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Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes.

AIMS: Our aim was to investigate associations between the single nucleotide polymorphisms (SNPs) in the SLCO1B1 (encoding OATP1B1) and ABCB1 (encoding P-glycoprotein) genes with the pharmacokinetics and efficacy of pravastatin in children with heterozygous familial hypercholesterolaemia (HeFH) and in paediatric cardiac transplant recipients. METHODS: Twenty children with HeFH (aged 4.9-15.6 years) and 12 cardiac transplant recipients (aged 4.4-18.7 years and receiving triple immunosuppressive medication) who had participated in previous pharmacokinetic and pharmacodynamic studies with pravastatin were genotyped for the -11187G > A and 521T > C SNPs in the SLCO1B1 gene and for the 2677G > T/A and 3435C > T SNPs in the ABCB1 gene. RESULTS: Two HeFH patients with the -11187GA genotype had a 81% lower peak plasma pravastatin concentration (Cmax) (difference in means -13.9 ng ml(-1), 95% CI -21.1, -6.7; P < 0.001) and a 74% smaller area under the plasma concentration-time curve (AUC0, infinity) (-25.3 ng ml(-1) h, 95% CI -35.6, -15.0; P < 0.0001) and significantly greater increase in high density lipoprotein (HDL) cholesterol after 2 months treatment with pravastatin than patients with the reference genotype. No significant differences were seen in the pharmacokinetics or effects of pravastatin between HeFH patients with the SLCO1B1 521TC and 521TT genotypes. The cardiac transplant recipients with the SLCO1B1 521TC genotype (n = 3) had a 46% lower Cmax (-67.7 ng ml(-1), 95% CI -135.7, 0.3; P = 0.055) and 62% lower AUC(0,24 h) (-228.5 ng ml(-1) h, 95% CI -402.7, -54.3; P = 0.016) and a shorter half-life (t1/2) (0.9 +/- 0.1 vs. 1.3 +/- 0.4 h, P = 0.015) of pravastatin than those with the reference genotype. Decreases in total and low-density lipoprotein cholesterol by pravastatin were significantly smaller, and the increase in HDL-cholesterol was greater in the transplant recipients with the 521TC genotype compared with patients with the 521TT reference genotype. CONCLUSIONS: In children with HeFH and in paediatric cardiac transplant recipients receiving immunosuppressive medication, the -11187G > A and SLCO1B1 521T > C SNPs were associated with decreased plasma concentrations of pravastatin. These differences are opposite to those seen previously in healthy adults. The mechanisms underlying these phenomena are unclear and warrant further study.

ATP Binding Cassette Transporter, Subfamily B↗

Asthma in emergency departments: combined adult and paediatric versus paediatric only centres.

OBJECTIVE: To compare the management of paediatric patients with mild or moderate asthma in paediatric-only emergency departments (POEDs) to treatment in a mixed adult-child emergency departments (mixed EDs). METHODS: Prospective, observational study conducted in 36 Australian emergency departments (EDs) for 2 weeks in 2001. Children aged 1-15 years with acute asthma classified as mild or moderate severity. Details of demography, severity assessment, and type of treatment facility, treatment and disposition were collected. Analysis used descriptive statistics, comparison of proportions by chi2, and multiple logistic regression. RESULTS: Two-hundred and nine children were treated at POEDs and 257 at mixed EDs. The groups had similar severity. Spacers to deliver beta-agonists were used more frequently in POEDs (67.5% vs 24.2%; P < 0.01). Children treated at POEDs with a mild attack were more likely to be admitted (20.6% vs 9.5%; P < 0.02) and given salbutamol (82.8% vs 71.9%; P = 0.03). For children with moderate asthma, oral steroid prescription on hospital discharge was more common for those treated in a mixed ED (81.0% vs 95.7%; P = 0.01). Ipratropium bromide (IB) was widely used at both types of ED but more commonly used in mixed EDs (41.7% vs 54.9%; P < 0.01). There were no differences in length-of-stay, representation rate within one month and oral steroid use for attack. Less than 2/3 of children with mild asthma attacks received steroid treatment in the ED. CONCLUSION: Treatment was similar between the two types of ED. IB was overused in mild asthma and oral steroids were underused in moderate asthma, by both ED types. Spacers were under-utilized in mixed EDs.

Adolescent↗

A countrywide programme of continuing professional development in Argentina. Argentine Society of Paediatrics, Subcommittee of Continuing Paediatric Education.

The Argentinean Society of Paediatrics introduced in 1993 a continuing professional development (CPD) programme to raise standards of clinical practice. The aims of the project were to introduce a structured, distance learning programme accessible to all paediatricians in the country, but especially for those working far from centres of paediatric excellence. The programme is planned on an annual basis. It includes four activities: a written manual designed by a team of medical experts and educationalists comprising 12 topics; field work for participants; annual meetings in several locations in the country for discussion of the subjects; and an evaluation based on centrally designed multiple choice questions distributed by mail. In spite of a registration free of 90 Pounds a year, participation in the programme increased from 3357 in 1993 to 4126 in 1996, from a membership of 10 216 paediatricians in Argentina. The popularity of the programme may result from an appropriate interpretation of professional needs of paediatricians in Argentina, adequate organisational arrangements that reach all colleagues, including those working in remote areas, and a genuine motivation of paediatricians for participating in a learning process.

Argentina↗

Evaluating student paediatric advanced nurse practitioners' experiences of a paediatric pharmacology module: in the context of reflective learning.

An evaluation of the first paediatric pharmacology module at Master's level was undertaken. The broad aims were: to ascertain whether the participants had achieved the modular learning outcomes; how their pharmacological knowledge base had altered as a result of the module; and whether their professional practice had been influenced subsequent to undertaking the module. The findings of the 12 participants who registered on the module are reported. Three tools were utilized to generate the data for this broadly qualitative study. The findings indicated that reflective thinking at the evaluative level enabled the participants to monitor their professional and personal performance and that their critical thinking skills and confidence had increased. The questionnaire survey had some limitations, but was seen as the only feasible method of achieving a representation as to whether the module had subsequently influenced the professional practice of the participants. The data presented convincing evidence of the relevance of study of a paediatric pharmacology module at Master's level for the professional and personal development of practitioners.

Child↗

Quality of paediatric IDDM care in Germany: a multicentre analysis. German Paediatric Diabetology Group.

Quality management has been applied in recent years to improve the care of children and adolescents with insulin dependent diabetes mellitus (IDDM). In 1995 the German Paediatric Diabetology Working Group published standards on quality control, in which relevant parameters on structure, process and outcome of care were defined. A computer software programme-developed at the University of Ulm under the auspices of the German Secretary of Health-has been used for quality control with central anonymous analysis in a nationwide survey. Data from 23 paediatric centres with 2407 patients seen between January and June 1996 were evaluated. The results showed an admission rate to hospital of 23.8 per 100 patient-years with an average duration of in-patient stay of 2.74 days/year. 80% of the patients were treated with an intensive insulin therapy regimen comprising three or more injections daily. The overall metabolic control was reasonably good with a mean HbA1c value of 7.8%. The rate of severe hypoglycaemia complicated by coma and/or convulsions was six per 100 patient-years and of ketoacidosis one per 100 patient-years. Unfortunately screening for diabetic retinopathy and nephropathy was not carried out consistently. The incidence was 44% and 33% respectively.

Adolescent↗

Paediatric life support instructors courses in Spain. Spanish Paediatric and Neonatal Resuscitation Group.

Between October 1996 and February 1998 we have provided five PLS instructors courses for 127 physicians. The instructor course takes 20-24 h over in 3 days, with 20-36 students per course. Theory classes last 5 h and practical stations between 14 and 18 h. Theory classes include: types and organisation of paediatric courses, resuscitation material, methodology of education, didactic methods, and methods of evaluation. The practical classes include techniques of oral expression, resuscitation material, and methodology, and evaluation of basic life support, airway and ventilation, venous and intraosseous access, diagnosis and treatment of arrythmias, neonatal resuscitation and advanced resuscitation. At the end of the course the students perform an anonymous written evaluation of the course with scores between 1 (very bad), 2, 3, 4 and 5 (very good). Theoretical aspects practical classes, methodology, and organisation of the PLS instructors courses are considered satisfactory by the students. We conclude that PLS instructors courses are important for assuring the uniformity and quality of paediatric life support courses.

Cardiopulmonary Resuscitation↗

Paediatric day care anaesthesia--our first two years experience at the Paediatric Institute, Hospital Kuala Lumpur.

The first two years anaesthetic experience of paediatric day care surgery is reviewed. Four hundred and three patients underwent 447 general surgical procedures. The mean age of the patients was 5.4 years with the youngest being 5 months old. The commonest procedures performed were herniotomy, circumcision, correction of hydrocoele and orchidopexy. The overall postoperative admission rare was 2.5%. No major complications were seen. Anaesthesia for paediatric day care surgery is safe provided patients are carefully selected and evaluated, appropriate anaesthetic management instituted and proper discharge criteria adhered to.

Adolescent↗

Burden and cost of inpatient care for HIV-positive paediatric patients--status in the Cape Town metropole during the second week of March 1999. Paediatric HIV Census Group.

OBJECTIVE: To determine the burden of the HIV epidemic on paediatric inpatient facilities in the teaching hospitals of the Cape metropole and tributaries to these hospitals. SETTING: Second- and third-level hospitals. METHOD: During the second week of March 1999 a multicentre collaborative census was performed of all paediatric beds in the teaching hospitals of Cape Town and all facilities draining to and from them. RESULTS: One hundred and six HIV-infected patients were identified from a total of 1,264 beds. Thirty-nine children were in second-level beds or in a long-term residential facility. Fifty-six children were in second-level beds designated for acute care, and occupied 12% of all such beds. Ten children were in beds designated for the care of tuberculosis. Thirty-two (56%) of the acute admissions were for gastro-enteritis, and 13 (23%) were for pneumonia. In 10 children (18% of all admissions) recognised complications of HIV infection were direct causes of admission. For 29 children (35% of all admissions) the current admission was the first; the remainder had had a mean of 2.4 previous admissions. Fourteen children (25%) had received oxygen, and 26 (46%) had received intravenous therapy. Mean lifetime hospitalisation cost per infected child was calculated to be R19,712. The projected cost of a local initiative to reduce mother-to-child transmission is between R8,326 and R10,806 per vertical infection prevented. CONCLUSION: The inpatient burden of HIV-infected children in Cape Town reflects an early stage of the epidemic. Compared with projected lifetime hospitalisation cost for infected children, an intervention to reduce vertical transmission cost would be cost effective.

Bed Occupancy↗

The paediatric training required by the general practitioner. A report by a Joint Working Party of the British Paediatric Association and the Royal College of General Practitioners.

This report has been written because special programmes of training for general practice are being developed in many parts of the country and there are questions about the paediatric component of training which need to be discussed nationally.An important part of this report is devoted to listing educational objectives which should be attained in paediatrics by the general practitioner at the end of his training.

Education, Medical↗

Presenting features of paediatric meningococcal disease--a five year experience from a paediatric accident and emergency department.

OBJECTIVES: To determine the clinical features, initial management and outcome of meningococcal disease presenting to a paediatric accident and emergency (A&E) department. DESIGN: A retrospective study of all cases of meningococcal disease seen in the department over a five year period. SETTING: A paediatric A&E department which treats approximately 30,000 patients a year. SUBJECTS: All children under the age of 13 years with a discharge diagnosis of meningococcal disease RESULTS: Fifty patients, forty-six with microbiological confirmation of their diagnosis were identified. Sixty six percent of patients were seen first by their general practitioner. However only 28% had received prehospital parenteral antibiotics. Twenty six percent of children had neither meningism nor a classical purpuric rash, 60% showed signs of shock and 66% had an altered conscious level. The case fatality rate was 4%, with 78% making a full recovery. CONCLUSION: Classical features of meningococcal disease are often absent. Assessing simple clinical parameters such as capillary refill, respiratory rate and conscious level adds to the detection of the disease. If meningococcal disease is suspected parental benzylpenicillin should be given and the child transferred to hospital.

Child↗

Establishing an internet-based paediatric cancer registration and communication system for the Hungarian paediatric oncology network.

Cancer registration has developed in Europe over the last 50 years, and in the last decade intensive joint activities between the European Cancer Registries, in response to the need of pan-European harmonization of registration practices, have taken place. The Hungarian Paediatric Cancer Registry has been functioning as the database of the Hungarian Paediatric Oncology Network since 1971, aiming to follow the incidence and the treatment efficacy of malignant diseases. The goals of this globally unique open source information system are the following: 1) to raise the quality of the registration system to the European level by developing an Internet-based registration and communication system, modernizing the database, establishing automatic statistical analyses and adding an Internet website, 2) to support clinical epidemiological studies that we conduct with international collaborators on detailed analyses of the characteristics of patients and their diseases, evaluation of new diagnostic and therapeutic methods, prevention programs, and long-term quality of life and side effects. The benefits of the development of the Internet-based registration and communication system are as follows: a) introduction of an Internet-based case reporting system, b) modernization of the registry database according to international recommendations, c) automatic statistical summaries, encrypted mail systems, document repository, d) application of data security and privacy standards, e) establishment of a website and compilation of educational materials. The overall objective of this scientific project is to contribute towards the improvement of cancer prevention and cancer care for the benefit of the public in general and of cancer patients in particular.

Child↗

Jubilee Lecture of the Scottish Paediatric Society. Do we really need community paediatricians? A summary of the lecture given at the Triennial Meeting of the Scottish Paediatric Society.

To summarise, I have supported the development of a specialty of "child development and rehabilitation" as an independent branch of paediatrics separate from neurology; emphasised the importance of expertise in child abuse for all paediatricians and not just those working in "the community"; described the changing role of specialist paediatric doctors in pre-school surveillance and the school health service; and suggested that we may need community paediatricians with a public health orientation. It is important to determine what community paediatricians should do and to ensure that the training they receive is relevant to the tasks required of them.

Community Medicine↗

The relationship between European paediatricians and commerce: ethical principles in paediatrics working group recommendations. Confederation of European Societies of Paediatrics (CESP).

UNLABELLED: It is important that doctors have an ethically proper relationship with commercial interests. The relationship between paediatricians, paediatric societies and industry is probably healthy. To further the interests of patients it is important that it remains so. CONCLUSION: This mentionship would be undermined if: there was a perceived conflict of interests between paediatricians, their patients and industry; paediatricians were seen to endorse companies whose marketing and other practices were unethical. It will be enhanced if: paediatricians did not receive individual gain from industry; industrial support for educational and research activities, whether to individuals or institutions, is open, proportionate and accountable.

Commerce↗

Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology.

The Cooperative German Paediatric Liver Tumour Study HB89 was conceived to evaluate the efficiency and toxicity of ifosfamide, cisplatin and doxorubicin (IPA) in children with resectable and non-resectable hepatoblastoma (HB) and to determine late sequelae including tubular nephropathy of tumour treatment. The study also assessed the results of a surgical strategy, which adapts the procedure at the initial operation to the tumour's extension in the liver. The relationship of the tumours' histological differentiation to response to chemotherapy was also examined. Patients with a HB restricted to one liver lobe underwent primary resection. Larger tumours were initially treated with IPA chemotherapy and resected at second-look surgery. All patients received IPA adjuvantly after tumour resection. The IPA regimen consisted of ifosfamide 3.5 g/m2 (over 72 h days 1-3), cisplatin 100 mg/m2 (over 5 days 4-8) and doxorubicin 60 mg/m2 (over 48 h, days 9-10). Median follow-up of survivors was 64 months (range 28-82). Long-term disease-free survival (DFS) was for stage I: 21/21; stage II: 3/6; stage III: 28/38; and stage IV: 2/7 (overall 75%). Severe surgical complications occurred in 15% (4/27) of primary and 21% (8/38) of secondary resections with no lethality. 44/45 stage III/IV HB displayed PR after two IPA courses. Drug resistance developed in 8/12 tumours after four or five chemotherapy courses. Acute toxicity was observed in 34/242 (14%) IPA courses. Late sequelae were found in 7/54 (13%) of survivors, and subclinical renal tubulopathy occurred in 7/41 investigated patients (17%). Despite a more favourable prognosis in pure fetal and predominantly fetal histology, statistical analysis revealed no relationship between tumour differentiation and response to chemotherapy. In conclusion, IPA chemotherapy in combination with delayed surgery was highly effective in the treatment of HB.

Antineoplastic Combined Chemotherapy Protocols↗

Rarity of surgical complications after postchemotherapy nephrectomy for nephroblastoma. Experience of the International Society of Paediatric Oncology-Trial and Study "SIOP-9". International Society of Paediatric Oncology Nephroblastoma Trial and Study Committee.

The aim of the study was to assess rates and types of nephrectomy-related complications in children nephrectomized for nephroblastoma after preoperative chemotherapy. Records of 598 Wilms' tumour patients registered in the International Society of Paediatric Oncology Trial & Study No. 9 (SIOP-9), and pretreated correctly according to the protocol with vincristine + actinomycin D +/- epirubicine or adriamycin prior to nephrectomy, were retrospectively reviewed. Forty-nine patients (8%), who suffered from 54 complications, were identified. Most frequent events were small-bowel occlusions (3.7%) and tumour ruptures (2.8%). Other complications were registered in 2.0% of cases. The low rate of nephrectomy complications and no deaths related to registered ones, are another argument for preoperative chemotherapy in Wilms' tumour patients.

Adolescent↗

Paediatric cardiology in Europe--medical/scientific statement of the Association of European Paediatric Cardiologists. Definition of profession and training requirements.

The treatment of growing and developing individuals with heart and circulation diseases demands expertise and organization. Due to the unification of Europe, international exchange of doctors can take place. The Association of European Paediatric Cardiologists had laid down professional and training requirements to harmonize the field of patient care, training and training institutes all over Europe.

Cardiology↗

Paediatric day surgery: day-case unit admission compared with general paediatric ward admission.

A small exploratory study (n = 20) is described which compares the experience of children admitted to a day-case unit with that of children admitted to a general paediatric ward. Both samples received inadequate amounts of information, particularly prior to discharge. The care offered in the day-case unit was found to be woefully deficient in many areas and the wisdom of utilizing occasional sessions in an adult day-case unit is questioned. The crucial role of skilled nurses trained in the care of sick children is emphasized.

Ambulatory Surgical Procedures↗

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes.

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.

Adolescent↗