Direct oral anticoagulant drug level testing in clinical practice: A single institution experience

We performed a review of all direct oral anticoagulant (DOAC) levels – ecarin times for dabigatran and anti-Xa levels for rivaroxaban and apixaban – ordered at our institution with the purpose of evaluating DOAC levels from “real-world” (non-clinical trial) patients taking DOACs long-term, in order to assess levels obtained, reasons for checking levels, and actions taken based on the testing result. A total of 28 patients had 48 levels sent over a 36-month period. The majority of outpatient levels were within or close to the range of published values. The setting in which levels were sent influenced how results affected management decisions: in the outpatient setting, the majority of levels served to reassure clinicians that DOAC levels were within expected ranges resulting in continuation of chosen management, whereas in the inpatient setting, DOAC levels were used most frequently to detect DOAC presence in urgent clinical situations and influenced clinical decision-making in the peri-procedural and pre-operative periods. Our results demonstrate that while testing may be useful if immediately available in urgent clinical situations where assessment of drug presence is needed, DOAC level monitoring is infrequently used overall, and the lack of use combined with the paucity of available evidence to guide clinical decision-making based on the results suggests there is little urgency to make the tests widely available for routine use outside of acute settings in the emergency department and urgent surgical setting

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance

Abstract Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery

A Comparative Look at Various Countries\u27 Legal Regimes Governing Automated Vehicles

News and commentary about automated vehicles (AVs) focus on how they look and appear to operate, along with the companies developing and testing them. Behind the scenes are legal regimes—laws, regulations, and implementing bodies of different kinds—that literally and figuratively provide the rules of the road for AVs. Legal regimes matter because public welfare hinges on aspects of AV design and operation. Legal regimes can provide gatekeeping for AV developers and operators seeking to use public roads, and they can allocate liability when something goes wrong. Guiding and complementing legal regimes is public policy. Policy documents such as articulations of national strategies are sometimes used to address issues related to legal regimes and to demonstrate a jurisdiction’s support for AV development. Building on its long history analyzing AV policy issues, RAND (with support of its Institute for Civil Justice) collaborated with the University of Michigan Law School’s Law and Mobility Program to study the nature of different AV legal regimes around the world. It selected countries known to be active in this domain. The research team reviewed and shared scholarly and gray literature (which is a type of scholarship produced by an entity in which commercial publications are not the primary focus, such as white papers from a government agency), and it also consulted experts in these regimes from the public and private sectors. Under the supervision of the Law and Mobility Fellow (a lawyer), law students collected and studied materials associated with country-specific legal regimes and drafted summaries guided by RAND’s enumeration of key factors. Availability of information about legal regimes varies—access to documentation, especially in English, is uneven, even for officials in different countries working collaboratively on these issues. That constrained availability is reflected in published legal comparisons, and it motivated the research team’s systematic research, which drew from materials in English and other languages. This article summarizes the makeup of AV legal regimes of Australia, China, France, Germany, Japan, and the United Kingdom. It highlights some key contrasts, which will be developed further as the project continues. It focuses on law and policy relating to highly to fully automated vehicles (SAE Levels 4 and 5). Although guided by a common set of topics for each country, each profile reflects the material available and the factors that differentiate national approaches. The remainder of this article introduces the legal regimes of the covered countries in turn. It then provides an overview of key points of comparison and outlines future work

A chrysophyte stomatocyst-based reconstruction of cold-season air temperature from Alpine Lake Silvaplana (AD 1500-2003); methods and concepts for quantitative inferences

Relatively little is known about past cold-season temperature variability in high-Alpine regions because of a lack of natural cold-season temperature proxies as well as under-representation of high-altitude sites in meteorological, early-instrumental and documentary data sources. Recent studies have shown that chrysophyte stomatocysts, or simply cysts (sub-fossil algal remains of Chrysophyceae and Synurophyceae), are among the very few natural proxies that can be used to reconstruct cold-season temperatures. This study presents a quantitative, high-resolution (5-year), cold-season (Oct-May) temperature reconstruction based on sub-fossil chrysophyte stomatocysts in the annually laminated (varved) sediments of high-Alpine Lake Silvaplana, SE Switzerland (1,789ma.s.l.), since AD 1500. We first explore the method used to translate an ecologically meaningful variable based on a biological proxy into a simple climate variable. A transfer function was applied to reconstruct the ‘date of spring mixing' from cyst assemblages. Next, statistical regression models were tested to convert the reconstructed ‘dates of spring mixing' into cold-season surface air temperatures with associated errors. The strengths and weaknesses of this approach are thoroughly tested. One much-debated, basic assumption for reconstructions (‘stationarity'), which states that only the environmental variable of interest has influenced cyst assemblages and the influence of confounding variables is negligible over time, is addressed in detail. Our inferences show that past cold-season air-temperature fluctuations were substantial and larger than those of other temperature reconstructions for Europe and the Alpine region. Interestingly, in this study, recent cold-season temperatures only just exceed those of previous, multi-decadal warm phases since AD 1500. These findings highlight the importance of local studies to assess natural climate variability at high altitude

A chrysophyte stomatocyst-based reconstruction of cold-season air temperature from Alpine Lake Silvaplana (AD 1500–2003); methods and concepts for quantitative inferences

Relatively little is known about past cold-season temperature variability in high-Alpine regions because of a lack of natural cold-season temperature proxies as well as under-representation of high-altitude sites in meteorological, early-instrumental and documentary data sources. Recent studies have shown that chrysophyte stomatocysts, or simply cysts (sub-fossil algal remains of Chrysophyceae and Synurophyceae), are among the very few natural proxies that can be used to reconstruct cold-season temperatures. This study presents a quantitative, high-resolution (5-year), cold-season (Oct–May) temperature reconstruction based on sub-fossil chrysophyte stomatocysts in the annually laminated (varved) sediments of high-Alpine Lake Silvaplana, SE Switzerland (1,789 m a.s.l.), since AD 1500. We first explore the method used to translate an ecologically meaningful variable based on a biological proxy into a simple climate variable. A transfer function was applied to reconstruct the ‘date of spring mixing’ from cyst assemblages. Next, statistical regression models were tested to convert the reconstructed ‘dates of spring mixing’ into cold-season surface air temperatures with associated errors. The strengths and weaknesses of this approach are thoroughly tested. One much-debated, basic assumption for reconstructions (‘stationarity’), which states that only the environmental variable of interest has influenced cyst assemblages and the influence of confounding variables is negligible over time, is addressed in detail. Our inferences show that past cold-season air-temperature fluctuations were substantial and larger than those of other temperature reconstructions for Europe and the Alpine region. Interestingly, in this study, recent cold-season temperatures only just exceed those of previous, multi-decadal warm phases since AD 1500. These findings highlight the importance of local studies to assess natural climate variability at high altitudes

Heparin-induced thrombocytopenia testing is over-utilized in cirrhosis & correlates with poor clinical outcomes

Introduction. Heparin-induced thrombocytopenia (HIT) is a serious complication seen in hospitalized, medically-ill patients. Evaluation for HIT using a commercially-available ELISA-based test has become increasingly common; however, it does have a high false positive rate. Implications of HIT testing in patients with cirrhosis have not yet been reported.Material and methods. We conducted a single-institution, retrospective review of all patients with cirrhosis admitted over a 29-month period. The student’s t-test and the χ2 test were used for comparisons. We performed a stratified survival analysis using Kaplan-Meier and log rank testing.Results. A total of 1,305 patients had a HIT Ab sent during the study period. Of these patients, 106 had cirrhosis and were included in the study. Eighteen (17%) of the patients with cirrhosis were HIT Ab positive and four of the eighteen had a positive Serotonin Release Assay (SRA) confirmatory test. No difference was found in platelet nadir, thrombotic rate, length of stay, and patient survival between patients with positive HIT Ab and negative HIT Ab testing. No consistent treatment was used among patients who were HIT Ab positive, despite hematology service consultation. Patients who were HIT Ab negative were more likely to have undergone liver transplantation compared to those who were positive (27 vs. 5.5%, respectively; p = 0.048).Conclusion. Our data suggest that HIT Ab testing is over-used in patients with cirrhosis and is poorly predictive of outcomes. With a poor positive predictive value, HIT testing may add unnecessary complexity to an already complicated patient population

A Comparative Look at Various Countries\u27 Legal Regimes Governing Automated Vehicles

News and commentary about automated vehicles (AVs) focus on how they look and appear to operate, along with the companies developing and testing them. Behind the scenes are legal regimes—laws, regulations, and implementing bodies of different kinds—that literally and figuratively provide the rules of the road for AVs. Legal regimes matter because public welfare hinges on aspects of AV design and operation. Legal regimes can provide gatekeeping for AV developers and operators seeking to use public roads, and they can allocate liability when something goes wrong. Guiding and complementing legal regimes is public policy. Policy documents such as articulations of national strategies are sometimes used to address issues related to legal regimes and to demonstrate a jurisdiction’s support for AV development. Building on its long history analyzing AV policy issues, RAND (with support of its Institute for Civil Justice) collaborated with the University of Michigan Law School’s Law and Mobility Program to study the nature of different AV legal regimes around the world. It selected countries known to be active in this domain. The research team reviewed and shared scholarly and gray literature (which is a type of scholarship produced by an entity in which commercial publications are not the primary focus, such as white papers from a government agency), and it also consulted experts in these regimes from the public and private sectors. Under the supervision of the Law and Mobility Fellow (a lawyer), law students collected and studied materials associated with country-specific legal regimes and drafted summaries guided by RAND’s enumeration of key factors. Availability of information about legal regimes varies—access to documentation, especially in English, is uneven, even for officials in different countries working collaboratively on these issues. That constrained availability is reflected in published legal comparisons, and it motivated the research team’s systematic research, which drew from materials in English and other languages. This article summarizes the makeup of AV legal regimes of Australia, China, France, Germany, Japan, and the United Kingdom. It highlights some key contrasts, which will be developed further as the project continues. It focuses on law and policy relating to highly to fully automated vehicles (SAE Levels 4 and 5). Although guided by a common set of topics for each country, each profile reflects the material available and the factors that differentiate national approaches. The remainder of this article introduces the legal regimes of the covered countries in turn. It then provides an overview of key points of comparison and outlines future work

Direct oral anticoagulant drug level testing in clinical practice: A single institution experience

We performed a review of all direct oral anticoagulant (DOAC) levels – ecarin times for dabigatran and anti-Xa levels for rivaroxaban and apixaban – ordered at our institution with the purpose of evaluating DOAC levels from “real-world” (non-clinical trial) patients taking DOACs long-term, in order to assess levels obtained, reasons for checking levels, and actions taken based on the testing result. A total of 28 patients had 48 levels sent over a 36-month period. The majority of outpatient levels were within or close to the range of published values. The setting in which levels were sent influenced how results affected management decisions: in the outpatient setting, the majority of levels served to reassure clinicians that DOAC levels were within expected ranges resulting in continuation of chosen management, whereas in the inpatient setting, DOAC levels were used most frequently to detect DOAC presence in urgent clinical situations and influenced clinical decision-making in the peri-procedural and pre-operative periods. Our results demonstrate that while testing may be useful if immediately available in urgent clinical situations where assessment of drug presence is needed, DOAC level monitoring is infrequently used overall, and the lack of use combined with the paucity of available evidence to guide clinical decision-making based on the results suggests there is little urgency to make the tests widely available for routine use outside of acute settings in the emergency department and urgent surgical setting