888 resultados para Therapeutic drug monitoring


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Bleeding related wound complications cause significant morbidity in lower limb arthroplasty surgery. Patients who require therapeutic anticoagulation in the peri operative period are potentially at higher risk of these complications. This is a retrospective case control study reviewing all primary total hip replacements performed in a single center over a five year period and comparing outcomes of the patients on warfarin with a double-matched control group of patients not on warfarin. The warfarin group had significantly higher risk of deep joint infection (9% vs 2.2%), haematoma/ wound ooze (28% vs 4%) and superficial infection (13.5% vs 2.2%). Managing the total hip arthroplasty patient with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding related complications. Improved understanding of this risk will better allow the patient to make an informed decision regarding their elective arthroplasty surgery.

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Many clinicians in the area of drug addiction believe that emotional problems arise from particular styles of parenting. To investigate this link, 63 young male and female addicts who had sought treatment completed the Parental Bonding Instrument which tapped their perceptions of their relationship with each parent. Addicts reported early parental experiences differing from those of a control group. Drug abusers judged their parents as cold, indifferent, controlling and intrusive. In addition, these perceptions were shared by male and female addicts. These results, together with previous research suggest that these perceptions might well point to a general risk factor for the development of a broad range of psychological and psychiatric disorders. In addition, the issue of family factors in the design and implementation of drug treatment programs needs to be addressed.

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The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

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The ability to forecast machinery health is vital to reducing maintenance costs, operation downtime and safety hazards. Recent advances in condition monitoring technologies have given rise to a number of prognostic models which attempt to forecast machinery health based on condition data such as vibration measurements. This paper demonstrates how the population characteristics and condition monitoring data (both complete and suspended) of historical items can be integrated for training an intelligent agent to predict asset health multiple steps ahead. The model consists of a feed-forward neural network whose training targets are asset survival probabilities estimated using a variation of the Kaplan–Meier estimator and a degradation-based failure probability density function estimator. The trained network is capable of estimating the future survival probabilities when a series of asset condition readings are inputted. The output survival probabilities collectively form an estimated survival curve. Pump data from a pulp and paper mill were used for model validation and comparison. The results indicate that the proposed model can predict more accurately as well as further ahead than similar models which neglect population characteristics and suspended data. This work presents a compelling concept for longer-range fault prognosis utilising available information more fully and accurately.

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Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.

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Knowledge of cable parameters has been well established but a better knowledge of the environment in which the cables are buried lags behind. Research in Queensland University of Technology has been aimed at obtaining and analysing actual daily field values of thermal resistivity and diffusivity of the soil around power cables. On-line monitoring systems have been developed and installed with a data logger system and buried spheres that use an improved technique to measure thermal resistivity and diffusivity over a short period. Results based on long term continuous field data are given. A probabilistic approach is developed to establish the correlation between the measured field thermal resistivity values and rainfall data from weather bureau records. This data from field studies can reduce the risk in cable rating decisions and provide a basis for reliable prediction of “hot spot” of an existing cable circuit

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Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

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In this paper we demonstrate how to monitor a smartphone running Symbian operating system and Windows Mobile in order to extract features for anomaly detection. These features are sent to a remote server because running a complex intrusion detection system on this kind of mobile device still is not feasible due to capability and hardware limitations. We give examples on how to compute relevant features and introduce the top ten applications used by mobile phone users based on a study in 2005. The usage of these applications is recorded by a monitoring client and visualized. Additionally, monitoring results of public and self-written malwares are shown. For improving monitoring client performance, Principal Component Analysis was applied which lead to a decrease of about 80 of the amount of monitored features.

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Brief interventions are effective for problem drinking and reductions are known to occur in association with screening and assessment. Design and methods: This study aimed to determine how much change occurred between baseline assessment and a one-session brief intervention (S1), and the predictors of early change among adults with comorbid depression and alcohol misuse (n=202) participating in a clinical trial. The primary focus was on changes in Beck Depression Inventory fastscreen scores and alcohol consumption (standard drinks per week) prior to random allocation to nine further sessions addressing either depression, alcohol, or both problems. Results: There were large and clinically significant reductions between baseline and S1, with the strongest predictors being baseline scores in the relevant domain and change in the other domain. Client engagement was also predictive of early depression changes. Discussion and Conclusion: Monitoring progress in both domains from first contact, and provision of empathic care, followed by brief intervention appear to be useful for this high prevalence comorbidity...

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The Therapeutic Advice and Information Service was funded by the National Prescribing Service to provide a national drug information service for health professionals working in the community. For ten years the service achieved high levels of client satisfaction, and reached its contracted target of 6000 enquiries about medicines per year, however the service ceased on 30 June 2010.

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This article proposes an approach for real-time monitoring of risks in executable business process models. The approach considers risks in all phases of the business process management lifecycle, from process design, where risks are defined on top of process models, through to process diagnosis, where risks are detected during process execution. The approach has been realized via a distributed, sensor-based architecture. At design-time, sensors are defined to specify risk conditions which when fulfilled, are a likely indicator of negative process states (faults) to eventuate. Both historical and current process execution data can be used to compose such conditions. At run-time, each sensor independently notifies a sensor manager when a risk is detected. In turn, the sensor manager interacts with the monitoring component of a business process management system to prompt the results to process administrators who may take remedial actions. The proposed architecture has been implemented on top of the YAWL system, and evaluated through performance measurements and usability tests with students. The results show that risk conditions can be computed efficiently and that the approach is perceived as useful by the participants in the tests.