| 1. |
- Joerger, Markus, et al.
(author)
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Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients : a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group.
- 2007
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:21, s. 6410-6418
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Journal article (peer-reviewed)abstract
- Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 μmol/L (tC > 0.05−0.2) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. Experimental Design: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m2) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. Results: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel tC > 0.05 was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel tC > 0.05 > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel tC > 0.05 < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel tC > 0.05 was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (Cmax and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10−4). Conclusions: In this group of patients, paclitaxel tC > 0.05 is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.
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| 2. |
- Khan, N. K., et al.
(author)
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Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge
- 2007
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In: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:5, s. 491-501
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS: The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115 hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934 had cardiac imaging tests. The utility of the ECG was assessed for excluding or diagnosing major structural heart disease (MSHD) or major left ventricular systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%, respectively, if the ECG was entirely normal. However, <2% of patients had a normal ECG. No single ECG characteristic identified a probability <25% of MSHD or <20% of MLVSD. Patients with QRS width >/=120 ms or anterior pathological Q-waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models suggested that electrocardiographic criteria alone were not accurate for the diagnosis or exclusion of important heart disease in this population. However, 2468 patients (42%) had an electrocardiographic finding that should be used to guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with suspected HF but has limited diagnostic value in this setting. The ECG has an important role in guiding therapy.
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| 3. |
- Rich, Rebecca L., et al.
(author)
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A global benchmark study using affinity-based biosensors
- 2009
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In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Journal article (peer-reviewed)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 4. |
- Blomström, Per, et al.
(author)
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Cost effectiveness of cardiac resynchronization therapy in the Nordic region : an analysis based on the CARE-HF trial
- 2008
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 10:9, s. 869-877
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was 4800 euros in Denmark, 3600 euros in Finland and 6700 euros in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of 1169 euros in Finland to an upper limit of 17,482 euros in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.
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