Differences in retinopathy prevalence and associated risk factors across 11 countries in three continents: A cross-sectional study of 156,090 children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). SUBJECTS AND METHODS: Data on individuals aged 10-21 years with T1D for >1 year during the period 2000-2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. RESULTS: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper-1-year-increase  = 1.04, 95% CI: 1.03-1.04, p < 0.0001), and decreased over time (aORper-1-year-increase  = 0.99, 95% CI: 0.98-1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper-1-mmol/mol-increase-in-HbA1c  = 1.03, 95% CI: 1.03-1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11-1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17-1.44, p < 0.0001). CONCLUSIONS: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking.

Skin autofluorescence is increased in young people with type 1 diabetes exposed to secondhand smoking.

Skin autofluorescence is increased in diabetes, rises with age, and predicts diabetes-related complications. Exposure to secondhand smoke, because one or more family members are smokers, further increases skin autofluorescence in children and young adults with type 1 diabetes. Elimination of passive smoking should be a goal in diabetes education. Association between age and skin autofluorescence (SAF), in arbitrary units (AU), in young people with type 1 diabetes exposed (black dots) and not exposed (open dots) to secondhand smoke. Regression lines show correlations between these parameters in exposed (solid line) and not exposed (dashed line) patients.

Passive immunisation against respiratory syncytial virus: a cost-effectiveness analysis.

AIM: The cost-effectiveness of passive immunisation against respiratory syncytial virus (RSV) in the Netherlands was studied by assessing incremental costs to prevent one hospitalisation in high-risk children using a novel individualised monthly approach. METHODS: Cost-effectiveness analysis was performed by combining estimates of individual hospitalisation costs and monthly hospitalisation risks, with immunisation costs, parental costs and efficacy of passive immunisation for a reference case with the highest hospitalisation risks and costs of hospitalisation during the RSV season (male, gestational age < or =28 weeks, birth weight < or =2500 g, having bronchopulmonary dysplasia (BPD), aged 0 months at the beginning of the season (October)). Various sensitivity analyses and a cost-neutrality analysis were performed. RESULTS: Cost-effectiveness of passive immunisation varied widely by child characteristics and seasonal month. For the reference case it was most cost effective in December at euro13,190 per hospitalisation averted. Cost-effectiveness was most sensitive to changes in hospitalisation risk. For the reference case, cost neutrality was reached in December, if acquisition costs of passive immunisation decreased from euro 930 to euro 375, monthly hospitalisation risk increased from 7.6% to 17%, or hospitalisation costs increased from euro 10 250 to euro 23 250 per hospitalisation. Even if passive immunisation prevented all hospitalisations, costs per hospitalisation averted in December would still exceed euro 2645. CONCLUSIONS: Although cost-effectiveness of passive immunisation varied strongly by child characteristics and seasonal month, incremental costs per hospitalisation averted were always high. A restrictive immunisation policy only immunising children with BPD in high-risk months is therefore recommended. The costs of passive immunisation would have to be considerably reduced to achieve cost-effectiveness.

The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.

To determine whether the CLCA gene family of calcium-activated chloride channels is a modulator of the basic defect of cystic fibrosis (CF), an association study was performed with polymorphic microsatellite markers covering a 40-Mbp region spanning the CLCA gene locus on human chromosome 1p in CF patients displaying CF transmembrane conductance regulator (CFTR)-independent residual chloride conductance in gastrointestinal epithelia. Statistically significant association of the electrophysiological phenotype with the allele distribution of markers 5' of and within the CLCA locus was observed. Transmission disequilibrium and the significance of the association decreased within the locus from hCLCA2 towards hCLCA4. Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by microarray analysis. The CLCA gene region was identified to encode mediators of DIDS-sensitive anion conductance in the human gastrointestinal tract that modulate the CF basic defect.

Anticipated costs of hospitalization for respiratory syncytial virus infection in young children at risk.

BACKGROUND: Reliable estimates of hospitalization costs for severe respiratory syncytial virus (RSV) infection are necessary to perform economic analyses of preventive strategies of severe RSV disease. We aimed to develop a model that predicts anticipated mean RSV hospitalization costs of groups of young children at risk for hospitalization, but not yet hospitalized, based on readily available child characteristics. METHODS: We determined real direct medical costs of RSV hospitalization from a societal perspective, using a bottom-up strategy, in 3458 infants and young children hospitalized for severe RSV disease during the RSV seasons 1996-1997 to 1999-2000 in the Southwest of the Netherlands. We used a linear regression model to predict anticipated mean RSV hospitalization costs of groups of children at risk, based on 4 child characteristics [age, gestational age, birth weight and bronchopulmonary dysplasia (BPD)], expressed in EC Euros as of the year 2000. FINDINGS: The mean RSV hospitalization costs of all patients were 3110 Euros. RSV hospitalization costs were higher for patients with lower gestational age (5555 Euros; gestational age,

Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated residual chloride secretion does not protect against early chronic Pseudomonas aeruginosa infection in F508del homozygous cystic fibrosis patients.

Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl-) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa (PA). In this study, we investigated whether or not the presence of residual Cl- secretion protects against early chronic PA colonization of patients' airways. Excluding influences on the phenotype caused by different CFTR mutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl- secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n = 14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n = 10). We determined the Cl- transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl- secretion, most likely due to the CFTR Cl- channel, was observed in 63% of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl- secretion determine the age of onset of PA colonization.