Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis

The intense airway inflammatory response associated with respiratory syncytial virus (RSV) infection may be an important determinant in the severity of the disease. Interleukin (IL)-10 is a key regulatory cytokine known to be secreted during this infection. We investigated the role that IL-10 plays in RSV disease by studying the effects that variation in the IL10 gene has on the outcome of the disease. Eight single nucleotide polymorphisms (SNPs) spanning the IL10 gene were selected, and haplotypes were constructed. SNPs that efficiently tagged these haplotypes were then typed in 580 infants with severe RSV bronchiolitis and in 580 control subjects. None of the SNPs or haplotypes was associated with RSV bronchiolitis. In a subgroup analysis, 2 SNPs (IL10-1117 and IL10-3585) were associated (odds ratio, 1.7; P=.004) with the need for mechanical ventilation. These data are consistent with the theory that IL10 plays a role in the severity of RSV infection in infants.     

The German 19-item version of the Child Oral Health Impact Profile: translation and psychometric properties

Objectives

This study seeks to develop and validate the 19-item German version of the Child Oral Health Impact Profile (COHIP-G19), an instrument to assess the oral health-related quality of life (OHRQoL) in children and adolescents.

Materials and methods

The 19 items of the original English-language COHIP were translated into German using an established forward–backward approach. For the assessment of the psychometric properties of the COHIP-G19, children and adolescents aged 7–17 years came from two samples: 112 patients were consecutively recruited at a university-based orthodontic clinic and 313 came from a convenience sample of students in public schools.

Results

Internal consistency of the COHIP-G19 was satisfactory in both populations (Cronbach’s alpha, 0.78/0.80; average inter-item correlation, 0.16/0.17). The COHIP-G19 summary scores were correlated in the expected direction with a global oral health rating (r?=?0.46/0.40) and two measures for perceived general health (EQ-5D-Y: r?=?0.26/0.29; KIDSCREEN-27: r?=?0.40/0.33). While COHIP-G19 summary scores did not significantly differ with respect to the presence of caries or gingivitis (p?>?0.05), malocclusion and insufficient oral hygiene behavior were related to more impaired OHRQoL, represented in significantly lower COHIP-G19 summary scores in students in public schools (p?<?0.05), but not in orthodontic patients.

Conclusions

While this study revealed some potential to improve reliability and validity in scores of the German version of the COHIP-19, overall, the study proved the instrument has sufficient psychometric properties and is well comparable to the original English-language version.

Clinical relevance

The COHIP-G19 is a valid and reliable instrument to assess OHRQoL in German children and adolescents in clinical and community settings.

     

Nevirapine use in HIV-1-infected children

OBJECTIVES: To evaluate the safety, efficacy, and clinical, virological, and immunological responses in HIV-1-infected children receiving nevirapine as part of combination antiretroviral therapy (ART). METHODS: A review of case notes of all HIV-1-infected children 96 weeks after starting nevirapine, under a national compassionate access scheme between August 1997 and March 1999 in the UK. Nevirapine was dosed according to the manufacturer's guidelines. RESULTS: Seventy-four children (36 boys, 28 naive to ART) were enrolled, with a median age of 5.2 years, viral load of 5.1 log copies/ml and CD4 lymphocyte count of 13.5%. The liquid formulation and tablets of nevirapine were well tolerated. The proportions of patients achieving undetectable viral load levels at weeks 12, 24, 48 and 96 were 30, 40, 36 and 33%, respectively (intention-to-treat analysis). Of children not on a protease inhibitor who received more than 300 mg/m2/day of nevirapine, 60% had undetectable viral loads at week 96, compared with 17% on recommended doses. Outcomes were similar for patients receiving nevirapine once or twice daily. CD4 cell count percentages increased significantly, with median values sustained above 25% by week 48 onwards. Z-scores for weight and height increased significantly during 96 weeks of treatment. Rash occurred in 20%, of which four (5%) were severe. There were no cases of Stevens-Johnson syndrome. CONCLUSION: Nevirapine was mostly well tolerated, and was associated with encouraging clinical and immunological responses. Virological responses in this cohort support the use of nevirapine doses greater than 300 mg/m2/day, which is higher than currently recommended by the manufacturers.     

Maize-targeted mutagenesis: A knockout resource for maize

We describe an efficient system for site-selected transposon mutagenesis in maize. A total of 43,776 F1 plants were generated by using Robertson's Mutator (Mu) pollen parents and self-pollinated to establish a library of transposon-mutagenized seed. The frequency of new seed mutants was between 10-4 and 10-5 per F1 plant. As a service to the maize community, maize-targeted mutagenesis selects insertions in genes of interest from this library by using the PCR. Pedigree, knockout, sequence, phenotype, and other information is stored in a powerful interactive database (maize-targeted mutagenesis database) that enables analysis of the entire population and the handling of knockout requests. By inhibiting Mu activity in most F1 plants, we sought to reduce somatic insertions that may cause false positives selected from pooled tissue. By monitoring the remaining Mu activity in the F2, however, we demonstrate that seed phenotypes depend on it, and false positives occur in lines that appear to lack it. We conclude that more than half of all mutations arising in this population are suppressed on losing Mu activity. These results have implications for epigenetic models of inbreeding and for functional genomics.     

Economic burden of cardiovascular diseases in the enlarged European Union.

AIMS: Cardiovascular disease (CVD), together with its main components, coronary heart disease (CHD), and cerebrovascular diseases, is the main source of morbidity and mortality in the European Union (EU), but to date, there has not been any systematic cost-of-illness study to assess the economic impact of CVD in the EU. METHODS AND RESULTS: CVD-related expenditure was estimated using aggregate data on morbidity, mortality, and healthcare resource use. Healthcare costs were estimated from expenditure on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and premature death were included in the study. CVD was estimated to cost the EU Euro 169 billion annually, with healthcare accounting for 62% of costs. Productivity losses and informal care represented 21% and 17% of costs, respectively. CHD represented 27% and cerebrovascular diseases 20% of overall CVD costs. CONCLUSION: CVD is a leading public health problem. Our study is the first to assess the economic burden of CVD across the EU, and our results should help policy makers evaluate policy impact and prioritize research expenditures. However, because of data unavailability, our study has important limitations, which highlight the need for more accurate and comparable CVD-specific information.     

The role of blood transfusion in the management of upper and lower intestinal tract bleeding

Patients with gastrointestinal (GI) haemorrhage use 13.8% of all red blood cell transfusions in England. This review addresses the evidence for red blood cell, fresh frozen plasma and platelet transfusions in acute and chronic blood loss, from both the upper and lower intestinal tract. It reviews the indications for transfusion in GI bleeding, the haematological consequences of massive blood loss and massive transfusion, and the importance of managing coagulopathy in bleeding patients. It also looks at the safety and risks of blood transfusion, and provides clinicians with evidence to reduce unnecessary transfusion. Large controlled clinical trials of blood transfusion specifically in GI bleeding are required, along with further research into the use of adjuvant therapies such as recombinant activated factor VIIa. Changing clinician behaviour to reduce inappropriate blood transfusion remains a key target for future transfusion research.     

Developing and validating a center-specific preoperative prediction calculator for risk of outcomes following major hepatectomy procedures

Background

The American College of Surgeons NSQIP^® Surgical Risk Calculator (SRC) was developed to estimate postoperative outcomes. Our goal was to develop and validate an institution-specific risk calculator for patients undergoing major hepatectomy at Carolinas Medical Center (CMC).

Percutaneous Left Atrial Appendage Closure With the Ultraseal Device: Insights From the Initial Multicenter Experience

Objectives

This study sought to evaluate the feasibility, safety, and efficacy of the Ultraseal device for left atrial appendage closure (LAAC) (Cardia, Eagan, Minnesota) in patients with nonvalvular atrial fibrillation at high bleeding risk.