The Experts below are selected from a list of 531 Experts worldwide ranked by ideXlab platform
Zuzana Walker - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of 10 clinical trials and for 13 years after first approval of Ioflupane 123I injection datscan
The Journal of Nuclear Medicine, 2014Co-Authors: Donald G Grosset, Klaus Tatsch, Wolfgang H Oertel, Eduardo Tolosa, Nin Bajaj, Andreas Kupsch, John T Obrien, John Seibyl, Zuzana Walker, Paul SherwinAbstract:Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane 123I Injection is also known as DaTscan or DaTSCAN (123I-Ioflupane is also called 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or 123I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor’s clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (
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individual reader diagnostic performance and between reader agreement in assessment of subjects with parkinsonian syndrome or dementia using 123I Ioflupane injection datscan imaging
The Journal of Nuclear Medicine, 2014Co-Authors: John Seibyl, Donald G Grosset, Nin Bajaj, Andreas Kupsch, Zuzana Walker, Jan Booij, D C Costa, Robert A Hauser, Jacques Darcourt, Kenneth MarekAbstract:Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane 123I Injection (DaTscan, 123I-Ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of 123I-Ioflupane in a variety of clinical scenarios is essential. Methods: Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of 123I-Ioflupane: on-site versus 3–5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia. Results: Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%–91.2% to 81.6%–95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%–73.7%; specificity, 75.0%–83.3%) was compared versus month-36 diagnosis (77.5%–80.3% and 90.3%–96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%–89.9% and 77.4%–95.0%, respectively) and subjects with movement disorders (67.0%–97.9% and 71.4%–98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers. Conclusion: Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of 123I-Ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
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changes in dementia diagnostic category and diagnostic confidence following dopamine transporter spect imaging datscantm Ioflupane 123I in people with an uncertain diagnosis of dementia with lewy bodies possible dlb
Alzheimers & Dementia, 2013Co-Authors: Zuzana Walker, Alan J Thomas, Naji Tabet, Fraser Inglis, Alessandro Padovani, Gilberto Pizzolato, Michael Rainer, Emilio MorenoAbstract:AD stages or a predisposition to the disease:Preclinical AD stage TDR0: 9 (11.11%) direct relatives of patients with primary involutive changes in the brain; MMSE 26-28 points; Early AD stage TDR-1: 24 (29.63%) patients with mild dementia, mild cognitive impairment, had previously been diagnosed with AD; MMSE 20-25 points; Middle AD stage TDR-2: 31 (38.27%)patients with moderate dementia, sufficiently resistant cognitive impairment, had previously been diagnosed with AD; MMSE 12-19 points;Late AD stage TDR-3: 17 (20.99%) patients with a fairly severe dementia, gross cognitive impairment, had previously been diagnosed with AD; MMSE 7-11 points. Control Group: 59 patients with the most common brain lesions accompanied by neurodegenerative changes and development of dementia and cognitive impairment, but not suffering from AD. Results: Patients with different AD stages revealed the following changes in angioarchitectonics and microcirculation:Absence of marked atherosclerotic lesions of intracranial vessels;Degeneration of the capillary bed in the temporal and fronto-parietal regions;Development of multiple arteriovenous shunts in the same regions;Early venous dumping;Abnormal extension of venous trunks that receive blood from arteriovenous shunts in the temporal and fronto-parietal regions;Stagnation of venous blood on the border of the frontal and parietal regions;Increased looping of intracranial arteries. Control Group patients had no combination of such changes. Conclusions: These vascular changes are specific for AD and form the vascular factor of the disease which plays an important role in AD etiology and pathogenesis. Patients suffering from other diseases associated with neurodegenerative changes in the brain do not have similar lesions.
John Seibyl - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of 10 clinical trials and for 13 years after first approval of Ioflupane 123I injection datscan
The Journal of Nuclear Medicine, 2014Co-Authors: Donald G Grosset, Klaus Tatsch, Wolfgang H Oertel, Eduardo Tolosa, Nin Bajaj, Andreas Kupsch, John T Obrien, John Seibyl, Zuzana Walker, Paul SherwinAbstract:Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane 123I Injection is also known as DaTscan or DaTSCAN (123I-Ioflupane is also called 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or 123I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor’s clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (
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individual reader diagnostic performance and between reader agreement in assessment of subjects with parkinsonian syndrome or dementia using 123I Ioflupane injection datscan imaging
The Journal of Nuclear Medicine, 2014Co-Authors: John Seibyl, Donald G Grosset, Nin Bajaj, Andreas Kupsch, Zuzana Walker, Jan Booij, D C Costa, Robert A Hauser, Jacques Darcourt, Kenneth MarekAbstract:Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane 123I Injection (DaTscan, 123I-Ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of 123I-Ioflupane in a variety of clinical scenarios is essential. Methods: Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of 123I-Ioflupane: on-site versus 3–5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia. Results: Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%–91.2% to 81.6%–95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%–73.7%; specificity, 75.0%–83.3%) was compared versus month-36 diagnosis (77.5%–80.3% and 90.3%–96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%–89.9% and 77.4%–95.0%, respectively) and subjects with movement disorders (67.0%–97.9% and 71.4%–98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers. Conclusion: Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of 123I-Ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
Donald G Grosset - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of 10 clinical trials and for 13 years after first approval of Ioflupane 123I injection datscan
The Journal of Nuclear Medicine, 2014Co-Authors: Donald G Grosset, Klaus Tatsch, Wolfgang H Oertel, Eduardo Tolosa, Nin Bajaj, Andreas Kupsch, John T Obrien, John Seibyl, Zuzana Walker, Paul SherwinAbstract:Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane 123I Injection is also known as DaTscan or DaTSCAN (123I-Ioflupane is also called 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or 123I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor’s clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (
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individual reader diagnostic performance and between reader agreement in assessment of subjects with parkinsonian syndrome or dementia using 123I Ioflupane injection datscan imaging
The Journal of Nuclear Medicine, 2014Co-Authors: John Seibyl, Donald G Grosset, Nin Bajaj, Andreas Kupsch, Zuzana Walker, Jan Booij, D C Costa, Robert A Hauser, Jacques Darcourt, Kenneth MarekAbstract:Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane 123I Injection (DaTscan, 123I-Ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of 123I-Ioflupane in a variety of clinical scenarios is essential. Methods: Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of 123I-Ioflupane: on-site versus 3–5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia. Results: Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%–91.2% to 81.6%–95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%–73.7%; specificity, 75.0%–83.3%) was compared versus month-36 diagnosis (77.5%–80.3% and 90.3%–96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%–89.9% and 77.4%–95.0%, respectively) and subjects with movement disorders (67.0%–97.9% and 71.4%–98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers. Conclusion: Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of 123I-Ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
Nin Bajaj - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of 10 clinical trials and for 13 years after first approval of Ioflupane 123I injection datscan
The Journal of Nuclear Medicine, 2014Co-Authors: Donald G Grosset, Klaus Tatsch, Wolfgang H Oertel, Eduardo Tolosa, Nin Bajaj, Andreas Kupsch, John T Obrien, John Seibyl, Zuzana Walker, Paul SherwinAbstract:Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane 123I Injection is also known as DaTscan or DaTSCAN (123I-Ioflupane is also called 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or 123I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor’s clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (
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individual reader diagnostic performance and between reader agreement in assessment of subjects with parkinsonian syndrome or dementia using 123I Ioflupane injection datscan imaging
The Journal of Nuclear Medicine, 2014Co-Authors: John Seibyl, Donald G Grosset, Nin Bajaj, Andreas Kupsch, Zuzana Walker, Jan Booij, D C Costa, Robert A Hauser, Jacques Darcourt, Kenneth MarekAbstract:Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane 123I Injection (DaTscan, 123I-Ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of 123I-Ioflupane in a variety of clinical scenarios is essential. Methods: Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of 123I-Ioflupane: on-site versus 3–5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia. Results: Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%–91.2% to 81.6%–95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%–73.7%; specificity, 75.0%–83.3%) was compared versus month-36 diagnosis (77.5%–80.3% and 90.3%–96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%–89.9% and 77.4%–95.0%, respectively) and subjects with movement disorders (67.0%–97.9% and 71.4%–98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers. Conclusion: Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of 123I-Ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
Andreas Kupsch - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of 10 clinical trials and for 13 years after first approval of Ioflupane 123I injection datscan
The Journal of Nuclear Medicine, 2014Co-Authors: Donald G Grosset, Klaus Tatsch, Wolfgang H Oertel, Eduardo Tolosa, Nin Bajaj, Andreas Kupsch, John T Obrien, John Seibyl, Zuzana Walker, Paul SherwinAbstract:Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane 123I Injection is also known as DaTscan or DaTSCAN (123I-Ioflupane is also called 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or 123I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor’s clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (
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individual reader diagnostic performance and between reader agreement in assessment of subjects with parkinsonian syndrome or dementia using 123I Ioflupane injection datscan imaging
The Journal of Nuclear Medicine, 2014Co-Authors: John Seibyl, Donald G Grosset, Nin Bajaj, Andreas Kupsch, Zuzana Walker, Jan Booij, D C Costa, Robert A Hauser, Jacques Darcourt, Kenneth MarekAbstract:Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane 123I Injection (DaTscan, 123I-Ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of 123I-Ioflupane in a variety of clinical scenarios is essential. Methods: Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of 123I-Ioflupane: on-site versus 3–5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia. Results: Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%–91.2% to 81.6%–95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%–73.7%; specificity, 75.0%–83.3%) was compared versus month-36 diagnosis (77.5%–80.3% and 90.3%–96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%–89.9% and 77.4%–95.0%, respectively) and subjects with movement disorders (67.0%–97.9% and 71.4%–98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers. Conclusion: Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of 123I-Ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
