Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

SARM-S4 and metabolites detection in sports drug testing: a case report.

Recently, pharmaceutical industry developed a new class of therapeutics called Selective Androgen Receptor Modulator (SARM) to substitute the synthetic anabolic drugs used in medical treatments. Since the beginning of the anti-doping testing in sports in the 1970s, steroids have been the most frequently detected drugs mainly used for their anabolic properties. The major advantage of SARMs is the reduced androgenic activities which are the main source of side effects following anabolic agents' administration. In 2010, the Swiss laboratory for doping analyses reported the first case of SARMs abuse during in-competition testing. The analytical steps leading to this finding are described in this paper. Screening and confirmation results were obtained based on liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Additional information regarding the SARM S-4 metabolism was investigated by ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS).

Development of a Database for Drilled Shaft Foundation Testing (DSHAFT), June 2012

Drilled shafts have been used in the US for more than 100 years in bridges and buildings as a deep foundation alternative. For many of these applications, the drilled shafts were designed using the Working Stress Design (WSD) approach. Even though WSD has been used successfully in the past, a move toward Load Resistance Factor Design (LRFD) for foundation applications began when the Federal Highway Administration (FHWA) issued a policy memorandum on June 28, 2000.The policy memorandum requires all new bridges initiated after October 1, 2007, to be designed according to the LRFD approach. This ensures compatibility between the superstructure and substructure designs, and provides a means of consistently incorporating sources of uncertainty into each load and resistance component. Regionally-calibrated LRFD resistance factors are permitted by the American Association of State Highway and Transportation Officials (AASHTO) to improve the economy and competitiveness of drilled shafts. To achieve this goal, a database for Drilled SHAft Foundation Testing (DSHAFT) has been developed. DSHAFT is aimed at assimilating high quality drilled shaft test data from Iowa and the surrounding regions, and identifying the need for further tests in suitable soil profiles. This report introduces DSHAFT and demonstrates its features and capabilities, such as an easy-to-use storage and sharing tool for providing access to key information (e.g., soil classification details and cross-hole sonic logging reports). DSHAFT embodies a model for effective, regional LRFD calibration procedures consistent with PIle LOad Test (PILOT) database, which contains driven pile load tests accumulated from the state of Iowa. PILOT is now available for broader use at the project website: http://srg.cce.iastate.edu/lrfd/. DSHAFT, available in electronic form at http://srg.cce.iastate.edu/dshaft/, is currently comprised of 32 separate load tests provided by Illinois, Iowa, Minnesota, Missouri and Nebraska state departments of transportation and/or department of roads. In addition to serving as a manual for DSHAFT and providing a summary of the available data, this report provides a preliminary analysis of the load test data from Iowa, and will open up opportunities for others to share their data through this quality–assured process, thereby providing a platform to improve LRFD approach to drilled shafts, especially in the Midwest region.

Demonstration of Load Rating Capabilities through Physical Load Testing: Sioux County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Sioux County Bridge (FHWA #308730), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Ida County Bridge (FHWA #186070) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Ida County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Ida County Bridge (FHWA #186070), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Johnson County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Johnson County Bridge (FHWA #205750), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Ida County Bridge (FHWA #186070). A tech brief provides overall information about the project.

Pilot Project - Demonstration of Load Rating Capabilities through Physical Load Testing: Tech Transfer Summary, RB32-013, 2013

This project demonstrated the capabilities for load testing bridges in Iowa, developed and presented a webinar to local and state engineers, and produced a spreadsheet and benefit evaluation matrix that others can use to preliminarily assess where bridge testing may be economically feasible given truck traffic and detour lengths.

Demonstration of Load Rating Capabilities through Physical Load Testing (4 vol), RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. The three final reports document one each of three bridges inspected, load tested, and load rated as part of the project. The bridges include the Sioux County Bridge (FHWA #308730), the Ida County Bridge (FHWA #186070), and the Johnson County Bridge (FHWA #205750). Actions included testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. A Tech Transfer Summary provides overall information about the project.

Quality Control/Quality Assurance Testing for Joint Density and Segregation of Asphalt Mixtures, TR-623, 2013

Longitudinal joint quality control/assurance is essential to the successful performance of asphalt pavements and it has received considerable amount of attention in recent years. The purpose of the study is to evaluate the level of compaction at the longitudinal joint and determine the effect of segregation on the longitudinal joint performance. Five paving projects with the use of traditional butt joint, infrared joint heater, edge restraint by milling and modified butt joint with the hot pinch longitudinal joint construction techniques were selected in this study. For each project, field density and permeability tests were made and cores from the pavement were obtained for in-lab permeability, air void and indirect tensile strength. Asphalt content and gradations were also obtained to determine the joint segregation. In general, this study finds that the minimum required joint density should be around 90.0% of the theoretical maximum density based on the AASHTO T166 method. The restrained-edge by milling and butt joint with the infrared heat treatment construction methods both create the joint density higher than this 90.0% limit. Traditional butt joint exhibits lower density and higher permeability than the criterion. In addition, all of the projects appear to have segregation at the longitudinal joint except for the edge-restraint by milling method.

Laboratory and Field Testing of an Accelerated Bridge Construction Demonstration Bridge: US Highway 6 Bridge over Keg Creek, RB02-012, 2013

The US Highway 6 Bridge over Keg Creek outside of Council Bluffs, Iowa is a demonstration bridge site chosen to put into practice newly-developed Accelerated Bridge Construction (ABC) concepts. One of these new concepts is the use of prefabricated high performance concrete (HPC) bridge elements that are connected, in place, utilizing advanced material closure-pours and quick-to-install connection details. The Keg Creek Bridge is the first bridge in the US to utilize moment-resisting ultra-high performance concrete (UHPC) joints in negative moment regions over piers. Through laboratory and live load field testing, performance of these transverse joints as well as global bridge behavior is quantified and examined. The effectiveness of the structural performance of the bridge is evaluated to provide guidance for future designs of similar bridges throughout the US.

Chemical variability in clays and pottery from a traditional cooking pot production village: Testing assumptions in Pereruela

This paper explores analytically the contemporary pottery-making community of Pereruela (north-west Spain) that produces cooking pots from a mixture of red clay and kaolin. Analyses by different techniques (XRF, NAA, XRD, SEM and petrography) showed an extremely high variability for cooking ware pottery produced in a single production centre, by the same technology and using local clays. The main source of chemical variation is related to the use of different red clays and the presence of non-normally distributed inclusions of monazite. These two factors induce a high chemical variability, not only in the output of a single production centre, but even in the paste of a single pot, to an extent to which chemical compositions from one"workshop", or even one"pot", could be classified as having different provenances. The implications for the chemical characterization and for provenance studies of archaeological ceramics are addressed.

MEPDG Work Plan Task No. 8: Validation of Pavement Performance Curves for the Mechanistic-Empirical Pavement Design Guide, 2009

The objective of this research is to determine whether the nationally calibrated performance models used in the Mechanistic-Empirical Pavement Design Guide (MEPDG) provide a reasonable prediction of actual field performance, and if the desired accuracy or correspondence exists between predicted and monitored performance for Iowa conditions. A comprehensive literature review was conducted to identify the MEPDG input parameters and the MEPDG verification/calibration process. Sensitivities of MEPDG input parameters to predictions were studied using different versions of the MEPDG software. Based on literature review and sensitivity analysis, a detailed verification procedure was developed. A total of sixteen different types of pavement sections across Iowa, not used for national calibration in NCHRP 1-47A, were selected. A database of MEPDG inputs and the actual pavement performance measures for the selected pavement sites were prepared for verification. The accuracy of the MEPDG performance models for Iowa conditions was statistically evaluated. The verification testing showed promising results in terms of MEPDG’s performance prediction accuracy for Iowa conditions. Recalibrating the MEPDG performance models for Iowa conditions is recommended to improve the accuracy of predictions. ****************** Large File**************************

Non-Destructive Evaluation of Iowa Pavements Phase 2: Development of a Fully Automated Software System for Rapid Analysis/Processing of the Falling Weight Deflectometer Data, 2009

The Office of Special Investigations at Iowa Department of Transportation (DOT) collects FWD data on regular basis to evaluate pavement structural conditions. The primary objective of this study was to develop a fully-automated software system for rapid processing of the FWD data along with a user manual. The software system automatically reads the FWD raw data collected by the JILS-20 type FWD machine that Iowa DOT owns, processes and analyzes the collected data with the rapid prediction algorithms developed during the phase I study. This system smoothly integrates the FWD data analysis algorithms and the computer program being used to collect the pavement deflection data. This system can be used to assess pavement condition, estimate remaining pavement life, and eventually help assess pavement rehabilitation strategies by the Iowa DOT pavement management team. This report describes the developed software in detail and can also be used as a user-manual for conducting simulation studies and detailed analyses. *********************** Large File ***********************