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

Lactulose vs PEG

Question: Should Lactulose vs Polyethylene glycol (PEG) be used for chronic constipation or fecal impaction ?¹
Settings: Children 3 months-18 years in a variety of different settings²
Bibliography: Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene Glycol for Chronic Constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Lactulose

Polyethylene glycol (PEG)

Relative
(95% CI)

Absolute

Relief of abdominal pain (follow-up 14-84 days; assessed with: A score or dichotomised (y/n))

2³

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

None

66/119
(55.5%)

88/116
(75.9%)

OR 0.40 (0.23 to 0.69)

202 fewer per 1000 (from 74 fewer to 339 fewer)

⊕⊕⊝⊝
LOW

IMPORTANT⁶

Defecation frequency (follow-up 2-12 weeks; measured with: Bowel diary; range of scores: 0-30; Better indicated by higher values)

3⁷

randomised trials

serious⁸

no serious inconsistency

no serious indirectness

serious⁵

None

113

114

MD 1.57 lower (2.77 to 0.36 lower)

⊕⊕⊝⊝
LOW

IMPORTANT⁶

¹ According to ROME III criteria
² Participants: both adults and children with chronic constipation (ROME III) and treated with lactulose or PEG. We will only discuss pediatric trials
³ Dupont and Wang: see Cochrane review. Not included in this analysis: Candy, Gremse and Voskuijl: not using comparable data for meta-analysis
⁴ Dupont: no risk of bias, Wang: incomplete outcome data, unclear if free of selective reporting
⁵ Small sample size
⁶ Mean score of the 6 working group members
⁷ Candy, Gremse and Voskuijl: see Cochrane review. Not included in this analysis: Dupont: they reported def. frequency using medians and interquartile ranges. Wang: Def frequency was reported although this appeared to be for 2 weeks rather than 1 week. Also no standard deviation was provided
⁸ Candy: unclear allocation of concealment, unclear if incomplete outcome data, Gremse: unclear allocation of concealment, no blinding, Voskuijl: unclear if free of selective reporting (did not report on form of stool, relief of abd.pain and use of additional products)

PEG vs Placebo

Question: Should Polyethylene glycol vs Placebo be used for functional constipation?^1,2
Settings: Children aged 24 months to 11 years, outpatient pediatric clinics in United Kingdom
Bibliography: Thomson MA, Jenkins HR, Bisset WM, Heuschkel R, Kalra DS, Green MR, Wilson DC, Geraint M. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study. Arch Dis Child. 2007; 92 (11): 96-1000. 2.Nurko S, Youssef NN, Sabri M, Langseder A, McGowan J, Cleveland M, Di Lorenzo C. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. J Pediatr. 2008;153(2):254-61, 261.e1.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Polyethylene glycol

Placebo

Relative
(95% CI)

Absolute

Defecation frequency (follow-up 4 weeks; measured with: Bowel diary; range of scores: 0-30; Better indicated by lower values)

randomised trials³

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

MD 1.64 higher (0.99 to 2.88 higher)

⊕⊕⊝⊝
LOW

IMPORTANT⁷

Pain on defecation (follow-up 4 weeks; measured with: Bowel diary: scored as 0 = none, 1 = mild, 2 = moderate, 3 = severe; range of scores: 0-3; Better indicated by lower values)

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

MD 0.28 lower (0.52 to 0.01 lower)

⊕⊕⊝⊝
LOW

CRITICAL⁷

Straining on defecation(follow-up 2-4 weeks⁸; measured with: Bowel diary⁹; range of scores: 0-3 or 4; Better indicated by lower values)

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

74¹⁰

Thomson: mean difference -0.65 (95% CI -0.97 to -0.33) Nurko: mean difference -1.2 (95% CI -0.37-0.97)

⊕⊕⊝⊝
LOW

CRITICAL⁷

Fecal incontinence frequency(follow-up 2-4 weeks⁸; measured with: Bowel diary; range of scores: 0-30; Better indicated by lower values)

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

74¹¹

Thomson: mean difference -0.15 (95% CI: -3,.04-2.74) Nurko: mean difference -0.70 (95% CI -2.9-1.5)

⊕⊕⊝⊝
LOW

CRITICAL⁷

Safety/Adverse events (follow-up 4 weeks; assessed with: Bowel diary)

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

31/49
(63.3%)¹²

28/49
(57.1%)¹²

RR 1.1 (0.8 to 1.53)

57 more per 1000 (from 114 fewer to

303 more)

⊕⊕⊝⊝
LOW

CRITICAL⁷

¹ polyethylene glycol 3350 plus electrolytes. Starting dose < 7 years 6.9 g/day, 7-11 years 13.8 g/day.The dosage was adjusted over the first week of treatment in periods I and III and could be adjusted in the second week of each treatment period to determine a dose at which symptoms of constipation as defined by the Rome criteria did not occur.
² children with chronic constipation (lasting >3 months), defined as < 3 bowel movements per week and one of the following: pain on defaecation on 25% of days; >25% of bowel movements with straining; >25% of bowel movements with hard/lumpy stools
³ Randomised, double blind, placebo controlled crossover trial. All children entered a 1-week run-in period, during which they were able to continue any laxative treatment that they were already taking (with the exception of high doses of stimulantlaxatives). After this week, they were randomised to receive either PEG+E or matching placebo for 2 weeks, followed by a 2-week placebo washout period before they crossed over to receive the alternative treatment for another 2 weeks
⁴ Thomson: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
⁵ Small sample size
⁶ Thomson: study funded by industry
⁷ Mean score of the 6 working group members
⁸ Studies concerning a chronic condition should consider long-term outcomes
⁹Thomson: scored as 0 = none, 1 = mild, 2 = moderate, 3 = severe Nurko: Scale 0-4: 0 = “too easy-no effort” to 4 = “very difficult-much effort”
¹⁰ Nurko: Straining decreased significantly for those receiving PEG3350 (P= 0.05 for overall difference between groups and placebo; P =0.008 for a dose response trend). Absolute numbers (mean):placebo= -1,2 PEG 3350 0.2 g/kg: -1.1,PEG 3350 0.4 g/kg: -0.9, PEG 3350 0.8 g/kg: -1.1. For analysis, data on 0.4 g/kg are used because this dosage was recommended by the authors
¹¹ Nurko: Dosage 0.4g/kg. Authors stated that this dosage was recommended because it showed similar efficacy with fewer side effects.
¹² None of events were serious and most were judged by the investigator to be moderate or mild in severity. Twenty children (41%) on PEG+E and 22 children (45%) on placebo experienced 41 events and 45 events,respectively, that were judged by the investigator to be at least possibly related to the study treatment. Most of these treatment related events were gastro-intestinal disorders (particularly abdominal pain), which were reported for fewer children on PEG+E (39%, 39 events) than on placebo (45%, 41 events). However, data concerning side-effects are not clear reported

Question: Should Polyethylene glycol vs Placebo be used for functional constipation?^1,2
Settings: children 4 to 16 years with chronic constipation in tertiary outpatient clinics in the United States
Bibliography: Nurko S, Youssef NN, Sabri M, Langseder A, McGowan J, Cleveland M, Di Lorenzo C. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. J Pediatr. 2008;153(2):254-61, 261.e1.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Polyethylene glycol

Placebo

Relative
(95% CI)

Absolute

Defecation frequency 3 or more (response to treatment) (follow-up 2 weeks³; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁴

None

61/79
(77.2%)⁵

10/24
(41.7%)⁵

RR 1.85 (1.14 to 3.02)

354 more per 1000 (from 58 more to 842 more)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁶

Cramping (abd pain) (follow-up 2 weeks³; measured with: Bowel diary⁷; range of scores: 0-4; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁴

None

27⁸

MD 0.5 lower (1.18 lower to 0.18 higher)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁶

Safety/Adverse events 0,2gr/kg (follow-up 2 weeks; assessed with: Diary and laboratory tests⁹)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁴

None

9/26
(34.6%)

14/24
(58.3%)

RR 0.59 (0.32 to 1.11)

239 fewer per 1000 (from 397 fewer to 64 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁶

Safety/Adverse events 0,4 gr/kg (follow-up 2 weeks³; assessed with: Diary and laboratory tests⁹)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁴

None

16/27
(59.3%)

14/24
(58.3%)

RR 1.02 (0.64 to 1.61)

12 more per 1000 (from 210 fewer to 356 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁶

Safety/Adverse events 0,8 gr/kg (follow-up 2 weeks; assessed with: Diary and laboratory tests⁹)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁴

None

17/26
(65.4%)

14/24
(58.3%)

RR 1.12 (0.72 to 1.74)

70 more per 1000 (from 163 fewer to 432 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁶

¹ In different dosages: 0,2 g/kg (n=26), 0.4 g/kg (n=27) and 0.8 gr/kg (n=26)
² Chronic constipation was diagnosed when for at least 3 months there was a history of < 3 spontaneous bowel movements per week and 1 or more associated symptoms: straining, hard stools sensation of incomplete evacuation, production of large bowel movements that may obstruct the toilet, or painful defecation. Patients who were taking other laxatives were included only if they had < 3 BM/wk while taking the laxative, and all laxatives were stopped at least 2 days before the run-in period started
³ Studies concerning a chronic condition should consider long-term outcomes
⁴ Small sample sizes
⁵ A significantly higher proportion of children on PEG3350 responded to treatment compared with placebo (P = 0.026); 42% of children in the placebo group were successfully treated compared with 77%, 74%, and 73% of the 0.2, 0.4, and 0.8 g/kg groups (P =< 0.04 when comparing each group with placebo). There was no difference in the proportion of responders among the different PEG groups
⁶ Mean score of the 6 working group members
⁷ Scale 0-4: 0 = “none” to 4 = “very painful”
⁸ There was no significant difference in the total number of cramping. Absolute numbers (mean): placebo= -0.1 PEG 3350 0.2 g/kg: -0.5,PEG 3350 0.4 g/kg: -0.4, PEG 3350 0.8 g/kg: -0.1. No more precise data were given
⁹ Including chemistry panel, serum osmolarity and liver function tests

Lactulose vs Paraffine

Question: Should Lactulose vs Liquid paraffin be used for Functional constipation?^1,2
Settings: children aged 2–12 years, outpatient pediatric gastroenterology department in Turkey
Bibliography: Urganci N, Akyildiz B, Polat TB..A comparative study: the efficacy of liquid paraffin and lactulose in management of chronic functional constipation. Pediatr Int. 2005;47(1):15-9.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Liquid paraffin

Lactulose

Relative
(95% CI)

Absolute

Defecation frequency (follow-up 8 weeks; measured with: Bowel diary; Better indicated by lower values)

randomised trials

very serious³

no serious inconsistency

no serious indirectness

serious⁴

None

MD 3.7 higher (0.76 to 6.64 higher)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁵

¹ 1 ml/kg twice/day. Dose adapted by 25% every 3 days as is required to yield 2 firm loose stools per day. Max dose is 3ml /kg/day
² Children, 2-12 years, with chronic constipation with at least 2 of the following in the last 3 months: hard stools, painful defecation, rectal bleeding, encopresis and <3 bowel movements weekly
³ Unclear blinding and incomplete reporting of results
⁴ Small sample size
⁵ Mean score of the 6 working group members

Mineral oil (paraffine) vs PEG

Question: Should Mineral oil vs Polyethylene glycol be used for fecal impaction in idiopathic constipation?^1,2,3
Settings: children aged over 2 years in pediatric gastroenterology department in United States
Bibliography: Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of fecal impaction in children. Aliment Pharmacol Ther. 1993 Oct;7(5):523-9.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Mineral oil

Polyethylene glycol

Relative
(95% CI)

Absolute

Defecation frequency (> 1 after treatement) (follow-up 2 days⁴; assessed with: Bowel diary)

randomised trials

very serious⁵

no serious inconsistency

no serious indirectness

serious⁶

None

12/17
(70.6%)

17/19
(89.5%)

RR 0.79 (0.56 to 1.11)

188 fewer per 1000 (from 394 fewer to 98 more)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁷

¹ Mineral oil: 30ml/10 kg
² Polyethylene glycol : 20 ml/kg/h for 4 hours once daily on 2 consecutive days. Unclear from the paper whether this contained electrolytes or not
³ Constipation: infrequent, large, firm to hard stools, rectal pain or bleeding, small amounts of stool daily, incomplete stool evacuation, periodic passage of large amounts of stool, fecal impaction
⁴ Studies concerning a chronic condition should consider long-term outcomes
⁵ No blinding, allocation of concealment and unclear,loss to follow-up>20% in both groups
⁶ small sample size
⁷ Mean score of the 6 working group members

Question: Should Polyethylene glycol vs Liquid paraffin be used for functional constipation?^1,2,3
Settings: Children 2 to 12 years, outpatient clinic in Iran
Bibliography: Rafati M, Karami H, Salehifar E, Karimzadeh A. Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation. Daru. 2011;19(2):154-8.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Polyethylene glycol

Liquid paraffin

Relative
(95% CI)

Absolute

Defecation frequency at day 120 (follow-up 4 months; measured with: Unclear; range of scores: 0-10; Better indicated by lower values)

randomised trials

very serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

MD 1 higher (0.12 to 1.88 higher)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁷

Fecal incontinence frequency at week 4 (follow-up 4 months; assessed with: Unclear.)

randomised trials

very serious⁴

no serious inconsistency

no serious indirectness

serious⁵

none⁶

12/80
(15%)

10/78
(12.8%)

RR 1.17 (0.54 to 2.55)

22 more per 1000 (from 59 fewer to 199 more)

⊕⊝⊝⊝
VERY LOW

CRITICAL⁷

¹ PEG 3350 1.0-1.5 g/kg/day for 4 months
² Liquid paraffin 1.0-1.5 ml/kg/day for 4 months
³ A history of functional constipation (at least 3 months) was defined as < 3 stools/week, more than 1 encopresis/week or palpable abdominal or rectal fecal mass on physical examination
⁴ Unclear allocation of concealment, unclear blinding, no clear data about loss to follow-up and intention to treat principle
⁵ Small sample size
⁶ Sponsored by PEG-industry
⁷ Mean score of the 6 working group members

PEG vs Magnesiumhydroxide

Question: Should Polyethylene glycol vs Milk of magnesia be used for functional constipation and fecal incontinence?¹
Settings: children, 4 -16 years, in tertiary care pediatric clinics in United States
Bibliography: Loening-Baucke V, Pashankar DS. A randomized, prospective, comparison study of polyethylene glycol 3350 without electrolytes and milk of magnesia for children with constipation and fecal incontinence. Pediatrics. 2006;118(2):528-35.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Polyethylene glycol

Milk of magnesia

Relative
(95% CI)

Absolute

Defecation frequency (follow-up 12 months; measured with: Data from parent's verbal report or bowel diary; Better indicated by lower values)

randomised trials

very serious²

no serious inconsistency

no serious indirectness

serious³

None

MD 1.40 lower (3.36 lower to 0.56 higher)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁴

Fecal incontinence frequency (follow-up 12 months; measured with: Data from parent's verbal report or bowel diary; range of scores: 0-100; Better indicated by lower values)

randomised trials

very serious²

no serious inconsistency

no serious indirectness

serious³

None

MD 2.20 higher (3.48 lower to 7.88 higher)

⊕⊝⊝⊝
VERY LOW

CRITICAL⁴

¹ Inclusion criteria were age of ≥4 years and presence of functional constipation with fecal incontinence. Functional constipation was defined by a duration of ≥8 weeks and ≥2 of the following characteristics: frequency of bowel movements of <3 stools per week, >1 episode of fecal incontinence per week, large stools noted in the rectum or felt during abdominal examination, passing of stools so large that they obstructed the toilet, and retentive posturing
² Lack of blinding, high drop-out rate of 7 children in the PEG group and 20 children in the milk of magnesia group at 12 months' follow-up
³ Small sample size
⁴ Mean score of the 6 working group members

Question: Should Polyethylene glycol vs Milk of magnesia be used for functional constipation?^1,2,3
Settings: children, 1-4 years, in outpatient clinic in Thailand
Bibliography: Ratanamongkol P, Lertmaharit S, Jongpiputvanich S. Polyetylene glycol without electrolytes versus milk of magnesia for the treatment of functional constipation in infants and young children: a randomized controlled trial. Asian Biomedicine 3 (4)2009; 391-399.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Polyethylene glycol

Milk of magnesia

Relative
(95% CI)

Absolute

Improvement rate (follow-up 4 weeks; assessed with: Data from parent's verbal report or bowel diary): Proportion of children with 3 or more bowel movements per week, 2 or less episodes of fecal incontinence per month, and no painful defecation, with or without laxative therapy

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

None

42/46
(91.3%)

28/43
(65.1%)

RR 1.4 (1.11 to 1.78)

260 more per 1000 (from 72 more to 508 more)

⊕⊕⊝⊝
LOW

IMPORTANT⁶

Safety/adverse events (follow-up 4 weeks; assessed with: Data from parent's verbal report or bowel diary)

randomised trials

serious⁴

no serious inconsistency

no serious indirectness

serious⁵

None

20/46
(43.5%)⁷

24/43
(55.8%)⁷

RR 0.78 (0.51 to 1.19)

123 fewer per 1000 (from 273 fewer to 106 more)

⊕⊕⊝⊝
LOW

CRITICAL⁶

¹ PEG 4000 without electrolytes: 0.5 gr/kg/day, once daily. Parents were asked to increase the dosage if stools were still hard ( Bristol type 1-3) or not frequent enough and to decrease the dosage if stools were watery or too numerous. Compliance rate was 89%, p=0.041
² Milk of magnesia: 0.5 ml/kg/day once daily. Parents were asked to increase the dosage if stools were still hard ( Bristol 1-3) or not frequent enough and to decrease the dosage if stools were watery or too numerous. Compliance rate was 72 % (p=0.041)
³ According to ROME III-criteria. Median stool frequency was 3 at initial visit. Only 2 patients were suffering from fecal incontinence (one in PEG and 1 in milk of magnesia group).
⁴ Unclear information about blinding
⁵ Small sample size
⁶ Mean score of the 6 working group members

⁷ No serious adverse events occured. No significant differences in adverse events (abdominal pain/discomfort, bloating/flatulence and nausea/vomiting) in both groups, p=0.245. Only children in milk of magnesia group had more diarrhea than those in PEG group (28% vs 4.3%, p=0.002). Diarrhea was resolved by reducing the dosages

Klysma’s (KLYX) vs PEG

Question: Should Rectal medication vs Oral medication be used for fecal impaction in functional constipation?^1,2,3
Settings: Children 4-16 years with functional constipation and rectal fecal impaction in a tertiary outpatient clinic in The Netherlands
Bibliography: Bekkali NL, van den Berg MM, Dijkgraaf MG, van Wijk MP, Bongers ME, Liem O, Benninga MA. Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG. Pediatrics 2009;124(6):e1108-15.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Rectal medication

Oral medication

Relative
(95% CI)

Absolute

Fecal incontinence frequency (follow-up 2 weeks⁴; measured with: Bowel diary; range of scores: 0-50; Better indicated by lower values)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious⁶

None

mean 3.6 lower (8.34 lower to 1.14 higher)

⊕⊕⊝⊝
LOW

CRITICAL⁷

Abdominal pain (follow-up 2 weeks³; assessed with: Bowel diary)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious⁶

None

23/41
(56.1%)

17/39
(43.6%)

RR 1.29 (0.82 to 2.01)

126 more per 1000 (from 78 fewer to 440 more)

⊕⊕⊝⊝
LOW

IMPORTANT⁷

Defecation frequency (follow-up 2 weeks; measured with: Bowel dairy; range of scores: 0-20; Better indicated by lower values)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious⁶

None

mean 1.7 lower (3.98 lower to 0.58 higher)

⊕⊕⊝⊝
LOW

IMPORTANT⁷

¹ Klyx once daily for 6 days (60 ml children < 6 years, and 120 ml for children of 6 years and older). Maintenance therapy was started after 6 days of disimpaction: Movicolon 0.5 g/kg/day for at least 2 weeks (follow-up period)
² PEG 3350 with electrolytes (Movicolon) 1.5 gr/kg per day for 6 days. Maintenance therapy was started after 6 days of disimpaction: Movicolon 0.5 g/kg/day for at least 2 weeks (follow-up period)
³ Rectal fecal impaction and ≥ 1 of the other ROME-III criteria for functional constipation.

⁴ weeks after disimpaction
⁵ Ofcourse no blinding possible for patients and caregivers. However, caregivers fill in diary. No blinding clinician and outcome assessors
⁶Small sample size
⁷ Mean score of the 6 working group members

Overig (additionele toevoeging klysma’s)

Question: Should Education, behavioral strategies, oral laxatives and 3 rectal enemas weekly vs education, behavioral strategies and oral laxatives be used for chronic functional constipation?^1,2,3
Settings: children 8-18 years with chronic functional constipation in a tertiary oupatient clinic in The Netherlands
Bibliography: Bongers ME, van den Berg MM, Reitsma JB, Voskuijl WP, Benninga MA. A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation. Clin Gastroenterol Hepatol. 2009;7(10):1069-74.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Education, behavioral strategies, oral laxatives and 3 rectal enemas weekly

Education, behavioral strategies and oral laxatives

Relative
(95% CI)

Absolute

Abdominal pain (follow-up 52 weeks; assessed with: questionnaire4)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious6

None

10/50
(20%)7

15/50
(30%)7

RR 0.67 (0.33 to 1.34)8

99 fewer per 1000 (from 201 fewer to 102 more)

⊕⊕⊝⊝
LOW

IMPORTANT9

Painful defecation (follow-up 52 weeks; assessed with: questionnaire4)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious6

None

4/50
(8%)7

10/50
(20%)7

RR 0.4 (0.13 to 1.19)10

120 fewer per 1000 (from 174 fewer to 38 more)

⊕⊕⊝⊝
LOW

CRITICAL9

Treatment success: 3 or more bowel movements per week and < 1 fec incontinence episode per week, irrespective of laxative use. (follow-up 52 weeks; assessed with: questionnaire4)

randomised trials

serious⁵

no serious inconsistency

no serious indirectness

serious⁶

None

24/50
(48%)⁷

18/50
(36%)⁷

RR 1.33 (0.83 to 2.13)¹¹

119 more per 1000 (from 61 fewer to 407 more)

⊕⊕⊝⊝
LOW

CRITICAL⁹

¹ 3 rectal enemas were given during the first 3 months. Thereafter, frequency was reduced by 1 enema per week every 3 months.
² PEG starting dose 0,5 g/kg/day. If treatment was considered insufficient, the dose was optimized to a maximum of 1,5 g/kg/day
³ Chronic constipation was defined as constipation according to ROME III criteria for at least 2 years
⁴ Bowel diary
⁵ No blinding doctors and outcome assessors
⁶ Small sample size
⁷ By estimation, absolute numbers not reported
⁸ P=0.36 for overall test for differences between control and intervention group at all time points by using GEE analysis
⁹ Mean score of the 6 working group members
¹⁰ P=0.35 for overall test for differences between control and intervention group at all time points by using GEE analysis
¹¹ Overall treatment success was not significantly different between the 2 groups during trial period : p=0,67