Pharmacological treatment of gastro-oesophageal reflux in children.

BACKGROUND: Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014. OBJECTIVES: To assess the effects of pharmacological treatments for GOR in infants and children. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old. DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. MAIN RESULTS: We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean difference between the two different dosing regimens was 2.3 (95% CI -2 to 6.6), and for the lower-weight group, symptom score MD was 4.6 (95% CI -2.9 to 12). Pantoprazole: pantoprazole may or may not improve symptom scores at 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg pantoprazole in children aged one to five years by week eight, with no difference between 0.3 mg/kg and 1.2 mg/kg dosing (0.3 mg/kg mean -2.4 ± 1.7; 1.2 mg/kg -1.7 ± 1.2: MD 0.7 (95% CI -0.4 to 1.8)) (one study, 60 children; very low-certainty evidence). There were insufficient summary data to assess other medications. AUTHORS' CONCLUSIONS: There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H2antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).

A Clinical Investigation of the Performance and Safety of Epaderm®, an Emollient Cream.

INTRODUCTION: Emollients provide an occlusive barrier for dry and atopic skin, retain moisture, protect it from irritants, and form the basis of eczema treatment. METHODS AND ANALYSIS: A prospective interventional single arm study to evaluate the performance and safety of Epaderm® Cream, an emollient and cleanser containing 25% (w/w) paraffin and 5% (w/w) glycerine (thereafter, an emollient cream), in patients with dry skin conditions. The primary outcome measure was participant evaluation of skin moisturisation after treatment with an emollient cream for up to 4 weeks. Secondary outcome measures included: evaluation of skin softness using a questionnaire and of pruritus on a visual analogue scale (VAS); clinician assessment of xerosis using Overall Dry Skin (ODS) score and measurement of skin hydration using a non-invasive device (MoistureMeterEpiD, Delfin Technologies) at each visit. Sign test and Wilcoxon signed rank test were used to analyse changes from baseline. RESULTS: A total of 114 participants completed the study. 84.2% (80 out of 95) of participants or parents strongly agreed or agreed that the cream improved skin moisturisation at 4 weeks of treatment at the target area (p<0.0001). 86.3% of participants agreed that skin softness improved after 4 weeks (p <0.0001). ODS score improved from 2.1 (standard deviation (SD) 1.0) to 0.7 (SD 0.8) at 4 weeks. Skin hydration at the target area improved from 31.5 (SD 9.3) to 40.5 (SD 8.3) (p<0.001) at 4 weeks. Mean skin itchiness reduced from 38.0 (SD 25.4) to 17.7 (SD 19.8) at 4 weeks (p<0.0001). Ten (8.3%) adverse device events (ADEs) were reported. CONCLUSION: The emollient cream was well tolerated and demonstrated significant improvements in patient-reported skin moisturisation and softness as well as in clinical measurement of xerosis and skin hydration across all age groups including infants. The emollient cream can be recommended for dry skin conditions including atopic dermatitis and psoriasis.

Functional abdominal pain: what clinicians need to know.

Abdominal pain in childhood is extremely common and presents frequently to both primary and secondary care, with many children having recurrent pain which impacts on daily functioning. Despite this most children have no discernible underlying pathology. We discuss the underlying mechanism for functional abdominal pain (visceral hypersensitivity), the evidence base linking parental anxiety and patient symptoms, and how parents can be supported in managing their children's symptoms by addressing questions commonly asked by children and families. We look at the evidence for a one-stop rational approach to investigation including a coeliac screen, inflammatory markers and consideration of stool faecal calprotectin, in the absence of red flags. We evaluate commonly used treatments for functional abdominal pain, within a context of managing family expectations. Given the limitations in pharmacological treatment options, trials of probiotics, peppermint oil, mebeverine and (for short-term use only) hyoscine butylbromide may be appropriate. Psychological interventions including cognitive-behavioural therapy, distraction techniques and hypnotherapy have a better evidence base. There is also some evidence for other complementary therapies in children, including yoga and neurostimulation. Outcome is generally good providing there is child and family acceptance of the multiple factors implicated in the aetiology of the pain.

How to use faecal calprotectin in management of paediatric inflammatory bowel disease.

Faecal calprotectin (FC) is a neutrophil-derived protein released in stool in response to mucosal inflammation. It is a simple, cheap and non-invasive test with high sensitivity and moderate specificity, which can be useful in the diagnosis and monitoring of inflammatory bowel disease (IBD). FC levels correlate well with bowel inflammation (both macroscopic and histological activity) and are not influenced by disease location or type of IBD. Despite the shortcoming with regards to specificity, it is the high sensitivity of FC that makes it a valuable screening tool in the diagnosis of IBD. It is especially effective in identifying children with low probability of IBD who would not benefit from further investigations. The cut-off value selected has a significant impact on the diagnostic accuracy of the test, influencing its sensitivity and specificity, and must be interpreted judiciously. Its role in disease monitoring is as an add-on test to Paediatric Ulcerative Colitis Activity Index and Paediatric Crohn's Disease Activity Index scores and can be used to differentiate disease relapse from functional symptoms. High levels of FC are also seen in a number of other conditions, such as gastrointestinal infections and coeliac disease. It is recommended that infective causes affecting the gut must be excluded first, before FC is measured.

Nutrition and inflammatory bowel disease: primary or adjuvant therapy.

PURPOSE OF REVIEW: Our understanding of the importance of nutrition in inflammatory bowel disease (IBD) continues to improve. With increasing evidence or cumulative evidence, this article reviews the current data for the role of nutrition in IBD pathogenesis, disease exacerbation and its use in the treatment of IBD in a clinically relevant context. RECENT FINDINGS: Irritable bowel syndrome and obesity prevalence is rising, and is increasingly being recognized in patients with IBD. Exclusive enteral nutrition remains highly relevant because of its efficacy and superior side-effect profile, even when considered against new pharmacological treatments, but requires patient motivation. We are now beginning to understand the importance of micronutrients such as iron and vitamin D, which may not only alter the bowel flora but also have an immune-modulatory effect. More recently, a prebiotic and probiotic combination has been used in a randomized trial for the treatment of IBD. SUMMARY: Macronutrient and micronutrient assessment should be an essential part of nutritional assessment of all patients with IBD. Although research is needed to further our understanding of the immune-modulatory effects of nutrients and supplements, better and more effective therapies combining nutrition and drug treatments like immune-suppressants should be explored.

Constipation in children.

Constipation remains a frequent presentation to paediatricians, with significant health resource implications. We present a practical guide to the management of paediatric constipation and evaluate the current evidence for treatment regimens, to help the clinician in treating a condition that can be distressing and has a significant impact on affected families.

Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review.

Gastro-esophageal reflux (GER) is a common phenomenon, characterized by the regurgitation of the gastric contents into the esophagus. Gastro-esophageal reflux disease (GERD) is the term applied when GER is associated with sequelae or faltering growth. The main aims of treatment are to alleviate symptoms, promote normal growth, and prevent complications. Medical treatments for children include (i) altering the viscosity of the feeds with alginates; (ii) altering the gastric pH with antacids, histamine H(2) receptor antagonists, and proton pump inhibitors; and (iii) altering the motility of the gut with prokinetics, such as metoclopramide and domperidone. Our aim was to systematically review the evidence base for the medical treatment of gastro-oesophageal reflux in children. We searched PubMed, AdisOnline, MEDLINE, and EMBASE, and then manually searched reviews from the past 5 years using the key words 'gastro-esophageal' (or 'gastroesophageal'), 'reflux', 'esophagitis', and 'child$' (or 'infant') and 'drug$' or 'therapy'. Articles included were in English and had an abstract. We used the levels of evidence adopted by the Centre for Evidence-Based Medicine in Oxford to assess the studies for all reported outcomes that were meaningful to clinicians making decisions about treatment. This included the impact of clinical symptoms, pH study profile, and esophageal appearance at endoscopy. Five hundred and eight articles were reviewed, of which 56 papers were original, relevant clinical trials. These were assessed further. Many of the studies considered had significant methodological flaws, although based on available evidence the following statements can be made. For infant GERD, ranitidine and omeprazole and probably lansoprazole are safe and effective medications, which promote symptomatic relief, and endoscopic and histological healing of esophagitis. Gaviscon(R) Infant sachets are safe and can improve symptoms of reflux. There is less evidence to support the use of domperidone or metoclopramide. More evidence is needed before other anti-reflux medications can be recommended. For older children, acid suppression is the mainstay of treatment. The largest evidence base supports the early use of H(2) receptor antagonists or proton pump inhibitors.