Treatment intensification without improved HbA1c levels in children and adolescents with Type 1 diabetes mellitus.

AIMS: To examine trends in diabetes treatment in Danish children and adolescents with Type 1 diabetes mellitus, comparing treatment intensity with metabolic outcomes in the population, and to describe the challenges of population-based registries in a clinical setting with rapidly changing treatment methods. METHODS: This observational study is based on the Danish national population registry of childhood diabetes, which includes 99% of children diagnosed with Type 1 diabetes before the age of 15 years. We included 4527 people diagnosed between 2000 and 2012. Self-monitored blood glucose measurements, insulin injections/boluses, treatment method and metabolic control quantifications were analysed and adjusted for the effects of gender and ethnicity, the combined effect of age, visit year and duration, and for the random effects of individual and hospital settings. RESULTS: Treatment was intensified via an increasing number of self-monitored blood glucose measurements and injections/boluses. More than six injections/boluses and an increased number of self-monitored blood glucose measurements were significantly associated with lower metabolic control. No reduction, however, in the overall mean HbA1c concentration was observed between 2005 [66 mmol/mol (8.2%)] and 2012 [65 mmol/mol (8.1%)]. Changed registration practices in 2009 introduced artificial jumps in data. CONCLUSIONS: Intensifying treatment alone does not lead to improved metabolic control in the overall population despite the appearance of lower HbA1c in individuals with a greater number of self-monitored blood glucose measurements and injections/boluses. The contradictory results reflect difficulties in using observational studies to predict results of intervention in the individual. Data collected from population-based registries need to be adjusted continuously to reflect changes in care.

Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes.

OBJECTIVE: To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities. RESEARCH DESIGN AND METHODS: The study is based on data from DanDiabKids, a national diabetes register for children and adolescents. The register contains data on patients with type 1 diabetes with an ascertainment rate of 99%. Data from 3320 patients aged 0-18 yr was included in the study period from 1998 to 2009 and analyzed using a negative binomial model. RESULTS: One thousand nine hundred and ninety-nine episodes of severe hypoglycemia in 867 patients were registered conferring an overall incidence of severe hypoglycemia of 15.1 [95% confident interval (CI): 13.8; 16.4] per 100 patient years. This remained unchanged during the study period. Duration of diabetes, age and treatment in centers managing less than 100 patients significantly increased the risk of severe hypoglycemia (p < 0.001). Patients on insulin pump therapy had a 42% reduced risk of severe hypoglycemia compared with pen treated patients (p = 0.01). Patients treated with five or more daily insulin injections had a 31% (95% CI: 17; 49) reduced risk of severe hypoglycemia compared to patients on fewer daily injections (p = 0.015). CONCLUSIONS: Despite improvements in metabolic control over a decade the prevalence of severe hypoglycemic events remained unchanged. More intensive treatments such as insulin pump therapy and multiple daily injections on a national level seems to be a protective factor for developing severe hypoglycemia up to 2009.

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels.

AIMS/HYPOTHESIS: We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes. METHODS: The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996-2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods. RESULTS: The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA1c (%) levels (0.24; 95% CI 0.11, 0.36; p = 0.0003) and increased insulin dose-adjusted HbA1c (IDAA1c, 0.51; 95% CI 0.31, 0.70; p < 0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p < 0.0001); however, these children had a lower HbA1c (%) level over time (-0.35; 95% CI -0.46, -0.24; p < 0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA1c, changing the effect of DKA, after adjustment for covariates (p < 0.0001). CONCLUSIONS/INTERPRETATION: DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA1c and IDAA1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.

Reflex effects of aerosolized histamine on phrenic nerve activity.

Studies were conducted in anesthetized, paralyzed dogs on the effect of aerosolized histamine on phrenic nerve activity. The paralyzed dogs were ventilated in phase with their recorded phrenic nerve activity at a constant inspiratory flow-rate, using a cycle-triggered ventilator. Phrenic nerve activity was measured before and during administration of aerosolized histamine while the inspiratory flow-rate and arterial blood gases were kept constant. In addition, before and after histamine, phrenic nerve activity was recorded for single bursts during which the ventilator was switched off. The effects of histamine on respiratory resistance were prevented by prior administration of isoproterenol and atropine. Although no changes occurred in respiratory resistance, histamine increased the instantaneous magnitude of phrenic nerve activity. The effect was evident early in the inspiratory period and was found even when the lungs were not inflated. Inflation of the lungs excited phrenic nerve activity; this effect increased after histamine. All of these actions of histamine were abolished by vagotomy. We conclude that histamine increased phrenic nerve activity during inspiration by a vagal reflex.

Acuity card testing of retarded children.

Evaluating the vision of retarded children is important, but it is often very difficult because the children cannot cooperate with the usual symbol recognition acuity tests. A total of 33 unselected children with Down's syndrome were tested with a standard symbol recognition test (Osterberg) and with a new test using acuity cards, which contain black and white square-wave gratings. The acuity cards were found to be useful for testing this group, both in terms of the children's ability to cooperate with the test and the test-retest variability of the results. Although eyes with strabismic amblyopia showed better acuity for gratings than for symbols, there was general agreement with symbol recognition acuities of the same patients. Acuity cards were also used to test 19 severely retarded young children with cerebral palsy, who were unable to be tested with symbols. Acuity card tests were almost always possible with this group, too, though test-retest variability was greater for these children. Acuity card testing can provide useful information about the visual acuity of many retarded children in less than 10 minutes.

Acuity card testing of spastic children: preliminary results.

Acuity card testing of spastic children showed a high success rate. Agreement between repeated tests for children with mild motor handicaps was within the limits reported for non-handicapped children. Although more of the children with severe motor handicaps had greater test-retest variabilities, the majority of results from this group also showed an acceptable agreement. The high success rate and good test-retest agreement indicate that acuity cards can be very useful for testing children with cerebral palsy, who often have reduced acuity.

Fungal Parasites of the Cereal Cyst Nematode Heterodera avenae in Southern Sweden.

Fungal parasites of the cereal cyst nematode Heterodera avenae were isolated from four sites in southern Sweden. In all, 15 different fungi were isolated from different stages of the nematode life cycle. Among the egg parasites, Verticillium chlamydosporium was common in young cysts on roots, whereas an unidentified species of Verticillium (Verticillium sp. 1) was the dominating species in cysts from soil, especially if the soll had been stored for 8-12 months. V. chlamydosporium was frequently isolated from eggs in cysts from soil, when analyzed shortly after sampling. Verticillium sp. 1 is distinct from V. chlamydosporium because it does not produce dichtyo-chlamydospores in the aerial mycelium and because it grows at 6 C where V. chlamydosporium fails to grow. Paecilomyces lilacinus, Microdochium bolleyi, Cylindrocarpon sp., and several nonsporulating fungi were also isolated from eggs in cysts from soil. Between 10 and 20% of the eggs in cysts collected in the field were infected with fungi. In a pot test between < 1 and 29%, with a mean of 13%, of females on roots became infected, always by Nematophthora gynophila. Resting spores of N. gynophila extracted directly from field soil, collected at the four sites, varied from 3 to 49 spores/gram of air dried soil.

[Prognosis of children with very low birth weight in the county of Viborg. A follow-up of an unselected patient group]. / Prognosen for børn med meget lav fødselsvaegt i Viborg amt. Efterundersøgelse af en uselekteret patientgruppe.

Neonatal mortality and follow-up examination among children with birthweight < or = 1500 g born in the period 1983-1987 inclusive has been recorded in an unselected material from a Danish county (Viborg County). There were 100 with birthweight < or = 1500 g and the low-birthweight rate was 7/1000. The neonatal survival was 72% dispersed with 32% for children with birthweight < or = 1000 g and 90% for children with birthweight 1001-1500 g. Four children died before follow-up examination. Of the surviving 68 children 66 were examined between the ages 21 months to six and a half years, the average age being about three years. The test-results were based on a questionnaire to the parents, an objective examination including neuropaediatric assessment and a Denver developmental screening test. Seven children were found to have moderate to severe handicaps, equal to 10% of surviving children. Of these seven children, three (4.5%) have cerebral paresis. Five other children were found to have small "handicaps". In conclusion 12 children or 18% had varying degrees of disability while 54 children were without demonstrable disability at follow up examination.

[Exercise-induced asthma in children and oral terbutaline. A dose-response relationship study]. / Anstrengelsesudløst astma hos børn og oral terbutalin. Et dosis-respons-studie.

We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate in 17 asthmatic children aged 6-12 years (mean 9 years). Placebo, 2, 4, and 6 mg terbutaline were given b.i.d. for 14 days in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline/day, respectively. A small but statistically significant dose-related increase was seen in morning and evening peak expiratory flow (PEF) recordings. It is concluded that continuous treatment, even with high doses or oral terbutaline, does not offer clinically useful protection against exercise-induced asthma.

[Molybdenum cofactor deficiency. Clinical symptoms and diagnostic strategy]. / Molybdaen-kofaktormangel. Kliniske symptomer og diagnostisk strategi.

The clinical, neuroradiological and biochemical findings in two siblings with molybdenum cofactor deficiency are presented. A search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Early diagnosis is prompted by the often rapid fatal outcome and the availability of methods for prenatal diagnosis. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. Magnetic resonance imaging in this condition seems to be rather characteristic.

Use of the acuity card method to test retarded children in special schools.

Acuity cards were used to measure the visual acuity of students at a special school for retarded children, including some who were profoundly retarded and spastic. Almost all children could be tested by two testers on each of two days, and the agreement between different tests was good for children with acuities better than 0.2. Children with poorer acuities had poorer agreement between different test results. High success rate in testing and generally good inter-test agreement indicate that acuity cards can be used in a special school setting to obtain information about the vision of retarded children, who are much more likely than other children to suffer from poor vision.