ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp.

Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin ± Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.

The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome.

STUDY OBJECTIVE: To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder (ASD) and fragile X syndrome (FXS). METHODS: A 4-week, randomized, double blind, placebo-controlled, crossover design was conducted following a 1-week baseline period. Either melatonin, 3 mg, or placebo was given to participants for 2 weeks and then alternated for another 2 weeks. Sleep variables, including sleep duration, sleep-onset time, sleep-onset latency time, and the number of night awakenings, were recorded using an Actiwatch and from sleep diaries completed by parents. All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS. RESULTS: Data were successfully obtained from the 12 of 18 subjects who completed the study (11 males, age range 2 to 15.25 years, mean 5.47, SD 3.6). Five participants met diagnostic criteria for ASD, 3 for FXS alone, 3 for FXS and ASD, and 1 for fragile X premutation. Eight out of 12 had melatonin first. The conclusions from a nonparametric repeated-measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes (p = .02), mean sleep-onset latency was shorter by 28 minutes (p = .0001), and mean sleep-onset time was earlier by 42 minutes (p = .02). CONCLUSION: The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS.

Varicocèle de l'enfant et de l'adolescent [Children and adolescent varicocele]

About 15% of adolescent males present with a varicocele. It rarely causes symptoms and is often diagnosed on the routine physical examination. There are evidences of an association between duration of a varicocele and testicular impairment. Surgical treatment is indicated in case of testicular growth arrest, testicular asymmetry, grade II or more, symptoms i.e. pain or swelling, parental or patient's anxiety. Several treatment options include open surgery (with or without micro-anastomosis), laparoscopy, embolization by interventional radiology, antegrade scrotal sclerotherapy. Informations should include a recurrence rate as hight as 15% whatever the technique may be, postoperative hydroceles and some testicular atrophies. Those complications can be delayed.

Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis mansoni

Schistosomiasis control seems to be different in countries were low parasitic burden and asymptomatic clinical patients are the features of majority of cases. Immunological methods must substitute the traditional coprologic techniques used for some decades in the Control Program. Circumoval Precipitin Test (COPT), intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using as tools for seroepidemiologic studies. COPT and ELISA were performed after treatment to known their utility when impact of chemotherapy must be assessed. One hundred sixty five persons were followed up 3, 6, 9 and 12 months after treatment. The mean sensitivity of CPT studied by age groups was 95.6% which is very important considering that 88.4% of the studied population excreted less than 100 egg/gr of feces, while sensitivity of intradermal test was 58.2%. Children showed the highest ractivity to COPT. When treatment is effective, COPT reactivity progressively disminish until become negative one year later. In the non cure group, the COPT reactivity disminished but never below 20%. ELISA-SEA did not modify one year after treatment. Effort should be made to isolate fractions of eggs Schistosoma mansoni whose antibodies disappear after treatment.

Eosinophilic esophagitis: Updated consensus recommendations for children and adults.

Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.

Pédiatrie. 4. La calprotectine fécale en pédiatrie: utilisation et interprétation [Pediatrics. Fecal calprotectin in children: use and interpretation].

Fecal calprotectin is a small protein released mainly by neutrophils. It is recognized as a reliable, easy and non-invasive biomarker of gastro-intestinal inflammation. Normal values vary with age, with higher cut-off values during the first year of life (<350 microg/g) than in children (<275 microg/g) or adults (<50 microg/g). Fecal calprotectin can be a useful tool in initial evaluation of recurrent abdominal pain, helping to distinguish between functional gastro-intestinal disorders, where it is normal, and inflammatory bowel disease (IBD). It is not a specific marker of IBD but is increased in other situations of gastro-intestinal inflammation. In patients with IBD, fecal calprotectin is used to monitor treatment response.

Use of levosimendan as rescue therapy in children with low cardiac output syndrome.

Objective: Aim of post operative treatments after cardiac surgery is to avoid low cardiac output syndrome (LCOS). Levosimendan, a new inotrope agent, has been demonstrated in adult patient to be an effective treatment for this purpose when classical therapy is not effective. It shows a positive effect on cardiac output, with fewer adverse effects and lower mortality than with dopamine. There is very few data on its benefit in the paediatric population. The aim of this study is to evaluate the effect of levosimendan in cardiac children with LCOS.Methods: Retrospective analysis of 25 children hospitalised in our PICU after cardiac surgery that demonstrated LCOS not responding to classical catecholamine therapy and who received levosimendan as rescue. LCOS parameters like urine output, mixed venous oxygen saturation (SvO2), arterio-venous differences in CO2 (AVCO2) and plasmatic lactate were compared before therapy and at 12, 24, 48 and 72 hours after the beginning of the levosimendan infusion. We also analyzed the effect on the utilisation of amines (amine score), adverse events and mortality.Results: After the beginning of levosimendan infusion, urine output (3.1 vs 5.3ml/kg/h, p=0.003) and SVO2 (56 vs 64mmHg, p=0.001) increase significantly during first 72 hours and at the same time plasmatic lactate (2.6 vs 1.4 mmole/l, p<0.001), AVCO2 (11 vs 8 mmHg, p=0.002) and amine score (63 vs 39, p=0.007) decrease significantly. No side effects were noted during administration of levosimendan. In this group of patients, mortality was 0%.Conclusion: Levosimendan is an effective treatment in children after congenital heart surgery. Our study, with a greater sample of patient than other studies, confirms the improvement of cardiac output already shown in other paediatric studies.

Quantifying uncertainty: physicians' estimates of infection in critically ill neonates and children.

To determine the diagnostic accuracy of physicians' prior probability estimates of serious infection in critically ill neonates and children, we conducted a prospective cohort study in 2 intensive care units. Using available clinical, laboratory, and radiographic information, 27 physicians provided 2567 probability estimates for 347 patients (follow-up rate, 92%). The median probability estimate of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work-up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to 20% at initiation of antibiotic treatment (P&lt;.001). At initiation of treatment, predictions discriminated well between episodes subsequently classified as proven infection and episodes ultimately judged unlikely to be infection (area under the curve, 0.88). Physicians also showed a good ability to predict blood culture-positive sepsis (area under the curve, 0.77). Treatment and testing thresholds were derived from the provided predictions and treatment rates. Physicians' prognoses regarding the presence of serious infection were remarkably precise. Studies investigating the value of new tests for diagnosis of sepsis should establish that they add incremental value to physicians' judgment.

Spondylarthropathies in children--are they different from those in adults?

Juvenile spondylarthropathies (JSpAs) comprise a group of rheumatic diseases distinct from other categories of juvenile arthritis. Several classification systems have been applied, and some are specific for children, such as the seronegative enthesopathy and arthropathy (SEA) syndrome and the enthesitis-related arthritis, diagnostic forms in the International League of Associations for Rheumatism (ILAR) classification. JSpA seems more frequent than was previously believed, but actual epidemiological data show important variations between studies. Compared to adult patients, children with JSpA present with peripheral arthritis and enthesitis early in disease but sacroiliac and spine joints involvement many years later. A multidisciplinary team in a paediatric environment should be responsible for the management of children with spondylarthropathies to ensure the best care for these children with their chronic disease and risk of long-term disability. Recent advances in the treatment of rheumatic diseases with biological agents show promising results in children with JSpA. Further research needs to be conducted to increase our knowledge of the long-term outcome of these patients, to improve management, and to prevent long-term consequences of the disease.

Vincristine and intestinal pseudo-obstruction in children: report of 5 cases, literature review, and suggested management.

Summary: Intestinal pseudo-obstruction is a rare complication resulting from a variety of disorders. Symptoms include abdominal pain, nausea, vomiting, diarrhea, constipation, and malnutrition. Vincristine-related pseudo-obstruction has been reported in the literature, but its description in children and recommendations for management are lacking. A review of the literature revealed 21 reported pediatric cases of vincristine-related pseudo-obstruction. Most have, however, been attributed to a drug interaction with itraconazole, accidental vincristine overdose, or liver failure. Potential genetic causes are rarely addressed. We present here 5 cases of pseudo-obstruction related to vincristine without any identifiable predisposing factors, and a suggested algorithm for management

Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer.

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

IPH response to the Joint Committee on Health and Children and members of the Northern Ireland Assembly on “Cross-border cooperation on healthcare”

The Institute of Public Health in Ireland were asked to submit a paper on 'Cross-border cooperation on healthcare' for a joint meeting between the Oireachtas Joint Committee on Health and Children and the Northern Ireland Assembly Health Committee which took place in Leinster House on 1 March 2012. Key points from the submission included: o    The Institute of Public Health in Ireland (IPH) is an all-island organisation which promotes cooperation between the Republic of Ireland and Northern Ireland with the aim of improving population health on the island and tackling health inequalities. IPH work is focused on addressing the causes of ill health rather than the design and delivery of treatment services. o    North/South cooperation on health was mandated under the Belfast Agreement in 1998 in five domains, including health promotion. IPH has supported the North South Ministerial Council (NSMC) in respect of the health promotion strand since inception. o    The Department of Health and Department of Health, Social Services and Public Safety North-South Feasibility Study (December 2011) states that mutual benefits are most evident from cooperation in the areas of (i) anticipating trends and illnesses in a collective manner (ii) public health issues (iii) specialised services where the population or activity required to sustain the service cannot be met by either jurisdiction alone and (iv) in relation to those areas adjacent to the border. o    The European Directive on Cross-Border Healthcare will be implemented in the next few years which will have implications in relation to patients travelling for healthcare across the Republic of Ireland/Northern Ireland border. o    IPH is supporting the development of new public health strategies in the Republic of Ireland and Northern Ireland which are both due for publication this year. o    There are tangible benefits from cross-border cooperation in the health sector, both in public health and in health service planning and delivery and there are many examples of successful initiatives. However, developments are not occurring in the context of an agreed plan or overall strategic context and tend to be project-based and concentrated in border counties. o    Successful cross-border cooperation requires high level support and integration into departmental policy cycles. The provision of data on an all-island basis supports cross-border cooperation as does the operation of sustainable all-island organisations which can support research, evaluations and programmes. o    In the future, cross-border cooperation in health will be more effective if developed with a strategic planning process intrinsically linked to Departmental priorities. o    North-South cooperation in the areas of alcohol, obesity, tobacco health surveys and rare diseases will be particularly beneficial.

Imaging of Lemierre Syndrome in children and young adultsA case-series analysis

Background / Purpose : Lemierre Syndrome (LS) is defined by a recent oro-pharangeal infection, the clinical presence or radiological demonstration of internal jugular vein (IJV) thrombosis and documented anaerobe germ, principally Fusobacterium necrophorum (Fn) leading to septicaemia and septic embolization. It is a rare infection described since 1900 and it nearly disappeared since the beginning of the antibiotic area. Even if it is seldom described in the literature, this infection is reappearing in the last 10 years, either because of the increase of antibiotic resistance or by modification of antibiotic prescription. The aim of this study is to describe the role of medical imaging in the diagnosis, staging and follow up of Lemierre syndrome, as well as to describe the ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) findings of this rare disease. Patients and methods : Radiological and medical files of patients diagnosed with Lemierre syndrome in the past 6 years at CHUV hospital were analysed retrospectively. The CT scan, US, colour Doppler US (CDUS) and MRI examinations that were performed have been examined so as to define their specific imaging findings. Results IJV thrombosis was demonstrated in 2 cases by US, by CT in 6 cases and MRI in one case. Septic pulmonary emboli were detected by CT in 5 patients. Complications of the LS were depicted by MR in one case and by CT in 1 case. Conclusion : In the appropriate clinical settings, US, CT or MR evidence of IJV thrombosis and chest CT suggestive of septic emboli, should lead the physician to consider the diagnosis of LS. As a consequence, imaging allows a faster diagnosis and a more efficient treatment of this infection, which in case of insufficient therapy can lead to death.