| 1. |
- Stinner, B, et al.
(författare)
-
Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4) - Protocol of a controlled clinical trial developed by consensus of an international study group Part three : individual patient, complication algorithm and quality management
- 2001
-
Ingår i: Inflammation Research. - 1023-3830 .- 1420-908X. ; 50:5, s. 233-248
-
Forskningsöversikt (refereegranskat)abstract
- General design: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management. Objective: In part three of the protocol, the three major sections include: - The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. - A center based clinical practice guideline for the management of the most important postoperative complication anastomotic leakage - including evidence based support for each step of the algorithm. - Data management, ethics and organisational structure. Conclusions: Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or - if it fails - at least demonstrates new ways for explaining the failures.
|
|
| 2. |
- Ahmad, Amais, et al.
(författare)
-
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4 : Prediction accuracy and software comparisons with improved data and modelling strategies
- 2020
-
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 156, s. 50-63
-
Tidskriftsartikel (refereegranskat)abstract
- Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters.On average, PK parameters (Area Under the Concentration-time curve (AUC0-tlast), Maximal concentration (Cmax), half-life (t1/2)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC0-tlast and around 90% of the simulations were within 10-fold error for AUC0-tlast. Oral bioavailability (Foral) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC0-tlast predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC0-tlast for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
|
|
| 3. |
- Siewert, Matthias B., et al.
(författare)
-
Comparing carbon storage of Siberian tundra and taiga permafrost ecosystems at very high spatial resolution
- 2015
-
Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953 .- 2169-8961. ; 120:10, s. 1973-1994
-
Tidskriftsartikel (refereegranskat)abstract
- Permafrost-affected ecosystems are important components in the global carbon (C) cycle that, despite being vulnerable to disturbances under climate change, remain poorly understood. This study investigates ecosystem carbon storage in two contrasting continuous permafrost areas of NE and East Siberia. Detailed partitioning of soil organic carbon (SOC) and phytomass carbon (PC) is analyzed for one tundra (Kytalyk) and one taiga (Spasskaya Pad/Neleger) study area. In total, 57 individual field sites (24 and 33 in the respective areas) have been sampled for PC and SOC, including the upper permafrost. Landscape partitioning of ecosystem C storage was derived from thematic upscaling of field observations using a land cover classification from very high resolution (2x2m) satellite imagery. Nonmetric multidimensional scaling was used to explore patterns in C distribution. In both environments the ecosystem C is mostly stored in the soil (86%). At the landscape scale C stocks are primarily controlled by the presence of thermokarst depressions (alases). In the tundra landscape, site-scale variability of C is controlled by periglacial geomorphological features, while in the taiga, local differences in catenary position, soil texture, and forest successions are more important. Very high resolution remote sensing is highly beneficial to the quantification of C storage. Detailed knowledge of ecosystem C storage and ground ice distribution is needed to predict permafrost landscape vulnerability to projected climatic changes. We argue that vegetation dynamics are unlikely to offset mineralization of thawed permafrost C and that landscape-scale reworking of SOC represents the largest potential changes to C cycling.
|
|
| 4. |
|
|
| 5. |
|
|
