The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform

Babatunde A. Ogunnaike - One of the best experts on this subject based on the ideXlab platform.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    Journal of Process Control, 2016
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease featuring abnormally low Platelet Count, are susceptible to excessive bleeding. One of the more effective treatment regimens is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Count oscillates between dangerously low and extremely high values, as a consequence of the complex nonlinear dynamics associated with Platelet production. This study aims to determine the optimum romiplostim dose profile required to maintain a stable Platelet Count for a specific ITP patient. Using the specific patient’s Platelet Count data obtained in response to a series of romiplostim doses, a pharmacokinetics/pharmacodynamics model was developed, validated, and analyzed to obtain insight into the patient’s physiological characteristics. The model was subsequently used to investigate the performance of three control strategies for weekly and bi-weekly treatment regimens. A stable Platelet Count is more likely to be achieved in the specific patient with weekly treatments. Bi-weekly treatments are less effective because fundamental characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. Model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients. The strategies developed in this work provide potential solutions to the highly variable responses observed among ITP patients undergoing romiplostim treatment. The approach can also be applied to other diseases with complex system dynamics.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    IFAC Proceedings Volumes, 2014
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease characterized by abnormally low Platelet Count, are susceptible to excessive bleeding as a direct consequence. While the problem of low Platelet Count can be addressed fundamentally either by slowing down the rate of Platelet destruction or by increasing Platelet production, or both, one of the more effective means of treating ITP patients is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Counts oscillate between dangerously low values and extremely high peaks, as a direct consequence of the complex nonlinear dynamics associated with Platelet Count regulation. The objective of this study is to determine the optimum dose profile of romiplostim for a specific ITP patient required to maintain a Platelet Count of 70×109/L. Using clinical data of the specific patient's Platelet Count obtained in response to a series of subcutaneously applied doses of romiplostim, a standard pharmacokinetics/pharmacodynamics (PKPD) model was developed, validated, and analyzed to obtain insight into the patient's physiological characteristics. The model was subsequently used to investigate the performance of three control strategies: “fixed dose” open-loop control, “variable dose” discrete PI feedback control, and “variable dose” model-based open-loop optimal control. The control strategies were implemented for weekly and bi-weekly treatment regimens. With both treatment frequencies, the fixed dose open-loop control strategy resulted in unacceptable sustained oscillating Platelet Count. PI feedback control and model-based optimal open-loop control led to stable Platelet Count profiles after approximately 50 days but only for weekly injections. In summary, a stable Platelet Count is more likely to be achieved consistently in the specific patient with weekly treatments. Bi-weekly treatments are less effective because, as we show, fundamental pharmaceutical characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. The results show that model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients.

Pierre Deltenre - One of the best experts on this subject based on the ideXlab platform.

  • liver stiffness and Platelet Count for identifying patients with compensated liver disease at low risk of variceal bleeding
    Liver International, 2017
    Co-Authors: Astrid Marot, Eric Trepo, Christopher Doerig, Alain M Schoepfer, Christophe Moreno, Pierre Deltenre
    Abstract:

    SummaryBackground The 2015 Baveno VI guidelines recommend against performing upper gastrointestinal endoscopy in patients with compensated cirrhosis who have a liver stiffness 150'000/mm³ because of a low prevalence of varices at risk of bleeding in this population Aim Synthesize the available evidence on the usefulness of the combined use of liver stiffness and Platelet Count to identify patients without esophageal varices Methods Meta-analysis of trials evaluating the usefulness of a given cut-off for liver stiffness and Platelet Count to rule out the presence of esophageal varices Results Fifteen studies were included. All studies excepting 5 used the Baveno VI criteria. Compared to patients with either high liver stiffness or low Platelet Count, those with low liver stiffness and normal Platelet Count had a lower risk of varices at risk of bleeding (OR=0.22, 95% CI=0.13-0.39, p<0.001) with low heterogeneity between studies (I2=21%). They also had a lower risk of varices (OR=0.23, 95% CI=0.17-0.32, p<0.001) with moderate heterogeneity between studies (I2=28%). In patients with low liver stiffness and normal Platelet Count, the pooled estimate rates for varices at risk of bleeding was 0.040 (95% CI=0.027-0.059) with low heterogeneity between studies (I2=3%) Conclusion Patients with low liver stiffness and normal Platelet Count have a lower risk of varices than those with either high liver stiffness or low Platelet Count. Varices at risk of bleeding are found in no more than 4% of patients when liver stiffness is <20 kPa and Platelet Count is normal. This article is protected by copyright. All rights reserved.

  • Liver stiffness and Platelet Count for identifying patients with compensated liver disease at low risk of variceal bleeding
    Liver International, 2016
    Co-Authors: Astrid Marot, Eric Trepo, Christopher Doerig, Alain M Schoepfer, Christophe Moreno, Pierre Deltenre
    Abstract:

    SummaryBackground The 2015 Baveno VI guidelines recommend against performing upper gastrointestinal endoscopy in patients with compensated cirrhosis who have a liver stiffness 150'000/mm³ because of a low prevalence of varices at risk of bleeding in this population Aim Synthesize the available evidence on the usefulness of the combined use of liver stiffness and Platelet Count to identify patients without esophageal varices Methods Meta-analysis of trials evaluating the usefulness of a given cut-off for liver stiffness and Platelet Count to rule out the presence of esophageal varices Results Fifteen studies were included. All studies excepting 5 used the Baveno VI criteria. Compared to patients with either high liver stiffness or low Platelet Count, those with low liver stiffness and normal Platelet Count had a lower risk of varices at risk of bleeding (OR=0.22, 95% CI=0.13-0.39, p

Chiahung Tsai - One of the best experts on this subject based on the ideXlab platform.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    Journal of Process Control, 2016
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease featuring abnormally low Platelet Count, are susceptible to excessive bleeding. One of the more effective treatment regimens is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Count oscillates between dangerously low and extremely high values, as a consequence of the complex nonlinear dynamics associated with Platelet production. This study aims to determine the optimum romiplostim dose profile required to maintain a stable Platelet Count for a specific ITP patient. Using the specific patient’s Platelet Count data obtained in response to a series of romiplostim doses, a pharmacokinetics/pharmacodynamics model was developed, validated, and analyzed to obtain insight into the patient’s physiological characteristics. The model was subsequently used to investigate the performance of three control strategies for weekly and bi-weekly treatment regimens. A stable Platelet Count is more likely to be achieved in the specific patient with weekly treatments. Bi-weekly treatments are less effective because fundamental characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. Model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients. The strategies developed in this work provide potential solutions to the highly variable responses observed among ITP patients undergoing romiplostim treatment. The approach can also be applied to other diseases with complex system dynamics.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    IFAC Proceedings Volumes, 2014
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease characterized by abnormally low Platelet Count, are susceptible to excessive bleeding as a direct consequence. While the problem of low Platelet Count can be addressed fundamentally either by slowing down the rate of Platelet destruction or by increasing Platelet production, or both, one of the more effective means of treating ITP patients is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Counts oscillate between dangerously low values and extremely high peaks, as a direct consequence of the complex nonlinear dynamics associated with Platelet Count regulation. The objective of this study is to determine the optimum dose profile of romiplostim for a specific ITP patient required to maintain a Platelet Count of 70×109/L. Using clinical data of the specific patient's Platelet Count obtained in response to a series of subcutaneously applied doses of romiplostim, a standard pharmacokinetics/pharmacodynamics (PKPD) model was developed, validated, and analyzed to obtain insight into the patient's physiological characteristics. The model was subsequently used to investigate the performance of three control strategies: “fixed dose” open-loop control, “variable dose” discrete PI feedback control, and “variable dose” model-based open-loop optimal control. The control strategies were implemented for weekly and bi-weekly treatment regimens. With both treatment frequencies, the fixed dose open-loop control strategy resulted in unacceptable sustained oscillating Platelet Count. PI feedback control and model-based optimal open-loop control led to stable Platelet Count profiles after approximately 50 days but only for weekly injections. In summary, a stable Platelet Count is more likely to be achieved consistently in the specific patient with weekly treatments. Bi-weekly treatments are less effective because, as we show, fundamental pharmaceutical characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. The results show that model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients.

Giovanni Casazza - One of the best experts on this subject based on the ideXlab platform.

  • Platelet Count spleen length and Platelet Count to spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis
    Cochrane Database of Systematic Reviews, 2017
    Co-Authors: Agostino Colli, Juan Cristobal Gana, Jason Yap, Thomasin Adamswebber, Natalie Rashkovan, Simon C Ling, Giovanni Casazza
    Abstract:

    Background Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis. This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks, although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Platelet Count, spleen length, and Platelet Count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices. Objectives Primary objectives To determine the diagnostic accuracy of Platelet Count, spleen length, and Platelet Count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. We aimed to perform pair-wise comparisons between the three index tests, while considering predefined cut-off values. We investigated sources of heterogeneity. Search methods The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science) (14 June 2016). We applied no language or document-type restrictions. Selection criteria Studies evaluating the diagnostic accuracy of Platelet Count, spleen length, and Platelet Count-to-spleen length ratio for the diagnosis of oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age with chronic liver disease or portal vein thrombosis, who did not have variceal bleeding. Data collection and analysis Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. Main results We included 71 studies, 67 of which enrolled only adults and four only children. All included studies were cross-sectional and were undertaken at a tertiary care centre. Eight studies reported study results in abstracts or letters. We considered all but one of the included studies to be at high risk of bias. We had major concerns about defining the cut-off value for the three index tests; most included studies derived the best cut-off values a posteriori, thus overestimating accuracy; 16 studies were designed to validate the 909 (n/mm3)/mm cut-off value for Platelet Count-to-spleen length ratio. Enrolment of participants was not consecutive in six studies and was unclear in 31 studies. Thirty-four studies assessed enrolment consecutively. Eleven studies excluded some included participants from the analyses, and in only one study, the time interval between index tests and the reference standard was longer than three months. Diagnosis of varices of any size. Platelet Count showed sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000 to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources of heterogeneity, we found that of all predefined factors, only aetiology had a role: studies including participants with chronic hepatitis C reported different results when compared with studies including participants with mixed aetiologies (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from 110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and specificity of 0.84 (95% CI 0.75 to 0.91) in 17 studies, and 2637 participants had a cut-off value for Platelet Count-to-spleen length ratio of 909 (n/mm3)/mm. We found no effect of predefined sources of heterogeneity. An overall indirect comparison of the HSROCs of the three index tests showed that Platelet Count-to-spleen length ratio was the most accurate index test when compared with Platelet Count (P < 0.001) and spleen length (P < 0.001). Diagnosis of varices at high risk of bleeding. Platelet Count showed sensitivity of 0.80 (95% CI 0.73 to 0.85) and specificity of 0.68 (95% CI 0.57 to 0.77) (cut-off value of around 150,000/mm3 from 140,000 to 160,000/mm3; seven studies, 1671 participants). For spleen length, we obtained only a summary ROC curve as we found no common cut-off between studies (six studies, 883 participants). Platelet Count-to-spleen length ratio showed sensitivity of 0.85 (95% CI 0.72 to 0.93) and specificity of 0.66 (95% CI 0.52 to 0.77) (cut-off value of around 909 (n/mm3)/mm; from 897 to 921 (n/mm3)/mm; seven studies, 642 participants). An overall indirect comparison of the HSROCs of the three index tests showed that Platelet Count-to-spleen length ratio was the most accurate index test when compared with Platelet Count (P = 0.003) and spleen length (P < 0.001). DIagnosis of varices of any size in children. We found four studies including 277 children with different liver diseases and or portal vein thrombosis. Platelet Count showed sensitivity of 0.71 (95% CI 0.60 to 0.80) and specificity of 0.83 (95% CI 0.70 to 0.91) (cut-off value of around 115,000/mm3; four studies, 277 participants). Platelet Count-to-spleen length z-score ratio showed sensitivity of 0.74 (95% CI 0.65 to 0.81) and specificity of 0.64 (95% CI 0.36 to 0.84) (cut-off value of 25; two studies, 197 participants). Authors' conclusions Platelet Count-to-spleen length ratio could be used to stratify the risk of oesophageal varices. This test can be used as a triage test before endoscopy, thus ruling out adults without varices. In the case of a ratio > 909 (n/mm3)/mm, the presence of oesophageal varices of any size can be excluded and only 7% of adults with varices of any size would be missed, allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations. This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis. Future studies should assess the diagnostic accuracy of this test in specific subgroups of patients, as well as its ability to predict variceal bleeding. New non-invasive tests should be examined.

Stanley I. Sandler - One of the best experts on this subject based on the ideXlab platform.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    Journal of Process Control, 2016
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease featuring abnormally low Platelet Count, are susceptible to excessive bleeding. One of the more effective treatment regimens is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Count oscillates between dangerously low and extremely high values, as a consequence of the complex nonlinear dynamics associated with Platelet production. This study aims to determine the optimum romiplostim dose profile required to maintain a stable Platelet Count for a specific ITP patient. Using the specific patient’s Platelet Count data obtained in response to a series of romiplostim doses, a pharmacokinetics/pharmacodynamics model was developed, validated, and analyzed to obtain insight into the patient’s physiological characteristics. The model was subsequently used to investigate the performance of three control strategies for weekly and bi-weekly treatment regimens. A stable Platelet Count is more likely to be achieved in the specific patient with weekly treatments. Bi-weekly treatments are less effective because fundamental characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. Model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients. The strategies developed in this work provide potential solutions to the highly variable responses observed among ITP patients undergoing romiplostim treatment. The approach can also be applied to other diseases with complex system dynamics.

  • Platelet Count control in immune thrombocytopenic purpura patient optimum romiplostim dose profile
    IFAC Proceedings Volumes, 2014
    Co-Authors: Chiahung Tsai, James B Bussel, Allison Imahiyerobo, Stanley I. Sandler, Babatunde A. Ogunnaike
    Abstract:

    Abstract Patients with immune thrombocytopenic purpura (ITP), a disease characterized by abnormally low Platelet Count, are susceptible to excessive bleeding as a direct consequence. While the problem of low Platelet Count can be addressed fundamentally either by slowing down the rate of Platelet destruction or by increasing Platelet production, or both, one of the more effective means of treating ITP patients is to increase Platelet production with romiplostim. However, current romiplostim treatment strategies tend to produce undesirable responses where Platelet Counts oscillate between dangerously low values and extremely high peaks, as a direct consequence of the complex nonlinear dynamics associated with Platelet Count regulation. The objective of this study is to determine the optimum dose profile of romiplostim for a specific ITP patient required to maintain a Platelet Count of 70×109/L. Using clinical data of the specific patient's Platelet Count obtained in response to a series of subcutaneously applied doses of romiplostim, a standard pharmacokinetics/pharmacodynamics (PKPD) model was developed, validated, and analyzed to obtain insight into the patient's physiological characteristics. The model was subsequently used to investigate the performance of three control strategies: “fixed dose” open-loop control, “variable dose” discrete PI feedback control, and “variable dose” model-based open-loop optimal control. The control strategies were implemented for weekly and bi-weekly treatment regimens. With both treatment frequencies, the fixed dose open-loop control strategy resulted in unacceptable sustained oscillating Platelet Count. PI feedback control and model-based optimal open-loop control led to stable Platelet Count profiles after approximately 50 days but only for weekly injections. In summary, a stable Platelet Count is more likely to be achieved consistently in the specific patient with weekly treatments. Bi-weekly treatments are less effective because, as we show, fundamental pharmaceutical characteristics of romiplostim make oscillations in Platelet Count unavoidable at this treatment frequency. The results show that model-based decisions determined using patient-specific mathematical models are potentially useful for designing better treatment regimens for ITP patients.