scholarly journals A retrospective study on the evaluation of the appropriateness of oral anticoagulant therapy for patients with atrial fibrillation

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259199
Author(s):  
Yiyi Qian ◽  
Jiajun Zhang ◽  
Jiangya Li ◽  
Zhiying Weng
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Events ◽  
Low Dose ◽  
Standard Dose ◽  
Oral Anticoagulant Therapy ◽  
Anticoagulation Therapy ◽  
Inappropriate Drug ◽  
High Dose ◽  
Drug Selection ◽  
Inappropriate Prescriptions

Background The incidence of atrial fibrillation (AF) is increasing, and effective anticoagulation therapy can prevent adverse events. Selecting the appropriate OAC based on patient characteristics has become a challenge. Interventions are going to be a potential area of focus. Objectives To explore the discrepancies between clinician prescriptions and recommended guidelines of oral anticoagulants (OACs) for patients with atrial fibrillation (AF), and to provide direction for improving anticoagulation strategies for treating patients with AF. Materials and methods Data were collected from the electronic medical record system of Fuwai Yunnan Cardiovascular Hospital between July 2019 and January 2020. The suitability of prescribed OACs for patients with AF was assessed according to the Rules for Avoiding Prescription Inappropriateness, the prescribed medicine label, and any relevant antithrombotic guidelines for treating patients with AF. Results A total of 460 patients met the inclusion criteria. Of these, 53.7% received an appropriate prescription and 46.3% received an inappropriate prescription. Of the patients who received inappropriate prescriptions, 15.4% were prescribed without the presenting appropriate indicators, 1.3% were prescribed inappropriate drug selection, and 29.6% were prescribed inappropriate drug doses. For patients prescribed without providing appropriate indicators, 2.2% had no indication for medication and 13.3% had an indication for medication, but not a specific OAC. For patients with inappropriate drug selection, 1, 5 patients were on rivaroxaban, dabigatran respectively. The distribution of NOAC doses was as follows: dabigatran standard dose (45.2%), the low dose (54.8%). Rivaroxaban standard dose (58.9%), low dose (36.8%), high dose (4.3%). A total of 44 patients (9.6%) experienced bleeding events, 12 patients (2.6%) experienced embolic events, and 7 patients experienced other adverse events after dosing. Conclusions In clinical practice, it is common for patients with AF to receive inappropriate prescriptions of OACs. Therefore there is a need to enhance anticoagulation management in patients with AF to improve the appropriate use of OACs.

scholarly journals Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine Recipients

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
H Keipp Talbot ◽  
Andrew J Dunning ◽  
Corwin A Robertson ◽  
Victoria A Landolfi ◽  
David P Greenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Influenza Vaccine ◽  
Randomized Clinical Trial ◽  
Standard Dose ◽  
High Dose ◽  
Passive Surveillance ◽  
Prospective Randomized Clinical Trial ◽  
Gastrointestinal Events ◽  
Gastrointestinal Adverse Events

Abstract Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.

Abstract MP77: Patient, Provider, and Insurance Predictors of Oral Anticoagulation Initiation and Dosing in Atrial Fibrillation

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Inmaculada Hernandez ◽  
Yuting Zhang ◽  
Samir Saba
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulation ◽  
Clinical Characteristics ◽  
Low Dose ◽  
Antiplatelet Agents ◽  
High Dose ◽  
Strong Impact ◽  
Newly Diagnosed ◽  
Cost Index ◽  
Logistic Regression Models

Background: Recent research has shown strong provider-level variation in oral anticoagulation (OAC) use in atrial fibrillation (AF). The objective of the present study was to examine predictors of prescribing OAC to newly diagnosed AF patients, with special attention to prescribing low-dose direct oral anticoagulant agents (DOACs) to patients with no diagnosis of chronic kidney disease (CKD). Methods: Using 2013-2014 Medicare claims data, we identified patients newly diagnosed with AF who had CHA2DS2-VASc score≥2. Our sample included 19,390 patients who did not initiate OAC, and 22,299 OAC initiators, among whom 12,786 initiated warfarin, 5,984 high-dose DOACs and 3,529 low-dose DOACs. We constructed logistic regression models to estimate the effect of patient demographics, clinical characteristics, provider specialty, and insurance factors on OAC initiation and likelihood of prescribing low dose DOAC in patients with no CKD. Results: As shown in the table, age, gender, heart failure, and a history of bleeding affected the initiation of OAC as well as DOAC dosing. White patients were more likely to initiate OAC, but race did not affect DOAC dosing. Use of antiplatelet agents decreased the odds of OAC initiation by 27% (95%CI, 23%-31%), but did not impact DOAC dosing. The odds of OAC initiation decreased by 10% (95%CI, 6%-15%) for each point increase in the Geographic Practice Cost Index for malpractice. The odds of initiating low-dose DOACs were 30% (95%CI, 11%-38%) lower for patients seen by cardiologists than for those seen by internists or family practitioners. Conclusions: In addition to demographics and clinical characteristics, provider and insurance factors have a strong impact on initiation and dosing of OAC.

scholarly journals Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
S. Dian ◽  
V. Yunivita ◽  
A. R. Ganiem ◽  
T. Pramaesya ◽  
L. Chaidir ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Standard Dose ◽  
Geometric Mean ◽  
Phase Iii ◽  
High Dose ◽  
Treatment Area ◽  
Double Blind ◽  
Time Curve

ABSTRACT High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0–24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.)

scholarly journals P179 Glucocorticoid exposure and link to serious adverse events in patients with ANCA-associated vasculitis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Philip Spearpoint ◽  
Cormac Sammon ◽  
Antonio Ramirez de ◽  
Arellano Serna ◽  
Peter Rutherford
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Renal Disease ◽  
Real World ◽  
Low Dose ◽  
Remission Induction ◽  
High Dose ◽  
Anca Associated Vasculitis ◽  
Increased Risk ◽  
New Onset

Abstract Background Remission induction in ANCA-associated vasculitis (AAV) is with high dose glucocorticoids (GC) and immunosuppressants. Patients are exposed to high GC dose and/or prolonged low dose. EULAR/EDTA guidelines target 7.5-10mg at 3 months but acknowledge this is often achieved later. This study used UK real world practice data to examine the scale of GC exposure and associated clinical risks in AAV. Methods The study utilised the Clinical Practice Research Datalink (CPRD) - Hospital Episode Statistics (HES) linked database. AAV patients were identified using specific READ and ICD codes and followed between 01/01/1997 and 01/01/2018. GP prescriptions were used to describe periods of continuous GC use, stop and restart and when high dose (&gt; 30mg/day) and low dose (&lt;30mg/day) was prescribed. Diagnostic codes indicative of infections and adverse events linked to GCs were used to estimate rates in the AAV population using a generalized linear model with a Poisson distribution. Results 450 AAV patients with at least one GC prescription were analysed. The median dose decreased to 9.3 mg (IQR 5.0 - 17.0) at 6 months and 5.1 mg (0.00 - 10.0) at 12 months,50% patients were taking &gt; 10mg at 5 months and 25% were still &gt; 10mg at 12 months. However, within 6 months of achieving 10mg/day, 50% relapse to needing dose &gt;10mg, 75% within 2 years and 90% within 6 years. In adjusted Poisson model (age, gender, year of diagnosis before/after 2013) the rate of infection in AAV patients taking high dose was 2.59 times (CI95 1.95, 3.45) that of those on low dose and lower in those not taking GCs (IRR 0.27 (0.22-0.34)). Increased risk of new onset cardiovascular disease (IRR 2.55 (0.92, 7.04)) and new onset renal disease (IRR 3.4 (1.29-8.96)) were higher in patients receiving high dose. Conclusion AAV patients have significant exposure to high dose GCs and in real world practice, GC dose remains higher than recommended in current clinical guidelines. High dose GCs are associated with high risk of infection and new cardiovascular disease and renal disease. This creates a significant patient burden and has implications for healthcare resource use. Disclosures P. Spearpoint: Corporate appointments; Employee of Vifor Pharma. C. Sammon: Corporate appointments; Employee of PHMR. A. Ramirez de Arellano Serna: Corporate appointments; Employee of Vifor Pharma. P. Rutherford: Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.

scholarly journals High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Johan Ursing ◽  
Lars Rombo ◽  
Staffan Eksborg ◽  
Lena Larson ◽  
Anita Bruvoll ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adverse Events ◽  
Standard Dose ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
Chloroquine Resistance ◽  
High Dose ◽  
Qtc Interval ◽  
Content Type ◽  
Qt Interval Prolongation

ABSTRACT Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine. (This study has been registered at ClinicalTrials.gov under identifier NCT01814423.)

scholarly journals COMPARE: prospective, randomized, non-inferiority trial of high- vs. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions

2020 ◽  
Vol 41 (27) ◽  
pp. 2541-2552 ◽  
Author(s):  
Sabine Steiner ◽  
Andrej Schmidt ◽  
Thomas Zeller ◽  
Gunnar Tepe ◽  
Marcus Thieme ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lower Bound ◽  
Adverse Events ◽  
Low Dose ◽  
Primary Patency ◽  
High Dose ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Wide Range ◽  
Major Adverse Events

Abstract Aims Drug-coated balloons (DCBs) for femoropopliteal interventions have not been tested against each other. We aimed to directly compare efficacy and safety of a high-dose (In.Pact™) vs. low-dose (Ranger™) DCB with nominal paclitaxel densities of 3.5 vs. 2.0 μg/mm2. Methods and results Within a prospective, multicentre, non-inferiority, clinical trial 414 patients with symptomatic femoropopliteal lesions (Rutherford classification 2–4) were randomly assigned in a 1:1 ratio to endovascular treatment with either high- or low-dose DCB after stratification for lesion length. Primary efficacy and safety endpoints comprised primary patency and freedom from major adverse events (i.e. device and procedure-related deaths through 1 month, major amputations, and clinically driven target lesion revascularization through 12 months). We set a non-inferiority margin of −10% at 12 months. Total occlusions were observed frequently (&gt;40%) and provisional stenting was performed in every fourth intervention. Non-inferiority was determined for both primary efficacy and safety endpoints at 12 months. Primary patency was 81.5% in the high-dose and 83.0% in low-dose DCB group {difference: 1.5% [lower bound of the 90% two-sided confidence interval (CI) −5.2%]; Pnon-inferiority &lt; 0.01}. Freedom from major adverse events was determined in 92.6% in high-dose and in 91.0% in low-dose DCB group [difference −1.6% (lower bound of the 90% two-sided CI −6.5%); Pnon-inferiority &lt; 0.01]. Overall death rate was low (2.0%) and no major amputation occurred. Conclusion Two DCBs with different coating characteristics exhibited comparable results with excellent effectiveness and safety through 12 months for femoropopliteal interventions including a wide range of lesion lengths. Clinical trial registration The trial is registered with ClinicalTrials.gov (NCT02701543).

High Dose Plerixafor Is Safe and Mobilizes Higher Numbers of CD34+ Cells Compared with Standard Dose Plerixafor

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 585-585
Author(s):  
Jeremy M Pantin ◽  
Xin Tian ◽  
Matthew M. Hsieh ◽  
Lisa Cook ◽  
Theresa Donohue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
Adverse Events ◽  
Dose Level ◽  
Peripheral Blood ◽  
Standard Dose ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cell Numbers ◽  
Cd34 Cells

Abstract Abstract 585 Introduction Plerixafor is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. This results in therapid release of CD34+ cells into circulation, which can then be collected by apheresis. Plerixafor is FDA approved at the 240 μg/kg dose to be used in conjunction with G-CSF to mobilize autografts for transplantation. Allogeneic grafts can also be mobilized using single agent plerixafor without G-CSF, and following transplantation, result in sustained donor derived hematopoiesis. However, when the 240 μg/kg dose is used, 1/3 of donors fail to mobilize minimally acceptable doses of CD34+ cells. Recently, we demonstrated the safety of administration of a single dose of 480 μg/kg of subcutaneous (sc) plerixafor in humans. We subsequently conducted a randomized cross-over trial comparing CD34+ mobilization in healthy subjects mobilized with a single dose of sc plerixafor given at either a high dose (480 μg/kg) or a conventional dose (240 μg/kg). Methods Twenty normal healthy volunteers were randomized and received either a 240 or 480 μg/kg dose of sc plerixafor followed by at least a 2 week wash out period then were administered the other dose of plerixafor. Circulating numbers of leukocytes and CD34+ cells/μlwere measured at multiple time points for 24 hours following each plerixafor injection and the CD34+ AUC over 24 hours was calculated for each subject at each dose level. Peripheral blood colony forming unit (CFU) assays were performed at baseline and 6 hours after plerixafor dosing. Adverse events were graded using CTCAE version 3.A sample size of 20 subjects was determined to have over 90% power to detect an absolute CD34+ count difference of 10/μl using this crossover design and a two-sidedpaired t-test at the 0.05 level. Results Twenty-three subjects were enrolled and 20 completed administration of both doses. Peak circulating CD34+ cell numbers (median 31.5 vs 25, p=0.0009), circulating CD34+ cell numbers at 24hrs (median 15.5 vs 9, p<0.0001), and the CD34+ AUC over 24 hours (median 543 vs 411, p<0.0001) were all significantly higher following the administration of the 480 μg/kg plerixafor dose compared to the 240 μg/kg dose. The time to peak CD34+ was also slightly longer after the 480 μg/kg dose (median 10 vs 8 hrs, p=0.011). These differences were not related to the order of administration of the 2 different plerixafor doses. Although GM-CFUs from the peripheral blood at 6hrs following plerixafor were significantly higher compared to baseline levels at both plerixafordoses, there was no dose-effect relationship observed between drug dose and fold increase in GM-CFUs. The incidence and severity of AE's did not differ between lower and higher doses of plerixafor and no grade 3 or greater adverse events occurred at either dose level. Conclusion These preliminary data suggest high dose plerixafor can be administered safely and may mobilize more CD34+ cells than standard dose plerixafor. Furthermore, these data suggest mobilization following a single dose of plerixafor and a single apheresis procedure would result in graft collections containing higher CD34+ cell numbers when allogeneic stem cell donors are mobilized with high-dose plerixafor compared to standard-dose. Disclosures: Off Label Use: Plerixafor, a hematopoietic stem cell mobilizer, is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM).

The study of the treatment efficacy in metastatic castration-resistant prostate cancer of low dose abiraterone with food.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17571-e17571
Author(s):  
Kanta Makphanchareonkit ◽  
Thitiya Sirisinha Dejthevaporn ◽  
Dittapol Muntham ◽  
Phichai Chansriwong
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Adverse Events ◽  
Low Dose ◽  
Standard Dose ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response

e17571 Background: Abiraterone acetate and prednisolone (AAP) + ADT has been approved for treatment metastatic castration-resistant prostate cancer (CRPC) in the standard dose 1,000 mg with fasting state. Data in Ramathibodi hospital showed patients who had treated with standard dose of Abiraterone acetate (AA); had PSA response 47.83%. Previous studies showed using low dose AA of 250 mg with food had the non-inferiority results in efficacy. AA was not be reimbursed in Thailand, so the ability to use a highly effective drug at a quarter of the dose, could help in patient accessibility to cancer treatments. We sought to test the hypothesis that low-dose AA with food would have the comparable activity in Thai CRPC patients in both of the pre-Docetaxel and post Docetaxel treatment groups, and exploring the quality of life (QOL) of these patients. Methods: An observational cohort enrolled newly diagnosed metastasis CRPC at Ramathibodi hospital from 1st Jan 2019 to 31st Dec 2019. Patients were assigned to AA (250mg) with actual daily life meal. We collected the data of serum PSA and the adverse events every 4 weeks for 4 months. The QOL data was collected with the EuroQoL (EQ-5D) questionnaire which were done at baseline and every 4 weeks. The primary end point was PSA response that defined as PSA decreased ≥ 50% from PSA level at baseline. The secondary endpoint were the depth of PSA change, QOL and adverse events by using Fisher's exact test and T-test. Results: 21 patients were enrolled. At 12 weeks, there were 11 patients (52.38%) achieved 50% PSA response and 6 patients (28.57%) achieved 90% PSA response. The adverse events occurred 23.8%, and mostly were mild grade. The adverse events were comparable with the historical data in standard dose of AA. Low dose AA has significantly shown the improvement in quality of life from baseline (p < 0.001), and especially the significant improvement in pre-Docetaxel subgroup. Conclusions: Low-dose AA with food has good efficacy in PSA response, adverse events and QOL. Moreover, low dose AA shows more efficacy especially in pre-Docetaxel mCRPC patients. Low dose AA may be helping in reducing cost of cancer care, enabling in delivering affordable cancer care and increasing value of treatment.

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