misaligned / crooked teeth | - | - |
No or I don’t know | 115 | (60.85) |
Yes | 74 | (39.15) |
Toothbrush use | - | - |
Yes | 189 | (100) |
Toothpaste use | - | - |
Yes | 189 | (100) |
Dental floss use | - | - |
No | 69 | (36.51) |
Yes | 120 | (63.49) |
Mouthwash | - | - |
No | 63 | (33.33) |
Yes | 126 | (66.67) |
Dental cleaning by the dentist | - | - |
No or I don’t know | 7 | (3.70) |
Yes | 182 | (96.30) |
Daily tooth brushing | - | - |
Less than twice a day | 12 | (6.35) |
Two or more times a day | 177 | (93.65) |
Daily flossing | - | - |
I don’t use it or only once a week | 94 | (49.74) |
Once a day or every time I brush | 95 | (50.26) |
Visit to the dentist in the last year | - | - |
No | 66 | (34.92) |
Yes | 123 | (65.08) |
Perception of tooth brushing | - | - |
Regular / Bad | 12 | (6.35) |
Good / Very good | 177 | (93.65) |
Periodontal Health Self-Report | - | - |
Perception of the state of the gums | - | - |
Regular / Bad | 37 | (19.58) |
Good / Very good | 152 | (80.42) |
Gum bleeding during brushing | - | - |
Never / Sometimes | 173 | (91.53) |
Often / Always | 16 | (8.47) |
Appearance of reddish and/or swollen gums | - | - |
Never / Sometimes | 177 | (93.65) |
Often / Always | 12 | (6.35) |
Ψ Others: Work hand, unpaid family worker, the domestic worker
Table 2 presents general characteristics, habits and self-perceived periodontal health according to electronic cigarette use. A statistically significant difference in electronic cigarette use is observed according to gender, with 73.68% of women not engaging in such use (p=0.003). It was also found that the majority of those surveyed with postgraduate studies did not vape. Likewise, of those participants who used dental floss “once a day or every time they brushed”, 65.83% were not vapers compared to 34.17% who were, although this difference was not statistically significant. As for those who had a “regular or bad” perception of tooth brushing, 58% vaped, whilst the majority of those who had visited the dentist in the last year were non-vapers (59.35%). With regards to self-reported periodontal health, of those who reported regular or poor perceptions of the state of their gums, 59.46% were smokers, who were significantly more likely to report this outcome than non-smokers (p=0.005). The majority of respondents who reported having bleeding gums “sometimes or never” during toothbrushing and having reddish and/or swollen gums did not use electronic cigarettes.
Electronic Cigarette Use |
Yes N (%) |
No N (%) |
P-value* | |
---|---|---|---|---|
General Characteristics | - | - | - | |
Ageβ | 22 (25-21) | 22 (24-21) | 0.758 u | |
Gender | - | - | 0.003 | |
- | Male | 54 (47.79) | 59 (52.21) | - |
- | Female | 20 (26.32) | 56 (73.68) | - |
Residence | - | - | 0.8028 | |
- | South Lima | 14 (40.00) | 21 (60.00) | - |
- | Downtown lima | 48 (37.80) | 79 (62.20) | - |
- | North Lima | 7 (50.00) | 7 (50.00) | - |
- | East Lima | 5 (61.54) | 8 (61.54) | - |
Education | - | - | - | |
- | High school | 9 (47.37) | 10 (52.63) | 0.830 |
- | Non-university higher | 11 (42.31) | 15 (57.69) | - |
- | University higher | 51 (37.78) | 84 (62.22) | - |
- | Postgraduate | 3 (33.33) | 6 (66.67) | - |
Incomeβ | 7500(14000-2900) | 7500 (12000-3500) | 0.789 u | |
Occupation | - | - | 0.505 | |
- | Employer | 4 (3.5) | 5 (5.5) | - |
- | Self-employed | 24 (20.4) | 28 (31.6) | - |
- | Employee | 11 (14.1) | 25 (21.9) | - |
- | Other Ψ | 35 (36.0) | 57 (56.0) | - |
Alcohol Status | ||||
Never consumed | 0 (0.00) | 3 (100.00) | 0.281 F | - |
Consumed on at least one occasion | 74 (39.15) | 112 (60.22) | - | - |
Dental floss use | ||||
Yes | 41 (34.17) | 79 (65.83) | 0.064 | - |
- | No | 33 (47.83) | 36 (52.17) | - |
Mouthwash use | - | - | - | |
- | Yes | 50 (39.68) | 76 (60.32) | 0.833 |
- | No | 24 (38.10) | 39 (61.90) | - |
Daily tooth brushing | - | - | 0.372 F | |
Less than twice a day | 3 (25.00) | 9 (75.00) | - | - |
Two or more times a day | 71 (40.11) | 106 (59.89) | - | - |
Daily dental floss use | - | - | 0.121 | |
- | I don’t use it or only once a week | 42 (44.68) | 52 (55.32) | - |
- | Once a day or every time I brush | 32 (33.68) | 63 (66.32) | - |
General characteristics | - | - | - | |
Misaligned / crooked teeth | - | - | 0.547 | |
- | No or I don’t know | 47 (40.87) | 68 (59.13) | - |
- | Yes | 27 (36.49) | 47 (63.51) | - |
Perception of toothbrushing | - | - | 0.160 | |
- | Regular / Bad | 7 (58.33) | 5 (41.67) | - |
- | Good / Very good | 67 (37.85) | 110 (62.15) | - |
Professional dental cleaning | - | - | 0.707 F | |
- | No or I don’t know | 2 (28.57) | 5 (71.43) | - |
- | Yes | 72 (39.36) | 110 (60.44) | - |
Visit to the dentist in the last year | - | - | 0.565 | |
- | No or I don’t know | 24 (36.36) | 42 (63.64) | - |
- | Yes | 50 (40.65) | 73 (59.35) | - |
Periodontal Health Self-Report | - | - | - | |
Perception of the state of the gums | - | - | 0.005 | |
- | Regular or bad | 22 (59.46) | 15 (40.54) | - |
- | Good or very good | 52 (34.21) | 100 (65.79) | - |
Gum bleeding during brushing | - | - | 0.353 | |
- | Never / Sometimes | 66 (38.15) | 107 (61.85) | - |
- | Often / Always | 8 (50.00) | 8 (50.00) | - |
Appearance of reddish and/or swollen gums | - | - | 0.854 | |
- | Never / Sometimes | 69 (38.98) | 108 (61.02) | - |
- | Often / Always | 5 (41.67) | 7 (58.33) | - |
*: Chi-square test
u: U de Mann Whitney test
β: Median and interquartile range
Poor Perception of the State of the Gums | ||||||||
---|---|---|---|---|---|---|---|---|
Crude Modelα | Adjusted Modelβ | |||||||
PR | [95% CI] | p | PR | [95% CI] | p | - | - | - |
Electronic cigarette use | ||||||||
Yes | 0.81 | [0.69-0.95] | 0.011 | 0.82 | [0.69 – 0.97] | 0.021 | - | - |
No | Ref. | Ref. | Ref. | Ref. | Ref. | Ref. | - | - |
Gum bleeding during tooth brushing | ||||||||
Electronic cigarette use | ||||||||
Yes | 1.55 | [0.60-3.97] | 0.357 | 1.66 | [0.66-4.15] | 0.273 | - | |
No | Ref. | Ref. | Ref. | Ref. | Ref. | Ref. | - | |
Appearance of reddish and/or swollen gums | ||||||||
Electronic cigarette use | ||||||||
Yes | 1.11 | [0.36-3.38] | 0.854 | 1.05 | [0.24-4.55] | 0.939 | - | |
No | Ref. | Ref. | Ref. | Ref. | Ref. | Ref. | - |
β: Adjusted model includes the following variables: age, gender, place of residence, education, occupation, income, alcohol status, toothbrush use, toothpaste use, dental floss use, mouthwash use, prophylaxis with the dentist, daily tooth brushing, daily flossing and dentist visit in the last year.
CI: Confidence interval
Statistical significance level p<0.05
Finally, Table 3 evaluates the association of dimensions of self-perceived periodontal health electronic cigarette use. Outcomes of the Poisson regression model with robust variance reveal a statistically significant association between perceived gum health and vaping, with regards to both raw data (PR = 0.81; 95% CI: 0.69 – 0.95; p=0.011) and adjusted data (PR = 0.82; 95% CI 0.69-0.97; p = 0.021). However, no statistically significant associations were found between gum bleeding during brushing and the appearance of reddish and/or swollen gums.
4. DISCUSSION
The aim of the present study was to determine the association between self-perceptions of periodontal health and electronic cigarette use. A statistically significant association was found between poor perceptions of gum health and the use of electronic cigarettes in the young adults surveyed.
In the present study, most young people were observed to have good oral health habits. All respondents brushed their teeth and used toothpaste daily and 62% reported flossing. This is in accordance with a study carried out in Portugal in 2017 [19], which reported that 100% of young people brushed their teeth every day and the majority used dental floss, revealing good oral health habits. This may be because the young people surveyed mostly had a stable socioeconomic status and belonged to the middle class, meaning that they likely had greater purchasing power to buy oral hygiene instruments, whilst they were probably also exposed to a culture of prevention regarding general health [20. 21].
The present investigation was carried out during the COVID-19 pandemic. The frequency of electronic cigarette use corresponding to on “some days” was reported by 29% of the sample, whilst 10% reported “everyday” use. This is similar to that observed in the first confinement phase during the Italy pandemic [22]. This study showed an increase in the prevalence of electronic cigarette use due to anxiety surrounding the uncertainty caused by the state of emergency. Individuals with depression and anxiety disorders are more likely to use electronic cigarettes since engaging in this habit provides a feeling of relief from symptoms of anguish [23]. Further, it is worth noting that there is currently a social campaign underway against conventional tobacco, potentially leading young people to replace it with vaping devices [24].
Self-report periodontal health questionnaires have been used in different populations as valid tools to assess the prevalence of periodontal disease. In 1994, self-reports used pertained to a simple questionnaire for detecting signs or symptoms of gum disease with questions such as “do your gums bleed during brushing?” or “do you have inflammation in the gums?” Authors at the time highlighted that the questionnaire could be useful in terms of monitoring gingival health [25]. Over recent years, new questionnaires have been created such as the 12-item “Periodontal Screening Score” or “PESS” which is considered a useful and accurate tool for identifying people at risk of periodontal disease [26]. Similarly, Quiroz, et al. [15] developed a periodontal health self-report tool in Chile for population surveillance of periodontal status. This has been validated in Spanish and cataloged as reliable with acceptable internal consistency. For this reason, it was the chosen tool in the present study.
In the present research, good perceptions of periodontal health were found in young people. This is similar to that described in the United States, where self-reported periodontal status has been associated with hygiene, probing depth and alveolar bone level in young people and adults. Here, findings were further verified using clinical and radiographic examination alongside the questionnaire [3]. In response to the present questionnaire, the majority rated their periodontal status as between 5 and 8 along a 10-point scale, with this corresponding to moderate or good perceptions of periodontal status. This may be due to the age groups evaluated as periodontal disease is related to increasing age, being a common disease in adults aged 35 to 44 and people older than 65 to 74 [27].
Only 26.32% of women used electronic cigarettes, which is comparable to that found in a study conducted by Lee, et al. [28]. This previous research showed that women are less likely to use electronic cigarettes compared to men. In Peru, only 6.2% of young women are smokers [29]. It should be noted that more than half of conventional smokers migrate to using electronic cigarettes to reduce harmful tobacco habits. Thus, since there is a low prevalence of women using conventional cigarettes, the prevalence is even lower when it comes to electronic cigarette use [12].
With regards to self-reported periodontal health and vape use, 59.4% used electronic cigarettes and reported having regular or poor perceptions of the health of their gums. This is in accordance with findings reported in a study conducted by Irusa et al. [30], which indicated that the effect of electronic cigarettes on periodontal tissue is similar to that of conventional cigarettes. This may be due to the composition of the liquid contained by electronic cigarettes. Although these devices come in many shapes, sizes and colors, all share three common components, which are a base, nicotine and flavoring. The base of the device consists of a combination of propylene glycol or glycerin which promote an acidic environment in the oral cavity and increase microbial adhesion. This is a cause for concern because much of this vapor is retained in the oral tissues causing periodontal damage. Dentists should, therefore, routinely ask patients about e-cigarette use to prevent negative consequences to oral health [31].
When evaluating gum bleeding during brushing, it was observed that the majority of both vapers (38.1%) and non-vapers (61.8%) report presenting this symptom never or sometimes. Gingiva bleeding is reduced in people who smoke conventional cigarettes because it influences the cellular, molecular and microbiological scope of periodontal tissue [32]. The presence of nicotine in electronic cigarettes and the vasoconstrictor effect it exerts in the gingival blood vessels reduces bleeding and cellular scarring, in this way, obscuring the first signs of gingivitis. For this reason, vapers may not experience bleeding and so may not present with symptoms to warn them of these changes [33].
When examining the dimensions of self-reported periodontal health and electronic cigarette use, a statistically significant relationship was found between poor perceptions of gum health and vaping, both in relation to raw data and adjusted data considering covariates. This is in accordance with previous findings that when conventional smokers migrate to the use of electronic cigarettes they experience a significant increase in inflammation, which could be reflected in poor perceptions of gum health [34]. On the other hand, the association with perceptions of reddish and/ or swollen gums was not statistically significant. This finding is in contrast with that of an experimental in vitro study [35], which showed that electronic cigarettes increased oxidative stress and the level of pro-inflammatory cytokines in the periodontal ligament and the gums. From this, it was concluded that electronic cigarette use could generate periodontal damage [36].The difference in outcomes could be because surveyed individuals may not have an accurate awareness of good oral health or may have incomplete perceptions of their own periodontal health. Additionally, as outcomes come from self-report measures, it is also possible that respondents misinterpret terms or experience confusion when responding to questionnaires [37]. Dental professionals need to stay informed of new evidence to advise patients of potential implications for their oral and dental health [38].
CONCLUSION
The outcomes of the present research establish the importance of recording the frequency of electronic cigarette use in patients’ clinical history, as well as the need for health professionals to implement educational strategies to reduce electronic cigarette use and prevent harmful effects on general health. Likewise, it is recommended that future studies be conducted to evaluate the progression of periodontal status with prolonged electronic cigarette use and compare outcomes from self-report data with clinical evaluations.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
The research project was approved by a research ethics subcommittee at Universidad Peruana de Ciencias Aplicadas, Lima, Peru (PI440-20).
HUMAN AND ANIMAL RIGHTS
No animals were used in this research. All human research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2013.
CONSENT FOR PUBLICATION
All participants were involved voluntarily after providing informed consent.
STANDARDS OF REPORTING
STROBE guidelines were followed.
AVAILABILITY OF DATA AND MATERIALS
The data supporting the findings of the article is available in the “Repositorio Académico UPC” at http://hdl.handle.net/ 10757/661942.
FUNDING
None.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.