Evaluation of area under the concentration curve adjusted by the terminal‐phase as a metric to reduce the impact of variability in bioequivalence testing

2021 ◽  
Author(s):  
Adam J. Lucas ◽  
Kayode Ogungbenro ◽  
Shuying Y. Yang ◽  
Leon J. Aarons ◽  
Chao Chen
Keyword(s):  
Concentration Curve ◽  
Terminal Phase ◽  
Bioequivalence Testing ◽  
The Impact

Caring for the caregiver: factors associated with the quality of life of family caregivers to palliative care patients

2015 ◽  
Vol 3 (3) ◽  
pp. 352
Author(s):  
Macarena Quesada ◽  
Manuel Madrigal ◽  
Aurelio Luna ◽  
Maria D Perez-Carceles
Keyword(s):  
Quality Of Life ◽  
Palliative Care ◽  
Family Caregivers ◽  
Care Patient ◽  
Terminal Phase ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Factors Associated ◽  
The Impact

Purpose: The aim was to investigate the factors associated with the quality of life (QoL) of family caregivers to palliative care patients. Methods: A cross-sectional survey was conducted of 125 family caregivers of patients in the terminal phase of their illness and included in palliative care programs. Data were collected using WHOQOL-BREF, the socio-demographic characteristics of both caregiver and patient, clinical questions and information about caregiving. Results: The QoL of caregivers was lower than that of the national average for healthy people. Significantly lower QoL scores were obtained in the case of caregivers if they were women, over 55 years, uneducated, unemployed or the patient’s spouse. Cancer diagnosis and patients who were dependent for their Activities of Daily Living also lower caregiver QoL. The factors associated with higher caregiver QoL in each domain differed: being employed in the physical domain (OR:3.3; 95% CI:1.47-7.4), the patient receiving palliative care in hospital in the psychological domain (OR:3.05; 95% CI:1.19-7.7), a higher level of caregiver´s education in the social domain (OR:3.3; 95% CI:1.4-9.8) and caregivers between 45-55 years in the environmental domain (OR:5.4; 95% CI:1.6-9.2).Conclusion: Family caregivers of palliative care patients are highly burdened during caregiving. Characteristics of the patient and caregiver and the conditions under which care is performed, significantly affect QoL. We consider it essential to increase health professionals’ awareness of the importance of the role of the caregiver in providing services to the terminally ill, given the impact of the caregiver’s QoL on the QoL of the palliative care patient and its importance for the delivery of person-centered care at the end of life.    

scholarly journals A mechanistic pharmacokinetic model with drug and antidrug antibody interplay, and its application for assessing the impact of immunogenicity response on bioequivalence testing

2020 ◽  
Vol 86 (11) ◽  
pp. 2182-2191
Author(s):  
Kai H. Liao ◽  
Chandrasekhar Udata ◽  
Donghua Yin ◽  
K. Lea Sewell ◽  
Constantino Kantaridis ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Antidrug Antibody ◽  
Bioequivalence Testing ◽  
The Impact

scholarly journals THE IMPACT OF THE MELD SCORE ON LIVER TRANSPLANT ALLOCATION AND RESULTS: AN INTEGRATIVE REVIEW

2017 ◽  
Vol 30 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Ana Claudia Oliveira de MORAES ◽  
Priscilla Caroliny de OLIVEIRA ◽  
Olival Cirilo Lucena da FONSECA-NETO
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Liver Transplant ◽  
Alcoholic Cirrhosis ◽  
Meld Score ◽  
Terminal Phase ◽  
Post Surgery ◽  
End Stage ◽  
Donor Criteria ◽  
The Impact

ABSTRACT Introduction: Liver transplantation is intended to increase the survival of patients with chronic liver disease in terminal phase, as well as improved quality of life. Since the first transplant until today many changes have occurred in the organ allocation system. Objective: To review the literature on the Model for End-stage Liver Disease (MELD) and analyze its correlation with survival after liver transplantation. Method: An integrative literature review in Lilacs, SciELO, and Pubmed in October 2015, was realized. Were included eight studies related to the MELD score and its impact on liver transplant. Results: There was predominance of transplants in male between 45-55 y. The main indications were hepatitis C, hepatocellular carcinoma and alcoholic cirrhosis. The most important factors post-surgery were related to the MELD score, the recipient age, expanded donor criteria and hemotransfusion. Conclusion: The MELD system reduced the death rate in patients waiting for a liver transplant. However, this score by itself is not a good predictor of survival after liver transplantation.

scholarly journals Idarucizumab, a Specific Reversal Agent for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran-Induced Anticoagulation in Japanese Healthy Male Volunteers

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2627-2627 ◽  
Author(s):  
Joanne van Ryn ◽  
Masahiro Yasaka ◽  
Ippei Ikushima ◽  
Akiko Harada ◽  
Atsushi Taniguchi ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Antibody Fragment ◽  
Terminal Phase ◽  
Thrombin Time ◽  
Healthy Male ◽  
Coagulation Parameters ◽  
Reversal Agents ◽  
Complete Reversal ◽  
The Impact ◽  
D Dimer

Abstract Background: Specific reversal agents for oral anticoagulants may be necessary to manage life-threatening bleeding or prior to emergency surgical procedures. While many reversal agents are in development, idarucizumab is approved and now available commercially in many countries. Idarucizumab is a humanized antibody fragment that specifically binds to dabigatran with high affinity and has shown immediate, complete and sustained reversal of dabigatran-induced anticoagulation in healthy male Caucasian volunteers. The present study investigated the safety, tolerability and pharmacokinetics of idarucizumab (part 1) and explored the effective dose of idarucizumab to reverse the dabigatran-induced anticoagulant effect (part 2) in healthy male Japanese volunteers. Methods: This was a two-part, phase I, randomized, placebo-controlled, double-blind, single-center, rising dose study. In part 1, subjects (n = 32) were randomized to receive either placebo (n = 2/dose group) or single intravenous doses of idarucizumab, 1, 2, or 4 g as a 5-minute infusion or 8 g as a 1-hour infusion (n = 6/group). In part 2, subjects (n = 48) were treated orally for 3 days with dabigatran etexilate (DE, 220 mg bid). On day 4, subjects received a final DE dose, followed a 3-day wash out period. Subjects were again treated orally for 3 days with DE, 220 mg bid. On Day 11, subjects received a final DE dose followed 2 hours later by placebo (n = 3/group) or idarucizumab (1, 2, 4, or 5 g [2.5 g followed by 2.5 g given 15 minutes apart]) as a 5-minute intravenous infusion, n = 9/group). The number of subjects with adverse events (AEs), emergence of anti-idarucizumab antibodies (ADAs), pharmacokinetics and the impact of idarucizumab on coagulation parameters were assessed (diluted thrombin time, ecarin clotting time, activated partial thromboplastin time, and thrombin time). In addition, potential procoagulant effects were monitored as D-dimer and prothrombin fragment F1.2. Results: Idarucizumab attained a maximum concentration in plasma around the end of each infusion followed by a biphasic decline in plasma concentrations with a rapid initial phase and a longer terminal phase.. Dabigatran treatment prolonged the clotting times of all coagulation parameters. Idarucizumab infusion resulted in immediate and complete reversal of dabigatran-induced anticoagulation, reducing coagulation parameters below the upper limit of normal. The duration was dose-dependent; at 4 and 5 g of idarucizumab, complete reversal was sustained up to 72 hours, at lower doses ≤ 2 g a partial return of the anticoagulation activity of dabigatran was observed 1-2 hours after idarucizumab administration. Concentration of unbound dabigatran decreased to below the limit of quantification immediately after administration of a single dose of idarucizumab. Idarucizumab was safe and well tolerated, and no AEs were reported. There was no elevation of either D-dimer or F1.2 levels post idarucizumab as compared to levels prior to infusion in any of the dose groups. Treatment-emergent ADAs occurred in 6 of 60 patients receiving idarucizumab. Conclusion: Idarucizumab infusion achieved immediate, complete and sustained reversal of dabigatran-associated anticoagulation in healthy male Japanese volunteers. Idarucizumab was safe and well tolerated with no procoagulant effects. Disclosures van Ryn: Boehringer Ingelheim: Employment. Yasaka:Sanofi: Research Funding; Nippon Boehringer Ingelheim: Other: received lecture fees (over 1 million Yen); Bristol-Myers Squibb: Other: received lecture fees (over 1 million Yen); Bayer Yakuhin: Other: received lecture fees (over 1 million Yen); Daiichi-Sankyo: Other: received lecture fees (over 1 million Yen). Harada:Boehringer Ingelheim: Employment. Taniguchi:Boehringer Ingelheim: Employment. Imazu:Boehringer Ingelheim: Employment. Norris:Boehringer Ingelheim: Employment. Gansser:Boehringer Ingelheim: Employment. Stangier:Boehringer Ingelheim: Employment.

The Impact of Hospice Care on Families

1984 ◽  
Vol 13 (2) ◽  
pp. 153-165 ◽  
Author(s):  
Michael A. Godkin ◽  
Melvin J. Krant ◽  
Nancy J. Doster
Keyword(s):  
Cancer Patients ◽  
Late Stage ◽  
Hospice Care ◽  
Well Being ◽  
Terminal Phase ◽  
Large Problem ◽  
Loved One ◽  
Late Stage Cancer ◽  
The Impact ◽  
Practical Sense

The impact of a hospital-based Hospice service for late-stage cancer patients, on the families of fifty-eight bereaved spouses was studied, retrospectively. Hospice care in general was rated significantly higher when compared to the prior care ( p < .001) received by patients and families. Hospice care contributed to improved family functioning and well-being, with the vast majority of spouses reporting feelings of increased support, improved coping by all family members and increased closeness, when compared to prior care. Consequently, over three-quarters of the families reported being emotionally prepared, and prepared in a practical sense, for the death of their loved one. Families appear to be coping reasonably well during bereavement especially those who reported feeling emotionally prepared for the death. Health problems were reported as a large problem in 15 percent of the respondents, which compares favorably to previously documented research on bereavement and illness. These findings indicate that a Hospice mode of care, with its support of families during terminal and bereavement stages, impacts significantly on families' abilities to cope with the terminal phase and adapt afterwards.

scholarly journals Evaluation of a rate-adjusted area under the curve method to reduce the impact of variability in bioequivalence testing

2020 ◽  
Author(s):  
Adam Lucas ◽  
Kayode Ogungbenro ◽  
Shuying Yang ◽  
Leon Aarons ◽  
Chao Chen
Keyword(s):  
Area Under The Curve ◽  
Curve Method ◽  
Bioequivalence Testing ◽  
The Impact

scholarly journals Final Evaluation of Randomized CML-Study IV: 10-Year Survival and Evolution of Terminal Phase

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 897-897
Author(s):  
Rüdiger Hehlmann ◽  
Michael Lauseker ◽  
Susanne Saussele ◽  
Markus Pfirrmann ◽  
Stefan W. Krause ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Initial Treatment ◽  
Research Funding ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Relative Survival ◽  
Treatment Center ◽  
Terminal Phase ◽  
Survival Difference ◽  
The Impact

Abstract Background Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). Methods From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. The impact of patients' and disease factors on survival was prospectively analyzed. At the time of evaluation, at least 62% of patients still received imatinib, 26.2% were switched to 2nd generation tyrosine kinase inhibitors. Results After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival 80% and 10-year relative survival 92%. In spite of a faster response with IM800mg, the survival difference between IM400mg and IM800mg was only 3% at 5 years. In a multivariate analysis, the influence on survival of risk-group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs. other) was significant in contrast to any form of initial treatment optimization. Patients that reached the response milestones 3, 6 and 12 months, had a significant survival advantage of about 6% after 10 years regardless of therapy. The progression probability to blast crisis was 5.8%. Blast crisis was proceeded by high-risk additional chromosomal aberrations. Conclusions For responders, monotherapy with IM400mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease and blast crisis, more life-time can currently be gained by carefully addressing non-CML determinants of survival. Disclosures Hehlmann: Novartis: Research Funding; BMS: Consultancy. Saussele: Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Pfirrmann: BMS: Honoraria; Novartis: Honoraria. Krause: Novartis: Honoraria. Baerlocher: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Bruemmendorf: Novartis: Research Funding. Müller: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Jeromin: MLL Munich Leukemia Laboratory: Employment. Hänel: Roche: Honoraria; Novartis: Honoraria. Burchert: BMS: Honoraria. Waller: Mylan: Consultancy, Honoraria. Mayer: Eisai: Research Funding; Novartis: Research Funding. Link: Novartis: Honoraria. Scheid: Novartis: Honoraria. Schafhausen: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Hochhaus: Incyte: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; ARIAD: Research Funding.

Formation of Lunar Craters and Bright Rays as a Result of Meteorite Impacts

1962 ◽  
Vol 14 ◽  
pp. 415-418
Author(s):  
K. P. Stanyukovich ◽  
V. A. Bronshten
Keyword(s):  
Explosive Charge ◽  
The Moon ◽  
Meteorite Impacts ◽  
The Earth ◽  
Lunar Craters ◽  
The Impact

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.

The Geosciences Applied to Lunar Exploration

1962 ◽  
Vol 14 ◽  
pp. 169-257 ◽  
Author(s):  
J. Green
Keyword(s):  
Lunar Surface ◽  
Probable Mechanism ◽  
Point Of View ◽  
Lunar Exploration ◽  
Geological Model ◽  
Apply Geophysics ◽  
Surface Features ◽  
The Impact

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.

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