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Burgess Hill, United Kingdom

Although new oral anticoagulants (NOACs) represent an advance in anticoagulant therapy over vitamin K antagonists (VKAs), they nevertheless have a low, but significant risk for bleeding complications. Reversal agents for VKAs, such as prothrombin complex concentrates (PCCs), are currently being evaluated in preclinical studies for NOAC reversal. This article reviews the preclinical data for the most extensively studied PCC for NOAC reversal, Beriplex, a 4-factor PCC. The results from the Beriplex studies are also compared with those obtained with other reversal agents, including different nonactivated PCCs, activated PCCs, and recombinant activated factor VII. © 2014 Elsevier Inc.

Magee G.,Premier Research Services | Zbrozek A.,CSL Behring
ClinicoEconomics and Outcomes Research | Year: 2013

Background: Fluid overload, including transfusion-associated circulatory overload (TACO), is a serious complication of fresh frozen plasma (FFP) transfusion. The incidence of fluid overload is underreported and its economic impact is unknown. An evaluation of fluid overload cases in US hospitals was performed to assess the impact of fluid overload on length and cost of hospital stay. Study design and methods: Retrospective analysis was performed using a clinical and economic database covering >600 US hospitals. Data were collected for all inpatients discharged during 2010 who received ≥1 unit FFP during hospitalization. Incidence of fluid overload was determined through International Classification of Diagnosis (ICD-9) codes. Multivariate regression analysis was performed for primary outcome measures: hospital length of stay (LOS) and total hospital costs. Results: Data were analyzed for 129,839 FFP-transfused patients, of whom 4,138 (3.2%) experienced fluid overload (including TACO). Multivariate analysis, adjusting for baseline characteristics, found that increased LOS and hospital costs were independently associated with fluid overload. Patients diagnosed with fluid overload had longer mean LOS (12.9 days versus 10.0 days; P < 0.001) and higher mean hospital cost per visit ($46,644 versus $32,582; P < 0.001) compared with patients without fluid overload. Conclusion: For a population of US inpatients who received FFP during hospitalization, fluid overload was associated with a 29% increase in LOS and a $14,062 increase in hospital costs per visit. These findings suggest that the incidence of fluid overload in the general population is greater than historically reported. A substantial economic burden may be associated with fluid overload in the US. © 2013 Magee and Zbrozek, publisher and licensee Dove Medical Press Ltd.

Dickneite G.,CSL Behring | Hoffman M.,Duke University
Thrombosis and Haemostasis | Year: 2014

Newer oral anticoagulants offer several advantages over traditional agents (e.g. warfarin), but they are still associated with a bleeding risk and currently there is no validated reversal treatment for them. While there is little support for the use of fresh frozen plasma, and limited data available on the effects of activated recombinant factor VII, pre-clinical data suggest that prothrombin complex concentrates (PCCs) may have potential in this setting. PCCs are currently used to successfully reverse warfarin-induced anticoagulation; however, clinical evidence for their use with new oral anticoagulants is lacking, with most of the available data coming from preclinical animal studies. Furthermore, there appears to be variation in the ability of different PCCs to reverse the coagulopathy induced by the new anticoagulants, and a lack of correlation between the reversal of laboratory test results and the reversal of anticoagulant-induced bleeding. Although there have been encouraging results, care must be taken in generalising findings from animal models and nonbleeding human subjects to the situation in bleeding patients. Ultimately, more evidence supporting anticoagu-lation reversal for new anticoagulants is needed, particularly regarding the treatment of bleeding in human patients in a clinical setting. According to the current evidence, use of PCCs may be considered a reasonable approach in dire clinical situations; however, a consensus has not yet been reached regarding PCC use or dosing, due to lack of clinical data. © Schattauer 2014.

Palsson O.S.,University of North Carolina at Chapel Hill | Baggish J.,CSL Behring | Whitehead W.E.,University of North Carolina at Chapel Hill
The American journal of gastroenterology | Year: 2014

The objectives of this study were to determine whether the symptoms of diarrhea (defined as loose or watery stools), constipation (hard or lumpy stools), abdominal pain, and bloating occur in episodes rather than sporadically in patients with irritable bowel syndrome (IBS); to identify rules for defining the onset and termination of symptom episodes; and to assess the overlap of these episodes. IBS patients kept a symptom log in which they rated the consistency of each bowel movement (BM) on the Bristol Stool Scale for 3 months. Each night they transferred these data to an internet website and also rated abdominal pain and bloating for that day. Data were analyzed for 124 patients who completed at least 21 consecutive diary days (mean of 73 days) without taking laxative, antidiarrheal, or IBS-specific medications. For each symptom in each patient, we computed the correlation between consecutive observations (autocorrelations) in the diary to determine whether the symptom tended to occur in clusters of several instances, as would happen in episodes vs. happening randomly. Next, we compared different patterns by which diarrhea and nondiarrhea stools alternate to identify episode definitions that captured at least 75% of loose/watery stools. A similar pattern analysis was performed for constipation. Pain and bloating episodes were defined as days with an intensity rating >3 on a 0-10 scale. These patterns were converted into rules for defining the onset and termination of symptom episodes. Last, we used these episode definitions to examine the overlap of pain with episodes of diarrhea, constipation, and pain. Significant (P<0.05) autocorrelations were found in the Bristol Stool Scale ratings of 69.4% of patients and in the daily abdominal pain and bloating ratings of 52.4% and 68.5% of patients, respectively. Defining a diarrhea episode as two or more loose/watery stools never separated by >1 nonloose/watery stool or by a day without a BM captured 76% of all loose/water stools. Defining constipation episodes as two or more hard/lumpy stools never separated by >1 nonhard/lumpy stool captured 80% of hard/lumpy stools. Sequences of 3 or more days without a BM were also defined as constipation episodes because they were strongly associated with hard stools. Average episode durations were 2.1 days for diarrhea, 4.5 days for constipation, 3.1 days for pain, and 3.5 days for bloating. Overlap analysis showed that only 41.6% of constipation episode days and 67.0% of diarrhea episode days were pain episode days. Bloating and pain coexisted on 59.1% of days on which either type occurred. Loose/watery stools and hard/lumpy stools occur in well-defined episodes. Pain and bloating also occur in episodes, but contrary to the Rome criteria more than half of the pain episodes occur outside episodes of abnormal stool consistency.

Whyte J.L.,CSL Behring | Engel-Nitz N.M.,OptumInsight Health Economics and Outcomes Research | Teitelbaum A.,OptumInsight Health Economics and Outcomes Research | Gomez Rey G.,OptumInsight Health Economics and Outcomes Research | Kallich J.D.,Amgen Inc.
Medical Care | Year: 2015

Background: Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. Objectives: Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. Methods: Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. Results: The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. Conclusions: Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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