Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort.

BACKGROUND: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. METHODS: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. RESULTS: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year. CONCLUSION: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.

Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD-results from COSYCONET.

BACKGROUND: MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. METHODS: The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable "recently diagnosed mild to moderate COPD" defined by GOLD grades 0-2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. RESULTS: 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n = 1470 finally). CONCLUSION: In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.

Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET.

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1-4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85-4.15, p < 0.0001) for values <12.5 g/dL. For comparison, the hazard ratio for WBC > 8000/µL was 2.33 (95% CI: 1.60-3.39, p < 0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO2. It thus appears well suited for clinical use with minimal equipment, especially for GPs.

Combined effects of lung function, blood gases and kidney function on the exacerbation risk in stable COPD: Results from the COSYCONET cohort.

RATIONALE: Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. METHODS: We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. RESULTS: 1506 patients with stable COPD (GOLD grade 1-4; mean age 64.5 ±â€¯8.1 y; mean FEV1 54 ±â€¯18 %predicted, mean eGFR 82.3 ±â€¯16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. CONCLUSION: Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Long-term persistence of MRSA in re-admitted patients.

BACKGROUND: A better knowledge of methicillin-resistant Staphylococcus aureus (MRSA) persistence in hospitalised patients may impact on specific prevention strategies. We have investigated the persistence of MRSA-carriage in patients admitted and re-admitted to a university hospital. PATIENTS AND METHODS: Between January 2002 and October 2005 all MRSA-positive patients admitted to the university hospital of Hannover Medical School were assessed at first admission and all subsequent re-admissions. Patients re-admitted at least once were analysed for the persistence or loss of MRSA. The association of possible factors influencing the persistence of MRSA colonisation or infection (age group, gender, decolonisation therapy during first hospital stay due to MRSA positivity and colonisation of different anatomical sites) was analysed using univariate, multivariate and time-dependent analyses. RESULTS: A total of 1,032 patients who had tested positive at least once for MRSA were admitted to our hospital during the study period, accounting for 2,038 admissions. Of these patients, 403 (39.1%) were admitted more than once (from two times to 21 times), and 238 (59.1%) of the re-admitted patients remained MRSA positive during all subsequent admissions. Fifty-five (13.6%) patients tested MRSA negative at their last admission, and 61 (15.1%) tested MRSA negative at at least two consecutive admissions. In 27 (6.7%) patients, the MRSA status differed more than once between subsequent admissions. Overall, the half-life time (HLT) of MRSA persistence was 549 days, with the duration of persistence dependent on the colonisation of different anatomical sites (HLT only wounds 117 days; HLT mouth, throat, bronchial secretions 627 days; HLT nose, wounds and other body sites 801 days; p < 0.01) and was prolonged if more than one body site was MRSA-positive (HR 2.18, 95% confidence interval 1.52-3.15). CONCLUSION: A detailed knowledge of the dynamics of the loss of MRSA infection could result in a reduction of the incidence of MRSA in the future. Multiple anatomical site carriage of MRSA appeared to predict a prolonged persistence in our cohort of patients re-admitted to a university hospital.

Adverse effects of rabies pre- and postexposure prophylaxis in 290 health-care-workers exposed to a rabies infected organ donor or transplant recipients.

The recent unfortunate rabies transmissions through solid organ transplants of an infected donor in Germany required the initiation of a vaccination program to protect health care workers (HCWs) with close contact to rabies-infected patients. A systematic follow-up of adverse effects was initiated. Rabies postexposure prophylaxis (PEP) was started in 269 HCWs at four German hospitals. Pre-exposure prophylaxis (PreEP) was administered to 74 HCWs caring for an already diagnosed rabies patient. At each vaccination date, HCWs were interviewed for symptoms possibly representing adverse effects. Adverse effects of PEP and PrePEP were compared. Out of 269 HCWs, 216 were included for the investigation of adverse effects. Of these 216 HCWs, 114 (53%) individuals developed at least one systemic adverse effect. Incidences of tiredness (30.6%), malaise (26.4%), headache (26.9%), dizziness (14.8%), and chills (13.0%) declined in the course of PEP (p < 0.05), whereas incidences of fever (7.4%), paraesthesias (7.9%), arthralgias (1.9%), myalgias (4.2%), nausea (9.3%), diarrheas (2.8%) and vomiting (1.4%) did not. In 11 (5.1%) HCWs PEP was discontinued mostly due to adverse reactions (four suffered strong headaches, two HCWs meningeal irritations, two chills, one paraesthesia, one malaise, and one a rush). Systemic effects of PEP or PreEP did not differ significantly. Despite relatively high incidences of moderate severe adverse reactions rabies PEP is safe. Strong headache, tiredness, dizziness, and paraesthesias are the most important postvaccinal symptoms. Vaccinees suffering from adverse effects of PEP must be strongly encouraged to complete PEP, as it is to date the only protection against fatal rabies.