Kooperativer Bibliotheksverbund

In: Inorganic Chemistry, American Chemical Society (ACS), Vol. 52, No. 4 ( 2013-02-18), p. 1860-1871

Type of Medium: Online Resource

ISSN: 0020-1669 , 1520-510X

URL: Article

DOI: 10.1021/ic301968j

Language: English

Publisher: American Chemical Society (ACS)

Publication Date: 2013

detail.hit.zdb_id: 7558-9

detail.hit.zdb_id: 1484438-2

In: Pulmonary Circulation, Wiley, Vol. 1, No. 2 ( 2011-04), p. 239-243

Abstract: Our aim was to determine what proportion of patients with pulmonary hypertension (PH) has undertaken air travel contrary to the general medical advice and to characterize these patients according to disease severity and medical treatment. In cooperation with Pulmonale Hypertonie e.V., the German patient organization, a questionnaire was distributed. In total, 430 of 720 questionnaires were returned completed. Of the 179 patients who travelled at least once by air, the distribution of New York Heart Association functional classes I/ II/ III/ IV was 2/ 77/ 74/ 8, respectively; 83 patients were receiving monotherapy; 58 patients were receiving a combination of two or more therapies; 57 patients were on long‐term ambulatory oxygen treatment; and 29 patients used supplemental oxygen while travelling. Overall, 20 adverse events were reported, mostly of mild to moderate severity (i.e., peripheral edema, dyspnea), with need of medical intervention in only 7 cases. The 251 patients who did not travel by air were, on average, in more advanced stages of disease and/or clinically unstable. In conclusion, a majority of patients (159 out of 179) did not experience any complications during or directly after the fight even though no special precautions were taken. Thus we conclude that for patients with PH in a stable clinical condition, air travel can be safe and well tolerated.

Type of Medium: Online Resource

ISSN: 2045-8940 , 2045-8940

URL: Article

DOI: 10.4103/2045-8932.83451

Language: English

Publisher: Wiley

Publication Date: 2011

detail.hit.zdb_id: 2638089-4

In: Justice System Journal, Informa UK Limited, Vol. 31, No. 3 ( 2010-09-01), p. 249-272

Type of Medium: Online Resource

ISSN: 0098-261X , 2327-7556

URL: Article

DOI: 10.1080/0098261X.2010.10767970

Language: English

Publisher: Informa UK Limited

Publication Date: 2010

detail.hit.zdb_id: 2402954-3

SSG: 2

In: Phys. Chem. Chem. Phys., Royal Society of Chemistry (RSC), Vol. 16, No. 5 ( 2014), p. 1814-1819

Type of Medium: Online Resource

ISSN: 1463-9076 , 1463-9084

URL: Article

DOI: 10.1039/C3CP54878C

Language: English

Publisher: Royal Society of Chemistry (RSC)

Publication Date: 2014

detail.hit.zdb_id: 1476283-3

detail.hit.zdb_id: 1476244-4

detail.hit.zdb_id: 1460656-2

In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 128, No. 18 ( 2013-10-29), p. 2005-2015

Abstract: This study sought to analyze a new approach to assess exercise-induced pulmonary artery systolic pressure (PASP) increase by means of stress Doppler echocardiography as a possible measure of right ventricular contractile reserve in patients with severe pulmonary hypertension and right heart failure. Methods and Results— In this prospective study, patients with invasively diagnosed pulmonary arterial hypertension or inoperable chronic thromboembolic pulmonary hypertension and impaired right ventricular pump function despite a stable targeted pulmonary arterial hypertension medication underwent a broad panel of noninvasive assessments, including stress echocardiography and cardiopulmonary exercise testing. On the basis of the assumption that exercise-induced PASP is a measure of right ventricular contractile reserve, patients were classified into 2 groups according to an exercise-induced PASP increase above or below the median. Patients were followed up for 3.0±1.8 years. Univariate and multivariate analyses were used for factors predicting survival. Of 124 patients, 66 were below the median exercise-induced PASP increase of 30 mm Hg (low PASP), and 58 patients were above the median (high PASP). These groups were not significantly different in terms of medication and resting hemodynamics. Low PASP was associated with a significantly lower 6-minute walking distance, peak o 2 per kilogram, and 1-, 3-, and 4-year survival rates (92%, 69%, and 48%, respectively, versus 96%, 92%, and 89%). In the multivariate Cox model analysis adjusted for age and sex, PASP increase during exercise and peak o 2 per kilogram remained independent prognostic markers (hazard ratio, 2.56 for peak o 2 per kilogram and 2.84 for PASP increase). Conclusions— Exercise-induced PASP increase is of high clinical and prognostic relevance in pulmonary hypertension patients and may indicate right ventricular contractile reserve. Stress Doppler echocardiography may be a useful tool for prognostic assessment in pulmonary hypertension patients.

Type of Medium: Online Resource

ISSN: 0009-7322 , 1524-4539

URL: Article

DOI: 10.1161/CIRCULATIONAHA.113.001573

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2013

detail.hit.zdb_id: 1466401-X

In: Blood, American Society of Hematology, Vol. 120, No. 12 ( 2012-09-20), p. 2405-2411

Abstract: A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2012-05-429688

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Respiration, S. Karger AG, Vol. 88, No. 1 ( 2014), p. 24-30

Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Patients with pulmonary arterial hypertension (PAH) present with an altered inspiratory capacity (IC) reflecting dynamic hyperinflation (DH) that leads to mechanical constraints and excessive ventilatory demand, particularly during exercise, resulting in exertional dyspnea. 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 Assessment of the long-term consequences of altered IC and DH in PAH. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 50 patients with newly diagnosed PAH were prospectively recruited. All patients were assessed by means of right heart catheterization, 6-min walking distance (6MWD) test, lung function and cardiopulmonary exercise testing, including the assessment of IC. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 37 patients with idiopathic PAH and 13 patients with conditions associated with PAH (29 female; mean age 51.6 ± 15.1 years; World Health Organization, WHO class, 2.7 ± 0.6) presented with a mean pulmonary arterial pressure of 42.8 ± 15.9 mm Hg and pulmonary vascular resistance (PVR) of 737.2 ± 592.8 dyn*s/cm 〈 sup 〉 5 〈 /sup 〉 . The mean IC at rest was 87.2 ± 17.3% pred. Kaplan-Meier analysis revealed that patients with an IC at rest 〉 89% pred. had a significantly better 5-year survival than those with lower values (94.1 vs. 75.1%; log-rank p = 0.036). Univariate analysis identified IC at rest (% pred.) as a predictor of survival with a hazard ratio (HR) of 5.05 (95% confidence interval, CI, 0.97-26.24, p = 0.054). In multivariate analysis including PVR, WHO class, 6MWD and peak oxygen uptake as covariates, IC at rest remained an independent predictor of survival (HR: 8.06, 95% CI 0.92-70.34; p = 0.059). DH expressed as & #x0394;IC or static hyperinflation expressed as IC/total lung capacity at rest revealed no prognostic significance. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In patients with PAH, IC at rest is of prognostic significance at the time of diagnosis.

Type of Medium: Online Resource

ISSN: 0025-7931 , 1423-0356

URL: Article

DOI: 10.1159/000360481

Language: English

Publisher: S. Karger AG

Publication Date: 2014

detail.hit.zdb_id: 1464419-8

In: Pulmonary Circulation, Wiley, Vol. 3, No. 3 ( 2013-09), p. 523-532

Abstract: Hemodynamic measurements provide important parameters for determining prognosis and therapy in patients with pulmonary arterial hypertension (PAH). Current guidelines do not incorporate the possible predictive value of individual changes in hemodynamic variables during the disease time course, and there is no consensus about the time point for hemodynamic reevaluation. We aimed to assess the long‐term prognostic value of short‐term changes in hemodynamic parameters. The study included 122 patients with PAH from the Giessen Pulmonary Hypertension Registry who underwent hemodynamic evaluation at baseline and at 16 weeks (±2.5 standard deviations [SDs]; range: 4–29 weeks) after initial assessment. At baseline, mean pulmonary vascular resistance (PVR) was 1,109 dyn s cm −5 , and 82% of patients were in World Health Organization (WHO) functional class III or IV. Fifty patients died, and 2 underwent lung transplantation during long‐term observation (≤10 years; mean: 4.7 years). Kaplan‐Meier estimates for transplant‐free survival were 93.3%, 76.1%, 57.8%, and 53.1% at 1, 3, 5, and 7 years, respectively. When assigned to prognostic groups, improvements in cardiac output of 〉 0.22 L min −1 (hazard ratio [HR]: 2.05; P = 0.015) and a decrease in PVR of 〉 176 dyn s cm −5 (HR: 1.89; P = 0.044) at 4–29 weeks were associated with long‐term transplant‐free survival. Changes in mean pulmonary arterial pressure did not predict long‐term prognosis. Of 2 noninvasive parameters assessed in this selected patient group, change in WHO functional class, but not in 6‐minute walk distance, predicted long‐term prognosis. Short‐term assessment of changes in hemodynamic parameters at 16 weeks ± 2.5 SDs after initial invasive evaluation is useful to determine long‐term prognosis in patients with PAH.

Type of Medium: Online Resource

ISSN: 2045-8940 , 2045-8940

URL: Article

DOI: 10.1086/674338

Language: English

Publisher: Wiley

Publication Date: 2013

detail.hit.zdb_id: 2638089-4

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 205-205

Abstract: Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII:C). Immunosuppressive treatment may result in remission of disease over a period of days to months. Until remission, patients are at high risk of bleeding and complications from immunosuppression. Prognostic parameters to predict remission and the time needed to achieve remission could be helpful to guide treatment intensity, but have not been established so far. GTH-AH01/2010 was a prospective multicenter cohort study using a standardized immunosuppressive treatment protocol. The primary study endpoint was time to achieve partial remission (PR, defined as FVIII:C activity 〉 50 IU/dl after cessation of any hemotherapy for 〉 24h, and no active bleeding). Secondary endpoints were time to achieve complete remission (CR, defined as PR plus negative FVIII:C inhibitor, steroid tapered to 〈 15 mg/d prednisolone, and cessation of any other immunosuppressive treatment), and overall survival (OS). Enrolment was strictly prospective and only allowed within 7 days of starting immunosuppression. Outcome data were recorded in all patients enrolled. The treatment protocol consisted of prednisolone (100 mg/d from day 1 to the day of PR, then tapered down to 〈 15 mg/d over 5 weeks), oral cyclophosphamide (150 mg/d, from day 21-42, unless PR was achieved), and rituximab (375 mg/m2 weekly for 4 weeks starting on day 43, unless PR was achieved). If AHA was first diagnosed in patients previously on prednisolone 〉 15 mg/d, or equivalent, they received prednisolone (100 mg/d) and rituximab from day 1. If cyclophosphamide was contraindicated, patients received prednisolone (100 mg/d) and rituximab from day 21. One hundred twenty-four patients from 21 treatment centers in Germany and Austria were enrolled between April 2010 and April 2013 (36 months). The patients from two centers not compliant with the treatment protocol were excluded (N=18), as were patients in whom AHA was not confirmed (N=2) or follow-up was too short at the time of this analysis (N=7). The remaining 97 patients from 17 centers were followed for a median of 256 days (interquartile range [IQR] 84-561). Median age was 74 years (IQR 64-82). AHA was associated with other autoimmune disorders (19%), malignancy (12%), pregnancy or puerperium (5%), but was most often idiopathic (66%). The median FVIII:C activity at baseline was 1 IU/dl (IQR 〈 1-3), and the median inhibitor titer was 20 BU/ml (IQR 7.7-78). PR and CR were achieved after a median time of 35 and 102 days, respectively. Patients achieving PR prior to day 21 (N=22) compared with patients not achieving PR within 21 days (N=75) had a higher baseline FVIII:C activity (median 3 vs. 〈 1 IU/dl, p 〈 0.01) and a lower FVIII:C inhibitor (median 12 vs. 29 BU/ml, p 〈 0.05). Multivariate analysis with adjustment for age, sex, underlying disorder, and WHO performance status on admission demonstrated that baseline FVIII:C activity ( 〈 1 IU/dl vs. 〉 =1 IU/dl) had a strong impact on the time to achieve PR (HR 2.76 [95% confidence interval 1.73-4.42] , p 〈 0.001) and CR (HR 2.36 [1.34-4.14], p 〈 0.01). Baseline FVIII:C activity was also a predictor of PR and CR when other cutoffs were used (2 or 3 IU/dl instead of 1 IU/dl), or when it was analyzed as a continuous variable in Cox regression analysis. In contrast, FVIII:C inhibitor titer assessed by the local laboratory did not affect time to PR or CR significantly. OS after 300 days, estimated by the Kaplan Meier method, was 69%. Age, WHO performance status, and FVIII:C activity at baseline were independent predictors of OS. In summary, GTH-AH 01/2010 is the largest prospective study of patients with AHA treated according to a standardized protocol. The study demonstrated a robust effect of baseline FVIII:C activity on the time needed to achieve PR and CR. Baseline FVIII:C activity, together with age and performance status, also affected OS. Therefore, baseline FVIII:C activity may be considered to guide individually tailored immunosuppression in future studies. Disclosures: Tiede: Baxter: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy; CSL Behring: Consultancy, Honoraria, Research Funding. Off Label Use: Prednisolone, cyclophosphamid, and rituximab for immunosuppression in acquired hemophilia. Klamroth:Bayer: Honoraria, Research Funding; Baxter: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding. Gottstein:Novo Nordisk: Honoraria; Baxter: Honoraria. Holstein:Baxter: Honoraria, Speakers Bureau. Scharf:CSL Behring: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Biotest: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Baxter: Consultancy, Honoraria, Research Funding. Huth-Kühne:SRH Kurpfalz Hospital and Hemophilia Center: Consultancy, Employment, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Greil:Roche: Consultancy, Honoraria, Research Funding. Miesbach:Novo Nordisk: Consultancy, Honoraria, Research Funding; Baxter: Consultancy, Honoraria, Research Funding. Trappe:Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel Other; AMGEN: Research Funding, Travel, Travel Other; CSL Behring: Honoraria, Research Funding, Speakers Bureau, Travel, Travel Other; Mundipharma: Research Funding, Travel, Travel Other; Takeda: Consultancy, Research Funding, Travel Other; Novartis: Consultancy, Research Funding, Travel, Travel Other; Novartis: Research Funding, Travel Other; Cellgen: Travel, Travel Other. Knoebl:Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.205.205

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: The Journal of Heart and Lung Transplantation, Elsevier BV, Vol. 31, No. 10 ( 2012-10), p. 1109-1114

Type of Medium: Online Resource

ISSN: 1053-2498

URL: Article

DOI: 10.1016/j.healun.2012.08.014

Language: English

Publisher: Elsevier BV

Publication Date: 2012