Die Prävalenz der COPD in Österreich – die erwartete Entwicklung bis 2020

BACKGROUND: In 2020 Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death world-wide causing considerable health costs. Epidemiological data to estimate the future development of COPD in Austria were not available so far. METHODS: In the context of the international Burden of Obstructive Lung Disease (BOLD) study, a random sample of the population of Salzburg was surveyed to determine the prevalence of COPD. The definition of COPD followed the GOLD classification. A prior physician's diagnosis of COPD, emphysema or chronic bronchitis was evaluated by questionnaire. The age- and sex-specific prevalence of COPD was extrapolated using demographic data of the Austrian population for the years 2005, 2010, 2015 and 2020. Undiagnosed COPD was considered present, whenever irreversible airways obstruction was measured (FEV1/FVC < 0.7), but a doctor's diagnosis of COPD, emphysema or chronic bronchitis has not been made. RESULTS: For 2005 1.047.150 Austrians aged 40 years and older were estimated in GOLD stage I-IV. 431.080 persons over 40 years were affected by COPD in GOLD stage II-IV needing therapy. The percentage of undiagnosed COPD was 88,5%. For the years 2010, 2015 and 2020 GOLD stage I-IV COPD was projected to rise by 7,8%, 16.1% and 24%, respectively. CONCLUSION: Measures to prevent COPD are absolutely necessary to forestall the projected burden of this disease in Austria.     

Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes

A significant proportion of endogenously processed CD8(+) T cell epitopes are derived from newly synthesized proteins and rapidly degrading polypeptides (RDPs). It has been hypothesized that the generation of rapidly degrading polypeptides and CD8(+) T cell epitopes from these RDP precursors may be influenced by the efficiency of protein translation. Here we address this hypothesis by using the Epstein-Barr virus-encoded nuclear antigen 1 protein (EBNA1), with or without its internal glycine-alanine repeat sequence (EBNA1 and EBNA1DeltaGA, respectively), which display distinct differences in translation efficiency. We demonstrate that RDPs constitute a significant proportion of newly synthesized EBNA1 and EBNA1DeltaGA and that the levels of RDPs produced by each of these proteins directly correlate with the translation efficiency of either EBNA1 or EBNA1DeltaGA. As a consequence, a higher number of major histocompatibility complex-peptide complexes can be detected on the surface of cells expressing EBNA1DeltaGA, and these cells are more efficiently recognized by virus-specific cytotoxic T lymphocytes compared to the full-length EBNA1. More importantly, we also demonstrate that the endogenous processing of these CD8(+) T cell epitopes is predominantly determined by the rate at which the RDPs are generated rather than the intracellular turnover of these proteins.     

Academic microsystems: adapting Clinical Microsystems as an evaluation framework for community-based nursing education

When an academic nursing program and clinical agency form a partnership to both educate students and effect changes in the health care of the community, evaluation presents a challenge for measuring structure, processes, and outcomes at three levels: student educational processes and outcomes; student-sensitive outcomes for the community; and the effectiveness of the partnership itself. This article describes how we adapted the Clinical Microsystems model as an Academic Microsystems model to evaluate the complementary processes and outcomes for the community and for the nursing program in a senior Community Capstone course. The Capstone is a community-based initiative in which students assess community needs, intervene appropriately, evaluate their intervention, and pass the initiative on to the next year's class. Although outcomes for students and the community were positive, the model revealed that developing the frontline microsystem of student/faculty/community nurse mentor was the key to success.     

Fatal Adverse Event with Dabigatran in Elderly Patient with Reduced Kidney Function

An elderly man with decreased kidney function was admitted to hospital with gastrointestinal bleeding. After remaining stable for 2 days in hospital, he became haemodynamically unstable and an adverse effect of dabigatran was suspected, but efforts to treat the patient failed and the following morning he passed away. In conjunction with the autopsy, blood samples from his hospital stay were analysed for dabigatran, revealing the highest concentration (6400 ng/mL) apparently reported to date. Supra‐therapeutic dosing was, however, never suspected. Dabigatran is largely excreted through the kidneys. A possible cause of the high dabigatran concentrations could be a rapid decrease in kidney function that seemingly occurred over a period of 2 months, sometime between his initiation of treatment (eGFR 51–55 mL/min/1.73 m²) and subsequent hospital admission (eGFR 31 mL/min/1.73 m²). The increasing dabigatran concentrations in the patient was, however, not apparent to the prescribing doctor, as therapeutic drug monitoring of dabigatran is not recommended in current guidelines and no such analyses were performed. There may be a need to evaluate blood concentrations of dabigatran, in the light of the reported differences in interindividual concentrations, along with the increased risks of thromboembolic events with lower concentrations and major bleeding events with higher concentrations. Functional assays to assess concentrations of dabigatran in blood have been developed and are available in some hospitals to be used in suspected overdoses or before emergency surgeries. Methods to determine concentrations of dabigatran specifically have also been developed and can additionally be used for therapeutic drug monitoring in an outpatient setting, especially in high‐risk individuals.     

Impact of COVID-19 on outpatient visits and intravitreal treatments in a referral retina unit: let’s be ready for a plausible “rebound effect”

Graefe's Archive for Clinical and Experimental Ophthalmology - To quantify the shrinking in outpatient and intravitreal injections’ volumes in a tertiary referral retina unit secondary to...     

High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant

BACKGROUND: The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. METHODS: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. RESULTS: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) microg/L vs 36.8 (11.0) microg/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 microg/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) microg/L vs 44.1 (14.1) microg/L; P <0.001). CONCLUSIONS: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.     

Genetic association signal near NTN4 in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10⁻³) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry‐matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10⁻⁴) remained significant after Bonferroni correction. Meta‐analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10⁻⁷). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case–control status (p = 0.042), suggesting that many of these variants are true TS risk alleles. Ann Neurol 2014;76:310–315     

Plasma Apolipoprotein L1 Levels Do Not Correlate with CKD

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m² (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.Nondiabetic CKD in individuals of African ancestry have been linked to polymorphisms in the gene for apolipoprotein L1 (APOL1),^1–5 a protein component of HDL particles with a known function in the immune clearance of Trypanosoma brucei infections.⁶ CKD is associated with two coding variants of the APOL1 gene known as G1 and G2, both of higher allele frequency in African and African descendent populations compared with white populations where they are almost absent. Evidence suggests that the prevalence of the G1 and G2 variants may have increased in African populations because of a selective advantage from their ability to kill a broader range of Trypanosoma species.^1,2,7 Individuals carrying at least one G1 or G2 allele have additional protection from trypanosomiasis; however, individuals with two G1 or G2 alleles are at increased risk for nondiabetic CKD.^2,4,5The pathogenic mechanisms responsible for CKD associated with APOL1 risk variants are unknown. We recently showed that, in addition to being secreted and circulated in the blood,⁸ APOL1 is localized in podocytes, proximal tubular epithelial cells, and small-artery endothelium in normal kidney.⁹ Thus, the contribution of circulating versus kidney-localized variant APOL1s to CKD pathogenesis is unknown. In kidney transplantation, two studies suggest that graft loss is associated with the APOL1 genotype of the allograft, not the recipient.^10,11 However, the association of APOL1 plasma levels with CKD phenotypes or APOL1 genotype has not been studied.To address these issues, we examined circulating APOL1 levels with APOL1 genotype and renal function in HIV-infected African Americans in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort because the occurrence of HIV-associated nephropathy (HIVAN) and renal outcomes in HIV-infected patients are strongly associated with APOL1 risk alleles.^12–14 In addition, we examined the relationship between circulating APOL1 levels and proinflammatory cytokines known to induce APOL1 expression and previously associated with CKD and HIV/AIDS progression.^15,16 Additional analyses examined associations of APOL1 levels with dyslipidemia and the role of APOL1 genotype on CKD progression using longitudinal data.