Background: Population cohort studies are useful to study infectious diseases episodes not attended by health care services, but conventional paper diaries and questionnaires to capture cases are prone to noncompliance and recall bias. Use of smart technology in this setting may improve case finding. Objective: The objective of our study was to validate an interactive mobile app for monitoring occurrence of acute infectious diseases episodes in individuals, independent of health care seeking, using acute otitis media (AOM) symptom episodes in infants as a case study. We were interested in determining participant compliance and app performance in detecting and ascertaining (parent-reported) AOM symptom episodes with this novel tool compared with traditional methods used for monitoring study participants. Methods: We tested the InfectieApp research app to detect AOM symptom episodes. In 2013, we followed 155 children aged 0 to 3 years for 4 months. Parents recorded the presence of AOM symptoms in a paper diary for 4 consecutive months and completed additional disease questionnaires when AOM symptoms were present. In 2015 in a similar cohort of 69 children, parents used an AOM diary and questionnaire app instead. Results: During conventional and app-based recording, 93.13% (17,244/18,516) and 94.56% (7438/7866) of symptom diaries were returned, respectively, and at least one symptom was recorded for 32.50% (n=5606) and 43.99% (n=3272) of diary days (P<.01). The incidence of AOM symptom episodes was 605 and 835 per 1000 child-years, respectively. Disease questionnaires were completed for 59% (17/29) of episodes when participants were using conventional recording, compared with 100% (18/18) for app-based recording. Conclusions: The use of the study's smart diary app improved AOM case finding and disease questionnaire completeness. For common infectious diseases that often remain undetected by health care services, use of this technology can substantially improve the accurateness of disease burden estimates.

OBJECTIVES:The aim of our diagnostic accuracy study Child Abuse Inventory at Emergency Rooms (CHAIN-ER) was to establish whether a widely used checklist accurately detects or excludes physical abuse among children presenting to ERs with physical injury. DESIGN:A large multicentre study with a 6-month follow-up. SETTING:4 ERs in The Netherlands. PARTICIPANTS:4290 children aged 0-7 years attending the ER because of physical injury. All children were systematically tested with an easy-to-use child abuse checklist (index test). A national expert panel (reference standard) retrospectively assessed all children with positive screens and a 15% random sample of the children with negative screens for physical abuse, using additional information, namely, an injury history taken by a paediatrician, information provided by the general practitioner, youth doctor and social services by structured questionnaires, and 6-month follow-up information. MAIN OUTCOME MEASURE:Physical child abuse. SECONDARY OUTCOME MEASURE:Injury due to neglect and need for help. RESULTS:4253/4290 (99%) parents agreed to follow-up. At a prevalence of 0.07% (3/4253) for inflicted injury by expert panel decision, the positive predictive value of the checklist was 0.03 (95% CI 0.006 to 0.085), and the negative predictive value 1.0 (0.994 to 1.0). There was 100% (93 to 100) agreement about inflicted injury in children, with positive screens between the expert panel and child abuse experts. CONCLUSIONS:Rare cases of inflicted injury among preschool children presenting at ERs for injury are very likely captured by easy-to-use checklists, but at very high false-positive rates. Subsequent assessment by child abuse experts can be safely restricted to children with positive screens at very low risk of missing cases of inflicted injury. Because of the high false positive rate, we do advise careful prior consideration of cost-effectiveness and clinical and societal implications before de novo implementation.

Objective To quantify the critical age period of first episode of acute otitis media (AOM) and its consequences for AOM recurrences and AOM health care use.Study design Children enrolled in the Wheezing-Illnesses-STudy-LEidsche-Rijn cohort with at least 1 episode of AOM documented in their primary care health record before 2 years of age were followed until 6 years of age. Data on episodes of AOM and associated primary care consultations, antibiotic prescriptions, and specialist referrals were retrieved. Regression models assessed the presence and shape of the associations between age of first AOM and subsequent episodes of AOM and health care use.Results A total of 796 of 2026 children (39%) experienced a first AOM before 2 years of age. Each month decrease in age at first AOM in the first 2 years of life increased the risk of developing recurrent AOM (>= 3 AOM episodes in 6 months or >= 4 in 1 year) linearly by 6% (adjusted risk ratio: 1.06; 95% CI: 1.02-1.10). For first AOM occurring before 9 months, the cumulative 6-year primary care consultation rate increased by 8% (adjusted incidence rate ratio: 1.08; 95% CI: 1.03-1.15) and the associated specialist referral increased by 16% (adjusted risk ratio: 1.16; 95% CI: 1.07-1.27) for each month decrease in age. No associations were found between age at first AOM and total AOM episodes or antibiotic prescriptions.Conclusions The association between earlier age of first AOM and recurrent AOM as well as total health care use during childhood is particularly strong before 9 months of age.

The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning.

Background:Physical activity has long been proposed as an important modifiable cardiovascular risk factor in adults. We assessed whether physical activity already has an effect on childhood vasculature. Methods:In the Wheezing-Illnesses-Study-in-Leidsche-Rijn birth cohort, we performed vascular ultrasound to measure carotid intima-media thickness (cIMT) and functional properties (distensibility, elastic modulus) at 5 and 8 years of age. Child typical physical activities were inquired using a questionnaire completed by parents. Linear regression was used with physical activity level, expressed as a standardized value of time-weighted metabolic equivalent (MET) as the independent variable and vascular properties as dependent variables with further confounder adjustment and evaluation for possible body mass index and sex effect modifications. Results:In 595 5-year-old children and in 237 of those who had reached the age of 8 years, we did not find statistically significant associations between total time-weighted MET and each vascular parameter, neither in pooled nor stratified analysis. However, sport activities were associated with thinner cIMT (-3.20 mu m/SD, 95% CI -6.34, -0.22, p=0.04) at 5 years of age; a similar pattern was seen for organized sport. This effect was strongest in children in the highest body mass index tertile (-5.38 mu m/SD, 95% CI -10.54, -0.19, p=0.04). At the age of 8 years, higher sport level tended to be associated with higher vascular distensibility (2.64x10(3)kPa/SD, 95% CI -0.18, 5.45, p=0.07) although this was not statistically significant. Conclusions:Sport activity may have beneficial effects on arteries of young children, particularly those with higher relative body weight.

BACKGROUNDLittle is known about factors that determine prescribing of asthma therapy in infancy.OBJECTIVETo describe factors related to the initiation and refill of asthma therapy in infancy.METHODSThis study included 1202 infants who participated in a prospective birth cohort study: the 'Wheezing Illnesses Study Leidsche Rijn (WHISTLER)'. Outcomes, asthma therapy initiation and refill, were assessed using prescription data. Logistic regression analysis was used to study determinants of therapy initiation in two groups: total population and infants with a respiratory system symptom diagnosis. In addition, determinants of refilling prescriptions were studied in infants who started therapy in their first year of life.RESULTSFifteen per cent of all infants started asthma therapy in their first year of life. Respiratory symptoms were an important driver of both initiation and refill of prescriptions. In the total population, therapy initiation was associated with male gender [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.1-2.6], day-care attendance (OR: 1.6, 95% CI: 1.0-2.5) and breastfeeding (OR: 0.6, 95% CI: 0.3-1.0). For infants with a respiratory system symptom diagnosis, day-care attendance was associated with an increased chance of therapy initiation (OR: 5.3, 95% CI: 1.8-16.2) and breastfeeding was associated with a lower chance of starting therapy (OR: 0.4, 95% CI: 0.1-1.1). Dutch children had a higher chance of refilling prescriptions in infancy (OR: 5.3, 95% CI: 1.1-26.8).CONCLUSIONSApart from other factors involved, the principal reason for initiation and refill of asthma therapy in infancy was the presence of respiratory symptoms. This appeared the only reason to prescribe medication and physicians are not distracted by other factors.

Objective: The potential burden of a congenital heart defect on adult life is scarcely investigated. Our aim was to evaluate whether the presence and severity of congenital heart disease (CHD) influences socioeconomic status, household situation and life style in the adult population. Methods: Patients were randomly selected from CONCOR (n=11,047), the national registry of adult patients with CHD in the Netherlands, to complete a questionnaire addressing employment status, educational attainment, marital status & offspring, and life style. The reference group was derived from the Utrecht Health Project (n=6,810). Logistic regression models were used to adjust for age, gender and socio-economic status. Results: A total of 1571 adult patients (51% male; median age 39 years (range 18-94)) with mild (45%), moderate (45%), and severe (10%) CHD completed the questionnaire (response rate of 87%). Employment rates were significantly lower among patients with mild, moderate, and severe CHD (61% vs. 70% vs. 65% res...

To determine whether the association between non-right-handedness and mental problems among adolescents is specific for psychotic symptoms, we included a group of 2096 adolescents with a mean age of 14 years from the general population. Mental health problems were assessed using the parent, self-report, and teacher versions of the Child Behavior Checklist. Internalising problems comprised anxious and depressed, withdrawn and depressed, and somatic complaints. Externalising problems consisted of delinquent behaviour and aggressive behaviour. The remaining problems consisted of social problems, attention problems, and thought problems. The latter were divided into psychotic and non-psychotic items. A total of 14.3% of the adolescents were non-right-handed. We observed positive associations of non-right-handedness with thought problems, social problems, and being withdrawn and depressed. Externalising problems showed no associations with handedness. Within the thought problems subscale, the effect sizes associated with non-right-handedness for psychotic and non-psychotic items were 0.18 (p=.005) and 0.04 (p=.459), respectively. In conclusion, non-right-handedness is predominantly associated with psychosis-related mental problems as early as in adolescence. Handedness could be taken into account when identifying adolescents at risk for psychosis.

PURPOSE:Respiratory symptoms account for the majority of drug prescriptions in the first year of life. We investigated the influence of child, parent and physician factors on drug prescriptions for respiratory symptoms in primary care in infancy. METHODS:Infants participated in the WHeezing Illnesses STudy LEidsche Rijn (WHISTLER), a prospective birth cohort on respiratory illnesses. Outcome was defined as having received a prescription of antibiotics or of anti-asthma medication for respiratory symptoms by a physician. RESULTS:Nearly 60% of all children ever visited a physician for respiratory symptoms during the first year of life, of which 40% received a prescription. Every extra day with symptoms during the month before consultation and each extra visit to a physician were associated with a higher chance for prescription (respectively odds ratios (OR) 1.07/2.63, 95% confidence intervals (CI) 1.02-1.12/1.83-3.76). Further, we found a higher chance for drug prescribing for boys (2.7, 2.0-3.7), children attending day care (1.17, 1.09-1.25), mothers with higher education (2.3, 1.2-4.6), working mothers (4.5, 0.9-22.0) and older mothers (years) (1.09, 1.02-1.16). Furthermore, physicians' years of experience was a determinant for receiving a prescription (2.5, 1.1-6.0). Accounting for symptoms and visits as strong predictors of prescribing, infant gender and day care attendance were still predictors. Furthermore, infant gender, day care attendance, family history of asthma and physicians' years of experience were independent determinants of the number of prescriptions besides symptoms and visits. CONCLUSION:In young infancy, besides the severity of symptoms there are child, physician and particularly maternal characteristics that influence the decision of general practitioners to prescribe drugs for respiratory symptoms.

BackgroundIn the large and expanding population of adults with congenital heart disease, little is known about their long-term outcome. By means of a systematic literature search, we aimed to assess the quantity and quality of data on long-term survival and morbidity in adults with common congenital heart defects.MethodsAll literature on MEDLINE from January 1980 to January 2007 was searched, using a broad range of keywords for atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, aortic coarctation, and transposition of the great arteries. After study selection using pre-specified criteria and quality assessment, data were extracted and weighed according to number of patients. Pooled estimates were obtained.ResultsWe identified 322 articles. Selection yielded 35 articles comprising 7894 patients. Data on survival were mainly available up until 40 years of age. In this young population, survival varied from 87.4% in aortic coarctation to 99.6% in atrial septal defect. Data on morbidity were sparse. Based on these data, morbidity was substantial.ConclusionsUntil the age of 40 years, survival is decreased in patients with congenital heart defects, albeit most pronounced among patients with complex heart defects. Moreover, morbidity is considerable in all defects. Sufficient data on long-term survival and morbidity beyond the age of 40 years are lacking, yet crucial for optimal clinical care.

Animal studies have shown that corticosteroids (dexamethasone) cause neuronal loss in the hippocampus and deficits in short term memory. Proton magnetic resonance spectroscopy can measure brain metabolites in vivo and give an indication of neuronal integrity. We investigated whether prolonged administration of hydrocortisone during the neonatal period for bronchopulmonary dysplasia (BPD) in preterm born children changes the metabolism in the hippocampus, measured at school age. Secondly, we investigated whether hippocampal metabolism and short-term memory and neurodevelopmental outcome are related. In this observational study 37 preterm born children (≤ 32 wk (range 25.0-33.0) and/or a birth weight ≤ 1500 g) underwent proton spectroscopy of the hippocampus at school age. Eighteen children were treated with hydrocortisone for BPD (starting dose 5 mg/kg/d tapered over a minimum period of 22 d, median duration 28 d) and 19 never received corticosteroids during the perinatal period. N-acetyl aspartate/ Choline + Creatine/phosphocreatine (NAA/(Cho+Cr)) ratios were determined. A 15-word recall memory test and an IQ measurement were obtained on the same day. Hydrocortisone treated children were younger, lighter and sicker than their nonsteroid treated counterparts. Mean NAA/(Cho+Cr) ratios in the hippocampus were not significantly different in the hydrocortisone group compared with the non-steroid group. Performance on the 15-word memory test and IQ were similar in the two groups. There was no relation between NAA/(Cho+Cr) ratios and memory nor between NAA/(Cho+Cr) ratios and IQ. We conclude that hydrocortisone in the mentioned dose, administered in the neonatal period for BPD, does not appear to have any long-term effects on memory and/or hippocampal metabolism.

Clinical ineffectiveness of combined vaccination with 7-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in children with recurrent acute otitis media; a randomised double-blind study Objective. To determine the effectiveness of a combined vaccination with 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in children with recurrent acute otitis media (AOM). Design. Prospective, double-blind, randomised study. Method A total of 383 patients aged I-6 years with two or more episodes of AOM in the year prior to study entry were included. Randomisation was stratified in 4 groups according to age (I2-24 months versus 25-83 months) and the number of previous AOM episodes per year (2-3 versus 4 or more). Children from the intervention group received either 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine and the control group was vaccinated with hepatitis-A or -B vaccines. All recurrences of AOM were established during an I8-month follow-up period. Secondary outcomes were nasopharyngeal pneumococcal carriage and pneumococci as pathogens of recurrent AOM episodes. Results. No reduction of AOM episodes was observed in the pneumococcal vaccine group compared to the control group (intention to treat analysis: relative risk: I.25; 95%-CI: 0.99-I.57). In the nasopharynx a shift from conjugate vaccine type pneumococci to non-vaccine types was observed. Conclusion. Combined 7-valent pneumococcal conjugate and 23-valent polysaccharide vaccination does not prevent AOM in children aged over I year who had already experienced recurrent episodes of AOM.

Background. Gram-negative bacteremia in children, a major cause of morbidity and mortality, may in part be induced by intensive treatment procedures and nonspecific use of antibiotics. Our primary objective was to study the causal relationship between the use of vancomycin and Gram-negative bacteremia, for which this antibiotic is not specifically indicated. Methods. The study was conducted in a 105-bed tertiary care children’s hospital in the period of 1994 to 1997. The study pertains to a cohort of children with suspected bacteremia, in whom a blood culture was performed during hospital stay. Using the bacteriologic laboratory registration system, we selected all pediatric cases with bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample of 225 pediatric controls with negative blood cultures. Using logistic regression analysis we examined associations between Gram-negative bacteremia and the following factors: preceding use of antibiotics, antacids, corticosteroids, surgery, mechanical ventilation, parenteral nutrition, and invasive instrumentation; and the intensity of care assessed with the Therapeutic Intensity Scoring System (TISS 28). Results. Gram-negative bacteremia was positively associated with the use of aminoglycosides, cephalosporins, surgical interventions, central venous catheters, parenteral nutrition, antacids and dexamethasone. The strongest association was with the use of vancomycin (odds ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic regression model containing all above-mentioned variables, the use of vancomycin remained positively and strongly associated with Gram-negative bacteremia (odds ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and restrictions in the analysis did not materially change these findings concerning vancomycin. Conclusions. Among children suspected of bacteremia there are several drugs and clinical procedures influencing the risk for Gram-negative bacteremia. Empiric use of vancomycin is strongly and independently associated with Gram-negative bacteremia. The safety of using vancomycin solely on the basis of suspicion of bacteremia in children may not be warranted.