Atomoxetine-Related Change in Sluggish Cognitive Tempo Is Partially Independent of Change in Attention-Deficit/Hyperactivity Disorder Inattentive Symptoms

Abstract

Objectives:

To evaluate effects of atomoxetine versus placebo on sluggish cognitive tempo (SCT) and determine factors affecting improvement of SCT in children with attention-deficit/hyperactivity disorder (ADHD) with dyslexia (ADHD+D) or dyslexia only.

Methods:

This is a post hoc analysis of a 16-week placebo-controlled, double-blind randomized phase of a previously reported atomoxetine study in children aged 10–16 years with ADHD+D, Dyslexia-only, or ADHD-only (no placebo arm). Least squares mean changes from baseline to endpoint for atomoxetine versus placebo on the Kiddie-Sluggish Cognitive Tempo Interview (K-SCT) (Parent, Teacher, and Youth) were analyzed using analysis of covariance and multiple regression (partial R²) analyses to test contributions of ADHD and dyslexia to improvements in K-SCT scores.

Results:

Results were examined for the three informants within the three diagnostic groups (nine outcomes). Atomoxetine treatment was associated with significant reductions from baseline in seven of the nine outcomes using the p = 0.05 significance level, appropriate for exploratory analysis. When change in ADHD symptom severity was controlled, all of the seven SCT outcomes remained significant; changes in effect sizes were minimal. Regression analyses using SCT change as the criterion found a significant contribution by inattention change only for parent report, whereas, baseline SCT severity was a significant predictor in the randomized groups with the exception of teacher report in the Dyslexia-only group.

Conclusion:

Given that controlling for change in ADHD symptoms had little effect on change in SCT scores, findings suggest that change in SCT is substantially independent of change in ADHD. By inference, SCT and its response to treatment is a partially distinct phenomenon from ADHD response. Regression analyses did not reveal global effects of inattention change on SCT change; instead, baseline SCT severity was the strongest predictor of placebo-controlled treatment effect on SCT. Atomoxetine effects on SCT appear to be best predicted by how much room for improvement exists for SCT rather than by severity or improvement in inattention.

Clinical trial registration:

NCT00607919, www.clinicaltrials.gov

Introduction

Attention-deficit/hyperactivity disorder (ADHD) and its symptom dimensions (inattention, hyperactivity–impulsivity) have been well described (Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5]) (American Psychiatric Association 2013; Barkley 2015). The inattentive symptom dimension includes symptoms of distraction, forgetfulness, and disorganization (American Psychiatric Association 2013). Sluggish cognitive tempo (SCT) has been reported to be moderately associated with the inattentive symptoms of ADHD (ADHD-I). Of those diagnosed with ADHD-I, it is estimated that 30%–50% also have symptoms of SCT. The SCT symptoms include core cognitive symptoms such as daydreaming, sleepiness, staring, “spaciness,” and mental fogginess and confusion, as well as a motor dimension of slow movement, hypoactivity, lethargy, and passivity (McBurnett et al. 2001; Hartman et al. 2004; Penny et al. 2009; Garner et al. 2010; Skirbekk et al. 2011). Factor analyses repeatedly demonstrate that ADHD-I symptoms are distinct and separate symptoms from SCT, indicating that SCT is a cognitive dimension with distinct core features (Garner et al. 2010; Becker et al. 2016). Moreover, SCT symptoms have effects on various domains of impairment in daily functioning that are independent of those associated with ADHD (McBurnett et al. 2001; Hartman et al. 2004; Penny et al. 2009; Becker et al. 2016). SCT symptoms show a pattern of comorbidity that differs from that of other disorders, such as a lack of association with oppositional defiant disorder, compared to that seen in ADHD (Becker et al. 2016). While it has not yet been firmly established whether SCT is a dimension within ADHD or is a completely separate disorder, research increasingly supports the hypothesis that SCT and ADHD may be distinct disorders with a high rate of comorbidity in affected individuals (Penny et al. 2009; Garner et al. 2010; Barkley 2012; Lee et al. 2014).

A randomized, placebo-controlled double-blind trial of atomoxetine in children and adolescents with ADHD and dyslexia (ADHD+D), Dyslexia-only, or ADHD-only reported significant changes in ADHD symptoms, reading measures, and SCT symptoms (Wietecha et al. 2013; Shaywitz et al. 2014). Specifically, atomoxetine-treated patients with ADHD + D experienced significantly greater improvements than placebo-treated patients in SCT symptoms (parent and teacher report) (Wietecha et al. 2013). Pearson's correlation coefficients showed positive correlations between changes in SCT symptom scores (parent report) and changes in ADHD symptom scores (r = ∼0.50; p < 0.001). This study used post hoc analyses to determine the specific effects of atomoxetine treatment on SCT symptoms. We hypothesized that atomoxetine would result in improvements in SCT symptoms that are independent of improvements in ADHD symptoms.

Methods

The detailed description of the study design and outcomes for the primary efficacy, secondary efficacy, and safety measures for this study were reported in an earlier publication (Wietecha et al. 2013). These methods are briefly summarized here.

Study design

The trial was a multicenter, randomized, placebo-controlled, 16-week double-blind study of atomoxetine (0.5 mg/[kg·day] for 3 days, then 1.0–1.4 mg/[kg·day]) once daily in children and adolescents with ADHD+D, Dyslexia-only, or ADHD-only. Subjects with ADHD + D and ADHD-only met Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) (American Psychiatric Association 2000) diagnostic criteria for ADHD. Subjects with ADHD + D and Dyslexia-only met criteria for dyslexia defined as a ≥22-point discrepancy between the Wechsler Abbreviated Scale of Intelligence Verbal Intelligence Quotient or Performance Intelligence Quotient (whichever was higher) and the Woodcock Johnson III (WJIII) Basic Reading Skills score, Letter Word Identification score, or Word Attack score; or a score ≤89 on any of the WJIII subscales. After a screening phase of ∼2 weeks, ADHD + D and Dyslexia-only patients were randomized 1:1 to atomoxetine or placebo treatment for 16 weeks. All ADHD-only patients received atomoxetine (no placebo arm) in a blinded manner for 16 weeks. Before study initiation, the protocol was reviewed and approved by the appropriate institutional review boards. Parents or guardians of all patients provided written informed consent before the subjects received study medication or underwent study procedures (Wietecha et al. 2013).

Efficacy measures: scale descriptions

The primary efficacy measure used to assess the change from baseline to 16 weeks in ADHD symptoms was the ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Score (ADHDRS) (investigators administered the scale to parents). This 18-item scale produced a Total score, ranging from 0 to 54 with each item scored on a 0–3 scale: 0 = never or rarely (none); 1 = sometimes (mild); 2 = often (moderate); 3 = very often (severe), and Inattentive and Hyperactive/Impulsive subscale scores (DuPaul et al. 1998). The assessment of SCT was performed with the Kiddie-Sluggish Cognitive Interview (K-SCT) scale (Lee et al. 2014). The K-SCT is a 17-item scale that is completed by the parent (Parent), the teacher (Teacher, language arts teacher or equivalent), and the clinician in a semistructured interview style with the patient (Youth) and queries SCT symptoms such as daydreams, lost in a fog, and sluggish/drowsy. The total score ranges from 0 to 51, with each item scored on a 0–3 scale (0 = never or rarely; 1 = sometimes; 2 = often; 3 = very often) (Lee et al. 2014).

Statistical analyses

A Spearman correlation analysis was conducted to explore the associations between high baseline K-SCT Total score (all patients) and 49 other demographic, symptom, and reading measure variables. High baseline K-SCT scores were defined as scores in the top quartile. The variables of specific interest were the WJIII Word Attack score (a surrogate for dyslexia), age, sex, and ADHDRS Total score and Inattentive subscale score. Data were then re-examined on the K-SCT Total score for the Parent, Teacher, and Youth variations using a regression analysis with forward selection. The partial r-squared (R ²) value generated from the regression analysis estimates the amount of variation in the outcome variable (change in K-SCT score) that is explained by the independent (predictor) variables. The following variables were evaluated: treatment, investigator (study site), sex, baseline K-SCT score, baseline ADHDRS Inattentive score, change in ADHDRS Inattentive score, baseline WJIII Word Attack score, change in WJIII Word Attack score, age, and interaction between treatment and baseline K-SCT score.

In the a priori analysis reported previously, data were analyzed with the last observation carried forward (LOCF) method using a fixed-effects analysis of covariance (ANCOVA) with terms for treatment group, investigator (study site), sex, baseline score, age, and baseline score-by-treatment interaction (Wietecha et al. 2013). Similar ANCOVA models were used to assess diagnostic group differences with terms for diagnosis, investigator (study site), sex, baseline score, age, and baseline score-by-diagnosis interaction. Type III sums of squares were used for between-treatment tests. Changes within treatment were assessed using Student's t-test applied to the least squares (LS) mean for the group from the ANCOVA model.

Post hoc analyses of K-SCT data presented in this report were performed with the LOCF method using a fixed-effects ANCOVA with the same terms as specified a priori, but with the addition of the term for change from baseline to 16 weeks for the ADHDRS Total score (Wietecha et al. 2013).

Results

Patient disposition

The full details of the baseline demographics and characteristics, and disposition of the patients are described elsewhere and were unchanged in the post hoc analysis (Wietecha et al. 2013). Briefly, of the 209 randomized patients who entered the 16-week double-blind portion of the trial, 58 had Dyslexia-only (n = 29 atomoxetine; n = 29 placebo), 124 had ADHD + D (n = 64 atomoxetine; n = 60 placebo), and 27 had ADHD-only (n = 27 atomoxetine). A total of 86 patients in the atomoxetine group and 73 patients in the placebo group completed the acute phase of the study. More than half of the patients were male (62%) and the mean age of patients was 12 years (range 10–17 years old). Nearly equal numbers of patients presented with the inattentive or combined ADHD subtypes and the distribution between treatment groups was similar.

Efficacy results

Table 1 presents K-SCT change from baseline to 16 weeks for the atomoxetine-treated patients with adjustment for K-SCT baseline score, with and without adjustment for ADHDRS Total score change. Significant changes for within-group change as well as change significantly greater than placebo are reflected. In the a priori analysis (Wietecha et al. 2013), the K-SCT scores were adjusted for the baseline K-SCT change scores, but not adjusted for the ADHDRS Total change score. The LS mean change from baseline to 16 weeks in the K-SCT scores was significantly greater in atomoxetine-treated patients compared with placebo in the ADHD + D group for both the Parent and Teacher versions, and for the Dyslexia-only group, for the Youth version (all p < 0.05; Table 1). In the current analyses, when adding the change in the ADHDRS Total score to the model, the LS mean change in the K-SCT scores continued to be significantly greater for the atomoxetine-treated patients compared with placebo in the ADHD + D group, but only for the Teacher version (p = 0.003). In the atomoxetine-treated Dyslexia-only group, the LS mean change continued to be significantly greater compared with placebo for the Youth version (p = 0.014) (Table 1).

Table 1.

Kiddie-Sluggish Cognitive Tempo Interview, Change From Baseline to 16 Weeks in Atomoxetine-Treated Patients

	Adjusted for K-SCT baseline score	Adjusted for K-SCT baseline and ADHDRS Total score change
K-SCT versions by diagnostic group	LS mean change (SE)	LS mean change (SE)
ADHD + D
Parent	−8.23 (1.32) ^{† *}	−7.13 (1.05)^†
Teacher	−6.88 (1.86) ^{† *}	−7.69 (1.81) ^{† *}
Youth	−4.03 (1.11)^†	−3.87 (1.12)^†
Dyslexia-only
Parent	−2.51 (1.66)	−2.50 (1.63)
Teacher	−6.69 (2.25)^†	−6.24 (2.48)^†
Youth	−4.42 (1.41) ^{† *}	−4.46 (1.42) ^{† *}
ADHD-only^a
Parent	−7.07 (1.85)^†	−9.01 (1.57)^†
Teacher	−4.78 (3.43)	−4.23 (3.79)
Youth	−6.64 (1.68)^†	−6.94 (1.73)^†

Adjustment for K-SCT baseline score, with and without adjustment for ADHDRS total score change.

Bolded values indicate change greater than placebo (p ≤ 0.05).

No placebo arm comparison group.

p < 0.02, atomoxetine versus placebo.

†

Within-group change from baseline to 16 weeks, p < 0.05.

Results were examined for the three informants within the three diagnostic groups (nine outcomes). Atomoxetine treatment was associated with significant reductions in seven of the nine outcomes using the p = 0.05 significance level appropriate for exploratory analysis. When change in ADHD symptom severity was controlled, all of the seven SCT outcomes remained significant; changes in effect sizes were minimal. The full table of changes on the K-SCT scales from baseline to 16 weeks when the ADHDRS Total score was added to the ANCOVA model is shown in Supplementary Table S1 (Supplementary Data are available online at www.liebertpub.com/cap).

Correlation and regression analyses

The correlation analysis to determine relationships between baseline characteristics and K-SCT change scores showed primarily weak correlations. The highest correlations, although weak to moderate, were between the K-SCT scores for the Parent, Teacher, and Youth versions and the ADHDRS Inattentive score (range r = 0.21 to r = 0.39) and ADHDRS Total score (r = 0.10 to r = 0.29). There were no strong correlations between high baseline K-SCT scores and 49 possible baseline variables that included age, sex, and the total and subscores for ADHD, dyslexia, and reading efficacy measures.

The regression analysis results are presented in Table 2 and are detailed by informant, diagnostic, and treatment group. Regression analyses using SCT change as the criterion found a significant contribution from inattention change only for parent report; whereas, baseline SCT severity was a significant predictor of SCT change as reported by all informants, with the exception of teacher report in the Dyslexia-only group.

Table 2.

Regression Analysis

	ADHD + D (n = 124)			Dyslexia-only (n = 58)
	K-SCT version			K-SCT version
	Parent	Teacher	Youth	Parent	Teacher	Youth
Variables	Partial R²			Partial R²
Baseline ADHDRS Inattentive score	0.03^*	<0.01	<0.01	0.02	0.08	0.08^*
Change in ADHDRS Inattentive score	0.33^*	0.03	0.03	0.16^*	0.36	<0.01
Baseline WJIII Word Attack score	<0.01	<0.01	0.02	0.05	0.28	0.05
Change in WJIII Word Attack score	<0.01	<0.01	<0.01	<0.01	<0.01	0.13^*
Baseline K-SCT score	0.30^*	0.49^*	0.12^*	0.24^*	0.01	0.18^*
Treatment-by-baseline interaction	<0.01	0.04	<0.01	0.11^*	0.08	<0.01
Treatment	<0.01	<0.01	<0.01	<0.01	<0.01	0.03

Partial R ² values for variables tested for effects on change from baseline to 16 weeks in K-SCT score.

p < 0.05.

ADHD, attention-deficit/hyperactivity disorder; ADHD+D, ADHD+Dyslexia; ADHDRS, ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Score; K-SCT, Kiddie-Sluggish Cognitive Tempo Interview; n, sample size for diagnostic group and includes both atomoxetine- and placebo-treated patients; NE, not evaluable; WJIII, Woodcock Johnson III.

Discussion

Previous research has established the partial independence of SCT and ADHD symptoms in cross-sectional study designs (Becker et al. 2016). However, there is a lack of studies evaluating how changes in these symptoms might be related. In this post hoc analysis from a randomized, placebo-controlled trial in children with ADHD and dyslexia or dyslexia alone, the greater improvement in SCT symptoms with atomoxetine treatment compared to placebo treatment was further evaluated. Key objectives of the analyses were to determine the extent to which improvement in SCT symptoms that resulted from atomoxetine treatment was accounted for by improvement in ADHD symptoms and provide additional evidence of the effects of atomoxetine treatment on SCT symptom improvement, independent of ADHD symptom improvement. To accomplish these objectives, analyses controlled for the overlapping improvements in ADHD and SCT symptoms to isolate the direct impact of atomoxetine on SCT symptom changes.

In patients with Dyslexia-only, after controlling for change in ADHD symptoms, the atomoxetine treatment effect on SCT (placebo controlled) remained significant by the patient's rating.

In patients with ADHD+D, after covarying the change in ADHD symptoms, the atomoxetine treatment effect remained significant by teacher rating, whereas the atomoxetine treatment effect became nonsignificant for the parent report. Particularly relevant to the purpose of this article are the change scores from baseline to 16 weeks. Statistical control of change in ADHD had modest effects on significance and effect size of SCT change variables. This robust effect suggests that change in SCT is not a derivative of change in ADHD symptoms.

Regression analyses revealed that change in ADHD inattentive symptoms accounted for a significant proportion of variance only in parent-rated SCT improvement (up to 33%). Even so, baseline SCT simultaneously predicted SCT change in all outcomes except that reported by teachers in the Dyslexia-only group. This is consistent with the interpretation that change in SCT is partially independent of change in inattention and atomoxetine tends to have more effect on SCT when it is elevated at baseline, and thus has room for improvement.

Study limitations

The overlap between ADHD and SCT symptoms was criticized as a study limitation of the Wietecha et al. (Wietecha et al. 2013; Yang and Li 2014). Yang and Li (2014) suggested that because of the controversial issue regarding the linkage between ADHD and SCT, a statistical analysis excluding the influence of ADHD symptoms on change in K-SCT score should have been conducted (Burns et al. 2013; Barkley 2014; Saxbe and Barkley 2014; Yang and Li 2014; Becker et al. 2016). The current analyses addressed this criticism and further analyzed the contributions of ADHD and SCT to better delineate the treatment effect. However, the very nature of a post hoc analysis is a limiting factor of the results.

The original study was not designed to specifically evaluate SCT. The subsample of patients with dyslexia without comorbid ADHD and without clinically elevated inattention was included in the post hoc analysis. Although this may have reduced range restriction of inattention symptoms, it may have affected change by including subjects with little possibility of improvement in already low ADHDRS Inattentive scores. The lack of a placebo control group for the ADHD-only group warrants extra caution in generalizing our findings to ADHD without dyslexia, although we have no plausible reason to doubt that these findings would be replicated in that group. Additional controlled, prospective studies are needed to further clarify the dimensions and features of SCT in relation to ADHD symptomology.

Conclusions

This analysis provided preliminary evidence that change in SCT symptoms is partially independent from change in ADHD inattentive symptoms. The improvement in ADHD inattentive symptoms as a result of atomoxetine treatment partially explained the change in SCT symptom scores; however, it did not fully account for improvement in SCT symptoms. These results suggest that in atomoxetine-treated patients, improvement on SCT was largely independent of improvement in ADHD and atomoxetine may exert a direct effect on SCT.

Clinical Significance

The improvement in SCT symptoms following atomoxetine treatment may be independent of the improvement in ADHD inattentive symptoms. This finding holds promise that atomoxetine and other agents may prove effective in reducing SCT symptoms even when ADHD is not clinically diagnosable. This is an important implication, given that it is now firmly established that SCT is associated with functional impairment that is partially independent of ADHD (Barkley 2012; Becker et al. 2016). A final implication concerns the development of new therapeutics to address attention problems and other cognitive difficulties in general. Inclusion of measures of SCT in investigational treatment protocols may yield additional information on the scope of treatment effects. This may lead to discoveries that would guide the selection of treatments for individuals, depending on whether SCT, inattention, or both are prominent.

Footnotes

Acknowledgments

The authors thank Millie Hollandbeck (Synchrogenix) for assistance in article preparation and Courtneay Parsons (Synchrogenix) for editorial assistance.

Author's Contribution

Data analysis: D.W., InVentiv Health Clinical.

Disclosures

K.M.: Research Support—Alcobra Pharma, BioMarin, Bristol-Myers Squibb Co., National Institute of Mental Health, Merck & Co., Inc., Pfizer, Inc., Shire, Sunovion Pharmaceuticals, Inc., U.S. Department of Education; D.C.: An employee and minor shareholder of Eli Lilly and Company and/or one of its subsidiaries; D.W.W: An employee of inVentiv Health Clinical and former employee of Eli Lilly and Company (employee until October 2010); M.V.: Research Support—Florida Institute for Child Welfare, The Children's Trust of Miami; L.W.: An employee and minor shareholder of Eli Lilly and Company and/or one of its subsidiaries; R.B.: Consultant—Ironshore Pharmaceuticals & Development, Inc. Speaker: Eli Lilly and Company. Royalties—Guilford Press, Premier Educational Seminars, Inc., ContEdCourses.net, and PsychContEd.com

References

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Publishing; 2000.

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders 5th ed. Washington, DC: American Psychiatric Publishing; 2013.

Barkley

: Distinguishing sluggish cognitive tempo from attention-deficit/hyperactivity disorder in adults. J Abnorm Psychol, 121:978–990, 2012.

Barkley

: Sluggish cognitive tempo (concentration deficit disorder?): Current status, future directions, and a plea to change the name. J Abnorm Child Psychol, 42:117–125, 2014.

Barkley

(ed): Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. New York, The Guilford Press, 2015.

Becker

, Leopold

, Burns

, Jarrett

, Langberg

, Marshall

, McBurnett

, Waschbusch

, Willcutt

: The internal, external, and diagnostic validity of sluggish cognitive tempo: A meta-analysis and critical review. J Am Acad Child Adolesc Psychiatry, 55:163–178, 2016.

Burns

, Servera

, Bernad Mdel

, Carrillo

, Cardo

: Distinctions between sluggish cognitive tempo, ADHD-IN, and depression symptom dimensions in Spanish first-grade children. J Clin Child Adolesc Psychol, 42:796–808, 2013.

DuPaul

, Power

, Anastopoulos

, Reid

: ADHD Rating Scale-IV-Children-Adolescents: Checklists, Norms, and Clinical Interpretation. New York, The Guilford Press, 1998.

Garner

, Marceaux

, Mrug

, Patterson

, Hodgens

: Dimensions and correlates of attention deficit/hyperactivity disorder and sluggish cognitive tempo. J Abnorm Child Psychol, 38:1097–1107, 2010.

10.

Hartman

, Willcutt

, Rhee

, Pennington

: The relation between sluggish cognitive tempo and DSM-IV ADHD. J Abnorm Child Psychol, 32:491–503, 2004.

11.

Lee

, Burns

, Snell

, McBurnett

: Validity of the sluggish cognitive tempo symptom dimension in children: Sluggish cognitive tempo and ADHD-inattention as distinct symptom dimensions. J Abnorm Child Psychol, 42:7–19, 2014.

12.

McBurnett

, Pfiffner

, Frick

: Symptom properties as a function of ADHD type: An argument for continued study of sluggish cognitive tempo. J Abnorm Child Psychol, 29:207–213, 2001.

13.

Penny

, Waschbusch

, Klein

, Corkum

, Eskes

: Developing a measure of sluggish cognitive tempo for children: Content validity, factor structure, and reliability. Psychol Assess, 21:380–389, 2009.

14.

Saxbe

, Barkley

: The second attention disorder? Sluggish cognitive tempo vs. attention-deficit/hyperactivity disorder: Update for clinicians. J Psychiatr Pract, 20:38–49, 2014.

15.

Shaywitz

, Williams

, Fox

, Wietecha

: Reading outcomes of children and adolescents with attention-deficit/hyperactivity disorder and dyslexia following atomoxetine treatment. J Child Adolesc Psychopharmacol, 24:419–425, 2014.

16.

Skirbekk

, Hansen

, Oerbeck

, Kristensen

: The relationship between sluggish cognitive tempo, subtypes of attention-deficit/hyperactivity disorder, and anxiety disorders. J Abnorm Child Psychol, 39:513–525, 2011.

17.

Wietecha

, Williams

, Shaywitz

, Hooper

, Wigal

, Dunn

, McBurnett

: Atomoxetine improved attention in children and adolescents with attention-deficit/hyperactivity disorder and dyslexia in a 16 week, acute, randomized, double-blind trial. J Child Adolesc Psychopharmacol, 23:605–613, 2013.

18.

Yang

, Li

: Could atomoxetine improve sluggish cognitive tempo symptoms?. J Child Adolesc Psychopharmacol, 24:462, 2014.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.03 MB

0.00 MB