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  • 11
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    Short-Term Exposure to Wildfire-Specific PM2.5 and Hospitalization for Diabetes Morbidity: A Study in Multiple Countries and Territories
    American Diabetes Association ; 2024
    In:  Diabetes Care ( 2024-07-16)
    Details
    In: Diabetes Care, American Diabetes Association, ( 2024-07-16)
    Abstract: To evaluate associations of wildfire fine particulate matter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000–2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011–1.022), 1.023 (1.011–1.035), 1.023 (1.015–1.032), 0.962 (0.823–1.032), 1.033 (1.001–1.066), and 1.013 (1.004–1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. Relative risks (95% CI) of 0.67% (0.16–1.18%) and 1.02% (0.20–1.81%) for all cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc24-0703
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 12
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    Greater effect of stroke thrombolysis in the presence of arterial obstruction
    Wiley ; 2011
    In:  Annals of Neurology Vol. 70, No. 4 ( 2011-10), p. 601-605
    Details
    In: Annals of Neurology, Wiley, Vol. 70, No. 4 ( 2011-10), p. 601-605
    Abstract: Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth. Methods: We analyzed 175 ischemic stroke patients treated in the 3–6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion‐weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA). Results: Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI] , 1–50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, −3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21–43, p 〈 0.001). Interpretation: The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis. ANN NEUROL 2011;70:601–605
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v70.4
    DOI: 10.1002/ana.22444
    Language: English
    Publisher: Wiley
    Publication Date: 2011
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  • 13
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    Reply
    Wiley ; 2012
    In:  Annals of Neurology Vol. 71, No. 3 ( 2012-03), p. 433-434
    Details
    In: Annals of Neurology, Wiley, Vol. 71, No. 3 ( 2012-03), p. 433-434
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v71.3
    DOI: 10.1002/ana.23525
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 80362-5
    detail.hit.zdb_id: 2037912-2
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  • 14
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    Optimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation
    Elsevier BV ; 2002
    In:  Experimental Hematology Vol. 30, No. 6 ( 2002-06), p. 546-554
    Details
    In: Experimental Hematology, Elsevier BV, Vol. 30, No. 6 ( 2002-06), p. 546-554
    Type of Medium: Online Resource
    ISSN: 0301-472X
    URL: Article
    DOI: 10.1016/S0301-472X(02)00795-6
    RVK:
    XA 42470
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
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  • 15
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    Regional analysis of a cohort compassionate-use program (CUP) and early access program (EAP) with cabazitaxel (Cbz) plus prednisone (P; Cbz + P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D).
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 242-242
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 242-242
    Abstract: 242 Background: Cbz is an established second-line treatment for pts with mCRPC, having demonstrated an overall survival benefit (with P) vs mitoxantrone with P in the Phase III TROPIC trial. The global CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) aimed to provide access to Cbz + P before commercial availability and to document safety in a real-world population. We present a regional analysis of interim data from the CUP and EAP. Methods: Expected total enrolment is 1,450 pts. Pts received Cbz 25 mg/m 2 IV Q3W + P 10 mg QD until disease progression (PD), death, unacceptable toxicity or physician/pt decision. Granulocyte colony-stimulating factor (G-CSF) was administered per ASCO guidelines. The cut-off date for this analysis was 30 May 2012. Results: Globally, 1,301 pts have been included from eight regions (Eastern Europe [EE], Western Europe [WE] , Northern Europe [NE] and Southern Europe [SE] ; Asia [As]; Canada [Ca] ; Latin America [LA]; and Australia [Aus] ). Key data by region are shown in the Table. Median age varied from 65 years (Ca) to 70 years (Aus, LA, SE). In pts who progressed after last D line, time from last D dose to last PD ranged from 2.3 months (EE, LA) to 6.6 months (Ca). G-CSF use (therapeutic or prophylactic) at Cycle 1 varied widely between regions, from 23% (WE) to 79% (As). Between 11% (LA) and 30% (NE) of patients received ≥10 cycles of Cbz. Conclusions: In this extensive, real-world CUP/EAP cohort of mCRPC pts, substantial regional variation was observed for baseline and on-treatment parameters, including time from last D dose to last PD and G-CSF use. The low proportion of patients receiving ≥10 cycles in LA, Ca and WE may result from a limit of 10 cycles of therapy in some centers. Clinical trial information: NCT01254279. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.242
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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  • 16
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    Abstract 95: Regional Very Low Cerebral Blood Volume with Subsequent Local Reperfusion Predicts Hemorrhagic Transformation in Acute Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. suppl_1 ( 2012-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Background and Purpose Regions of very low cerebral blood volume (VLCBV) on MR perfusion imaging have been shown to predict hemorrhagic transformation (HT) following stroke thrombolysis. We tested the hypothesis that local reperfusion in a region of VLCBV is a pre-requisite for hemorrhagic transformation using pooled imaging data from the EPITHET and DEFUSE studies. Methods Standard CBV maps were calculated and smoothed (Gaussian) to reduce noise. The volume of VLCBV was calculated within the acute Tmax 〉 4sec perfusion lesion using fully automated techniques and a range of VLCBV thresholds relative to CBV values in the non-stroke hemisphere. Receiver operating characteristic (ROC) analysis was used to determine the optimal definition and threshold of VLCBV to predict parenchymal hematoma (PH, ECASS definition). Regional reperfusion was assessed using co-registered subacute Tmax perfusion images (DEFUSE 3-6hrs post thrombolysis, EPITHET 3-5 days post thrombolysis/placebo). The risk of PH associated with VLCBV was assessed with and without exclusion of regions of VLCBV within persistently hypoperfused regions. Results Of 145 patients with baseline perfusion imaging, 22 (15.2%) had PH (13 PH1, 9 PH2). A VLCBV definition of either 〈 2.5 th percentile of the contralateral CBV distribution (VLCBV 〈 2.5pctile) or 〈 15% of the mean contralateral CBV (VLCBV 〈 15%) had similar performance in predicting PH (AUC 0.73 for both). To achieve sensitivity of 95% required a VLCBV 〈 2.5pctile threshold of 〉 2mL (specificity 47%) or a VLCBV 〈 15% threshold of 〉 0.5mL (specificity 41%). There were 130 patients with subacute perfusion imaging, at which time 15 (11.5%) had developed PH. A further 3 patients (without reperfusion at subacute MRI) later developed PH and were excluded as reperfusion status at the time of PH was unknown. In the remaining 127 patients, the AUC for PH increased from 0.77 to 0.92 (p 〈 0.001, VLCBV 〈 2.5pctile definition) when regions of VLCBV without reperfusion on subacute imaging were excluded. The specificity of the 〉 2mL threshold (VLCBV 〈 2.5pctile) increased from 46 to 75%, positive predictive value increased from 20 to 35%, likelihood ratio for PH increased from 1.9 to 4.0 (sensitivity and negative predictive value were both 100% in these 127 patients). No patient developed PH at the time of subacute imaging in the absence of local reperfusion, including one patient where reperfusion of basal ganglia infarction had occurred (with CBV normalisation) prior to thrombolysis. Conclusions Local reperfusion is a critical factor in determining the risk of HT associated with regional VLCBV. This is consistent with the hypothesis that the severe ischemia represented by VLCBV is associated with focal blood-brain-barrier disruption and potential HT should reperfusion subsequently occur. Assessment of VLCBV can be automated and may be useful in clinical risk-benefit decisions regarding thrombolysis.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.43.suppl_1.A95
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 17
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    Advanced imaging improves prediction of hemorrhage after stroke thrombolysis
    Wiley ; 2013
    In:  Annals of Neurology Vol. 73, No. 4 ( 2013-04), p. 510-519
    Details
    In: Annals of Neurology, Wiley, Vol. 73, No. 4 ( 2013-04), p. 510-519
    Abstract: Very low cerebral blood volume ( VLCBV ), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. Methods The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging ( MRI ) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator ( tPA ) or placebo, and all DEFUSE patients received tPA . VLCBV was defined as cerebral blood volume 〈 2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma ( PH ) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging. Results In DEFUSE , 69 patients were analyzed, including 9 who developed PH . The 〉 2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH ), regression models using VLCBV ( p 〈 0.001) and tPA ( p =0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum 〉 8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. Interpretation VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post‐thrombolysis PH . VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;73:510–519
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v73.4
    DOI: 10.1002/ana.23837
    Language: English
    Publisher: Wiley
    Publication Date: 2013
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  • 18
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    RAPID Automated Patient Selection for Reperfusion Therapy : A Pooled Analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 6 ( 2011-06), p. 1608-1614
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1608-1614
    Abstract: The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome. Methods— Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥8-point improvement on the National Institutes of Health Stroke Scale score at Day 90. Results— In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10±23 mL with reperfusion versus 40±44 mL without reperfusion; P 〈 0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85±74 mL with reperfusion versus 95±79 mL without reperfusion; P =0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10±15 mL with reperfusion versus 17±30 mL without reperfusion; P =0.9) in No Mismatch patients. Conclusions— MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.110.609008
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 80381-9
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  • 19
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    Abstract WP45: Comparison of Automated Whole Brain CT Perfusion Analysis with Perfusion-Diffusion MRI in Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Stroke Vol. 44, No. suppl_1 ( 2013-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. suppl_1 ( 2013-02)
    Abstract: Background and purpose: CT perfusion (CTP) provides rapid and accessible imaging of ischemic stroke pathophysiology. Studies with limited brain coverage CTP have suggested that relative cerebral blood flow (relCBF) is the optimal CTP parameter to define irreversible infarction. We analyzed patients with whole brain CT perfusion and contemporaneous MR perfusion-diffusion imaging to confirm the optimal CTP parameter for infarct core and compare mismatch classification between MR and CT. Methods: Acute ischemic stroke patients 〈 6hr after onset had whole brain CTP (320slice) closely followed by perfusion-diffusion MRI. Maps of CBF, CBV and time-to-peak of the deconvolved tissue residue function (Tmax) were generated by RAPID automated perfusion analysis software (Stanford University) using delay insensitive deconvolution. The optimal CTP map to identify infarct core was selected by maximizing the average Dice co-efficient across the same threshold range for all patients using co-registered diffusion lesion (manually outlined to its maximal visual extent) as reference region. Mismatch classification agreement between CT and MRI was then assessed using 2 definitions: mismatch ratio a) 〉 1.2 or b) 〉 1.8, absolute mismatch a) 〉 10mL or b) 〉 15mL, infarct core 〈 70mL. Results: In 28 patients imaged 〈 6hr from stroke onset (median age 69, median onset to CT 180min, median CT to MR 69min), relCBF provided the most accurate estimate for infarct core, significantly better than absolute or relative CBV (both p 〈 0.001). Using relCBF to generate acute CTP infarct core volumes, the median magnitude of volume difference versus diffusion MR was 6.9mL, interquartile range 1.6-27.4mL. CTP mismatch between relCBF core and Tmax 〉 6sec perfusion lesion was assessed in 25 patients (3/28 had no MR perfusion). CTP and MR perfusion-diffusion mismatch classification agreed in 23/25 (92%) patients (kappa 0.84) using either definition. Conclusions: This study using whole brain CTP confirms the greater accuracy of CBF over CBV for estimation of the infarct core. The 〉 90% agreement in mismatch classification between CTP and MRI supports the concept that both modalities can identify similar patient populations for clinical trials of reperfusion therapies.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.44.suppl_1.AWP45
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 80381-9
    detail.hit.zdb_id: 1467823-8
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  • 20
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    Real-world treatment with abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 6_suppl ( 2017-02-20), p. 239-239
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 239-239
    Abstract: 239 Background: In the COU-AA-302 trial, abiraterone acetate plus prednisone (AAP) resulted in extension of radiographic progression-free survival (rPFS) and overall survival in chemotherapy-naïve mCRPC patients compared to prednisone alone. However, limited data on AAP treatment and outcomes is available in the real-world in this setting. The aim of this study is to describe the duration of AAP treatment in routine clinical practice in mCRPC patients prior to chemotherapy. Methods: The study was designed as a retrospective chart review of mCRPC patients identified through oncology and urology practice in Belgium, France, Germany and the UK. This first analysis reports baseline patient characteristics at AAP initiation for the first 224 patients. Treatment duration, PFS and rPFS were estimated using Kaplan-Meier curves. Potential factors associated with treatment duration were explored using the log-rank test. Results: Data from 224 mCRPC patients treated with AAP (Belgium: 67; Germany: 150; UK: 7; none from France) across 19 centres was considered in this initial analysis. At baseline, the median age was 75.5 years (interquartile range [IQR]: 69.0-82.0) and the median PSA level was 50.0 ng/mL (IQR: 21.0-121.0). Patients with visceral metastases (9.8%) and ECOG 2-3 (9.4%) were included in this study, in contrast to those included in the COU-AA-302 study. Median duration of AAP treatment was 11.6 months (95% confidence interval [CI] : 10.2-12.8), whilst median PFS and rPFS were 11.9 months (95% CI: 10.8-13.3) and 16.5 months (95% CI: 13.5-20.0), respectively. Reasons for discontinuing AAP involved PSA progression (52.2%), radiographic progression (38.9%), symptomatic progression (27.8%), non-toxic death (19.4%) and toxicity (2.2%). Treatment duration was significantly longer in mCRPC patients with either baseline ECOG status 0, lower PSA, alkaline phosphatase, aspartate aminotransferase, or lactate dehydrogenase levels (p 〈 0.05). Conclusions: The results of this study suggest similar treatment duration and rPFS for mCRPC patients in this real-life cohort with poorer clinical features compared to those observed in the COU-AA-302 trial population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.6_suppl.239
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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