Prebiotics for induction and maintenance of remission in ulcerative colitis.

BACKGROUND: People affected by ulcerative colitis (UC) are interested in dietary therapies as treatments that can improve their health and quality of life. Prebiotics are a category of food ingredients theorised to have health benefits for the gastrointestinal system through their effect on the growth and activity of intestinal bacteria and probiotics. OBJECTIVES: To assess the efficacy and safety of prebiotics for the induction and maintenance of remission in people with active UC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP on 24 June 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) on people with UC. We considered any type of standalone or combination prebiotic intervention, except those prebiotics combined with probiotics (known as synbiotics), compared to any control intervention. We considered interventions of any dose and duration. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We included 9 RCTs involving a total of 445 participants. Study duration ranged from 14 days to 2 to 3 months for induction and 1 to 6 months for maintenance of remission. All studies were on adults. Five studies were on people with mild to moderate active disease, three in remission or mild activity, and one did not mention. We judged only one study as at low risk of bias in all areas. Two studies compared prebiotics with placebo for induction of remission. We cannot draw any conclusions about clinical remission (70% versus 67%; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.57 to 1.94); clinical improvement (mean Rachmilewitz score on day 14 of 4.1 versus 4.5; mean difference (MD) -0.40, 95% CI -2.67 to 1.87); faecal calprotectin levels (mean faecal calprotectin on day 14 of 1211 µg/mL versus 3740 µg/mL; MD -2529.00, 95% CI -6925.38 to 1867.38); interleukin-8 (IL-8) levels (mean IL-8 on day 7 of 2.9 pg/mL versus 5.0 pg/mL; MD -2.10, 95% CI -4.93 to 0.73); prostaglandin E2 (PGE-2) levels (mean PGE-2 on day 7 of 7.1 ng/mL versus 11.5 ng/mL; MD -4.40, 95% CI -20.25 to 11.45); or withdrawals due to adverse events (21% versus 8%; RR 2.73, 95% CI 0.51 to 14.55). All evidence was of very low certainty. No other outcomes were reported. Two studies compared inulin and oligofructose 15 g with inulin and oligofructose 7.5 g for induction of remission. We cannot draw any conclusions about clinical remission (53% versus 12.5%; RR 4.27, 95% CI 1.07 to 16.96); clinical improvement (67% versus 25%; RR 2.67, 95% CI 1.06 to 6.70); total adverse events (53.5% versus 31%; RR 1.71, 95% CI 0.72 to 4.06); or withdrawals due to adverse events (13% versus 25%; RR 0.53, 95% CI 0.11 to 2.50). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics and anti-inflammatory therapy with anti-inflammatory therapy alone for induction of remission. We cannot draw any conclusions about clinical improvement (mean Lichtiger score at 4 weeks of 6.2 versus 10.3; MD -4.10, 95% CI -8.14 to -0.06) or serum C-reactive protein (CRP) levels (mean CRP levels at 4 weeks 0.55 ng/mL versus 0.50 ng/mL; MD 0.05, 95% CI -0.37 to 0.47). All evidence was of very low certainty. No other outcomes were reported. Three studies compared prebiotics with placebo for maintenance of remission. There may be no difference between groups in rate of clinical relapse (44% versus 33%; RR 1.36, 95% CI 0.79 to 2.31), and prebiotics may lead to more total adverse events than placebo (77% versus 46%; RR 1.68, 95% CI 1.18 to 2.40). The evidence was of low certainty. We cannot draw any conclusions about clinical improvement (mean partial Mayo score at day 60 of 0.428 versus 1.625; MD -1.20, 95% CI -2.17 to -0.22); faecal calprotectin levels (mean faecal calprotectin level at day 60 of 214 µg/mL versus 304 µg/mL; MD -89.79, 95% CI -221.30 to 41.72); quality of life (mean Inflammatory Bowel Disease Questionnaire (IBDQ) score at day 60 of 193.5 versus 188.0; MD 5.50, 95% CI -8.94 to 19.94); or withdrawals due to adverse events (28.5% versus 11%; RR 2.57, 95% CI 1.15 to 5.73). The evidence for these outcomes was of very low certainty. No other outcomes were reported. One study compared prebiotics with synbiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 176.1; MD 6.30, 95% CI -6.61 to 19.21) or withdrawals due to adverse events (23% versus 20%; RR 1.13, 95% CI 0.48 to 2.62). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics with probiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 168.6; MD 13.60, 95% CI 1.22 to 25.98) or withdrawals due to adverse events (22.5% versus 22.5%; RR 1.00, 95% CI 0.44 to 2.26). All evidence was of very low certainty. No other outcomes were reported. AUTHORS' CONCLUSIONS: There may be no difference in occurrence of clinical relapse when adjuvant treatment with prebiotics is compared with adjuvant treatment with placebo for maintenance of remission in UC. Adjuvant treatment with prebiotics may result in more total adverse events when compared to adjuvant treatment with placebo for maintenance of remission. We could draw no conclusions for any of the other outcomes in this comparison due to the very low certainty of the evidence. The evidence for all other comparisons and outcomes was also of very low certainty, precluding any conclusions. It is difficult to make any clear recommendations for future research based on the findings of this review given the clinical and methodological heterogeneity among studies. It is recommended that a consensus is reached on these issues prior to any further research.

Vitamin D for the treatment of inflammatory bowel disease.

BACKGROUND: Vitamin D possesses immunomodulatory properties and has been implicated in the pathogenesis and severity of inflammatory bowel disease (IBD). Animal studies and emerging epidemiological evidence have demonstrated an association between vitamin D deficiency and worse disease activity. However, the role of vitamin D for the treatment of IBD is unclear. OBJECTIVES: To evaluate the benefits and harms of vitamin D supplementation as a treatment for IBD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was Jun 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people of all ages with active or inactive IBD comparing any dose of vitamin D with another dose of vitamin D, another intervention, placebo, or no intervention. We defined doses as: vitamin D (all doses), any-treatment-dose vitamin D (greater than 400 IU/day), high-treatment-dose vitamin D (greater than 1000 IU/day), low-treatment-dose vitamin D (400 IU/day to 1000 IU/day), and supplemental-dose vitamin D (less than 400 IU/day). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. clinical response for people with active disease, 2. clinical relapse for people in remission, 3. quality of life, and 4. withdrawals due to adverse events. Our secondary outcomes were 5. disease activity at end of study, 6. normalisation of vitamin D levels at end of study, and 7. total serious adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 22 RCTs with 1874 participants. Study duration ranged from four to 52 weeks. Ten studies enroled people with Crohn's disease (CD), five enroled people with ulcerative colitis (UC), and seven enroled people with CD and people with UC. Seventeen studies included adults, three included children, and two included both. Four studies enroled people with active disease, six enroled people in remission, and 12 enroled both. We assessed each study for risk of bias across seven individual domains. Five studies were at low risk of bias across all seven domains. Ten studies were at unclear risk of bias in at least one domain but with no areas of high risk of bias. Seven studies were at high risk of bias for blinding of participants and assessors. Vitamin D (all doses) versus placebo or no treatment Thirteen studies compared vitamin D against placebo or no treatment. We could not draw any conclusions on clinical response for UC as the certainty of the evidence was very low (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.51 to 10.57; 1 study, 60 participants). There were no data on CD. There may be fewer clinical relapses for IBD when using vitamin D compared to placebo or no treatment (RR 0.57, 95% CI 0.34 to 0.96; 3 studies, 310 participants). The certainty of the evidence was low. We could not draw any conclusions on quality of life for IBD (standardised mean difference (SMD) -0.13, 95% CI -3.10 to 2.83 (the SMD value indicates a negligent decrease in quality of life, and the corresponding CIs indicate that the effect can range from a large decrease to a large increase in quality of life); 2 studies, 243 participants) or withdrawals due to adverse events for IBD (RR 1.97, 95% CI 0.18 to 21.27; 12 studies, 1251 participants; note 11 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 12). The certainty of the evidence was very low. High-treatment-dose vitamin D versus low-treatment-dose vitamin D Five studies compared high treatment vitamin D doses against low treatment vitamin D doses. There were no data on clinical response. There may be no difference in clinical relapse for CD (RR 0.48, 95% CI 0.23 to 1.01; 1 study, 34 participants). The certainty of the evidence was low. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 0.89, 95% CI 0.06 to 13.08; 3 studies, 104 participants; note 2 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 3). The data on quality of life and disease activity could not be meta-analysed, were of very low certainty, and no conclusions could be drawn. Any-treatment-dose vitamin D versus supplemental-dose vitamin D Four studies compared treatment doses of vitamin D against supplemental doses. There were no data on clinical response and relapse. There were no data on quality of life that could be meta-analysed. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 3.09, 95% CI 0.13 to 73.17; 4 studies, 233 participants; note 3 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 4). AUTHORS' CONCLUSIONS: There may be fewer clinical relapses when comparing vitamin D with placebo, but we cannot draw any conclusions on differences in clinical response, quality of life, or withdrawals, due to very low-certainty evidence. When comparing high and low doses of vitamin D, there were no data for clinical response, but there may be no difference in relapse for CD. We cannot draw conclusions on the other outcomes due to very low certainty evidence. Finally, comparing vitamin D (all doses) to supplemental-dose vitamin D, there were no data on clinical relapse or response, and we could not draw conclusions on other outcomes due to very low certainty evidence or missing data. It is difficult to make any clear recommendations for future research on the basis of the findings of this review. Future studies must be clear on the baseline populations, the purpose of vitamin D treatment, and, therefore, study an appropriate dosing strategy. Stakeholders in the field may wish to reach consensus on such issues prior to new studies.

Psychosocial Interventions for the Treatment of Functional Abdominal Pain Disorders in Children: A Systematic Review and Meta-analysis.

Importance: Functional abdominal pain disorders (FAPDs) can severely affect the life of children and their families, with symptoms carrying into adulthood. Management of FADP symptoms is also a financial and time burden to clinicians and health care systems. Objective: To systematically review various randomized clinical trials (RCTs) on the outcomes of cognitive behavioral therapy (CBT), educational support, yoga, hypnotherapy, gut-directed hypnotherapy, guided imagery, and relaxation in the management of FAPDs. Data Sources: PubMed, MEDLINE, Embase, PsycINFO, and Cochrane Library. Study Selection: All RCTs that compared psychosocial interventions with any control or no intervention, for children aged 4 to 18 years with FAPDs. Data Extraction and Synthesis: Pairs of the authors independently extracted data of all included studies, using a predesigned data extraction sheet. One author acted as arbitrator. Risk of bias was assessed using the Cochrane risk of bias tool, and certainty of the evidence for all primary outcomes was analyzed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Main Outcomes and Measures: Primary outcomes were treatment success, pain frequency, pain intensity, and withdrawal owing to adverse events. Dichotomous outcomes were expressed as risk ratio (RR) with corresponding 95% CIs. Continuous outcomes were expressed as mean difference (MD) or standardized MD with 95% CI. Results: A total of 33 RCTs with 2657 children (median [range] age, 12 [7-17] years; 1726 girls [67.3%]) were included. Twelve studies compared CBT with no intervention, 5 studies compared CBT with educational support, 3 studiescompared yoga with no intervention, 2 studies compared hypnotherapy with no intervention, 2 studies compared gut-directed hypnotherapy with hypnotherapy, and 2 studies compared guided imagery with relaxation. Seven studies evaluated other unique comparisons (eg, visceral osteopathy vs normal osteopathy). Per the GRADE framework, owing to risk of bias, there was moderate certainty in evidence that CBT was associated with higher treatment success numbers (n = 324 children; RR, 2.37; 95% CI 1.30-4.34; number needed to treat [NNT] = 5), lower pain frequency (n = 446 children; RR, -0.36; 95% CI, -0.63 to -0.09), and lower pain intensity (n = 332 children; RR, -0.58; 95% CI, -0.83 to -0.32) than no intervention. Owing to high imprecision, there was low certainty in evidence that there was no difference between CBT and educational support for pain intensity (n = 127 children; MD, -0.36; 95% CI, -0.87 to 0.15). Owing to risk of bias and imprecision, there was low certainty in evidence that hypnotherapy resulted in higher treatment success compared with no intervention (n = 91 children; RR, 2.86; 95% CI, 1.19-6.83; NNT = 5). Owing to risk of bias and imprecision, there was low certainty in evidence that yoga had similar treatment success to no intervention (n = 99 children; RR, 1.09; 95% CI, 0.58-2.08). Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that CBT and hypnotherapy may be considered as a treatment for FAPDs in childhood. Future RCTs should address quality issues to enhance the overall certainty of the results, and studies should consider targeting these interventions toward patients who are more likely to respond.

Dietary interventions for functional abdominal pain disorders in children: a systematic review and meta-analysis.

BACKGROUND: Functional abdominal pain disorders (FAPDs) are common among children and are associated with decreased quality of life and school attendance. Several dietary interventions have been suggested to improve symptoms of FAPDs. This systematic review assessed the efficacy and safety of dietary interventions for pediatric FAPDs. DESIGN AND METHODS: Electronic databases were searched (inception-October 2021). Systematic reviews or RCTs were included if children (4-18 years) with FAPDs were treated with dietary interventions and compared to placebo, no diet or any other diet. Data extraction and assessment of quality of evidence based on GRADE system was independently performed by two review authors. Outcomes were treatment success, pain intensity and frequency, and withdrawal due to adverse events. RESULTS: Twelve articles were included, representing data of 819 pediatric FAPD patients. Trials investigating fibers, FODMAP diet, fructans, fructose-restricted diet, prebiotic (inulin), serum-derived bovine immunoglobulin, and vitamin D supplementation were included. We found very low-certainty evidence that the use of fibers leads to higher treatment success (NNT = 5). CONCLUSION: Based on current evidence, the use of fibers can be discussed in daily practice. High-quality intervention trials are highly needed to investigate if other dietary interventions are effective in the treatment of pediatric FAPD.

Interventions for the management of abdominal pain in Crohn's disease and inflammatory bowel disease.

BACKGROUND: Crohn's disease is a remitting and relapsing disorder that can affect the whole gastrointestinal tract. Active disease symptoms include abdominal pain, fatigue, weight loss, and diarrhoea. There is no known cure; however, the disease can be managed, and therefore places a huge financial burden on healthcare systems. Abdominal pain is a common and debilitating symptom of Crohn's and other inflammatory bowel diseases (IBDs), and is multifaceted. Abdominal pain in Crohn's disease could be a symptom of disease relapse or related to medication adverse effects, surgical complications and strictures or adhesions secondary to IBD. In the absence of these factors, around 20 to 50% of people with Crohn's in remission still experience pain. OBJECTIVES: To assess the efficacy and safety of interventions for managing abdominal pain in people with Crohn's disease and IBD (where data on ulcerative colitis and Crohn's disease could not be separated). SEARCH METHODS: We searched CENTRAL, MEDLINE, three other databases, and clinical trials registries on 29 April 2021. We also searched the references of trials and systematic reviews for any additional trials. SELECTION CRITERIA: All published, unpublished, and ongoing randomised trials that compared interventions for the management of abdominal pain in the setting of Crohn's disease and IBD, with other active interventions or standard therapy, placebo, or no therapy were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS: Five review authors independently conducted data extraction and 'Risk of bias' assessment of the included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. MAIN RESULTS: We included 14 studies (743 randomised participants). Five studies evaluated participants with Crohn's disease; seven studies evaluated participants with IBD where the data on ulcerative colitis and Crohn's disease could not be separated; and two studies provided separate results for Crohn's disease participants. Studies considered a range of disease activity states. Two studies provided intervention success definitions, whilst the remaining studies measured pain as a continuous outcome on a rating scale. All studies except one measured pain intensity, whilst three studies measured pain frequency. Withdrawals due to adverse events were directly or indirectly reported in 10 studies. No conclusions could be drawn about the efficacy of the majority of the interventions on pain intensity, pain frequency, and treatment success, except for the comparison of transcranial direct current stimulation to sham stimulation. The certainty of the evidence was very low in all but one comparison because of imprecision due to sparse data and risk of bias assessed as unclear or high risk. Two studies compared a low FODMAP diet (n=37) to a sham diet (n=45) in IBD patients. The evidence on pain intensity was of very low certainty (MD -12.00, 95% CI -114.55 to 90.55). One study reported pain intensity separately for CD participants in the low FODMAP group [n=14, mean(SD)=24 (82.3)] and the sham group [n=12, mean(SD)=32 (69.3)]. The same study also reported pain frequency for IBD participants in the low FODMAP group [n=27, mean(SD)=36 (26)] and sham group [n=25, mean(SD)=38(25)] and CD participants in the low FODMAP group [n=14, mean(SD)=36 (138.4)] and sham group [n=12, mean(SD)=48 (128.2)]. Treatment success was not reported. One study compared a low FODMAP diet (n=25) to high FODMAP/normal diet (n=25) in IBD patients. The data reported on pain intensity was unclear. Treatment success and pain frequency were not reported. One study compared medicine-separated moxibustion combined with acupuncture (n=51) versus wheat bran-separated moxibustion combined with shallow acupuncture (n=51) in CD patients. The data reported on pain intensity and frequency were unclear. Treatment success was not reported. One study compared mindfulness with CBT (n=33) versus no treatment (n=33) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity and frequency (MD -37.00, 95% CI -87.29 to 13.29). Treatment success was not reported. One study compared soft non-manipulative osteopathic treatment (n=16) with no treatment besides doctor advice (n=14) in CD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD 0.01, 95% CI -1.81 to 1.83). Treatment success and pain frequency were not reported. One study compared stress management (n=15) to self-directed stress management(n=15) and to standard treatment (n=15) in CD patients. The evidence is very uncertain about the effect of these treatments on pain intensity (MD -30.50, 95% CI -58.45 to -2.55 and MD -34.30, 95% CI -61.99 to -6.61). Treatment success and pain frequency were not reported. One study compared enteric-release glyceryl trinitrate (n=34) with placebo (n=36) in CD patients. The data reported on pain intensity was unclear. Treatment success and pain frequency were not reported.  One study compared 100 mg olorinab three times per day (n=8) with 25 mg olorinab three times per day (n=6) in CD patients. Pain intensity was measured as a 30% reduction in weekly average abdominal pain intensity score for the 100mg group (n=5) and the 25mg group (n=6). The evidence is very uncertain about the effect of this treatment on pain intensity (RR 0.66, 95% CI 0.38 to 1.15). Treatment success and pain frequency were not reported. One study compared relaxation training (n=28) to a waitlist (n=28) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.72, 95% CI -1.85 to 0.41). Treatment success and pain frequency were not reported. One study compared web-based education (n=30) with a book-based education (n=30) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.13, 95% CI -1.25 to 0.99). Treatment success and pain frequency were not reported. One study compared yoga (n=50) with no treatment (n=50) in IBD patients. The data reported on treatment success were unclear. Pain frequency and intensity were not reported. One study compared transcranial direct current stimulation (n = 10) to sham stimulation (n = 10) in IBD patients. There may be an improvement in pain intensity when transcranial direct current is compared to sham stimulation (MD -1.65, 95% CI -3.29 to -0.01, low-certainty evidence). Treatment success and pain frequency were not reported. One study compared a kefir diet (Lactobacillus bacteria) to no intervention in IBD patients and provided separate data for their CD participants. The evidence is very uncertain about the effect of this treatment on pain intensity in IBD (MD 0.62, 95% CI 0.17 to 1.07) and CD (MD -1.10, 95% CI -1.67 to -0.53). Treatment success and pain frequency were not reported. Reporting of our secondary outcomes was inconsistent. The most adverse events were reported in the enteric-release glyceryl trinitrate and olorinab studies.  In the enteric-release glyceryl trinitrate study, the adverse events were higher in the intervention arm. In the olorinab study, more adverse events were observed in the higher dose arm of the intervention.  In the studies on non-drug interventions, adverse events tended to be very low or zero. However, no clear judgements regarding adverse events can be drawn for any interventions due to the low number of events. Anxiety and depression were measured and reported at the end of intervention in only one study; therefore, no meaningful conclusions can be drawn for this outcome. AUTHORS' CONCLUSIONS: We found low certainty evidence that transcranial direct current stimulation may improve pain intensity compared to sham stimulation. We could not reach any conclusions on the efficacy of any other interventions on pain intensity, pain frequency, and treatment success. The certainty of the evidence was very low due to the low numbers of studies and participants in each comparison and clinical heterogeneity amongst the studies. While no serious or total adverse events were elicited explicitly with any of the treatments studied, the reported events were very low. The certainty of the evidence for all comparisons was very low, so no conclusions can be drawn.

Interventions for the management of abdominal pain in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn's disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC. OBJECTIVES: To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis. SEARCH METHODS: We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials. SELECTION CRITERIA: All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS: We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease.   No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias. One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported. One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported. One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported. One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported. One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported. Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome.  We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence. The reporting of secondary outcomes was inconsistent. Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events. Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes. AUTHORS' CONCLUSIONS: We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions. While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn. There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.

Probiotics for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008. OBJECTIVES: To assess the efficacy and safety of probiotics for the induction of remission in CD. SEARCH METHODS: The following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes. MAIN RESULTS: There were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: The available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.

Patient/service user involvement in medical education: A best evidence medical education (BEME) systematic review: BEME Guide No. 58.

Background: The extent to which patients and service users are involved in medical education varies widely. There is a need for an up to date systematic review of the literature that examines what involvement (description), the potential outcome of such involvement (justification) and 'why' such involvement impacts students (clarification).Methods: Systematic searches of four databases were undertaken. Citations were screened and consensus reached for inclusion/exclusion of studies. Quality of study design and interventional presentation were assessed.Results: Of the 39 studies included in the review, 4 studies were encounter based, 17 sharing experiences, 16 with patients involved in teaching, 2 studies describing consumers as tutors, and none with involvement at the institutional level. Outcomes in terms of benefits to learners included increased empathy and understanding of illness as experienced by patients, improved communication with patients and a greater understanding of patient-center care. Educational quality assessment showed specific weaknesses in theoretical underpinning, curriculum outcomes, content or pedagogy.Conclusions: Patients can enrich medical education by allowing learners to explore patient-centered perspectives in holistic care. For educators this review highlights the lack of an underpinning conceptual basis for which to translate theory into practice.

Interventions for maintenance of surgically induced remission in Crohn's disease: a network meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic disease of the gut. About 75% of people with CD undergo surgery at least once in their lifetime to induce remission. However, as there is no known cure for the disease, patients usually experience a recurrence even after surgery. Different interventions are routinely used in maintaining postsurgical remission. There is currently no consensus on which treatment is the most effective. OBJECTIVES: To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn's disease and rank the treatments in order of effectiveness. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, and Embase from inception to 15 January 2019. We also searched reference lists of relevant articles, abstracts from major gastroenterology meetings, ClinicalTrials.gov, and the WHO ICTRP. There was no restriction on language, date, or publication status. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) that compared different interventions used for maintaining surgically induced remission in people with CD who were in postsurgical remission. Participants had to have received maintenance treatment for at least three months. We excluded studies assessing enteral diet, diet manipulation, herbal medicine, and nutritional supplementation. DATA COLLECTION AND ANALYSIS: Two review authors independently selected relevant studies, extracted data, and assessed the risk of bias. Any disagreements were resolved by discussion or by arbitration of a third review author when necessary. We conducted a network meta-analysis (NMA) using a Bayesian approach through Markov Chain Monte Carlo (MCMC) simulation. For the pairwise comparisons carried out in Review Manager 5, we calculated risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). For the NMA, we presented hazard ratios (HR) with corresponding 95% credible intervals (95% CrI) and reported ranking probabilities for each intervention. For the NMA, we focused on three main outcomes: clinical relapse, endoscopic relapse, and withdrawals due to adverse events. Data were insufficient to assess time to relapse and histologic relapse. Adverse events and serious adverse events were not sufficiently or objectively reported to permit an NMA. We used CINeMA (Confidence in Network Meta-Analysis) methods to evaluate our confidence in the findings within networks, and GRADE for entire networks. MAIN RESULTS: We included 35 RCTs (3249 participants) in the review. The average age of study participants ranged between 33.6 and 38.8 years. Risk of bias was high in 18 studies, low in four studies, and unclear in 13 studies. Of the 35 included RCTs, 26 studies (2581 participants; 9 interventions) were considered eligible for inclusion in the NMA. The interventions studied included 5-aminosalicylic acid (5-ASA), adalimumab, antibiotics, budesonide, infliximab, probiotics, purine analogues, sulfasalazine, and a combination of sulfasalazine and prednisolone. This resulted in 30 direct contrasts, which informed 102 mixed-treatment contrasts.The evidence for the clinical relapse network (21 studies; 2245 participants) and endoscopic relapse (12 studies; 1128 participants) were of low certainty while the evidence for withdrawal due to adverse events (15 studies; 1498 participants) was of very low certainty. This assessment was due to high risk of bias in most of the studies, inconsistency, and imprecision across networks. We mainly judged individual contrasts as of low or very low certainty, except 5-ASA versus placebo, the evidence for which was judged as of moderate certainty.We ranked the treatments based on effectiveness and the certainty of the evidence. For clinical relapse, the five most highly ranked treatments were adalimumab, infliximab, budesonide, 5-ASA, and purine analogues. We found some evidence that adalimumab (HR 0.11, 95% Crl 0.02 to 0.33; low-certainty evidence) and 5-ASA may reduce the probability of clinical relapse compared to placebo (HR 0.69, 95% Crl 0.53 to 0.87; moderate-certainty evidence). However, budesonide may not be effective in preventing clinical relapse (HR 0.66, 95% CrI 0.27 to 1.34; low-certainty evidence). We are less confident about the effectiveness of infliximab (HR 0.36, 95% CrI 0.02 to 1.74; very low-certainty evidence) and purine analogues (HR 0.75, 95% CrI 0.55 to 1.00; low-certainty evidence). It was unclear whether the other interventions reduced the probability of a clinical relapse, as the certainty of the evidence was very low.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing endoscopic relapse. Whilst there might be some evidence of prevention of endoscopic relapse with adalimumab (HR 0.10, 95% CrI 0.01 to 0.32; low-certainty evidence), no other intervention studied appeared to be effective.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing withdrawal due to adverse events. Withdrawal due to adverse events appeared to be least likely with sulfasalazine (HR 1.96, 95% Crl 0.00 to 8.90; very low-certainty evidence) and most likely with antibiotics (HR 53.92, 95% Crl 0.43 to 259.80; very low-certainty evidence). When considering the network as a whole, two adverse events leading to study withdrawal (i.e. pancreatitis and leukopenia) occurred in more than 1% of participants treated with an intervention. Pancreatitis occurred in 2.8% (11/399) of purine analogue participants compared to 0.17% (2/1210) of all other groups studied. Leukopenia occurred in 2.5% (10/399) of purine analogue participants compared to 0.08% (1/1210) of all other groups studied. AUTHORS' CONCLUSIONS: Due to low-certainty evidence in the networks, we are unable to draw conclusions on which treatment is most effective for preventing clinical relapse and endoscopic relapse. Evidence on the safety of the interventions was inconclusive, however cases of pancreatitis and leukopenia from purine analogues were evident in the studies. Larger trials are needed to further understand the effect of the interventions on endoscopic relapse.

Dietary interventions for induction and maintenance of remission in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity. OBJECTIVES: To evaluate the efficacy and safety of dietary interventions on IBD outcomes. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE. MAIN RESULTS: The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events. AUTHORS' CONCLUSIONS: The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.

Significant variations in nutritional supplementation amongst neonates in the United Kingdom.

AIM: To ascertain United Kingdom adherence to European society of Paediatric Gastroenterology, Hepatology and Nutrition guidance (ESPGHAN). METHODS: A national cross sectional questionnaire study of neonatal units across England was completed between January and March 2014. All 174 units in the country were attempted to be contacted to complete a telephone survey. This included all level 1, 2 and 3 units. They were initially contacted by phone and asking any senior member of the team about their current practice and procedures. The first ten telephone interviews were completed with two researchers present to ensure consistency of approach. If no response was received or no details were available, one further attempt was made to contact the unit. The results were recorded in a proforma and then collated and entered into a spreadsheet for analysis. Comparison to United Kingdom adherence to ESPGHAN guidance was completed. RESULTS: Response rate was 53%. There was variation in use of all supplements. The survey collected data from 91 neonatal units (53% response rate). It was found that 10% of neonatal units had no fixed policy on supplements. The protocols regarding supplementation involved predominantly folic acid, vitamin A, vitamin D and iron, with much variation in doses and regimens. The criteria for prescribing supplements was largely based on age (47%) with only 7% using a weight targets to initiate supplements. Summary data regarding the appropriateness of each nutritional supplement for a variety of different weights are presented, as well as comparison to ESPGHAN guidance which suggests issues with both underdoing of Breast Fed infants and overdosing of infants on several artificial formulas which already contain significant amounts of these nutritional elements. CONCLUSION: There is significant heterogeneity in neonatal policies when prescribing supplements to neonates. National policies which take international guidance into account are recommended.

Osmotic and stimulant laxatives for the management of childhood constipation.

BACKGROUND: Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice. OBJECTIVES: We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialized Trials Register from inception to 10 March 2016. There were no language restrictions. We also searched the references of all included studies, personal contacts and drug companies to identify studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives to placebo or another intervention, with participants aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. DATA COLLECTION AND ANALYSIS: Relevant papers were identified and two authors independently assessed the eligibility of trials, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. For continuous outcomes we calculated the mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated the risk ratio (RR) and 95% CI using a fixed-effect model. The Chi(2) and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity. We assessed the overall quality of the evidence supporting the primary and secondary outcomes using the GRADE criteria. MAIN RESULTS: Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95). AUTHORS' CONCLUSIONS: The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation.

Are we talking the same paradigm? Considering methodological choices in health education systematic review.

For the past two decades, there have been calls for medical education to become more evidence-based. Whilst previous works have described how to use such methods, there are no works discussing when or why to select different methods from either a conceptual or pragmatic perspective. This question is not to suggest the superiority of such methods, but that having a clear rationale to underpin such choices is key and should be communicated to the reader of such works. Our goal within this manuscript is to consider the philosophical alignment of these different review and synthesis modalities and how this impacts on their suitability to answer different systematic review questions within health education. The key characteristic of a systematic review that should impact the synthesis choice is discussed in detail. By clearly defining this and the related outcome expected from the review and for educators who will receive this outcome, the alignment will become apparent. This will then allow deployment of an appropriate methodology that is fit for purpose and will indeed justify the significant work needed to complete a systematic. Key items discussed are the positivist synthesis methods meta-analysis and content analysis to address questions in the form of 'whether and what' education is effective. These can be juxtaposed with the constructivist aligned thematic analysis and meta-ethnography to address questions in the form of 'why'. The concept of the realist review is also considered. It is proposed that authors of such work should describe their research alignment and the link between question, alignment and evidence synthesis method selected. The process of exploring the range of modalities and their alignment highlights gaps in the researcher's arsenal. Future works are needed to explore the impact of such changes in writing from authors of medical education systematic review.

Glutamine for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. OBJECTIVES: To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. SEARCH METHODS: We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. MAIN RESULTS: Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. The other study (24 patients) compared glutamine-supplemented total parenteral nutrition to non-supplemented total parenteral nutrition in adult patients (> 18 years of age) with acute exacerbation of inflammatory bowel disease. The paediatric study was rated as low risk of bias. The study in adult patients was rated as unclear risk of bias for blinding and low risk of bias for all other items. It was not possible to pool data for meta-analysis because of significant differences in study populations, nature of interventions, and the way outcomes were assessed. Data from one study showed no statistically significant difference in clinical remission rates at four weeks. Forty-four per cent (4/9) of patients who received a glutamine-enriched polymeric diet achieved remission compared to 56% (5/9) of patients who received a standard low-glutamine polymeric diet (RR 0.80, 95% CI 0.31 to 2.04). A GRADE analysis indicated that the overall quality of evidence for this outcome was low due to serious imprecision (9 events). In both included studies, no statistically significant changes in intestinal permeability were found between patients who received glutamine supplementation and those who did not. Neither study reported on clinical response, quality of life or growth in children. Adverse event data were not well documented. There were no serious adverse events in the paediatric study. The study in adult patients reported three central catheter infections with positive blood cultures in the glutamine group compared to none in the control group (RR 7.00, 95% CI 0.40 to 122.44). AUTHORS' CONCLUSIONS: Currently there is insufficient evidence to allow firm conclusions regarding the efficacy and safety of glutamine for induction of remission in Crohn's disease. Data from two small studies suggest that glutamine supplementation may not be beneficial in active Crohn's disease but these results need to be interpreted with caution as they are based on small numbers of patients. This review highlights the need for adequately powered randomised controlled trials to investigate the efficacy and safety of glutamine for induction of remission in Crohn's disease.

Cochrane Review: Osmotic and stimulant laxatives for the management of childhood constipation (Review).

BACKGROUND: Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice. OBJECTIVES: We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation. SEARCH METHODS: The search (inception to May 7, 2012) was standardised and not limited by language and included electronic searching (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register), reference searching of all included studies, personal contacts and drug companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives with either placebo or another intervention, with patients aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. DATA COLLECTION AND ANALYSIS: Relevant papers were identified and the authors independently assessed the eligibility of trials. Methodological quality was assessed using the Cochrane risk of bias tool.The Cochrane RevMan software was used for analyses. Patients with final missing outcomes were assumed to have relapsed. For continuous outcomes we calculated a mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated an odds ratio (OR) and 95% confidence intervals (95% CI) using a fixed-effect model. The chi square and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity MAIN RESULTS: Eighteen RCTs (1643 patients) were included in the review. Nine studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Meta-analysis of 4 studies with 338 participants comparing PEG with lactulose showed significantly greater stools per week with PEG (MD 0.95 stools per week, 95% CI 0.46 to 1.44), although follow up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent of PEG patients required additional therapies compared to 30% of lactulose patients (OR 0.49, 95% CI 0.27 to 0.89). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools/wk was significantly greater with PEG (MD 0.69 stools per week, 95% CI 0.48 to 0.89). However, the magnitude of this difference is quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring paraffin (MD 4.94 stools per week, 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), and PEG and liquid paraffin (1 study, 158 patients, MD 0.70, 95% CI -0.38 to 1.78). AUTHORS' CONCLUSIONS: The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow up. However, PEG appears safe and well tolerated. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil), which was also well tolerated.There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long-term use of PEG for childhood constipation, as well as the role of liquid paraffin. PLAIN LANGUAGE SUMMARY: Laxatives for the management of childhood constipation Constipation within childhood is an extremely common problem. Despite the widespread use of laxatives by health professionals to manage constipation in children, there has been a long standing lack of evidence to support this practice. This review included eighteen studies with a total of 1643 patients that compared nine different agents to either placebo (inactive medications) or each other. The results of this review suggest that polyethylene glycol preparations may increase the frequency of bowel motions in constipated children. Polyethylene glycol was generally safe, with lower rates of minor side effects compared to other agents. Common side effects included flatulence, abdominal pain, nausea, diarrhoea and headache. There was also some evidence that liquid paraffin (mineral oil) increased the frequency of bowel motions in constipated children and was also safe. Common side effects with liquid paraffin included abdominal pain, distention and watery stools. There was no evidence to suggest that lactulose is superior to the other agents studied, although there were no trials comparing it to placebo. The results of the review should be interpreted with caution due to methodological quality and statistical issues in the included studies. In addition, these studies were relatively short in duration and so it is difficult to assess the long-term effectiveness of these agents for the treatment of childhood constipation. Long-term effectiveness is important, given the often chronic nature of this problem in children.

Application of the team objective structured clinical encounter (TOSCE) for continuing professional development amongst postgraduate health professionals.

Educators in healthcare face significant challenges trying to improve interprofessional teamworking skills, with a lack of clarity on how to teach and evaluate such skills. Previously, the team objective structured clinical encounter (TOSCE) has been reported as a teaching and assessment tool, but it has been used primarily in homogenous groups of undergraduates. An interprofessional team of educators set out to evaluate the TOSCE as a teaching intervention amongst a large interprofessional group of postgraduate nurses and midwives. After the TOSCE, 83% of participants reported that they were more aware of potential weaknesses in teamworking and 60% felt more able to work in a team. Mean Likert scale ratings were 4/5 for usefulness, enjoyment and relevance. The TOSCE is a feasible tool for teamwork skill assessment in the demanding postgraduate interprofessional setting and requires further investigation to ascertain its potential for formative and summative assessment of skills.