Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients.

Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.

Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

Purpose To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim). Patients and Methods From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 μg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled. Results The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest. Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.

Neurologie [Therapeutic advances in neurology].

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Development of a pediatric eosinophilic esophagitis activity index (ped-EEsAI): International experts propose dysphagia, whitish exudates on endoscopy , and intraepithelial eosinophili count as major items related to EoE activity

Background and Aims: The international EEsAI study group aims to develop, validate and evaluate the first pediatric EoE activity index (ped-EEsAI). We report on results of phase 1, which aims to generate candidate items. Methods: This study involves 3 phases: (1) item generation, (2) index derivation and testing on a first patient cohort, and (3) validation in a second cohort. In phase 1, item generation, weighting and reduction are achieved through a Delphi process with an international EoE expert group. The experts proposed and ranked candidate items on a 7-point Likert scale (0 = no, 6 = perfect relationship with EoE activity). Results: 23 international EoE experts proposed and ranked 39 items (20 clinical, 6 endoscopic, 8 histologic, 5 laboratory items). Rank order for clinical items: dysphagia related to food consistencies (median 5, range 2-6), severity of dysphagia (5, 3-6), frequency of dysphagia episodes (5, 3-6), regurgitation and vomiting (4, 2-5), response to dietary restrictions (4, 1-6); endoscopic items: whitish exudates (5, 3-6), furrowing (4, 3-6), corrugated rings (4, 2-6), linear shearing (4, 2-6), strictures (3, 2-6); histologic items: intraepithelial eosinophil count (5, 4-6), lamina propria fibrosis (3, 2-6), basal layer enlargement (3, 1-5); laboratory items: % blood eosinophils (3, 0-5). Conclusions: These items will now be reduced in further Delphi rounds, tested on a cohort of 100 pediatric EoE patients and validated in a second independent cohort, resulting in a robust, broadly accepted disease activity index for use in clinical trials and daily care.

Iterative statistical reconstruction method: A new way to reduce dose in pediatric cardiac CT

Purpose: Although several approaches have been already used to reduce radiation dose, CT doses are still among the high doses in radio-diagnostic. Recently, General Electric introduced a new imaging reconstruction technique, adaptive statistical iterative reconstruction (ASIR), allows to taking into account the statistical fluctuation of noise. The benefits of ASIR method were assessed through classic metrics and the evaluations of cardiac structures by radiologists. Methods and materials: A 64-row CT (MDCT) was employed. Catphan600 phantom acquisitions and 10 routine-dose CT examinations performed at 80 kVp were reconstructed with FBP and with 50% of ASIR. Six radiologists then assessed the visibility of main cardiac structures using the visual grading analysis (VGA) method. Results: On phantoms, for a constant value of SD (25 HU), CTDIvol is divided by 2 (8 mGy to 4 mGy) when 50% of ASIR is used. At constant CTDIvol, MTF medium frequencies were also significantly improved. First results indicated that clinical images reconstructed with ASIR had a better overall image quality compared with conventional reconstruction. This means that at constant image quality the radiation dose can be strongly reduced. Conclusion: The first results of this study shown that the ASIR method improves the image quality on phantoms by decreasing noise and improving resolution with respect to the classical one. Moreover, the benefit obtained is higher at lower doses. In clinical environment, a dose reduction can still be expected on 80 kVp low dose pediatric protocols using 50% of iterative reconstruction. Best ASIR percentage as a function of cardiac structures and detailed protocols will be presented for cardiac examinations.

Sternal wound infection after heart operations in pediatric patients associated with nasal carriage of Staphylococcus aureus.

A cluster of six pediatric cases of deep-seated Staphylococcus aureus infection after heart operations prompted us to perform molecular typing of the S. aureus isolates by pulsed-field gel electrophoresis. This revealed the presence of genotypically distinct isolates in four of the six patients. Isolates of two patients were genotypically identical. All patients carried S. aureus in the anterior nares. In each patient, the banding pattern of deoxyribonucleic acid in these isolates was indistinguishable from that in strains isolated from blood or wound cultures. Molecular typing with pulsed-field gel electrophoresis ruled out nosocomial transmission of S. aureus between four patients; at the same time, it provided evidence for an association between nasal colonization and postoperative wound infection. Epidemiologic investigation of potential links between two patients with identical isolates did not provide any evidence for nosocomial transmission of S. aureus between these patients. Because nasal colonization with S. aureus may be a risk factor for surgical wound infection in pediatric patients undergoing heart operations, preoperative decolonization appears to be warranted.

Model-based iterative reconstruction in pediatric chest CT: assessment of image quality in a prospective study of children with cystic fibrosis.

BACKGROUND: The potential effects of ionizing radiation are of particular concern in children. The model-based iterative reconstruction VEO(TM) is a technique commercialized to improve image quality and reduce noise compared with the filtered back-projection (FBP) method. OBJECTIVE: To evaluate the potential of VEO(TM) on diagnostic image quality and dose reduction in pediatric chest CT examinations. MATERIALS AND METHODS: Twenty children (mean 11.4 years) with cystic fibrosis underwent either a standard CT or a moderately reduced-dose CT plus a minimum-dose CT performed at 100 kVp. Reduced-dose CT examinations consisted of two consecutive acquisitions: one moderately reduced-dose CT with increased noise index (NI = 70) and one minimum-dose CT at CTDIvol 0.14 mGy. Standard CTs were reconstructed using the FBP method while low-dose CTs were reconstructed using FBP and VEO. Two senior radiologists evaluated diagnostic image quality independently by scoring anatomical structures using a four-point scale (1 = excellent, 2 = clear, 3 = diminished, 4 = non-diagnostic). Standard deviation (SD) and signal-to-noise ratio (SNR) were also computed. RESULTS: At moderately reduced doses, VEO images had significantly lower SD (P < 0.001) and higher SNR (P < 0.05) in comparison to filtered back-projection images. Further improvements were obtained at minimum-dose CT. The best diagnostic image quality was obtained with VEO at minimum-dose CT for the small structures (subpleural vessels and lung fissures) (P < 0.001). The potential for dose reduction was dependent on the diagnostic task because of the modification of the image texture produced by this reconstruction. CONCLUSIONS: At minimum-dose CT, VEO enables important dose reduction depending on the clinical indication and makes visible certain small structures that were not perceptible with filtered back-projection.

Targeting burn prevention in the pediatric population : a prospective study of children's burns in the Lausanne area

Rapport de synthèse : But de l'étude : Les accidents domestiques représentent un problème significatif en médecine pédiatrique. Le but de cette étude est de mieux comprendre les mécanismes et causes des brûlures afin de pouvoir cibler la prévention. Méthode : Il s'agit d'une étude prospective d'une durée d'une année, d'Août 2004 à Août 2005. Les patients ayant consulté pour des brûlures à l'Hôpital de l'Enfance de Lausanne (HEL) ou au CHUV ont été répertoriés. Le mécanisme et les circonstances des brûlures ont été analysées, de même que l'environnement et les données psycho-sociales. Résultats : huitante-neuf patients ont été inclus dans l'étude, âgés de 2 mois à 15 ans. Septante-huit pour cent des patients avaient moins de 5 ans. Plus de la moitié étaient des garçons. Les brûlures par échaudement prédominaient. Nous n'avons pas pu mettre en évidence d'incidence augmentée de brûlures chez des patients de familles immigrées ou de niveau social bas. Dans la majorité des cas, un adulte était présent au moment de l'accident. Conclusion : Si l'on devait établir un profil type de l'enfant à risque de se brûler dans notre région, il s'agirait d'un garçon âgé de 15 mois-5ans, se brûlant en se versant une tasse de liquide chaud sur la main, à son domicile, en présence de l'un ou de ses deux parents. Le message de prévention devrait donc s'adresser directement aux parents, toutes nationalités et niveau social confondus afin de leur expliquer les dangers de brûlures présents au quotidien à leur domicile. A chaque contrôle, les pédiatres devraient parler des accidents domestiques aux parents. En insistant sur les dangers que représentent les tasses de café, la porte du four et la plaque de la cuisinière, qui sont des éléments du quotidien et qui méritent une attention à chaque utilisation. Les brûlures chez le petit enfant pourraient ainsi être fortement réduites.

Diagnostic algorithm for a validated displacement grading of pediatric supracondylar fractures.

Background: The first AO comprehensive pediatric long bone fracture classification system has been established following a structured path of development and validation with experienced pediatric surgeons. Methods: A follow-up series of agreement studies was applied to specify and evaluate a grading system for displacement of pediatric supracondylar fractures. An iterative process comprising an international group of 5 experienced pediatric surgeons (Phase 1) followed by a pragmatic multicenter agreement study involving 26 raters (Phase 2) was used. The last evaluations were conducted on a consecutive collection of 154 supracondylar fractures documented by standard anteroposterior and lateral radiographs. Results: Fractures were classified according to 1 of 4 grades: I = incomplete fracture with no or minimal displacement; II = Incomplete fracture with continuity of the posterior (extension fracture) or anterior cortex (flexion fracture); III = lack of bone continuity (broken cortex), but still some contact between the fracture planes; IV = complete fracture with no bone continuity (broken cortex), and no contact between the fracture planes. A diagnostic algorithm to support the practical application of the grading system in a clinical setting, as well as an aid using a circle placed over the capitellum was proposed. The overall kappa coefficients were 0.68 and 0.61 in the Phase 1 and Phase 2 studies, respectively. In the Phase 1 study, fracture grades I, II, III, and IV were classified with median accuracies of 91%, 82%, 83%, and 99.5%, respectively. Similar median accuracies of 86% (Grade I), 73% (Grade II), 83%(Grade III), and 92% were reported for the Phase 2 study. Reliability was high in distinguishing complete, unstable fractures from stable injuries [ie, kappa coefficients of 0.84 (Phase 1) and 0.83 (Phase 2) were calculated]; in Phase 2, surgeons' accuracies in classifying complete fractures were all above 85%. Conclusions: With clear and unambiguous definition, this new grading system for supracondylar fracture displacement has proved to be sufficiently reliable and accurate when applied by pediatric surgeons in the framework of clinical routine as well as research.

Mycobacterium avium subsp. paratuberculosis in an Italian Cohort of Type 1 Diabetes Pediatric Patients.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease in ruminants. Recent studies have linked MAP to type 1 diabetes (T1D) in the Sardinian population. The aim of this study was to investigate the prevalence of MAP infection in a T1D cohort from continental Italy compared with healthy control subjects. 247 T1D subjects and 110 healthy controls were tested for the presence of MAP. MAP DNA was detected using IS900-specific polymerase chain reaction (PCR). The presence of antibodies towards a MAP antigen, heparin binding hemoagglutinin (HBHA), was detected by ELISA. We demonstrated a higher MAP DNA prevalence in plasma samples from T1D patients and a stronger immune response towards MAP HBHA, compared with healthy control subjects. Moreover, in the recent onset patients, we observed an association between anti-MAP antibodies and HLA DQ2 (DQA1 0201/DQB1 0202). These findings taken together support the hypothesis of MAP as an environmental risk factor for the development of T1D in genetically predisposed subjects, probably involving a mechanism of molecular mimicry between MAP antigens and pancreatic islet β-cells.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of &gt;50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (&gt;3 yrs of intensive care vs. &lt;3 yrs, 4.1 vs. 4.95 nmol/L, p &lt; .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with &gt;8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p &lt; .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.