Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.

A simple and sensitive LC-MS method was developed and validated for the simultaneous quantification of aripiprazole (ARI), atomoxetine (ATO), duloxetine (DUL), clozapine (CLO), olanzapine (OLA), sertindole (STN), venlafaxine (VEN) and their active metabolites dehydroaripiprazole (DARI), norclozapine (NCLO), dehydrosertindole (DSTN) and O-desmethylvenlafaxine (OVEN) in human plasma. The above mentioned compounds and the internal standard (remoxipride) were extracted from 0.5 mL plasma by solid-phase extraction (mix mode support). The analytical separation was carried out on a reverse phase liquid chromatography at basic pH (pH 8.1) in gradient mode. All analytes were monitored by MS detection in the single ion monitoring mode and the method was validated covering the corresponding therapeutic range: 2-200 ng/mL for DUL, OLA, and STN, 4-200 ng/mL for DSTN, 5-1000 ng/mL for ARI, DARI and finally 2-1000 ng/mL for ATO, CLO, NCLO, VEN, OVEN. For all investigated compounds, good performance in terms of recoveries, selectivity, stability, repeatability, intermediate precision, trueness and accuracy, was obtained. Real patient plasma samples were then successfully analysed.

A CT-based study investigating the relationship between pedicle screw placement and stimulation threshold of compound muscle action potentials measured by intraoperative neurophysiological monitoring.

PURPOSE: Neurophysiological monitoring aims to improve the safety of pedicle screw placement, but few quantitative studies assess specificity and sensitivity. In this study, screw placement within the pedicle is measured (post-op CT scan, horizontal and vertical distance from the screw edge to the surface of the pedicle) and correlated with intraoperative neurophysiological stimulation thresholds. METHODS: A single surgeon placed 68 thoracic and 136 lumbar screws in 30 consecutive patients during instrumented fusion under EMG control. The female to male ratio was 1.6 and the average age was 61.3 years (SD 17.7). Radiological measurements, blinded to stimulation threshold, were done on reformatted CT reconstructions using OsiriX software. A standard deviation of the screw position of 2.8 mm was determined from pilot measurements, and a 1 mm of screw-pedicle edge distance was considered as a difference of interest (standardised difference of 0.35) leading to a power of the study of 75 % (significance level 0.05). RESULTS: Correct placement and stimulation thresholds above 10 mA were found in 71 % of screws. Twenty-two percent of screws caused cortical breach, 80 % of these had stimulation thresholds above 10 mA (sensitivity 20 %, specificity 90 %). True prediction of correct position of the screw was more frequent for lumbar than for thoracic screws. CONCLUSION: A screw stimulation threshold of >10 mA does not indicate correct pedicle screw placement. A hypothesised gradual decrease of screw stimulation thresholds was not observed as screw placement approaches the nerve root. Aside from a robust threshold of 2 mA indicating direct contact with nervous tissue, a secondary threshold appears to depend on patients' pathology and surgical conditions.

Estimate of Groundwater Recharge Based on Water Balance in The Unsaturated Soil Zone

ABSTRACT Groundwater management depends on the knowledge on recharge rates and water fluxes within aquifers. The recharge is one of the water cycle components most difficult to estimate. As a result, despite the chosen method, the estimates are subject to uncertainties that can be identified by means of comparison with other approaches. In this study, groundwater recharge estimates based on the water balance in the unsaturated zone is assessed. Firstly, the approach is evaluated by comparing the results with those of another method. Then, the estimates are used as inputs in a transient groundwater flow model in order to assess how the water table would respond to the obtained recharges rates compared to measured levels. The results suggest a good performance of the adopted approach and, despite some inherent limitations, it has advantages over other methods since the data required are easier to obtain.

Assessing the impact of DRGs on patient care and professional practice in Switzerland (IDoC) : a potential model for monitoring and evaluating healthcare reform.

QUESTIONS UNDER STUDY: The starting point of the interdisciplinary project "Assessing the impact of diagnosis related groups (DRGs) on patient care and professional practice" (IDoC) was the lack of a systematic ethical assessment for the introduction of cost containment measures in healthcare. Our aim was to contribute to the methodological and empirical basis of such an assessment. METHODS: Five sub-groups conducted separate but related research within the fields of biomedical ethics, law, nursing sciences and health services, applying a number of complementary methodological approaches. The individual research projects were framed within an overall ethical matrix. Workshops and bilateral meetings were held to identify and elaborate joint research themes. RESULTS: Four common, ethically relevant themes emerged in the results of the studies across sub-groups: (1.) the quality and safety of patient care, (2.) the state of professional practice of physicians and nurses, (3.) changes in incentives structure, (4.) vulnerable groups and access to healthcare services. Furthermore, much-needed data for future comparative research has been collected and some early insights into the potential impact of DRGs are outlined. CONCLUSIONS: Based on the joint results we developed preliminary recommendations related to conceptual analysis, methodological refinement, monitoring and implementation.

Flow-microfluorometric monitoring of oligoclonal CD8+ T cell responses to an immunodominant Moloney leukemia virus-encoded epitope in vivo.

The TCR repertoire of CD8+ T cells specific for Moloney murine leukemia virus (M-MuLV)-associated Ags has been investigated in vitro and in vivo. Analysis of a large panel of established CD8+ CTL clones specific for M-MuLV indicated an overwhelming bias for V beta4 in BALB/c mice and for V beta5.2 in C57BL/6 mice. These V beta biases were already detectable in mixed lymphocyte:tumor cell cultures established from virus-immune spleen cells. Furthermore, direct ex vivo analysis of PBL from BALB/c or C57BL/6 mice immunized with syngeneic M-MuLV-infected tumor cells revealed a dramatic increase in CD8+ cells expressing V beta4 or V beta5.2, respectively. M-MuLV-specific CD8+ cells with an activated (CD62L-) phenotype persisted in blood of immunized mice for at least 2 mo, and exhibited decreased TCR and CD8 levels compared with their naive counterparts. In C57BL/6 mice, most M-MuLV-specific CD8+ CTL clones and immune PBL coexpressed V alpha3.2 in association with V beta5.2. Moreover, these V beta5.2+ V alpha3.2+ cells were shown to recognize the recently described H-2Db-restricted epitope (CCLCLTVFL) encoded in the leader sequence of the M-MuLV gag polyprotein. Collectively, our data demonstrate a highly restricted TCR repertoire in the CD8+ T cell response to M-MuLV-associated Ags in vivo, and suggest the potential utility of flow-microfluorometric analysis of V beta and V alpha expression in the diagnosis and monitoring of viral infections.

Using step activity monitoring to assess ambulatory activity before and after total ankle arthroplasty : FM103

Introduction: The aim of this study is to compare the walking activity of a cohort of individuals before and after total ankle arthroplasty (TAA). Methods: Nineteen consecutive patients (ten males and nine females) with mean age of 58.72, selected for TAA between January and June 2006, were prospectively reviewed with the use of a dedicated ambulatory activity-monitoring device to assess their natural ambulatory activity. Patients were tested in the community for two weeks duration, one month prior to and at least eighteen months after surgery. The ambulatory parameters were assessed through measurement of the number of steps at different cadence, and the time spent walking at different walking paces. Data were analyzed by using specific statistical methods. Results: This study revealed a significant improvement in the number of steps walked at normal cadence (b = 331.63, p = .00) and significantly reduced at low cadence (b = -402.52, p = .00) and medium cadence (b = -386.29, p = .00), before and after TAA. However, there are no significant different between two phases of assessment in term of time spent walking. Conclusion: These quantitative data allow a clear comparative assessment of walking ability following TAR and demonstrates that this intervention improves patient's walking pace.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Therapeutic drug monitoring in cancer - Are we missing a trick?

Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in biological samples to individualise treatment by adapting drug dose to improve efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep dose-response relationships and narrow therapeutic windows. Inter-individual pharmacokinetic (PK) variability is often substantial. There are, however, a multitude of reasons why TDM has never been fully implemented in daily oncology practice. These include difficulties in establishing appropriate concentration target, common use of combination chemotherapies and the paucity of published data from pharmacological trials. The situation is different with targeted therapies. The large interindividual PK variability is influenced by the pharmacogenetic background of the patient (e.g. cytochrome P450 and ABC transporters polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure correlates with treatment response in various cancers. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug-drug interactions and concerns over adherence treatment. There are still few data with monoclonal antibodies (mAbs) in favour of TDM approaches, even if data showed encouraging results with rituximab and cetuximab. TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.

Monitoring Disease Activity and Progression in Crohn's Disease. A Swiss Perspective on the IBD Ahead 'Optimised Monitoring' Recommendations.

BACKGROUND AND AIMS: The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. METHODS: The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. RESULTS: A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. CONCLUSION: The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations. © 2014 S. Karger AG, Basel.

Utilization of Remote Traffic Monitoring Devices for Urban Freeway Work Zone Assessment Final Report, January 2012

The objective of this project was to promote and facilitate analysis and evaluation of the impacts of road construction activities in Smart Work Zone Deployment Initiative (SWZDI) states. The two primary objectives of this project were to assess urban freeway work-zone impacts through use of remote monitoring devices, such as radar-based traffic sensors, traffic cameras, and traffic signal loop detectors, and evaluate the effectiveness of using these devices for such a purpose. Two high-volume suburban freeway work zones, located on Interstate 35/80 (I-35/I-80) through the Des Moines, Iowa metropolitan area, were evaluated at the request of the Iowa Department of Transportation (DOT).

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Wind Monitoring of the Saylorville and Red Rock Reservoir Bridges with Remote, Cellular-Based Notifications, May 2012

Following high winds on January 24, 2006, at least five people claimed to have seen or felt the superstructure of the Saylorville Reservoir Bridge in central Iowa moving both vertically and laterally. Since that time, the Iowa Department of Transportation (DOT) contracted with the Bridge Engineering Center at Iowa State University to design and install a monitoring system capable of providing notification of the occurrence of subsequent high winds. Although measures were put into place following the 2006 event at the Saylorville Reservoir Bridge, knowledge of the performance of this bridge during high wind events was incomplete. Therefore, the Saylorville Reservoir Bridge was outfitted with an information management system to investigate the structural performance of the structure and the potential for safety risks. In subsequent years, given the similarities between the Saylorville and Red Rock Reservoir bridges, a similar system was added to the Red Rock Reservoir Bridge southeast of Des Moines. The monitoring system developed and installed on these two bridges was designed to monitor the wind speed and direction at the bridge and, via a cellular modem, send a text message to Iowa DOT staff when wind speeds meet a predetermined threshold. The original intent was that, once the text message is received, the bridge entrances would be closed until wind speeds diminish to safe levels.

State Legislation Monitoring Report FY 2005, February 2006

The Division of Criminal and Juvenile Justice Planning issued its first state legislation monitoring report in February 2002, covering the first six months’ impact of Senate File 543 (which enacted a number of sentencing changes) on the justice system; monitoring of the correctional impact of this bill was at the request of several members of the legislature. Since then, the Criminal and Juvenile Justice Planning Advisory Council has requested that CJJP monitor the correctional impact of enacted legislation of particular interest.