Morbidity and Mortality after High-dose Transfusion

2016 ◽  
Vol 124 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Daniel J. Johnson ◽  
Andrew V. Scott ◽  
Viachaslau M. Barodka ◽  
Sunhee Park ◽  
Jack O. Wasey ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Dose Response ◽  
Dose Range ◽  
Adverse Outcomes ◽  
Morbidity And Mortality ◽  
High Dose ◽  
Clinical Predictors ◽  
Response Curves ◽  
Wide Range ◽  
Very High

Abstract Background It is well recognized that increased transfusion volumes are associated with increased morbidity and mortality, but dose–response relations between high- and very-high-dose transfusion and clinical outcomes have not been described previously. In this study, the authors assessed (1) the dose–response relation over a wide range of transfusion volumes for morbidity and mortality and (2) other clinical predictors of adverse outcomes. Methods The authors retrospectively analyzed electronic medical records for 272,592 medical and surgical patients (excluding those with hematologic malignancies), 3,523 of whom received transfusion (10 or greater erythrocyte units throughout the hospital stay), to create dose–response curves for transfusion volumes and in-hospital morbidity and mortality. Prehospital comorbidities were assessed in a risk-adjusted manner to identify the correlation with clinical outcomes. Results For patients receiving high- or very-high-dose transfusion, infections and thrombotic events were four to five times more prevalent than renal, respiratory, and ischemic events. Mortality increased linearly over the entire dose range, with a 10% increase for each 10 units of erythrocytes transfused and 50% mortality after 50 erythrocyte units. Independent predictors of mortality were transfusion dose (odds ratio [OR], 1.037; 95% CI, 1.029 to 1.044), the Charlson comorbidity index (OR, 1.209; 95% CI, 1.141 to 1.276), and a history of congestive heart failure (OR, 1.482; 95% CI, 1.062 to 2.063). Conclusions Patients receiving high- or very-high-dose transfusion are at especially high risk for hospital-acquired infections and thrombotic events. Mortality increased linearly over the entire dose range and exceeded 50% after 50 erythrocyte units.

scholarly journals Nonmonotonic Dose–Response Curves Occur in Dose Ranges That Are Relevant to Regulatory Decision-Making

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581879828 ◽  
Author(s):  
Corinne E. Hill ◽  
J. P. Myers ◽  
Laura N. Vandenberg
Keyword(s):  
Dose Response ◽  
Endocrine Disrupting Chemicals ◽  
Toxicity Testing ◽  
Adverse Outcomes ◽  
High Dose ◽  
Human Populations ◽  
Response Curves ◽  
Regulatory Decision ◽  
Adverse Effect Level ◽  
Dose Response Curves

Non-monotonic dose response curves (NMDRCs) occur in cells, tissues, animals and human populations in response to nutrients, vitamins, pharmacological compounds, hormones and endocrine disrupting chemicals (EDCs). Yet, regulatory agencies have argued that NMDRCs are not common, are not found for adverse outcomes, and are not relevant for regulation of EDCs. Under the linear dose response model, high dose testing is used to extrapolate to lower doses that are anticipated to be ‘safe’ for human exposures. NMDRCs that occur below the toxicological no-observed-adverse-effect level (NOAEL) would falsify a fundamental assumption, that high dose hazards can be used to predict low dose safety. In this commentary, we provide examples of NMDRCs and discuss how their presence in different portions of the dose response curve might affect regulatory decisions. We provide evidence that NMDRCs do occur below the NOAEL dose, and even below the ‘safe’ reference dose, for chemicals such as resveratrol, permethrin, chlorothalonil, and phthalates such as DEHP. We also briefly discuss the recent CLARITY-BPA study, which reported mammary adenocarcinomas only in rats exposed to the lowest BPA dose. We conclude our commentary with suggestions for how NMDRCs should be acknowledged and utilized to improve regulatory toxicity testing and in the calculation of reference doses that are public health protective.

scholarly journals Assessing the maximum limit of SAR-OSL dating using quartz of different grain sizes

2018 ◽  
Vol 45 (1) ◽  
pp. 146-159 ◽  
Author(s):  
Valentina Anechitei-Deacu ◽  
Alida Timar-Gabor ◽  
Daniela Constantin ◽  
Oana Trandafir-Antohi ◽  
Laura Del Valle ◽  
...  
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Range ◽  
Osl Dating ◽  
Dose Response Curve ◽  
High Dose ◽  
Response Curves ◽  
Grain Sizes ◽  
Coarse Grains ◽  
Dose Response Curves

Abstract SAR-OSL dating studies of Romanian, Serbian and Chinese loess using fine and coarse quartz have previously resulted in a series of controversial issues. We extend here the investigations using fine (4–11 μm) and different coarse quartz (>63 μm) grains extracted from aeolianites from a site on Eivissa Island (southwestern Mediterranean). Aeolianites were chosen since they contain quartz from a different geological context and have significantly lower environmental dose rates. The dose response curves of the OSL signals for fine and coarse quartz are similar to those for loess and are also represented by the sum of two saturating exponential functions. For doses up to ~200 Gy, the dose response curves of fine and coarse grains from aeolianites can be superimposed and the ages obtained for the different grain sizes are in agreement up to ~250 ka, increasing our confidence in the accuracy of the ages obtained for samples with such doses, irrespective of the magnitude of the environmental dose rate. Particularly for the fine quartz fraction, a mismatch between the SAR dose response curve and the dose response curve obtained when doses are added to the natural is reported, indicating that the application of the SAR protocol in the high dose range is problematic. This dose dependent deviation is much less pronounced for coarse grains. Thus, it seems reasonable to infer that the dose response curves for the coarse grains, although saturating earlier can be regarded as more reliable for equivalent dose calculation than those for the fine grains.

Comparison of Dose–Response Curves between EBT-XD and EBT3 Radiochromic Films at High Dose Range (2000–4500 cGy) for a 175 MeV Proton Beam

2021 ◽  
Vol 18 (6) ◽  
pp. 691-699
Author(s):  
D. M. Borowicz ◽  
M. Kruszyna-Mochalska ◽  
K. Shipulin ◽  
A. Molokanov ◽  
G. Mytsin ◽  
...  
Keyword(s):  
Proton Beam ◽  
Dose Response ◽  
Dose Range ◽  
High Dose ◽  
Response Curves ◽  
Radiochromic Films ◽  
Dose Response Curves

scholarly journals Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

2015 ◽  
Vol 81 ◽  
pp. 150-156 ◽  
Author(s):  
A. Timar-Gabor ◽  
D. Constantin ◽  
J.P. Buylaert ◽  
M. Jain ◽  
A.S. Murray ◽  
...  
Keyword(s):  
Dose Response ◽  
Dose Range ◽  
High Dose ◽  
Response Curves ◽  
Dose Response Curves

In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma.

1990 ◽  
Vol 8 (6) ◽  
pp. 1070-1082 ◽  
Author(s):  
J M Kirkwood ◽  
M S Ernstoff ◽  
T Trautman ◽  
G Hebert ◽  
Y Nishida ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Dose Response ◽  
Dose Range ◽  
Cell Subset ◽  
Optimal Dosage ◽  
Antitumor Effects ◽  
Ifn Gamma ◽  
Recombinant Interferon ◽  
Wide Range

Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment-associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established.

scholarly journals Dose–Response of TLD-100 in the Dose Range Useful for Hypofractionated Radiotherapy

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581989408 ◽  
Author(s):  
Raffaele Liuzzi ◽  
Consiglia Piccolo ◽  
Vittoria D’Avino ◽  
Stefania Clemente ◽  
Caterina Oliviero ◽  
...  
Keyword(s):  
Dose Response ◽  
Radiation Treatment ◽  
Dose Range ◽  
Information Criterion ◽  
High Dose ◽  
Thermoluminescent Dosimeters ◽  
Dose Monitoring ◽  
Coefficients Of Variation ◽  
Best Fitting ◽  
Quadratic Models

Purpose: The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved. Methods: Dose–response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test. Results: The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose–response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above. Conclusion: The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.

scholarly journals Establishing a common standardised growth curve for single-aliquot OSL dating of quartz from sediments in the Jilantai area of North China

2020 ◽  
Vol 47 (1) ◽  
pp. 71-92
Author(s):  
Zhenjun Li ◽  
Xuesong Mou ◽  
Yuxin Fan ◽  
Qingsong Zhang ◽  
Guangliang Yang ◽  
...  
Keyword(s):  
Least Squares ◽  
Growth Curve ◽  
Dose Response ◽  
North China ◽  
Dose Range ◽  
Optically Stimulated Luminescence ◽  
Osl Dating ◽  
Response Curves ◽  
Sedimentary Environments ◽  
Saturation Dose

AbstractEstablishing a common standardised growth curve (SGC) can substantially reduce the instrumental time for equivalent-dose (De) measurements in optically stimulated luminescence (OSL) dating. Several studies have indicated that different samples have different dose–response curves (DRCs) and therefore that it is difficult to construct a common SGC, although an SGC has been proposed in some cases. In this study, our aims were to construct a regional SGC based on small aliquots of sedimentary quartz from more than 100 samples from different sedimentary environments in the Jilantai Basin in North China and to investigate the applicability of different methods of establishing an SGC for the area. The precision of the De values of aliquots which were obtained using the SGC was compared with those obtained using the single-aliquot regenerative (SAR) protocol. Our results indicate the following: (1) for establishing an SGC using the regenerative normalisation (Re-SGC) method, selecting a suitable re-normalisation dose that is close to double the characteristic saturation dose, 2D0, can reduce the inter-aliquot/inter-sample variation in the form of DRCs within a larger dose range. (2) A common regional SGC can be established for the Jilantai area using the Re-SGC and least-squares normalisation (LS-SGC) methods, which provides reliable dating results within the 200 Gy De range.

scholarly journals Single Aliquot Regeneration (SAR) Optically Stimulated Luminescence Dating Protocols Using Different Grain-Sizes of Quartz: Revisiting the Chronology of Mircea Vodă Loess-Paleosol Master Section (Romania)

2020 ◽  
Vol 3 (1) ◽  
pp. 19 ◽  
Author(s):  
Ștefana-M. Groza-Săcaciu ◽  
Cristian Panaiotu ◽  
Alida Timar-Gabor
Keyword(s):  
Dose Range ◽  
Test Dose ◽  
Optically Stimulated Luminescence ◽  
Luminescence Dating ◽  
High Dose ◽  
Response Curves ◽  
Fine Grain ◽  
Current State ◽  
Optically Stimulated Luminescence Dating ◽  
Fine Quartz

The loess-paleosol archive from Mircea Vodă (Romania) represents one of the most studied sections in Europe. We are applying here the current state of the art luminescence dating protocols for revisiting the chronology of this section. Analysis were performed on fine (4–11 µm) and coarse (63–90 µm) quartz extracts using the single aliquot regenerative (SAR) optically stimulated luminescence (OSL) dating protocol. Laboratory generated SAR dose response curves in the high dose range (5 kGy for fine quartz and 2 kGy for coarse quartz) were investigated by employing a test dose of either 17 or 170 Gy. The results confirm the previously reported different saturation characteristics of the two quartz fractions, with no evident dependency of the equivalent dose (De) on the size of the test dose. The OSL SAR ages are discussed and compared to the previously obtained results on quartz and feldspars. The previous reports regarding the chronological discrepancy between the two quartz fractions are confirmed. However, while previous investigations on other sites concluded that this discrepancy appears only above equivalent doses of about 100 Gy, here fine grain quartz ages underestimate coarse quartz ages starting with equivalent doses as low as around 50 Gy.

scholarly journals Clozapine antipsychotic polypharmacy: audit of use and patient monitoring

2013 ◽  
Vol 37 (10) ◽  
pp. 322-325 ◽  
Author(s):  
Sam Wilson ◽  
Ross Hamilton ◽  
John Callender ◽  
Angela MacManus ◽  
Sheila Howitt ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Patient Monitoring ◽  
Dose Range ◽  
Clinical Implications ◽  
High Dose ◽  
Antipsychotic Medications ◽  
Dose Monitoring ◽  
Wide Range

Aims and methodWe audited prescribing within our area to ascertain how widespread the practice of antipsychotic polypharmacy using clozapine was, and whether it was being carried out within existing standards, including those of high-dose monitoring when required.ResultsData on 169 patients were reviewed in year one, rising to 193 in year three. Around 30% of patients on clozapine received additional antipsychotic medication. A disturbingly low proportion of patients on clozapine whose antipsychotic polypharmacy brought them into the high-dose range were being monitored appropriately after three audit cycles (the proportion rose from 10% in cycle 1 to 28% in cycle 3). A wide range of additional antipsychotic medications was used.Clinical implicationsClozapine antipsychotic polypharmacy was prevalent at just below a third of all patients in this review. Prescribers should be alert to the fact that clozapine antipsychotic polypharmacy can push patients into the high-dose range and ensure appropriate monitoring.

scholarly journals A New Model Describing Copper Dose–Toxicity to Tomato and Bok Choy Growth in a Wide Range of Soils

2019 ◽  
Vol 16 (2) ◽  
pp. 264 ◽  
Author(s):  
Bao Jiang ◽  
Yibing Ma ◽  
Guangyun Zhu ◽  
Jun Li
Keyword(s):  
Soil Properties ◽  
Dose Response ◽  
Predictive Models ◽  
Contaminated Soils ◽  
Ethylenediaminetetraacetic Acid ◽  
Heavy Metal Concentration ◽  
Exposure Dose ◽  
Exchange Capacity ◽  
Response Curves ◽  
Wide Range

Phytotoxicity thresholds for heavy metals are derived from dose–response curves, which show the relationships between exposure dose and toxicity response. However, the results of tests or observations are commonly based on total heavy metal concentration, not the exposure dose that causes phytotoxicity; additionally, the phytotoxicity response differs with plant species. In the present study, the ethylenediaminetetraacetic acid (EDTA)-extractable copper (Cu) concentration was determined in order to evaluate Cu extractability. As two important horticultural food crops in Asia, tomato (Lycopersicon esculentum ‘Meifen No. 1’) and bok choy (Brassica rapa var. chinensis ‘Susheng 28’) were used to investigate Cu phytotoxicity in a wide range of Chinese soils with and without leaching treatment, after which relationships between Cu phytotoxicity thresholds based on EDTA-extractions and soil properties were established. The phytotoxicity thresholds showed that biomass of bok choy was more sensitive to Cu than tomato. Multiple linear regression analyses showed that soil factors, including organic carbon (OC), citrate dithionate extractable manganese (CD-Mn), cation exchange capacity (CEC), and CaCO3 explained over 85% of the variance in Cu phytotoxicity thresholds. The EDTA-extractable Cu dose–response relationships were further improved by incorporating soil properties. The new phytotoxicity predictive models indicated soil properties (soil pH, OC, CEC, and oxalate-extractable Mn) and EDTA-extractable Cu concentration explained more than 90% of the variance in the phytotoxicity response of tomato and bok choy biomass. The new phytotoxicity predictive models could be used to develop a reasonable remediation strategy for contaminated soils.

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