Melatonin for the management of sleep problems in children with neurodevelopmental disorders: a systematic review and meta-analysis

Children with neurodevelopmental disorders have a higher prevalence of sleep disturbances. Currently there is variation in the use of melatonin; hence, an up-to-date systematic review is indicated to summarise the current available evidence. To determine the efficacy and safety of melatonin as therapy for sleep problems in children with neurodevelopmental disorders. PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials were searched from inception up to January 2018. Two reviewers performed data assessment and extraction. We assessed randomised controlled trials that compared melatonin with placebo or other intervention for the management of sleep disorders in children (<18 years) with neurodevelopmental disorders. We identified 3262 citations and included 13 studies in this meta-analysis. Main outcomes included total sleep time, sleep onset latency, frequency of nocturnal awakenings and adverse events. Thirteen randomised controlled trials (n=682) met the inclusion criteria. A meta-analysis of nine studies (n=541) showed that melatonin significantly improved total sleep time compared with placebo (mean difference (MD)=48.26 min, 95% CI 36.78 to 59.73, I =31%). In 11 studies (n=581), sleep onset latency improved significantly with melatonin use (MD=-28.97, 95% CI -39.78 to -18.17). No difference was noted in the frequency of nocturnal awakenings (MD=-0.49, 95% CI -1.71 to 0.73). No medication-related serious adverse event was reported. Melatonin appeared safe and effective in improving sleep in the studied children. The overall quality of the evidence is limited due to heterogeneity and inconsistency. Further research is needed. [Abstract copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Interventions for the management of abdominal pain in Crohn's disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of interventions for managing abdominal pain in people with Crohn's disease

Interventions for the management of abdominal pain in ulcerative colitis

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of interventions for managing abdominal pain in ulcerative colitis

Probiotics to prevent infantile colic

Background Infantile colic is typically defined as full‐force crying for at least three hours per day, on at least three days per week, for at least three weeks. Infantile colic affects a large number of infants and their families worldwide. Its symptoms are broad and general, and while not indicative of disease, may represent a serious underlying condition in a small percentage of infants who may need a medical assessment. Probiotics are live microorganisms that alter the microflora of the host and provide beneficial health effects. The most common probiotics used are of Lactobacillus, Bifidobacterium and Streptococcus. There is growing evidence to suggest that intestinal flora in colicky infants differ from those in healthy infants, and it is suggested that probiotics can redress this balance and provide a healthier intestinal microbiota landscape. The low cost and easy availability of probiotics makes them a potential prophylactic solution to reduce the incidence and prevalence of infantile colic. Objectives To evaluate the efficacy and safety of prophylactic probiotics in preventing or reducing severity of infantile colic. Search methods In January 2018 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 10 other databases and two trials registers. In addition, we handsearched the abstracts of relevant meetings, searched reference lists, ran citation searches of included studies, and contacted authors and experts in the field, including the manufacturers of probiotics, to identify unpublished trials. Selection criteria Randomised control trials (RCTs) of newborn infants less than one month of age without the diagnosis of infantile colic at recruitment. We included any probiotic, alone or in combination with a prebiotic (also known as synbiotics), versus no intervention, another intervention(s) or placebo, where the focus of the study was the effect of the intervention on infantile colic. Data collection and analysis We used standard methodological procedures of Cochrane. Main results Our search yielded 3284 records, and of these, we selected 21 reports for full‐text review. Six studies with 1886 participants met our inclusion criteria, comparing probiotics with placebo. Two studies examined Lactobacillus reuteri DSM, two examined multi‐strain probiotics, one examined Lactobacillus rhamnosus, and one examined Lactobacillus paracasei and Bifidobacterium animalis. Two studies began probiotics during pregnancy and continued administering them to the baby after birth. We considered the risk of bias for randomisation as low for all six trials; for allocation concealment as low in two studies and unclear in four others. All studies were blinded, and at low risk of attrition and reporting bias. A random‐effects meta‐analysis of three studies (1148 participants) found no difference between the groups in relation to occurrence of new cases of colic: risk ratio (RR) 0.46, 95% confidence interval (CI) 0.18 to 1.19; low‐certainty evidence; I2 = 72%. A random‐effects meta‐analysis of all six studies (1851 participants) found no difference between the groups in relation to serious adverse effects (RR 1.02, 95% CI 0.14 to 7.21; low‐certainty evidence; I2 not calculable (only four serious events for one comparison, two in each group: meconium plug obstruction, patent ductus arteriosus and neonatal hepatitis). A random‐effects meta‐analysis of three studies (707 participants) found a mean difference (MD) of –32.57 minutes per day (95% CI –55.60 to –9.54; low‐certainty evidence; I2 = 93%) in crying time at study end in favour of probiotics. A subgroup analysis of the most studied agent, Lactobacillus reuteri, showed a reduction of 44.26 minutes in daily crying with a random‐effects model (95% CI –66.6 to –21.9; I2 = 92%), in favour of probiotics. Authors' conclusions There is no clear evidence that probiotics are more effective than placebo at preventing infantile colic; however, daily crying time appeared to reduce with probiotic use compared to placebo. There were no clear differences in adverse effects. We are limited in our ability to draw conclusions by the certainty of the evidence, which we assessed as being low across all three outcomes, meaning that we are not confident that these results would not change with the addition of further researc

Enteral nutrition for maintenance of remission in Crohn's disease [Review]

Background Prevention of relapse is a major issue in the management of quiescent Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6‐mercaptopurine and azathioprine) may be effective for maintaining remission in CD, but these drugs may cause significant adverse events. Interventions that are effective and safe for maintenance of remission in CD are desirable. Objectives The primary objectives were to evaluate the efficacy and safety of enteral nutrition for the maintenance of remission in CD and to assess the impact of formula composition on effectiveness. Search methods We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register and clinicaltrials.gov from inception to 27 July 2018. We also searched references of retrieved studies and reviews. Selection criteria Randomised controlled trials (RCTs) including participants of any age with quiescent CD were considered for inclusion. Studies that compared enteral nutrition with no intervention, placebo or any other intervention were selected for review. Data collection and analysis Two authors independently screened studies for inclusion, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included anthropometric measures (i.e. height and weight), quality of life (QoL), adverse events, serious adverse events and withdrawal due to adverse events. We calculated the risk ratio and 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference and 95% CI. A random‐effects model was used for the statistical analysis. We used the GRADE criteria to assess the overall certainty of the evidence supporting the primary outcome and selected secondary outcomes. Main results Four RCTs (262 adult participants) met the inclusion criteria. One study (N = 33) compared an elemental diet to a non‐elemental (polymeric) diet. One study (N = 51) compared a half elemental diet to a regular free diet. Another study (N = 95) compared an elemental diet to 6‐mercaptopurine (6‐MP) or a no treatment control group. One study (N= 83) compared a polymeric diet to mesalamine. Two studies were rated as high risk of bias due to lack of blinding or incomplete outcome data. The other two studies were judged to have an unclear risk of bias. The studies were not pooled due to differences in control interventions and the way outcomes were assessed. The effect of an elemental diet compared to a polymeric diet on remission rates or withdrawal due to adverse events is uncertain. Fifty‐eight per cent (11/19) of participants in the elemental diet group relapsed at 12 months compared to 57% (8/14) of participants in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty evidence). Thirty‐two per cent (6/19) of participants in the elemental diet group were intolerant to the enteral nutritional formula because of taste or smell and were withdrawn from the study in the first 2 weeks compared to zero participants (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty evidence). Anthropometric measures, QoL, adverse events and serious adverse events were not reported as outcomes. The effect of an elemental diet (half of total daily calorie requirements) compared to a normal free diet on relapse rates is uncertain. Thirty‐five per cent (9/26) of participants in the elemental diet group relapsed at 12 months compared to 64% (16/25) of participants in the free diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No adverse events were reported. This study reported no differences in weight change between the two diet groups. Height and QoL were not reported as outcomes. The effect of an elemental diet compared to 6‐MP on relapse rates or adverse events is uncertain. Thirty‐eight per cent (12/32) of participants in the elemental diet group relapsed at 12 months compared to 23% (7/30) of participants in the 6‐MP group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent (1/32) of participants in the elemental diet group had an adverse event compared to 13% (4/30) of participants in the 6‐MP group (RR 0.23, 95% CI 0.03 to 1.98; low certainty evidence). Adverse events in the elemental diet group included surgery due to worsening CD. Adverse events in the 6‐MP group included liver injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No serious adverse events or withdrawals due to adverse events were reported. Weight, height and QoL were not reported as outcomes The effect of a polymeric diet compared to mesalamine on relapse rates and weight is uncertain. Forty‐two per cent (18/43) of participants in the polymeric diet group relapsed at 6 months compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI 0.49 to 1.19; low certainty evidence). The mean difference in weight gain over the study period was 1.9 kg higher in the polymeric diet group compared to mesalamine (95% CI ‐4.62 to 8.42; low certainty evidence). Two participants in the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had an adverse event. Height, QoL, serious adverse events and withdrawal due to adverse events were not reported as outcomes. Authors' conclusions The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn. More research is needed to determine the efficacy and safety of using enteral nutrition as maintenance therapy in CD. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available

Antibiotics for the induction and maintenance of remission in ulcerative colitis

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine whether antibiotic therapy is safe and effective for the induction and maintenance of remission in ulcerative colitis (UC)

Inverted appendix mistaken for a polyp during colonoscopy and leading to intussusception

AbstractA spectrum of appendiceal diseases, ranging from simple mucous distension to acute perforated appendicitis, are seen in patients with CF. We report a 6 year old boy with CF and recurrent periumbilical pain. During colonoscopy, a fleshy pedunculated mass at the junction of the ascending colon and caecum was mistaken for a polyp and excised. However, histopathological examination suggested it was a segment of inverted appendix. The remnant of the inverted appendix was subsequently found to be associated with an intussusception

Patient education interventions for the management of Inflammatory Bowel Disease

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To identify the different types of educational interventions, how they are delivered, and to determine their effectiveness and safety in people with IBD

Treatments for intractable constipation in childhood

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the efficacy and safety of treatments used for intractable constipation in children