Natural History Of Children Research Articles

Natural history of spinal cord compression stage AFMS3 in infants with achondroplasia: retrospective cohort study

Background and objectiveForamen magnum stenosis (FMS) is a common, serious complication of achondroplasia in infancy and associated with sudden infant death. The Achondroplasia Foramen Magnum Score (AFMS; 0–4) is used...

Clinical Profile and Natural History of Children with Ventricular Septal Defects in Tripoli, Libya from 1996 through 2009

Introduction and Objectives: Ventricular septal defect (VSD) is the most common congenital heart diseases, it accounts 40%. This study carried out to describe the epidemiological characters and clinical presentation of patients with VSD in Western and Southern Libya, and to evaluate spontaneous versus surgical closure in different types.  Patients and Methods It is hospital case series study conducted by reviewing the medical records of 1092 patients followed at cardiology outpatient department (OPD) of Tripoli Children Hospital from 1996 through 2009, the data abstracted from medical records and filed in a worked sheet, Excel and SPSS software used to analyze the data.  Results We identified 1092 patients. The results revealed that 30.9% diagnosed during the first month, and 49.7% from1 to 12 months. From 1092 patients; 50.8% have peri- membranous VSD, 18.8% muscular, and 13% having an apical type. 97.2% of males have peri-membranous VSD where muscular and apical seen more in female, p value = 0.001. Cardiac murmur is the common presenting sign 61.3%, 9.3% have feature of Down syndrome. Positive Family history of CHD in 9.9% with significant relationship between family history and type of VSD (peri- membranous type), P value = 0.001. Small VSDs accounts 66.9%, large VSDs 16.1%, followed by medium size VSD 11.8% of cases. Patients with large VSDs more prone for hospital admission as 101 (57.4%) from 176 patients were admitted to hospital, followed by moderate size (45%), P value = 0.001. 70.3% of patients with large VSD need either medical or surgical treatment, P value = 0.001. Spontaneous closure seen in 17%, 0.6% died, while 41.9% still on follow up. Muscular VSD shows the highest tendency for spontaneous closer as 72% closed by the age of 2 years.  Conclusion We conclude that peri- membranous VSD is the most common type. Two thirds of patients had been diagnosed in the first year of life. Big defects and some of moderate VSDs need either medical or surgical treatment. Spontaneous closer is usually seen in the first 2 years of life.  Recommendations We highly recommend for further multi-center study all over the country to get reliable data on the prevalence of congenital heart diseases and the incidence of ventricular septal defect in our population.

P210 Long-term outcome of very early onset inflammatory bowel disease associated with primary sclerosing cholangitis: a multicenter study from the Pediatric IBD Porto Group of ESPGHAN

Abstract Background Primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed under the age of 6 years (i.e., VEO-IBD) may have unique characteristics and disease course. We aimed to analyze the characteristics and natural history of children with VEO PSC-IBD and compare them to children diagnosed with PSC-IBD at an older age. Methods This was a multicenter, retrospective, study evaluating patients diagnosed with both IBD and PSC before (VEO-PSC-IBD) or after the age of 6 years (PSC-IBD), followed at 14 centers affiliated with the Porto IBD Interest group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every six months thereafter for a minimum follow-up of 12 months. IBD-related (clinical remission, need for systemic steroids, therapy escalation and surgery) and PSC-related outcomes (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, and death) were analyzed at 1, 3, and 5 years. Results A total of 69 children with both IBD and PSC were included: 28 with VEO PSC-IBD [median age 5.2 (3.7-5.9) years, 21 UC (75%), 4 IBDU (14%) and 3 (15%) CD] and 41 with PSC-IBD [median age 15.7 (13.3-16.9) years, 34 UC (83%), 6 IBDU (1.5%) and 1 (0.2%) CD]. IBD was diagnosed prior to PSC in 28 of the 69 patients (40%), simultaneously in 30 (43%), and after PSC in 11 (16%), with no significant differences between VEO PSC-IBD and PSC-IBD. Most patients with UC presented with extensive disease at diagnosis (89% in VEO PSC-UC vs. 89% in PSC-UC, p = 0.72). Both groups presented most often with mild intestinal disease at diagnosis (mean PUCAI of VEO IBD-PSC 34±16, vs 31±19 of IBD-PSC, p=0.11; mean PCDAI 31±33 vs. 21±27, respectively, p=0.14). A higher number of VEO-IBD-PSC patients were diagnosed with autoimmune sclerosing cholangitis than older children [24 (86%) vs. 27 (66%) PSC-IBD, p=0.04], whereas no other differences were found for PSC-related variables. During follow-up, no significant differences were found in major IBD outcomes. The risk of developing biliary strictures and escalating therapy to vancomycin from ursodeoxycholic acid was lower in the VEO-PSC-IBD group (Figure 1 and 2, Log-rank p=0.02 and p=0.02), while no difference was found for portal hypertension and liver transplantation at 5-year follow-up. No cases of cholangiocarcinoma or death were reported. Conclusion IBD-PSC has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. However, a milder disease course in terms of biliary complications and the need for PSC-related therapy escalation, with an overall mild intestinal disease at presentation in all patients, characterize this specific subcohort of patients.

IgE-mediated fish allergy in Singaporean children.

Fish is one of the common causes of food allergy and there is limited literature about fish allergy in Singapore. We aimed to describe the demographics, clinical features, and natural history of children with IgE-mediated fish allergy. A retrospective review was conducted for children diagnosed with fish allergy in a tertiary pediatric hospital in Singapore between 2015 and 2020. The diagnosis of fish allergy was made in 108 patients based on a convincing history of IgE-mediated allergic reaction and a positive skin prick test. The median age at first reaction was 12 months (range 6-168) with most reacting on first ingestion (62.0%). The most common fish causing reactions were threadfin (48.1%), salmon (33.3%) and cod (31.5%). Majority presented with cutaneous symptoms (97.2%). Anaphylaxis occurred in 6.5%. Five were mono-sensitized (4.6%), 77 were oligo-sensitized (71.3%) and 26 were polysensitized (24.1%). Most can tolerate another species of fish (75.9%), most commonly salmon (37.0%), tuna (24.1%) and cod (22.2%). Median duration of follow up was 24 months (range 0-176). Twenty-eight out of 108 children (25.9%) acquired natural tolerance to index fish at a median age of 60 months (range 18-159). Most children with fish allergy can tolerate at least one other species of fish and resolution of fish allergy is possible. Thus, it is important to follow-up with an allergist to evaluate which fish species can be included in their diet to avoid unnecessary dietary restrictions.

Natural history of children and adults with phenylketonuria in the NBS-PKU Connect registry

PurposePhenylalanine hydroxylase deficiency, or phenylketonuria (PKU), is a rare autosomal recessive metabolic disorder. Early diagnosis via newborn screening (NBS) and initiation of treatment prevent the development of cognitive impairment and other co-morbidities. The purpose of this study is to describe the natural history of PKU in the United States, including prevalence of co-morbidities and predictors of outcomes. MethodsWe analyzed data from a self-report survey in the NBS-PKU Connect online registry. We describe the participants' nutrition management strategies, barriers to management, outcomes of bone disorders, skin, and psychological co-morbidities, and the use of special education or other special services. Predictors of outcomes were identified and assessed, including the impact of sex, age, age at diagnosis, blood phenylalanine concentration, use of sapropterin, use of medical food, adherence to prescribed diet, use of low protein modified foods, whether they had ever been off-diet, and use of tyrosine supplementation. ResultsThe 219 respondents included individuals with PKU or hyperphenylalanemia (n = 78), or their caregivers (n = 141). Most (84.3%) started treatment before the age of two weeks. About one-third indicated that they had been off-diet at some point in their lives, and 81.4% reported that they currently adhered to their prescribed diet, with adherence to prescribed diet decreasing with age. Blood phenylalanine concentration was under the recommended threshold of 360 μmol/L for 68.5% of participants. One-quarter of respondents reported psychological co-morbidities, with anxiety and ADD/ADHD being the most common. The incidence of psychological co-morbidities increased with age and with ever having been off diet. Special education or other special services were more likely to be reported by individuals who were diagnosed after one week of age. Skin disorders such as acne and eczema were more common in females than males, and a minority of participants reported bone disorders. ConclusionsDespite recommendations to maintain blood phenylalanine concentrations in the therapeutic range throughout life, it is not uncommon for adults with PKU to discontinue dietary management of their disorder. Early diagnosis was associated with reduced need for special education or other special services, and continuous treatment was associated with decreased psychological co-morbidities.

Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

Cerliponase alfa changes the natural history of children with neuronal ceroid lipofuscinosis type 2: The first French cohort.

Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution: cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa. CLN2 Clinical Rating Scale Motor-Language (CLN2 ML) assesses the motor and language evolution of CLN2 patients. We retrospectively studied patients' medical records: clinical symptoms, MRI conclusions, gene mutation, side effects of infusions, patient's age and CLN2 ML scores at diagnosis, at the beginning of enzyme replacement therapy (ERT) and at the last evaluation. Seven patients were included. Average age at diagnosis was 50 months ( ±10) with CLN2 ML score equal to 3.6 [1.5-5]. Average age at the beginning of ERT was 56 months ( ±13) with CLN2 ML score equal to 3.1 [1-5]. At the last available evaluation, average age was 82 months ( ±20) with CLN2 ML score equal to 2.8 [0-5]. Thus, in 26 months, the mean CLN2 ML score only decreased by 0.3 points. However, patients with a CLN2 ML score greater than three at the onset of ERT experienced a stabilisation or improvement of clinical signs, whereas patients with a CLN2 ML score less than three at baseline continue to deteriorate. For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms.

EP.80The effects of steroid treatment on respiratory function in adults with Duchenne muscular dystrophy after loss of ambulation

Several years of extensive data collection of natural history in children with Duchenne muscular dystrophy (DMD) has resulted in better knowledge and understanding of the role of corticosteroids in patients' treatment and management. Despite currently published standards of care in the UK as well as, pulmonary function data from the cohort of 397 patients both suggesting beneficial role of corticosteroids in preservation of respiratory function and effectively slowing down the disease progression, there is limited evidence regarding corticosteroid use in adults with DMD. A retrospective multi-site clinical audit will be performed to assess the effects of corticosteroid treatment on respiratory function in adults with DMD after loss of ambulation. We will present data from non-ambulant adult patients and compare longitudinal outcomes for patients where corticosteroids are continued after loss of ambulation vs the effect of stopping corticosteroids. Preliminary data on the use of corticosteroids in adults with DMD after loss of ambulation in the UK will be presented and discussed.

Natural history of children with mild Crohn's disease.

BACKGROUNDThere is a small and poorly studied population of patients with mild and limited Crohn’s disease (CD), who either spontaneously enter remission and can discontinue therapy, or be maintained on milder anti-inflammatory treatment.AIMTo identify a group of children with mild CD who were not escalated to immunomodulators (azathioprine, mercaptopurine, or methotrexate) or biologics (infliximab or adalimumab) within the first two years after their Crohn’s diagnosis and outline the natural history and phenotypic features of these patients.METHODSIn a retrospective chart review of the inflammatory bowel disease database at Boston Children’s Hospital we reviewed all the mild CD patient’s clinic visits, laboratory studies, and procedures for the duration of time they were followed at the center. Patients were included if they had clear diagnosis of Crohn’s disease, and they were not escalated to immunosuppressive therapies for at least 2 years after the date of diagnosis. These mild CD patients were compared to controls diagnosed at a similar time, that were treated with immunomodulators or biologics. Data that was abstracted included: Age at diagnosis, sex, disease location utilizing the Paris classification, medical treatment, surgical treatment, endoscopic findings, histology, and hospitalizations. We also analyzed differences in the phenotypic features between those with mild CD and those with moderate to severe disease.RESULTSOut of 1205 patients with CD diagnosed between 1990 and 2013, we identified 29 patients that met the inclusion criteria, and they were matched with 58 controls. There were no significant differences between the disease behaviors at presentation, with approximately 90% of patients in each group having inflammatory disease. However, patients with mild disease were more likely to have disease limited to the colon (31% vs 12%, P = 0.03). In contrast, patients with moderate to severe disease (aka control group) were more likely to have ileocolonic disease (70% vs 45% in the mild group, P = 0.02). Of the 29 patients, only 8 required medication escalation to immunomodulators during the period of follow-up. The primary indication for escalation to immune suppressive therapies was corticosteroid dependence. We also found that patients treated without immunomodulators or biologics for mild CD continue to exhibit histologic intestinal inflammation. Of the 29 patients, three developed significant complications of ileal disease, though only one required surgical intervention during the period of follow-up.CONCLUSIONWe identified a cohort of children with mild CD, who were able to avoid the institution of immune suppressive therapies for several years, and generally had good outcomes during the period of follow-up. While a subset of these patients will eventually require either immunosuppression or surgery, the majority of them have a good quality of life despite having low-grade intestinal inflammation. Importantly, this subset of patients has managed to avoid the potential toxicities of immune suppression for several years. The majority of these patients have either colonic disease with minimal small bowel involvement or limited ileal disease.

Friday, September 28, 2018 10:30 AM–12:00 PM abstracts: deformity: technical factors: 164. Incidence, risk factors and the natural history of proximal junctional kyphosis: review of long term surgical outcomes using hybrid fusion constructs for adolescent idiopathic scoliosis

BACKGROUND CONTEXT Proximal junctional kyphosis (PJK) is an unsolved radiographic phenomenon after corrective spinal deformity surgery with a high, but variable reported incidence. While known to influence outcomes in adults, the long-term clinical significance and natural history in children has not been well defined.Identifying incidence, risk-factors and natural course of PJK based on several proposed definitions in the literature using a large cohort may aid in enhancing our understanding of the disease entity. PURPOSE In a single-surgeon series of AIS patients undergoing deformity correction using hybrid hooks or screw constructs, the study attempted to identify potential risk-factors associated with the long-term development of PJK. Additionally, the study also defines PJK incidence and highlights the natural course of PJK development in children based on commonly proposed definitions in the literature. STUDY DESIGN/SETTING Retrospective, single-surgeon series with a minimum 2-year follow-up. PATIENT SAMPLE Overall, 253 eligible AIS patients with complete information on the proximal junctional angle (PJA) that underwent spinal deformity fusion (PSF) surgery by a single surgeon (SLW) at the University of Iowa between 2006 and 2015 that met the minimal criteria of 2-year follow-up were included. OUTCOME MEASURES The primary outcome was to assess incidence of PJK development form preoperative to postoperative measurements based on two commonly utilized definitions: Glattes et al. that defines PJK as PJA> 10°, and Bridwell et al. classification that defines the disease entity based on the critical PJA above 20°. Secondary outcome was to investigate factors associated with PJK development based on patient demographics, radiological indices and outcomes, and describe the natural course of PJK development in AIS patients undergoing deformity correction. METHODS AIS patients aged between 9 and 18 years undergoing primary long-construct PSF (UIV T2-4) between 2006 and 2015 with a minimum 2 years follow-up were included. Proximal junctional kyphosis was defined as a change in the PJA, according to Glattes et al. and Bridwell et al. classification from preop to postop. The incidence of PJK was defined at 6-week and last follow-up. Multivariable regression models were used to assess risk factors (patient characteristics, disease severity, radiographic parameters) associated with long-term PJK development. RESULTS A total of 253 eligible patients (mean age: 13.7 years; 82% female) with an average follow-up of 3.7 years (range: 24-123 months). Proximal junctional kyphosis (10°) occurred in 10.3% at 6 weeks (PJK 20: 0.4%) and 25.7% at final FU (PJK 20: 4.3%). Based on Glattes definition, a high proportion of patients developing PJK had Risser grade 3(19 vs. 6%; p=.003) and Lenke 5(13% vs. 5%; p=.028) at baseline. In an unadjusted analysis, Risser grade 3(OR:3.6; p=.01), Lenke 5(OR:3.0; p=.03) and those with UIV as T4 (vs. T2) were associated with higher odds of PJK development. In multivariable model, we noted Risser grade 3(OR:4.6; p=.045) as a factor for PJK development. Low reoperation rate (0.04%;1/253) was noted. CONCLUSIONS PJK after AIS deformity surgery varies according to follow up time and definition. In contrast to adults, there does not appear to be any clear risk factors for PJK in an AIS population. Long-term reoperation for PJK appears to be exceedingly low at 0.4%. Radiographic PJK should be followed but generally thought of a benign condition in pediatric deformity surgery. Likely risk factors for PJK include short instrumentation (upto T4 compared to T2), Risser grade 3 and Lenke 5. Consensus on PJK definition is warranted to better define the pathological entity.

Esofagitis eosinofílica: diagnóstico y tratamiento actual basado en la evidencia

Eosinophilic oesophagitis (EoE) is a disease caused by an immune response to food antigens in contact with the oesophageal mucosa. Its diagnosis is defined by the combination of oesophageal dysfunction symptoms and inflammation of the oesophageal mucosa predominantly by eosinophils. Its chronic course and frequent progression to subepithelial fibrosis and oesophageal strictures indicate the need for treatment. The information provided by recent clinical trials and systematic reviews has led to the development of new clinical guidelines, endorsed by several European scientific societies. This review includes the most relevant aspects of the new guidelines, updates the EoE concept and reports its epidemiology and risk factors, associated conditions and its natural history in children and adults. Diagnostic criteria are provided, and tests for EoE diagnosis and monitoring and therapeutic options are analysed based on the best scientific evidence and consensus opinion of experts.

Natural history of children and adults with maple syrup urine disease in the NBS-MSUD Connect registry

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder (OMIM #248600) in which affected individuals cannot metabolize branched-chain amino acids (BCAA) (leucine, isoleucine, and valine) due to pathogenic variations in one of three genes: BCKDHA, BCKDHB, and DBT encoding the E1α, E1β, and E2 subunits of the branched-chain α-ketoacid dehydrogenase (BCKDH) enzyme complex [1]. Consequently, these amino acids and their corresponding α-ketoacids accumulate in the body. In the United States of America (USA), the incidence of MSUD is approximately 1:198,000 [2], although it is considerably higher in some populations such as Old Order Mennonite (1:358) [3] and Ashkenazi Jewish populations (1:26,000) [4]. Without treatment, MSUD can lead to feeding difficulties, lethargy, seizures, urine and cerumen that smell like maple syrup, vomiting, coma, and death [5]. Early diagnosis and treatment can optimize outcomes, although treated individuals have an increased rate of anxiety, depression, attention deficit hyperactivity disorder (ADHD), movement disorders, and small reductions in intelligence and global function [5]. Treatment consists of a protein-restrictive diet that limits the amount of branched-chain amino acids consumed, along with synthetic formula consisting of the other amino acids and various micronutrients [6]. The goal of treatment is to maintain plasma leucine concentrations, with frequent monitoring, between 75 and 200 μmol/L for infants and children age five years and younger, and between 75 and 300 μmol/L for individuals older than five years of age [7]. Even with dietary treatment, metabolic decompensation can occur during times of stress (e.g., infection) and must be treated promptly [5]. Liver transplants may allow for relaxation of the diet, and can help prevent further brain damage but cannot reverse existing damage [8], [9]. Because treatment must be initiated as soon as possible after birth, screening for MSUD was first included in newborn screening (NBS) programs in the USA in 1964 [10]. In 1999, MSUD was included on the American College of Medical Genetics list of recommended diseases for inclusion in tandem mass spectrometry-based NBS panels [11], and is currently screened for in all states in the USA [2]. In order to add to the literature on outcomes of this rare condition, we report the characteristics of a group of respondents with MSUD from NBS-MSUD Connect, the first self-reported patient registry for metabolic NBS disorders. NBS Connect was launched in 2012 with NBS-PKU Connect for phenylketonuria (PKU) as the pilot registry, and NBS-MSUD Connect was added in 2013 [12]. The purpose of this report is to provide a snapshot of respondents with MSUD, including management techniques employed, clinical symptoms, and factors potentially associated with metabolic control of plasma leucine levels.

Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS).

Little is known about the natural history of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). This study prospectively followed 33 children with PANDAS for up to 4.8years (mean 3.3±0.7years) after enrollment in a 24-week randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin (IVIG) (N=35). Fourteen of eighteen children randomized to placebo received open label IVIG 6weeks after the blinded infusion, so follow-up results reported below largely reflect outcomes in a population of children who received at least one dose of IVIG. Telephone interviews with the parents of participants found that at the time of phone follow-up, 29 (88%) were not experiencing clinically significant obsessive-compulsive symptoms. During the interim period (6-57months after entering the clinical trial), 24 (72%) had experienced at least one exacerbation of PANDAS symptoms, with a median of one exacerbation per child (range 1-12; interquartile range 0-3). A variety of treatment modalities, including antibiotics, IVIG, psychiatric medications, cognitive behavioral therapy, and others, were used to treat these exacerbations, and were often used in combination. The outcomes of this cohort are better than those previously reported for childhood-onset OCD, which may support conceptualization of PANDAS as a subacute illness similar to Sydenham chorea. However, some children developed a chronic course of illness, highlighting the need for research that identifies specific symptoms or biomarkers that can be used to predict the longitudinal course of symptoms in PANDAS.

Eosinophilic esophagitis: current evidence-based diagnosis and treatment in children and adults.

Eosinophilic esophagitis (EoE) is a disease caused by an immune response to food antigens in contact with the esophageal mucosa that has arisen as a common disorder in current clinical practice. Its diagnosis is defined by the combination of symptoms of esophageal dysfunction and inflammation of the esophageal mucosa predominantly by eosinophils. Its chronic course and frequent progression to subepithelial fibrosis leading to strictures and narrow esophagus indicate the need for treatment. Information provided by recent clinical trials and systematic reviews allowed for the development of new clinical guidelines, endorsed by several European scientific societies. This review summarizes its most relevant aspects, updates the concept of EoE, reports its epidemiology and risk factors, associated conditions and its natural history in children and adults. Diagnostic criteria of EoE were updated, after the relationships discovered between the disease and gastroesophageal reflux disease. Endoscopy with biopsies remains as the only accurate test for diagnosis and monitoring, which warrants research on minimally invasive methods. Therapeutic options for EoE are analyzed based on best scientific evidence and expert opinion. Drugs with anti-inflammatory efficacy include proton pump inhibitors and topic swallowed steroids. Empiric food elimination diets have been shown to be superior to skin allergy testing food elimination. Since only one or two foods are involved in causing EoE in 90% of patients who respond to diets, novel steep-up schemes on empiric elimination diets warrant further evaluation. Endoscopic dilation should be considered in patients with esophageal narrowing and persistent symptoms unresponsive to diet or drugs-based anti-inflammatory treatments.

The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study.

The objective of the manuscript was to describe the natural history of complaints and disability in children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the constructs that underlie functional decline. One hundred and one JHS/EDS-HT children were observed over 3 years and assessed at three time points on the following: functional impairments, quality of life, connective tissue laxity, muscle function, postural control and musculoskeletal and multi-systemic complaints. Cluster analysis was performed to identify subgroups in severity. Clinical profiles were determined for these subgroups, and differences were assessed by multivariate analysis of covariance. Mixed linear regression models were used to determine the subsequent trajectories. Finally, an exploratory factor analysis was used to uncover the underlying constructs of functional impairment. Three clusters of children were identified in terms of functional impairment: mild, moderately and severely affected. Functional impairment at baseline was predictive of worsening trajectories in terms of reduced walking distance and decreased quality of life (P ⩽ 0.05) over 3 years. Multiple interactions between the secondary outcomes were observed, with four underlying constructs identified. All four constructs (multi-systemic effects, pain, fatigue and loss of postural control) contributed significantly to disability (P ⩽ 0.046). Children diagnosed with JHS/EDS-HT who have a high incidence of multi-systemic complaints (particularly, orthostatic intolerance, urinary incontinence and diarrhoea) and poor postural control in addition to high levels of pain and fatigue at baseline are most likely to have a deteriorating trajectory of functional impairment and, accordingly, warrant clinical prioritization.

Children are likely to grow out of irritable bowel syndrome

Objectives: Irritable bowel syndrome (IBS) includes weekly abdominal pain/discomfort associated with: constipation (C-IBS), diarrhea (D-IBS) or alternating C and D (A-IBS). Few data exist on IBS natural history in children. We investigated symptoms evolution over time in a pediatric IBS cohort.

International Paediatric Mitochondrial Disease Scale.

ObjectiveThere is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study.MethodsA clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6–16 years) from five different expert centres from four different continents were evaluated in this study.ResultsThe feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23–0.99).ConclusionIn conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9948-7) contains supplementary material, which is available to authorized users.

The natural history of pancreatic acinar cell cystadenoma: Is resection better than surveillance? An update to a case report from 2010

Abstract Cystic lesions of the pancreas are a rare entity, and few reports have described their natural history in children. A previously published report described a 9-year-old boy with an acinar cell cystadenoma, discovered during a laparoscopic appendectomy. Initially asymptomatic and followed by serial MRI, this patient presented to our institution several years later with chronic obstructive symptoms that required surgical intervention. Planning for resection included multidisciplinary input from the genetics and endocrinology services. Initially, a partial pancreatic resection was performed in an attempt to preserve normal pancreatic tissue and islet cell function. Progression of the cystic disease and recurrent obstruction necessitated further surgical intervention. Here we present the updated clinical course and outcome of a 12-year-old boy who underwent a total pancreaticoduodenectomy for a symptomatic acinar cell cystadenoma.

OP23A CONSENSUS WORKSHOP TO DEVELOP RISK-BASED SELECTION CRITERIA FOR THE NEXT SIOP TRIAL OF “SIGHT-SAVING THERAPY” FOR CHILDREN WITH NF1-ASSOCIATED OPTIC PATHWAY GLIOMA (NF1-OPG)

INTRODUCTION: The natural history of children with NF1-OPG is unpredictable, indications for therapy to save vision, using patient, imaging and visual factors have not been studied in Europe. The aim of this multi-disciplinary workshop was to promote a revised and standardised approach for the next SIOP LGG trial. METHOD: Eight SIOP-LGG2004 centres contributed 83 NF1-OPG cases with complete imaging, visual and clinical datasets (age at diagnosis: median 4.8 yrs range 1.1-13.1; m:F 37:46, median follow-up 19.2 months range 1.8-121 months). Severe visual impairment/blindness (LogMAR >= 1.0) at diagnosis and last follow up, respectively: unilateral 16,21; bilateral 3,7. Anatomical distribution at diagnosis: Dodge Stage A (nerves) 35; Stage B (chiasm) 16; Stage C (nearby structures) 32. Imaging evidence of: response 31: no change:46; progression 6. Analysis of this dataset informed consensus discussion and voting of representative cases for proposed trial criteria for observation, treatment and randomisation. RESULTS: Consensus on imaging and visual classification was achieved, including a schematic for recording patient, visual and imaging details. Criteria for case selection were: age, history of visual decline, presence of severe visual symptoms, unreliable visual assessment, proptosis and post-chiasmatic tumour involvement. A subsequent 19 case web-based questionnaire was completed by 15 workshop participants. The respondents allocated 8 cases to observation; 8 to immediate treatment and 3 for consideration for randomisation. CONCLUSION: A new consensus on selection criteria using a contemporary trial cohort was reached. We have piloted a web-based questionnaire to assess feasibility of a randomised trial.

G305(P) Referral and investigation of paediatric urinary tract infections in a general practice setting – are we getting it right?

<h3>Introduction</h3> Urinary Tract Infection (UTI) is a common bacterial infection. Natural history in children has changed over the last 30–50 years due to antibiotics and improvements in healthcare. There remains uncertainty about the most appropriate and effective way to manage UTIs in children including whether or not investigations, follow-up and prophylaxis are justified. The correct timeframe during which these should occur depends on presentation and age of the child. <h3>Aims</h3> NICE clinical guideline 54 is often confusing due to the complex nature of follow up and the range of investigations required depending on presentation and age. The guideline can be quite challenging to follow in a busy general practice environment. The aim is to assess current management in terms of referral and further investigations and suggest any necessary improvements to facilitate this process. <h3>Method</h3> Retrospective audit looking at management of patients under 16 years old presenting to an inner city general practice from September 2010–14 with suspected UTI. Culture positive UTIs were identified and patients who fulfilled the NICE criteria for referral were highlighted. Referrals were categorised as appropriate, inappropriate or missed. Grade of clinician who assessed the patient was also categorised as trainee, GP or locum. Results: n = 15. Overall 13% referrals were appropriate, 33% inappropriate and 53% missed. 100% trainee referrals were inappropriate, 80% GP referrals were missed and 50% locum referrals were inappropriate. There was confusion about whether to refer to paediatric urology or paediatrics (40% and 30% respectively). 88% missed referrals related to atypical UTIs. <h3>Conclusion</h3> NICE clinical guideline 54 is not easy to follow in a time pressured environment. This is evident across all grades of clinician. It was noted that patients presenting to out-of-hours or A&amp;E often do not have a urine sample sent for culture, hindering decisions regarding referral and further investigation. There was confusion about whether to refer to paediatrics or paediatric urology. Atypical UTIs were most likely to be mis-managed. An intuitive UTI flowchart has therefore been designed to facilitate easier identification of children who require tertiary referral and hence improve management.