Selection for and initiation of continuous subcutaneous insulin infusion. Proceedings from a workshop

Continuous subcutaneous insulin infusion (CSII) has been used in the paediatric age group for more than 20 years. The technique is not yet widely used in most countries but there has recently been increasing interest in pump therapy for young children and adolescents. In 1999, 7.5% of Swedish children and adolescents with diabetes used pumps, now the figure is approaching 12%. The indication for starting pump therapy has usually been a medical problem, but today quality of life issues are becoming increasingly important. One technique sometimes used is to start CSII by wearing the pump only at night. Daily insulin requirements are usually decreased compared with injection therapy. Studies have shown that it is possible to lower HbA1c when using an insulin pump and that the risk of severe hypoglycaemia can be lowered. The use of CSII has also been successful in preventing recurrent admission for diabetic ketoacidosis. While starting pump therapy does take an extra effort from both the diabetes team and the family, routine visits are generally no more time-consuming than for patients on multiple injection therapy. CSII can be initiated during admission to hospital but most pumps are started on an outpatient basis. Our department has the patients on the day care ward for 3-4 days of 'pump school'. Parents wear a saline pump for practice. The total daily insulin dose is usually lowered 15-20% compared with multiple injections; on average 40-50% (sometimes up to 60%) of the daily dose is given as basal rate. We start all pumps on rapid-acting analogues and use 40 IU/ml if the basal rate is <0.3 IU/h. In conclusion, the use of CSII in children and adolescents is well accepted and can be managed safely.     

Iron overload in paediatrics undergoing cardiopulmonary bypass

Pathological changes in iron status are known to occur during bypass and will be superimposed upon physiological abnormalities in iron distribution, characteristic of the neonatal period. We have sought to define the severity of iron overload in these patients. Plasma samples from 65 paediatric patients undergoing cardiopulmonary bypass (CPB) were analysed for non-haem iron, total iron binding capacity, transferrin and bleomycin-detectable iron. Patients were divided into four age groups for analysis. Within each age group, patients who were in iron overload at any time point were statistically compared to those who were not. The most significant changes in iron chemistry were seen in the plasma of neonates, with 25% in a state of plasma iron overload. 18.5% of infants and 14.3% of children at 1-5 years were also in iron overload at some time point during CPB. No children over 5 years, however, went into iron overload. Increased iron saturation of transferrin eliminates its ability to bind reactive forms of iron and to act as an antioxidant. When transferrin is fully saturated with iron, reactive forms of iron are present in the plasma which can stimulate iron-driven oxidative reactions. Our data suggest that paediatric patients are at greater risk of iron overload during CPB, and that some form of iron chelation therapy may be advantageous to decrease oxidative stress.     

Results of polychemotherapy and immunotherapy in acute leukemias]

For the purpose of evaluating the efficiency of an unspecific immunostimulation in acute leukaemias the results of treatment obtained from two groups of patients (a total of 55 children) were compiled. In the first group an unspecific immunostimulation with vaccination (BCG, diphtheria-tetanus-pertussis, measles) could be observed after the induction of remission during a cytostatic maintenance therapy. In the second group a polychemical therapy and the CNS-irradiation was applied according to the treatment scheme developed by the working team of Donald Pinkel. The group of patients treated with unspecific immunostimulation involved a high percentage of surviving children. In total there was no essential difference between the treatment results of both schemes of therapy during our period of observation. As before, the treatment of hyperleukocytic forms of leukaemias will cause particular difficulties.     

Leukemic chromosome clone. I. Risk factor in the acute lymphatic leukemia of children]

As long as the aetiology of acute lymphatic leukaemia of children is not known its therapy is based on clinical experience. Among the values of experience those factors will play a part, the evidence of which during the ALL initial stage will be a risk for successful therapy and survival rate. This results in a choice of more aggressive variants of modern therapy schemes. In a cytogenetic study made in 35 children with ALL it was tested, whether even leukaemic chromosome clones will be a risk for the course of acute leukaemia. The duration of the first remission and survival rate were considered as criteria. The evidence of a leukaemic chromosome clone could be shown to be followed by a short survival rate, irrespective of the stage of the disease where the clone had been observed first. Thus, cytostatic therapy in those ALL patients who are affected with luekaemic chromosome aberration of stem line character should be aimed at the complete annihilation of the clone, irrespective of other remission criteria. The failure of blood and bone-marrow cultures as early as during the untreated initial stage indicated a primary cellular immuno-insufficiency. This combination of cell immuno-depression with high peripheral leukocytes connts and a primary mediastinal tumour or a generalizing lymphosarcoma respectively, was the highest risk up till now for the course of the disease. Judging from the duration of the first remission and the survival rates, the consecutive schemes of therapy did not differ in their effect on leukaemia with pathological stem lines. On the basis of the present study the impression could not be excluded that up till now long term survival rates could be attributed rather to individual manners of response than to the modern therapy scheme.     

Evaluation of joint flexibility and cardiovascular efficiency in children and adolescents with haemophilia and their healthy peers

BACKGROUND: Problems concerning treatment of patients with haemophilia are long-term and exist even in the present days. Thanks to interdisciplinary complex therapy the results of treatment are constantly better than many years ago. AIM: The goal of this study is to analyse the current state of management of haemophilia and to suggest a comprehensive concept of rational and effective rehabilitation of children with haemophilia. METHOD: In the clinical study, two different measurements were used (goniometry and functional step test) and a special questionnaire. Four different groups of participants were created for the clinical measurements (a set of patients and a control group) and for the questionnaire (a set of patients and a control group). RESULTS: This study concluded that there were no significant differences in the outcomes of the goniometry and the step test, and in the restriction of movement activities between the patients and healthy individuals. CONCLUSIONS: The concept of physiotherapy in patients with coagulopathies in the Czech Republic is comparable with rehabilitation concepts in other European and non-European countries. Current rehabilitation care is of good quality and necessary for effective lifelong therapy of haemophilia, however, it is used insufficiently.     

Psychologische Aspekte des Diabetes in Kindheit und Adoleszenz

The intensified insulin therapy of type 1 diabetes imposes considerable demands in everyday life of children, adolescents and their families that often interfere with normal developmental tasks. Accordingly current guidelines on paediatric diabetes stated that psychosocial factors are the most important influences affecting the care and management of the chronic illness. This article reviews the main research findings from studies on psychological coping, family burden and dynamics, neurocognitive functioning, stress, psychosocial risk factors, psychological health and psychiatric disorders. In addition psychological support, age-appropriate educational and behavioural interventions as an integral part of every type 1 diabetes long-term therapy are described. Finally the vital role and the current situation of psychologists and social workers as members of the interdisciplinary paediatric diabetes teams especially in the context of the German Disease –Management Program for type 1 diabetes are discussed.     

Acute thyroiditis in a child: misleading result of fine-needle aspiration biopsy

We report a case of acute thyroiditis in a 6-year-old girl, whose initial borderline clinical and sonographic data, coupled with the absence of leucocytes and bacteria on the fine-needle aspiration biopsy, led to the reversal of the initial diagnostic impression of acute thyroiditis and the institution of an inappropriate glucocorticoid treatment. Since both diseases are rare in the paediatric age group and therapy is completely different, we conclude that in borderline cases careful clinical observation and the response to the initial antibiotic therapy should be considered more reliable than any single morphologic or microbiologic result. We also suggest that acute bacterial thyroiditis could be usefully classified into two forms, suppurative and non-suppurative.     

Head Injuries in Children

Two-hundred children with head injury admitted consecutively to paediatric wards in the two main hospitals in Newcastle upon Tyne have been studied. Eight children required neurosurgical operation. There were two deaths. Details of the cause and consequences of the accidents have been analysed and an attempt has been made to identify psychological or physical factors that may predispose to injury. There was a slightly higher proportion of children with what are regarded as adverse personality factors among the head injuries than in a control group and there were more left-handed children than would be expected in the general population. The results suggest that the modern “high-rise” bicycle may carry a special risk of head injury.     

Healthcare without borders: A cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng Province of South Africa

BackgroundHuman migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been noted in their healthcare provision.The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA.Methods and findingsA cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility.ConclusionsAlthough there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.     

On the clinical importance of Dientamoeba fragilis infections in childhood

Clinical and laboratory findings among 123 paediatric patients infected by intestinal protozoa were analysed. Dientamoeba fragilis (D. f) was found in 102 cases. The other patients proved to be carriers of Giardia lamblia or of mixed infections with several protozoa. Acute and recurrent diarrhoea have been found to be the most common symptoms, whereas abdominal pain was most common in children with chronic infections. Peripheral blood eosinophilia was seen in a third of the children with dientamoebiasis. Metronidazole, oxytetracycline, doxycycline, and erythromycin were effective drugs in the treatment of D. f. infections. The therapy coincidentally led to the elimination of protozoal infections as well as the abdominal complaints. These results underline the pathogenic role of D. f. in children with gastrointestinal symptoms.     

Tolerance,safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: A prospective,open, multicentre postmarketing study in 9657 patients

In this postmarketing study 9657 patients (5181 children) with bronchitis (acute or chronic bronchial inflammatory disease) were treated with a syrup containing dried ivy leaf extract. After 7 days of therapy, 95% of the patients showed improvement or healing of their symptoms. The safety of the therapy was very good with an overall incidence of adverse events of 2.1% (mainly gastrointestinal disorders with 1.5%). In those patients who got concomitant medication as well, it could be shown that the additional application of antibiotics had no benefit respective to efficacy but did increase the relative risk for the occurrence of side effects by 26%. In conclusion, it is to say that the dried ivy leaf extract is effective and well tolerated in patients with bronchitis. In view of the large population considered, future analyses should approach specific issues concerning therapy by age group, concomitant therapy and baseline conditions.     

Excess benign melanocytic naevi after chemotherapy for malignancy in childhood.

OBJECTIVE--To see whether children who have had chemotherapy develop increased numbers of moles. DESIGN--Blind assessment of patients having chemotherapy and subsequent comparison with the first suitable patients matched for age and sex who were attending the clinic during the same period after having completed treatment. Controls were obtained the following year by taking the first suitable patients attending a routine dermatology outpatient clinic who matched the study groups for age and sex. SETTING--Referrals to a paediatric oncology clinic and a dermatology clinic at two city hospitals. PATIENTS--The group receiving chemotherapy comprised all 32 patients with acute lymphatic leukaemia, lymphoma, and rhabdomyosarcoma who were attending the paediatric oncology clinic on two mornings a week during October 1987 to March 1988. The group who had completed treatment comprised 32 patients who were attending for follow up during the same period and who matched the first group for age and sex. Thirty two other patients attending the dermatology outpatient clinic with unrelated skin conditions served as controls. END POINT--Definite increase in numbers of moles on children after a course of chemotherapy. MEASUREMENTS AND MAIN RESULTS--Moles were counted by one observer on defined areas of the body and divided into those less than 3 mm and greater than or equal to 3 mm diameter. Patients receiving chemotherapy had a similar number of moles to the control group. By contrast patients who had completed chemotherapy had significant increases both in moles less than 3 mm and greater than or equal to 3 mm and in the total number of moles. These patients were more likely to have moles on acral sites. CONCLUSIONS--Children with substantially increased numbers of moles (benign melanocytic naevi) after successful chemotherapy for malignancy may have an increased risk of melanoma. They should be offered prolonged surveillance and cautioned about exposure to ultraviolet light.     

Anthelmintics as a risk factor in intestinal obstruction by Ascaris lumbricoides in children]

In a retrospective study the authors analyzed the clinical records of 199 children ages one month to 16 years hospitalized, with the diagnosis of intestinal ascariasis, in the Instituto Nacional de Pediatria of Mexico from 1984 to 1999. The purpose of the study was to evaluate the use of anthelmintics drugs as a risk factor of intestinal obstruction by A. lumbricoides. Two groups were made for the study: Group A (n = 66) of children who presented intestinal obstruction, Group B (n = 133) children with no complications. A comparative analysis of clinical data of both groups was made by means of chi square with Yates correction and a stratified analysis by means of chi square. Possible confusing elements were overcrowding, age and the use of antiparasitic drugs. The calculus of risk factors for intestinal obstruction by A. lumbricoides was done by means of contingency tables of 2 x 2 and odds ratio with an IC of 95%. The significant risk factors were included in a model of logistics regression with an impact variable consting in the presence or absence of intestinal obstruction in order to establish a multivariate model of predictive risk at level of significance of p < 0.05. Twenty-seven patients (40.90%) in group A (n = 66) were given anthelmintics medications prior to the intestinal obstruction: mebendazol, 14 (51-85%); two, albedazol (7.4%); eight, a non-specified anthelmintic (29.6%). In addition, an anthelmintic medication without a specified time of ingestion: two with mebendazol and one with piperazine (11.3%). In the case of mebendazol, the drug most frequently associated with intestinal obstruction, seven patients received it on the same day of the obstruction; five patients received it between one and seven days prior to the obstruction; two received it seven days prior to the complication. In the control group, only 7% had taken the anthelmintic one to seven days before the diagnosis of uncomplicated intestinal ascariasis diagnosis was made. With the step by step (Backward) logistic regression conditioned by the treatment variable with an anthelmintic, an X2 = 38.15 gl, p < 0.000 was obtained for which reason it was considered by A. lumbricoides. Of the probable risk factors analyzed in this study, the only one capable of influencing and predicting the presentation of intestinal obstruction by A. lumbricoides in children, was the prior anthelmintic treatment particularly with mebendazol.     

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. METHODS: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. CONCLUSIONS: The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Trial registration Clinicaltrials.gov Identifier NCT01046942.     

Diabetes mellitus following paediatric renal transplantation: a single centre experience

BACKGROUND/AIMS: Post-transplant diabetes mellitus (PTDM) has a variably reported incidence of 4-41% among adults and children. We describe our recent experience of four children with PTDM in a paediatric renal transplantation centre. METHODS: We undertook a retrospective analysis of the glycaemic status of all paediatric patients undergoing renal transplantation at our centre in the 2-year study period. The clinical features and investigations of those who developed PTDM were further reviewed. RESULTS: Five episodes of PTDM occurred in 4/32 children. There was a variable onset and a wide range of symptoms. Investigations revealed a combination of insulinopenia with peripheral insulin resistance. Insulin therapy was required for variable durations with resolution of PTDM in four episodes. PTDM did not adversely affect the renal graft function. CONCLUSION: PTDM requires increased awareness among paediatric nephrologists and endocrinologists for early recognition and prompt effective intervention.     

Paediatric Drug Development and Formulation Design—a European Perspective

The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize “better” medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the “Guideline on the Pharmaceutical Development of Medicines for Paediatric Use.” Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline’s key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.     

Rapid assay for antibodies to Varicella-Zoster virus (VZV) using a VZV-HEM preparation

A freeze-dried, formalized-erythrocytes-bound VZV antigen for indirect haemagglutination, VZV-HEM, was prepared. It was used to test serologically 46 children, all of them patients of Prague paediatric clinics, with a known history of chickenpox. For comparison, the same sera were tested by the indirect haemagglutination reaction with freshly prepared VZV antigen and by ELISA. All three serological tests gave congruent results in 97.8% of cases. The advantages of the VZV-HEM assay are results obtainable within 2 hours of serum dilution and simplicity. The assay is especially suitable for emergency testing the immunity of persons at risk.     

Failure of sequential therapy to eradicate Helicobacter pylori in previously treated subjects

BACKGROUND: Recently, studies in adults and subsequently in children have demonstrated a very high success rate for sequential therapy as a primary therapy when compared to traditional therapy regimens. METHODs: We report our experience with a sequential therapy regimen for the eradication of Helicobacter pylori in five infected children and a young adult, whose conventional therapy regimens had been unsuccessful. RESULTS: Five patients failed the sequential therapy. All of them experienced between two and four failures of traditional therapy prior to the sequential treatment protocol. The only patient who succeeded on the sequential therapy had just one previous failure. All of our patients who had failed sequential therapy achieved eradication of the bacteria with quadruple therapy. CONCLUSIONS: In view of our disappointing results, sequential therapy is unsuccessful as a therapy for children and young adults who have failed previous treatment regimens. At the present time, quadruple therapy is indicated for this group. Well-designed placebo-controlled trials are indicated to further characterize this group of patients.     

Henoch schonlein purpura--a 5-year review and proposed pathway

Henoch Schonlein Purpura (HSP) is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition.A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year) and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression) was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5) years vs. normal outcome 6.0 (3.7-8.5) years; p<0.01). A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99%) negative predictive value in predicting a normal renal outcome.Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources.The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials.