Probiotika zur Behandlung von funktionellen Bauchschmerzen bei Kindern
Referencias
References to studies included in this review
References to studies excluded from this review
References to studies awaiting assessment
References to ongoing studies
Additional references
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods | Study design: single‐blinded, placebo‐controlled randomised controlled trial Setting: Valiasr Hospital of Imam Khomeini Hospital Complex, Tehran, Iran Study period: September 2012 to August 2014 | |
| Participants | Inclusion criteria: abdominal pain at least weekly for past 2 months Exclusion criteria: right lower quadrant or right upper quadrant pain, weight loss or growth impairment, dysphagia, vomiting, anaemia, diarrhoea (especially nocturnal), fever, arthritis, familial history of inflammatory bowel disease (IBD) or any abnormal finding in physical examination or primary lab tests. Patients with mentioned red flags and probable diagnosis of abdominal migraine were excluded. Condition duration intervention group 1: > 2 months Condition duration intervention group 2: > 2 months Condition duration control group: > 2 months Concurrent therapy intervention group 1: none stated Concurrent therapy intervention group 2: none stated Concurrent therapy control group: none stated Number randomised to intervention group 1: 40 Number randomised to intervention group 2: 40 Number randomised to control group: 40 Number assessed in intervention group 1: 34 Number assessed in intervention group 2: 29 Number assessed in control group: 25 Age at randomisation intervention group 1: mean 7.06 (SD ± 2.38) Age at randomisation intervention group: mean 7.44 (SD ± 2.44) Age at randomisation control group: mean 7.42 (SD ± 2.49) Sex (M/F) intervention group 1: 19/15 Sex (M/F) intervention group 2: 13/16 Sex (M/F) control group: 8/17 | |
| Interventions | Intervention group 1: Colpermin Intervention group 2: Lactol tablet (Bacillus coagulans + fructo‐oligosaccharide) Control group: folic acid tablet | |
| Outcomes | The outcome measure was changes in the severity, duration and frequency of pain after the 1‐month intervention in each group and between groups. Pain severity assessment was done based on patients’ or their parents’ reports with numbers from 0 to 10 (numerical rating scale). Duration of pain as minutes per day and frequency as pain episodes in a week was assessed. | |
| Notes | Funding source: not stated Author contact: Masoumeh Asgarshirazi, Pediatric Department, Valiasr Hospital, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98‐2166581596, Fax: +98‐2166591315, Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Randomly allocated", but no stated means of randomisation. We emailed the authors about this and received no response. |
| Allocation concealment (selection bias) | Unclear risk | No stated method of allocation concealment. We emailed the authors about this and received no response. |
| Blinding of participants and personnel (performance bias) | High risk | Placebo‐controlled but unclear language about who was blinded. In their discussion the authors mention that this was a single‐blind study and the nurse who administered the questionnaires was blinded. We emailed the authors about this and received no response. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Unclear as above. We emailed the authors about this and received no response. |
| Incomplete outcome data (attrition bias) | Low risk | 88/120 patients completed the 1‐month trial and periodic visits (32 in Colpermin, 29 in Lactol, 25 in the placebo group). 32 patients were excluded during the trial because they did not complete 1‐month drug consumption due to journey or lack of 2‐week visit. |
| Selective reporting (reporting bias) | Low risk | Prospective trial registration with outcomes matching registration. |
| Other bias | Low risk | None. |
| Study characteristics | ||
| Methods | Study design: randomised, double‐blind, controlled trial Setting: Akdeniz University Pediatric Gastroenterology Outpatient Clinic Study period: September 2014 to May 2015 | |
| Participants | Inclusion criteria: ages 4 to 16 Exclusion criteria: none stated Condition duration intervention group 1: not stated Condition duration intervention group 2: not stated Condition duration control group: not stated Concurrent therapy intervention group 1: none stated Concurrent therapy intervention group 2: none stated Concurrent therapy control group: none stated Number randomised to intervention group 1: 26 Number randomised to intervention group 2: 25 Number randomised to control group: 25 Number assessed in intervention group 1: 23 Number assessed in intervention group 2: 24 Number assessed in control group: 24 Age at randomisation intervention group 1: mean 12.33 (SD ± 4.65) Age at randomisation intervention group 2: mean 10.20 (SD ± 3.78) Age at randomisation control group: mean 12.33 (SD ± 4.65) Sex (M/F) intervention group 1: 12/12 Sex (M/F) intervention group 2: 10/14 Sex (M/F) control group: 12/12 | |
| Interventions | Intervention group 1: synbiotic: B. lactis and inulin Intervention group 2: probiotic: B. lactis Control group: prebiotic inulin | |
| Outcomes | The primary endpoint criterion was complete benefit of the patient with resolution of all present complaints with synbiotic or probiotic treatment for 4 weeks The secondary endpoint criterion was resolution at the end of the 4‐week treatment of one or more of the symptoms such as postprandial swelling, belching, abdominal distension, mucoid defecation, difficulty in defecation, feeling of incomplete defecation and urgent defecation | |
| Notes | Funding source: the authors declared that this study has received no financial support Author contact: Ahmet Baştürk; email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The randomisation process was strange: "Patients... were directed to the paediatric gastroenterology nurse and drug boxes that were labelled with code numbers only. The package ingredients were unknown and were randomly given to the patients, thus randomization was provided". Even though this is an unconventional way to randomise a study we deemed that it was low risk as the contents of the packages were unknown to everyone involved and so this method would be similar to throwing a die, for example. |
| Allocation concealment (selection bias) | Low risk | Patients received medication from a gastroenterology nurse. The ingredients of the package were unknown to the doctor, nurse and patient but only the manufacturer knew which code number included which drug. As there were no conflicts of interest involving the manufacturer we think allocation concealment was achieved. |
| Blinding of participants and personnel (performance bias) | Low risk | Same colour, odour, taste and package properties |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded study. |
| Incomplete outcome data (attrition bias) | Unclear risk | Randomisation and adverse effects data are not presented for the 5 patients who could not complete their treatment. We emailed the authors and they responded on 10 December 2020, clarifying the groups where the missing patients had been randomised but did not explain the reasons they discontinued the study. |
| Selective reporting (reporting bias) | Unclear risk | No trial registration mentioned or found. |
| Other bias | Low risk | None |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Children's Medical Centre, Dayton, Ohio Study period: July 2003 to June 2004 | |
| Participants | Inclusion criteria: active symptoms of abdominal pain over a period of at least 2 weeks Exclusion criteria: under the age of 5 or over the age of 21; receiving any medication for the treatment of IBS; receiving drugs known to cause abdominal pain Condition duration intervention group: mean (SD) 18.6 (18.4) months range (1 to 72 months) Condition duration control group: mean (SD) 13.4 (10.9) months range (1 to 49 months) Concurrent therapy intervention group: none Concurrent therapy control group: none Number randomised to intervention group: 32 Number randomised to control group: 32 Number assessed in intervention group: 25 Number assessed in control group: 25 Age at randomisation intervention group: mean 11.6 (3.2) (min 6, max 17) Age at randomisation control group: mean 12.4 (2.9) (min 6, max 17) However authors mention an overall age range of 6 to 20 Sex (M/F) intervention group: 6/19 Sex (M/F) control group: 4/21 | |
| Interventions | Intervention group: Lactobacillus GG Control group: placebo | |
| Outcomes | The primary outcome was the change in abdominal pain severity score from baseline to the end of the treatment period. Secondary outcomes included the number of responders versus non‐responders in each group and changes in the remaining symptoms of the GSRS by syndrome. Patients were classified as responders if they experienced a decrease in abdominal pain severity of 1 or more levels (1 point or more) on the 4‐point Likert scale from baseline to the end of treatment. Baseline abdominal pain and other GSRS scores were averaged from the daily scores recorded by the patients/parents during the week preceding treatment. Post‐treatment scores were averaged for each week of data collected after baseline measurements. | |
| Notes | Funding source: not stated Author contact: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated random list. |
| Allocation concealment (selection bias) | Low risk | A pharmacy separate to the study generated the random list, and each patient was assigned by the central pharmacy in order of entry by the study. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical taste, appearance and colour. |
| Blinding of outcome assessment (detection bias) | Low risk | The code was revealed by the vendor after recruitment, data collection and statistical |
| Incomplete outcome data (attrition bias) | Low risk | Study flow described in detail. 22% of patients withdrew or were lost to follow‐up and not included in the analysis, however this was balanced between groups. |
| Selective reporting (reporting bias) | Unclear risk | All outcomes from the methods were reported, appropriate and complete. No trial registration was mentioned or found. |
| Other bias | Low risk | Baseline characteristics were balanced between groups. |
| Study characteristics | ||
| Methods | Study design: randomised, double‐blind, placebo‐controlled trial Setting: Gastroenterology Clinic of Ayatollah Mousavi Hospital, Zanjan, Iran Study period: 2012 to 2013 | |
| Participants | Inclusion criteria: age 4 to 16 Exclusion criteria: abdominal pain with known organic cause; history of abdominal and gastrointestinal surgery; FTT or weight loss more than 5% of body weight; any abnormal paraclinical finding including complete blood count, urinalysis, stool examination for occult blood, biochemistry, abdominal ultrasound, liver function tests, serum amylase and lipase; history of drug use in the past 3 months including antidepressants or laxatives; any kind of chronic illness; history of abdomen blunt trauma Condition duration intervention group: > 2 months Condition duration control group: > 2 months Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 40 Number randomised to control group: 40 Number assessed in intervention group: 40 Number assessed in control group: 40 Age at randomisation intervention group: mean 6.26 (SD ± 2.10) Age at randomisation control group: mean 6.26 (SD ± 2.61) Sex (M/F) intervention group: 20/20 Sex (M/F) control group: 21/19 | |
| Interventions | Intervention group: Lactobacillus reuteri Control group: placebo | |
| Outcomes | During follow‐up the researcher assessed intensity pain scores, frequency of pain and ultimately response to treatment | |
| Notes | Funding source: financial support was provided by the Vice Chancellor for Research of Zanjan University of Medical Sciences Author contact: Kambiz Eftekhari, Department of Pediatrics, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98‐2173013000, Fax: +98‐2177568809, Email: k‐[email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation. |
| Allocation concealment (selection bias) | Low risk | Not described adequately. Emailed the author and confirmed on 16 July 2019 that a staff member "not involved in the research" was used and therefore ensured allocation concealment of the computer‐generated number list. |
| Blinding of participants and personnel (performance bias) | Low risk | The physicians and the patients were unaware of the contents of the medications prescribed (double‐blind study). |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded study. |
| Incomplete outcome data (attrition bias) | Low risk | All randomised patients completed the study and were included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | Conflicting reporting of the results for the primary outcomes. The protocol IRCT2014083018971N1 was retrospectively registered (22 September 2014). We emailed the authors about this and received no response. |
| Other bias | Low risk | No other concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Southern Italy Study period: 2004 to 2008 | |
| Participants | Inclusion criteria: aged 5 to 14 Exclusion criteria: any chronic diseases; received treatment with antibiotics/probiotics in the previous 2 months; had a pain history suggestive of functional dyspepsia/aerophagia/abdominal migraine; exhibited growth failure; had gastroparesis; had gastrointestinal obstructions/stricture; displayed alarming signs of organic conditions; had previous abdominal surgery; had abnormal baseline test results (including complete blood counts; erythrocyte sedimentation rate; liver‐pancreas‐kidney function tests; tissue transglutaminase with immunoglobulin A measurement; stool examination for occult blood, ova and parasites; faecal calprotectin; urinalysis; 13C‐urea breath test; and abdominal ultrasound) Condition duration intervention group: mean (SD) 2.1 (1.7) years Condition duration control group: mean (SD) 2.6 (2.5) years Concurrent therapy intervention group: not reported Concurrent therapy control group: not reported Number randomised to intervention group: 71 Number randomised to control group: 70 Number assessed in intervention group: 69 Number assessed in control group: 67 Age at randomisation intervention group: mean 6.5 (SD ± 2.1) Age at randomisation control group: mean 6.3 (SD ± 2.0) Sex (M/F) intervention group: 43/24 Sex (M/F) control group: 35/23 | |
| Interventions | Intervention group: oral Lactobacillus GG Control group: placebo | |
| Outcomes | The primary outcome was the change in abdominal pain (frequency/severity) according to the VAS score from baseline to the end of the treatment period. We chose pain as the primary outcome measure consistent with the proposed points to consider for IBS trials. Secondary outcomes were (1) a decrease of at least 50% in the number of episodes and intensity of pain (treatment success), (2) a decrease in the perception of children’s pain according to their parents, and (3) modification of intestinal permeability. | |
| Notes | Funding source: the authors have indicated they have no financial relationships relevant to this article to disclose. Author contact: Ruggiero Francavilla, MD, PhD, Clinica Pediatrica “B. Trambusti,” Piazza Giulio Cesare, 11‐Policlinico, Bari, Italy. Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Children were assigned consecutive numbers, starting with the lowest number available, and were randomly assigned, with the use of a computer‐generated randomisation list created by using a permuted block design, |
| Allocation concealment (selection bias) | Low risk | Group assignment was concealed from participants and investigators. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical in size, taste and appearance. |
| Blinding of outcome assessment (detection bias) | Low risk | Adequate blinding. |
| Incomplete outcome data (attrition bias) | Low risk | Only 4% of randomised patients not included in the analysis. |
| Selective reporting (reporting bias) | Low risk | Prospective trial registration. All outcomes reported appropriately and in line with study plan. |
| Other bias | Low risk | No other concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw Study period: October 2003 to May 2006 | |
| Participants | Inclusion criteria: aged 6 to 16 Exclusion criteria: organic disease (as established by medical history, complete blood count, urinalysis, stool examination for occult blood, ova and parasites, blood chemistries, abdominal ultrasound, breath hydrogen testing and endoscopy, if needed), other chronic disease and growth failure Condition duration intervention group: > 12 weeks Condition duration control group: > 12 weeks Concurrent therapy intervention group: 16 use of drug treatment for abdominal pain Concurrent therapy control group: 15 use of drug treatment for abdominal pain Number randomised to intervention group: 52 Number randomised to control group: 52 Number assessed in intervention group: 52 Number assessed in control group: 52 Age at randomisation intervention group: mean 11.9 (SD ± 3) Age at randomisation control group: mean 11.2 (SD ± 2.7) Sex (M/F) intervention group: 29/23 Sex (M/F) control group: 19/33 | |
| Interventions | Intervention group: Lactobacillus GG Control group: placebo | |
| Outcomes | The primary outcome measure was treatment success defined as no pain (a relaxed face, score of 0, on the Faces Pain Scale) at the end of the intervention The secondary outcome measures were improvements defined as a change in (1) the Faces Pain Scale by at least 2 faces scores; (2) self‐reported severity of pain during the preceding week measured on the Faces Pain Scale; (3) self‐reported frequency of pain during the preceding week; (4) use of medication for abdominal pain and (5) school absenteeism because of abdominal pain | |
| Notes | Funding source: grant from the Medical University of Warsaw Author contact: Prof. H. Szajewska, The Second Department of Paediatrics, The Medical University of Warsaw, 01–184 Warsaw, Dzialdowska 1, Poland. Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated list. |
| Allocation concealment (selection bias) | Low risk | Not specified. Emailed the author and received a response on 27 June 2018 confirming sealed, opaque envelopes. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical active and placebo treatments. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | All randomised participants included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | No trial registration mentioned or found. All expected outcomes reported. |
| Other bias | Low risk | There is a gender imbalance between the intervention (29/23) and control (19/33) groups but we did not think it posed a high risk of bias. |
| Study characteristics | ||
| Methods | Study design: randomised, double‐blind, placebo‐controlled, cross‐over trial Setting: Naples and Foggia, Italy Study period: January 2014 to December 2014 | |
| Participants | Inclusion criteria: ages 8 to 17 Exclusion criteria: chronic organic gastrointestinal diseases; previous abdominal surgery, diseases affecting bowel motility, or concomitant psychiatric, neurological, metabolic, renal, hepatic, infectious, haematological, cardiovascular or pulmonary disorders; patients treated with antibiotics, proton‐pump inhibitors, H2 antagonists or receiving any commercial preparation of probiotics during the previous 3 months Condition duration intervention group: not stated Condition duration control group: not stated Concurrent therapy intervention group: not stated Concurrent therapy control group: not stated Number randomised to intervention group: 78 total patients randomised (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number randomised to control group: 78 total patients randomised (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number assessed in intervention group: 75 total patients assessed (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number assessed in control group: 75 total patients assessed (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Age at randomisation IBS: median 11.2 (range 8 to 17.9) Age at randomisation FD: median 11.6 (range 8 to 16.6) Sex (M/F) IBS: 21/27 Sex (M/F) FD: 11/14 | |
| Interventions | Intervention group: bifidobacteria Control group: placebo | |
| Outcomes | The main outcome parameter considered was AP resolution, defined as no episodes of pain during the treatment period, as reported in the questionnaire of symptoms | |
| Notes | Funding source: none stated Author contact: Annamaria Staiano, MD, Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Via S. Pansini, Naples 5‐80131, Italy (email: [email protected]) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Described randomisation according to a computer‐generated table. |
| Allocation concealment (selection bias) | Low risk | We contacted the author and received a response from Prof Staiano on 11 November 2020 confirming that each assignment was in sealed opaque envelopes that were opened sequentially. |
| Blinding of participants and personnel (performance bias) | Low risk | Double‐blinded study. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded and author responded and confirmed this was also the case for those assessing outcomes. |
| Incomplete outcome data (attrition bias) | Low risk | 5/78 patients not included in the analysis; reasons given in the paper. |
| Selective reporting (reporting bias) | Unclear risk | Trial registered after enrolment complete and posted to NCT after completion of trial period. The outcomes are reported as presented in the methods section. |
| Other bias | Unclear risk | The results are unclear as the authors have combined pre‐ and post‐cross‐over data and present their results per condition (FD and IBS) instead of per intervention and control group. They have not provided randomisation numbers for each therapy. We emailed the authors about this and received no response. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled, cross‐over trial Setting: 5 paediatric tertiary care centres located in Italy (4) and in India (1) Study period: April 2006 to October 2007 | |
| Participants | Inclusion criteria: ages 4 to 18 Exclusion criteria: any chronic organic gastrointestinal disorders, as assessed by full clinical history and examination, and supported by normal results of initial limited laboratory investigation; any disease that may affect bowel motility such as diabetes mellitus, sarcoidosis, connective tissue disease or poorly controlled hypo‐/hyperthyroidism; previous abdominal surgery, as well as significant concomitant psychiatric, neurological, metabolic, renal, hepatic, infectious, haematological, cardiovascular or pulmonary illnesses; patients who had been using any commercial preparation of probiotics during the previous 3 months Condition duration intervention group: > 12 weeks Condition duration control group: > 12 weeks Concurrent therapy intervention group: none allowed Concurrent therapy control group: none allowed Number randomised to intervention group: 67 total patients randomised (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number randomised to control group: 67 total patients randomised (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number assessed in intervention group: 59 total patients assessed (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Number assessed in control group: 59 total patients assessed (it is a cross‐over trial and the authors have combined pre‐ and post‐cross‐over data in the presentation of their results) Age at randomisation mean 12.5 (range 5 to 18) Sex (M/F): 31/28 | |
| Interventions | Intervention group: patented probiotic preparation Control group: placebo | |
| Outcomes | The primary endpoint was improvement in the participant’s global assessment of relief (SGARC) | |
| Notes | Funding source: locally available grants. There was no industry support except for providing product and placebo. No extramural financial support was provided for this investigator‐initiated study. Author contact: Stefano Guandalini, MD, Professor of Pediatrics, University of Chicago Section of Pediatric Gastroenterology, Hepatology and Nutrition, 5839 S. Maryland Ave, MC 4065, Chicago, IL 60637 (email: [email protected]) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated list. |
| Allocation concealment (selection bias) | Low risk | Central pharmacy dispensed medication. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical products and double‐blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | Only 8/67 randomised patients not included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | No trial registration mentioned or found. Outcomes are reported as presented in the methods section. |
| Other bias | Unclear risk | The results are unclear as the authors have combined pre‐ and post‐ cross‐over data. We emailed the authors for clarification and received no response. |
| Study characteristics | ||
| Methods | Study design: randomised, double‐blind, placebo‐controlled trial Setting: referral centre for Paediatric Gastroenterology, Children's Hospital, Zagreb Study period: May 2012 to December 2014 | |
| Participants | Inclusion criteria: age 4 to 18 with diagnosis of FAP or IBS according to Rome III criteria Exclusion criteria: known or suspected immunodeficiency, treatment with probiotic and/or prebiotic products 7 days before enrolment, known neoplastic disorder or any chronic disease, and presence of ‘red flags’ for other organic disease Condition duration intervention group: not stated Condition duration control group: not stated Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 26 Number randomised to control group: 29 Number assessed in intervention group: 26 Number assessed in control group: 29 Age at randomisation intervention group: median 10.5, IQR 5.4 to 17 Age at randomisation control group: median 9.5, IQR 5.5 to 16.5 Sex (M/F) intervention group: 11/15 Sex (M/F) control group: 12/17 | |
| Interventions | Intervention group: L. reuteri DSM 17938 Control group: placebo | |
| Outcomes | Primary endpoints were number of days without pain and difference in the duration of the pain in minutes between the beginning and end of the study; difference in the severity of the pain assessed by the Faces scale between the beginning and the end of the study Secondary endpoints were severity of the pain assessed by the Faces scale during the first, second, third and fourth month; duration of pain in minutes during the first 2 and the last 2 months | |
| Notes | Funding source: probiotic and placebo provided by Biogaia Author contact: Iva Hojsak, MD, PhD, referral centre for Pediatric Gastroenterology and Nutrition, Children’s Hospital Zagreb, Klaic´eva 16, 10000 Zagreb, Croatia (email: [email protected]) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random allocation software. |
| Allocation concealment (selection bias) | Low risk | Opaque, sealed envelopes opened sequentially. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical and packaged. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors not aware of allocation. |
| Incomplete outcome data (attrition bias) | Low risk | All randomised patients included in the analysis. Because of a low recruitment rate it was decided among the researchers that an interim analysis would be performed after 55 children were recruited. |
| Selective reporting (reporting bias) | Unclear risk | Baseline data for severity and frequency of pain are not clear. Study protocol prospectively registered (NCT01587846). Protocol presents as an outcome only the intensity of pain and outcomes for chronic constipation, which was not finally included. In a pooled analysis they performed (Jadrešin 2020), the results are different to those presented here. |
| Other bias | Low risk | More girls than boys in total (32 girls/23 boys) but we did not think this posed a risk of bias. |
| Study characteristics | ||
| Methods | Study design: randomised, double‐blind, placebo‐controlled trial Setting: referral centre for Paediatric Gastroenterology, Children's Hospital, Zagreb Study period: January 2017 to March 2019 | |
| Participants | Inclusion criteria: age 4 to 18 with diagnosis of FAP or IBS according to Rome III criteria Exclusion criteria: known or suspected immunodeficiency, treatment with probiotic and/or prebiotic products 7 days before enrolment, known neoplastic disorder or any chronic disease, and presence of ‘red flags’ for other organic disease Condition duration intervention group: none stated Condition duration control group: none stated Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 24 Number randomised to control group: 22 Number assessed in intervention group: 24 Number assessed in control group: 22 Age at randomisation intervention group: median age 10.1 years, range 5 to 17 years Age at randomisation control group: median age 10.6 years, range 5 to 17 years Sex (M/F) intervention group: 13/11 Sex (M/F) control group: 9/13 | |
| Interventions | Intervention group: L. reuteri DSM 17938 Control group: placebo | |
| Outcomes | Primary endpoints were: number of days without pain; difference in the duration of the pain in minutes between beginning and the end of the study; difference in the severity of the pain assessed between beginning and the end of the study Secondary endpoints were: severity of the pain assessed by VAS during the 1st, 2nd, 3rd and 4th month; duration of pain in minutes during first 2 and last 2 months Secondary endpoint was to assess difference in the severity of pain between beginning and end of the study in each group. This seems to have been added retrospectively. Exploratory variables included: number of days without school/activities (absence from school or other activities due to pain); complete resolution of abdominal pain until the end of the study (number of children). This also seems to have been retrospectively added. | |
| Notes | Funding source: probiotic and placebo provided by Biogaia Author contact: not given Other: this is a second analysis after the interim analysis from Jadrešin 2017; the data above are from the second analysis only and not pooled data | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random allocation software. |
| Allocation concealment (selection bias) | Low risk | Opaque, sealed envelopes opened sequentially. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical and packaged. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors not aware of allocation. |
| Incomplete outcome data (attrition bias) | Low risk | All randomised patients included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | Baseline data for severity and frequency of pain are not clear. Study protocol prospectively registered (NCT01587846) is the same as for Jadrešin 2017. Protocol presents as an outcome only the intensity of pain and outcomes for chronic constipation, which was not finally included. In a pooled analysis they performed (Jadrešin 2020), the results are different to those presented here. |
| Other bias | Low risk | No concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Dr. Sheikh Hospital, Mashhad University of Medical Sciences, Iran Study period: August 2012 to September 2012 | |
| Participants | Inclusion criteria: aged 4 to 18 Exclusion criteria: "Differential diagnoses must have been excluded by laboratory evaluation"; patients taking any drugs or had underlying diseases (cardiac disease, renal disease, asthma, failure to thrive, cystic fibrosis) Condition duration intervention group: > 2 weeks Condition duration control group: > 2 weeks Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised (not reported per group): initially 60 patients were randomised but 5 were excluded due to lack of follow‐up and 3 because they had to start antibiotics. It is not mentioned to which groups they had been randomised. Number assessed in intervention group: 26 Number assessed in control group: 26 Age at randomisation intervention group: mean 6.8 (SD ± 0.4) Age at randomisation control group: mean 7.3 (SD ± 0.5) Sex (M/F) intervention group: 13/13 Sex (M/F) control group: 14/12 | |
| Interventions | Intervention group: Lactobacillus GG Control group: placebo (inulin) | |
| Outcomes | The primary outcome was any change in the severity of the patients’ pain, on a 5‐point Likert scale Secondary outcomes were changes of the functional scale, stool patterns and associated problems | |
| Notes | Funding source: grant from the Vice Chancellor for Research at the Mashhad University of Medical Sciences Author contact: Assistant Professor Dr. Maryam Khalesi, Department of Pediatrics, Ghaem Medical Center, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98.5138012469, +98.9151037242, Fax: +98.5138417451, Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated list using a block design. |
| Allocation concealment (selection bias) | Unclear risk | No details given. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical, with blinding of both investigators and patient. |
| Blinding of outcome assessment (detection bias) | Low risk | Identical, with blinding of both investigators and patient. |
| Incomplete outcome data (attrition bias) | Low risk | Initially 60 patients were randomised but 5 were excluded due to lack of follow‐up and 3 because they had to start antibiotics. It is not mentioned to which groups they had been randomised. |
| Selective reporting (reporting bias) | Low risk | All reported. Trial registered while recruiting: IRCT201205219825N1. The trial registration outcomes correspond with those outlined in the paper. |
| Other bias | Low risk | No concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: university hospitals of Athens in Greece, Ljubljana in Slovenia and Warsaw in Poland Study period: January 2013 to December 2015 | |
| Participants | Inclusion criteria: aged 5 to 16, pain of at least 40 mm on a 0 to 100 mm VAS Exclusion criteria: chronic illness; prior surgery of the gastrointestinal tract; a weight loss of 5% or more over the preceding 3 months; exposure to any drugs for FAP in the past 2 weeks; exposure to probiotics or antibiotics in the 4 weeks before the study; participation in other interventional clinical trials in the past 3 months; special dietary needs or any symptoms or signs of organic disease Condition duration intervention group: not stated Condition duration control group: not stated Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 27 Number randomised to control group: 27 Number assessed in intervention group: 26 Number assessed in control group: 26 Age at randomisation intervention group: mean 9.2 (SD ± 4.3) Age at randomisation control group: mean 9.0 (SD ± 3.2) Sex (M/F) intervention group: 14/13 Sex (M/F) control group: 11/16 | |
| Interventions | Intervention group: Lactobacillus reuteri DSM 17938 Control group: placebo | |
| Outcomes | The primary endpoints were the reduction in pain frequency and pain intensity in the L. reuteri group compared with the placebo group over the 4‐week treatment period, which were measured by the participants’ diaries. There were also a number of secondary endpoints, which were measured and compared in the L. reuteri and the placebo groups at the end of treatment and at the end of the follow‐up period compared to baseline. These were as follows: (1) any reduction in the frequency and intensity of other gastrointestinal symptoms, as measured by the GSRS; (2) any reduction in the days when the child was absent from school or could not take part in other activities due to abdominal pain; (3) any reduction in the days that parents were absent from work to care for their child; (4) any reduction in need for drugs to relieve pain. In addition, the treatment success rate, defined as a reduction in the pain score of more than 50%, was measured at 4 and at 8 weeks. | |
| Notes | Funding source: the study was funded by a non‐restricted grant from BioGaia, Sweden Author contact: email: a.papadopoulou@paidon‐agiasofia.gr | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Method of randomisation described, using computer software. |
| Allocation concealment (selection bias) | Low risk | Not specified in methods. Contacted author and reply received on 27 June 2018 confirming appropriate allocation concealment of randomised list. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical active and placebo treatments. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | All patients accounted for. |
| Selective reporting (reporting bias) | Low risk | Outcomes reported. The protocol was prospectively registered (NCT01719107). The protocol outcomes correspond with the stated outcomes in the paper. |
| Other bias | Low risk | No other concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Uludag University Medical Faculty Study period: January 2015 to May 2015 | |
| Participants | Inclusion criteria: not stated Exclusion criteria: not stated Condition duration intervention group: not stated Condition duration control group: not stated Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 39 Number randomised to control group: 41 Number assessed in intervention group: 39 Number assessed in control group: 41 Age at randomisation intervention group: not broken down by arm of trial Age at randomisation control group: not broken down by arm of trial Sex (M/F) intervention group: not broken down by arm of trial Sex (M/F) control group: not broken down by arm of trial | |
| Interventions | Intervention group: synbiotic Control group: placebo | |
| Outcomes | Pain intensity and frequency, number of days of school without attendance, limitation of daily activities and serum levels of proinflammatory (TNF alpha, IFN gamma) and anti‐inflammatory (IL‐10, TGF beta, IL‐13) cytokines were evaluated both at the beginning and at the end of the study. Treatment success (resolution of pain) and rate of reduction of complaints were also evaluated following the treatment. | |
| Notes | Funding source: not declared Author contact: T.B. Ozkan, Uludag University, Faculty of Medicine, Pediatric Gastroenterology, Bursa, Turkey | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised by time of admission to trial; no further details provided. We have contacted the author and have not received a response. |
| Allocation concealment (selection bias) | Unclear risk | Not specified in methods. We have contacted the author and have not received a response. |
| Blinding of participants and personnel (performance bias) | Low risk | Described as double‐blind. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Unclear risk | Unclear: no information on patient flow in the abstract. We have contacted the author and have not received a response. |
| Selective reporting (reporting bias) | Unclear risk | All outcomes reported as stated but the methodology is not described. No protocol available and no full methods as abstract only. |
| Other bias | Low risk | No other concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Tehran University of Medical Sciences, Tehran, Iran Study period: June 2017 to June 2018 | |
| Participants | Inclusion criteria: aged 6 to 16 years with diagnosis of FAP according to the Rome III criteria Exclusion criteria: the presence of any one of the red flag items; use of antibiotics in the last 1 month, organic disorder based on clinical and paraclinical findings; participants or parents who did not co‐operate in regards to medications and referrals Condition duration intervention group: not specified Condition duration control group: not specified Concurrent therapy intervention group: none mentioned Concurrent therapy control group: none mentioned Number randomised to intervention group: 65 Number randomised to control group: 60 Number assessed in intervention group: 65 Number assessed in control group: 60 Age at randomisation intervention group: 6 to 16 years (7.3 ± 1.7) Age at randomisation control group: 6 to 16 years (7.7 ± 2.1) Sex (M/F) intervention group: 27/38 Sex (M/F) control group: 30/30 | |
| Interventions | Intervention group: L. reuteri Control group: placebo | |
| Outcomes | Pain intensity based on the WBFPRS 2 (Wang‐Baker FACES Pain Rating Scale); frequency of pain and recurrence; duration of each episode of pain; pattern of pain (colic cramps or permanent); the number of days that day‐to‐day activities affected (such as school absenteeism); the need for other medications to relieve pain | |
| Notes | Funding source: Research Funding Centre, Tehran University of Medical Sciences, Iran Author contact: Alireza Moradzadeh, MD, Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Randomly assigned into two groups as quadruple blocks of case and control using Block‐Randomization method" |
| Allocation concealment (selection bias) | Unclear risk | No information on allocation concealment given. |
| Blinding of participants and personnel (performance bias) | Low risk | Similar in the shape, size and taste. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Unclear risk | All patients accounted for; unclear how many patients were excluded on the basis of the exclusion criteria versus how many were excluded for non‐compliance. |
| Selective reporting (reporting bias) | Unclear risk | No trial registration mentioned or found. All expected outcomes reported. |
| Other bias | Low risk | Well‐balanced groups. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial, multi‐centre Setting: paediatric departments of the Universities of Messina, Palermo, Catania and the Pediatric Unit of Vittoria (Sicily) Study period: not stated | |
| Participants | Inclusion criteria: aged 6 to 16 Exclusion criteria: organic disease (established by medical history, complete blood count, urine analysis, stool examination for occult blood and parasites, abdominal ultrasound and screening for celiac disease), other chronic disease and growth failure Condition duration intervention group: not specified Condition duration control group: not specified Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 32 Number randomised to control group: 28 Number assessed in intervention group: 2 were lost due to poor compliance but unclear if included in the analysis Number assessed in control group: 2 were lost due to poor compliance but unclear if included in the analysis Age at randomisation intervention group: mean 10.2 (SD ± 2.5) Age at randomisation control group: mean 9.6 (SD ± 0.4) Sex (M/F) intervention group: 14/16 Sex (M/F) control group: 11/15 | |
| Interventions | Intervention group: L. reuteri DSM 17938 Control group: placebo | |
| Outcomes | The primary outcome was defined as the reduction of the intensity of FAP and the secondary outcome was the reduction of the frequency of the symptoms. | |
| Notes | Funding source: not stated Author contact: Claudio Romano, Gastroenterology and Endoscopy Section, Genetic and Immunology Unit, Department of Pediatrics, University of Messina, 98122 Messina, Italy. Fax: +390902217005; email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated list. |
| Allocation concealment (selection bias) | Low risk | Randomisation list was retained by the dispensing pharmacist at each centre to ensure allocation concealment. This was also confirmed to us by the author. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical active and placebo treatments. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | Two children from each group were lost to completion due to poor compliance; unclear if they were included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | No trial registration mentioned or found. All methods section outcomes reported, but in graph‐bars with no data numbers provided. The number of participants the results were based on is also unclear: whether it was the total number randomised or without the children lost due to poor compliance. |
| Other bias | Low risk | No concerns. |
| Study characteristics | ||
| Methods | Study design: randomised controlled trial Setting: Belcolle Hospital, Italy Study period: not stated | |
| Participants | Inclusion criteria: children with functional abdominal pain Exclusion criteria: not stated Condition duration intervention group: not stated Condition duration control group: not stated Concurrent therapy intervention group: not stated Concurrent therapy control group: not stated Number randomised to intervention group: not stated (61 in total) Number randomised to control group: not stated (61 in total) Number assessed in intervention group: not stated Number assessed in control group: not stated Age at randomisation intervention group: not stated Age at randomisation control group: not stated Sex (M/F) intervention group: not stated Sex (M/F) control group: not stated | |
| Interventions | Intervention group: Lactobacillus GG Control group: placebo | |
| Outcomes | Frequency and severity of abdominal pain | |
| Notes | Funding source: not stated Author contact: not stated and could not find any | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised but no information. We could not contact the author. |
| Allocation concealment (selection bias) | Unclear risk | No information and we could not contact the author. |
| Blinding of participants and personnel (performance bias) | Low risk | Double‐blind study, placebo‐controlled. |
| Blinding of outcome assessment (detection bias) | Unclear risk | No information and we could not contact the author. |
| Incomplete outcome data (attrition bias) | Unclear risk | No information on patient flow and we could not contact the author. |
| Selective reporting (reporting bias) | Unclear risk | The authors only state that their results were significant and we could not contact the author. |
| Other bias | Unclear risk | No information to judge and we could not contact the author. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Isfahan, Iran Study period: February 2013 to December 2013 | |
| Participants | Inclusion criteria: aged 6 to 18 Exclusion criteria: those with organic diseases as the cause of abdominal pain, other concomitant gastrointestinal disorders, or immune‐compromised conditions, and those with recent history (preceding 2 months) of or current treatment with antibiotics, antidepressants, antispasmodics or probiotics were not included in the study Condition duration intervention group: > 2 months Condition duration control group: > 2 months Concurrent therapy intervention group: none stated Concurrent therapy control group: none stated Number randomised to intervention group: 59 Number randomised to control group: 56 Number assessed in intervention group: 45 Number assessed in control group: 43 Age at randomisation intervention group: mean 9.0 (SD ± 2.2) Age at randomisation control group: mean 8.5 (SD ± 2.2) Sex (M/F) intervention group: 25/20 Sex (M/F) control group: 24/19 | |
| Interventions | Intervention group: Bacillus coagulans Control group: placebo | |
| Outcomes | The primary outcome measure was treatment response, defined as at least a 2‐point reduction in the Wong‐Baker FACES Pain Rating Scale or “no pain” after medication Secondary outcomes included the physician‐rated global severity and improvement using the Clinical Global Impression Severity and Improvement scales (control groupI‐S, control groupI‐I), scored 1 to 7 | |
| Notes | Funding source: Isfahan University of Medical Sciences Author contact: Zahra Pourmoghaddas, MD, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated list. |
| Allocation concealment (selection bias) | Low risk | Dispensed by central pharmacy. |
| Blinding of participants and personnel (performance bias) | Low risk | States double‐blinded, with confirmation that the bottles and preparations ensured blinding of participant and physician. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | 27 (13/14) randomised participants in total not included in the final analysis but all the reasons are explained and the numbers are well balanced between groups. |
| Selective reporting (reporting bias) | Unclear risk | Prospective trial registration; report appears to be partial results as the trial registration mentions 2 further groups receiving citalopram and mebeverine. Outcomes described in registration do not completely match those described in report, mentions use of Wong‐Baker scale but not that reduction of 2 points or 'no pain' would be defined as 'treatment response'. |
| Other bias | Low risk | No other concerns. |
| Study characteristics | ||
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial Setting: Soroka Medical Center, Israel and at 3 community childcare centres in the Beer‐Sheva area Study period: March 2011 to October 2013 | |
| Participants | Inclusion criteria: aged 6 to 15 Exclusion criteria: chronic illness, growth failure, previous abdominal surgery, or any alarming signs of organic conditions (such as vomiting, chronic diarrhoea, bloody stools); 16 participants who were treated with antibiotics, probiotics or prebiotics in the previous 8 weeks were excluded Condition duration intervention group: 1.8 (1.4) mean (SD) years Condition duration control group: 2.2 (1.9) mean (SD) years Concurrent therapy intervention group: only stated that 13/47 were using drugs for abdominal pain Concurrent therapy control group: only stated that 16/46 were using drugs for abdominal pain Number randomised to intervention group: 52 Number randomised to control group: 49 Number assessed in intervention group: 47 Number assessed in control group: 46 Age at randomisation intervention group: mean 12.2 (SD ± 2.8) Age at randomisation control group: mean 11.7 (SD ± 3.2) Sex (M/F) intervention group: 28/19 Sex (M/F) control group: 25/21 | |
| Interventions | Intervention group: Lactobacillus reuteri DSM 17938 Control group: placebo | |
| Outcomes | The primary outcome measures included frequency and intensity of abdominal pain Secondary measures included school absenteeism because of abdominal pain, additional gastrointestinal symptoms and adverse effects | |
| Notes | Funding source: not stated Author contact: Zvi Weizman, MD, Pediatric Gastroenterology and Nutrition Unit, Soroka Medical Center, Faculty of Health Sciences, Ben‐Gurion University, PO Box 151, Beer‐Sheva, Israel 84101. Email: [email protected] | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Described as computer‐generated. |
| Allocation concealment (selection bias) | Low risk | Details described, performed independently. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical, with procedures described. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinded. |
| Incomplete outcome data (attrition bias) | Low risk | All patient flow details confirmed and accounted for. No major differences between groups. |
| Selective reporting (reporting bias) | Low risk | All outcomes reported. Trial registered prospectively (NCT01180556). |
| Other bias | Low risk | No other concerns. |
AP: abdominal pain
F: female
FAP: functional abdominal pain
FD: functional dyspepsia
FTT: failure to thrive
GSRS: Gastrointestinal Symptom Rating Scale
IBS: irritable bowel syndrome
IFN: interferon
IQR: interquartile range
M: male
NR: not reported
SD: standard deviation
TNF: tumour necrosis factor
VAS: visual analogue scale
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
| Commentary | |
| Letter to journal | |
| Review article | |
| Wrong condition | |
| Review article | |
| Review article | |
| Adult study | |
| Review article | |
| Letter to journal | |
| Adult study | |
| Wrong intervention | |
| Studied antibiotics | |
| Review article | |
| Adult study | |
| Letter to journal | |
| Review article | |
| Adult study | |
| Review article | |
| Adult study | |
| Adult study | |
| Not an RCT | |
| Letter to editor | |
| Review article | |
| Review article | |
| Adult study | |
| Adult study | |
| Study in to use of probiotics in functional constipation, not FAPD | |
| Adult study | |
| Adult study |
FAPD: functional abdominal pain disorder
RCT: randomised controlled trial
Characteristics of studies awaiting classification [ordered by study ID]
| Methods | RCT |
| Participants | 60 children |
| Interventions | Probiotics and antidiarrhoeal faecal softener vs antidiarrhoeal faecal softener |
| Outcomes | Content, release and reuptake of serotonin |
| Notes | Could not find any author contact information, therefore we were unable to contact the authors |
| Methods | RCT |
| Participants | Intervention group: 35 Control group: 35 |
| Interventions | Intervention group: synbiotic preparation Control group: placebo |
| Outcomes | The primary outcome was at least a 50% reduction in the number of pain episodes |
| Notes | Identified during pre‐publication update search and will be included in an update of the review. |
| Methods | RCT, single group assignment |
| Participants | 44 |
| Interventions | Intervention group: Probaclac Control group: placebo |
| Outcomes | Primary outcome measures: Secondary outcome measures: |
| Notes | Principal Investigator: Christophe M Faure, MD Ste‐Justine Hospital |
| Methods | RCT |
| Participants | 60 |
| Interventions | Behavioural: gut‐directed hypnotherapy |
| Outcomes | Primary outcome measures: Secondary outcome measures: Change in pain‐related coping (Pediatric Pain Coping Inventory (PPCI)) (time frame: baseline, at week 10 and at 3 months follow‐up) |
| Notes | Contact: Marco D Gulewitsch, PhD, Tel: 004970712977187, Email: marco‐daniel.gulewitsch@uni‐tuebingen.de |
| Methods | Study design: double‐blind, randomised, placebo‐controlled trial, multicentre Setting: Angel Healthcare Paediatric outpatient clinic and Life Veda Treatment and Research Centre in Mumbai, India Study period: February 2014 to October 2016 |
| Participants | Inclusion criteria: age between 4 and 12; IBS as defined by the Rome III criteria Exclusion criteria: structural or metabolic abnormalities to explain the symptoms; other diseases affecting gut motility other than IBS; history of lactose intolerance or other malabsorption; previous abdominal surgery; severe systemic disease; use of commercial probiotic preparation in preceding 3 months; history of digestive disease; symptoms suggestive of rectal bleeding; weight loss of more than 3 kg in last 3 months; acute gastroenteritis in the 4 weeks prior to inclusion; calprotectin assay of > 500 µg/g stool Condition duration intervention group: none stated Condition duration control group: none stated Concurrent therapy intervention group: "rescue medication", not stated Concurrent therapy control group: "rescue medication", not stated Number randomised to intervention group: 77 Number randomised to control group: 77 Number assessed in intervention group: 72 Number assessed in control group: 69 Age at randomisation intervention group: mean 7.86 (min 4, max 11) Age at randomisation control group: mean 7.89 (min 4, max 10) Sex (M/F) intervention group: 43/29 Sex (M/F) control group: 37/32 |
| Interventions | Intervention group: B. coagulans Control group: placebo |
| Outcomes | The intensity of pain was measured with an 11‐point Likert scale. For children aged less than 8 years, the parent/caretaker was instructed to fill the patient diary. For children aged between 8 and 12 years, the patient diary was filled by the child and if required they were assisted by the parent/caretaker. Secondary efficacy variables were measured as: (1) change in the severity of symptoms score which consisted of 8 domains (abdominal discomfort, bloating, urgency, incomplete evacuation, straining, passage of gas, bowel habit satisfaction and overall assessment of IBS) with a Likert scale of 1 to 5; (2) stool consistency (relief in stool disturbances or trouble with bowel habits, which is "either going more or less often than normal, diarrhoea or constipation, or having a different kind of stool, thin, hard, or soft and liquid" measured with the Bristol stool scale of 1 to 7 and recorded by the patients in the diary; (3) Subject’sGlobal Assessment of Relief (SGARC), a globally accepted/validated questionnaire, which includes the assessment of overall wellbeing, abdominal pain/discomfort and bowel function (Likert scale 0 to 4). Drug compliance, usage of rescue medications, and adverse events (AE), if any, were monitored throughout the study. |
| Notes | Funding source: Unique Biotech Ltd. Author contact: [email protected] This study was classified under awaiting classification. Initially, it was included, but we noted concerns with the outlying data as these were highly positive, as well as significant conflicts from the team. We sought advice from the Cochrane research integrity unit and the Cochrane Gut team and based on this we attempted to contact the authors on numerous occasions, as well as the editors of the journal for clarification. No response has been received (2 named authors were directly employed by the manufacturer of their interventional agent, and the study was funded by the same manufacturer). This is in line with the Cochrane policy for managing potentially problematic studies. |
F: female
IBS: irritable bowel syndrome
M: male
RCT: randomised controlled trial
Characteristics of ongoing studies [ordered by study ID]
| Study name | 'Evaluation of the effectiveness of Lactobacillus reuteri probiotics in the treatment of chronic functional abdominal pain in children aged 5 to 15 years' |
| Methods | RCT |
| Participants | 180 children |
| Interventions | A group of 90 patients will receive a probiotic sachet every day for 28 days A control group of 90 patients will receive a placebo sachet with the same original packaging every day for 28 days |
| Outcomes | Pain intensity; pain frequency |
| Starting date | 21 January 2022 |
| Contact information | Maryam Shiehmorteza: [email protected] |
| Notes | End date: 23 August 2022 |
| Study name | 'Comparison of the effect of Prokid with Rotflore sachet in reducing functional abdominal pain in children' |
| Methods | RCT |
| Participants | 116 children |
| Interventions | One group will receive ProCID capsules and will continue at regular intervals and the other group will be given Reuteflore sachets with the same conditions |
| Outcomes | Percentage of children with functional abdominal pain |
| Starting date | 1 January 2020 |
| Contact information | Sajad Jafari: [email protected] |
| Notes | End date: 30 December 2020 |
RCT: randomised controlled trial
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Treatment success Show forest plot | 6 | 554 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [1.05, 2.36] |
| Analysis 1.1  Comparison 1: Probiotic versus placebo, Outcome 1: Treatment success | ||||
| 1.1.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.37] |
| 1.1.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.34] |
| 1.1.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 6 | 554 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.49 [1.23, 1.80] |
| Analysis 1.2  Comparison 1: Probiotic versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model) | ||||
| 1.2.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.58 [1.17, 2.12] |
| 1.2.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.07, 1.72] |
| 1.2.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.33 [0.68, 8.01] |
| 1.3 Complete resolution of pain Show forest plot | 6 | 460 | Risk Ratio (M‐H, Random, 95% CI) | 1.55 [0.94, 2.56] |
| Analysis 1.3  Comparison 1: Probiotic versus placebo, Outcome 3: Complete resolution of pain | ||||
| 1.3.1 Lactobacillus reuteri | 4 | 306 | Risk Ratio (M‐H, Random, 95% CI) | 1.35 [0.76, 2.41] |
| 1.3.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.3.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.4 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | 1.18 [0.84, 1.67] |
| Analysis 1.4  Comparison 1: Probiotic versus placebo, Outcome 4: Complete resolution of pain (sensitivity analysis: risk of bias) | ||||
| 1.4.1 Lactobacillus reuteri | 3 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.76, 1.34] |
| 1.4.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.4.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.5 Severity of pain Show forest plot | 7 | 665 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐0.67, 0.12] |
| Analysis 1.5  Comparison 1: Probiotic versus placebo, Outcome 5: Severity of pain | ||||
| 1.5.1 Faces scales | 6 | 524 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.19 [‐0.61, 0.23] |
| 1.5.2 Combination VAS‐Faces scale | 1 | 141 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.76 [‐1.10, ‐0.41] |
| 1.6 Frequency of pain (episodes per week) Show forest plot | 6 | 605 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐0.92, 0.07] |
| Analysis 1.6  Comparison 1: Probiotic versus placebo, Outcome 6: Frequency of pain (episodes per week) | ||||
| 1.6.1 Lactobacillus reuteri | 4 | 360 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐1.42, 0.56] |
| 1.6.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.7 Frequency of pain (episodes per week) (sensitivity analysis: risk of bias) Show forest plot | 4 | 400 | Mean Difference (IV, Random, 95% CI) | ‐0.58 [‐0.81, ‐0.35] |
| Analysis 1.7  Comparison 1: Probiotic versus placebo, Outcome 7: Frequency of pain (episodes per week) (sensitivity analysis: risk of bias) | ||||
| 1.7.1 Lactobacillus reuteri | 2 | 155 | Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐2.80, 2.55] |
| 1.7.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.8 Withdrawals due to adverse events Show forest plot | 8 | 544 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| Analysis 1.8  Comparison 1: Probiotic versus placebo, Outcome 8: Withdrawals due to adverse events | ||||
| 1.8.1 Lactobacillus reuteri | 6 | 390 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.9 Adverse events Show forest plot | 7 | 489 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| Analysis 1.9  Comparison 1: Probiotic versus placebo, Outcome 9: Adverse events | ||||
| 1.9.1 Lactobacillus reuteri | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Treatment success Show forest plot | 4 | 310 | Risk Ratio (M‐H, Random, 95% CI) | 1.34 [1.03, 1.74] |
| Analysis 2.1  Comparison 2: Synbiotics versus placebo, Outcome 1: Treatment success | ||||
| 2.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 4 | 310 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.04, 1.77] |
| Analysis 2.2  Comparison 2: Synbiotics versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model) | ||||
| 2.3 Treatment success (sensitivity analysis: risk of bias) Show forest plot | 3 | 230 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.88, 1.82] |
| Analysis 2.3  Comparison 2: Synbiotics versus placebo, Outcome 3: Treatment success (sensitivity analysis: risk of bias) | ||||
| 2.4 Complete resolution of pain Show forest plot | 2 | 131 | Risk Ratio (M‐H, Random, 95% CI) | 1.65 [0.97, 2.81] |
| Analysis 2.4  Comparison 2: Synbiotics versus placebo, Outcome 4: Complete resolution of pain | ||||
| 2.5 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 1 | 51 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.88, 9.44] |
| Analysis 2.5  Comparison 2: Synbiotics versus placebo, Outcome 5: Complete resolution of pain (sensitivity analysis: risk of bias) | ||||
| 2.6 Severity of pain Show forest plot | 4 | 319 | Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.78, 0.37] |
| Analysis 2.6  Comparison 2: Synbiotics versus placebo, Outcome 6: Severity of pain | ||||
| 2.6.1 Likert scales | 2 | 124 | Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐1.21, 0.94] |
| 2.6.2 Faces scales | 1 | 115 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐0.81, 0.21] |
| 2.6.3 Visual analogue scales | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐0.31 [‐0.84, 0.22] |
| 2.7 Frequency of pain (episodes per week) Show forest plot | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐1.26 [‐1.77, ‐0.75] |
| Analysis 2.7  Comparison 2: Synbiotics versus placebo, Outcome 7: Frequency of pain (episodes per week) | ||||
| 2.8 Withdrawals due to adverse events Show forest plot | 4 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 4.58 [0.80, 26.19] |
| Analysis 2.8  Comparison 2: Synbiotics versus placebo, Outcome 8: Withdrawals due to adverse events | ||||
| 2.9 Adverse events Show forest plot | 3 | 189 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.32, 25.92] |
| Analysis 2.9  Comparison 2: Synbiotics versus placebo, Outcome 9: Adverse events | ||||
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Probiotic versus placebo, Outcome 1: Treatment success
Comparison 1: Probiotic versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model)
Comparison 1: Probiotic versus placebo, Outcome 3: Complete resolution of pain
Comparison 1: Probiotic versus placebo, Outcome 4: Complete resolution of pain (sensitivity analysis: risk of bias)
Comparison 1: Probiotic versus placebo, Outcome 5: Severity of pain
Comparison 1: Probiotic versus placebo, Outcome 6: Frequency of pain (episodes per week)
Comparison 1: Probiotic versus placebo, Outcome 7: Frequency of pain (episodes per week) (sensitivity analysis: risk of bias)
Comparison 1: Probiotic versus placebo, Outcome 8: Withdrawals due to adverse events
Comparison 1: Probiotic versus placebo, Outcome 9: Adverse events
Comparison 2: Synbiotics versus placebo, Outcome 1: Treatment success
Comparison 2: Synbiotics versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model)
Comparison 2: Synbiotics versus placebo, Outcome 3: Treatment success (sensitivity analysis: risk of bias)
Comparison 2: Synbiotics versus placebo, Outcome 4: Complete resolution of pain
Comparison 2: Synbiotics versus placebo, Outcome 5: Complete resolution of pain (sensitivity analysis: risk of bias)
Comparison 2: Synbiotics versus placebo, Outcome 6: Severity of pain
Comparison 2: Synbiotics versus placebo, Outcome 7: Frequency of pain (episodes per week)
Comparison 2: Synbiotics versus placebo, Outcome 8: Withdrawals due to adverse events
Comparison 2: Synbiotics versus placebo, Outcome 9: Adverse events
| Probiotic compared to placebo for management of functional abdominal pain disorders in children | ||||||
| Patient or population: children (4 to 18 years) with functional abdominal pain disorders | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with probiotics | |||||
| Treatment success (at study end, as reported by study authors) | Study population | RR 1.57 (1.05 to 2.36) | 554 (6 studies) | ⊕⊕⊝⊝ | — | |
| 339 per 1000 | 532 per 1000 | |||||
| Complete resolution of pain (at study end, as reported by study authors) | Study population | RR 1.55 (0.94 to 2.56) | 460 (6 studies) | ⊕⊝⊝⊝ Very low b | — | |
| 272 per 1000 | 422 per 1000 (256 to 696) | |||||
| Severity of pain (at study end, using the Faces Pain Scale) | Severity of pain using the Faces Pain Scale when comparing probiotics versus placebo: SMD ‐0.28 (95% CI ‐0.67 to 0.12) | 665 participants | ⊕⊝⊝⊝ | — | ||
| Frequency of pain (at study end, episodes per week) | Frequency of pain episodes (per week) when comparing probiotics versus placebo: MD ‐0.43 (95% CI ‐0.92 to 0.07) | 605 participants | ⊕⊝⊝⊝ | — | ||
| Withdrawals due to adverse events | Study population | RR 1.00 (0.07 to 15.12) | 544 | ⊕⊝⊝⊝ Very low e | — | |
| 4 per 1000 | 4 per 1000 | |||||
| Serious adverse events | There were no SAEs reported within these studies in either group. | 685 | ⊕⊝⊝⊝ Very low e | — | ||
| Adverse events (any) | Study population | RR 1.00 (0.07 to 15.12) | 489 | ⊕⊝⊝⊝ Very low e | — | |
| 4 per 1000 | 4 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level due to inconsistency (I² = 59% for both outcomes) and one level for risk of bias. bDowngraded three levels due to very high inconsistency (I² = 70%) and risk of bias (allocation concealment, attrition and reporting bias). cDowngraded three levels due to very high inconsistency (I² = 70%) and risk of bias (reporting bias). dDowngraded one level due to risk of bias. eDowngraded two levels due to imprecision because of very low numbers of adverse event cases and one level due to risk of bias. | ||||||
| Synbiotic compared to placebo for management of functional abdominal pain disorders in children | ||||||
| Patient or population: children (4 to 18 years) with functional abdominal pain disorders | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with synbiotic | |||||
| Treatment success (at study end, as reported by study authors) | Study population | RR 1.34 (1.03 to 1.74) | 310 | ⊕⊕⊝⊝ | — | |
| 350 per 1000 | 469 per 1000 | |||||
| Complete resolution of pain (at study end, as reported by study authors) | Study population | RR 1.65 (0.97 to 2.81) | 131 (2 studies) | ⊕⊕⊝⊝ | — | |
| 319 per 1000 | 405 per 1000 | |||||
| Severity of pain (at study end, using the Faces Pain Scale) | Severity of pain measured using the Faces Pain Scale for synbiotics versus placebo: MD ‐0.21 (95% CI ‐0.78 to 0.37) | 319 (4 studies) | ⊕⊝⊝⊝ | — | ||
| Frequency of pain (at study end, episodes per week) | The mean in the placebo group was 3.4 | MD 1.26 lower | — | 80 (1 study) | ⊕⊝⊝⊝ | — |
| Withdrawals due to adverse events | Study population | RR 4.58 | 302 | ⊕⊝⊝⊝ | — | |
| 7 per 1000 | 31 per 1000 | |||||
| Serious adverse events | There were no SAEs reported within these studies in either group | 302 | ⊕⊝⊝⊝ | — | ||
| Adverse events (any) | Study population | RR 2.88 | 189 | ⊕⊝⊝⊝ | — | |
| 11 per 1000 | 30 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision due to low participant numbers. bDowngraded one level due to risk of bias. cDowngraded two levels due to very serious unexplained heterogeneity, and one level due to risk of bias. dDowngraded two levels for severe risk of bias, due to unclear/high risk of bias for the single study that provided data for this outcome. eDowngraded two levels due to very serious imprecision from very low event numbers, and one level due to risk of bias. | ||||||
| Study ID | Interventional agent | Dosage (amount and frequency) | Control | Dosage (amount and frequency) | Trial registered(prospective/retrospective/none) | Trial registry outcomes published? | Conflicts of interest |
|---|---|---|---|---|---|---|---|
| Synbiotic group: Bifidobacterium coagulans + fructo‐oligosaccharide | 150 million spores of Bifidobacterium coagulans + fructo‐oligosaccharide twice daily | Peppermint group: peppermint oil (Colpermin)
Placebo group: folic acid | Peppermint group: 187 mg 3 times daily
Placebo group: 1 mg once daily | Prospective | Yes | None declared | |
| Synbiotic group: Bifidobacterium lactis B94 + inulin | 5 × 109 CFU Bifidobacterium lactis 900 mg inulin twice daily | Probiotic group: Bifidobacterium lactis
Prebiotic group: inulin
| Probiotic group: 5 × 109 CFU twice daily
Prebiotic group: 900 mg twice daily
| None | NA | None declared, no financial support received | |
| Synbiotic group: Lactobacillus GG + inulin | 1 x 1010 bacteria/capsule twice daily | Prebiotic group: inulin | Dose unstated (1 capsule twice daily) | None | NA | None declared | |
| Probiotic group: Lactobacillus reuteri | 1 x 108 CFU (5 drops per day) | Placebo group: unidentified placebo | Unstated | Retrospective | Yes | None declared, financial support from Zanjan University of Medical Sciences | |
| Probiotic group: Lactobacillus rhamnosus GG | 3 x 109 CFU twice daily | Placebo group: inert powder | Unstated dose twice daily | Retrospective | Yes | None declared, no financial support received | |
| Probiotic group: Lactobacillus rhamnosus GG | 3 x 109 CFU twice daily | Placebo group: powder | Unstated dose twice daily | None | NA | None declared, financial support from the Medical University of Warsaw | |
| Giannetti 2017 (cross‐over) | Probiotic group: Bifidobacterium longum BB536/ Bifidobacterium infantis M‐63/Bifidobacterium breve M‐16V | 1 sachet daily (3 billion/1 billion/1 billion per bacterium) | Placebo group: unidentified placebo | Unstated (1 sachet daily) | Retrospective | Yes | None declared |
| Guandalini 2010 (cross‐over) | Probiotic group: a patented probiotic preparation, which contains live, freeze‐dried lactic acid bacteria, at a total concentration of 450 billion lactic acid bacteria per sachet, comprising 8 different strains: Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus bulgaris and Streptococcus thermophilus | 1 sachet once daily if 4 to 11 years old or twice daily if 12 to 18 years old | Placebo group: unidentified placebo | 1 sachet once daily if 4 to 11 years old or twice daily if 12 to 18 years old) | None | NA | None declared, funding from locally available grants; no industry support other than providing probiotic and placebo products |
| Probiotic group: Lactobacillus reuteri DSM 17938 (tablet also containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid) | 1 x 108 CFU once daily (1 x 450 mg chewable tablet) | Placebo group: tablet containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid | Once daily (1 x 450 mg chewable tablet) | Prospective | Yes | None declared, no industry support other than providing probiotic and placebo products | |
| Probiotic group: Lactobacillus reuteri DSM 17938 (tablet also containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid) | 1 x 108 CFU once daily (1 x 450 mg chewable tablet) | Placebo group: tablet containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid | Once daily (one x 450 mg chewable tablet) | Prospective | Yes | Three contributing authors (Iva Hojsak, Sanja Kolacek, Zrinjka Misak) received either payment/honoraria for lectures or consultation, travel grants or lecture fees from several industry sources. All other authors declare no conflict of interest. | |
| Synbiotic group: Lactobacillus GG + inulin | 1 x 1010 CFU capsule twice daily | Prebiotic group: inulin | Unstated dose (1 capsule twice daily) | Prospective | Yes | None declared, funding received from Mashhad University of Medical Sciences, Iran | |
| Probiotic group: Lactobacillus reuteri DSM 17938 | 2 x 108 CFU (in the form of 2 chewable tablets once daily) | Placebo group: unidentified placebo | Unstated (2 chewable tablets once daily) | Prospective | Yes | Three contributing authors received research grants from BioGaia, 2 authors have been speakers for Biogaia and the remaining author had no conflicts to declare | |
| Synbiotic group | Not stated | Placebo group: unidentified | Not stated | None | NA | Abstract only, none declared | |
| Probiotic group: Lactobacillus reuteri | 1 x 108 CFU twice daily in the form of chewable tables | Placebo group: unidentified | Unstated dose (twice daily in the form of chewable tablets) | None | NA | None declared, funding from research centre | |
| Probiotic group: Lactobacillus reuteri DSM 17938 (product also containing sunflower oil, medium‐chain triglyceride oil from coconut oil) | 1 x 108 CFU twice daily in the form of a 10 mL bottle | Placebo group: product containing sunflower oil, medium‐chain triglyceride oil from coconut oil | 10 mL bottle twice daily | None | NA | None declared | |
| Probiotics group: Lactobacillus GG | Unstated dose | Placebo group: unidentified placebo | Unstated dose | None | NA | Abstract only, none declared | |
| Synbiotic group: Bacillus coagulans + fructo‐oligosaccharide | 150 million spores + fructo‐oligosaccharides 100 mg twice daily in the form of tablets | Placebo group: unidentified placebo | 1 tablet twice daily | Prospective | Yes | None declared, funding from Isfahan University of Medical Sciences | |
| Probiotic group: Lactobacillus reuteri DSM 17938 | 1 x 108 CFU once daily in the form of chewable tablet | Placebo group: unidentified placebo | Once daily in the form of chewable tablet | Prospective | Yes | One author (Zvi Weizman) has been a speaker for Biogaia AB which supplied the probiotic. No other conflicts of interest declared, and statement that Biogaia had no role in 'conception, design, and conduct of the study'. | |
| CFU: colony‐forming unit | |||||||
| Study ID | Methods of diagnosis | FAPD diagnosis | Separate data per sub‐diagnosis reported (yes/no) | Age range | Number of participants | Length of intervention | Time points of outcome measurements |
|---|---|---|---|---|---|---|---|
| Rome III | FAP/IBS/FD | No | 4 to 13 | 54 | 1 month | End of intervention | |
| Rome III | IBS | Not relevant as they only included one | 4 to 16 | 76 | 4 weeks | End of intervention | |
| Rome II | IBS | Not relevant as they only included one | 5 to 17 | 50 | 6 weeks | End of intervention | |
| Rome III | FAP | Not relevant as they only included one | 4 to 16 | 80 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| Rome II | FAP/IBS | Yes | 5 to 14 | 136 | 8 weeks | End of intervention; 8 weeks after end of intervention | |
| Rome II | FAP/IBS/FD | Yes | 6 to 16 | 104 | 4 weeks | End of intervention | |
| Giannetti 2017 (cross‐over) | Rome III | IBS/FD | Yes | 8 to 17 | 48 | 2 week run‐in period 6 weeks pre‐cross‐over phase 2 weeks washout 6 weeks post‐cross‐over phase | At the end of each period/phase and data combined at the end per intervention |
| Guandalini 2010 (cross‐over) | Rome II | IBS | Not relevant as they only included one | 4 to 18 | 59 | 2 week run‐in period 6 weeks pre‐cross‐over phase 2 weeks washout 6 weeks post‐cross‐over phase | Every 2 weeks and data combined at the end per intervention |
| Rome III | FAP/IBS | No | 4 to 18 | 55 | 12 weeks | 1 month into intervention; end of intervention; 1 month after end of intervention | |
| Rome III | FAP/IBS | No | 4 to 18 | 46 | 12 weeks | 1 month into intervention; end of intervention; 1 month after end of intervention | |
| Rome III | IBS | Not relevant as they only included one | 4 to 18 | 52 | 1 month | Weekly until end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 5 to 16 | 48 | 4 weeks | At 2 weeks and end of intervention | |
| Rome III | FAP/FD | No | Not stated | 80 | 8 weeks | End of intervention | |
| Rome III | FAP/IBS/FD/abdominal migraine | Yes | 6 to 16 | 125 | 4 weeks | At 2 weeks and end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 16 | 60 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| Unstated | FAP | Not relevant as they only included one | Unstated | 61 | 6 weeks | End of intervention; 4 weeks after end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 18 | 115 | 4 weeks | End of intervention; 8 weeks after end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 15 | 101 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| FAP: functional abdominal pain | |||||||
| Study ID | 1a. Global improvement or treatment success | 1b. Complete resolution of pain | 1c. Severity of pain | 1d. Frequency of pain |
|---|---|---|---|---|
| NR | NR | Intervention group: 3.93 ± 1.06 Control group: 4.24 ± 1.33 | Intervention group: 2.14 ± 0.87 Control group: 3.40 ± 1.41 | |
| NR | Intervention group 1: 9/26 Intervention group 2: 7/25 Control group: 3/25 | NR | NR | |
| Intervention group: 11/32 Control group: 10/32 | NR | Change in pain intervention group: ‐1.3 (± 0.3) Change in pain control group: ‐1.7 (± 0.6) | NR | |
| No pain episodes per week, end of first month Intervention group: 20; control group: 26
No pain episodes per week, end of second month Intervention group: 19; control group: 21 | NR | End of first month intervention group: mean (SD) 2.50 (1.45); control group: mean (SD) 2.08 (1.56)
End of second month intervention group: mean (SD) 2.53 (1.43); control group: mean (SD) 2.25 (1.46) | At first month intervention group: mean (SD) 0.68 (0.76); control group: mean (SD) 0.40 (0.59)
At second month intervention group: mean (SD) 0.70 (0.75); control group: mean (SD) 0.53 (0.59) | |
| Decrease of at least 50% in the number of episodes and intensity of pain at 12 weeks Intervention group: 48/69; control group: 37/67
Decrease of at least 50% in the number of episodes and intensity of pain at end of follow‐up Intervention group: 53/69; control group: 43/67 | NR | At 12 weeks intervention group: mean (SD) 2.3 (1.3); control group: 3.4 (2.1)
At end of follow‐up intervention group: mean (SD) 0.9 (0.5); control group: 1.5 (1.0) | Number of episodes per week at 12 weeks intervention group: 1.1 (0.8); control group: 2.2 (1.2)
At end of follow‐up intervention group: 0.9 (0.5); control group: 1.5 (1.0) | |
| NR | Intervention group: 13/52 (FD 1/10, IBS 6/18, FAP 6/24)
Control group: 5/52 (FD 2/10, IBS 6/18, FAP 2/23) | At 4 weeks Intervention group: mean 2.5 (SD ± 1.9) (FD 2.9 ± 1.5, IBS 2.2 ± 2.1, FAP 2.6 ± 2.0) Control group: mean 2.9 (SD ± 1.5) (FD 1.9 ± 1.3, IBS 3.2 ± 1.5, FAP 3.0± 1.5) | At 4 weeks Intervention group: mean 2.2 (SD ± 1.7) (FD 2.7 ± 1.3, IBS 1.8 ± 1.7, FAP 2.3 ± 1.8) Control group: mean 2.6 (SD ± 1.4) (FD 2.0 ± 1.6, IBS 3.1 ± 1.1, FAP 2.4 ± 1.4) | |
| Giannetti 2017 (cross‐over) | NR | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data |
| Guandalini 2010 (cross‐over) | NR | NR | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data |
| NR | Intervention group: 16/26 Control group: 16/29 | End of first month intervention group/control group: 0.75/0.96 End of second month intervention group/control group: 0.17/0.64 End of third month intervention group/control group: 0.32/0.71 End of fourth month intervention group/control group: 0.21/0.6
Difference in the severity of pain between first and fourth month, Wong‐Baker FACES/day intervention group: median 0.42 (range 0.31 to 2.9); control group: median 0.23 (range 1.2 to 2.2) | Number of days without pain intervention group at 4 months: 89.5 (range 5 to 108); control group at 4 months: 51 (range 0 to 107) | |
| NR | Intervention group: 10/24 Control group: 9/22 | End of first month intervention group/control group: 1.35 (IQR 0.64 to 1.98)/1.1 (IQR 0.76 to 2.04) End of second month intervention group/control group: 1.0 (IQR 0.09 to 2.12)/0.8 (IQR 0.37 to 1.68) End of third month intervention group/control group: 0.83 (IQR 0.025 to 2.26)/0.78 (IQR 0.43 to 2.0) End of fourth month intervention group/control group: 0.035 (IQR 0 to 1.0)/0.81 (IQR 0.2 to 1.48)
Change in severity of pain from 1st to 4th month intervention group: 0.55 (IQR 0.28 to 0.55); control group: median 0.36 (IQR ‐0.14 to 0.36) | Number of days without pain intervention group at 4 months: 90 (IQR 54 to 99); control group at 4 months: 59.5 (IQR 21.5 to 89.25) | |
| NR | NR | 1 week: intervention group/control group 1.5 (1.0)/1.8 (0.6) 2 weeks: intervention group/control group 1.2 (1.1)/1.9 (0.8) 3 weeks: intervention group/control group 1.0 (0.9)/1.8 (0.6) 4 weeks: intervention group/control group 0.8 (0.9)/1.5 (0.8) | NR | |
| Reduction in pain score of greater than 50% at 4 weeks intervention group: 19/27 (70.4%); control group: 16/27 (58.3%)
Reduction in pain score of greater than 50% at 8 weeks intervention group: 17/25 (65.4%); control group: 13/23 (56.5%) | NR | Intervention group/control group: mean (SD) 2 weeks: 10.4 (18.8)/12.2 (17.3) 4 weeks: 4.3 (8.5)/4.0 (5.6) 8 weeks: 7.2 (17.7)/2.5 (3.4) | Intervention group/control group: mean (SD) 2 weeks: 5.6 (8.1)/8.2 (10.7) 4 weeks: 2.9 (4.5)/3.1 (4.1) 8 weeks: 4.8 (9.9)/2.8 (3.3) | |
| NR | Intervention group: 25/39 Control group: 18/41 | NR | NR | |
| Intervention group = 32/65 (FAP 13/28, FD 11/16, IBS 6/15, AM 2/6)
Control group = 8/60 (FAP 8/29, FD 0/13, IBS 0/6, AM, 0/3)
| NR (in Rahmani 2020, treatment success was defined as pain intensity = 0) | Text: severity at 4 weeks in intervention group = 1.3 ± 1.1 (Table 1 reports: 1.1 ± 1.3)
Text: severity at 4 weeks in control group = 1 ± 2 (Table 1 reports: 2 ± 1)
FAP (intervention group/control group): 1.2 ± 1.3; 2 ± 1 FD (intervention group/control group): 0.8 ± 1.5; 2.0 ± 6 IBS (intervention group/control group): 1.4 ± 1.4; 2.8 ± 0.8 AM (intervention group/control group): 1.3 ± 1.5; 2.3 ± 0.5 | Text: frequency of repetitive pain at 4 weeks intervention group 3.6 ± 2.2 (Table 1 reports: intervention group 2.2 ± 3.6)
Text: frequency of repetitive pain at 4 weeks control group 4.6 ± 4.9 (Table 1 reports: control group 4.9 ± 4.6)
FAP (intervention group/control group): 2.1 ± 2.7; 4.1 ± 4.4 FD (intervention group/control group): 1.6 ± 3.0; 6.0 ± 5.0 IBS (intervention group/control group): 3.7 ± 5.5; 6.3 ± 0.8 AM (intervention group/control group): 1.1 ± 0.9; 1.3 ± 0.5 | |
| NR | NR | Mean (SD) as we interpreted it from the figures: Week 4 intervention group/control group: 1.25 (0.9)/2 (0.8) Week 8 intervention group/control group: 1 (0.7)/2 (0.8) | Mean (SD) as we interpreted it from the figures: Week 4 intervention group/control group: 1.4 (1.1)/2.2 (0.5) per day Week 8 intervention group/control group: 2.1 (0.6)/2 (0.5) per day | |
| NR | NR | NR | NR | |
| Response at week 4 intervention group: 27/45; control group: 17/43
Response at week 12 intervention group: 29/45; control group: 23/43 | NR | Change in pain scale from start of intervention to week 4 intervention group: mean ‐1.7 (SD ± 1.5); control group: mean ‐1.6 (SD ± 1.5)
Change in pain scale from start of intervention to week 12 intervention group: mean ‐2.1 (SD ± 1.4); control group: mean ‐1.8 (SD ± 1.4) | NR | |
| NR | NR | Improvement in intensity of abdominal pain at 4 weeks intervention group: mean 4.3 (SD ± 2.7); control group: mean 7.2 (SD ± 3.1)
Improvement in intensity of abdominal pain at end 8 weeks intervention group: mean 4.8 (SD ± 3.3); control group: mean 6.4 (SD ± 4.1) | Number of episodes of pain per week at 4 weeks intervention group: mean 1.9 (SD ± 0.8); control group: mean 3.6 (SD ± 1.7)
Number of episodes of pain per week at 8 weeks intervention group: mean 3.4 (SD ± 2.6); control group: mean 4.4 (SD ± 2.9)
| |
| Numbers presented as per the original study reports. AM: abdominal migraine | ||||
| Study ID | 2a. Serious adverse events | 2b. Withdrawal due to adverse events | 2c. Adverse events | 2d. School performance | 2e. Social and psychological functioning | 2f. Quality of life |
|---|---|---|---|---|---|---|
| 0 | 0 | 0 | NR | NR | NR | |
| NR | Intervention group 1: 3 | Intervention group 1: 3 | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | 0 | 0 | School absenteeism at end of intervention | NR | NR | |
| Giannetti 2017 (cross‐over) | 0 | 0 | 0 | NR | NR | NR |
| Guandalini 2010 (cross‐over) | 0 | 0 | 0 | NR | NR | Questionnaire of disruption to family life (change in score) Intervention group: mean ‐0.9 (SD ± 0.2); control group: mean ‐0.51 (SD ± 0.3) |
| NR | 0 | NR | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| 0 | 0 | 0 | NR | Functional changes on a 3 point Likert scale at end of intervention Intervention group: mean 2.4 (SD ± 0.5); control group: mean 1.9 (SD ± 0.4) | NR | |
| 0 | 0 | 0 | Average number of school absences per week at end of follow‐up Intervention group: mean 0.0 (SD ± 0.0); control group: mean 0.11 (SD ± 0.52) | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | Intervention group: 5; control group:0 | NR as numbers of people with adverse events
Total number of adverse events intervention group: 45; control group: 43 | NR | NR | NR | |
| 0 | 0 | 0 | Days of school absenteeism over 4 weeks Intervention group: mean 2.7 (SD ± 0.9); control group: mean 1.9 (SD ± 1.1) | NR | NR | |
| Numbers presented as per the original study reports. NR: not reported | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Treatment success Show forest plot | 6 | 554 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [1.05, 2.36] |
| 1.1.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.37] |
| 1.1.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.34] |
| 1.1.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 6 | 554 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.49 [1.23, 1.80] |
| 1.2.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.58 [1.17, 2.12] |
| 1.2.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.07, 1.72] |
| 1.2.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.33 [0.68, 8.01] |
| 1.3 Complete resolution of pain Show forest plot | 6 | 460 | Risk Ratio (M‐H, Random, 95% CI) | 1.55 [0.94, 2.56] |
| 1.3.1 Lactobacillus reuteri | 4 | 306 | Risk Ratio (M‐H, Random, 95% CI) | 1.35 [0.76, 2.41] |
| 1.3.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.3.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.4 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | 1.18 [0.84, 1.67] |
| 1.4.1 Lactobacillus reuteri | 3 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.76, 1.34] |
| 1.4.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.4.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.5 Severity of pain Show forest plot | 7 | 665 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐0.67, 0.12] |
| 1.5.1 Faces scales | 6 | 524 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.19 [‐0.61, 0.23] |
| 1.5.2 Combination VAS‐Faces scale | 1 | 141 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.76 [‐1.10, ‐0.41] |
| 1.6 Frequency of pain (episodes per week) Show forest plot | 6 | 605 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐0.92, 0.07] |
| 1.6.1 Lactobacillus reuteri | 4 | 360 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐1.42, 0.56] |
| 1.6.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.7 Frequency of pain (episodes per week) (sensitivity analysis: risk of bias) Show forest plot | 4 | 400 | Mean Difference (IV, Random, 95% CI) | ‐0.58 [‐0.81, ‐0.35] |
| 1.7.1 Lactobacillus reuteri | 2 | 155 | Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐2.80, 2.55] |
| 1.7.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.8 Withdrawals due to adverse events Show forest plot | 8 | 544 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.8.1 Lactobacillus reuteri | 6 | 390 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.9 Adverse events Show forest plot | 7 | 489 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.9.1 Lactobacillus reuteri | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Treatment success Show forest plot | 4 | 310 | Risk Ratio (M‐H, Random, 95% CI) | 1.34 [1.03, 1.74] |
| 2.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 4 | 310 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.04, 1.77] |
| 2.3 Treatment success (sensitivity analysis: risk of bias) Show forest plot | 3 | 230 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.88, 1.82] |
| 2.4 Complete resolution of pain Show forest plot | 2 | 131 | Risk Ratio (M‐H, Random, 95% CI) | 1.65 [0.97, 2.81] |
| 2.5 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 1 | 51 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.88, 9.44] |
| 2.6 Severity of pain Show forest plot | 4 | 319 | Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.78, 0.37] |
| 2.6.1 Likert scales | 2 | 124 | Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐1.21, 0.94] |
| 2.6.2 Faces scales | 1 | 115 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐0.81, 0.21] |
| 2.6.3 Visual analogue scales | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐0.31 [‐0.84, 0.22] |
| 2.7 Frequency of pain (episodes per week) Show forest plot | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐1.26 [‐1.77, ‐0.75] |
| 2.8 Withdrawals due to adverse events Show forest plot | 4 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 4.58 [0.80, 26.19] |
| 2.9 Adverse events Show forest plot | 3 | 189 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.32, 25.92] |
