bluuebunny/crossref_metadata_2025_split huggingface dataset:
Off‐label use of drugs in Italy: a prospective, observational and multicentre study
Authors: Pandolfini C , Impicciatore P , Provasi D , Rocchi F , Campi R , Bonati M ,   Italian Paediatric Off‐label Collaborative Group
Published: August 2010

The aims of the study were to measure the paediatric, off‐label use of drugs in the Italian hospital setting and to reveal areas for priority intervention by investigating the therapeutic indications most involved. Prescriptions given to all children admitted to nine general paediatric hospital wards from December 1998 to February 1999 were analysed. In total, 4265 prescriptions were given to 1461 children, 10 of which were unlicensed and excluded from further analysis. Sixty percent of prescriptions (range between centres: 44‐71%) were off‐label and concerned 89% of children receiving medications (80–96%). The main drug classes were antibacterials, antiasthmatics and analgesics, and represented 56% of off‐label prescriptions. Paracetamol (385 prescriptions) and beclomethasone (339) were the generic substances most often used off‐label. The most common off‐label categories were dosage/frequency (50% of prescriptions), indication and lack of paediatric licence (7% each). Fifty‐four per cent of all indications that led to off‐label prescribing involved only respiratory problems, fever, respiratory tract infections and bronchospasm. Conclusions: Despite prescription profile differences among centres, off‐label use was high everywhere. Immediate action for more rational drug use is necessary and requires not only regulatory intervention but also a more evidence‐based, therapeutic approach.
Non‐classical 21‐hydroxylase deficiency in children: association of adrenocorticotropic hormone‐stimulated 17‐hydroxyprogesterone with the risk of compound heterozygosity with severe mutations
Authors: Ezquieta B , Cueva E , Varela J , Oliver A , Fernández J , Jariego C 
Published: August 2010

Aim: To investigate the association between levels of 17‐hydroxyprogesterone (17‐OHP) and the risk of being compound heterozygous for severe mutations in children with non‐classical 21‐hydroxylase deficiency (NC21OHD). Methods: In 86 Spanish NC21OHD children (75 families) an analysis of the 21‐hydroxylase (21‐OH) gene was performed by CYP21B‐specific polymerase chain reaction amplification, allele‐specific oligonucleotide hybridization and Southern blotting. Familial analysis established how the alleles segregated, and allowed the selection of 21‐OH‐genotyped normal and carrier children, which proved useful in determining a more precise definition of the cut‐off for diagnosis. Receiver operating characteristics (ROC) curve analyses were performed to determine the potential value of 17‐OHP in predicting compound heterozygosity for severe mutations. Results: Thirty‐four of the 86 children (39%) were found to carry one severe 21‐OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% I172N, 1.3% R356W, and 3.3% double microconversions or small conversions involving single exons). The predominant mutation was V281L (56.7%). P453S and P30L were less frequent (3.3 and 2%). No patient showed two severe mutations. The degree of enzymic deficiency, as measured by basal or adrenocorticotropic hormone (ACTH)‐stimulated 17‐OHP levels in fully genotyped patients, but not clinical severity (age and number of symptoms at diagnosis), was found to be significantly greater in children with the severe/mild genotype. ROC curve analyses revealed a strong association between ACTH‐17‐OHP and genotype (area under the curve 0.908, SE 0.057). Conclusion: ACTH‐stimulated 17‐OHP may predict the risk of severe mutations in compound heterozygosity in children (maximum predictive value 93% sensitivity and 83% specificity for a cut‐off at 151 nmol 1‐1), although a certain overlap in individual values is observed and performance of molecular analysis should never be obviated in the genetic counselling of these patients.
Acute abdominal attack of hereditary angioneurotic oedema associated with ultrasound abnormalities suggestive of acute hepatitis
Authors: Farkas H , Harmat G , Fekete B , Karadi I , Visy B , Varga L 
Published: August 2010

Hereditary angioneurotic oedema (HANO) is an autosomal dominant disorder caused by a deficiency of the inhibitor protein C1‐esterase. Recurrent subcutaneous and/or submucosal oedema formation is a hallmark of this disease. HANO is a rare, but potentially life‐threatening disorder with a mortality around 20–30%. Acute oedematous abdominal attacks of HANO can mimic a surgical emergency; this is exemplified by the case of a 14‐y‐old male patient with HANO admitted for such clinical manifestations. Conclusion: Diagnostic clues include ascites and abnormalities of hepatic structure visible with ultrasound during the oedematous attack. The importance of appropriate treatment is emphasized.
Sexual behaviour and early coitarche in a national sample of 17‐year‐old Swedish boys
Authors: Edgardh K 
Published: August 2010

Aim: To describe sexual behaviour as reported by 17‐year‐old boys in Sweden. Methods: The national cross‐sectional SAM 73–90 questionnaire survey was performed in 1990, and comprised 2% of students and school non‐attenders born in 1973. The respondents included 814 students and 92 non‐students, response rates 90.6% and 40.2%, respectively. Data from the two groups are treated separately. Results: In the student group, 54.2% of boys had experienced vaginal intercourse and 16.7% were “early starters” with coitarche before 15 y of age. Independent predictors for coital experience were the vocational study programme OR (odds ratio) 1.91 (95% CI 1.31–2.78), early puberty OR 1.69 (95% CI 1.11–2.57), use of tobacco OR 5.32 (95% CI 2.43–11.7) and alcohol OR 4.09 (2.79–5.98). Sexually transmitted infections (STIs) were reported by 4.1% of coitally active student boys, and impregnating a girlfriend by 4.3%. Of the early starters, 14.6% reported having more than 10 sex partners as compared with 2.5% of the later starters (p > 0.0001) and this was predictive of STI, OR 5.4 (95% CI 1.5–19.7). First‐date intercourse more than twice was predictive of pregnancy, OR 14.4 (95% CI 3.8–54.5). Among school non‐attenders, 74.2% reported coital experience, 33.7% were early starters, and 12.5% had impregnated a girl. Conclusion: Boys' early sexual experience was related to early puberty, and to general adolescent risk‐taking behaviour. Early coitarche per se was not predictive of STI or pregnancy, but the associated high number of “lifetime” sexual partners and first‐date intercourse were predictive factors. School non‐attenders constituted a group at risk.
Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage
Authors: Aronis S , Bouza H , Pergantou H , Kapsimalis Z , Platokouki H , Xanthou M 
Published: August 2010

Aim: To investigate whether the factor V Leiden mutation (FVL), the prothrombin gene G20210A variant or the methylenetetrahydrofolate reductase (MTHFR) C677T genotype are risk factors for central nervous system (CNS) thrombosis or intraventricular hemorrhage (IVH) in neonates. Methods: Thirteen full‐term infants with cerebral infarct documented with magnetic resonance imaging were assessed with the whole spectrum of assays for thrombophilia including the three DNA‐based prothrombotic factors. The frequency of congenital defects was compared with that observed in 38 healthy full‐term infants. The genetic defects were also assessed in 55 premature neonates, gestational age <32wk, 17 of whom developed IVH, grade II‐IV. The remaining 38 premature neonates without IVH were used as controls. Results: In the CNS thrombosis group: a prothrombotic factor was detected in 53% of patients and an underlying disease or a triggering event in 61.5%. The frequency of FVL in thrombosed neonates was higher (23%) than in the group of healthy full‐term infants (10.5%), although it did not reach statistical significance. IVH developed in 30.9% of premature neonates. Apart from several maternal or neonatal risk factors for IVH, FII G20210A was found in a considerably higher prevalence in the cohort of neonates with IVH (12%) than in those without (2%), although the difference was not statistically significant. Conclusion: The pathogenesis of cerebral thrombosis or IVH in neonates is multifactorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FVL or FII G20210A) showed a trend towards a higher frequency in full‐term infants with CNS thrombosis or premature neonates with IVH than in controls. However, their contribution to neonatal cerebral thrombosis or IVH remains to be determined.
Deficient interferon‐γ receptor‐mediated signaling in neonatal macrophages
Authors: Maródi L 
Published: August 2010

Aim: To describe functional and molecular characteristics of interferon‐γ (IFN‐γ) activation in neonatal mononuclear phagocytes (monocytes and macrophages). Methods and Results: Exposure of cord and adult macrophages to IFN‐γ gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2−). At concentrations of 100 U ml−1 IFN‐γ, maximal increase in these functions with adult macrophages was achieved, whereas no enhancement of killing and O2− release by cord macrophages could be detected. Expression of IFN‐γ receptors was comparable on cord and adult cells and specific binding of [125I]IFN‐γ to cord monocytes and macrophages was even higher compared with adult cells. By flow cytometry, elements of IFN‐γ receptor‐mediated signaling in cord and adult monocytes and macrophages were studied. Monoclonal antibodies against the native form of the signal transducer and activator of transcription‐1 (STAT‐1) revealed comparable expression of this protein in cord and adult macrophages. However, STAT‐1 phosphorylation in response to IFN‐γ was significantly decreased in neonatal monocytes (p < 0.05) and macrophages (p < 0.01) compared with adult cells. Conclusion: These data suggest deficient cytokine receptor signaling in neonatal mononuclear phagocytes exposed to IFN‐γ.
X‐chromosome inactivation and human genetic disease
Authors: Lyon MF 
Published: August 2010

The inactivation of one X‐chromosome in females in early development is the process by which the effective dosage of X‐linked genes is equalized between XX females and XY males. The mechanism that brings this about is the subject of intense research. The X‐linked gene Xist is a key player, which is necessary but not sufficient for the initiation of X‐inactivation. It codes for an untranslated RNA that coats the inactive X‐chromosome, which takes on properties characteristic of heterochromatin, but how this change in chromatin is brought about remains unknown. Because of X‐inactivation, females heterozygous for X‐linked genes are mixtures of two types of cells and show a variable phenotype. The proportion s of the two types of cells can depart from equality due to cell selection either at the tissue or whole organism level. In rare cases, changes in the Xist gene can cause skewing of X‐inactivation. A few genes escape from X‐inactivation either wholly or partially. Conclusion: X‐chromosome inactivation is a physiological mechanism that equalizes gene‐dosage effects on the sex chromosomes. The occurrence of this normal process affects the phenotype seen in females carrying X‐linked mutant genes or chromosome anomalies.
Preschool children with developmental coordination disorder: a short‐term follow‐up of motor status at seven to eight years of age
Authors: Pless M , Carlsson M , Sundelin C , Persson K 
Published: August 2010

At a population‐based screening of 5–6‐y‐old children, 37 children were identified as having definite or borderline motor difficulties consistent with developmental coordination disorder. When 7–8 y old they were re‐examined to determine their current motor status and to compare it with that at the age of 5–6 y. The motor status was investigated from three perspectives: by a motor test, by the use of a self‐perceived motor competence scale, and from the parents' descriptions. On a group level the children had not changed their motor status when 7–8 y old, according to the total scores in the Movement ABC motor test and the Perceived Motor Competence scale. On an individual level most children with definite motor difficulties remained in their category regarding motor difficulties at the follow‐up, while most children with borderline motor difficulties did not. The parents' descriptions indicated an association between willingness to engage in physical activities and degree of motor difficulties. Conclusion: Over a period of 1.5 y most children with definite motor difficulties continued to have such difficulties. The parents' descriptions of their children's motor status and development were in agreement with the children's motor status as measured by a motor test, but were not in total accordance with the children's self‐perceived competence.
Vaccination coverage estimates by EPI cluster sampling survey of children (18–24 months) in Flanders, Belgium
Authors: Vellinga A , Depoorter AM , Van Damme P 
Published: August 2010

A random cluster sample according to the EPI cluster sampling technique was conducted in 1999 in Flanders (North Belgium) to ascertain the vaccination coverage of 18 to 24‐mo‐old children. Polio is the only mandatory vaccine. Diphtheria‐tetanus‐pertussis (DTP), Haemophilus influenzae type b (Hib), hepatitis B (HB) and measles‐mumps‐rubella (MMR) are included in the recommended schedule of vaccinations. For Hib and HB, a minimal cost was charged. Professional interviewers conducted interviews with the parents of 1110 children randomly selected in 89 municipalities. Analysis was conducted on the results of 1005 children. The coverage level (95% confidence interval) for the full schedule was 96% (95–97) for polio, 89% (87–91) for DTP, 78% (74–82) for Hib, 68% (64–72) for HB and 83% (81–87) for MMR. The vaccinations were administered by the regional children's health organization (70%), paediatricians (17%) and GPs (11%). No sociodemographic factors could be associated with vaccination coverage. One province showed significantly (p >0.01) lower vaccination coverage levels compared with those of the other four provinces for DTP (91% vs 82%), Hib (78% vs 53%), HB (73% vs 46%) and MMR (87% vs 66%). Conclusion: There is a need for more and better information about vaccination for parents as well as for the healthcare providers.
Lung function and asthma symptoms in children: relationships and response to treatment
Authors: Mitra AD , Ogston S , Crighton A , Mukhopadhyay S 
Published: August 2010

The aim of this study was to determine the relationships between the forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and asthma symptom scores, as well as their response to treatment, in children with no recent exacerbations of asthma. Asthma symptom scores, FEV1 and PEF were characterised, and their relationships and changes at follow‐up studied in 64 children (mean age 9.5 y) referred to asthma outpatients. The mean FEV1 and PEF at the initial clinic visit were 94% of predicted values. At follow‐up, mean FEV1 and PEF were similar. However, symptom scores (maximum obtainable score for each variable = 3) for exercise, nocturnal cough and morning cough were abnormal at the initial visit (mean ± SD, exercise 1.0 ± 0.7, nocturnal cough 1.7 ± 1.2, morning cough 1.6 ± 1.2) and improved significantly at follow‐up (exercise 0.8 ± 0.7, nocturnal cough 0.9 ± 1.1, morning cough 1.0 ± 1.2) (p > 0.05). A significant relationship was not observed between lung function and total symptom score, at either the initial or follow‐up clinic visit. Neither FEV1 nor PEF significantly correlated with individual symptom scores. While symptom control improved, no significant relationships between change in asthma symptom scores and change in FEV1 and PEF between the initial and follow‐up visits were observed. Conclusion: Clinic (“office”) spirometry, currently performed world‐wide, cannot be uniformly regarded as an indicator of asthma status. In addition to the measurement of lung function, quantitative symptom scoring may be a helpful tool for physicians in the assessment of childhood asthma status.
Pain management in French neonatal intensive care units
Authors: Debillon T , Bureau V , Savagner C , Zupan‐Simunek V , Carbajal R ,   on behalf of the French National Federation of Neonatologists
Published: August 2010

The aim of this study was to investigate pain management in neonatal intensive care units (NICUs) in France and to identify factors associated with variability across units. A questionnaire sent to 143 heads of level II or III NICUs investigated the use of pain scores, pain management organization and pharmacological treatment in five clinical situations (endotracheal intubation, prolonged mechanical ventilation, acute stage of necrotizing enterocolitis, central venous catheter insertion and cephalhaematoma). The response rate was 81%. Among the 35 (30%) units that used no pain scores, 40% ascribed this to lack of knowledge. Factors associated with failure to use pain scores were level II status, no university affiliation, no surgical patients and neonatal patients only. Among the units that scored pain, 78% used valid scores for acute pain and 73% for prolonged pain. Written guidelines were available for acute pain in 65% of units and for prolonged pain in 36%. The rate of pharmacotherapy use varied widely across the five clinical situations studied (from 16 to 77%) and across units for a given clinical situation. Also extremely variable were the regimens used in each situation and the dosages of analgesics and sedatives. Only 11% of units adjusted dosages to gestational age. Conclusion: Pain assessment was performed in the most French NICUs, but a strong heterogeneity for pain treatment was observed. Reference to recently published pain management guidelines and new randomized trials could be useful to optimize pain treatment in NICUs.
Understanding and circumventing the blood‐brain barrier
Authors: Begley DJ 
Published: August 2010

The blood‐brain barrier presents a challenging obstacle to effective drug delivery to the central nervous system (CNS). Although biologically intended to protect the brain and spinal cord and provide a very stable fluid environment, the presence of a blood‐brain barrier makes treatment of many CNS diseases difficult to achieve, as the required therapies cannot be delivered across the barrier in sufficient quantities or at all. Until relatively recently the blood‐brain barrier was viewed largely as a physical barrier to diffusion, and the presence of tight junctions between endothelial cells simply prevented the passive diffusion of solutes from blood into the brain. Recent advances in cell and molecular biology have provided new insights into the function of the blood‐brain barrier and it is now appreciated that, in addition to being a physical barrier, it is a complex transport and metabolic barrier and is a highly reactive and dynamic endothelium. Advances in understanding of the cell biology of the blood‐brain barrier have opened new avenues and possibilities for improved drug delivery to the CNS. The challenges posed by the blood‐brain barrier and the possibilities for overcoming them are reviewed. Conclusion: Increased understanding of the molecular biology of the blood‐brain barrier is now opening the way for new strategies to deliver drugs to the CNS.
Stress and lack of social support as risk factors for small‐for‐gestational‐age birth
Authors: Pryor JE , Thompson JMD , Robinson E , Clark PM , Becroft DMO , Pattison NS , Galvish N , Wild CJ , Mitchell EA 
Published: August 2010

Aim: To determine the contributions of social support and perceived stress to the risk of small‐for‐gestational‐age birth. Methods: The investigation was a case‐control study of mothers of infants born at 37 or more completed weeks of gestation. Cases weighed less than the sex‐specific 10th percentile for gestational age at birth (small for gestational age (SGA), n= 836), and controls (appropriate for gestational age (AGA), n= 870) comprised a random selection of heavier babies. Results: In univariate analyses measures of informal social support, but not perceived stress or formal social support, were associated with SGA birth. It was found that Asian mothers are less likely to receive support from families and friends. After adjustment for ethnicity, informal social support was not associated with SGA. Conclusions: Support appears to reduce the risk of SGA births, but after adjustment for ethnicity this is no longer the case. Stress during pregnancy was not associated with SGA birth.
Children with nutritional rickets referred to hospitals in Copenhagen during a 10‐year period
Authors: Pedersen P , Michaelsen KF , Mølgaard C 
Published: August 2010

Aim: To describe the prevalence of nutritional rickets among children admitted to three large paediatric departments in the Copenhagen area during a 10 y period. Methods: Retrospective analysis of cases identified from the diagnosis registers fulfilling the diagnostic criteria for nutritional rickets. Results: Forty cases were identified, distributed in two distinct age groups: 0.5–4 y (n= 31) and 9–15 y (n= 9). All cases were immigrants, of whom 95% were born in Denmark. The main symptoms in the younger age group were bowed legs and clumsy walk, and in the peri‐pubertal group were painful joints. Two children had generalized convulsions. None of the cases had received vitamin D supplementation. Conclusion: Nutritional rickets is still present among immigrants in Denmark, and it is likely that the prevalence of mild cases is high. Prevention through vitamin D supplementation is important, but requires a dedicated health education effort.
Frequency of and risk factors for necrotizing enterocolitis in infants born before 33 weeks of gestation
Authors: Hällström M , Koivisto A‐M , Janas M , Tammela O 
Published: August 2010

Aim: To investigate the frequency of and risk factors for necrotizing enterocolitis (NEC) among infants of <33 wk of gestation. Methods: Prospective follow‐up of 140 inpatients. Results: 26 (18.6%) subjects developed NEC stage I‐III and 12 (8.6%) severe NEC (stage II‐III). Breast milk fortifier and duration of morphine infusion emerged as the statistically significant factors associated with NEC stage I‐III, but only the latter had a significant association with severe NEC. Conclusion: Future studies are needed to be established whether morphine is a causative factor in NEC.
Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer
Authors: Lando A , Holm K , Nysom K , Rasmussen Å Krogh , Madsen M Høier , Feldt‐Rasmussen U , Müller J 
Published: August 2010

Aim: To evaluate serum thyroglobulin (Tg) level as a marker of the development of thyroid disease when following individuals who Received neck irradiation therapy in childhood. Methods: In a non‐randomized cross‐sectional study Tg was assessed in 172 survivors of childhood cancer 10.8 y (1.9‐24) median (range) after diagnosis and 7.9 y. (0.9‐24.3) median (range) after the end of treatment. The patients were divided into two groups: group 1 included 47 patients who had Received irradiation to the neck and group 2 included 125 patients who did not receive irradiation to the neck. Results: Patients who had Received irradiation to the neck had significantly higher Tg levels compared with those who did not receive neck irradiation: median 14.0 (1.0–189.0) μg/L vs median 8.8, (0.7–112.2) μg/L (p < 0.001). Six out of seven patients with elevated Tg levels (>70 μg/L) had Received neck irradiation. Among these six patients, two patients developed secondary differentiated thyroid cancer and two patients developed benign thyroid neoplasms. None of the patients who had normal levels of Tg developed thyroid cancer. Conclusion: A high Tg level should be a cause for further investigation in the follow‐up of individuals who have Received irradiation therapy in childhood.