BPI19-016: Evaluation of the Use of a Single Dose Rasburicase in Prophylaxis and Management of Tumor Lysis Syndrome (TLS) Among Cancer Patients in Qatar

2019 ◽  
Vol 17 (3.5) ◽  
pp. BPI19-016
Author(s):  
Nancy Kassem ◽  
Halima El Omri ◽  
Mohamed Yassin ◽  
Shereen Elazzazy
Keyword(s):  
Single Dose ◽  
Tumor Lysis Syndrome ◽  
Lactate Dehydrogenase Level ◽  
Primary Objective ◽  
Urate Oxidase ◽  
Multiple Doses ◽  
Oxidase Enzyme ◽  
Secondary Objective ◽  
Significant Cost Reduction ◽  
The Impact

Introduction: Rasburicase is a urate oxidase enzyme used for prophylaxis and treatment of hyperuricemia associated with TLS. The recommended dose of rasburicase is 0.2 mg/kg/day for 5 days; however, recent studies have demonstrated the effectiveness of a single rasburicase dose in prophylaxis and management of hyperuricemia associated with TLS. Our institution’s TLS guideline was updated to recommend the use of a single rasburicase dose (0.2 mg/kg). The primary objective of this study was to assess the efficacy of a single rasburicase dose in controlling uric acid (UA); the secondary objective was to evaluate the impact of the institutional TLS guidelines update on consumption and cost of rasburicase. Methods: This is a single center retrospective cohort study including all patients who received rasburicase from August 2012 to March 2016 at the National Center for Cancer Care and Research (NCCCR) in Qatar. Patients were divided into 2 groups based on the prescribed number of rasburicase doses (single dose vs multiple doses). Collected data included patients’ diagnosis, laboratory parameters rasburicase dose, duration, and number of dispensed vials. UA levels within 24 hours and on day 5 of initial rasburicase dose were evaluated. Risk stratification was determined according to institutional guidelines based on disease, white blood cell count, lactate dehydrogenase level, renal function, and UA level. Results: A total of 103 patients who received rasburicase were evaluated retrospectively; rasburicase was prescribed as single dose for 65 patients (63%) and multiple doses for 38 patients (37%). The majority of patients who received rasburicase as single or multiple doses were at high risk of developing TLS, representing 68% and 84%, respectively. Baseline mean UA levels were similar in both groups: 5.4±2.9 mg/dL vs 4.7±3.2 mg/L respectively (P=.7). Normal or undetectable UA levels were observed within 24 hours in 98% of patients in the single dose group and 100% of patients in the multiple doses group. All patients in both groups had normal UA on day 5 of rasburicase with relatively similar UA levels: 1.5±1.2 mg/dL vs 0.8±1 mg/dL (P=.18). Rasburicase consumption and cost were reduced by 42.5% after the guidelines update. Conclusion: The single rasburicase dose demonstrated efficacy in controlling serum UA levels. Updating the institutional TLS guidelines had a significant impact on rasburicase consumption and led to significant cost reduction.

scholarly journals A Multi-Objective Approach to Mitigate Negative Side Effects

2020 ◽  
Author(s):  
Sandhya Saisubramanian ◽  
Ece Kamar ◽  
Shlomo Zilberstein
Keyword(s):  
Side Effects ◽  
Empirical Evaluation ◽  
Primary Objective ◽  
Maximum Deviation ◽  
Negative Side ◽  
Multi Objective ◽  
Markov Decision ◽  
Secondary Objective ◽  
Negative Side Effects ◽  
The Impact

Agents operating in unstructured environments often create negative side effects (NSE) that may not be easy to identify at design time. We examine how various forms of human feedback or autonomous exploration can be used to learn a penalty function associated with NSE during system deployment. We formulate the problem of mitigating the impact of NSE as a multi-objective Markov decision process with lexicographic reward preferences and slack. The slack denotes the maximum deviation from an optimal policy with respect to the agent's primary objective allowed in order to mitigate NSE as a secondary objective. Empirical evaluation of our approach shows that the proposed framework can successfully mitigate NSE and that different feedback mechanisms introduce different biases, which influence the identification of NSE.

Impact of cetuximab sequence on progress-free survival (PFS) and overall survival (OS) in patients with RAS wild-type metastatic colorectal cancer (mCRC): A real-world study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16042-e16042
Author(s):  
Qirong Geng ◽  
Wenxiu Cheng ◽  
Zhiyu Chen ◽  
Wen Zhang ◽  
Xiaodong Zhu ◽  
...  
Keyword(s):  
Real World ◽  
Primary Tumour ◽  
Primary Objective ◽  
Wild Type ◽  
Line Therapy ◽  
Investigation Methods ◽  
Secondary Objective ◽  
Line Of Therapy ◽  
Metastatic Sites ◽  
The Impact

e16042 Background: Cetuximab provides a clear clinical benefit in the treatment in patients with RAS wild-type mCRC irrespective of treatment line, but the best sequence is still under investigation. Methods: Patients with RAS wild-type mCRC (2011-2019) who received cetuximab therapy were retrospectively analyzed. They were stratified based on the cetuximab treatment sequence, into the 1st, 2nd, 3rd or later-lines groups. The primary objective was to investigate the impact on Cetuximab sequence (2nd vs. 3rd and later-line) in PFS and OS. As for patients received the 3rd or later-line cetuximab with irinotecan therapy after refractory to the prior 1st and 2nd-line combined chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan, they will get another PFS of 2nd-line chemotherapy (PFSchemo) besides the PFS of 3rd or later-line cetuximab compared with the cetuximab 2nd-line used patients. We combined the PFSchemo to the PFS of 3rd or later-line cetuximab, then compared with PFS of 2nd -line cetuximab to evaluate the primary objective in PFS. As for the OS of primary objective, we calculated it from start of the 2nd-line of treatment. The secondary objective was to compare the efficacy of cetuximab sequence (1st vs. 2nd and later-lines) in OS calculated from start of the 1st-line of treatment. Results: In total, 193 patients were included: 106 in the 1st, 41 in the 2nd, and 46 in the 3rd-line groups. No difference was observed in baseline characteristics as sex,age,site of primary tumour,number of metastatic sites in the three groups. The median PFS of the 2nd-line and 3rd or later-line groups were 7.1 (95% CI 6.39-7.80) and 13.87 months(95% CI 11.44-16.29) respectively. PFS of the 3rd or later-line group was significantly longer than that of the 2nd-line group (hazard ratio[HR], 0.552; 95% CI, 0.349 to 0.871; P = 0.01). Median OS was 17.8 months (95% CI 13.5-22.1) in the 2nd-line and 27.4 months (95% CI 20.69-34.16) in the 3rd or later-line group (HR, 0.597; 95% CI 0.341 to 1.043; P = 0.07) from start of 2nd-line therapy. The median OS was 28.17 months (95% CI 22.11-34.22) in the 1st-line group and 33.10 months (95% CI 26.88-39.31) in the 2nd and later-lines group (HR, 0.724; 95% CI 0.507 to 1.304; P = 0.075) calculated from the 1st-line of therapy. Conclusions: In a real-world cohort we found that later-line especially 3rd or later-line therapy of cetuximab, may be more benefit for patients with RAS wild type mCRC, as 3rd or later-line use of cetuximab give one more line therapy chance.

scholarly journals A Comparison of Single Dose Rasburicase 3 Mg Versus 6 Mg for the Management of Tumor Lysis Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4511-4511
Author(s):  
Sarah K Kraus ◽  
Catherine E Burdalski ◽  
Colleen Timlin ◽  
Tracy M Krause ◽  
Todd A Miano ◽  
...  
Keyword(s):  
Single Dose ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Tumor Lysis Syndrome ◽  
Wholesale Price ◽  
Cost Savings ◽  
Urate Oxidase ◽  
Categorical Variables ◽  
Tumor Lysis ◽  
Dosing Strategies

Abstract Introduction: Rasburicase, a recombinant form of urate oxidase, is a highly effective treatment for tumor lysis syndrome (TLS). Although the FDA-approved dose for rasburicase is 0.2 mg/kg/day for up to five days, many centers have adopted alternative dosing strategies to decrease cost, the most common being a single 6 mg dose. We hypothesized that further reducing the dose to 3 mg would result in similar efficacy and yield significant cost savings compared to the 6 mg dose strategy. Methods: We conducted a retrospective cohort study to examine the comparative effectiveness of a single 3 mg dose of rasburicase versus a single 6 mg dose in 108 adults with hematological malignancies presenting with a baseline uric acid (UA) ≤ 12 mg/dL between June 2009 and February 2015. Prior to January 2012, our institutional policy recommended a single 6 mg dose for all patients who met criteria for rasburicase for TLS. In January 2012, the policy was amended to recommend a single 3 mg dose for patients with a baseline UA ≤ 12 mg/dL. Thus, the study included 56 patients with UA ≤ 12 who received a single 6 mg dose prior to the policy modification and 52 patients with UA ≤ 12 given the 3 mg dose after the amendment. The primary endpoint was the percentage of patients who achieved a UA ≤ 8 mg/dL (the upper limit of normal at our institution) 24 hours after a single dose of rasburicase. Fisher's exact test was used to analyze categorical variables and t-tests were used to analyze continuous variables. The a priori level of significance was set at α < 0.05. Results: The mean baseline UA was 9.3 mg/dL and 9.8 mg/dL in the 3 mg arm and 6 mg arm, respectively (P = .19). At 24 hours there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL (92% vs. 98%; P = 0.36). In addition, there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL at 48 hours (98% vs. 100%; P = 0.48). Six (11.5%) patients in the 3 mg arm and one (1.8%) patient in the 6 mg arm required a second dose of rasburicase to achieve a UA <8 mg/dL (P = 0.1). Of note, the 6 mg group had a greater percent reduction in UA from baseline compared to the 3 mg group at both 24 hours (-68.1% vs. -48.6%; P < .01) and 48 hours (-69.3% vs. -51.3%; P = 0.02) after rasburicase administration. There was no difference in the percent change of serum creatinine between the two dosing strategies at 24 hours (-6.5% vs. 0.1%; P = 0.11) or 48 hours (-4.5% vs. -2.5%; P = 0.22). In addition, no difference was observed with respect to the percent of patients who required renal replacement therapy within 7 days of rasburicase administration (8.9% vs. 9.6% P = 1.0). Based on the average wholesale price of $815 for one 1.5 mg vial of rasburicase, the single 3 mg dose was associated with approximately $1,500 cost savings per encounter compared to the 6 mg dose. Conclusion: A single 3 mg dose of rasburicase was as effective as 6 mg in normalizing UA within 24 hours. Our findings demonstrate that administering a single 3 mg dose of rasburicase is a cost-effective alternative for TLS management in patients with hematological malignancies presenting with a UA ≤ 12 mg/dL. Disclosures Svoboda: Immunomedics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding. Ganetsky:Onyx: Speakers Bureau.

The value of low, fixed, single dose rasburicase in the prevention and treatment of tumor lysis syndrome.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18558-e18558
Author(s):  
Bharadwaj Ponnada ◽  
Saadvik Raghuram ◽  
Sanketh Kotne ◽  
Pavithran Keechilat
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Low Dose ◽  
Medical Center ◽  
Day Treatment ◽  
Tumor Lysis Syndrome ◽  
Urate Oxidase ◽  
Fixed Dose ◽  
Tumor Lysis ◽  
Prevention And Treatment

e18558 Background: Rasburicase is a recombinant urate oxidase drug approved by the US FDA for the management of hyperuricemia in Tumor Lysis Syndrome (TLS). Recommended dose of 0.2 mg/kg/day for 5 days is expensive and the benefit of extended schedule compared to a single fixed dose of 1.5 mg is not known. Methods: This is a retrospective cohort study done at a tertiary medical center including 165 (144 adult and 21 pediatrics) patients admitted between January 2013 and December 2018. We analyzed the efficacy of single low dose rasburicase 1.5 mg irrespective of bodyweight in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) intravenously over 30 min for prevention and treatment of TLS and subsequent doses were given based on clinical and biochemical response. Plasma samples for uric acid were collected at baseline, 6–24 hrs, 48 hrs post-rasburicase, and daily during treatment. The primary outcome was achieving a uric acid level less than 7.0 mg/dl after a single dose of rasburicase in the groups. Secondary outcomes included need for repeat rasburicase doses, and a cost analysis. Results: Children accounted for 12.1% (n = 20) and adults 87.9% (n = 145). The median ages in pediatric and adult groups were 7.9 years and 54 years respectively. Rasburicase was used prophylactically in 35 (21.2%), for laboratory TLS in 105 (63.6%) and for clinical TLS in 25 (15.2%) patients. SDR prevented laboratory/clinical TLS in 89% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. However, 92%(n=23) of the patients with clinical TLS required more than one dose rasburicase. The average total monthly cost of rasburicase was reduced by 96% ($2850 to $114) after adoption of the above protocol. Conclusions: Single low dose rasburicase is a highly economical and clinically effective way of managing patients with TLS and could serve as an alternative to the 5-day treatment. This dose, therefore, balances cost and efficacy of treatment.

scholarly journals A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pedro M. Folegatti ◽  
Kate Harrison ◽  
Lorena Preciado-Llanes ◽  
Fernando Ramos Lopez ◽  
Mustapha Bittaye ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Chikungunya Virus ◽  
Phase 1 ◽  
Primary Objective ◽  
Open Label ◽  
Cell Responses ◽  
Single Intramuscular Injection ◽  
Secondary Objective ◽  
Vectored Vaccine

AbstractChikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.

The Impact of Different Validation Datasets on Air Quality Modeling Performance

2018 ◽  
Vol 2672 (25) ◽  
pp. 57-66 ◽  
Author(s):  
Haneen Khreis ◽  
Kees de Hoogh ◽  
Josias Zietsman ◽  
Mark J. Nieuwenhuijsen
Keyword(s):  
Air Quality ◽  
Spatial Resolution ◽  
Atmospheric Dispersion ◽  
Health Impact ◽  
Primary Objective ◽  
Validation Dataset ◽  
Health Impact Assessments ◽  
Secondary Objective ◽  
Pollution Modeling ◽  
The Impact

Many studies rely on air pollution modeling such as land use regression (LUR) or atmospheric dispersion (AD) modeling in epidemiological and health impact assessments. Generally, these models are only validated using one validation dataset and their estimates at select receptor points are generalized to larger areas. The primary objective of this paper was to explore the effect of different validation datasets on the validation of air quality models. The secondary objective was to explore the effect of the model estimates’ spatial resolution on the models’ validity at different locations. Annual NOx and NO2 were generated using a LUR and an AD model. These estimates were validated against four measurement datasets, once when estimates were made at the exact locations of the validation points and once when estimates were made at the centroid of the 100m×100m grid in which the validation point fell. The validation results varied substantially based on the model and validation dataset used. The LUR models’ R2 ranged between 21% and 58%, based on the validation dataset. The AD models’ R2 ranged between 13% and 56% based on the validation dataset and the use of constant or varying background NOx. The validation results based on model estimates at the exact validation site locations were much better than those based on a 100m×100m grid. This paper demonstrated the value of validating modeled air quality against various datasets and suggested that the spatial resolution of the models’ estimates has a significant influence on the validity at the application point.

The Impact of Addressing Adherence in Pharmacist-Managed Pharmacotherapy Clinics

2016 ◽  
Vol 30 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Nora H. Sharaya ◽  
Megan F. Dorrell ◽  
Nick A. Sciacca
Keyword(s):  
Standard Of Care ◽  
Pharmacist Intervention ◽  
Primary Objective ◽  
Primary Care Clinics ◽  
Medication Therapy ◽  
Adherence To Medication ◽  
Medication Information ◽  
Secondary Objective ◽  
The Impact

Purpose: The primary objective of this study was to determine the change in the adherence questionnaire score from the initial pharmacist intervention to 60 to 90 days follow-up. The secondary objective of this study was to investigate the impact of the type of pharmacist intervention on questionnaire scores. Methods: Administration of an adherence questionnaire to guide interventions has become the standard of care for patients during appointments with clinical pharmacy specialists at 3 primary care clinics. Subjects who received a questionnaire between November 4, 2013, and January 15, 2014, were included. These subjects received a second questionnaire 60 to 90 days after the first questionnaire to identify changes resulting from the pharmacist’s interventions. A scoring system was utilized to quantify patients’ responses to both the preintervention and postintervention questionnaires. The type of intervention completed was determined at each pharmacist’s clinical discretion. Results: Adherence scores increased significantly 60 to 90 days after administration of the questionnaire with a pharmacist’s intervention. Medication reminders, simplifying medication regimens, discount program referrals, disease-state information, medication information, and therapeutic interchanges, all increased adherence scores. Conclusion: A standardized tool to assess and address adherence was effectively utilized by 9 pharmacists at 3 clinics. The use of a standardized tool to guide adherence interventions is an effective way to increase adherence to medication therapy.

Methemoglobinemia induced by rasburicase in a pediatric patient: A case report and literature review

2011 ◽  
Vol 18 (4) ◽  
pp. 425-431 ◽  
Author(s):  
John S Ng ◽  
Elisa M Edwards ◽  
Tosha A Egelund
Keyword(s):  
High Risk ◽  
G6pd Deficiency ◽  
Pediatric Patients ◽  
Tumor Lysis Syndrome ◽  
Turnaround Time ◽  
Urate Oxidase ◽  
Life Threatening ◽  
Oxidase Enzyme ◽  
Deficiency Screening ◽  
Glucose 6 Phosphate Dehydrogenase

Rasburicase is a recombinant urate oxidase enzyme indicated for tumor lysis syndrome (TLS), a potential life-threatening oncologic emergency that occurs most commonly during chemotherapy for hematological malignancies. As a result of the defects in the physiological antioxidant pathway, erythrocytes of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are not protected against the oxidating stress exerted by hydrogen peroxide generated with the administration of rasburicase. Therefore, rasburicase is contraindicated in patients with known G6PD deficiency and the manufacturer recommends screening all patients with high risk for G6PD deficiency before initiating rasburicase therapy. However, it is logistically difficult in clinical settings because of the high risk of morbidity and mortality associated with TLS if treatment is delayed and the long turnaround time of the G6PD deficiency screening. Therefore, administering rasburicase to patients developing TLS before confirming a patient’s G6PD status is practically inevitable. Methemoglobinemia, and/or hemolysis, may result from the oxidative stress. Descriptions of the clinical course should it happen are limited in the literature. There are eight reported cases of rasburicase-related methemoglobinemia, with or without hemolytic anemia, in the literature of which five are pediatric patients. Six reports (including three pediatric patients) had detailed descriptions of the event and management. The recent reports of methemoglobinemia observed in patients with probable G6PD activity further complicated the picture. We are reporting a 16-year-old patient diagnosed with Burkitt’s lymphoma who developed methemoglobinemia after receiving one dose of rasburicase. He was managed by transfusion and oxygen support. The patient recovered well and the observed methemoglobinemia was reversible.

scholarly journals Half of purposeful sandbaggers undetected by ImPACT's embedded invalidity indicators

Neurology ◽  
2018 ◽  
Vol 91 (23 Supplement 1) ◽  
pp. S4.3-S5
Author(s):  
Courtney Raab ◽  
Amy Peak
Keyword(s):  
Impact Assessment ◽  
Neuropsychological Tests ◽  
Primary Outcome ◽  
Primary Objective ◽  
Cognitive Test ◽  
Control Group ◽  
Secondary Objective ◽  
Composite Scores ◽  
The Impact ◽  
Test Impact

ObjectiveThe primary objective of this study is to determine the ability of embedded invalidity indicators (EIIs) within the Immediate Post-concussion Assessment and Cognitive Test (ImPACT) to accurately identify individuals purposefully underperforming (sandbagging) on the baseline assessment. The secondary objective is to determine if any of the 5 specific EIIs are more or less likely to identify purposeful sandbaggers.BackgroundSandbagging baseline neuropsychological tests is a growing problem with significant potential consequences including premature post-concussion clearance.Design/methodsVolunteers were recruited to complete a baseline ImPACT assessment. Participants were randomized to either a control group or a coached sandbagging group. Primary outcome measures were the number of participants identified as invalid via any EII, as well as mean raw composite scores and percentiles for each sub-section within the ImPACT assessment.ResultsSeventy-seven participants (37 control and 40 sandbaggers) completed the study. Only half (50%, n = 20) of the purposeful sandbaggers were identified via any EII. Appropriately, no participants in the control group were identified as invalid. The Working Memory EII correctly identified 40% of the purposeful sandbaggers, and the Three Letters EII identified 35% of purposeful sandbaggers. All other EIIs identified 15% of purposeful sandbaggers. Twenty-six purposeful sandbaggers achieved at least 1 composite sub-score, 1st percentile; 27% of those were not identified via any EII. One participant scored ≤ 1st percentile in every composite category and was not identified via any EII.ConclusionSandbagging baseline ImPACT assessments without detection likely occurs more often than previous literature suggests. Half of purposeful sandbaggers were not identified via current EIIs, and 3 of 5 EIIs identified 15% of purposeful sandbaggers. Re-evaluation or recalibration of ImPACT's current EIIs may be appropriate.Disclosures: Dr. Raab has nothing to disclose. Dr. Peak has nothing to disclose.

The effect of crossbred ewe type and ram genotype on lamb output and carcass quality

2001 ◽  
Vol 2001 ◽  
pp. 225-225 ◽  
Author(s):  
L.E.R. Dawson ◽  
A.F. Carson
Keyword(s):  
Growth Index ◽  
Primary Objective ◽  
Growth Potential ◽  
Carcass Quality ◽  
Sheep Industry ◽  
Lean Growth ◽  
Secondary Objective ◽  
Terminal Sire ◽  
The Hill ◽  
The Impact

In view of the stratified nature of the sheep industry, changes in breeding policies in the hill sector impinge on the performance of the lowland sector. Carson et al (2000) investigated the effect of choice of ram and ewe breed on lamb output and carcass quality in the hill sheep sector. First cross (F1) ewes were produced as a result of crossing Scottish Blackface and Cheviot ewes with a range of ram breeds. The primary objective of the present study was to provide information on the performance of these crossbred females in terms of lamb output and carcass quality and thus determine the impact of changing hill genetics on all strata of the sheep industry. Within the terminal sire breeds significant improvements in lean growth potential have been made through genetic improvement schemes. The secondary objective of this study was to provide information on the effects of using high lean growth index rams on lamb growth and carcass quality.

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