Use of electronic health records by child primary healthcare providers in Europe.

BACKGROUND: There is limited data on the use and functionality level of electronic health records (EHRs) supporting primary child health care in Europe. Our objective was to determine European primary child healthcare providers' use of EHRs, and functionality level of the systems used. METHODS: European primary care paediatricians, paediatric subspecialists and family doctors were invited by European Academy of Paediatrics Research in Ambulatory Setting Network (EAPRASnet) country coordinators to complete a web-based survey on the use of EHRs and the systems' functionalities. Binomial logistic analysis has been used to evaluate the effect of specialty and type of practice on the use of EHRs. RESULTS: The survey was completed by 679 child primary healthcare providers (response rate 53%). Five hundred and fifty four responses coming from 10 predominant countries were taken for further analysis. EHR use by respondents varied widely between countries, all electronic type use ranging between 7% and 97%. There was no significant difference in EHR use between group practice and solo practitioners, or between family doctors and primary care paediatricians. History and physical examination can be properly recorded by respondents in most countries. However, growth chart plotting capacity in some countries ranges between 22% and 50%. Vaccination recording capacity varies between 50% and 100%, and data exchange capacity with immunization databases is mostly limited, ranging between 0% and 54%. CONCLUSIONS: There is marked heterogeneity in the use and functionalities of EHRs used among child primary child healthcare providers in Europe. More importantly, lack of critical paediatric supportive functionalities like growth tracking and vaccination status has been documented in some countries. There is a need to explore the reasons for these findings, and to develop a cross European paediatric EHR standards.

Diagnosis of invasive fungal infections in immunocompromised children.

Early recognition and rapid initiation of effective treatment is a prerequisite for successful management of children with invasive fungal infections. The increasing diversity of fungal pathogens in high-risk patients, the differences in the antifungal spectra of available agents and the increasing rates of resistance call for identification of the infecting isolate at the species level and for information on drug resistance, in order to provide state-of-the-art patient care. Microscopy and culture of appropriate specimens remain the reference standard for mycological diagnosis, despite difficulties in obtaining appropriate and/or sufficient specimens, long durations of culture and false-negative results. Modern imaging studies and detection of circulating fungal cell wall components and DNA in blood and other body fluids or in affected tissues may improve the laboratory diagnosis of invasive mycoses.

A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT.

We compared the efficacy and safety of empirical plus PCR-based vs empirical liposomal amphotericin B treatment after Allo-SCT. Allo-SCT recipients were randomized to receive either PCR-based preemptive therapy (group A; n=198) or empirical antifungal therapy (group B; n=211) with liposomal amphotericin B. In group A, therapy was started after one positive PCR result or after 120 h of febrile neutropenia refractory to broad-spectrum antibacterial therapy. In group B, liposomal amphotericin B was started after 120 h of refractory febrile neutropenia. Demographic and clinical characteristics were well balanced. A total of 112 (57.1%) patients in group A and 76 (36.7%) patients in group B received antifungal therapy (P<0.0001). Twelve patients in group A and 16 patients in group B developed proven invasive fungal infection (IFI). Survival curves showed better survival until day 30 when close PCR monitoring was performed (mortality 1.5 vs 6.3%; P=0.015), but there was no difference at day 100. At day 100, no difference was observed in the incidence of IFI (primary end point) and survival between the two arms. Further studies are required to assess the benefit of using PCR in patients after SCT.

Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients.

BACKGROUND: The administration of high-dose interleukin-2 (IL-2) seems to be a therapeutic option for children with refractory and metastatic solid malignancies. METHODS: We prospectively studied treatment-related toxicities, quality of life and laboratory parameters in 10 children with progressive or metastatic solid tumors (metastatic osteosarcoma, n=4; neuroblastoma stage IV, n=3; metastatic Ewing's sarcoma, n=2; metastatic Wilms' tumor, n=1) during IL-2 therapy. Patients were scheduled to receive five cycles of high-dose IL-2 by continuous infusion for 5 days every 3 weeks. RESULTS: All patients developed fever >39 degrees C and influenza-like symptoms, with a significant decrease in Karnofsky score. In two patients treatment had to be stopped after three cycles because of severe side-effects. During IL-2 therapy a statistical significant increase in white blood cells (WBC), creatinine, gamma-glutamyltransferase, C-reactive protein, glucose and body weight was observed. In contrast, red blood cells, platelets, protein, albumin and cholinesterase significantly decreased. When results from day 1 of the first and of the fifth cycle were compared, an increase of WBC and a decrease of alkaline phosphatase was shown. No constant quantitative changes in total lymphocytes and subsets were observed during IL-2 therapy. CONCLUSIONS: IL-2 treatment in children with refractory and relapsed solid malignancies is associated with severe, but reversible, side-effects. However, five of the 10 patients with diseases of worst prognosis could be rescued by this treatment.

Procalcitonin--a marker of invasive fungal infection?

Procalcitonin (PCT) has been described as a marker of bacterial sepsis. However, little is known of its diagnostic value in fungal infections. We calculated the sensitivity of PCT for detection of invasive fungal infections (IFI) by analyzing 55 episodes of proven or probable IFI (three in our series, 52 reported in the recent literature). In the early phase of IFI, PCT was elevated in fewer than half of invasive candidiasis episodes and in only one patient (5.3%) with invasive aspergillosis. Due to low sensitivity and specificity, PCT adds little to the diagnosis of IFI.

High-risk AML complicated by pulmonary aspergillosis: successful treatment with nonmyeloablative stem cell transplantation and long-term administration of voriconazole.

Acute myeloid leukemia (AML) associated with central diabetes insipidus (DI) and chromosomal aberrations is characterised by a very poor prognosis. We present a 28-year-old female with AML FAB M0, preceding DI and cytogenetic abnormalities (monosomy 7 and inversion of chromosome 9). Complete remission was achieved with FLAG after she was refractory to two different induction regimens. Prolonged neutropenia resulted in invasive pulmonary aspergillosis. Allogeneic stem cell transplantation from a matched unrelated donor was performed using a reduced-intensity conditioning regimen. Desmopressin substitution for DI was withdrawn after transplant without recurrence of symptoms. Initial antifungal treatment, including liposomal amphotericin B, caspofungin and itraconazole, was replaced by voriconazole after deterioration of pulmonary aspergillosis, resulting in improvement, stabilisation and finally, also as the combined effect of discontinuation of the immunosuppressive therapy, in disappearance of signs and symptoms. Thirteen months after transplant, the patient is in continuous complete remission. The presented case study thus demonstrates that high-risk AML with concomitant invasive fungal infection may be safely and effectively treated by nonmyeloablative stem cell transplantation and long-term administration of voriconazole.

Procalcitonin and C-reactive protein do not discriminate between febrile reaction to anti-T-lymphocyte antibodies and Gram-negative sepsis.

Treatment with antibodies against T-lymphocytes usually triggers a febrile response potentially mimicking or masking infection. Procalcitonin (PCT) is considered a sensitive and specific marker of systemic bacterial and fungal infection. It was the aim of this study to investigate the characteristics of PCT and C-reactive protein (CRP) during treatment with polyclonal or monoclonal anti-T-cell antibodies, in order to examine the ability of these parameters to distinguish between systemic bacterial infection and reaction to antibody treatment. Thus, 15 consecutive febrile episodes after T-cell antibody infusion without clinical signs of infection were compared with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gram-negative sepsis. Therefore, during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release.

Tunneled femoral central venous catheters in children with cancer.

OBJECTIVE: We discuss the feasibility of long-term femoral venous access by means of a cuffed subcutaneously tunneled central venous catheter (Broviac catheter) in selected pediatric cancer and stem cell transplant patients in whom access via the veins of the upper part of the torso is difficult or contraindicated and in whom alternative routes must be used. PATIENTS AND METHODS: We report on our experience with 9 patients (3 of whom underwent stem cell transplantation) who received femoral Broviac catheters between December 1990 and November 1999. Results. Time in place ranged from 4 to 155 days with a median of 58 days (mean: 71.2 days). Three catheters had to be removed: 1 because of infection of the subcutaneous tunnel and 2 because of catheter obstruction. The remaining 6 catheters functioned well without problems as long as they were needed; 1 of them got accidentally dislodged while the patient was off treatment. No episodes of catheter-related septicemia, thrombosis, kinking, or drug extravasation were noted; there were no catheter-related infectious complications in the transplant patients. CONCLUSIONS: Our experience indicates that in those instances in which customary access to the superior vena cava is precluded, long-term venous access by way of the femoral vein is a feasible and safe alternative in children, even in the setting of stem cell transplantation.

Cytomegalovirus diagnosis in renal and bone marrow transplant recipients: the impact of molecular assays.

BACKGROUND: Cytomegalovirus (CMV) infections are a major threat in transplant recipients. In recent years, new assays for routine CMV diagnosis, based on molecular techniques, have become available. OBJECTIVE: The impact of molecular assays for CMV diagnosis in transplant recipient was evaluated. STUDY DESIGN: A total of 51 transplant recipients were screened for CMV infection. Serological (AxSYM CMV IgG and recombinant CMV IgM assays), antigenemia, CMV DNA (qualitative in house PCR and the quantitative COBAS AMPLICOR CMV MONITOR Test), and CMV mRNA (NucliSens CMV pp67 Test) tests were compared. RESULTS: In 11/20 bone marrow transplant (BMT) recipients and 10/31 renal transplant (RTX) recipients there was no evidence of active CMV infection. Ten RTX recipients and one BMT recipient were antigenemia positive, 21 RTX and seven BMT recipients were PCR positive (qualitative CMV PCR). There were more BMT recipients CMV DNA positive in serum (7/21) than antigenemia positive (1/21). CMV mRNA was found positive in two BMT recipients (one case with no other evidence of CMV infection, the other one CMV DNA positive and antigenemia negative). The only antigenemia positive BMT recipient was found negative for CMV mRNA, but positive in all other tests. Eight RTX recipients were found positive for CMV mRNA. Six of them were also antigenemia positive and five of those were also found positive for CMV IgM. One CMV mRNA positive RTX recipient was CMV IgM positive but antigenemia negative and the other one CMV mRNA positive RTX recipient was found negative in all other tests. Two antigenemia positive RTX recipients were found negative for mRNA and CMV IgM. CONCLUSION: Antigenemia was found to be a good screening test for CMV infection in RTX recipients. In BMT recipients, tests based on molecular techniques appeared to be superior compared to antigenemia.

Interferon-alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy.

OBJECTIVE: Chronic hepatitis C is a major long-term problem for children who survive cancer. Interferon (IFN)-alpha has been shown to be effective in treating patients with chronic hepatitis C; however, the rate of sustained response is low. Combining IFN-alpha and ribavirin (RBV) has been shown to significantly improve the response in adult patients with chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and safety of a combined virostatic treatment with IFN-alpha and RBV in a small cohort of children and adolescents with chronic hepatitis C and previous malignancy. METHODS: Twelve patients with a history of a hematooncologic disease (median follow-up: 13.5 years; range: 7-14.7 years) and chronic hepatitis C were treated with recombinant IFN-alpha-2a (6 megaunits/m(2) body surface area, 3 times a week, subcutaneously) combined with RBV (15 mg/kg body weight/day, orally) for 12 months. They were tested monthly for blood counts and liver function, and for serum virus concentrations (hepatitis C virus RNA by polymerase chain reaction) every 3 months. RESULTS: At the end of the treatment, hepatitis C virus RNA could not be detected in the serum of 8 of the 12 patients; 2 of these patients relapsed soon after therapy withdrawal, whereas 6 patients maintained in sustained virologic and biochemical remission (follow-up: 12 months). Treatment-induced toxicity was moderate and reversible with influenza-like symptoms and a decrease in blood counts in all 12 patients, alopecia in 5 of the 12, hemolysis in 4 of the 12, and weight loss of >10% in 2 of the 12. CONCLUSIONS: As demonstrated in adults with chronic hepatitis C, treatment with IFN-alpha and RBV also seems to be an effective and safe therapeutic option for children and adolescents with chronic hepatitis C after malignancy.

Hypernasality--a rare initial symptom of a cerebellar astrocytoma.

Nasality is a disorder due to nasal resonance, which may be induced by a variety of etiologies. Transitional hypernasality is frequently seen in children after adenoidectomy. The alleged post-surgical hypernasality in the case presented was shown to be related to the late detection of an astrocytoma of the cerebellum and the brain stem in a 6-year-old boy. This case was characterized by increased hypernasality which failed speech therapy. A developing one-sided vocal fold palsy in combination with an ipsilateral soft-palate palsy indicated further investigation. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a brain stem-tumor with a maximum size of 6 cm involving parts of the cerebellum. These findings demonstrated the need for a strict follow-up, even after adenoidectomy, in the presence of hypernasality for identifying concurrent etiologies as well as cases suitable for speech therapy.

Unrelated partially matched peripheral blood stem cell transplantation with highly purified CD34+ cells in a child with Wiskott-Aldrich syndrome.

Stem cell transplantation is the only curative approach to the treatment of Wiskott-Aldrich syndrome. However, using grafts from partially matched unrelated donors is associated with increased risk of graft rejection and graft-versus-host disease. In an attempt to prevent these problems, a 6-year-old boy with Wiskott-Aldrich syndrome lacking a suitable family donor, was transplanted with large numbers of unrelated highly purified CD34+ peripheral blood stem cells mismatched at one C locus. Conditioning consisted of busulfan 16 mg/kg body weight, cyclophosphamide 200 mg/kg body weight and antithymocyte globulin 20 mg/kg body weight x 3 days. The boy had a rapid hematopoietic engraftment and showed immunologic reconstitution by day +92. Although he did not receive prophylactic immunosuppression he did not develop any graft-versus-host disease and is well and alive up to now, 25 months after transplantation.

Unrelated peripheral blood stem cell transplantation with 'megadoses' of purified CD34+ cells in three children with refractory severe aplastic anemia.

Three children with refractory severe aplastic anemia were transfused with high numbers of unrelated matched (n = 2) or C-locus haploidentical mismatched (n = 1) CD34-selected peripheral blood stem cells in the absence of an HLA-identical family donor. Two leukaphereses of the donors yielded a median number of 10.1 x 10(10) nucleated cells (range 9.7-15.4) with a median number of 9.89 x 10(8) CD34+ cells (range 7.46-26.1) and a median percentage of CD34+cells of 0.98% (range 0.77-1.7). After positive selection by magnetic cell sorting the patients received a median of 14.3 x 10(6) CD34+ cells/kg (range 11.7-24.3) and of 1.3 x 10(4) CD3+ cells/kg (range 0.57-5.8). Median time to ANC >/=0.5 x 10(9)/l was 7 days (range 7-12) and to platelets >/=20 x 10(9)/l 13 days (range 13-27). Chimerism analysis of peripheral blood after transplantation revealed permanent 100% donor hematopoiesis in all patients. The patient with the C-locus haploidentical mismatch presented with acute GVHD (grade III-IV) of the skin, liver and lower gastrointestinal tract (onset day +40) and died despite intensive immunosuppressive treatment on day +238. The two survivors developed lymphopoietic recovery of B and T lymphocytes within 3 months after transplantation. To our knowledge this experience represents the first report of transplantation with unrelated CD34+ enriched peripheral blood stem cell in children with refractory severe aplastic anemia. Bone Marrow Transplantation (2000) 25, 513-517.

Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a causal relationship?

Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection.

[Ureaplasma urealyticum pneumonia and isolation of U. urealyticum from endotracheal tube aspirates of preterm and full-term infants]. / Ureaplasmapneumonien und Nachweis von Ureaplasma urealyticum im Tubussekret bei Früh- und Neugeborenen.

OBJECTIVE: Our purpose was to investigate how many preterm infants with a birth weight 1,250 g with clinical symptoms had Ureaplasma urealyticum in their endotracheal tube aspirates, and how many of them had pneumonia. METHODS: The patients were divided into two groups (group 1: birth weight 1,250 g, n = 45), and these two groups were subdivided into two subgroups (subgroup a: U. urealyticum in aspirate without pneumonia; subgroup b: U. urealyticum in aspirate with pneumonia). RESULTS: In group 1, there were 25 patients. Nine patients (36%) had U. urealyticum in their aspirates, 5 patients (20%) had pneumonia (group 1b), and 4 patients (16%) did not (group 1a). Infants with pneumonia showed a significant increase in parameters of mechanical ventilation, in the duration of mechanical ventilation, and in the duration of oxygen dependence as compared with subgroup 1a. In group 2, there were 45 patients. Six patients of group 2 (13%) had U. urealyticum in their aspirates, 2 patients (4.4%) had a pneumonia (group 2b), and 4 patients (8.8%) did not (group 2b). CONCLUSIONS: In preterm infants as well as in term newborns one should consider U. urealyticum as a potential cause of neonatal pneumonia.

Unrelated 5/6-locus matched umbilical cord blood transplantation in a 23-month-old child with hemophagocytic lymphohistiocytosis.

A diagnosis of familial hemophagocytic lymphohistiocytosis (FHL) was established in an 18-month-old boy who presented with prolonged fever of unknown origin, severe pancytopenia, hepatosplenomegaly and hypofibrinogenemia. Serum levels of ferritin and soluble interleukin-2 receptor (SIL2R) were highly elevated, and the number of natural killer (NK) cells was markedly decreased. An allogeneic stem cell donor was neither found in the family nor in unrelated donor registries; however, an umbilical cord blood (UCB) donor request revealed a 5/6 HLA-matched UCB. After conditioning with busulphan 16 mg/kg body weight (BW), cyclophosphamide 120 mg/kg BW and etoposide (VP-16) 900 mg/m2 the patient received 19.6 x 10(7)UCB nucleated cells/kg BW. White blood count (WBC) reached 1.0 x 10(9)/l on day +45. Chimerism studies showed full and permanent hematopoietic and lymphopoietic engraftment on day +16. However despite full engraftment the patient still experienced two severe relapses of his disease after stem cell transplantation with the highest ferritin level in the range of 10 3967 microg/l (n = 7-142). NK cell function appeared only 6 months after UCB transplantation followed by a decrease of FHL markers and resolution of disease activity. This clinical outcome indicates that unless competent immunologic engraftment after transplantation is established, FHL is capable of relapsing even if complete three-lineage engraftment is achieved.

Treatment of invasive pulmonary aspergillosis in severely neutropenic children with malignant disorders using liposomal amphotericin B (AmBisome), granulocyte colony-stimulating factor, and surgery: report of five cases.

Five children with malignancies developed invasive pulmonary aspergillosis during chemotherapy-induced neutropenia. All patients were treated with liposomal amphotericin B and human recombinant granulocyte colony-stimulating factor. Two patients did not recover from bone marrow aplasia and died from organ-infiltrating fungal invasion. Two patients who recovered from bone marrow aplasia survived after surgery of the pulmonary lesions. The fifth patient had a complete resolution of invasive pulmonary aspergillosis after neutrophil recovery without surgical intervention. We conclude that not only the antifungal treatment but also the recovery of granulocytes are important in localizing invasive forms of Aspergillus infections in patients with profound immunosuppression.

Tick-borne encephalitis in a 3-month-old child.

Tick-borne encephalitis has not been reported in infants younger than 12 months of age. We report a 3.5-month-old child with a serologically proven tick-borne encephalitis. The infant had a history of a tick bite 3.5 weeks before the first symptoms of encephalitis appeared. The family lives in an endemic area of the disease. There were no prodromal signs and the course of the disease was monophasic. In an endemic area, prophylactic treatment with hyperimmunoglobulin after a tick bite should be considered even in very young infants, but in most children active immunization is probably not necessary because of infrequent exposure. Active immunization is still recommended after the 1st year of life.