165 research outputs found
Computerised advice on drug dosage decisions in childhood leukaemia: A method and a safety strategy
No full textCurrently over 95% of children who are diagnosed with Acute Lymphoblastic Leukaemia in the UK are enrolled into Medical Research Council trials. The trial protocol specifies that following initial treatment there is a 2-3 year maintenance period during which drug dosage decisions are made weekly according to a set of pre-defined rules. These rules are complex, and there is a significant frequency of error in clinical practice, which can lead to patient harm. We have built a web-based decision support system (called LISA) to address this problem. The dose alteration rules from lie MRC protocol were formalised in the PROforma guideline modeling language as a state transition problem, and dose adjustment recommendations are provided into the clinical setting by a PROforma enactment engine. The design and implementation of the decision support module, the safety issues raised and the strategy adopted for resolving them are discussed. System safety is very likely to become a major professional challenge for the medical AI community and it can be addressed, in this case, with relatively straightforward techniques
LISA: a web-based decision-support system for trial management of childhood acute lymphoblastic leukaemia
No full textContinuation chemotherapy is a key component of the treatment of childhood acute lymphoblastic leukaemia. During this treatment phase, weekly dose adjustments are carried out based on current and historical full blood counts (FBCs). The dose decision pathway is complex and suboptimal therapy may result if information on FBC results is not readily available and/or the prescriber is inexperienced. A web-based decision-support system (Leukaemia Intervention Scheduling and Advice, ‘LISA’) was designed to facilitate access to FBC information across geographical locations and to assist with dosage adjustments. A balanced-block crossover analysis was performed to evaluate the system. Thirty-six clinicians with varying degrees of experience were each asked to decide on appropriate oral chemotherapy dosages for eight simulated cases: four using LISA and four without. LISA significantly reduced the number of erroneous prescriptions (zero of 144 with LISA vs. 54 of 144 without; P < 0·0001) without affecting the number of times subjects deliberately overrode the protocol (seven of 144 times using LISA and six of 144 without). Using LISA reduced the time taken by novices to reach a decision for each case but increased the time taken by experts. Thirty-five of 36 subjects said they would be likely to use the system if it were available. A system like LISA is likely to be acceptable to clinicians, and has the potential to increase protocol compliance and decrease prescribing errors while allowing clinicians to override the protocol in specific cases where sound reasons exist for doing so
A Quantitative and Qualitative Evaluation of LISA, a Decision Support System for Chemotherapy Dosing in Childhood Acute Lymphoblastic Leukaemia.
No full textObjectives: to assess the acceptability to clinicians of a web-based decision support system designed to assist with dosage adjustments during maintenance therapy for childhood Acute Lymphoblastic Leukaemia (ALL), and to evaluate the potential impact of the system on decision-making and dosage calculations.Design: balanced-block crossover experiment with simulated cases; questionnaire study and semi-structured interviews.Participants: 36 clinicians with differing experience in the management of ALL.Interventions: subjects were asked to decide on appropriate levels of chemotherapy dosing for 8 simulated cases, 4 using the LISA decision support system, 4 using conventional paper-based records and guidance.Main outcome measures: number of protocol-consistent dosage decisions made; time taken to manage each case; accuracy of dosage calculations; subjects' opinions as to whether or not they would use the system in practice. ADDITIONAL OUTCOME MEASURES: Functions subjects would like to see in an idealised system; subjects' satisfaction with the implementation of the functions provided by LISA; qualitative data on issues subjects felt would impact upon the successful deployment of the system
Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial
No full textWe report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) treated on the UK Medical Research Council (MRC) trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Forty-two (2·3%) patients were Ph+. Nineteen (45%) had <25% blasts in bone marrow (BM) within the first 2 weeks of treatment and were defined as a good response group (GRG), the others as a poor response group (PRG). Thirty-six (86%) achieved first complete remission (CR1) at the end of induction, of which 28 underwent BM transplantation (BMT). The median follow-up was 42 months (range, 21–84). The 3-year event-free survival (EFS; 52%, 95% CI, 36–66%) was a considerable improvement on the previous MRC UKALL XI trial (27%). EFS for the GRG and PRG were 68% (43–84%) and 39% (18–59%), respectively (P = 0·03); presenting white cell count <50 × 10^9/l (P = 0·02) was predictive for overall survival. Changes in the MRC ALL97 trial within the study period resulted in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction. Though the use of daunorubicin during induction was not a prospective study question, EFS was significantly better for those whose induction included this drug (P = 0·02). Steroid randomization was not stratified for Ph+ ALL patients and was not predictive for EFS. BMT in CR1 appeared to reduce the risk of a subsequent BM relapse. These results show significant improvement on previous MRC trials; future therapeutic strategies should include early intensive therapy and BMT in CR1
Synthesis of climate-water-food nexus in Illinois – data analysis and modeling
Full text linkThe climate is expected to change in the near future due to the global warming caused by anthropogenic release of greenhouse gases. Global warming is going to affect the atmospheric process (climate), biosphere process (hydrology) and the biological process (crop yield). Thus, the global warming will impact the nexus between climate-water-food. In this study, a methodology was developed to explore the threat posed by global warming on the climate-water-food nexus in the US Midwest dominated by rain-fed agricultural systems by leveraging data analysis and simulation modeling approaches. In accordance with the first step of the nexus, the historical temperature and precipitation time-series data were analyzed. The main objective of this analysis was to identify if these two climatic parameters have undergone any long-term change in the last half century when the impacts of global warming started to manifest themselves. Once the changes in temperature and precipitation were analyzed, the hydrological time-series data was also analyzed to determine if the climate change, and more specifically, precipitation change had driven any change in the hydrological regime. Under the condition that a shift in the hydrological regime is established, the next objective of this study was to determine the driver of such shift. Hydrological patterns are known to change by changes in atmospheric conditions driving the change in precipitation and temperature. The land phase of the hydrological process is also affected by the changes in the land use patterns such as deforestation, urbanization, and intensification in agricultural practices. In the rain-fed watersheds of the central Illinois, an upgrade in tile drainage systems in the 1970s, followed by the intensification of the cropping density in the recent decades have been identified to have driven a change in runoff processes from the land surface and tile drains. The next step in the implementation of the methodology involved the use of climate projections to analyze the impacts of climate change in the early and late century. But before the climate projection data can be used, it had to be tested for its ability to replicate the historical climate observations. If any bias in the projections are detected during such comparison, the data has to be processed to rectify such bias. In this study, the historical projections of temperature and precipitation were bias-corrected using quantile-mapping techniques. The bias-corrected data was then compared with the historical observations to identify if the bias-correction was able to improve the predictive skills of the climate projections. After that, the bias-corrected future climate data was explored to acquire an understanding of the long term outlook of the climate in the state of Illinois. Finally, a hydrological model for Embarras watershed – an agriculturally dominant rain-fed watershed of central Illinois – was developed. The model was calibrated for hydrology, nutrient transport and crop yield. The model was then forced with the bias-corrected climate projections data and the impacts of climate change on hydrology, nutrient transport and crop yield was analyzed.
No significant change in average daily, daily maximum and daily minimum temperature was detected for Illinois. From the analysis of the extreme temperature events it was observed that number of extremely hot days is decreasing and the number of warm nights is increasing. It was also found out that within the cropping season, the number of days with temperature within the growing degree days temperature for corn are increasing. From the analysis of precipitation data, it was found out that 40% of the observed stations had evidence of significant increase in precipitation. With further analysis, it was established that the increase in precipitation was driven by increase in both precipitation days and extreme precipitation events. From the study of the hydrological data from 6 watersheds of Illinois, significant shift in runoff was detected for the agricultural watersheds, whereas, no such shift could be established for forested watersheds. With precipitation not increasing in the watersheds with increasing runoff, it was established that the land-use changes was the major driving factor behind the change in hydrological regime over the agricultural watersheds. It was also established that the bias-correction of the climate projections using quantile-mapping techniques was able to improve the predictive skills of the projections. An exploration of bias-corrected future climate data established that Illinois will experience an increase in both temperature and precipitation in near and far future. By forcing the hydrological model of Embarras watershed with bias-corrected climate projections, it was observed that climate change will drive an increase in surface runoff and tile runoff, and consequently, nutrient transport from the tile drains. An increase in corn yield was also predicted under various scenarios.
Thus, the nexus between the climate-water-food was explored in this study that helped us analyze the impacts of global warming on these three components of the nexus in the recent past and the future.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-12-01The student, Vaskar Dahal, accepted the attached license on 2019-09-11 at 23:17.The student, Vaskar Dahal, submitted this Dissertation for approval on 2019-09-11 at 23:18.This Dissertation was approved for publication on 2019-09-16 at 15:42.DSpace SAF Submission Ingestion Package generated from Vireo submission #14450 on 2020-02-28 at 17:20:13Made available in DSpace on 2020-03-02T22:10:21Z (GMT). No. of bitstreams: 3
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Previous issue date: 2019-09-16Embargo set by: Seth Robbins for item 113853
Lift date: 2022-03-02T22:10:26Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 113853
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Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 113853
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Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 113853
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Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 113853
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Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 113853 on 2022-03-03T10:15:08Z
Impact of dose and duration of therapy on dexamethasone pharmacokinetics in childhood acute lymphoblastic leukaemiada report from the UKALL 2011 trial
No full textThe use of dexamethasone in acute lymphoblastic leukaemia therapy contributes to short- and long-term toxicities. The UKALL 2011 randomised trial investigated whether a more intense dexamethasone dose (10 mg/m2/d x 14d, short vs 6 mg/m2/d x 28d,standard) would lead to a more rapid cytoreduction and reduced adverse effects associated with longer durations of steroids in induction. The impact of dose and duration on dexamethasonepharmacokinetics was investigated. Methods: Blood samples were obtained on one of the first three and last three days of inductiondexamethasone dosing at time points up to 8 h after oral administration. Plasma dexamethasonelevels were quantified in 1084 plasma samples obtained from 174 children and apopulation pharmacokinetic model developed. Results: Drug exposure varied significantly between patients, with a >12-fold variation inAUC0e12h values and a marked overlap in dexamethasone exposures between dose levels. Intuitively, AUC0e12h was significantly higher with short dosing (10 mg/m2/d), but cumulative exposure was significantly higher with standard dosing over 28 days, after a higher cumulative dose. Concomitant rasburicase administration was associated with a 60% higher dexamethasone clearance. Day 8 bone marrow response was comparable between dosing arms, but those with <5% blast count exhibited a greater mean dexamethasone exposure than those with >5%. No statistical differences were observed between arms in terms of steroid-related toxicity or minimal residual disease at the end of induction. Conclusion: The potential significance of dexamethasone AUC0e12h on early response and higher cumulative exposure on the standard arm suggest that duration of therapy and exposure may be more important factors than absolute dose from a clinical pharmacology perspectiv
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