Mistakes in paediatric functional constipation diagnosis and treatment and how to avoid them

October 13, 2016 By: Marc A. Benninga and Daniel R. Hoekman

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Mistakes in paediatric functional constipation diagnosis and treatment and how to avoid them 

Have a look at the major mistakes that are made when diagnosing and treating children with functional constipation. 

Constipation is a bothersome problem for many children. It may present as one or more of the following: infrequent bowel movements with faecal incontinence, hard and often large stools, painful defecation and abdominal pain. No organic cause of the constipation can be found in approximately 95% of children—these children suffer from functional constipation. The prevalence of functional constipation ranges between 0.7% and 29.6% and it occurs in girls more often than in boys (ratio 2.1:1).1

The diagnosis of functional constipation is based on the paediatric diagnostic Rome criteria for functional gastrointestinal disorders.2,3 Additional investigations are indicated only if the diagnosis is not clear or in order to rule out an underlying organic disease, such as Hirschsprung disease.4 Education, demystification of constipation, following a reward-based toilet program and keeping a daily bowel diary form part of the nonpharmacological management process.4 Disimpaction, maintenance treatment and weaning of medication are all elements of pharmacological treatment.4 Polyethylene glycol (PEG) is the first-choice laxative for both disimpaction and maintenance treatment; however, if PEG is not available or is poorly tolerated, lactulose is recommended. Other laxatives are available as a second-line or additional treatment if treatment with PEG is insufficient.

Here we discuss the major mistakes that are made when diagnosing and treating children with functional constipation. The discussion that follows is evidence based in the majority of cases, but where evidence is lacking the discussion is based on the lead author’s clinical experience of more than 20 years in the field as a paediatric gastroenterologist.

Mistake 1 | Diagnosing a child with functional constipation on the basis of an abdominal radiograph

A thorough medical history and a complete physical examination are in >95% of cases sufficient to differentiate children with an organic cause of constipation from those with functional constipation. Nonetheless, abdominal radiographs are often used to rate faecal loading.
A systematic review including six studies that evaluated the value of abdominal radiography reported a sensitivity of 60–80% and specificity of 43–99%.5 The radiological scoring systems used to rate the degree of faecal loading are based on the amount of stool in the bowel and, to a certain extent, on the importance of bowel dilatation. For the diagnosis of constipation, however, each system uses different objective criteria that are not clearly defined. Consequently, the rating scales rely on subjective assessments that can vary based on personal experience and interpretation. The ESPGHAN/NASPGHAN and NICE guidelines recommend not using a plain abdominal radiograph for the diagnosis of functional constipation.4,6

Mistake 2 | Adopting a ‘wait and see’ policy to treating childhood constipation

Despite solid evidence that early and prolonged treatment with a laxative is beneficial for the child, and is even positively related to recovery, many health-care professionals follow a ‘wait and see’ policy in children with functional constipation.4 In one study, the clinical course of 47 children who had constipation in the first year of life and were referred to a tertiary clinic was retrospectively evaluated.7 Children who had constipation for <3 months before presentation to the outpatient clinic achieved earlier success than children who had constipation for >3 months before presentation. At the 6-month follow-up, 79% of the children who presented after <3 months were successfully defecating without using laxatives, in contrast to 32% of the children who presented after >3 months (P<0.002.)
The negative association between longer duration of symptoms and good clinical outcome might indicate that therapeutic intervention in an early phase of constipation is more likely to be beneficial. Those children treated <2 months before presentation reached first success without using laxatives earlier than children who were treated with oral or rectal laxatives for >2 months (84% versus 36%, P<0.002) at 6 months of follow-up. The poor prognostic outcome in children treated with laxatives for >2 months before enrolment is probably related to the longer period of time they had inadequately treated symptoms. As a consequence of repeated painful defecations and accumulation of faeces in the rectum, children may develop stool-withholding behaviour, which exacerbates the problem.4

Mistake 3 | Treating a child who has functional constipation by using fibres

The prevalence of constipation in children is associated with a diet low in fibre.8–10 The ESPGHAN/NASPGHAN and NICE guidelines recommend having a normal fibre intake (i.e. 5 g + the age in years of the child).4,6 Two systematic reviews, however, illustrate the limited clinical value of fibre in the management of childhood constipation.11,12 In addition, increasing dietary fibre intake accompanied by extensive behavioural interventions does not increase bowel frequency or reduce the requirement for laxatives.13

Mistake 4 | Increasing the fluid intake above normal to treat childhood constipation

Increasing fluid intake has been suggested to soften the stools. One study assessing extra fluid intake in children with functional constipation, however, showed insufficient evidence for its advantageous effect on constipation symptoms.14 Therefore, it is not recommended that the fluid intake in children with functional constipation exceeds normal levels.4,6 An exception should be made for the extra fluid that is required for certain medications to be taken, such as PEG, which needs to be dissolved in water.

Mistake 5 | Giving probiotics to treat a child who has constipation

There are some data indicating that constipation is associated with alterations in the gut microbiota in both adults and children.15,16 Consequently, modulation of the gut microbiota with probiotics is a potential therapeutic approach for constipation. Indeed, in adults who have constipation, some probiotic strains (such as Bifidobacterium lactis) have been shown to have a beneficial effect on stool frequency and consistency and to reduce the gut transit time.17 Nonetheless, larger studies are required to determine which species/strains, doses and duration of treatment are efficacious in adults with constipation.17
By contrast, studies to date do not indicate that probiotics are more effective than placebo for the treatment of constipation in children.18,19 Thus, there is currently no evidence to support the use of any probiotic strain for the treatment of children with functional constipation.

Mistake 6 | Using olive oil to treat childhood constipation

Mineral oil (or liquid paraffin), consisting of hydrocarbons, is not absorbed in the intestine. Consequently, it can be used in the treatment of constipation as a lubricant of faeces. The efficacy of mineral oil in the treatment of childhood constipation has been demonstrated in multiple studies.20
Olive oil, on the other hand, mainly consists of triglycerides,21 which are almost completely absorbed in the small intestine. Therefore, except for children with malabsorption, olive oil does not reach the colon to be able to exert a laxative effect. Furthermore, there is no evidence from clinical trials to support the use of olive oil for the treatment of constipated children. 

Mistake 7 | Treating a child who has constipation with laxatives for a duration of 2 weeks

After successful disimpaction, maintenance therapy should be initiated to prevent the reaccumulation of faeces.22 Osmotic laxatives are the first step in the pharmacological treatment of functional constipation. They are poorly absorbed by the intestinal wall, which leads to intraluminal accumulation of hyperosmolar particles. This stimulates retention of water in the intestinal lumen, softening the stools and increasing peristalsis through intestinal distension. Furthermore, some osmotic laxatives increase peristalsis through a decrease in intraluminal pH.
PEG (or macrogol) is the first-choice osmotic laxative in children with functional constipation. It is a linear polymer, in which water molecules are retained by means of hydrogen connections, causing an intraluminal fluid volume increase. It is not metabolized and is minimally (<1%) absorbed in the intestine.23 Lactulose is a synthetic derivative of lactose. This hyperosmolar agent is not hydrolyzed by digestive enzymes in the small intestine and is, for that reason, poorly absorbed by the intestinal mucosa. In the colon, this disaccharide is fermented into hyperosmolar low molecular weight acids by intraluminal bacteria.24 This results in intraluminal water retention and a decrease in intraluminal pH, which induces an increase in colonic peristalsis. The bacterial fermentation of these agents also leads to formation of gas, which induces additional intestinal distension and increases peristalsis.
Maintenance treatment should be gradually weaned rather than abruptly discontinued in order to prevent a relapse.25 If maintenance treatment has stabilised symptoms for a duration of at least 1 month (i.e. the defecation frequency is ≥3 times per week) and the child does not fulfil any other Rome IV criteria, weaning can be considered.21,22 It is recommended to evaluate symptoms again 2 months after the cessation of treatment, to prevent or detect relapses.

Mistake 8 | Using biofeedback training in children who have constipation

Approximately 50% of children with functional constipation contract rather than relax their sphincter muscles during an attempt to defecate. Biofeedback training utilizes reinforcing stimuli in an attempt to achieve a recognizable sensation and to encourage an appropriate learnt response. In theory, biofeedback training may help children with dyssynergia to adapt their defecation dynamics. Indeed, several studies have shown the efficacy of biofeedback for correcting defecation dynamics, but a well-conducted, large, randomized controlled trial failed to demonstrate a clinical benefit of biofeedback in children with constipation compared with standard management.26 Current evidence, therefore, does not support biofeedback training for the treatment of childhood constipation.26

Mistake 9 | Treating childhood constipation with a behavioural intervention

Stool withholding has a major role in the development of constipation in infancy and early childhood. Passing a hard stool leading to pain, strict early toilet training, stubbornness and concentration on other activities that are more exciting than going to the toilet are possible risk factors for stool withholding.
Although the precise pathophysiological mechanisms underlying functional constipation are not always clear, psychosocial factors such as major life events, socioeconomic status, educational level and parental child-rearing attitudes might be important.27,28 Furthermore, there is an increased risk of constipation in children with behavioural disorders, such as autism spectrum disorders and attention deficit hyperactivity disorder.29,30
Psychoeducation is crucial for parents to change their behaviour towards the child with constipation and faecal incontinence.31 A positive nonaccusatory approach to the child is necessary to carry out therapeutic procedures at home. It is expected from parents to reinforce appropriate toileting behaviour and to ignore the inappropriate behaviour of pant soiling and stool-withholding behaviour. Before applying a behavioural intervention program, it is of major importance to tackle negative perceptions of parents. If parents still assume the faecal incontinence is their child’s fault and that he/she is doing it on purpose to tease parents, the treatment becomes very difficult and may be even impossible.

Mistake 10 | Using laxatives to treat faecal incontinence in the absence of any other symptom of constipation

Stool-withholding behaviour is an important aetiologic factor in the development of childhood constipation. It can lead to the accumulation of a large faecal mass in the rectum that is difficult to evacuate. In 75% of children with constipation, faecal impaction leads to overflow faecal incontinence, which is the involuntary loss of soft stools that pass the solid, obstructing, faecal mass. In approximately 10% of the children (mainly boys), faecal incontinence is not accompanied by any other symptom of constipation. These children have nonretentive faecal incontinence according to the Rome IV criteria.3
It has been hypothesized that children with nonretentive faecal incontinence ignore or neglect the urge to defecate. Indeed, a randomized controlled trial showed no beneficial effect of laxatives for the treatment of these children.32 By contrast, however, the number of faecal incontinence episodes increased. The treatment of these children is difficult and often long lasting and should include education about the pathophysiology, treatment and prognosis of functional nonretentive faecal incontinence, a strict toilet training program in combination with a reward system and a daily bowel diary, and/or cognitive behavioural therapy. In a minority of cases rectal irrigation or treatment with loperamide is a useful alternative.33 Lastly, counselling and treatment of comorbid psychosocial disorders is sometimes needed.

Article information

© UEG 2016 Benninga and Hoekman.


Cite this article as:
Benninga MA and Hoekman DR. Mistakes in paediatric functional constipation diagnosis and treatment and how to avoid them. UEG Education 2016: 16; 34–36.

Marc A. Benninga and Daniel R. Hoekman are at the Department of Paediatrics at the Emma Children’s Hospital/Academic Medical Centrr, Amsterdam, the Netherlands.

Correspondence to: m.a.benninga@amc.nl

Published online: 12 October 2016

Conflicts of interest: M.A.B. is a consultant for Shire, Sucampo, Astrazeneca, Norgine and Coloplast. D.R.H. declares there is no conflict of interest.

A pdf of this article can be found in the UEG Education Library.

References

1. Mugie SM, Benninga MA and Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol 2011; 25: 3–18.

2. Benninga MA, Faure C, Hyman PE, et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2016; 150: 1443–1455.

3. Hyams JS, Di Lorenzo C, Saps M, et al. Functional disorders: children and adolescents. Gastroenterology 2016; 150: 1456–1468.

4. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr 2014; 58: 258–274. 

5. Berger MY, Tabbers MM, Kurver MJ, et al. Value of abdominal radiography, colonic transit time, and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children: a systematic review. J Pediatr 2012; 161: 44–50.

6. Bardisa-Ezcurra L, Ullman R, Gordon J, et al. Diagnosis and management of idiopathic childhood constipation: summary of NICE guidance. BMJ 2010; 340: c2585.

7. van den Berg MM, van Rossum CH, de Lorijn F, et al. Functional constipation in infants: a follow-up study. J Pediatr 2005; 147: 700–704.

8. Morais MB, Vítolo MR, Aguirre AN, et al. Measurement of low dietary fiber intake as a risk factor for chronic constipation in children. J Pediatr Gastroenterol Nutr 1999; 29: 132–135.

9. Roma E, Adamidis D, Nikolara R, et al. Diet and chronic constipation in children: the role of fiber. J Pediatr Gastroenterol Nutr 1999; 28: 169–174.

10. Lee WT, Ip KS, Chan JS, et al. Increased prevalence of constipation in pre-school children is attributable to under-consumption of plant foods: A community-based study. J Paediatr Child Health 2008; 44: 170–175.

11. Tabbers MM, Boluyt N, Berger MY, et al. Nonpharmacologic treatments for childhood constipation: systematic review. Pediatrics 2011; 128: 753–761.

12. Pijpers MA, Tabbers MM, Benninga MA, et al. Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures. Arch Dis Child 2009; 94: 117–131.

13. Sullivan PB, Alder N, Shrestha B, et al. Effectiveness of using a behavioural intervention to improve dietary fibre intakes in children with constipation. J Hum Nutr Diet 2012; 25: 33–42.

14. Young RJ, Beerman LE and Vanderhoof JA. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs 1998; 21: 156–161.

15. Zhu L, Liu W, Alkhouri R, et al, Structural changes in the gut microbiome of constipated patients. Physiol Genomics 2014; 46: 679–686.

16. Zoppi G, Cinquetti M, Luciano A, et al. The intestinal ecosystem in chronic functional constipation. Acta Paediatr 1998; 87: 836–841.

17. Dimidi E, Christodoulides S, Fragkos KC, et al. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2014; 100: 1075–1084.

18. Korterink JJ, Ockeloen L, Benninga MA, et al. Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. Acta Paediatr 2014; 103: 365–372. 

19. Tabbers MM and Be1. Mugie SM, Benninga MA and Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol 2011; 25: 3–18.

2. Benninga MA, Faure C, Hyman PE, et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2016; 150: 1443–1455.

3. Hyams JS, Di Lorenzo C, Saps M, et al. Functional disorders: children and adolescents. Gastroenterology 2016; 150: 1456–1468.

4. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr 2014; 58: 258–274. 

5. Berger MY, Tabbers MM, Kurver MJ, et al. Value of abdominal radiography, colonic transit time, and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children: a systematic review. J Pediatr 2012; 161: 44–50.

6. Bardisa-Ezcurra L, Ullman R, Gordon J, et al. Diagnosis and management of idiopathic childhood constipation: summary of NICE guidance. BMJ 2010; 340: c2585.

7. van den Berg MM, van Rossum CH, de Lorijn F, et al. Functional constipation in infants: a follow-up study. J Pediatr 2005; 147: 700–704.

8. Morais MB, Vítolo MR, Aguirre AN, et al. Measurement of low dietary fiber intake as a risk factor for chronic constipation in children. J Pediatr Gastroenterol Nutr 1999; 29: 132–135.

9. Roma E, Adamidis D, Nikolara R, et al. Diet and chronic constipation in children: the role of fiber. J Pediatr Gastroenterol Nutr 1999; 28: 169–174.

10. Lee WT, Ip KS, Chan JS, et al. Increased prevalence of constipation in pre-school children is attributable to under-consumption of plant foods: A community-based study. J Paediatr Child Health 2008; 44: 170–175.

11. Tabbers MM, Boluyt N, Berger MY, et al. Nonpharmacologic treatments for childhood constipation: systematic review. Pediatrics 2011; 128: 753–761.

12. Pijpers MA, Tabbers MM, Benninga MA, et al. Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures. Arch Dis Child 2009; 94: 117–131.

13. Sullivan PB, Alder N, Shrestha B, et al. Effectiveness of using a behavioural intervention to improve dietary fibre intakes in children with constipation. J Hum Nutr Diet 2012; 25: 33–42.

14. Young RJ, Beerman LE and Vanderhoof JA. Increasing oral fluids in chronic constipation in children. Gastroenterol Nurs 1998; 21: 156–161.

15. Zhu L, Liu W, Alkhouri R, et al, Structural changes in the gut microbiome of constipated patients. Physiol Genomics 2014; 46: 679–686.

16. Zoppi G, Cinquetti M, Luciano A, et al. The intestinal ecosystem in chronic functional constipation. Acta Paediatr 1998; 87: 836–841.

17. Dimidi E, Christodoulides S, Fragkos KC, et al. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2014; 100: 1075–1084.

18. Korterink JJ, Ockeloen L, Benninga MA, et al. Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. Acta Paediatr 2014; 103: 365–372. 

19. Tabbers MM and Benninga MA. Constipation in children: fibre and probiotics. BMJ Clin Evid 2015; 2015: 0303.

20. Gordon M, Naidoo K, Akobeng AK, et al. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst Rev 2012; 7: CD009118.

21. Blekas G, Vassilakis C, Harizanis C, et al. Biophenols in table olives. J Agric Food Chem 2002; 50: 3688–3692.

22. Tabbers MM, Boluyt N, Berger MY, et al. Clinical practice: diagnosis and treatment of functional constipation. Eur J Pediatr 2011; 170: 955–963.

23. Brady CE, DiPalma JA, Morawski SG, et al. Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution. Gastroenterology 986; 90: 1914–1918.

24. Hoekman DR and Benninga MA. Functional constipation in childhood: current pharmacotherapy and future perspectives. Expert Opin Pharmacother 2013; 14: 41–51.

25. Felt B, Wise CG, Olson A, et al. Guideline for the management of pediatric idiopathic constipation and soiling. Multidisciplinary team from the University of Michigan Medical Center in Ann Arbor. Arch Pediatr Adolesc Med 1999; 153: 380–385.

26. Rao SSC, Benninga MA, Bharucha AE, et al. ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol Motil 2015; 27: 594–609.

27. van Dijk M, de Vries G-J, Last BF, et al. Parental child-rearing attitudes are associated with functional constipation in childhood. Arch Dis Child 2014; 100: 329–333. 

28. Philips EM, Peeters B, Teeuw AH, et al. Stressful life events in children with functional defecation disorders. J Pediatr Gastroenterol Nutr 2015; 61: 384–392. 

29. McKeown C, Hisle-Gorman E, Eide M, et al. Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder. Pediatrics 2013; 132: e1210–e1215. 

30. Peeters B, Noens I, Philips EM, et al. Autism spectrum disorders in children with functional defecation disorders. J Pediatr 2013; 163: 873–878. 

31. van Dijk M, Benninga MA, Grootenhuis MA, et al. Chronic childhood constipation: a review of the literature and the introduction of a protocolized behavioral intervention program. Patient Educ Couns 2007; 67: 63–77.

32. van Ginkel R, Benninga MA, Blommaart PJ, et al. Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children. J Pediatr 2000; 137: 808–813.

33. Koppen IJ, von Gontard A, Chase J, et al. Management of functional nonretentive fecal incontinence in children: Recommendations from the International Children's Continence Society. J Pediatr Urol 2016; 12: 56–64.

nninga MA. Constipation in children: fibre and probiotics. BMJ Clin Evid 2015; 2015: 0303.

20. Gordon M, Naidoo K, Akobeng AK, et al. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst Rev 2012; 7: CD009118.

21. Blekas G, Vassilakis C, Harizanis C, et al. Biophenols in table olives. J Agric Food Chem 2002; 50: 3688–3692.

22. Tabbers MM, Boluyt N, Berger MY, et al. Clinical practice: diagnosis and treatment of functional constipation. Eur J Pediatr 2011; 170: 955–963.

23. Brady CE, DiPalma JA, Morawski SG, et al. Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution. Gastroenterology 986; 90: 1914–1918.

24. Hoekman DR and Benninga MA. Functional constipation in childhood: current pharmacotherapy and future perspectives. Expert Opin Pharmacother 2013; 14: 41–51.

25. Felt B, Wise CG, Olson A, et al. Guideline for the management of pediatric idiopathic constipation and soiling. Multidisciplinary team from the University of Michigan Medical Center in Ann Arbor. Arch Pediatr Adolesc Med 1999; 153: 380–385.

26. Rao SSC, Benninga MA, Bharucha AE, et al. ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol Motil 2015; 27: 594–609.

27. van Dijk M, de Vries G-J, Last BF, et al. Parental child-rearing attitudes are associated with functional constipation in childhood. Arch Dis Child 2014; 100: 329–333. 

28. Philips EM, Peeters B, Teeuw AH, et al. Stressful life events in children with functional defecation disorders. J Pediatr Gastroenterol Nutr 2015; 61: 384–392. 

29. McKeown C, Hisle-Gorman E, Eide M, et al. Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder. Pediatrics 2013; 132: e1210–e1215. 

30. Peeters B, Noens I, Philips EM, et al. Autism spectrum disorders in children with functional defecation disorders. J Pediatr 2013; 163: 873–878. 

31. van Dijk M, Benninga MA, Grootenhuis MA, et al. Chronic childhood constipation: a review of the literature and the introduction of a protocolized behavioral intervention program. Patient Educ Couns 2007; 67: 63–77.

32. van Ginkel R, Benninga MA, Blommaart PJ, et al. Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children. J Pediatr 2000; 137: 808–813.

33. Koppen IJ, von Gontard A, Chase J, et al. Management of functional nonretentive fecal incontinence in children: Recommendations from the International Children's Continence Society. J Pediatr Urol 2016; 12: 56–64.

About the authors

Marc Benninga, MD, PhD, is Professor of Paediatrics at Emma Children’s Hospital/Academic Medical Centre. He is a paediatric gastroenterologist and expert in functional gastrointestinal disorders in childhood. To date he has published more than 325 peer-reviewed articles.

Daniel Hoekman, MD, is a PhD
student at Emma Children’s Hospital/Academic Medical Centre. He is a medical doctor specializing in functional gastrointestinal disorders and inflammatory bowel disease. To date he has published 8 peer-reviewed articles. 

 

Comments

Hanna Kuzi, October 19, 2016 12:17
It's perfectly!! I'm very happy, really))))
Milica Stojkovic, October 19, 2016 10:26
Very educational
Mila Kovacheva-Slavova, October 19, 2016 10:21
Very nice!
Francesca D'Errico, October 18, 2016 17:23
Amazing
Marco Della Coletta, October 18, 2016 17:09
Amazing
Lucia Pallotta, October 18, 2016 17:07
Very interesting meeting
Marilia Carabotti, October 18, 2016 16:37
A Great Book !
Merighi Alberto, October 18, 2016 16:32
Very intristing
Mahmoud El-Bendary, October 18, 2016 15:45
Behavioral TT is important
Zakariyya Al-Mrayat, October 18, 2016 13:57
very educational, great problem-based learning.

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