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A model-based approach to characterize the incubation period of paediatric transfusion-associated acquired immunodeficiency syndrome.

Traditional statistics, such as the average, currently provide a misleading statistical description of the incubation periods of paediatric transfusion-associated acquired immunodeficiency syndrome (TA-AIDS). Two types of length-biased sampling, left censoring and right censoring, occur in the 37 cases diagnosed before 1986 and reported to the Centers for Disease Control by 15 September 1986. To correct for these problems, we propose a truncated Weibull distribution with use of a maximum likelihood technique. This approach suggests that the mean incubation period of paediatric TA-AIDS cases is 2.4 years with a 90 per cent confidence interval ranging from 1.5 years to 7.2 years. The mode is 1.25 years. These estimates are much shorter than those recently published for adults, therefore the success of TA-AIDS prevention strategies may be seen sooner in the paediatric age group.

Acquired Immunodeficiency Syndrome↗

Supportive care of the paediatric cancer patient.

Cytotoxic therapy for paediatric malignancy continues to be associated with significant mortality and morbidity. However, survival figures continue to improve despite increasingly toxic treatment protocols. Aggressive supportive care, more than any other modality, has produced a dramatic reduction in mortality during the past 30 years, and includes the appropriate management of infection, provision of adequate nutrition, and proper use of blood and blood products. The paediatric surgeon plays an integral role in the multidisciplinary team of cancer management and together with other team specialists is responsible for the planning of surgical intervention and also ensuring the safe passage of immunologically impaired patients through the additional stress of surgery. This paper details essential aspects of supportive care as commonly practiced in paediatric patients undergoing therapy and surgery.

Catheterization, Central Venous↗

Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours.

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.

Adolescent↗

The development of paediatric neuroradiology.

The development of paediatric neuroradiology is a specific persuasion within neuroradiology and has increased in scope and significance throughout the last ten years. The emergence of computed tomography has altered the indications for types of neuroradiological procedures in infants and children. The sophistication, accuracy, and safety of standard neuroradiological procedures have been increased by the accuracy and safety of computed tomography, particularly in the premature infant. There is a growing need for education and instruction in paediatric neuroradiological techniques and paediatric neuroradiological diseases within the neuroradiological fraternity as a whole.

Adolescent↗

Chronic peritoneal dialysis in paediatrics: experience of a national registry.

The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986-1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. the incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.

Adolescent↗

Escherichia coli verotoxin binding to human paediatric glomerular mesangial cells.

Haemolytic uraemic syndrome (HUS) remains the leading cause of acute renal failure in children. Although an Escherichia coli-produced verotoxin (VT) has been implicated in the pathogenesis of HUS, the precise mechanisms of disease are not well defined. We hypothesise that the pathogenesis of renal failure in HUS includes the binding of E. coli VT to the glomerular mesangial cell, with consequent effects on renal function. Using human paediatric mesangial cells, we studied the binding and biological effects of the purified verotoxin VT-1. We isolated, purified and characterised paediatric glomerular mesangial cells. The mesangial cells were characterised by their immunoreactivity with both smooth muscle actin and vimentin antibodies, and lack of immunoreactivity with cytokeratin or factor VIII antibodies. Using an fluorescein isothiocyanate-conjugated VT (10(-7)-10(-8) M), we demonstrated specific binding to the mesangial cell membrane by immunofluorescence microscopy. We also demonstrated a dose-dependent inhibition of mesangial cell mitogenesis at concentrations from 10(-9) to 10(-17) M. Our data demonstrate that VT-1 binds to paediatric human glomerular mesangial cells and this binding results in specific biological actions, including an inhibition of cell mitogenesis.

Bacterial Toxins↗

Intensive care management of paediatric organ donors and its effect on post-transplant organ function.

OBJECTIVES: 1. To document the clinical course of paediatric beating heart organ donors. 2. To evaluate the effect of the ICU management of pediatric donors on the immediate function of transplanted organs. 3. To examine the validity of current donor selection criteria. DESIGN: Retrospective chart review and case series study. SETTING: Multidisciplinary ICU of tertiary referral paediatric hospital. PATIENTS: All patients who became solid organ donors between January 1980 and July 1990. OUTCOME MEASURES: 1. Incidence of major physiological abnormalities of the cardiovascular, pulmonary, renal and metabolic systems. 2. Number of organs retrieved and transplanted, reasons for non-transplantation of donated organs. 3. Immediate post-transplant function of transplanted organs. RESULTS: Seventy-seven organ donors were identified from whom 134 kidneys, 31 livers and 12 hearts were transplanted. Sixty (78%) patients developed diabetes insipidus. Sustained hypotension occurred in 41 (53.2%) and was commoner in patients treated with inotropic agents in the presence of a low central venous pressure and in patients with diabetes insipidus who did not receive anti-diuretic hormone replacement. Twenty-seven patients suffered at least one cardiac arrest. The data on post-transplant function were obtained for 129 kidneys (from 70 donors) 30 livers and 9 hearts. Fifty-two kidneys, 10 livers and 2 hearts were transplanted from donors who had suffered at least one cardiac arrest without apparent adverse effect on post-transplant organ function. Thirty-six kidneys from 31 donors suffered either acute tubular necrosis (ATN) or primary non-function. The donors of these organs spent longer in ICU (60.6 +/- 45.7 h versus 41.8 +/- 30.1 h p = 0.045) and had a higher mean maximum serum sodium concentration (163.4 +/- 10.9 versus 158.5 +/- 9.5 mmol/l p = 0.05) than those without these complications. The serum creatinine concentration and degree of inotropic support did not predict post-transplant function. Standard biochemical tests for hepatic function, the dose of inotropic agent received, time in ICU and incidence of hypotension did not predict post-transplant liver function. CONCLUSIONS: Aggressive fluid resuscitation and management of diabetes insipidus may promote stability in paediatric organ donors. Donor cardiac arrest does not alter the ICU course or compromise post-transplant organ function. The current criteria used for donor selection failed to predict post-transplant organ function and their use may increase organ wastage.

Adolescent↗

Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype.

Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours.

Antigens, CD↗

Histamine release in paediatric cardiopulmonary bypass--a possible role in the capillary leak syndrome.

Recent studies have reported pathologically elevated plasma histamine levels in adult patients during and after open heart surgery. In paediatric practice, the increased use of donor-blood primes might be expected to produce even greater rises in the histamine levels, by creating histamine release in the prime before initial perfusion commences. The present study covered 40 arbitrarily chosen paediatric cases. Pathologically elevated plasma histamine levels (greater than 1 ng/ml) were found in the prime of 26 out of 37 cases (73%). Histamine levels were substantially higher than levels encountered in previously reported studies, and massively elevated prime histamine levels (greater than 80 ng/ml) were encountered in 9 out of the 40 cases (22%). These results suggest that in conventional paediatric cardiac surgical practice, the prime content of histamine is markedly elevated in the majority of patients. The inevitable delivery of this prime histamine load at the onset of perfusion might be expected to produce systemic pathological effects.

Adolescent↗

Rational use of diagnostic imaging in paediatrics. The report of a World Health Organization Study Group.

The World Health Organization (WHO) is the agency of the United Nations with primary responsibility for international health matters and public health. Through the exchange of the knowledge and experience of health professionals from 165 nations WHO promotes comprehensive health services worldwide. As a part of this effort WHO has in recent years been concerned with improving the availability and utilization of diagnostic imaging, especially as it relates to health services in developing countries. Having devised and specified suitable basic radiographic equipment (the WHO BRS) a WHO Scientific Group was convened in 1982 to study the utilization of radiographic procedures and to to recommend their more efficacious and rational use. Then in 1984, recognizing the implications of newer imaging technology on world health, a second WHO Scientific Group considered the design, impact and future use of ultrasonography and computed tomography in developing countries. The findings of these scientific groups were published as part of the WHO Technical Report Series which makes available the recommendations of such international groups of experts. Although some of the needs of children were considered in these previous Technical Reports, WHO felt that the size and socioeconomic importance of the paediatric population worldwide warranted a further study and report to address the particular technical and clinical problems of diagnostic imaging in the paediatric age group. Thus a third WHO Scientific Group met in Geneva from 18 to 24 November 1985 to review established practices and experience in paediatric imaging throughout the world; and to recommend rational guidelines for diagnostic imaging for children to age 14 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

[New perspectives for simulator-based training in paediatric anaesthesia and emergency medicine].

Anaesthesia and emergency medical care for infants and toddlers is often associated with high clinical demands and specific challenges. Nevertheless, a significant proportion of interventions is performed by anaesthetists and emergency physicians with no specialised paediatric training and little experience in the management of anaesthetic incidents and emergencies specific to these age groups. Extensive studies have demonstrated a close inverse correlation between the level of specialisation and perioperative morbidity and mortality. However, clinical circumstances and the relatively small number of paediatric cases at many institutions often hinder the establishment of improved training concepts. Recently, high-fidelity infant simulators have become available, which permit authentic exposure to a large spectrum of scenarios in paediatric anaesthesia and emergency medicine. A multimodular concept of training, including such simulator-based techniques, may relieve the widespread shortage in clinical experience, and hence greatly facilitate improvement of quality of care and patient safety.

Anesthesiology↗

[Awareness: a problem in paediatric anaesthesia?].

Intraoperative awareness has been reported to occur in 0.8-5.0% of paediatric patients undergoing anaesthesia and, therefore, seems to be more common than in adults (incidence 0.1-0.2%). In adult patients, the consequences of intraoperative awareness are well known and can be severe, in children, however, they have not yet been adequately studied. The causes for intraoperative awareness can be divided into three broad categories: First, no or only a light anaesthetic is given on purpose, second, an insufficient dose of an anaesthetic is given inadvertently, third, there is equipment malfunction or the anaesthesiologist makes an error. Unfortunately, especially in young children, painful interventions are still performed without adequate analgesia, e.g. awake intubation or fracture manipulation under midazolam sedation alone. The key issue is, however, that pharmacokinetics and pharmacodynamics change enormously from the 500 g preterm baby to the adolescent patient. Adequate dosing is much more difficult in paediatric patients compared to standard adult surgical patients. Solid knowledge of the pharmacokinetic and pharmacodynamic characteristics of commonly used drugs in different paediatric age groups, as well as aiming for perfection in daily care will help to reduce the incidence of awareness. Methods for monitoring the depth of hypnosis, e.g. the bispectral index, will be used increasingly, at least in children above 1 year of age. In addition to clinical parameters, they will hopefully help to further reduce the incidence of intraoperative awareness.

Adult↗

Desflurane or isoflurane for paediatric ENT anaesthesia. A comparison of intubating conditions and recovery profile.

BACKGROUND: The inhaled anaesthetic desflurane is characterized by a rapid wash-in and wash-out and may be useful for short paediatric ENT procedures. Therefore, this study was designed to compare the effects of desflurane or isoflurane on intubating conditions and recovery characteristics in paediatric ENT patients. METHODS: In this prospective, randomised investigation, we studied 44 children scheduled for ENT surgery, aged 4-12 yr and classified ASA I-II. After thiopentone induction (5-8 mg/kg) the lungs were ventilated by face mask and the vaporizer was dialed to 1 MAC (age-adapted) of desflurane of isoflurane. A reduced dose of vecuronium (0.05 mg/kg) was administered, and intubating conditions were rated 3 min later. Following tracheal intubation, 50% nitrous oxide were added, and the concentration of desflurane or isoflurane was adjusted according to clinical needs. At the end of surgery all anaesthetics were discontinued simultaneously and recovery times were recorded. RESULTS: Intubating conditions were rated significantly better for desflurane (excellent or good 20 of 22) than for isoflurane (12 of 22). Recovery times were significantly shorter for desflurane than for isoflurane (mean +/- SE): spontaneous ventilation 4.0 +/- 0.5 min vs. 6.0 +/- 0.7 min, extubation 8.4 +/- 0.7 vs. 11.4 +/- 1.1 min and arrival at PACU 11.5 +/- 0.8 vs. 16.6 +/- 1.5 min. No airway complications (coughing, laryngospasm, or desaturation < 97%) were noted for either anaesthetic. CONCLUSIONS: Following an intravenous induction improved intubating conditions, shorter recovery times and the lack of airway complications make desflurane a suitable alternative to isoflurane for paediatric ENT anaesthesia.

Anesthesia Recovery Period↗

Recombinant activated factor VII in paediatric cardiac surgery.

OBJECTIVE: To review the use of recombinant activated factor VII in paediatric cardiac surgery. DESIGN: Retrospective chart review. SETTING: Paediatric intensive care unit in a stand-alone university-affiliated children's hospital. PATIENTS AND PARTICIPANTS: Cardiac surgical patients who received recombinant activated factor VII (rFVIIa, NovoSeven; NovoNordisk, Copenhagen, Denmark) between June 2002 and June 2003 at The Children's Hospital at Westmead. RESULTS: Six children undergoing cardiac surgery received rFVIIa. Recombinant activated factor VII was administered if bleeding was excessive and persisted despite appropriate investigation and attention to haemostasis by surgical and medical staff. An intravenous dose of 180 microg/kg was given and repeated 2 h later. All of the six patients responded well to rFVIIa with achievement of haemostasis. No adverse events were noted. CONCLUSIONS: Recombinant activated factor VII achieved haemostasis in six paediatric cardiac surgical patients. Good outcomes and no adverse events were noted in these children.

Child, Preschool↗

Safe paediatric intensive care. Part 1: Does more medical care lead to improved outcome?

Neonatal and paediatric intensive care has improved the prognosis for seriously sick infants and children. This has happened because of a pragmatic approach focused on stabilisation of vital functions and immense technological advances in diagnostic and therapeutic procedures. However, the belief that more medical care must inevitably lead to improved health is increasingly being questioned. This issue is especially relevant in developing countries where the introduction of highly specialised paediatric intensive care may not lead to an overall fall in child mortality. Even in developed countries, the complexity and availability of therapeutics and invasive procedures may put seriously ill children at additional risk. In both developing and industrialised countries the use of safe and simple procedures for appropriate periods, particular attention to drug prescription patterns and selection of appropriate aims and modes of therapy, including non-invasive methods, may minimise the risks of paediatric intensive care.

Biomedical Technology↗

Safe paediatric intensive care. Part 2: workplace organisation, critical incident monitoring and guidelines.

In order to optimise safety within the paediatric intensive care unit (PICU), it is essential to optimise organisation, identify problem areas and implement standards and guidelines for safe practice (with appropriate monitoring). Organisational issues have a major impact on safety: the introduction and-recently-centralisation of paediatric intensive care, the appointment of dedicated paediatric intensivists, nursing staffing, handovers, rounds, the number of work hours and night shifts with the associated problems of disturbed circadian rhythms. The technique of voluntary, anonymous, non-punitive critical incident reporting has the potential to identify incidents and latent errors before they become self-evident through a major incident. This systems approach focuses on organisational and communication problems. Standards and guidelines may help in weighing up the benefits and risks of invasive procedures, and interventional studies have shown that implementation of standards and guidelines can improve outcome. Mortality prediction models enable us to monitor quality of care and, thus, to investigate the best ways of organising intensive care and monitoring the effects of changes in practice.

Child↗

Heparin-induced thrombocytopenia in paediatrics: clinical characteristics, therapy and outcomes.

OBJECTIVE: Reports on heparin-induced thrombocytopenia (HIT) in paediatrics are confined to isolated case reports. The objective was to systematically combine the published data. DESIGN AND SETTING: Cases were identified by MEDLINE search and review of bibliographies. PATIENTS: We included subjects reported with HIT, collecting patient demographics, clinical and laboratory characteristics, therapeutic regimens and outcomes. MEASUREMENTS AND RESULTS: Reports on 70 patients were retrieved. In a majority of children, HIT occurred during hospitalisation in a paediatric ICU. In most patients, the typical onset pattern was reported, although rapid-onset-pattern HIT occurred in some. The median platelet-count nadir was 54x10(9)/l; 11% of reported patients had nadirs in the normal range. Clinical symptoms included isolated thrombocytopenia and solitary or combined venous, arterial and intracardiac thromboembolism, sometimes catheter-related. Pulmonary embolism and major bleeding were rarely described. Confirmatory functional or antigenic testing of HIT antibodies showed a similar cumulative sensitivity of about 88%. An unfavourable outcome (death/limb amputation) was reported in 42.1% of patients without therapy and in 18% of patients treated with danaparoid, lepirudin, or argatroban. CONCLUSIONS: HIT in children mainly occurs in paediatric intensive care with diagnostic features and outcomes similar to those seen in adults. HIT cannot be ruled out based on normal platelet counts or occurrence after fewer than 5 days of heparin exposure. Children should be presumed to suffer from HIT based on clinical grounds and treated accordingly (immediate heparin withdrawal and alternative anticoagulation). Alternative anticoagulation with danaparoid, lepirudin and argatroban appears to improve outcomes.

Anticoagulants↗

The relation between TISS and real paediatric ICU costs: a case study with generalizable methodology.

OBJECTIVE: To determine the quantitative relation between the Therapeutic Intervention Scoring System (TISS) in combination with other relevant clinical variables and the real costs of (paediatric) intensive care. DESIGN: A prospective, observational study. SETTING: A Ten-bed paediatric intensive care unit in a university children's hospital. PATIENTS AND PARTICIPANTS: In a 17-months registration period we collected patient- and treatment-related data for all 611 consecutive admissions. A 21-day calibration period was used to collect detailed data to calculate the real costs of 33 consecutive admissions, in addition to the same data as in the registration period. MEASUREMENTS AND RESULTS: We used the Multi Moment Measurement method to measure time spent by nurses and physicians and medication used in the 21-day calibration period. The calibration period data set with explanatory variables including TISS was used to build a regression model to estimate nurse and physician time, which were converted to personnel costs, and to estimate medication costs. The regression models built from the calibration period were subsequently used to estimate the total costs per day and per admission in different patient groups in the registration period. CONCLUSION: It was feasible to calculate total direct medical costs based on a limited number of readily available clinical variables related to patient characteristics and treatment, of which TISS was the most important determinant. The proposed methods provide further tools for assessment of (paediatric) intensive care unit performance.

Direct Service Costs↗