Headache, diarrhoea, constipation and nausea are idiosyncratic effects of PPIs that happen in 14% of children. allergy and drug interactions. = 0.275Responder rate: 54% (44/81) PPI 54% (44/81) Placebo; = 1.000Responder rate: ITGA2 12% PPI 11% Placebo; = 1.000Mean daily vomiting/regurgitation episodes decreased by 4.34/d (0.5 mg/kg; 2.97/d C 1.0 mg/kg 4.35/d C 1.5 mg/kg; 0.50 in all group comparisonsChange from baseline of parent-recorded 24 h crying and fussing time and visual analogue scores of parental impression of the intensity of irritability Reflux index; -8.9% 5.6% PPI; -1.9% 2.0% Placebo 0.001 Cry/fuss times (min/24 h); 191 120 (PPI); 201 100 (Placebo) = 0.400 Combined PPI and Placebo organizations total cry fuss time2 Baseline 2 wk = 0.040 Baseline 4 wk = 0.008 VA Score 5.0 3.1 (PPI); 5.9 2.1 (Placebo) = 0.214Discontinuation rates owing to sign worsening were 48.8% (20/41) for placebo-treated 38.5% (15/39) for esomeprazole-treated individuals (risk ratio 0.69; = 0.28)Limitations of studiesSmall sample size Symptom-based diagnosis Subjective assessmentSmall sample size; Symptom-based analysis; Subjective assessmentSmall sample size Symptom-based analysis 5-Methylcytidine Subjective assessmentSingle blinded; Not placebo-controlled; Small sample size; Symptom-based analysis; Subjective assessmentSmall sample 5-Methylcytidine size; Subjective assessmentSmall sample size; Symptom-based analysis; Subjective assessment Open in a separate window 1All babies were given empirical pharmacologic treatment (excluding PPIs) including cisapride (87%), H2 receptor antagonists (73%), antacid (67%) and thickening agent (20%); 2Significant decrease in cry-fuss time self-employed of treatment; 3Ninty percent of individuals were more youthful than 12 mo; 4Entry into study required a reflux index of 5% or endoscopic biopsy evidence of oesophagitis. Data adapted from Chen et al; Moore et al; Orenstein et al; Shakhnovich et al. PPI: Proton pump inhibitor; GORD: Gastro-oesophageal reflux disease; PGA: Physician global assessment; VA: Visual analogue. Security OF GASTRIC Acidity INHIBITORS With any pharmacological agent, there is potential for side effects. Headache, diarrhoea, constipation and nausea are idiosyncratic effects of PPIs that happen in 14% of children. Acute interstitial nephritis, a rare, idiosyncratic hypersensitivity reaction to medications including PPIs, has also been reported in observational adult studies. Increased risk of infection, for example, Clostridium Difficile, is increasingly being recognised. Part effects related to the direct inhibition of gastric acid and reflex hypergastrinaemia, immunosuppression and drug metabolism have also been suggested (Table ?(Table22). Table 2 Outline of the proposed side effects associated with proton pump inhibitors use, and the evidence assisting the association varieties speciesLevel IPneumonia (Community-acquired)Level INecrotizing enterocolitisLevel III1Blood stream infections, including candidemiaLevel III1Allergic sensitization in adults and in children with inoculation resulted in similar rates of infection, toxin production and colon injury compared with a group of mice pretreated with ampicillin. Spore germination was also favoured by high pH levels and the presence of potassium chloride. Blockage of potassium pumps in the belly could potentially lead to improved potassium as the proton pumps exchange potassium for hydrogen ions. Inside a systematic review, Bavishi and Dupont found that while it was hard to establish causation in some studies due to other contributing factors such as advanced age and hospital exposure, individuals on PPIs shown a greater-than 4-collapse risk for recurrent C. difficile illness. A meta-analysis by Eom et al also found significant association between PPIs and pneumonia (modified OR = 1.27, 95%CI: 1.11-1.46), with an even greater risk for community-acquired pneumonia (OR = 1.34, 95%CI: 1.14-1.57). This risk of pneumonia was markedly higher within the 1st week of PPI use (OR = 3.95, 95%CI: 2.86-5.45) suggesting that patients who have been already susceptible to pneumonia would become ill soon after PPI treatment. With a small number of studies investigating the relationship between PPIs and hospital-acquired pneumonia, only an increased risk of hospital-acquired pneumonia was observed with H2RA therapy. Paediatric studies The few paediatric studies available have made related conclusions. Notably, a prospective study of 93 paediatric individuals (4-36 mo) with endoscopically diagnosed GORD, showed that children treated with either ranitidine or omeprazole for 8 wk were 3.58 and 6.39 times more likely to develop acute gastroenteritis and community-acquired pneumonia respectively, compared with healthy children during the 4 mo follow-up. Comparing 4 mo before 5-Methylcytidine and after enrolment, a significant increase in the incidence of acute gastroenteritis and pneumonia was found only in the treatment group, demonstrating that illness susceptibility could continue actually after therapy cessation. The results of security studies on the use of gastric acid.