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Up to 50% of infants present with symptoms of regurgitation, infantile colic and/or constipation during the first 12 months of life. Although they are often classed as functional disorders, there is an overlap with cows' milk allergy. We present practical algorithms for the management of such disorders, based on existing evidence and general consensus, with a particular focus on primary health care. Management consists of early recognition of warning signs of organic disease, parental reassurance and nutritional strategies. ConclusionThe proposed algorithms aim to help healthcare providers manage frequent gastrointestinal and cows' milk-related symptoms in infants safely and effectively.

Aim: Implementing international guidelines guarantees high standards of clinical care. A group of experts developed an algorithm to drive the management of common gastrointestinal symptoms in infancy by paediatricians and general practitioners. Methods: The algorithm started from the evidence-based recommendations of the European Society of Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Infectious Diseases and an updated review of the literature. We used the structured quantitative method of nominal group technique to reach a consensus. Results: A practical algorithm for the management of infants with acute diarrhoea was designed based on the consensus reached for each statement. The management of an infant with acute diarrhoea should include a sequence of actions: (i) a semiquantitative estimate of infant dehydration through validated clinical scores, (ii) rehydration therapy and early refeeding with breast milk or regular formula and (iii) effective agents to reduce the severity and duration of the diarrhoea. Finally, in children with prolonged diarrhoea, the search for aetiology should include persistent infections or reinfections, cows' milk protein allergy and coeliac diseases. Lactose should always be withdrawn. Conclusion: This algorithm provides an evidence-based sequence of interventions to optimise the management of infants with acute diarrhoea.

ObjectiveTo estimate selected direct medical care costs of children with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP).MethodsWe performed a cross-sectional study of data from International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE), a multinational registry of children with ARP or CP. We determined health care utilization and estimated costs of hospitalizations, surgical and endoscopic procedures, and medications in our study population. Health care utilization data were obtained from all subjects enrolled in the study, and costs were calculated using national United States costs.ResultsWe included 224 subjects (median age 12.7 years), 42% of whom had CP. Mean number of hospitalizations, including for surgery and endoscopic retrograde cholangiopancreatography, was 2.3 per person per year, costing an estimated average $38,755 per person per year. Including outpatient medications, estimated total mean cost was $40,589 per person per year. Subjects using surgical procedures or endoscopic retrograde cholangiopancreatography incurred mean annual costs of $42,951 per person and $12,035 per person, respectively. Estimated annual costs of pancreatic enzyme replacement therapy, diabetic medications, and pain medications were $4114, $1761, and $614 per person, respectively. In an exploratory analysis, patients with the following characteristics appear to accrue higher costs than those without them: more frequent ARP attacks per year, reported constant or episodic pain, family history of pancreatic cancer, and use of pain medication.ConclusionsARP and CP are uncommon childhood conditions. The severe burden of disease associated with these conditions and their chronicity results in high health care utilization and costs. Interventions that reduce the need for hospitalization could lower costs for these children and their families.

ObjectiveTo determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis.Study designWe performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test.ResultsAmong 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%).ConclusionsChronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial.

Background: The role of nasal potential difference (NPD) measurement as a diagnostic test for cystic fibrosis (CF) is a subject of global controversy because of the lack of validation studies, clear reference values, and standardized protocols for diagnostic NPD. Methods: To determine diagnostic NPD frequency, protocols, interpretation, and rater agreement, we surveyed the 18 NPD centres of the European Cystic Fibrosis Society Diagnostic Network Working Group. Results: Fifteen centres reported performing 373 diagnostic NPDs in 2012. Most use the CFF-TDN-SCIP (67%) and the chloride-free + isoproterenol response of the side with the largest response (47%) as diagnostic criteria and use centre-specific reference ranges. Rater agreement for five NPD tracings in general was good, but poor in tracings with different responses between the two nostrils. Conclusions: NPD is frequently used as a diagnostic and research tool for CF. Performance is highly standardized, centre-specific reference ranges are established, and rater agreement in general is good. Centre-independent diagnostic criteria and reference ranges must be defined by multicentre validation studies to improve standardized interpretation for diagnostic use. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Background Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. Methods This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged >= 6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV1] >= 40% and <= 90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV1. The primary endpoint was relative change in percent-predicted FEV1 from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. Findings Between Sept 8,2009, and Nov 30,2010,238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV1 did not differ significantly between ataluren and placebo at week 48 (-2.5% vs -5.5%; difference 3.0% [95% CI -0.8 to 6.3]; p=0.12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0.77 [95% CI 0.57-1.05]; p=0.0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7% difference (95% CI 1.5-10.1) in relative change from baseline in percent-predicted FEV1 between the ataluren and placebo groups at week 48 (-0.7% [-4.0 to 2.1] vs -6.4% [-9.8 to -3.7]; nominal p=0.0082), and

Background: Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. Methods: This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged ≥6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV1] ≥40% and ≤90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV1. The primary endpoint was relative change in percent-predicted FEV1 from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. Findings: Between Sept 8, 2009, and Nov 30, 2010, 238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV1 did not differ significantly between ataluren and placebo at week 48 (-2·5% vs -5·5%; difference 3·0% [95% CI -0·8 to 6·3]; p=0·12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0·77 [95% CI 0·57-1·05]; p=0·0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5·7% difference (95% CI 1·5-10·1) in relative change from baseline in percent-predicted FEV1 between the ataluren and placebo groups at week 48 (-0·7% [-4·0 to 2·1] vs -6·4% [-9·8 to -3·7]; nominal p=0·0082), and, SCOPUS: ar.j, info:eu-repo/semantics/published

ObjectivesAcute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are rare and poorly understood diseases in children. Better understanding of these disorders can only be accomplished via a multicenter, structured, data collection approach.MethodsThe International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was created to investigate the epidemiology, etiologies, pathogenesis, natural history, and outcomes of pediatric ARP and CP. Patient and physician questionnaires were developed to capture information on demographics, medical history, family and social history, medications, hospitalizations, risk factors, diagnostic evaluation, treatments, and outcome information. Information collected in paper questionnaires was then transferred into Research Electronic Data Capture (REDCap), tabulated, and analyzed.ResultsThe administrative structure of the INSPPIRE consortium was established, and National Institutes of Health funding was obtained. A total of 14 sites (10 in the United States, 2 in Canada, and 2 overseas) participated. Questionnaires were amended and updated as necessary, followed by changes made into the REDCap database. Between September 1, 2012 and August 31, 2013, a total of 194 children were enrolled into the study: 54% were girls, 82% were non-Hispanic, and 72% were whites.ConclusionsThe INSPPIRE consortium demonstrates the feasibility of building a multicenter patient registry to study the rare pediatric diseases, ARP and CP. Analyses of collected data will provide a greater understanding of pediatric pancreatitis and create opportunities for therapeutic interventional studies that would not otherwise be possible without a multicenter approach.