GRADE evidence profiles geïncludeerde studies

Voor meer details verwijzen we naar de in 2014 gepubliceerde internationale richtlijn: “Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.” ⁴⁵

Glucomannan vs Placebo

Question: Should Glucomannan vs Placebo be used for chronic functional constipation ?^1,2,3
Settings: 31 children, 4.5–11.7 y of age, from tertiary pediatric gastroenterology in United States
Bibliography: Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics 2004; 113(3 Pt 1):e259-e264. For outcome measures abd pain and successful treatment, we have also included: Chmielewska A, Horvath A, Dziechciarz P, Szajewska H.Glucomannan is not effective for the treatment of functional constipation in children: a double-blind, placebo-controlled, randomized trial.Clin Nutr. 2011;30(4):462-8. Epub 2011 : see for more information their GRADE evidence profiles

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Glucomannan

Placebo

Relative
(95% CI)

Absolute

Successful treatment ⁴ (follow-up 4 weeks; measured with: Bowel diary; Better indicated by higher values)

2⁵

randomised trials

serious⁶

very serious

no serious indirectness

serious⁷

None

Loening-Baucke: RR 3,50 (95% CI 1,30-9,45). Chmielewska: RR 0,10 (95% CI 0,02-0,38). Not pooled⁴

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁸

Abdominal pain⁹ (follow-up 4 weeks; measured with: Bowel diary; Better indicated by lower values)

2⁵

randomised trials

serious⁶

very serious

no serious indirectness

serious⁷

none

Loening-Baucke: RR 0,23 (95% CI 0,07-0,73). Chmielewska: RR 1,50 (95% CI 0,78-2,88). Not pooled⁴

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁸

Defecation frequency (change) (follow-up 4 weeks; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

very serious⁶

no serious inconsistency

no serious indirectness

serious⁷

none

MD 0.7 higher (0.4 lower to 1.8 higher)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁸

¹ Glucomannen: 100 mg/kg per day up to 5 g/day,Patients continued with their preevaluation laxative
² Placebo: maltodextrins. Patients continued with their preevaluation laxative
³ Complaints for at least 6 months. Constipation was defined by Loening- Baucke as a delay or difficulty in defecation, present for >2 weeks, and sufficient to cause significant distress to the child ⁴

⁴Loening-Baucke: defined as at least 3 bm/wk and <1 soiling/3 weeks with no abdominal pain in the last 3 weeks

Chmielewska: defined as at least 3 stools per week with no soiling. Chmielewska: post-hoc analyses used in order to faciltiate the interpretation of results and to make it more relevant from a clinical decision making point of view. We refrained from pooling these results due to inconsistency.
⁵ Study Loening-Baucke and Chmielewska

⁶ Loening-Baucke: high risk of bias: Adequate randomisation procedure,but no information on blinding of the outcome assessor was provided and an intention-to-treat analysis was not performed. Other major shortcomings were unclear definition of constipation and the unexplained high rate of loss to follow-up monitoring of 32%. Studies concerning a chronic condition should consider long-term outcomes and therefore a cross-over design may not be the most appropriate way to look at chronic constipation.Chmielewska: low risk of bias
⁷ Both studies: small sample sizes
⁸ Mean score of the 6 working group members

Question: Should Glucomannan vs Placebo be used for functional constipation?^1,2
Settings: 72 children, 3-16 years, from outpatient pediatric clinic in Poland
Bibliography: Chmielewska A, Horvath A, Dziechciarz P, Szajewska H.Glucomannan is not effective for the treatment of functional constipation in children: a double-blind, placebo-controlled, randomized trial.Clin Nutr. 2011;30(4):462-8. Epub 2011

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Glucomannan

Placebo

Relative
(95% CI)

Absolute

Defecation frequency (median) (follow-up 4 weeks; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

MD 1 higher (0 to 3 higher)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

Fecal incontinence (follow-up 4 weeks; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

11/36
(30.6%)

4/36
(11.1%)

RR 2.75 (0.97 to 7.83)

194 more per 1000 (from 3 fewer to 759 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁴

Pain at defecation (follow-up 4 weeks; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

10/36
(27.8%)

7/36
(19.4%)

RR 1.43 (0.61 to 3.34)

84 more per 1000 (from 76 fewer to 455 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁴

¹ Dosage of 2.52 g/day, i.e., 1 sachet of 1.26 g two times a day
² Placebo (maltodextrine) at the same dosage as intervention
³ Small sample size
⁴ Mean score of the 6 working group members, post-hoc analyses used in order to faciltiate the interpretation of results and to make it more relevant from a clinical decision making point of view

Cocoa husk supplement vs Placebo

Question: Should Cocoa husk supplement vs Placebo be used for chronic idiopathic constipation?^1,2
Settings: 56 children, 3–10 y of age, recruited from tertiary gastroenterology clinic in Spain
Bibliography: Castillejo G, Bullo M, Anguera A, Escribano J, Salas-Salvado J. A controlled, randomized, double-blind trial to evaluate the effect of a supplement of cocoa husk that is rich in dietary fiber on colonic transit in constipated pediatric patients. Pediatrics 2006;118(3):e641-e648.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Cocoa husk supplement

Placebo

Relative
(95% CI)

Absolute

Defecation frequency (change) (follow-up mean 4 weeks; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

MD 0.40 higher (1.14 lower to 1.94 higher)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

¹ 10.4 g/d (3–6 y) or 20.8 g/d (7–10 y)
² according to ROME II criteria
³ Small sample size
⁴ Mean score of the 6 working group members

Vezels vs Lactulose

Question: Should Fiber vs Lactulose be used for functional constipation?^1,2,3
Settings: 97 children from 1-13 y of age, from general pediatric practice clinic in the Netherlands
Bibliography: Kokke FT, Scholtens PA, Alles MS, et al. A dietary fiber mixture versus lactulose in the treatment of childhood constipation: a double-blind randomized controlled trial. J Pediatr Gastroenterol Nutr. 008;47(5):592–597

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Fiber

Lactulose

Relative
(95% CI)

Absolute

At least 1 fecal incontinence episode per week (follow-up 8 weeks)

randomised trials

very serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none

9/42
(21.4%)

5/55
(9.1%)

RR 2.36 (0.85 to 6.25)

124 more per 1000 (from 14 fewer to 477 more)

⊕⊝⊝⊝
VERY LOW

CRITICAL⁶

¹ 10 g in 125-mL yogurt drink consisting of a mix of fibers: 3.0 g transgalacto-oligosaccharides, 3.0 g inulin, 1.6 g soy fiber and 0.33 g resistant starch 3 per 100 mL.
² 10 g in 125-mL yogurt drink
³ With at least 2 of 4 criteria: <3 bowelmovements per wk, 2 or more fecal incontinence episodes per wk, periodic passage of stool at least once every 7–30 d, or palpable abdominal or rectal mass
⁴ Adequate randomisation procedure, but no information on blinding of the outcome assessor was provided, no intention-to-treat analysis was performed, and the dropout rate was high and not equally distributed. Polyethylene glycol (macrogol 3350) was added if no clinical improvement was observed after 3 weeks
⁵ Small sample size
⁶ Mean score of the 6 working group members

Question: Should Partially hydrolyzed guar gum (phhg) vs Lactulose be used in Functional constipation?^1,2,3
Settings: 61 children, 4-16 years,admitted to the outpatient pediatric gastroenterology clinic of a Turkish University hospital.
Bibliography: Üstündağ G, Kuloğlu Z, Kirbaş N, Kansu A. Can partially hydrolyzed guar gum be an alternative to lactulose in treatment of childhood constipation?Turk J Gastroenterol. 2010;21(4):360-4.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Partially hydrolyzed guar gum (phhg)

Lactulose

Relative
(95% CI)

Absolute

Defecation frequency (change) (follow-up 4 weeks; measured with: Bowel diary; Better indicated by lower values)

randomised trials

very serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none

MD 1 lower (1.64 to 0.36 lower)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁶

Abdominal pain (follow-up 4 weeks; assessed with: Bowel diary)

randomised trials

very serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none

5/31
(16.1%)⁷

3/30
(10%)⁷

RR 1.61 (0.42 to 6.16)

61 more per 1000 (from 58 fewer to 516 more)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁶

¹ PHGG (for children between 4-6 years: 3 g/day; 6-12 years: 4 g/day;and 12-16 years: 5 g/day). Both groups were given an equal diet with fiber. However, the group given PHGG was recommended to increase their fluid intake
² 1 ml/kg/day, in divided doses
³ According to ROME III criteria
⁴ Lack of blinding, Co-intervention not similar in both groups: the group given PHGG was recommended to increase their fluid intake.
⁵ Small sample size, sparse data
⁶ Mean score of the 6 working group members
⁷ By estimation, absolute numbers not given