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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]

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]

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]

Approximately one third of boys with X-linked adrenoleukodystophy (X-ALD) develop an acute, progressive inflammatory process of the central nervous system, resulting in rapid neurologic deterioration and death. Hematopoietic cell transplantation (HCT) can halt the progression of neurologic disease if performed early in the course of the cerebral form of X-ALD. We describe a retrospective cohort study of 90 boys with X-ALD evaluated at our institution between 2000 and 2009, to determine if early diagnosis of X-ALD following the diagnosis of unexplained adrenal insufficiency (AI) improves outcomes. We describe seven cases with a delay in the diagnosis of X-ALD and compare their outcomes to ten controls with the diagnosis of ALD made within 12 months following diagnosis of AI. At the time of evaluation for HCT, boys with a delay in the diagnosis of X-ALD had more extensive cerebral involvement and more limited functioning. These boys also were 3.9 times more likely to die and had significant advancement of cerebral disease after HCT, compared with boys with a timely diagnosis of X-ALD. In conclusion, the early diagnosis of cerebral X-ALD following the diagnosis of unexplained AI, and subsequent treatment with HCT improves both neurological outcomes and survival in boys with cerebral X-ALD. [ABSTRACT FROM AUTHOR]

Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion. [ABSTRACT FROM AUTHOR]

Unlabelled: Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2 mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5-9.1) months) were included in the study. The median follow-up-time was 14 (9-20) months and 14 patients completed treatment at a median age of 14.3 (11.4-22.1) months, after a duration of 10.5 (7.5-16) months. In all patients, there was significant fading of colour (with a VAS of -9 (-6 to -9) after 7 months) and significant decrease in size of the IH (with a VAS of -8 (-3 to -10) after 7 months). Median thickness of the lesions assessed by ultrasound at baseline and after 1 month was 14 (7-28) mm and 10 (5-23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8 weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted.Conclusion: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for IH. [ABSTRACT FROM AUTHOR]

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration. [ABSTRACT FROM AUTHOR]

Introduction: The clinical manifestations and risk factors for developing coronary artery abnormalities (CAA) in Kawasaki disease (KD) might differ depending on age.Materials and Methods: From January 2001 to July 2007, 161 patients with an age younger than 1 year (younger group) and 60 patients with an age older than 5 years (older group) were diagnosed with KD at the Korea University Medical Center. Their medical records were reviewed retrospectively and the two groups were compared in terms of a number of variables commonly associated with the development of CAA, including clinical manifestations and laboratory findings.Results: While the overall incidence of KD-associated CAA in our hospital was 6.7%, CAA developed in 20 (12.4%) of the younger group and ten (16.7%) of the older group, respectively. The CAA (+) cases of the younger group had a longer duration of total fever (9.1 +/- 3.3 vs 6.3 +/- 1.9 days, p = 0.002) and showed fewer diagnostic symptoms (3.0 +/- 1.2 vs 4.3 +/- 1.1, p < 0.001) than the CAA (-) cases. The CAA (+) cases of the older group had a longer duration of total fever (14.1 +/- 10.4 vs 6.5 +/- 1.9 days, p = 0.045), especially with respect to post-intravenous gamma globulin (IVGG) fever (7.9 +/- 9.6 vs 1.1 +/- 0.8 days, p = 0.052), and had higher total white blood cell counts, erythrocyte sedimentation rates, C-reactive protein levels, total bilirubin levels, and Harada scores and lower serum albumin and sodium levels than the CAA (-) cases. Multivariable logistic regression analysis revealed that the factors that were associated significantly with the development of CAA were the number of total symptoms (OR = 0.494, 95% confidence interval (CI) = 0.281-0.871, p = 0.015) in the younger group and the duration of post-IVGG fever (OR = 1.958, 95% CI = 1.098-3.492, p = 0.023) and the Harada score (OR = 3.455, 95% CI = 1.012-11.796, p = 0.048) in the older group.Conclusion: Incomplete clinical manifestations in the younger group and IVGG nonresponsiveness in the older group are associated with the development of KD-associated CAA. These age-specific characteristics could aid the customization of the diagnostic and therapeutic strategies of KD, thereby helping to improve the outcome of this disease. [ABSTRACT FROM AUTHOR]

Human Bocavirus (HBoV) as a newly discovered parvovirus has been commonly detected in respiratory tract infections. However, its role in acute otitis media (AOM) has not been well studied. We examined HBoV in Japanese children with AOM and evaluated the virus prevalence together with clinical manifestations and bacterial findings. Overall, 222 nasopharyngeal swabs and 176 middle ear fluids (MEF) samples were collected from 222 children with AOM (median age, 19 months) between May 2006 and April 2007. HBoV detection was performed by PCR and bacterial isolation by standard culture methods. HBoV was found in the nasopharyngeal aspirates of 14 children (6.3%) and in the MEF of six children (2.7%). When HBoV detection results were evaluated with clinical characteristics of children, resolution time of AOM was significantly longer (p=0.04), and rate of fever symptom was also higher in HBoV-positive group (p=0.04). Furthermore, we found positive correlation between detection of HBoV and Streptococcus pneumoniae in the MEF (p=0.004). Nevertheless, nasopharyngeal proportion of S. pneumoniae was similar between virus positive and negative groups. Furthermore, S. pneumoniae was detected as a single pathogen in all MEF of HBoV-positive cases but one, while it presents mixed with other pathogenic bacteria in nasopharynx. In conclusion, HBoV may worsen the clinical symptoms and prolong the clinical outcome of AOM in pediatric population. Finally, HBoV may prime the secondary bacterial infection in the middle ear in favor of S. pneumoniae. [ABSTRACT FROM AUTHOR]

The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. In most patients, neurological and dermatological abnormalities are associated features. We report on the first Bosnian patient with triple A syndrome. Endocrine investigation confirmed primary adrenal insufficiency at the age of 5.8 years. Two months later, achalasia was diagnosed, and in the presence of alacrima, the patient satisfies the diagnostic criteria of triple A syndrome. In addition, a large number of associated neurological and dermatological features were present in this patient. Moreover, he has dysmorphic facial features, which have not been previously described in triple A syndrome. Triple A syndrome was confirmed by molecular analysis, revealing a nonsense mutation p.W84X in the AAAS gene. The parents are both heterozygous carriers of the mutation. The affected twin brother unfortunately died from hypoglycaemic shock, despite a normal cortisol rise in an ACTH stimulation test. Further, triple A syndrome patients carrying the identical homozygous p.W84X mutation have to be studied to assess a genotype-phenotype relationship for this mutation. [ABSTRACT FROM AUTHOR]

According to current guidelines, inhaled corticosteroids (ICS) are the preferred primary long-term treatment for asthmatic children of all age groups, but leukotriene receptor antagonists can be considered to be an alternative treatment for mild persistent asthma. In this article, all randomized double-blind efficacy studies comparing the long-term (>4-week) treatment using a leukotriene receptor antagonist with an inhaled corticosteroid in asthmatic children were critically reviewed. In school-aged children, five reports with an adequate study design were available. All of these studies compared montelukast with inhaled fluticasone. The meta-analysis of the two main outcome measures, forced expiratory volume in 1 s (weighted mean difference, 4.6% predicted, 95% confidence interval: 3.5-5.5) and asthma control days (respectively, 5.6%, 4.3-6.9) demonstrated the superiority of fluticasone over montelukast. Many other clinical and pulmonary outcomes also consistently showed that low-dose inhaled fluticasone was more effective than montelukast in the long-term management of mild to moderate persistent asthma. A more favorable response to fluticasone over montelukast was associated with more severe disease or markers of allergic inflammation. About a quarter of patients benefited more from montelukast than fluticasone. In children under school age, no comparative studies were available. However, long-term montelukast treatment was found to be effective in placebo-controlled studies in asthmatic children aged >2 years. These findings support the present international recommendations for ICS as the preferred first-line controller therapy for mild to moderate persistent childhood asthma. If montelukast is selected as a monotherapy and asthma is not adequately controlled within 4-6 weeks, the treatment should be discontinued and the preferred medication initiated. [ABSTRACT FROM AUTHOR]

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 ± 1.0 years and height standard deviation score (SDS) was –2.6 ± 0.6 in males. In females age was 13.1 ± 0.9 years and height SDS –2.6 ± 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 ± 0.79, untreated 0.10 ± 0.82, testosterone-treated 0.05 ± 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 ± 0.93, untreated 1.55 ± 0.92, testosterone-treated 1.53 ± 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated –0.49 ± 1.13; untreated 0.10 ± 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 ± 0.92; untreated 1.77 ± 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) ( P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex. [ABSTRACT FROM AUTHOR]

A retrospective chart review was performed of all patients with juvenile idiopathic arthritis (JIA) followed at our clinic who had an intra-articular steroid injection between 1 January 1997 and 31 December 2001. The aim of the study was to evaluate the outcome of intra-articular steroid injections (iaS) and determine prognostic factors. During the study period, 202 iaS were performed in 60 patients, of whom 37 had oligoarticular JIA, 15 had polyarticular, rheumatoid factor-negative JIA and four each had systemic and enthesitis-related JIA. The median duration of remission was 23.1 months (range: 0-69 months). At last follow-up, 103 joints (51%) of 47 patients were still in remission after a median follow-up time of 28 months (range: 1-69 months). For the total cohort, the remission was longer for wrist and finger joints [risk ratio (RR): 0.2], with concomitant treatment with methotrexate (RR: 0.28) and for enthesitis-related arthritis (RR: 0.34). For the group of knee joints, remission was longer with concomitant treatment with methotrexate (RR: 0.37), with triamcinolone hexacetonide (RR: 0.77) and with general anaesthesia for the procedure (RR: 0.56). Mild side effects were observed in 45 iaS (22.3%), and skin atrophy occurred at the injection site in 2% of injections, but no major adverse event occurred in our cohort. In conclusion, iaS is a safe procedure with a median duration of remission of 23.1 months. The remission was longer in the joints of the upper extremity, with concomitant treatment with methotrexate and when the injection was performed under general anaesthesia. [ABSTRACT FROM AUTHOR]

Published clinical experience with hamamelis ointment in children is limited. This observational study included children (age 27 days to 11 years) with minor skin injuries, diaper dermatitis, or localized inflammation of skin. The children received either hamamelis ointment or dexpanthenol ointment in groups at a 3-to-1 ratio. Baseline and post-treatment assessments compared the total scores of predefined signs and symptoms for each condition. Physicians and parents were asked for a global assessment of efficacy and tolerability of the respective treatments at the end of therapy. A total of 309 children were treated (hamamelis n = 231; dexpanthenol n = 78). The treatment groups were comparable regarding demographic data and baseline total scores of signs and symptoms. In all three diagnosis groups, the efficacy of hamamelis and dexpanthenol was shown by a statistically significant and clinically relevant decrease of total scores from baseline to endpoint (p < 0.0001 for each group, Wilcoxon signed-rank test). Overall, the results for the hamamelis and the dexpanthenol groups were similar. Descriptive advantages for the hamamelis group were observed for a number of parameters and diagnosis groups. Both treatments were well tolerated. Ratings of the tolerability of hamamelis were "excellent" or "good" in 99.1% (physicians) and 98.2% (parents) of cases, respectively. The corresponding ratings for dexpanthenol were 97.4 and 92.3%. In conclusion, hamamelis ointment is an effective and safe treatment for certain skin disorders in children up to the age of 11 years. The observed effects are similar to dexpanthenol. [ABSTRACT FROM AUTHOR]

Unlabelled: Although offered, two of our Hurler patients (OMIM 607014) had not undergone bone marrow transplantation at an early stage of their disease. Rapid disease progression had resulted in a range of signs and symptoms representative of advanced neurodegeneration and debilitating somatic Hurler disease. As general palliative care had only little impact on the burden of disease, laronidase (Aldurazyme) treatment was introduced in an attempt to alleviate somatic symptoms and to improve the quality of their lives. Therapeutic benefits from enzyme replacement therapy included improvements in general physical condition and mood, as well as normalisation of the sleep patterns, disappearance of sleep apnoea syndrome and reduction of hepatosplenomegaly. Improvements in the joint mobility were mainly limited to the wrists and hips. In addition, improvements in cardiac function, stool habits, visual acuity, corneal clouding and hearing were observed in one or both patients. Irreversible skeletal changes did not deteriorate. The neurological outcome of these patients is likely not influenced as laronidase is believed not to pass the blood-brain barrier. Therefore, the decision to initiate this therapy in transplant-naïve Hurler patients with an advanced stage of the disease should be taken after careful consideration.Conclusion: We are of the opinion that the option of enzyme therapy should not be excluded in severely affected Hurler patients who cannot undergo bone marrow transplantation. Stabilization or amelioration of somatic disease and improvement of the quality of their lives should be embraced as therapeutic goals. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus infection is among the most common causes of chronic liver disease in children. The aim of this study was to document prospectively our experiences related to lamivudine and high-dose interferon-alpha2a combination in naïve, e antigen positive, chronic hepatitis B virus infection treatment in children. Thirty-three children diagnosed as naïve, immunoactive chronic hepatitis B were treated with lamivudine (3 mg/kg/day) and interferon-alpha2a (10 MU/m2, thrice weekly). Initially, lamivudine was initiated three months before interferon-alpha for induction, and after June 2002, both drugs were started simultaneously. After interferon-alpha was stopped, lamivudine alone was continued for six months. HBeAg seroconversion with the normalization of serum ALT was achieved at the end of treatment and at the end of follow-up for 20/33 patients. Initial mean alanine aminotransferase, 142.9 IU/L, decreased to a mean value of 31.4. End-treatment response and sustained response rates were 66.7% (14/21) and 50% (6/12), respectively, in patients that underwent lamivudine induction before interferon-alpha and in patients that began to receive the two drugs simultaneously (p=0.4). Flu-like syndrome and anorexia were the most common complaints. As our conclusions, we propose that interferon-alpha2a plus lamivudine combination therapy is highly successful and safe in children suffering from chronic hepatitis B. Lamivudine induction before interferon does not seem to be necessary. [ABSTRACT FROM AUTHOR]

Clinical, laboratory, and echocardiographic data were retrospectively analyzed in 112 patients with acute Kawasaki disease who received high-dose (2 g/kg) intravenous gamma-globulin (IVIG) treatment within 2 days and were compared for those who were responsive and non-responsive to initial IVIG treatment. Coronary arteries adjusted for body surface area (BSA) were evaluated quantitatively by comparison with the mean dimensions for 85 normal control subjects. The incidence of coronary abnormalities was higher in IVIG-non-responsive patients as compared to IVIG-responsive patients (71% versus 5%, p<0.0001). Univariate analysis of pre-IVIG data showed that the neutrophil count and serum levels of C-reactive protein (CRP), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH) were significantly higher in IVIG-non-responsive versus responsive patients. Multivariate analysis selected CRP (p=0.009), TB (p<0.001), and AST (p=0.002) as independent predictors of non-responsiveness to initial IVIG treatment. By defining predictive values, patients with at least two of three predictors (CRP>or=7.0 mg, TB>or=0.9 mg, or AST>or=200 IU/L) are considered to be non-responsive to IVIG for acute Kawasaki disease. Alternatively, more intense initial therapy may be a promising therapeutic strategy for patients who are predicted to be IVIG-non-responsive. [ABSTRACT FROM AUTHOR]

The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2–17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234±58 mg/m2, median 240 mg/m2 versus 203±86 mg/m2, median 210 mg/m2, P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m2 of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group. Conclusion:Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups. [ABSTRACT FROM AUTHOR]

Unlabelled: To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5-15 months (average duration of treatment 11.7 +/- 3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2 +/- 3.7 months, range 6-17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost -6.27 +/- 5.4 kg, whereas those in the control group gained 4.16 +/- 6.45 kg (P < 0.001) during the study period. Patients in the orlistat group lost -7.65% +/- 6.5% of their initial body weight, whereas, those of the control group gained 5.7% +/- 8.3% (P < 0.001). The body mass index decreased in the orlistat group by -4.09 +/- 2.9 kg/m2 while it increased by + 0.11 +/- 2.49 kg/m2 in the control group (P < 0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group.Conclusion: Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents. [ABSTRACT FROM AUTHOR]

Unlabelled: Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A. This leads to the progressive accumulation of glycosphingolipids in lysosomes of most visceral tissues and in body fluids. Following successful clinical trials in adults, two recombinant enzyme preparations of alpha-galactosidase have recently been licensed in Europe for the treatment of Fabry disease and treatment in children has commenced. We now report the clinical findings and the levels of globotriaosylceramide in plasma and urine in three boys who have been treated with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2 years. In one boy there was a rapid improvement in all the clinical and biochemical parameters measured. This has been maintained. In the other two boys, who are siblings, there was no measurable clinical improvement after 1 year and the levels of globotriaosylceramide in plasma and urine, although lower than before treatment, were still considerably elevated. There was no evidence of blocking or neutralising antibodies so the dose of enzyme was increased to 2 mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this was not accompanied by any reduction in the plasma or urine globotriaosylceramide levels.Conclusion: Measurement of globotriaosylceramide in plasma and urine may not be the most appropriate marker to monitor the progression of treatment by enzyme replacement therapy in all patients. Certainly the subjective clinical improvement in the two brothers in this report outweighed the objective biochemical findings. [ABSTRACT FROM AUTHOR]

Unlabelled: To test the hypothesis that the administration of L -5-hydroxytryptophan (L -5-HTP) might exert beneficial effects on sleep terrors, we carried out an open pharmacological trial in a group of children with sleep terrors compared to a group of children with the same disorder but without L -5-HTP treatment. Participants in the trial were 45 children (34 males and 11 females; age range 3.2-10.6 years), referred to the Sleep Centre of the Department of Developmental Neurology and Psychiatry of the University of Rome "La Sapienza", affected by sleep terrors. All subjects underwent: (1) complete medical and sleep history; (2) complete neurological examination and EEG recording whilst awake and sleeping, (3) a structured sleep diary for 2 months, (4) after 1 month, all subjects were examined again from the clinical and EEG points of view and (5) after 6 months, a structured interview in order to evaluate the clinical outcome. After the first visit, L -5-HTP was administered (2 mg/kg per day) at bedtime to 31 randomly selected patients for a single period of 20 consecutive days. After 1 month of treatment, 29/31 (93.5%) of patients showed a positive response. In the comparison group without drug therapy, after 1 month, the episodes disappeared only in four children (28.6%) while ten children (71.4%) showed the persistence of episodes with the same frequency as before. After 6 months, 26/31 (83.9%) of children treated with L -5HTP were sleep terror-free, while in five children (16.1%) sleep terror episodes persisted. Of the children in the comparison group, ten (71.4%) continued to show sleep terrors at 6-month follow-up.Conclusion: to our knowledge, this is the first study demonstrating the efficacy of a new drug treatment for sleep terrors. These results confirm our initial hypothesis and represent evidence that treatment with L -5-hydroxytryptophan is able to modulate the arousal level in children and to induce a long-term improvement of sleep terrors. [ABSTRACT FROM AUTHOR]

Unlabelled: To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean age at start 7.4 years) and group B (n=11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2-L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above -1 in both groups (group A: BUA Z-score -0.21, SOS Z-score -0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score -0.93, SOS Z-score -0.40, BMD Z-score -0.86, BMDvol Z-score -0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero (P=0.03 and P=0.02 respectively). Mean Z-score BMDvol was not significantly different from zero (P=0.05), we found no significant difference between the groups for BMDvol (P=0.13).Conclusion: Although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health. [ABSTRACT FROM AUTHOR]

Unlabelled: This study evaluated whether the early use of high frequency ventilation (HFV) decreased the incidence of oxygen dependency at 36 weeks postconceptual age [chronic lung disease (CLD)] and improved developmental outcome. Neonates of less than 32 weeks gestational age needing ventilatory support for RDS who were admitted to a tertiary academic neonatal intensive care unit (NICU) within 6 h of birth were included in a prospective controlled clinical trial. With randomisation they were given either HFV (n=147) or conventional ventilation (CV) (n=153). As a primary outcome variable, ventilator and/or oxygen dependence at a postconceptual age of 36 weeks (CLD) was measured. Secondary outcome variables were: mortality at discharge, treatment failure, ventilator and/or oxygen dependence at 28-30 days (bronchopulmonary disease [BPD]), duration of ventilation, use of surfactant, days in oxygen and on continuous positive airway pressure (CPAP), survival without BPD or CLD, air leak, intracranial haemorrhages (ICH) grades 3 and 4, periventricular leukomalacia (PVL) grades 1 and 2, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), necrotising enterocolitis (NEC), developmental outcome at 7 to 12 months and if necessary at 18-24 months corrected age. The results showed that CLD (16.3 vs. 12.4%), BPD (33.3 vs. 36.6%), early cerebral abnormalities, mortality at discharge (17.2 vs. 13.2%), failure rate (11.6 vs. 6.5%) and motor and mental developmental outcome at a corrected age of 18 to 24 months (p>0.05) did not differ between the two groups.Conclusion: Under the present study design HFV compared with CV did not decrease chronic lung disease and no developmental outcome differences could be found at a corrected age of almost 2 years. [ABSTRACT FROM AUTHOR]

Unlabelled: Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (< 1 ml/kg per h) during treatment (P = 0.017).Conclusion: Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment. [ABSTRACT FROM AUTHOR]

Unlabelled: This study is based on clinical data from a retrospective series of 54 infants with meconium aspiration syndrome treated with porcine surfactant at a median age of 14 h (range 1-176 h). Median arterial/ alveolar oxygen tension ratio (a/A PO2 ratio) before treatment was 0.08 (range 0.02-0.23) and oxygenation index 25 (range 6-110). After treatment with surfactant at an initial dose of 50-200 mg/kg there was a modest but statistically significant increase in a/APO2 ratio associated with a reduction of oxygenation index. Ten (18%) babies showed a 3-4 fold increase in a/APO2 ratio within 1-2 h of treatment. Twenty-four (44%) babies showed little or no response by 1-2 h with the remaining infants showing modest improvement in oxygenation. One third of babies required repeated doses of surfactant. Twenty-eight day survival was 81%, with two babies requiring extracorporeal membrane oxygenation.Conclusion: Natural surfactant treatment of severe meconium aspiration may prove to be a useful intervention and randomised controlled clinical trials should be undertaken. [ABSTRACT FROM AUTHOR]

In order to test the ability of Ambroxol to improve the clinical course of respiratory distress syndrome and to reduce the incidence of complications a multicentre, randomized, placebo-controlled double-blind trial was conducted. Entry was limited to infants with a birth weight below 1500 g. A total of 179 neonates were enrolled, but 31 were later excluded because they had other diseases. Of the remaining 148 babies, 74 received Ambroxol (birth weight 1190 +/- 216 g; gestational age 29.1 +/- 1.9 weeks) and 74 placebo (birth weight 1168 +/- 216 g; gestational age 28.9 +/- 1.9 weeks). In the Ambroxol group 23 (31%) and in the placebo group 27 (37%) infants died during the first 5 months of life. In 28 day-survivors Ambroxol was able to significantly improve the PaO2/FiO2 ratio, mean airway pressure, phospholipid profile of tracheal effluent and pulmonary mechanics of spontaneously breathing infants. In addition, the incidences of bronchopulmonary dysplasia (29% vs 54%), intraventricular haemorrhage (25% vs 44%) and postnatally acquired pneumonia (15% vs 36%) were significantly reduced in the Ambroxol group as compared to the control group. No adverse events attributed to the Ambroxol treatment were reported. [ABSTRACT FROM AUTHOR]