Research in Autism Spectrum Disorders 7 (2013) 1339–1345

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Research in Autism Spectrum Disorders

Jo ur n al h o mep ag e: ht tp : / /ees .e ls evier .c o m/RA SD/d efau l t .asp

Comparing the rates of tantrum behavior in children with ASD

and ADHD as well as children with comorbid ASD and ADHDdiagnoses

Matthew J. Konst *, Johnny L. Matson, Nicole Turygin

Louisiana State University, United States

A R T I C L E I N F O

Article history:

Received 5 July 2013

Accepted 30 July 2013

Keywords:

Autism spectrum disorders

Tantrum behavior

Autism Spectrum Disorders-Comorbidity f-

or Children (ASD-CC)

Comorbidity

A B S T R A C T

The current study investigated the presentation of tantrum behaviors in individuals with

an autism spectrum disorder (ASD) diagnosis with and without a comorbid diagnosis of

attention deficit hyperactivity disorder (ADHD). Participants included 347 children

ranging in age from 2 to 18 years old. Diagnostic categories in the current study were based

upon clinical diagnosis. The severity of ASD symptomology was measured by the Autism

Spectrum Disorder-Diagnostic Child Version (ASD-DC). The presence and severity of

tantrum behaviors were measured by the Tantrum behavior subscale of the Autism

Spectrum Disorders-Comorbidity for Children (ASD-CC). The influence of diagnosis and

ASD symptomology had upon the expression of tantrum behaviors were examined,

controlling for participant age. Initial analysis revealed significant differences in the

expression of tantrum behavior between the ASD, ADHD and ASD/ADHD groups. However,

age did not have a significant influence on the exhibition of tantrum behaviors. Follow-up

analyses demonstrated that those individuals diagnosed with an ASD and a comorbid

ADHD diagnosis exhibited significantly greater tantrum behavior. Post hoc analyses

identified a significant positive correlation between increases in ASD symptomology and

elevations of the severity of tantrum behaviors for each group. The observed correlation for

the ADHD group was found to be significantly greater than the ASD group. Correlations for

individual item responses of the ASD-CC were also computed and discussed for each

diagnostic group.

� 2013 Elsevier Ltd. All rights reserved.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder which is first apparent in early childhood,characterized by deficits in socialization and communication, and the presence of repetitive behavior or restricted interests(Gillberg, 2010; Lo-Castro, Benvenuto, Galasso, Porfiro, & Curatolo, 2010; Matson, Beighley, & Turygin, 2012; Matson &Wilkins, 2009; Schroeder, Desrocher, Bebko, & Cappadocia, 2010). The presence of ASD often portends a need for supportsand treatment across the lifespan, and with an increasing prevalence rate, which is currently estimated at around .6–1.8%and as high as 2.64% (Baird et al., 2006; Fombonne, 2009; Kim et al., 2011), and is currently considered to be a major healthissue.

Individuals with ASD also exhibit a range of co-occurring conditions, including attention deficit/hyperactivity disorder(ADHD). ADHD presents as inattention, difficulties sustaining attention, or hyperactivity and impulsivity. Current prevalence

* Corresponding author at: Clinical Psychology, Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, United States.

Tel.: +1 225 578 1494.

E-mail address: mkonst1@tigers.lsu.edu (M.J. Konst).

1750-9467/$ – see front matter � 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.rasd.2013.07.023

M.J. Konst et al. / Research in Autism Spectrum Disorders 7 (2013) 1339–13451340

rates of ADHD in children are estimated to be approximately 8–9% of children. There has previously been some debate withregards to whether this disorder can co-occur with ASD, and recently researchers have investigated this issue. In a study byLeyfer et al. (2006), 31% of children with ASD also met full criteria for ADHD, and 24% exhibited significant symptoms. In aseparate clinical study, 28% of children who were diagnosed with ASD and referred for treatment also met criteria for ADHD(Mayes, Calhoun, Murray, Ahuja, & Smith, 2011).

Tantrum behaviors are generally defined as a cluster of challenging behaviors that occur together, often with oppositionalbehavior, screaming, crying, aggression, defiance, property destruction, and other disruptive behaviors (Green, Whitney, &Potegal, 2011). Tantrums have been studied in typically-developing toddlers and young children, and at this age they arecommon and often considered developmentally appropriate. This assumption is based on undeveloped emotion regulation(Giesbrecht, Miller, & Muller, 2010). Thus, for typically developing children, only tantrums that are excessive or continue lateinto childhood are associated with negative outcomes (Caspi, Elder, & Bem, 1987; Green et al., 2011; Stevenson & Goodman,2001; Stoolmiller, 2001). Research on typically developing children has associated tantrum behaviors with expressions ofnegative emotions, particularly anger and sadness (Green et al., 2011), and generally serve attention, escape, and tangiblefunctions (Matson, Sipes, et al., 2011).

Behavior problems including tantrum-related behaviors are common in individuals with ASD and have generally beenconceptualized differently in this population. Other common challenging behaviors include stereotyped behavior, self-injury, aggression, and property destruction (Matson, Dempsey, & Fodstad, 2009a; Matson & Rivet, 2008). The functions oftantrum behaviors in children with ASD are generally divided into five categories; attention, escape, nonsocial, physical, andtangible (Matson & Minshawi, 2007; Paclawskyj, Matson, Rush, Smalls, & Vollmer, 2000). These maintaining variables areoften associated with setting events including noise, routine change, and demands (Matson, 2009).

The co-occurrence of ADHD with ASD has been observed to exacerbate the presence of ‘‘externalizing behaviors’’ beyondthat which are observed in children with only ADHD (Jang et al., 2013; Tureck, Matson, May, & Turygin, 2013). In a previousstudy, Goldin, Matson, Tureck, Cervantes, & Jang (2013) observed that most tantrum-related behavior were higher inchildren with ASD and combined ASD/ADHD than ADHD alone.

Given the frequency of comorbid disorders among persons with ASD, it is important to examine the influence thepresence of comorbidities has upon symptom manifestation. The present study investigates the effect of ASD symptomologywithin three diagnostic groups (ASD, ASD/ADHD, and ADHD) on the expression of overall tantrum behaviors, as well asindividual tantrum behaviors. It was hypothesized that children with a comorbid ASD/ADHD diagnosis would exhibitsignificantly greater tantrum behaviors. The authors also hypothesized that increased levels of ASD symptoms inpopulations with and without an ASD diagnosis (i.e., ADHD) would be associated with increased rates of tantrum behaviors.

1. Methods

1.1. Participants

Children (N = 347) included in the study ranged in age from 2 to 18 years of age at the time of assessment (M = 8.51,SD = 3.67). The sample population included children and adolescents who presented to a University child psychology clinicdue to a variety of concerns. Two-hundred seventy-three children and adolescents were males (78.7%) and 74 were females(21.3%). Based upon informant report, the ethnicity of the children included in the sample were; African-American (9.2%),Caucasian (70.3%), Hispanic/other (2.3%), and not reported (18.2%). The current sample also included individuals with aclinical diagnosis of intellectual disabilities (ID). Comorbid ID diagnoses among the current studies diagnostic categoriesincluded: ASD (24), ADHD (1), and ASD/ADHD (5).

Clinical diagnosis was made by two psychologists with more than 30 years of combined experience in assessingchildhood disorders. Diagnostic consensus was ascertained following the review of data garnered from semi-structuredinterviews, checklists (e.g., high functioning autism/Asperger’s checklist, DSM-IV/ICD-10 checklist, and the DSM-5checklist), test results, and rating scales. Assessment procedures for ASD were selected based upon the child’s age and level offunctioning but included behavioral observations, a caregiver interview of medical and general developmental history, aswell as appropriate caregiver rating scales. Those participants diagnosed with ASD and comorbid ADHD were groupedexclusively into the ASD/ADHD group. The ASD group (n = 256) consisted of all ASD categories (i.e., autistic disorder [AD],Asperger syndrome [AS], pervasive developmental disorder-not otherwise specified [PDD-NOS]). Group membership for theADHD (n = 42) and ASD/ADHD (n = 49).

1.2. Measures

1.2.1. Autism Spectrum Disorders-Diagnostic Child Version (ASD-DC)

The ASD-DC was developed by Matson and Gonzalez (2007b) as an informant-based measure to assess children rangingin age from 2 to 18 years of age for the presence of symptoms associated with AS, AD, and PDD-NOS. Directions involveprompting informants to utilize a 3-point severity scale (i.e., 0 = ‘‘not different; no impairment’’; 1 = ‘‘somewhat different;mild impairment’’; 2 = ‘‘very different; severe impairment’’) to identify the degree to which each item is or has ever been aproblem for their child when compared to a typically-developing peer (Matson & Gonzalez, 2007b). Scoring the ASD-DCgenerates a total score for each child corresponding to a symptom severity scale (Table 1).

Table 1

ASD-DC diagnostic scale.

ASD-DC diagnostic category

ASD-DC score AS PDD-NOS AD Atypical Normal

Total score 53–80 40–52 33–39 9–32 0–9

Note: ASD-DC = Autism Spectrum Disorder-Diagnostic Child Version (Matson & Gonzalez, 2007b).

M.J. Konst et al. / Research in Autism Spectrum Disorders 7 (2013) 1339–1345 1341

Cumulative scores are structured in a hierarchical fashion to identify the severity of ASD symptom manifestation with thehighest scores corresponded with Autistic Disorder and the lower clinically significant scores represented those childrenwith PDD-NOS, Asperger disorder, atypical development, and normal development (Table 1; Matson, Dempsey, & Fodstad,2009b). The inter-rater reliability for the ASD-DC was observed to be good (k = .58) and the test–retest reliability was foundto be excellent (k = .72; Matson, Gonzalez, Wilkins, & Rivet, 2007). Additional analysis found the internal consistency of theASD-DC to be excellent (a = .99; Matson et al., 2007). Researchers reported the sensitivity of the ASD-DC based upon thecriteria provided by both the ICD-10 and DSM-IV-TR criteria to be 84.3% (Matson, Gonzalez, & Wilkins, 2009). Matson,Gonzalez, et al. (2009) indicated that the overall rate of accurate classification across diagnoses was 91.3%, while specificitywas 98.2%.

1.2.2. Autism Spectrum Disorders-Comorbidity Child Version (ASD-CC)

The ASD-CC is an informant-based measure designed for children two to eighteen years of age (Matson & Gonzalez,2007a). The item composition of the ASD-CC focuses on those concomitant problems that have been identified as frequentlyoccurring in children with ASDs (e.g., anxiety, depression, tic disorders, eating concerns, and ADHD; Matson & Gonzalez,2007a). Informants are instructed to provide ratings based upon on a 3-point severity scale: (0) no impairment, (1) mildimpairment, or (2) severe impairment for each of the 39 items. A factor analysis of the ASD-CC revealed a seven-factorstructure (i.e., repetitive behaviors, tantrum behaviors, over-eating, under-eating, conduct problems, worry/depressed, andavoidant behaviors; Matson, LoVullo, & Rivet, 2009).

Scoring and clinical cut-offs are different for each subscale due to the variance in the number of items composing eachfactor. The current study focused upon the Tantrum behavior subscale of the ASD-CC. For this subscale, a score greater than14 denotes ‘‘severe impairment’’, while a score of 11–14 is associated with ‘‘moderate impairment’’, and a score less than 10denotes ‘‘no impairment’’ (Thorson & Matson, 2012). Matson and colleagues (2009) demonstrated the ASD-CC’s convergentvalidity with the Behavior Assessment System for Children, Second Edition (Reynolds & Kamphaus, 2004). Moderate test-retest (k = .51) and inter-rater reliability (k = .46; Matson & Dempsey, 2008) have been observed in the ASD-CC, while internalreliability has been shown to be very good (a = .91; Matson & Wilkins, 2008a) The ASD-DC and ASD-CC are both componentsincluded in the larger Autism Spectrum Disorder Battery-Child Version (ASD-C) battery.

1.3. Procedure

The present study was approved by the institutional review board of a flagship state university in the southern UnitedStates. For the current study, the children’s biological parents or legal guardians served as respondents for the assessmentpackages. Whenever developmentally appropriate, the researchers also obtained the child’s assent to participate in research.In addition to other parent-report measures, the assessment packets included the ASD-C. The ASD-C includes the autismspectrum ASD-DC, the ASD-CC, and the Autism Spectrum Disorder-Problem Behavior Child Version (ASD-PB). Graduateclinicians remained available to the caregivers throughout the assessment process to answer specific questions. All measureswere administered, collected, and scored by trained graduate clinicians. In addition to test scores, relevant demographic anddiagnostic information was also collected and included in a database for further analysis.

1.4. Data analysis

Prior to conducting the main analysis, we determined whether diagnostic groups varied significantly on any of thediagnostic variables (i.e., ethnicity, gender, age, and presence of an intellectual disability [ID]). An analysis of variance(ANOVA) was carried out to explore group differences for age. A significant difference between group age was observedF(2,343) = 9.18, p = .00. An a priori Pearson Chi Square analysis indicated that the presence of IDs was significantly differentacross diagnostic groups (x2(2) = 6.37, p = .04). However, the results of the ANOVA indicated that age (F(1,346) = .86, p = .35)and ID (F(1,346) = 1.25, p = .27) were not significant factors influencing the expression of tantrum behaviors among the threegroups. A priori Chi Square tests indicated that the groups did not differ significantly for participant ethnicity (x2(2) = 1.18,p = .38) or gender (x2(2) = 3.42, p = .18). Differences in gender were not anticipated however due to the observed lowerprevalence of both ADHD and ASDs in females (Bauermeister et al., 2007; Fombonne, 2003). An ANOVA was computed withdiagnostic category (i.e., ASD, ASD/ADHD, and ADHD) as the predictor variable. The identified outcome variable for thecurrent analysis was the total score for the Tantrum behavior subscale of the ASD-CC, while participant age and the presenceof ID were entered as covariates. Due to the observed differences in the size of diagnostic categories Hochberg’s GT2 post hocprocedures were computed (Field, 2009).

Table 2

Correlation between ASD symptom severity and tantrum behaviors.

ASD-DC diagnostic category

ASD-CC item ASD ASD/ADHD ADHD

Total tantrum .19** .43** .62**

Easily upset (1) .12 .55** .51**

Crying (5) .13* .47** .26

Destroys (7) .14* .23 .30*

Compliance (12) .07 .15 .37*

Damages (19) .14* .22 .47**

Weepy (22) .08 .31* .41**

Finishes (26) .10 .09 .21

Easily angry (28) .09 .36* .53**

Tantrums (30) .16** .39** .57**

Irritable (35) .15* .32* .34*

Note: ASD-CC = Autism Spectrum Disorder-Comorbidity Child Version (Matson & Gonzalez, 2007a); ASD-DC = Autism Spectrum Disorder-Diagnostic Child

Version (Matson & Gonzalez, 2007b). N = 346. All alpha levels reported are two-tailed.

* p < .05.

** p < .01.

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Following a significant effect for diagnosis, follow up post hoc analyses were computed. Pearson bivariate correlationswere computed to analyze the influence of ASD symptom manifestation on the expression of tantrum behaviors for eachdiagnostic group. Additional analyses were included to determine if diagnostic category membership predicted the presenceof specific tantrum behaviors. Subsequent analyses involved Pearson bivariate correlations between each diagnosticcategory and individual item (n = 10) responses for the Tantrum behavior subscale of the ASD-CC.

2. Results

Results of the ANOVA indicated a significant difference in the expression of tantrum behaviors among the diagnosticcategories was observed F(4,343) = 3.57, p = .08. Post hoc comparisons using the Hochberg GT2 procedure indicated that theASD (M = 7.66, SD = 4.33) group expressed significantly higher rates of tantrum behaviors when compared to the ADHD(M = 5.67, SD = 5.21) group (p = .02). The ASD/ADHD (M = 9.22, SD = 4.22) group exhibited significantly greater rates oftantrum behavior than the ADHD group (p = .00). Additional statistical analysis indicated that the average difference intantrum behaviors (M = �1.63) between the ASD and ASD/ADHD groups was significant (p = .05).

Follow-up analyses were calculated to explore the association between tantrum behavior and ASD symptom severity foreach diagnostic group. Results of the Pearson bivariate correlations indicate that increases in ASD symptomology wereobserved to be positively associated with increases in overall tantrum behavior for the ADHD (r = .62, p = .00), ASD/ADHD(r = .43, p = .00), and ASD groups (r = .19, p = .00). A Fisher r-to-z transformation determined that the observed correlationwith respect to the Tantrum behavior subscale total and severity of ASD symptom manifestation between the ASD and ASD/ADHD groups (z = �1.57, p = .06) and the ADHD and ASD/ADHD groups (z = 1.21, p = .11) did not significantly differ. Thecorrelations were significantly greater for the ADHD group when compared to the ASD group (z = 3.23, p = .00).

Following the significant results from the Tantrum behavior subscale total, additional analyses were conducted toinvestigate the correlation between diagnostic category and individual item responses. The correlation between ASDsymptom severity and item responses for the ASD group was significant (p < .05) for items; ‘‘Crying’’, ‘‘Destroys othersproperty’’, ‘‘Damages property’’, ‘‘Tantrums child version’’, and ‘‘Irritable mood’’ on the Tantrum behaviors subscale (seeTable 2). Within the ASD/ADHD group, correlations between ASD symptomology and individual item responses weresignificant for items; ‘‘Easily becomes upset’’, ‘‘Crying’’, ‘‘Tearful or weepy’’, ‘‘Easily becomes angry’’, ‘‘Tantrums childversion’’, and ‘‘Irritable mood’’ (p < .05). Although the correlation observed between Crying (Item 5) and symptom severitywas significant for both the ASD and ASD/ADHD group, the correlation for the ASD/ADHD group was significantly greaterthan the ASD group (z = 2.37, p = .01). Individual item analysis for the ADHD diagnostic category revealed that 80% of theitems were significantly correlated with ASD symptom severity (p < .05) for this group. Although significant correlationswere observed between symptom severity and Property damage for the ASD (r = .14, p = .02) and ADHD (r = .48, p = .00)groups, the correlation was significantly stronger for the ADHD group (z = 2.15, p = .02). The observed correlation betweentantrum behavior (Item 30) and ASD symptomology was significant for each diagnostic group. However, the correlation wassignificantly greater for the ADHD group when compared to the ASD group (z = 2.83, p = .00).

3. Discussion

Many mental health related conditions are frequently comorbid with ASD (LoVullo & Matson, 2009; Matson, Dempsey,LoVullo, & Wilkins, 2008). Researchers examining primary care and mental health care practices indicated that tantrumbehaviors are one of the most frequent reasons for client referrals in adolescent populations (Robb, 2010). The need for abetter understanding of tantrum behaviors is necessitated not just with respect to their frequency, but also regarding the

M.J. Konst et al. / Research in Autism Spectrum Disorders 7 (2013) 1339–1345 1343

intrusive and severe nature and potential consequences of tantrum behaviors. Elevated rates of challenging behaviors havebeen found to be comorbid with high levels of tantrum behavior in atypically developing populations (Matson, Mahan, Sipes,& Kozlowski, 2010). The importance of understanding the manifestation of tantrum behavior transcends the immediateproblems due to concerns that such behavior may result in future externalizing behavior problems and ultimately conductproblems (Giesbrecht et al., 2010; Kennan & Wakschlag, 2000). As a result, it is necessary to increase our understanding ofthe factors influencing tantrum behaviors in the interest of developing efficacious interventions and improving overallquality of life for individuals exhibiting these behaviors (Dyches, Smith, Korth, Roper, & Mandleco, 2012; Giles, St. Peter,Pence, & Gilson, 2012; Matson et al., 2008; Matson & LoVullo, 2008; Matson & Wilkins, 2008b; Simonoff et al., 2008; vanSteensel, Bogels, & Dirksen, 2012).

In general, tantrum behaviors have not been found to be disorder specific, at least for many childhood mental healthconditions (Giesbrecht et al., 2010; Jenkins, Bax, & Hart, 1980; Richman, Stevenson, & Graham, 1975). Researchers havedemonstrated that regardless of diagnosis, between 5% and 20% of children exhibit frequent tantrum behaviors(Goldson & Reynolds, 2011). However, researchers have also demonstrated that tantrum behaviors are frequentlyobserved in individuals with an ASD diagnosis (Matson, 2009; Tureck et al., 2013). Lecavalier (2006) proposed that asmany as 20% of children with ASD exhibit irritable and aggressive behaviors (e.g., self-injurious behaviors, tantrums,and aggression).

Results from the current study confirm that individuals with ASD exhibit significantly greater tantrum behaviors thanindividuals with an ADHD diagnosis. However, additional analysis indicated that the presence of an ASD diagnosis with acomorbid ADHD diagnosis significantly increases the expression of tantrum behaviors beyond rates observed in eitherdiagnosis alone. This observation is in line with research conducted by Poon (2012) which suggested that comorbidpsychopathology may exacerbate challenging behaviors in infants and toddlers with ASD.

Konst, Matson, & Turygin (2013) demonstrated that increases in the prevalence and severity of tantrum behaviors arepositively associated with increases in ASD symptomology regardless of diagnosis (Lecavalier, 2006). Tureck et al. (2013)reported that in comparison to ADHD and typically developing control groups, individuals with an ASD diagnosis expresssignificantly more tantrum behaviors. While not significantly different, our results indicate that increases in ASD symptomsfor the ASD/ADHD group were more strongly correlated with increases in the severity of tantrum behavior than for the ASDgroup. An increase in the presence of ASD symptomology for those with ADHD was correlated with the increased expressionof tantrum behavior when compared to the ASD/ADHD group. When comparing the ADHD and ASD groups, a significantlygreater correlation between increases in tantrum behaviors and ASD symptomology was identified for the ADHD group.These observations are in-line with previous research which identified that the presence of ASD symptoms in non-ASDpopulations was an indicator for the increased severity of tantrum behaviors (Konst et al., 2013).

The correlation between items assessing tantrums and irritability and the presence of ASD symptoms was significant foreach diagnostic group. Correlations between ASD symptoms and tantrum severity were larger for the ADHD group and alsomore prevalent when examining the individual items of the ASD-CC. This finding in conjunction with the results from theinitial analysis (i.e., individuals with an ASD diagnosis exhibit greater tantrum behavior) suggests that the presence of ASDsymptoms in individuals with ADHD greatly increases the expression of tantrum behaviors. These results also confirmprevious research by Matson, Mahan, et al., 2011 who reported that when elevated levels of inattention and impulsivity arepresent, children exhibit more destructive and aggressive behaviors. Significant correlations between the presence of ASDsymptoms and individual items of the ASD-CC were observed for the ASD/ADHD and ADHD groups for items one (Easilyupset), twenty-two (Weepy), and twenty-eight (Easily angry). It should be noted that while these items were significantlycorrelated with these two groups, they were not significant for the ASD group. Increases in symptom severity for the ASD andASD/ADHD groups were significantly correlated with increased expression of crying behaviors. However, the correlationobserved for the ASD/ADHD group was significantly greater. Collectively this suggests that crying is not a significantbehavior in individuals with ADHD, but is significant among persons with ASD. When the two disorders co-occur however,this behavior increases in severity with the increase in ASD symptoms. This factor may be related to the decreased ability toappropriately express wants/needs in individuals with ASD (Matson & Boisjoli, 2008; Matson & Wilkins, 2007; Matson et al.,1996, 2007).

Although overall tantrum behavior is more prevalent in ASD populations (Matson, 2009; Tureck et al., 2013), the currentresults suggest that the presence of ASD symptomology increases the severity of tantrum behaviors in ADHD populations.These findings suggest that despite having a primary ADHD diagnosis, the manifestation of ASD symptoms may be asignificant factor influencing the expression of tantrum behaviors. The findings of the current research should be consideredwhen assessing and treating ADHD populations. An enhanced understanding of the factors influencing the expression oftantrum behaviors may enhance clinicians’ abilities to identify underlying factors and inform the development of efficaciousinterventions. These interventions may target symptoms traditionally associated with individuals with an ASD inpopulations without a formal ASD diagnosis (Smith & Matson, 2010a, 2010b, 2010c).

Future researchers should investigate how changes in the diagnostic criteria for an ASD diagnosis influence theprevalence of tantrum behaviors. Due to the significant influence of the presence of a comorbid disorder, researchers shouldalso explore the impact of other comorbid disorders in ASD populations (i.e., social anxiety disorder and obsessivecompulsive disorder; Holtmann, Bolte, & Poustka, 2007; Leyfer et al., 2006; Simonoff et al., 2008). Additionally, the findingsof the current study should be replicated as the comorbid diagnosis of ADHD with ASD increases with the release of the DSM-5 (APA, 2013).

M.J. Konst et al. / Research in Autism Spectrum Disorders 7 (2013) 1339–13451344

Conflict of interest

The authors report no conflicts of interests and are solely responsible for the content and writing of this paper.

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