scholarly journals An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance

2016 ◽  
Vol 116 (08) ◽  
pp. 337-348 ◽  
Author(s):  
Payman Shahabi ◽  
Laura Scheinfeldt ◽  
Daniel Lynch ◽  
Tara Schmidlen ◽  
Sylvie Perreault ◽  
...  
Keyword(s):  
Standard Dose ◽  
Anticoagulation Therapy ◽  
Standard Of Care ◽  
Clinical Decision ◽  
Drug Label ◽  
Therapy Decision ◽  
Dosing Algorithm ◽  
The Us ◽  
Supplementary Material ◽  
Warfarin Dosing

SummaryPharmacogenomics (PGx) guided warfarin dosing, using a comprehensive dosing algorithm, is expected to improve dose optimisation and lower the risk of adverse drug reactions. As a complementary tool, a simple genotype-dosing table, such as in the US Food and Drug Administration (FDA) Coumadin drug label, may be utilised for general risk assessment of likely over- or under-anticoagulation on a standard dose of warfarin. This tool may be used as part of the clinical decision support for the interpretation of genetic data, serving as a first step in the anticoagulation therapy decision making process. Here we used a publicly available warfarin dosing calculator (www.warfarindosing.org) to create an expanded gene-based warfarin dosing table, the CPMC-WD table that includes nine genetic variants in CYP2C9, VKORC1, and CYP4F2. Using two datasets, a European American cohort (EUA, n=73) and the Quebec Warfarin Cohort (QWC, n=769), we show that the CPMC-WD table more accurately predicts therapeutic dose than the FDA table (51 % vs 33 %, respectively, in the EUA, McNemar’s two-sided p=0.02; 52 % vs 37 % in the QWC, p<1×10−6). It also outperforms both the standard of care 5 mg/day dosing (51 % vs 34 % in the EUA, p=0.04; 52 % vs 31 % in the QWC, p<1×10−6) as well as a clinical-only algorithm (51 % vs 38 % in the EUA, trend p=0.11; 52 % vs 45 % in the QWC, p=0.003). This table offers a valuable update to the PGx dosing guideline in the drug label.Supplementary Material to this article is available at www.thrombosis-online.com.

scholarly journals Preliminary outcomes of preemptive warfarin pharmacogenetic testing at a large rural healthcare center

2019 ◽  
Vol 76 (6) ◽  
pp. 387-397 ◽  
Author(s):  
Emili Leary ◽  
Murray Brilliant ◽  
Peggy Peissig ◽  
Sara Griesbach
Keyword(s):  
Care Service ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Standard Of Care ◽  
International Normalized Ratio ◽  
Preliminary Evaluation ◽  
Thromboembolic Events ◽  
Rural Healthcare ◽  
Pharmacogenetic Testing ◽  
Warfarin Dosing

Abstract Purpose As a preliminary evaluation of the outcomes of implementing pharmacogenetic testing within a large rural healthcare system, patients who received pre-emptive pharmacogenetic testing and warfarin dosing were monitored until June 2017. Summary Over a 20-month period, 749 patients were genotyped for VKORC1 and CYP2C9 as part of the electronic Medical Records and Genomics Pharmacogenetics (eMERGE PGx) study. Of these, 27 were prescribed warfarin and received an alert for pharmacogenetic testing pertinent to warfarin; 20 patients achieved their target international normalized ratio (INR) of 2.0–3.0, and 65% of these patients achieved target dosing within the recommended pharmacogenetic alert dose (± 0.5 mg/day). Of these, 10 patients had never been on warfarin prior to the alert and were further evaluated with regard to time to first stable target INR, bleeds and thromboembolic events, hospitalizations, and mortality. There was a general trend of faster time to first stable target INR when the patient was initiated at a warfarin dose within the alert recommendation versus a dose outside of the alert recommendation with a mean (± SD) of 34 (± 28) days versus 129 (± 117) days, respectively. No trends regarding bleeds, thromboembolic events, hospitalization, or mortality were identified with respect to the pharmacogenetic alert. The pharmacogenetic alert provided pharmacogenetic dosing information to prescribing clinicians and appeared to deploy appropriately with the correct recommendation based upon patient genotype. Conclusion Implementing pharmacogenetic testing as a standard of care service in anticoagulation monitoring programs may improve dosage regimens for patients on anticoagulation therapy.

Treatment of venous leg ulcers using bilayered living cellular construct

2020 ◽  
Vol 9 (13) ◽  
pp. 907-918
Author(s):  
Aseel Bin Sawad ◽  
Fatema Turkistani
Keyword(s):  
Healthcare System ◽  
Cost Savings ◽  
Standard Of Care ◽  
Healthcare Resource Utilization ◽  
Psychological Status ◽  
Leg Ulcers ◽  
Venous Leg Ulcers ◽  
Time Period ◽  
The Us ◽  
Economic Analyses

Background: Venous leg ulcers (VLUs) present a significant economic burden on the US healthcare system and payers (US$14.9 billion). Aim: To evaluate the quality of life (QoL) of patients with VLUs; to analyze the limitations of standard of care (SOC) for VLUs; and to explain how using bilayered living cellular construct (BLCC) with SOC for treatment of VLUs can help heal more VLUs faster (than using SOC alone) as well as help improve QoL and help reduce the burden on the US healthcare system and payers. Materials & methods: This is a review study. The search was conducted in February 2020 by way of electronic databases to find relevant articles that provided information related to QoL of patients with VLUs, limitations of SOC for VLUs and economic analyses of using BLCC for treatment of VLUs. Results: VLUs impact patients’ physical, functional and psychological status and reduce QoL. A total 75% of VLU patients who used SOC alone failed to achieve healing in a timely fashion, which led to increased healthcare costs and healthcare resource utilization. Although the upfront cost is high, the greater effectiveness of BLCC offsets the added cost of the product during the time period of the studies. Therefore, BLCC helps to improve the QoL of VLU patients. As an example, for every 100 VLU patients in a healthcare plan, the use of BLCC can create cost savings of US$1,349,829.51. Conclusion: Payers’ coverage of BLCC results in reduction of the overall medical cost for treating VLU patients.

scholarly journals Comparison of an oncology clinical decision-support system’s recommendations with actual treatment decisions

2021 ◽  
Author(s):  
Suthida Suwanvecho ◽  
Harit Suwanrusme ◽  
Tanawat Jirakulaporn ◽  
Surasit Issarachai ◽  
Nimit Taechakraichana ◽  
...  
Keyword(s):  
Decision Support ◽  
Clinical Decision Support ◽  
Treatment Options ◽  
Stage Iv ◽  
Clinical Decision ◽  
Treatment Decisions ◽  
Therapeutic Options ◽  
Cancer Type ◽  
The Us ◽  
Rectal Cancers

Abstract Objective IBM(R) Watson for Oncology (WfO) is a clinical decision-support system (CDSS) that provides evidence-informed therapeutic options to cancer-treating clinicians. A panel of experienced oncologists compared CDSS treatment options to treatment decisions made by clinicians to characterize the quality of CDSS therapeutic options and decisions made in practice. Methods This study included patients treated between 1/2017 and 7/2018 for breast, colon, lung, and rectal cancers at Bumrungrad International Hospital (BIH), Thailand. Treatments selected by clinicians were paired with therapeutic options presented by the CDSS and coded to mask the origin of options presented. The panel rated the acceptability of each treatment in the pair by consensus, with acceptability defined as compliant with BIH’s institutional practices. Descriptive statistics characterized the study population and treatment-decision evaluations by cancer type and stage. Results Nearly 60% (187) of 313 treatment pairs for breast, lung, colon, and rectal cancers were identical or equally acceptable, with 70% (219) of WfO therapeutic options identical to, or acceptable alternatives to, BIH therapy. In 30% of cases (94), 1 or both treatment options were rated as unacceptable. Of 32 cases where both WfO and BIH options were acceptable, WfO was preferred in 18 cases and BIH in 14 cases. Colorectal cancers exhibited the highest proportion of identical or equally acceptable treatments; stage IV cancers demonstrated the lowest. Conclusion This study demonstrates that a system designed in the US to support, rather than replace, cancer-treating clinicians provides therapeutic options which are generally consistent with recommendations from oncologists outside the US.

scholarly journals Inadvertent Stent Retriever Detachment: A Multicenter Case Series and Review of Device Experience FDA Reports

2015 ◽  
Vol 4 (3-4) ◽  
pp. 75-82 ◽  
Author(s):  
Hesham Masoud ◽  
Thanh N. Nguyen ◽  
Coleman O. Martin ◽  
William E. Holloway ◽  
Sudheer Ambekar ◽  
...  
Keyword(s):  
First Generation ◽  
Mechanical Thrombectomy ◽  
Rare Complication ◽  
Case Series ◽  
Standard Of Care ◽  
Stent Retriever ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
The Us ◽  
Solitaire Fr

Mechanical thrombectomy using retrievable stents or stent retriever devices has become the mainstay of intra-arterial therapy for acute ischemic stroke. The recent publication of a series of positive trials supporting intra-arterial therapy as standard of care for the treatment of large vessel occlusion will likely further increase stent retriever use. Rarely, premature stent detachment during thrombectomy may be encountered. In our multicenter case series, we found a rate of detachment of less than 1% (n = 7/1,067), and all were first-generation Solitaire FR devices. A review of the US Food and Drug Administration database of device experience yielded 90 individual adverse reports of detachment. There were 82, 1 and 7 detachments of Solitaire FR (first generation), Solitaire FR2 (second generation) and Trevo devices, respectively. We conclude with a brief overview of the technical and procedural considerations which may be helpful in avoiding this rare complication.

Duration of Anticoagulation Therapy for Venous Thromboembolism

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 252-258 ◽  
Author(s):  
Henri Bounameaux ◽  
Arnaud Perrier
Keyword(s):  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Odds Ratio ◽  
Vitamin K Antagonists ◽  
Initial Period ◽  
Anticoagulation Therapy ◽  
Case Fatality ◽  
Clinical Decision ◽  
Venous Thromboembolic Event ◽  
Anticoagulant Treatment

Abstract Treatment of acute deep vein thrombosis and pulmonary embolism-often denominated together as venous thromboembolism (VTE)- consists of parenteral administration of heparin (usually low-molecular-weight heparin or alternatively unfractionated heparin or fondaparinux) overlapped and followed by oral vitamin K antagonists that are administered for a certain period (usually 3 to 12 months). Recommended or suggested durations differ according to guidelines. Practically, the clinical decision in an individual patient depends upon the estimated risks of VTE recurrence and treatment-induced bleeding. The risk of VTE recurrence is higher in idiopathic events (about 10% per year during the first two years and 3% per year thereafter) (odds ratio of 2.4, compared to secondary events); in male subjects (at least before the age of 60, with an odds ratio of 2–4); in patients with persistently elevated D-dimer level (odds ratio of 2.3, compared with normal level); and during the first two years after discontinuation of treatment. The annual risk of major bleeding on anticoagulant treatment vary largely in observational studies with figures of 2% to 29%, depending on the patient characteristics. The case-fatality rate is 8% (DVT), 12% (PE) for recurrent VTE, and about 10% for major bleed. These figures do not support long-term anticoagulant therapy, except in those patients exhibiting a very high risk of recurrence and/or a very low risk of bleeding. New therapeutic aspects might impact on the duration of anticoagulant therapy after a venous thromboembolic event. They include the possibility of pursuing anticoagulant treatment at a reduced INR after an initial period with an INR 2-3, and the advent of new, more specific and orally active anticoagulants. These features might modify the risk-benefit balance of extending anticoagulant therapy beyond the usual, limited duration.

Abstract 3070: Assessment of Manual Aspiration Therapy for the Treatment of Sinus Thrombosis

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Lance Bodily ◽  
Mouhammad Jumaa ◽  
Syed Zaidi ◽  
Tudor Jovin ◽  
Brian Jankowitz
Keyword(s):  
Sinus Thrombosis ◽  
Anticoagulation Therapy ◽  
Stable Condition ◽  
Standard Of Care ◽  
Mass Effect ◽  
Cerebral Venous Sinus Thrombosis ◽  
Venous Sinus ◽  
Motor Deficits ◽  
Aspiration Thrombectomy ◽  
Venous Sinus Thrombosis

Objective: While hydration and anticoagulation is typically the standard of care for cerebral venous sinus thrombosis, some patients remain refractory to medical management and continue to deteriorate. In these instances a number of more aggressive endovascular techniques have been reported to remove clots and restore blood flow in the venous sinuses. These techniques include direct thrombolysis, angioplasty, and various methods to disrupt and aspirate clot. Here we present the technique of endovascular transvenous manual aspiration thrombectomy (MAT) in five patients. Methods: We reviewed the records of five patients with medically refractory cerebral venous sinus thrombosis who received transvenous MAT. Presentation, technique, and outcome were evaluated. Results: Out of the five cases reviewed presentation included vomiting, dehydration, mental status changes, headaches, and acute motor deficits. On imaging three of the five patients had hemorrhage, edema, and mass effect present before treatment, while two had edema only. All of the patients reviewed were treated with anticoagulation therapy, intravenous heparin or subcutaneous lovenox, for a minimum of 24 hours. However, all of the patients continued to deteriorate despite early and aggressive medical anticoagulation therapy. All of the patients demonstrated rapid and progressive worsening of their neurological exam pre-operatively, including lack of arousal, pathological posturing, and expansion of secondary hemorrhages. This rapid deterioration warranted aggressive intervention, making the patients candidates for endovascular therapy. Direct thrombolysis with tPA was utilized with MAT via a distal access catheter(DAC) in all but one patient in which tPA was not used due to concern for hemorrhage. Aspiration of the superior sagittal sinus, transverse sinuses, straight sinus, and internal jugular were all included in this series. Catheters included the 0.070, 0.057, and 0.044 DAC and the 0.054 Penumbra microcatheter. Revascularization was achieved in all instances. One patient presented and remained neurologically devastated. She died 5 days after treatment. All other patients experienced improvement in their neurological examinations and were eventually discharged from the hospital in stable condition. Conclusions: Endovascular transvenous MAT is a feasible and effective revascularization technique to treat patients with cerebral venous sinus thrombosis.

scholarly journals ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Thayse Lozovoy Madsen Barbosa ◽  
Cleo Otaviano Mesa Junior ◽  
Hans Graf ◽  
Teresa Cavalvanti ◽  
Marcus Adriano Trippia ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
American Thyroid Association ◽  
Institutional Review ◽  
The Us ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

scholarly journals All You Need to Know About UGT1A1 Genetic Testing for Patients Treated With Irinotecan: A Practitioner-Friendly Guide

2021 ◽  
Author(s):  
Spinel Karas ◽  
Federico Innocenti
Keyword(s):  
Genetic Testing ◽  
Severe Neutropenia ◽  
Drug Label ◽  
Pancreatic Cancers ◽  
Homozygous Genotype ◽  
The Us ◽  
Wide Issue ◽  
Concise Information ◽  
Essential Knowledge ◽  
The Impact

Irinotecan is an anticancer agent widely used for the treatment of solid tumors, including colorectal and pancreatic cancers. Severe neutropenia and diarrhea are common dose-limiting toxicities of irinotecan-based therapy, and UGT1A1 polymorphisms are one of the major risk factors of these toxicities. In 2005, the US Food and Drug Administration revised the drug label to indicate that patients with UGT1A1*28 homozygous genotype should receive a decreased dose of irinotecan. However, UGT1A1*28 testing is not routinely used in the clinic, and specific reasons include lack of access to concise information on this wide issue as well as mixed recommendations by regulatory and professional entities. To assist oncologists in assessing whether and when to use UGT1A1 genetic testing in patients receiving irinotecan-based therapies, this article provided (1) essential knowledge of UGT1A1 polymorphisms; (2) an update on the impact of UGT1A1 polymorphisms on efficacy and toxicity of contemporary irinotecan-based regimens; (3) dosing adjustments based upon the UGT1A1 genotypes, and (4) recommendations from currently available guidelines from the US and international scientific consortia and major oncology societies.

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