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A large proportion of sexually active adults are infected with the human papillomaviruses (HPVs). Although largely asymptomatic, some types of HPVs (HPV-16, HPV-18) which infect the genitalia are known to cause cancers, including cervical cancer. Cervical cancer is an important public health concern and is the second most clinically important cancer to breast cancer in women aged 15-44 years. Until recently, cervical cancer strategies focussed on screening. However, as adolescents become sexually active at a much younger age, the focus is on the use of vaccination as an effective measure to prevent progression of HPV infection to cancer. HPV is also involved in the aetiology of cancers of the anus, vagina, vulva and penis as well as genital warts and laryngeal papillomatosis in young children. Primary prevention through vaccination is now possible in Europe using either the quadrivalent HPV vaccine, Gardasil® (Sanofi Pasteur MSD), or the bivalent HPV vaccine, Cervarix® (GSK), which are both highly immunogenic, with their effects persisting for at least 5 years. HPV vaccines are well tolerated, with serious vaccine-related events occurring in less than 0.1% of patients for both vaccines. Here, we review the possibilities for utilising vaccination programmes alongside current cervical cancer screening in comprehensive cervical cancer prevention programmes. The European Academy of Paediatrics Scientific Working Group on Vaccination concluded that the use of HPV vaccines will have a significant impact in primary prevention of cancers and other HPV-related disease. [ABSTRACT FROM AUTHOR]

Oral sucrose is included in almost all recommendations for treatment of pain in newborns, but evidence if multiple doses might be more effective than a single standard dose is lacking. We designed a single-centre, double-blind, randomised, controlled trial. We enrolled preterm infants needing the heel prick procedure. Each enrolled infant was randomised to receive a single standard dose of sucrose 2 min before or a double dose of sucrose 2 min before, and 30 s after heel prick. Primary outcome was the efficacy of the two interventions tested by the premature infant pain profile-PIPP scale obtained at 30 s, 60 s, and 120 s after heel prick. Secondary outcome was the evaluation of the concordance between the PIPP scale and other pain scores more feasible in clinical practice. Seventy-two infants were randomised. No difference in pain perception as measured by the PIPP scale was found between the groups: median PIPP values 4.0(IQR 3.0-4.0) vs 3.0(IQR 3.0-4.0) at baseline; 6.0(IQR 5.0-10.0) vs 6.0(IQR 4.0-8.5) at 30 s; 6.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-8.5) at 60 s and 5.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-7.5) at 2 min, in the experimental and standard treatment groups, respectively (p = 0.9020). There was no correlation between PIPP scores and other pain scales.Conclusion: We do not recommend doubling the dose during heel prick.What is Known:• Oral sucrose is included in almost all international position papers and recommendations for the treatment of mild to moderate pain in newborns, associated with non-nutritive sucking and facilitated tucking• Premature infant pain profile (PIPP) scale is the gold standard for evaluation of pain in preterms but it is difficult to use in clinical practiceWhat is New:• Repeating a dose of 24% sucrose is not effective in reducing pain during the recovery phase of a skin breaking procedure• Other pain scales, easier to use in clinical practice, are not comparable with PIPP for the evaluation of procedural pain in preterms. [ABSTRACT FROM AUTHOR]

Introduction: In this paper, we evaluated the feasibility of a telemedical (TM) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus (T1DM). Thirty-six adolescents (m=20, median age at the start of the study: 15.3 years (range: 10.7-19.3 years), median age at diagnosis: 9.3 years (2.1-13.8 years), median duration of disease: 6.4 years (1.0-12.8 years), HbA1c>8%, all on intensified insulin therapy) were randomized in a crossover trial over 6 months (3 months with TM, 3 months with conventional support and paper diary (PD)). During the TM phase, the patients sent their data (date, time, blood glucose, carbohydrate intake, insulin dosage) via mobile phone, at least daily, to our server and diabetologists sent back their advice via short message service (SMS) once a week.Results: Glycemic control improved during the TM phase, while it deteriorated during the PD phase: TM-PD group HbA1c (%, median (range)): 9.05 (8-11.3) (at 0 months), 8.9 (6.9-11.3) (at 3 months), and 9.2 (7.4-12.6) (at 6 months), and PD-TM group: 8.9 (8.3-11.6), 9.9 (8.1-11), and 8.85 (7.3-11.7) (p<0.05). Patients rated the TM support program to be a good idea. Technical problems with General Packet Radio Service (GPRS) data transmission led to data loss and decreased patient satisfaction.Conclusion: Our telemedical support program, VIE-DIAB, proved to be feasible in adolescents and helped to improve glycemic control. [ABSTRACT FROM AUTHOR]

Results of community-based childhood obesity intervention programs do not provide strong evidence for their effectiveness. In this study, we evaluated the effect of the Thao-Child Health Program (TCHP), a community-based, multisetting, multistrategy intervention program for healthy weight development and lifestyle choices. In four Catalan cities, a total of 2250 children aged 8 to 10 years were recruited. Two cities were randomly selected for the TCHP intervention, and two cities followed usual health care policy. Children were selected from 41 elementary schools. Weight, height, and waist circumference were measured at baseline and after a mean follow-up of 15 months. Physical activity and adherence to the Mediterranean diet were measured with validated questionnaires. Generalized estimating equations (GEE) models were fitted to determine the intervention's effect on body mass index (BMI) z-score, waist-to-height ratio, Mediterranean diet adherence, and physical activity. Fully adjusted models revealed that the intervention had no significant effect on the BMI z-score, incidence of general and abdominal obesity, Mediterranean diet adherence, and physical activity. Waist-to-height ratio was significantly lower in controls than in the intervention group at follow-up (p < 0.004).Conclusions: The TCHP did not improve weight development, diet quality, and physical activity in the short term. What is Known: • There is inconsistent evidence for the efficacy of school-based childhood obesity prevention programs. • There is little evidence on the efficacy of childhood obesity intervention programs in other settings. What is New: • This paper contributes information about the efficacy of a multisetting and multistrategy Community Based Intervention (CBI) program that uses the municipality as its unit of randomization. • This CBI had no effect on the prevention and treatment of childhood obesity in the short term. [ABSTRACT FROM AUTHOR]

The objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving.Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available. [ABSTRACT FROM AUTHOR]

Capillary blood samples on filter paper were assayed by means of an RIA method (Kit Nichols Institute USA) from 1096 newborns divided into full term, preterm and small-for-date infants. The somatomedin-C (Sm-C) mean value, which did not differ in the three groups, was 0.15 +/- 0.09 IU/ml. One hundred and ten (10%) showed Sm-C disc values less than or equal to 0.075 IU/ml, the minimum value measurable by our method. The day of life and birth weight had a significant influence on Sm-C levels. Gestational age did not have any significant effect. No significant interaction was found among the parameters considered. All the groups presented a progressive increase of Sm-C. Unlike preterm and small-for-date infants, in full term infants the latter increase seemed already to be evident from 5th day of life and reached higher levels from the 7th day of life onwards. In conclusion, Sm-C rates were reduced in the neonatal phase of life, but showed a tendency to rise later. [ABSTRACT FROM AUTHOR]

This paper describes the progress of two previously reported brothers with familial glucocorticoid deficiency, achalasia of the cardia, and alacrima. In their early 'teens both boys developed polyneuropathy with sensory, motor and autonomic components, Parkinsonism, and signs of both dorsal column and pyramidal tract damage. The older boy also showed signs of dementia. Red cell folate levels were markedly reduced but plasma and CSF folate were normal. Serum B12 and erythrocyte concentrations were at or below the lower limit of normal CSF levels of homovanillic acid and 5-hydroxyindole acetic acid (the major metabolites of dopamine and serotonin in brain) were low, indicating impaired turnover of the two amines within the nervous system. Positron emission photometry scans in the older boy showed low binding of c-methyl-spiperone and reduced uptake of 18-F-L-fluorodopa in the striatum, confirming the impairment in dopamine metabolism and suggesting both reduced synthesis and reduced receptor density. Treatment with L-dopa up to 800 mg/day (along with carbidopa 200 mg/day) corrected the low CSF homovanillic acid levels and produced some improvement in the Parkinsonism but no other obvious clinical benefit. Empirical treatment with hydroxycobalamin (1000 micrograms three times a week) and folinic acid (15 mg/day) was without clinical effect. The cause of the neurological disorder, low red-cell folate concentrations, and amine disturbance remains unknown, as does the pathogenesis of the adrenocortical failure. [ABSTRACT FROM AUTHOR]

There is emerging evidence that higher birth weight is associated with increased risk of cancer, in particular childhood leukemia. The purpose of this paper is to study whether this correlation is also significant with other childhood cancer. For this, we conducted a case-control study including 410 childhood cancer patients and 1,575 matched controls to investigate birth weight as a risk factor for leukemia, Wilms tumor, and non-Hodgkin's lymphoma. The estimated risk for all cancers has been found to be statistically and significantly higher in birth weight of more than 4,000 g (odds ratio, 2.50 and 95% confidence intervals (CI), 1.72-3.63). For leukemia, the estimated risk was 1.86 (95% CI, 1.04-3.30), for non-Hodgkin lymphoma, 1.99 (95% CI, 1.08-3.69), and being more remarkable for Wilms tumor, 4.76 (95% CI, 2.73-8.28). Moreover, moderate increased risk of both leukemia and non-Hodgkin lymphoma was also associated with birth weight between 3,000 and 3,999 g. High birth weight was associated with all cancers also when adjusted by gestational age, length at birth, and gender (odds ratio, 6.10 and 95% CI, 1.15-32.57). No associations were found for maternal alcohol consumption during pregnancy, maternal smoking, or smoking by other people at home or presence of obstetric variables (e.g., gestational diabetes, preeclampsia, and abruptio placentae). The present study supports the hypothesis that high birth weight is an independent risk factor for childhood Wilms tumor, leukemia, and non-Hodgkin lymphoma. Further studies should explore biological reasons to explain this relationship and, ultimately, to expand our knowledge about prenatal influences on the occurrence of this disease. [ABSTRACT FROM AUTHOR]

The current paper describes the natural history and management of mucopolysaccharidosis VI (MPS VI) in all patients currently diagnosed with the disease in Italy. Nine patients (5.5-14.4 years) were included in the data review in March 2008. Gestational and perinatal data were normal for all patients. Median age at diagnosis was 1.9 years. During the course of the disease, all patients developed coarsened facial features, short stature, heart valve disease, eye problems, musculoskeletal problems, hepatosplenomegaly and neurological abnormalities. All patients received rhASB enzyme replacement therapy (ERT) and showed improvement or stabilisation in clinical manifestations after onset of therapy. The most frequently reported improvements were increased joint mobility and reduced hepatosplenomegaly. No relevant safety issues of ERT were reported. In conclusion, patients in Italy with MPS VI are diagnosed early in life. All patients have access to ERT and appear to benefit from this therapy. [ABSTRACT FROM AUTHOR]

Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are licensed. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on the introduction of HPV vaccines in central Europe. Eight countries currently have medical representatives on CEVAG: the Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania, Slovakia and Turkey. By raising awareness and disseminating information, CEVAG aims to promote the efficient and safe use of vaccines to prevent, control and if possible eliminate infectious diseases. In January 2008, the European Centre for Disease Prevention and Control published a report entitled Guidance for the Introduction of HPV Vaccines in EU Countries. Members of CEVAG have taken the information relevant to their countries from this report and, with consideration of local issues, produced these guidance recommendations for the introduction of HPV vaccines in the CEVAG region, which may be adapted for use in individual countries. [ABSTRACT FROM AUTHOR]

Effective management of pain remains an important indicator of the quality of care provided to neonates. Since the review of McIntosh in this journal over a decade ago, an extensive number of papers on assessment, prevention, and treatment of pain have been reported. In addition, preclinical insights into neurodevelopmental aspects of pain processing and the neuro-apoptotic effects of analgesics and sedatives were unveiled. Based on the newly collected evidence, the practice of "one-drug, one dose and one treatment fits all" became obsolete, necessitating a more individualized analgesia, based on non-pharmacological and pharmacological therapies and preventive strategies for effective management of neonatal pain. The progress made is impressive, but the current major challenge is to implement the available knowledge in clinical care. Future research should therefore focus on the evaluation of the effectiveness of non-opioid and moderately potent opioids compared to morphine and should also describe the methods to facilitate effective implementation. Finally, there is an extensive field of procedural techniques that need to be evaluated on their pain related response. [ABSTRACT FROM AUTHOR]

In 2006 and 2007, the World Health Organization (WHO) released two sets of child growth standards (World Health Organization, WHO Child Growth Standards. Methods and development. Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. WHO, Geneva, 2006; World Health Organization, WHO Child Growth Standards: Methods and Development. Head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age and subscapular skinfold-for-age. WHO, Geneva, 2007) to replace the National Center for Health Statistics references (Hamill et al., National Center for Health Statistics, Vital and Health Statistics Series 11, No 165, 1977) as an international tool for growth and nutritional assessment. This paper explores the scope of implications for future anthropometric research, highlighting foreseeable effects on the choice of research questions, choice of nutritional indices, training of measurers, and issues of internal and external validity of research results. The conclusion drawn is that the introduction of the WHO child growth standards is expected to have wide implications for growth and nutrition research. The full scope of this effect will gradually become clear while researchers, similar to health care workers, make the transition to using the new standards, re-evaluate results of past approaches, and explore the uses and functional validity of the standards, including those for indices that were not previously available. [ABSTRACT FROM AUTHOR]

In this paper, we report the usefulness of magnetic resonance cholangiopancreatography (MRCP) in excluding biliary atresia (BA) as the cause of neonatal cholestasis. MRCP with a 1.5-T magnetic resonance (MR) imaging unit was performed on four jaundiced neonates and infants aged from 38 days to 106 days. The diagnosis of BA (n=2) was confirmed with surgery, liver biopsy and surgical cholangiography. Diagnosis of neonatal hepatitis (NH, n=2) was confirmed with clinical follow-up until jaundice resolved, while one of them was diagnosed with surgical cholangiography. In all discoloured acholic stools, increased direct bilirubin (4.4-11.3 mg/dl) with positive lipoprotein X prompted technetium 99mTc disofenin scanning, which showed no excretion. Computed tomography (CT) showed a gallbladder in one with hepatitis but no intrahepatic bile duct in two with BA. The Kasai operation was performed in two patients with BA. In two patients with BA, neither the common bile duct nor the common hepatic ducts were visible at MRCP. In two patients with NH, MRCP clearly depicted both the common hepatic and the common bile ducts. MRCP was accurate in excluding BA as the cause of neonatal cholestasis, while 99mTc disofenin cholescintigraphic findings were false-positive in two patients with non-obstructive cholestasis. We conclude that MRCP can be used to depict the major biliary structures of neonates and small infants and to exclude BA as the cause of neonatal cholestasis by allowing visualisation of the biliary tract. [ABSTRACT FROM AUTHOR]

Survival after childhood cancer has been improving since the late 1970s in most developed countries. The Childhood Cancer Registry of Piedmont has been recording malignant tumors in children (0-14 years) throughout Piedmont since 1967. The present paper is based on the records of the 2,970 children diagnosed during the period 1970-2001; survival rates are estimated up to June 30, 2004. Based on records from the Registrar Offices of the relevant towns of residence, 1,698 children were reported to be alive, 1,252 deceased, and 20 were of unknown vital status. Over the period 1970-2001, 5-year survival rates for all tumor types combined showed a statistically significant increasing trend (p<0.0001). For acute lymphocytic leukemia, the survival rate increased steadily from 24.7% (95% CI 15.0-34.3) in 1970-1974 to 87.8% (82.1-93.6) in 1995-1999. Five-year survival rates for central nervous system tumors increased from 32.8% (21.0-44.6) in 1970-1974 to 80.3% (72.6-88.0) in 1990-1994 and decreased thereafter. Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors. A white blood cell count greater than 50,000 x 10(6) cells/l was associated with decreased survival in children with acute lymphocytic leukemia and acute non-lymphocytic leukemia. We have found positive trends in survival for all tumor types in Piedmont, similar to those reported by other population-based cancer registries. Age, extent of disease, and white blood cell count at diagnosis are prognostic factors for selected cancer sites. [ABSTRACT FROM AUTHOR]

Unlabelled: The public health infrastructure of the former Soviet Union was impacted by both the Chernobyl disaster in 1986 and the Soviet breakup in 1991. This paper examines mortality patterns among children aged 1-14 years within the Mogilev region of Belarus between 1980 and 2000. This study utilized a regional cohort design that included all childhood deaths (ages 1-14 years) occurring among persons residing within the Mogilev oblast of Belarus between 1980 and 2000. Patterns of death and death rates were examined across three intervals: 1980-1985 (pre-Chernobyl), 1986-1991 (post-Chernobyl and pre-Former Soviet Union (FSU) breakup) and 1992-2000 (post-Chernobyl and post-FSU breakup) based upon administrative death files. Annual death rates among children aged 1-4 years declined between 1980 and 2000, while mortality rates among children aged 5-9 years and 10-14 years remained steady over this time period. Average annual mortality rates among males aged 5-9 years and 10-14 years increased significantly between 1986 and 1991. Compared to the baseline interval, mortality among both males and females aged 1-4 years was significantly decreased during 1986-1990 and 1992-2000. In general, mortality rates among males were 24%-95% greater compared to females. Injuries and poisonings accounted for the largest proportion of deaths across all age and gender groups examined. Subsequent to the Chernobyl disaster, significant decreases were noted in mortality rates among children aged 1-4 years while mortality rates among children aged 5-9 and 10-14 remained stable.Conclusion: Similar to the findings in other countries, injuries and poisonings predominated as the leading cause of death among Belarussian children. [ABSTRACT FROM AUTHOR]

Unlabelled: Deaths in temporal association with vaccination of hexavalent vaccines have been recently reported. The objective of this paper is to assess whether these temporal associations can be attributed to chance. Standardised mortality ratios (SMR) for deaths within 1 to 28 days after administration of either of the two hexavalent vaccines in the 1st and 2nd year of life were determined using the respective annual rates for sudden unexpected deaths (SUDs) from the national vital statistics. The distribution of SUD cases and the vaccination uptake by month were estimated from surveys and sales figures for the individual vaccines. Sensitivity analyses were performed to account for limitations in the data sources. For one of the vaccines, Vaccine B, all SMRs were well below one. For the other, Vaccine A, SMRs exceeded one insignificantly on the 1st day after vaccination in the 1st year of life. In the 2nd year of life, however, the SMRs for SUD cases within 1 day of vaccination with vaccine A were 31.3 (95% CI 3.8-113.1; two cases observed; 0.06 cases expected) and 23.5 (95% CI 4.8-68,6) for within 2 days after vaccination (three cases observed; 0.13 cases expected). Extensive sensitivity analyses could not attribute these findings to limitations of the data sources.Conclusion: These findings based on spontaneous reporting do not prove a causal relationship between vaccination and sudden unexpected deaths. However, they constitute a signal for one of the two hexavalent vaccines which should prompt intensified surveillance for unexpected deaths after vaccination. [ABSTRACT FROM AUTHOR]

Unlabelled: Mutations in the gene encoding phenylalanine hydroxylase (PAH) cause persistent hyperphenylalaninaemia. To date, more than 200 point mutations and microdeletions have been characterized. Each mutation has a particular quantitative effect on enzyme activity and recessive expression of different mutant alleles results in a marked interindividual heterogeneity of metabolic and clinical phenotypes. In this paper we demonstrate how a simple clinical test can be used to evaluate the correlation between mutation genotype and phenylalanine metabolism. In hyperphenylalaninaemic patients with known PAH mutation genotype, we have investigated phenylalanine turnover in vivo by measuring the ability to eliminate a test dose of L-phenylalanine. All patients could be considered functionally hemizygous for one of their mutant alleles by carrying on the other allele a mutation that is known to completely abolish PAH activity and encode a peptide with no immunoreactivity. Seven mutations (R408W, IVS-12nt1, R261Q, G46S, Y414C, A104D, and D415N) were characterized by oral phenylalanine loading, each mutation being represented by at least three patients. The elimination profile determined for a 3-day period provides a measure to compare residual activity of the mutant proteins and to assign each mutation to a particular metabolic phenotype. The established relation between genotype and phenotype may enable prediction of the severity of the disease by genotype determination in the newborn period. This will aid in the management of hyperphenylalaninaemia and may improve prognosis.Conclusion: The possibility of predicting the residual enzyme activity by DNA analysis performed already in the newborn period allows the prompt implementation of a diet that is adjusted to the degree of PAH deficiency. This may improve management and prognosis of hyperphenylalaninaemia. [ABSTRACT FROM AUTHOR]

This paper examines the development of maximal aerobic power as a function of maturation by a longitudinal study with annual examinations of representative samples of 56 boys and 56 girls in Norway and Western Germany. The age at which occurred peak height velocity (PHV) (i.e. the age at which the greatest height velocity was observed) was used as a reference of biological age and maturation. Before the PHV the mean maximal aerobic power was the same in two cohorts of children both in absolute values as well as in values relative to total and lean body mass. At and after PHV the boys were similar in their absolute values, but the German girls decreased their exercise fitness and became inferior to the Norwegian girls during later adolescence. When related to age of PHV the maximal aerobic power increased during the prepubertal years, mainly as an effect of growth in body size with little or no additional effect of other factors and approached a ceiling level at the end of adolescence. The boys exhibited clearly superior exercise fitness during all years of childhood and adolescence, this being in contrast to the widely accepted concept that no sex difference exists in exercise fitness before puberty. The maximum level for VO2-max, reached at the end of adolescence, averaged 3.2 1/min with a coefficient of variation of about 12% for the boys, and 2.5 1/min for the Norwegian girls and a similar coefficient of variation. As these ceiling values of maximal oxygen uptake agree with published averages for normal young adults representative for the normal population in these two countries, it is suggested that they represent optimal values brought about mainly by normal growth in body size with no or little additional effects of other factors. [ABSTRACT FROM AUTHOR]

The paper provides reference values with regard to pulmonary ventilation responses o progressively increasing bicycling up to the maximal level during the period of growth spurt. Data are based on longitudinal studies or rural Norwegian and German school children. A cluster sampling technique was used, starting with the total pupil-population at Lom in Norway at an age of 8 years, and annual tests were performed until the age of 15 years. In germany a similar pupil-population was tested from age 12 until age 17 years. Functional growth curves giving means and dispersions for ventilation rates, tidal volume, respiratory frequency, ventilatory equivalent and respiratory gas exchange ratio are constructed. Norwegian and German children's developmental processes with regard to the exercise ventilation variables were compared, and revealed no significant differences. [ABSTRACT FROM AUTHOR]

We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3-1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2-3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1-2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1-2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8-7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7-2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2-6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5-24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1-6.9) or PICU admission (aOR 9.7, 6.1-15.5).Conclusions: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions.What Is Known: • While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies.What Is New: • Children with comorbidities in general are more ill upon presentation than children without comorbidities. • Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever. [ABSTRACT FROM AUTHOR]

Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (-0.559 SDS (95%CI -1.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (-0.557 SDS (95%CI -0.736 to -0.419); P < 0.0001) and AH (-0.663 SDS (95%CI -0.803 to -0.524); P < 0.0001). In GnRH analog treated girls (n = 183), PAH before the start of treatment was slightly reduced (-0.939 SDS (95%CI -1.401 to -0.477; P < 0.0001) vs MPH (-0.678 SDS (95%CI -0.942 to -0.414); P < 0.0000), but AH (-0.604 SDS (95%CI -0.877 to -0.338); P < 0.0000) was close to MPH.Conclusion: Present meta-analysis indicates that girls with EP spontaneously reach their MPH and that GnRH analog treatment does not widely change growth outcome. Differences among the selected studies for definition of EP, inclusion criteria, treatment duration, age at discontinuation of therapy, definition of AH may affect results. What is Known: • Early puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents. • Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty. [ABSTRACT FROM AUTHOR]

In preterm neonates, the risk for intracerebral haemorrhage is linked to immaturity of cerebral autoregulation. The preterm's 2-5/min cyclic variation pattern of cerebral blood flow velocity is thought to reflect the degree of immaturity of autoregulation--a speculation to be tested. In a cross-sectional study 15 infants (gestational age 26-40 weeks, postconceptional age (PCA) 26-42 weeks, age 1-99 days were investigated. We performed a 10 min pulsed Doppler tracing on an internal carotid artery by means of a computer controlled 5 MHz Duplex device. Systolic velocity (Vs) was recorded pulse by pulse. After appropriate data transformation, in all infants the Fast Fourier Transform of the time course of Vs revealed the presence of a 2-5/min cyclic variation pattern (one sample z-test, P < 0.0001). There was no significant correlation between proportionate spectral power of the 2-5/min frequency band and either PCA (r = 0.23, P = 0.42) or age (r = 0.41, P = 0.13). Between 26 and 42 weeks PCA, the cycling phenomenon is constant thus not reflecting cerebral maturation, and its presence does not mean immaturity of cerebral autoregulation. [ABSTRACT FROM AUTHOR]

In recent years increased attention has been devoted to evoked potentials (EP) in newborns. This paper reviews the literature and data from our research group in an attempt to assess the diagnostic and prognostic value of evoked responses in the first weeks of life and their use in different age-specific clinical conditions. The results show that EP are a very sensitive measure of the integrity of the sensory pathways. They make it possible to follow normal physiological maturation and the abnormalities of development resulting from neurological lesions. Repeated measurements of visual evoked potentials and somatosensorial evoked potential are prognostically useful in term infants, but seem much more limited in preterm newborns in predicting neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Aromatherapy with essential oils can be used to relieve children. The aim of this study was to evaluate the correlations between psychological and physiologic findings after lavender oil inhalation among children assigned to undergo tooth extraction. A total of 126 children aged between 6 and 12 years were enrolled in the study. The groups were randomly divided into control and lavender groups. The lavender group inhaled 100% lavender oil for 3 min before the interventions, the control group received no prior application. Psychological assessments were made using face image scale (FIS), Face, Legs, Activity, Cry, Consolability (FLACC) and Wong-Baker pain rating scale (WBS). Physiologic changes were assessed using vital signs evaluations. All parameters were noted prior to applications, after inhalation, anesthesia injection, and tooth extraction. The lavender group showed significant lower anxiety and pain scores after tooth extraction (p < 0.05). Significantly lower levels of blood pressures and a significant pulse rate drop were found after inhalation in the lavender group. A statistically significant increase in heart rate was observed after anesthesia injection and tooth extraction in the control group (p < 0.05).Conclusion: Lavender oil can be preferred as a treatment of choice in routine pediatric dentistry.Trial registration number: NCT04115891 (Lavender Oil Inhalation Help to Overcome Dental Anxiety Among Children)What is Known:• Dental anxiety is the most common factor that causes children to have difficulty with the dentist and their parents during treatment.• Aromatherapy with essential oils can be used to relieve children.What is New:• Aromatherapy with lavender oil relieves the child by reducing the level of anxiety and facilitates dental treatment.• During surgical procedures such as local anesthesia and tooth extraction, lavender oil inhalation decreases pain levels of children. [ABSTRACT FROM AUTHOR]

To identify the risk factors of progression and persistence of small- and medium-sized coronary artery aneurysm (CAA) in a contemporary cohort of patients with Kawasaki disease (KD) and to determine the relationship between CAA progression and persistence. A total of 89 KD patients with small- and medium-sized CAA were prospectively enrolled. All patients were followed up at least for 2 years by serial echocardiography. Multivariate logistic regression analysis was conducted to evaluate independent risk factors for CAA progression and persistence. A total of 46 (51.7%) and 73 (82.0%) patients showed echocardiographic CAA regression by 1 month and 24 months of follow-up, respectively. CAA progression was documented in 12 (13.5%) patients during follow-up. The initial aneurysm size according to CAA classification (OR 0.089, 95% CI 0.013-0.634, P = 0.016) and CAA progression (OR 42.618, 95% CI 3.740-485.6, P = 0.003) were independently associated with CAA persistence. The number of involved coronary arteries (OR 0.223, 95% CI 0.065-0.767, P = 0.015) and lymphocyte proportion (OR 1.327, 95% CI 1.019-1.727, P = 0.040) were independently associated with CAA progression.Conclusion: Patients with KD and greater initial aneurysm size, CAA progression, more involved coronary arteries, and lower lymphocyte proportion may require intensive cardiac monitoring and adjuvant therapies.What is Known:• Long-term outcomes of patients with KD and CAA are primarily driven by the consequences of CAA regression and progression.• Regression and progression occurs more frequently in patients with small- and medium-sized CAAs, and less frequently for giant CAAs.What is New:• The CAA size at diagnosis, NCAI, and the proportion of lymphocytes are presumably associated with the small- and medium-sized CAA persistence or CAA progression.• The CAA progression was associated with CAA persistence. [ABSTRACT FROM AUTHOR]

Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults and children aged ≥ 6 years. Pharmacokinetic data for children aged 6-11 years were extracted post hoc from a study in which children (2-11 years) with allergic rhinoconjunctivitis or urticaria received oral bilastine (10 mg/day). Maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC) data were compared with adult pharmacokinetic data from seven clinical studies (bilastine 20 mg/day). Safety data for children aged 6-11 years were extracted post hoc from a phase III randomized controlled trial of children (2-11 years) with allergic rhinoconjunctivitis or chronic urticaria receiving once-daily bilastine 10 mg or placebo for 12 weeks. Exposure and Cmax values were similar for children (6-11 years) and adults: median pediatric/adult ratios for AUC0-24 and Cmax were 0.93 and 0.91, respectively. There was no significant difference in the incidence of treatment-emergent adverse in children (6-11 years) receiving bilastine 10 mg or placebo.Conclusion: Pharmacokinetic and safety analyses in children aged 6-11 years support the suitability of the pediatric dose of bilastine 10 mg and confirm that the safety profiles of bilastine and placebo are similar.What is Known:• Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults (20 mg/day) and children aged ≥ 6 years (10 mg/day).• An ontogenic model based on adult data and pharmacokinetic/pharmacodynamic simulations supported the selection of a bilastine dose of 10 mg/day in children aged 2-11 years. Bilastine 10 mg/day was shown to have a safety profile similar to that of placebo in a large phase III randomized clinical trial in children aged 2-11 years.What is New:• As bilastine is approved in Europe for children aged ≥6 years, the current study reports the results of two post hoc analyses of pharmacokinetic and safety data in children aged 6-11 years.• Analysis of pharmacokinetic and safety data in children aged 6-11 years supports the suitability of the pediatric dose of bilastine 10 mg and confirms that its safety profile is similar to that of placebo. [ABSTRACT FROM AUTHOR]

Early identification and intervention has shown better health outcomes for children with dysphagia. Instrumental swallowing assessments are vital and have been a focus of dysphagia research in the last two decades. This systematic review explores published quantitative instrumental measures of swallowing in children. Five subject-related databases were searched to identify original scientific articles published in English, using instrumental quantitative measures of swallowing to study swallowing/feeding mechanism in children since 1998. Two thousand two hundred and two articles were found from the initial database search and 36 were included in the final qualitative synthesis following PRISMA guidelines. Selected studies showed great diversity in target population, phase/s of swallowing studied, instrumentation used (n = 10) and quantitative measures reported (n = 144). Videofluoroscopy and manometry have been studied most repeatedly. With less frequency, a variety of other instruments has been used to describe suck-swallow patterns and swallowing-related respiration. High-resolution manometry shows the greatest increase in publications with validated, reliable quantitative measures of pharyngeal and oesophageal pressures and timing. More recently, quantification of videofluoroscopy analysis has been a focus.Conclusion: A diverse range of quantitative measures of swallowing is available for children in the literature. However, further reliability and validity testing is needed. Opportunities for clinical application of these quantitative manometric and videofluoroscopic measures are restricted by limited normative comparisons and vast variability in published measures.What is known?• Instrumental swallowing assessments are reliable and accurate in diagnosing swallowing difficulties in children.• However, subjective interpretation of observational findings often questions the optimal use of instrumentation.What is new?• High-resolution manometry has shown promising progress with the development of quantitative objective swallow measures for children. While attempts to quantify video-fluoroscopic measures have been increased in the recent past.• A vast variety of instruments has been used to obtain quantitative and/or objective swallow measures of children, yet clinical application is still in progress. [ABSTRACT FROM AUTHOR]

The aim of this study was to correlate ventricular size and volumes of deep gray matter (DGM) in MRI at term equivalent age (TEA) with outcome at a corrected age of 24 months in preterm infants and with handedness. Seventy-three infants born before 32 weeks of gestation or with birth weight < 1500 g  were included in this retrospective analysis and measurement of lateral ventricles, and DGM was performed on MRI scans. The left lateral ventricle was significantly larger than the right lateral ventricle (p = 0.001). There was no correlation between volumes of the right and left ventricles and the DGM volume (p = 0.207 and p = 0.597, respectively), nor with the head circumference at TEA (p = 0.177 and p = 0.976, respectively). The total volume of both lateral ventricles did not correlate with Mental Develomental Index (MDI, p = 0.336) or Psychomotor Developmental Index (PDI, p = 0.650) score (Bayley Scales of Infant Development, BSID II). However, a correlation of total DGM volume with birth weight (p = 0.0001; r = 0.437), head circumference at TEA (p < 0.0001; r = 0.640), MDI (p = 0.029; r = 0.310), and PDI (p = 0.002; r = 0.456) was observed. No significant difference between right- and left-handed infants was seen in relation to volumes of both lateral ventricles and of DGM.Conclusion: DGM volume at TEA was significantly associated with the outcome at a corrected age of 24 months. Handedness did not correlate with DGM or lateral ventricle size.What is Known:• White matter injury as well as altered development of deep gray matter is associated with neurodevelopmental disability in preterm infants.• No study analyzed the association between deep gray matter volume or volumes of lateral ventricle and handedness in former preterm infants so far.What is New:• Volume of deep gray matter, but not lateral ventricular size was significantly associated with outcome at a corrected age of 24 months in preterm infants.• There was no correlation of handedness with volumes of lateral ventricular size or with deep gray matter volumes. [ABSTRACT FROM AUTHOR]

This paper describes the percentile curves for red blood cell (RBC) count, Hb, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) values of beta zero-thalassaemia heterozygotes during infancy, childhood and adolescence. Hb values were about 2 g/dl below those of normal controls with a progressive increase with age paralleling the normal developmental trend. The Hb increase with age was due to a progressive rise in the Hb content per cell, the number of RBC remaining nearly constant. MCV and MCH values also increased with age with a pattern parallel to normal control. Because of the high prevalence of alpha-thalassaemia in the Sardinian population, to which all the subjects investigated belong, the 3rd MCH-MCV percentile curves of normal overlap the 97th curve of beta-thalassaemia heterozygotes. The HbA2 levels, however, were always increased as compared to normal. These results confirm in children than screening for heterozygous beta-thalassaemia in populations with a high incidence of alpha and beta-thalassaemia by MCV-MCH determination may overlook a sizeable proportion of beta-thalassaemia carriers. The knowledge of the extent of variation of RBC indices of beta-thalassaemia heterozygotes during infancy, childhood and adolescence, is very useful for the evaluation of a child presenting with a mild microcytic anaemia. [ABSTRACT FROM AUTHOR]

Early lung inflammation has been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). We aimed to establish the efficacy and safety of systemic hydrocortisone for the prevention of BPD. A systematic review and meta-analysis were undertaken, with a detailed electronic literature search. Trials involving preterm infants were included if they were randomised to receive systemic hydrocortisone or a placebo. The primary outcome was the composite of survival without BPD at 36-week postmenstrual age (PMA). Results are presented as relative risk (RR) or risk difference (RD) with 95% confidence intervals (CIs), along with numbers needed to treat (NNT) or harm (NNH). After filtering, 12 studies using early (within 1 week of birth) and two using late hydrocortisone were identified. Early systemic hydrocortisone significantly increased the chances of survival without BPD (RR 1.13, 95% CI [1.01, 1.26], NNT 18), and survival without moderate-to-severe neurodevelopmental impairment (1.13 [1.02, 1.26], NNT 14). Infants who received hydrocortisone had a higher risk of intestinal perforation (1.69 [1.07, 2.68], NNH 30), primarily with concurrent treatment for patent ductus arteriosus.Conclusion: Early systemic hydrocortisone is a modestly effective therapy for the prevention of BPD in preterm infants, although some safety concerns remain. No conclusions could be drawn for late hydrocortisone due to the paucity of studies. What is Known: • Preterm infants are at high risk of developing bronchopulmonary dysplasia (BPD) and early lung inflammation plays a significant role in its pathogenesis. • Both early and late systemic dexamethasone seems to reduce the incidence of BPD, but its use is associated with serious neurodevelopmental impairment at follow-up. What is New: • Early systemic hydrocortisone significantly improved survival without BPD at 36 weeks and survival without moderate to severe neurodevelopmental impairment on follow up. • Incidence of gastrointestinal perforation associated with concurrent treatment for PDA was significantly higher, although early systemic hydrocortisone reduced the need for treatment of PDAs. [ABSTRACT FROM AUTHOR]

Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). No direct comparison of these two modalities in children exists. We aimed to compare head-to-head the diagnostic accuracy of ALT and US and their combination for detecting NAFLD in children with obesity. Ninety-nine children with severe obesity underwent simultaneous serum-ALT and abdominal ultrasound (US steatosis score 0-3). Proton magnetic resonance spectroscopy was used as reference standard for detecting steatosis/NAFLD. ROC curve analyses were performed to determine diagnostic performance and to determine optimum screening cut-points aiming for a specificity ≥ 80%. The area under the ROC (AUROC) of ALT and US were not significantly different (0.74 and 0.70, respectively). At the optimal ALT threshold (≥40 IU/L), sensitivity was 44% and specificity was 89%. At the optimal US steatosis score (≥ 2), sensitivity was 51% and specificity was 80%. Combining ALT and US did not result in better accuracy than ALT or US alone.Conclusion: ALT and US have comparable and only moderate diagnostic accuracy for detecting hepatic steatosis in children with obesity. A stepwise screening strategy combining both methods does not improve diagnostic accuracy. What is Known: • Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). • ALT and ultrasound have mediocre accuracy in detecting steatosis in children with obesity. What is New: • In a head-to-head comparison, the difference in diagnostic accuracy of ALT and ultrasound in detecting steatosis is not significant. • A stepwise screening strategy combining both methods does not improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

The aim was to describe the psychological functioning of parents of school-age children with heart disease (HD) in a large-scale, transnational evaluation of parent dyads across the spectrum of cardiac diagnoses and a range of psychosocial domains. Parents of children with HD attending routine out-patient cardiology follow-up visits completed questionnaires assessing their mental health, coping, and family functioning. Parents (1197 mothers and 1053 fathers) of 1214 children (mean age: 12.6 years; S.D. 3.0 years; median time since last surgery: 8.9 years) with congenital or acquired HD from three centers each in the UK and the USA participated (80% response rate). Parents of children with milder HD demonstrated few differences from healthy norms and had significantly lower scores on measures of illness-related stress and post-traumatic stress than parents of children with single ventricle conditions or cardiomyopathy. Parents in these latter two diagnostic sub-groups had significantly higher levels of anxiety and depression than healthy norms but did not differ on other measures of family functioning and coping skills. There were few differences between parents from the UK and the USA. Agreement between mothers and fathers within a dyad was highest for the measure of frequency of illness-related stressors (ICC = 0.67) and lowest for anxiety (ICC = 0.12).Conclusion: Our results suggest two different pathways for the long-term psychological well-being of parents of children with HD: on the one hand, more complex HD is associated with poorer long-term psychosocial outcomes; in contrast, there are also grounds for optimism, particularly for parents of children with less complex conditions, with better psychological outcomes noted for some groups of parents compared to previously reported early psychosocial outcomes. Future work needs to identify factors other than disease severity which might explain poorer (or better) functioning in some parents of children with more complex HD. What is Known: • Parents of children with congenital heart disease report elevated levels of anxiety, depression, and stress after cardiac surgery in infancy. • Maternal mental health problems can have an adverse impact on the psychological adjustment of the child with congenital heart disease. What is New: • Parents of children with milder forms of heart disease do not differ from healthy norms in the longer term and psychological outcomes are better than might be expected from early findings. • More complex diagnoses, particularly functional single ventricle conditions and cardiomyopathy, are associated with poorer long-term psychosocial outcomes for parents. [ABSTRACT FROM AUTHOR]

A healthy lifestyle habits in adolescents consist of healthy eating patterns and active ways of spending leisure time. This study aimed to examine the relationship between organized leisure-time activities (OLTA) and eating habits in adolescence. Data from the 2013/2014 Health Behaviour in School-aged Children (HBSC) study on 10,494 Czech adolescents aged 11-15 years was used. The associations of participation in OLTA with ten specific eating habits were analyzed using logistic regression. Involvement in any type of OLTA was associated with higher consumption of daily breakfast, fruit, and vegetables and a lower intake of soft drinks. Participants in non-sport and sport and other activity reported lower rates of unhealthy eating habits (e.g., lower rates of eating crisps and eating in front of the TV or computer). Participation only in sport was related to more frequent eating at fast food restaurants but less frequent snacking in front of the computer and intake of crisps.Conclusion: Participation in OLTA was associated with healthier eating habits (e.g., consumption of fruit and vegetables) and a lower occurrence of unhealthy eating habits (e.g., consumption of soft drinks). Alternatively, our findings indicate that non-participation in OLTA can serve as an indicator of an unhealthy lifestyle in adolescence. What is Known • Unhealthy eating habits in youth tend to persist into adulthood and are related to adverse health consequences later in life. • The type of the leisure-time activity (participation in sport, non-sport, sport, and other activities) affects the strength of developmental outcomes in adolescents. What is New • Youth participating in non-sport activity and sport and other activity concurrently reported lower rates of unhealthy eating habits (e.g., eating junk food, eating in front of the TV/computer). • Non-participation in OLTA could be viewed as a potential risk factor for an unhealthy lifestyle in adolescents. [ABSTRACT FROM AUTHOR]

This cross-sectional study assessed the prevalence of bacteria isolated from Spanish children with suspected chronic lower respiratory tract infection (LRTI) for whom bronchoalveolar lavage (BAL) was indicated. BAL fluid (BALF) was collected from 191 children (aged ≥ 6 months to < 6 years, with persistent or recurrent respiratory symptoms, non-responders to usual treatment) and cultured. Nasopharyngeal swabs (NPSs) were also obtained and cultured to assess concordance of BALF and NPS findings in the same patient. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis were identified from BALF with a bacterial load indicative of infection (> 104 colony-forming units/mL) in 10.5, 8.9, and 6.3% of children, respectively. Clinical characteristics were similar among participants, regardless of positivity status for any of the bacteria. Approximately 26% of pneumococcal isolates were PCV13 serotypes, and 96% of H. influenzae isolates were non-typeable (NTHi). Concordance between BALF and NPS isolates was 51.0% for S. pneumoniae, 52.1% for H. influenzae, and 22.0% for M. catarrhalis.Conclusion: S. pneumoniae, NTHi, and M. catarrhalis were the main bacteria detected in BALF and NPS. Children with suspected chronic LRTI may benefit from a vaccine protecting against NTHi. What is Known: • Chronic lower respiratory tract infection (LRTI) in children can cause high morbidity and is a major use of healthcare resources worldwide. Despite this, their etiology or potential preventive measures are poorly assessed. • Bronchoalveolar lavage can be used to determine bacterial etiology of chronic LRTI. What is New: • We used conventional and molecular techniques to show that Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis were present in the LRT of Spanish children with suspected chronic LRTI • Concordance between isolates from bronchoalveolar lavage fluid and nasopharyngeal swabs was low, suggesting that samples from the upper respiratory tract could not reliably predict the bacterial etiology of suspected chronic LRTI. [ABSTRACT FROM AUTHOR]

The article discusses research on the relation of a blood urea nitrogen to serum creatinine ratio (BCR) to diarrhea-associated hemolytic uremic syndrome (D+HUS) in children. Topics include the use of BCR as a prognostic measure at the time of hospital admission, the impact of various comorbidities on prognosis, and the notion of a complicated course for children with D+HUS.

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001).Conclusions: Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function. [ABSTRACT FROM AUTHOR]

Nasal injuries with use of nasal continuous positive airway pressure (CPAP) range from blanching of nasal tip to septal necrosis and septal drop. This analysis was done in preterm neonates of < 34-week gestation, who received nasal CPAP as primary support as part of a randomized trial comparing Jet device with Bubble device for delivery of CPAP, both through nasal prongs of different structure, make and fixation methods. Nasal injury was assessed using a validated nasal injury score. Out of 170 neonates enrolled, 103 (61%) had nasal injuries; moderate and severe injuries were observed in 18 (11%) and 8 (5%) infants, respectively. Septum was the most common site injured. The incidence and severity of nasal injury were significantly lesser in Jet group compared to Bubble group [RR 0.6 (95% C.I. 0.5-0.8); p < 0.001]. Similarly, neonates in Jet group had lesser average [median (IQR): 3 (3,4) vs. 4 [8, 14]; p = 0.04] as well as peak N-PASS pain scores [median (IQR): 4 [8, 14] vs. 5 [13, 16]; p = 0.01] in comparison to Bubble group. However, Jet group neonates had significantly more common prong displacements.Conclusion: Bubble CPAP device with its nasal interface had higher and more serious incidence of nasal injuries in comparison to Jet CPAP device. What is known: • Nasal injuries are becoming increasingly common with use of nasal CPAP low gestational age, low birth weight, longer use of CPAP and longer NICU stay are risk factors for such injuries • Validated nasal injury scores have been created for assessment of nasal trauma in neonates What is new: • Bubble device with its interface had higher and more serious incidence of nasal injuries in comparison to Jet device • Even though pain assessed by N-PASS was less with Jet device, prong displacements were more frequent with its system. [ABSTRACT FROM AUTHOR]

We compared the level of attention capacity between adolescents from the center and south of Europe. The study included 627 European adolescents (54% girls), aged 12.5-17.5 years, who participated in the HELENA Study. The d2 Test of Attention was administered to assess attention capacity. The main results showed that adolescents from the south of Europe had significantly higher score in attention capacity compared with adolescents from central Europe (score + 8.1; 95%CI, 2.44-13.61) after adjustment for age, sex, socioeconomic indicators, body mass index, cardiorespiratory fitness and diet quality index (p = 0.012).Conclusion: Adolescents from the south of Europe had higher levels of attention capacity than their counterparts from central Europe independently of sociodemographic and health-related factors. These differences should be taken into account by educational institutions when promoting new approaches for putting into the practice student's capacities. What is Known? • Attention is a crucial capacity during adolescence. • Several health-related factors (i.e., physical activity, fitness or fatness) may influence attention capacity in adolescents. What is New? • Adolescents from the south of Europe had higher levels of attention capacity than their counterparts from the center, after accounting for socioeconomic factors, fitness, fatness and quality of diet. • These differences should be taken into account by educational institutions when promoting new approaches for putting into the practice student's capacities. [ABSTRACT FROM AUTHOR]

Upper Respiratory Tract Infections (URTI) are very common in children having no effective pharmacological treatment. This study aimed to compare the effect of caregivers' health education regarding children's respiratory infections and the effect of a rhinopharyngeal clearance protocol in children with URTI. A factorial trial was conducted in 138 children up to 3 years, attending day-care centres. Children were distributed into four groups: control group (CG) (n = 38); education group (EG) (n = 34); intervention group (IG) (n = 35); and education and intervention group (E + IG) (n = 31). A Diary of Records was kept by caregivers during 1 month. There were significant differences between groups concerning: Lower Respiratory Tract Infections (CG = 29.4%; EG = 10.7%; IG = 3.8%; E + IG = 0.0%; p = 0.014); acute otitis media (CG = 32.4%; EG = 7.1%; IG = 11.5%; E + IG = 7.7%; p = 0.014); medical consultations (CG = 70.6%; EG = 42.9%; IG = 38.5%; E + IG = 30.8%; p = 0.021); antibiotics (CG = 44.1%; EG = 7.1%; IG = 23.1%; E + IG = 15.4%; p = 0.006); days missed from day-care (CG = 55 days; EG = 22 days; IG = 14 days; E + IG = 6 days; p = 0.020); days missed from employment (CG = 31 days; EG = 20 days; IG = 5 days; E + IG = 1 day; p = 0.021); and nasal clearance techniques (CG = 41.4%; EG = 78.6%; IG = 57.7%; E + IG = 84.6%; p = 0.011).Conclusion: This study showed that the most positive impact on children's health outcomes occurred when combining health education of caregivers, regarding children's respiratory infections, with a rhinopharyngeal clearance protocol in children with URTI. What is Known: • Upper Respiratory Tract Infections are very common in children but still do not have an effective pharmacological treatment. • This generates a great burden of disease for the child and families, increasing the use of antibiotics. What is New: • This study is the first one that aims to analyze the effects of caregivers' health education in comparison to non-pharmacological intervention in acute respiratory infections in children. • It shows a positive impact on children's health outcomes, empowering caregivers regarding their child's health and reducing the burden of disease, medical consultations and the use of antibiotics. [ABSTRACT FROM AUTHOR]

Postoperative junctional ectopic tachycardia (JET) is a frequent complication after pediatric cardiac surgery. Current recommendations on how and when to treat JET are inconsistent. We evaluated the management strategies of postoperative JET in German-speaking countries. We sent an online survey to 30 centers of pediatric cardiology that perform surgery for congenital heart defects in Germany (24), Austria (4), and Switzerland (2). The survey asked 18 questions about how and in what treatment sequence postoperative JET was managed. All 30 centers completed the survey (100% return rate). There was general agreement that the management of JET is based on administration of antiarrhythmic drugs, body surface cooling, and temporary pacing. Many centers presented treatment algorithms based on published literature, all centers named amiodarone as the first drug of choice. Significant disagreement was found concerning the timing and sequential order of additional therapeutic measures and particularly about the dosing of amiodarone and the role of R-wave synchronized atrial pacing.Conclusion: This survey reveals that from center to center, the treatment of postoperative JET may vary substantially. Future work should focus on those treatment modalities where a high rate of variation is found. Such studies may be of value to achieve commonly adopted treatment recommendations. What is known: • Treatment of postoperative junctional ectopic tachycardia is predominantly based on administration of antiarrhythmic drugs, therapeutic cooling, and temporary pacing. • Amiodarone is the antiarrhythmic drug of choice in this context. What is new: • Dosing and duration of administration of amiodarone differ relevantly from center to center. • The sequential order of drug administration, therapeutic cooling, and pacing is not consistent. [ABSTRACT FROM AUTHOR]

In 2011, the 7-valent conjugated pneumococcal vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) and universal hepatitis B vaccination has been introduced in the Netherlands. A questionnaire study was conducted to assess the tolerability of DTaP-IPV-Hib + PCV7 (PCV7-cohort), DTaP-IPV-Hib + PCV10 (PCV10-cohort), and DTaP-IPV-Hib-HepB + PCV10 (HepB-cohort). Parents were asked to report in questionnaires local reactions and systemic adverse events (AEs) before and after vaccination of their infant at 2, 3, 4, and 11 months of age. For 29.0 and 29.4% infants of the PCV7-cohort, at least one local reaction was reported in the week after the first dose of DTaP-IPV (left leg) and PCV-7 vaccination (right leg). Significantly more infants from the PCV10-cohort (45.1%, p < 0.001 and 44.6%, p < 0.001) and HepB-cohort (42.6%, p < 0.001 and 41.9%, p < 0.001) reported at least one local reaction. This effect was less pronounced after the successive doses. Most of the infants experienced at least one systemic AE, and after dose 4, this was higher for infants in the PCV10-cohort (65.9%, p = 0.047) and HepB-cohort (70.6%, p = 0.000) compared to the PCV7-cohort (62.3%).Conclusion: Addition of antigens to a vaccine resulted in a higher reactogenicity, but the AEs were in general mild and transient. What is Known: • Assessment of adverse events is crucial for achieving the highest safety in immunization programs, in order to inform public health actions and maintain public confidence in immunization programs. What is New: • Newly introduced vaccines DTaP-IPV-Hib-HepB and PCV10 are generally safe and well tolerated in infants. • These results are useful for information purposes and for monitoring variations in rates of AEs in the general population or in the target group over time. [ABSTRACT FROM AUTHOR]

Neurodevelopmental outcome after prematurity is crucial. The aim was to compare two amplitude-integrated EEG (aEEG) classifications (Hellström-Westas (HW), Burdjalov) for outcome prediction. We recruited 65 infants ≤32 weeks gestational age with aEEG recordings within the first 72 h of life and Bayley testing at 24 months corrected age or death. Statistical analyses were performed for each 24 h section to determine whether very immature/depressed or mature/developed patterns predict survival/neurological outcome and to find predictors for mental development index (MDI) and psychomotor development index (PDI) at 24 months corrected age. On day 2, deceased infants showed no cycling in 80% (HW, p = 0.0140) and 100% (Burdjalov, p = 0.0041). The Burdjalov total score significantly differed between groups on day 2 (p = 0.0284) and the adapted Burdjalov total score on day 2 (p = 0.0183) and day 3 (p = 0.0472). Cycling on day 3 (HW; p = 0.0059) and background on day 3 (HW; p = 0.0212) are independent predictors for MDI (p = 0.0016) whereas no independent predictor for PDI was found (multiple regression analyses).Conclusion: Cycling in both classifications is a valuable tool to assess chance of survival. The classification by HW is also associated with long-term mental outcome. What is Known: •Neurodevelopmental outcome after preterm birth remains one of the major concerns in neonatology. •aEEG is used to measure brain activity and brain maturation in preterm infants. What is New: •The two common aEEG classifications and scoring systems described by Hellström-Westas and Burdjalov are valuable tools to predict neurodevelopmental outcome when performed within the first 72 h of life. •Both aEEG classifications are useful to predict chance of survival. The classification by Hellström-Westas can also predict long-term outcome at corrected age of 2 years. [ABSTRACT FROM AUTHOR]

Acute gastroenteritis (AGE) is one of the most frequent reasons for young children to visit emergency departments (EDs). We aimed to evaluate (1) feasibility of a nurse-guided clinical decision support system for rehydration treatment in children with AGE and (2) the impact on diagnostics, treatment, and costs compared with usual care by attending physician. A randomized controlled trial was performed in 222 children, aged 1 month to 5 years at the ED of the Erasmus MC-Sophia Children's hospital in The Netherlands ( 2010-2012). Outcome included (1) feasibility, measured by compliance of the nurses, and (2) length of stay (LOS) at the ED, the number of diagnostic tests, treatment, follow-up, and costs. Due to failure of post-ED weight measurement, we could not evaluate weight difference as measure for dehydration. Patient characteristics were comparable between the intervention (N = 113) and the usual care group (N = 109). Implementation of the clinical decision support system proved a high compliance rate. The standardized use of oral ORS (oral rehydration solution) significantly increased from 52 to 65%(RR2.2, 95%CI 1.09-4.31 p < 0.05). We observed no differences in other outcome measures.Conclusion: Implementation of nurse-guided clinical decision support system on rehydration treatment in children with AGE showed high compliance and increase standardized use of ORS, without differences in other outcome measures. What is Known: • Acute gastroenteritis is one of the most frequently encountered problems in pediatric emergency departments. • Guidelines advocate standardized oral treatment in children with mild to moderate dehydration, but appear to be applied infrequently in clinical practice. What is New: • Implementation of a nurse-guided clinical decision support system on treatment of AGE in young children showed good feasibility, resulting in a more standardized ORS use in children with mild to moderate dehydration, compared to usual care. • Given the challenges to perform research in emergency care setting, the ED should be experienced and adequately equipped, especially during peak times. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the pathological classifications, clinical features, and natural history of pediatric cardiac tumors to provide a basis for the selection of an appropriate therapeutic method. The medical records of in- or outpatients with cardiac tumors at four hospitals were classified to analyze various types of tumor growth locations, clinical manifestations, surgical indications, and long-term follow-up results. There were 166 patients, including 158 with primary cardiac tumors, six with metastatic cardiac tumors, and two with unclassified cardiac tumors. Among the 158 cases of primary cardiac tumor, 150 were benign and eight were malignant. The rhabdomyoma, fibroma, and myxoma are the most common types of benign cardiac tumors. The major clinical manifestations of cardiac tumors include outflow tract obstruction, arrhythmia, dyspnea, pericardial effusion, heart failure, and seizures. Among the 59 patients who underwent surgery, 49 had primary benign cardiac tumors, eight had primary malignant tumors, and two had malignant metastatic tumors. Post-surgery, nine of the patients had residual tumor tissues that did not significantly affect their hemodynamics. Following surgery, there were two cases of recurrence and nine deaths, including four of benign and five of malignant tumors with mortality rates of 8.2 and 50.0 %, respectively. Of the remaining 107 cases of patients who did not undergo surgery, five (4.7 %) died.Conclusion: The primary benign cardiac tumors are the predominant pediatric cardiac tumors, of which rhabdomyoma, fibroma, and myxoma are the most common types. If severe symptoms are nonexistent and the hemodynamics is unaffected, most of the patients can survive in the long term despite the tumors. What is known: • Pediatric cardiac tumors are rare and are predominantly primary and benign. • The symptoms of heart failure, arrhythmia, and outflow obstruction are the most severe complications of cardiac tumors. What is new: • The rhabdomyoma, fibroma, and myxoma are the most common types of primary benign cardiac tumors. • If severe symptoms are not present and the hemodynamics are unaffected, most of the patients can survive in the long term despite the tumors. [ABSTRACT FROM AUTHOR]

Unlabelled: Decisions at the limits of viability about initiating care are challenging. We aimed to investigate physicians' preferences on treatment decisions, against the background of the 2010 Dutch guideline offering active care from 24(+0/7) weeks of gestational age (GA). Obstetricians' and neonatologists' opinions were compared. An online survey was conducted amongst all perinatal professionals (n = 205) of the 10 Dutch level III perinatal care centers. Response rate was 60 % (n = 122). Comfort care was mostly recommended below 24(+0/7) weeks and intensive care over 26(+0/7) weeks. The professional views varied most at 24 and 25 weeks, with intensive care recommended but comfort care at parental request optional being the median. There was a wide range in perceived lowest limits of GA for interventions as a caesarian section and a neonatologist present at birth. Obstetricians and neonatologists disagreed on the lowest limit providing chest compressions and administering epinephrine for resuscitation. The main factors restricting active treatment were presence of congenital disorders, "small for gestational age" fetus, and incomplete course of corticosteroids.Conclusion: There was a wide variety in individually preferred treatment decisions, especially when aspects were not covered in the Dutch guideline on perinatal practice in extreme prematurity. Furthermore, obstetricians and neonatologists did not always agree.What Is Known: • Cross-cultural differences exists in the preferred treatment at the limits of viability • In the Netherlands since 2010, intensive care can be offered starting at 24 (+0/7)   weeks gestation What is new: • There was a wide variety in preferred treatment decisions at the limits of viability especially when aspects were not covered in the Dutch national guideline on perinatal practice in extreme prematurity. [ABSTRACT FROM AUTHOR]

Unlabelled: Empirical evidence has shown that international adoptees present physical growth delays, precocious puberty, behavioral problems, and mental health referrals more often than non-adoptees. We hypothesized that the higher prevalence of (mental) health problems in adoptees is accompanied by elevated consumption of prescription drugs, including antidepressants, attention deficit hyperactivity disorder (ADHD) medication, and medication for growth inhibition/stimulation. In an archival, population-based Dutch cohort study, data on medication use were available from the Health Care Insurance Board by Statistics Netherlands from 2006 to 2011. The Dutch population born between 1994 and 2005 and alive during the period of measurement was included (2,360,450 including 10,602 international adoptees, of which 4447 from China). Their mean age was 6.5 years at start (range 1-12 years) and 11.5 years at the end of the measurement period (range 6-17 years). Chinese female adoptees used less medication for precocious puberty (as treatment for precocious puberty; odds ratio (OR) = 0.57, effect size Cohen's d = -0.31) and contraception (OR = 0.65, d = -0.24) than non-adoptees. For both males and females, non-Chinese adoptees used more medication for ADHD than non-adoptees (males: OR = 1.22, females: OR = 1.32), but the effect was small (males: d = 0.11, females: d = 0.15).Conclusions: Adoptees in the Netherlands generally do not use more medication than their non-adopted peers.What Is Known: • Meta-analytical evidence shows that international adoptees present physical growth delays and mental health referrals more often than non-adopted controls. • With the exception of one Swedish study on ADHD medication, there is no other systematic research on medication use of international adoptees. What is New: • All differences in medication use between international adoptees in the Netherlands and non-adopted controls were below the threshold of a small effect with the exception of medication for precocious puberty, but this effect was in the opposite direction with female adoptees using less medication for precocious puberty than non-adoptees. • International adoptees in the Netherlands do not use more medication despite experiences of preadoption adversity and higher rates of mental health referrals during childhood and adolescence. [ABSTRACT FROM AUTHOR]

Unlabelled: Online communication is associated with offline romantic and sexual activity among college students. Yet, it is unknown whether online communication is associated with the initiation of romantic and sexual activity among adolescents. This two-wave panel study investigated whether chatting, visiting dating websites, and visiting erotic contact websites predicted adolescents' initiation of romantic and sexual activity. We analyzed two-wave panel data from 1163 Belgian adolescents who participated in the MORES Study. We investigated the longitudinal impact of online communication on the initiation of romantic relationships and sexual intercourse using logistic regression analyses. The odds ratios of initiating a romantic relationship among romantically inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites were two to three times larger than those of non-users. Among sexually inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites, the odds ratios of initiating sexual intercourse were two to five times larger than that among non-users, even after a number of other relevant factors were introduced.Conclusion: This is the first study to demonstrate that online communication predicts the initiation of offline sexual and romantic activity as early as adolescence. Practitioners and parents need to consider the role of online communication in adolescents' developing sexuality.What Is Known: • Adolescents increasingly communicate online with peers. • Online communication predicts romantic and sexual activity among college students. What is New: • Online communication predicts adolescents' offline romantic activity over time. • Online communication predicts adolescents' offline sexual activity over time. [ABSTRACT FROM AUTHOR]

Unlabelled: Despite the severity of HUS and the fact that it represents a leading cause of acute kidney injury in children, the general epidemiology of HUS is all but well documented. The present study provides updated, population-based, purely epidemiological information on HUS in childhood from a large and densely populated area of northern Italy (9.6 million inhabitants, 1.6 million children). We systematically reviewed the files concerning patients with STEC-HUS and atypical HUS (aHUS) over a 10-year observation period (January 2003-December 2012). We included all incident cases with a documented first episode of HUS before the age of 18 years. We identified 101 cases of HUS during the 10 years. The overall mean annual incidence was 6.3 cases/million children aged <18 years (range 1.9-11.9), and 15.7/million of age-related population (MARP) among subjects aged <5 years; aHUS accounted for 11.9 % of the cases (mean incidence 0.75/MARP). The overall case fatality rate was 4.0 % (3.4 % STEC-HUS, 8.3 % aHUS).Conclusion: Given the public health impact of HUS, this study provides recent, population-based epidemiological data useful for healthcare planning and particularly for estimating the financial burden that healthcare providers might have to face in treating HUS, whose incidence rate seems to increase in Northern Italy.What Is Known: • HUS is a rare disease, but it represents the leading cause of acute kidney injury in children worldwide. • STEC-HUS (also called typical, D + HUS) is more common compared to atypical HUS, but recent, population-based epidemiological data (incidence) are scanty. What is New: • Comprehensive, population-based epidemiological data concerning both typical and atypical HUS based on a long observational period. [ABSTRACT FROM AUTHOR]

Unlabelled: Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive disorder of ureagenesis presenting as life-threatening hyperammonemia. In this study, we present the main clinical features and biochemical and molecular data of six Malaysian patients with CPS1 deficiency. All the patients have neonatal-onset symptoms, initially diagnosed as infections before hyperammonemia was recognized. They have typical biochemical findings of hyperglutaminemia, hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate succumbed to the first hyperammonemic decompensation. Five neonatal survivors received long-term treatment consisting of dietary protein restriction and ammonia-scavenging drugs. They have delayed neurocognitive development of varying severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which were not previously reported. Five mutations were missense changes while another three were predicted to create premature stop codons. In silico analyses showed that these new mutations affected different CPS1 enzyme domains and were predicted to interrupt interactions at enzyme active sites, disturb local enzyme conformation, and destabilize assembly of intact enzyme complex.Conclusion: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of our study was to examine the association between problematic cell phone use (PCPU) for text messaging and substance abuse in young adolescents. This cross-sectional study was conducted on the basis of an ad hoc questionnaire, during the 2014-2015 school year in a province of the Veneto Region (Italy); it involved a sample of 1156 students in grades 6 to 8 (11 to 13 years old). A self-report scale based on the Short Message Service (SMS) Problem Use Diagnostic Questionnaire (SMS-PUDQ) was administered to assess the sample's PCPU. A multivariate logistic regression model was applied to seek associations between PCPU (as the dependent variable) and independent variables. The proportion of students who reported a PCPU increased with age in girls (13.5% in 6th grade, 16.4% in 7th grade, and 19.5% in 8th grade), but not in boys (14.3% in 6th grade, 18.0% in 7th grade, and 14.8% in 8th grade). Logistic regression showed that drunkenness at least once and energy drink consumption raised the odds of PCPU, whereas reading books, higher average school marks, and longer hours of sleep were associated with lower odds of PCPU in early adolescence.Conclusion: our findings confirm a widespread PCPU for text messaging among early adolescents. The odds of PCPU is greater in young people at risk of other substance abuse behavior. [ABSTRACT FROM AUTHOR]