Table 2: Study characteristics of 2 recent studies ...



|QUADAS items |Digital rectal exam |Abdominal radiography (AR) |Ultrasonography |Colonic Transit Time (CTT) |

| |Beckman 2001 |Barr 1979 |Benninga 1995 |Leech 1999 |Çayan 2001 |

| | | |(AR and CTT) | | |

|Beckmann 2001 |251 |2 to 12 |Consecutive children presenting at |Clinical constipation |Fecal loading on abdominal |

| | | |emergency department with |(not further defined) |radiograph according to |

| | | |gastrointestinal symptoms | |Blethyn |

| | | | | |Radiographically proven |

| | | | | |constipation defined as |

| | | | | |grade 1-3. |

Study characteristics of 1 study evaluating the diagnostic value of clinical symptoms and signs related to constipation using constipation on abdominal radiography as reference test

Individual symptoms of constipation related to fecal impaction on abdominal radiography

| |Sensitivity (%) |Specificity (%) |Likelihood Ratio |

| |(95% CI) ref |(95% CI) |(95% CI) |

|Stool present on rectal exam |69 (60 to 78) 16 |57 (45 to 69) |1.6 (1.2 to 2.0) |

|Tenderness left lower quadrant |20 (12 to 29) 16 |91 (82 to 97) |2.3 (0.3 to 4.3) |

|Absence of rebound tenderness |98 (94 to 100) 16 |10 (5 to 17) |1.1 (1.0 to 1.2) |

|History of hard stool |74 (67 to 82) 16 |38 (28 to 49) |1.2 (1.0 to 1.4) |

3.2 What is the diagnostic value of abdominal radiography in the diagnosis of functional constipation in children ?

Study characteristics of 2 recent studies, and 3 studies included in a previous review (Reuchlin et al), all evaluating the diagnostic value of abdominal radiography on diagnosis of idiopathic constipation, using a reference test based on a clinical definition of constipation

|Study |No of patients |Age range |Index test |Cases |Controls |

| |included in |(years) | | | |

| |analysis | | | | |

|Lorijn 2006 |89 |Median 9,8 y |Fecal loading on abdominal |At least two of the |Solitary encopresis and/or |

| | | |radiograph according to Leech et |following: defecation |Soiling without any of the |

| | | |al. Resulting in a score of 0 to |frequency of less than 3 |other criteria of constipation |

| | | |maximum of 15. A total score >9 |times per week; 2 or more |Functional abdominal pain |

| | | |is considered as constipation |episodes of fecal |(N=37) |

| | | | |incontinence per week; | |

| | | | |production of large amounts | |

| | | | |of stool once over a period | |

| | | | |of 7-30 days; the presence of| |

| | | | |a palpable abdominal or | |

| | | | |rectal mass (N=52) | |

|Çayan 2001 |125 |5 to 19 |Fecal loading on abdominal |Less than 3 bowel movements |Children with primary nocturnal|

| | | |radiography according to Blethyn |per week for a period of at |enuresis selected at day care |

| | | | |least 6 months |centers and schools, without |

| | | | | |clinical constipation |

|Leech 1999 |100 |1 mo to 14 y |Abdominal radiography |Children with a clinical |Children who underwent IVP for |

| | | |divided in 3 segments, each |diagnosis of constipation |suspected renal tract disorder.|

| | | |segment given a score from 0 to |(intractable idiopathic |N = 67 |

| | | |5, giving a total score of 0-15. |constipation); | |

| | | |Total score 8-15 indicates |N = 33; | |

| | | |significant constipation. | | |

|Benninga 1995 |101 |5 to 14 |Abdominal radiography |Consecutive children referred|Solitary encopresis and/or |

| | | |scored according to Barr: |for gastrointestinal |soiling without any of the |

| | | |Total score: 0-25; score |complaints. Constipation (pc)|other criteria of |

| | | |of >10 indicates fecal |defined as: at least 2 of the|constipation (N = 30). |

| | | |retention. |following 4 criteria: |Recurrent abdominal pain |

| | | | |Stool frequency 2 soiling/encopresis |least a 3-mo period without any|

| | | | |episodes per week; periodic |of the other symptoms of pc (N |

| | | | |passage of very large amounts|= 14). |

| | | | |of | |

| | | | |stools once every 7-30 d; | |

| | | | |a palpable abdominal or | |

| | | | |rectal mass (N = 57). | |

|Barr 1979 |42 |3 to 7 |Abdominal radiography |Symptomatic stool retention |Children who had abdominal |

| | | |scored according to Barr: |based on evidence of “pellet”|radiography for |

| | | |Total score: 0-25; a |stools, straining, having a |lead ingestion and who did not |

| | | |score of >10 indicated |bowel movement no more often |present with either abdominal |

| | | |fecal retention. |than every 3 d, blood |pain or constipation and who |

| | | | |streaking on stools, very |had blood lead levels >50 μg/dL|

| | | | |large stools, history of |(2.41 μmol/L); |

| | | | |soiling, positive rectal |N = 12; |

| | | | |examination or colonic stool | |

| | | | |palpated on abdominal | |

| | | | |examination. | |

| | | | |Patients with a present | |

| | | | |history of soiling were | |

| | | | |excluded; N = 30; | |

|Study |No of patients |Age range |Index test |Cases |Controls |

| |included in |(years) | | | |

| |analysis | | | | |

|Jackson 2009 |98 radiographs |Cases mean 8,8 |Radiographs resulting |Radiographs from CTT studies |1/Radiographs from children who|

| |from 53 |Controls mean |from CTT according to Metcalf: 24|were designated as |had undergone abdominal |

| |constipated |9,4 |markers each day for 3 days. On |constipated or nonconstipated|radiography for a variety of |

| |children | |day 4 an abdominal radiograph is |according to whether the CTT |indications such as trauma, |

| |100 radiographs| |obtained. If any markers have |was greater than 60 h (75 |ureteric colic, insertion of a |

| |from controls | |passed, no further radiographs |radiographs) |shunt or nonspecific abdominal |

| | | |are obtained. If all markers are | |pain. Case notes were reviewed |

| | | |present, one further radiograph |Constipated children referred|to ensure that constipation was|

| | | |is obtained on day 7. |to a tertiary service, who |not a symptom, and any |

| | | |Radiograps on a not specified day|have failed to improve after |radiographs from children with |

| | | |were scored according to Barr and|at least 3 years of treatment|this symptom were excluded (100|

| | | |Blethyn. |supervised by pediatricians |radiographs) |

| | | |A Barr score ≥ 10 is defined as |in a local hospital. They | |

| | | |constipation. |undergo CTT on a routine |2/CTT radiographs |

| | | | |basis |with a CTT of less than 60 h |

| | | | | |(23 radiographs) . |

Study characteristics of 1 study evaluating the diagnostic value of abdominal radiography on diagnosis of idiopathic constipation, using CTT as reference test

3.3 What is the diagnostic value of Colonic Transit Time in the diagnosis of functional constipation in children ?

Study characteristics of studies evaluating the diagnostic value of Colonic Transit Time (CTT) in the diagnosis of idiopathic constipation

|Study |No of patients |Age range |Index test |Cases |Controls |

| |included in |(years) | | | |

| |analysis | | | | |

|De Lorijn 2006 |89 |Median 9,8 y |CTT according to Bouchacha.. The|At least two of the |Solitary encopresis and/or |

| | | |radiography on day 7 was used to|following: defecation |Soiling without any of the |

| | | |count the number of markers |frequency of less than 3 |other criteria of constipation |

| | | |visible in the colon. Cut-off |times per week; 2 or more |Functional abdominal pain |

| | | |value for constipation is CTT>62|episodes of fecal |(N=37) |

| | | |h |incontinence per week; | |

| | | | |production of large amounts | |

| | | | |of stool once over a period | |

| | | | |of 7-30 days; the presence | |

| | | | |of a palpable abdominal or | |

| | | | |rectal mass (N=52) | |

|Gutiérrez 2002 |60 |2 to 14 |CTT according to Bouchacha. The |Chronic idiopathic |Normal bowel habits (between 3 |

| | | |radiography on day 7 was used to|constipation for more than 6|defecations daily and 3 |

| | | |count the number of markers |months, with or wihout |defecations weekly, without |

| | | |visible in the colon. No |secondary encopresis. (N=30)|straining at stool, and faeces |

| | | |cutt-off value for constipation | |of normal consistency) for at |

| | | |defined | |least 12 month before the |

| | | | | |study; |

|Zaslavsky 1998 |26 |12 to 18 |CTT according to Metcalf. The |Hard stools, difficulty in |No digestive complaints and |

| | | |radiography on day 7 was used to|evacuating, less than 3 |more than 3 bowel movements per|

| | | |count the number of markers |bowel movements a week, no |week |

| | | |visible in the colon. No |evidence of palpable rectal | |

| | | |cutt-off value for constipation |mass, and a history of | |

| | | |defined |constipation of at least 1 | |

| | | | |year’s duration | |

|Benninga 1995 |206 |5 to 14 |CTT according to Metcalf. All |Consecutive children |Solitary encopresis and/or |

| | | |patients ingested 20 markers. |referred for |soiling without any of the |

| | | |Abdominal radiographs were taken|gastrointestinal complaints.|other criteria of constipation |

| | | |at 1, 4, 7, 10, and 13 days. |Constipation (pc) defined |(N = 54). |

| | | |Counting dy not mentioned. The |as: at least 2 of the |Recurrent abdominal pain |

| | | |cut off for delayed total CTT |following 4 criteria: |Severe enough to interfere with|

| | | |was set at 62h |Stool frequency 2 soiling/encopresis |of the other symptoms of pc (N |

| | | | |episodes per week; periodic |= 23). |

| | | | |passage of very large | |

| | | | |amounts of | |

| | | | |stools once every 7-30 d; | |

| | | | |a palpable abdominal or | |

| | | | |rectal mass (N = 129). | |

3.4 What is the diagnostic value of transabdominal rectal ultrasonography in the diagnosis of functional constipation in children ?

Study characteristics of studies evaluating the diagnostic value of rectal ultrasonography in the diagnosis of idiopathic constipation

|Study |No of patients |Age range |Index test |Cases |Controls |

| |included in |(years) | | | |

| |analysis | | | | |

|Bijos 2007 |120 |Not described |A rectopelvic ratio was |Rome II criteria for |Children with a normal |

| | | |calculated by dividing the |constipation (N=15) |defecation pattern who were |

| | | |transverse diameter of the | |diagnosed and treated for |

| | | |rectal ampulla by the transverse| |various symptoms (chronic |

| | | |diameter of the pelvis | |abdominal pain, food allergies)|

| | | | | |(N=105) |

|Singh 2005 |177 |0,3 to 16,4 |Transverse rectal crescent |2 or more of the following: |Children with no bowel problems|

| | | |behind the bladder at |less than 3 bowel movements |or history of constipation |

| | | |ultrasonography. Participants |per week; periodic passage |(N=82) |

| | | |had a partly full bladder at |of a large stool with | |

| | | |examination. |discomfort or pain; a | |

| | | | |palpable abdominal fecal | |

| | | | |mass; fecal soiling in the | |

| | | | |presence of any of the above| |

| | | | |(N=95) | |

|Joensson 1997 |51 |4 to 12 |Transverse rectal diameter |Rome III criteria of |Healthy controls (N=24) |

| | | |behind the bladder at |constipation (N=27) | |

| | | |ultrasonography as described by | | |

| | | |Klijn et al (27). Participants | | |

| | | |had a partly full bladder at | | |

| | | |examination. | | |

|Klijn 1986 |49 |5 to 13 |Transverse rectal diameter |At least 2 of the following:|Urological patients without |

| | | |behind the bladder at |2 or fewer bowel movements |lower tract dysfunction and a |

| | | |ultrasonography. Participants |weekly without laxative |normal defecation pattern |

| | | |had a partly full bladder at |treatment; 2 or more |(N=26) |

| | | |examination. |episodes of fecal soiling | |

| | | | |weekly; periodic passage of | |

| | | | |a large amount of stool once| |

| | | | |every 7 to 30 days; a | |

| | | | |palpable abdominal or rectal| |

| | | | |mass (N=23) | |

Summary of the test characteristics of included studies.

|Source |Number of patients with clinical |Sensitivity |Specificity, |Area under curve |

| |constipation / number of patients |% (95% CI) |% (95% CI) |AUC (95% CI) |

| |without clinical constipation | | | |

|Radiography |

|De Lorijn 2006 |52/37 |75 (61-86) |59 (42-75) |0.68 (0.58-0.80) |

|Çayan 2001 |10/115 |70 (35-93) |99 (95-100) |Not available |

|Leech 1999 |33/67 |76 (58-89) |75 (63-85) |Not available |

|Benninga 1995 |57/44 |60 (46-72) |43 (18-71) |Not available |

|Barr 1979 |30/12 |80 (65-90) |90 (74-98) |Not available |

|CTT |

|De Lorijn 2006 |52/37 |71 (57-83) |95 (82-99) |0.90 (0.83-0.96) |

|Benninga 1995 |129/77 |52 (43-61) |91 (85-97) |Not available |

|Ultrasonography |

|Singh |Not available | | |0,85 (0,79-0,90) |

|Joensson 1997 (26) |27/22 |56 (35-75) |96 (77-99) |Not available |

|Klijn 1986 (27) |23/26 |100 (85-100) |89 (70-98) |Not available |

Diagnostic value of abdominal radiography (clinical constipation as reference test), ultrasonography and CTT in diagnosing clinical constipation

Question 4

Which of the following diagnostic tests should be performed in children with constipation to diagnose an underlying disease?

4.1 Laboratory investigations to diagnose (cow’s milk) allergy, celiac disease, hypothyroidism and hypercalcaemia?

|Study |Quality of |Design |Participants |Patient characteristics |Intervention |Outcome |Follow up and remarks |

| |evidence | | | | | | |

|Bekkali et |A |Cohort |N=158 |Children with intractable|All children underwent |Overall group: |12 weeks |

|al, 2010 | | | |constipation (n = 130; 76|magnetic resonance imaging |MRI revealed lumbosacral spine (LSS) | |

| | | | |males; 6-18 years, mean |(MRI) and a neurologic |abnormalities in 3% (5/152). Neurologic | |

| | | | |duration of symptoms 58 |exami-nation by a pediatric |examination revealed no neurologic |All children with LSS |

| | | | |months (SD 41)), and |neurologist blinded to the |abnormalities in all these 5 patients. |abnormalities |

| | | | |patients with |MRI results. | |experienced |

| | | | |non-retentive fecal | |3 patients were not scheduled for MRI for |relief at the 12-week |

| | | | |incontinence (NRFI) |All children received toilet |unknown reasons and 3 did not undergo MRI: 1 |follow-up without |

| | | | |(n = 28; 18 males; 7-15 |training and a bowel diary. |refused and 2 did not appear for the MRI |neuro-surgical |

| | | | |years, mean duration of | |appointment. |inter-vention. |

| | | | |symptoms 50 months (SD |Constipated children received| | |

| | | | |34)) according to |also: daily rectal enemas |Constipated children: | |

| | | | |ROME-III criteria |during the first 3 days and |MRI of the LSS was abnormal in 4/125 patients | |

| | | | |participated. |subsequently, they received |(3%), including 1 patient with occult spina | |

| | | | | |oral poly-ethylene glycol |bifida (OSB) and 3 patients with a terminal | |

| | | | |All were referred to a |daily. |filum lipoma. Neurologic examina-tion revealed | |

| | | | |tertiary pediatric | |neurologic abnormal-lities in 4 patients with | |

| | | | |motility center | |normal MRI findings. Gluteal cleft deviation | |

| | | | | | |was found in 3 of 4 patients with an abno-mal | |

| | | | | | |MRI. | |

| | | | | | | | |

| | | | | | |Children with NRFI: | |

| | | | | | |MRI was abnormal in 1/27 patients (4%), with | |

| | | | | | |normal neurologic examination findings. No | |

| | | | | | |abnormal neurologic findings were found in this| |

| | | | | | |group of patients. | |

Question 6

What is the additional effect of the following nonpharmacological treatments in children with functional constipation?

Fiber

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 |

|25 |

|25 |

|1 |randomised trials |very serious6 |no serious |no serious |

| | | |inconsistency|indirectness |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |randomised trials |no serious risk of bias |no serious |no serious |

| | | |inconsistency|indirectness |

| | | | | |

|No of studies |

|1 |randomised trials|no serious risk of bias |no serious |no serious |

| | | |inconsistenc|indirectnes|

| | | |y |s |

| | | | | |

|No of studies |

|1 |randomised trials |very serious4 |no serious |no serious |

| | | |inconsisten|indirectness |

| | | |cy | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |very serious4 |no serious |no serious |

| | | |inconsisten|indirectness |

| | | |cy | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |serious4 |no serious |serious5 |

| | | |inconsistency| |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |

|1 |randomised trials |no serious risk of bias |no serious |no serious |

| | | |inconsistency|indirectness |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |

|1 |

|1 |

|1 |randomised trials |no serious risk of bias |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|1 |randomised trials |serious |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |serious3 |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|72 |randomised trials |very serious3 |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|23 |

|37 |randomised trials |serious8 |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|1 |

|1 |

|2 |

|2 |

|1 |randomised trials |serious4 |no serious |no serious |

| | | |inconsistency|indirectness |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |

|1 |

|1 |randomised trials |no serious risk of bias |no serious |no serious |

| | | |inconsistenc|indirectness |

| | | |y | |

| | | | | |

|No of studies |

|1 |randomised trials |very serious3 |no serious |no serious |

| | | |inconsisten|indirectness |

| | | |cy | |

| | | | | |

|No of studies |

|1 |randomised trials |very serious5 |no serious |no serious |

| | | |inconsisten|indirectness |

| | | |cy | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |very serious4 |no serious |no serious |

| | | |inconsisten|indirectness |

| | | |cy | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |very serious2 |no serious|no serious |

| | | |inconsiste|indirectness |

| | | |ncy | |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |serious4 |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |randomised trials |serious5 |no |no serious |

| | | |serious |indirectness |

| | | |inconsist| |

| | | |ency | |

| | | | | |

|No of studies |

|1 |

|1 |

|1 |randomised trials |serious5 |no serious |no serious |

| | | |inconsisten|indirectnes|

| | | |cy |s |

| | | | | |

|No of studies |

|1 |

|1 |randomised trials |very serious4 |no serious |no serious |very serious7 |none |16 |16 |- |

| | | |inconsistency5 |indirectness | | | | | |

|Banasz-kiewi|Pediatric |N=84 |1 yr. |amount of stools in the |training | |month | |constipa-tion and | |

| | |Severity: encopresis frequency: range 3- |rectum) |techniques | | | |encopresis; |P10/day | | | | | |soiling frequency;| |

| | |Excl: age ................
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