Drug interaction as a predictor of direct oral anticoagulant drug levels in atrial fibrillation patients

Data are limited on the effects of drug interactions on direct-acting oral anticoagulant (DOAC) levels. We evaluated the effects of the use of interacting drugs on DOAC levels in patients with atrial fibrillation (AF). We reviewed data of AF patients tested for DOAC levels in 2013–2017. The primary outcomes were drug levels exceeding the expected steady-state range, and in the highest quartile. A multivariate analysis was performed to evaluate the correlation of treatment by the use of interacting drugs, CYP3A4 and P-glycoprotein (P-gp) inhibitors, with the primary outcomes. Overall, 147 patients underwent DOAC level measurement [dabigatran (n?=?31), rivaroxaban (n?=?29), apixaban (n?=?87)]. Thirty-three (22.4%) had drug levels exceeding the expected range. Seventy-nine (53.7%) patients were treated with at least one interacting drug. In multivariate analysis, the concomitant use of interacting drugs was an independent predictor for drug levels exceeding the expected range (OR 3.3, 95% CI 1.20–9.05). The defined daily dose of the interacting drug correlated positively with DOAC levels (r?=?0.29, P?=?0.001). Co-treatment with interacting drugs was associated with extremely high levels of dabigatran, (OR 16.6, 95% CI 1.29–215.18) but not of the other DOAC examined. Concomitant use of interacting drugs is associated with high DOAC levels in patients with AF. Further investigation is warranted to establish the differences between specific DOAC, evaluate the effect on patient outcomes, and characterize the role of DOAC monitoring in this setting.     

Chapter 1. Introduction

Background

In December 2007, the European Society of Intensive Care Medicine established a Task Force to develop standard operating procedures (SOPs) for operating intensive care units (ICU) during an influenza epidemic or mass disaster.

Purpose

To provide direction for health care professionals in the preparation and management of emergency ICU situations during an influenza epidemic or mass disaster, standardize activities, and promote coordination and communication among the medical teams.

Methods

Based on a literature review and contributions of content experts, a list of essential categories for managing emergency situations in the ICU were identified. Based on three cycles of a modified Delphi process, consensus was achieved regarding the categories. A primary author along with an expert group drafted SOPs for each category.

Results

Based on the Delphi cycles, the following key topics were found to be important for emergency preparedness: triage, infrastructure, essential equipment, manpower, protection of staff and patients, medical procedures, hospital policy, coordination and collaboration with interface units, registration and reporting, administrative policies and education.

Conclusions

The draft SOPs serve as benchmarks for emergency preparedness and response of ICUs to emergencies or outbreak of pandemics.

     

An after-action review tool for EDs: learning from mass casualty incidents

Background

Conducting a thorough after-action review (AAR) process is an important component in improving preparedness for mass casualty incidents (MCIs).

Purposes

The study aimed to develop a structured AAR tool for use by medical teams in emergency departments after an MCI and to identify the best possible procedure for its conduct.

Basic procedures

On the basis of knowledge acquired from an extensive literature review, a structured tool for conducting an AAR in the emergency department was developed. A modified Delphi process was conducted to achieve content validity of the tool, involving 48 medical professionals from all 6 level I trauma centers in Israel. The AAR tool was tested during a simulated MCI drill.

Main findings

All experts support the conduct of an AAR in the ED after an MCI to build and maintain capacity for an adequate emergency response. More than 80% agreement was achieved regarding 14 components that were implemented in the proposed AAR tool. Ninety-four percent perceived that AARs should be conducted within 24 hours from the event using both written reports and face-to-face discussions. Both physicians and nurses should participate. The incident manager should lead the AAR, limiting the time allocated for each speaker and for the AAR in whole.

Principle conclusions

Conducting a structured AAR in all emergency departments after an MCI facilitates both learning lessons regarding the function of the medical staff and ventilation of feelings, thus mitigating anxieties and expediting a speedy return to normalcy.     

Excitatory–inhibitory network in the visual cortex: Psychophysical evidence

At early stages in visual processing cells respond to local stimuli with specific features such as orientation and spatial frequency. Although the receptive fields of these cells have been thought to be local and independent, recent physiological and psychophysical evidence has accumulated, indicating that the cells participate in a rich network of local connections. Thus, these local processing units can integrate information over much larger parts of the visual field; the pattern of their response to a stimulus apparently depends on the context presented. To explore the pattern of lateral interactions in human visual cortex under different context conditions we used a novel chain lateral masking detection paradigm, in which human observers performed a detection task in the presence of different length chains of high-contrast-flanked Gabor signals. The results indicated a nonmonotonic relation of the detection threshold with the number of flankers. Remote flankers had a stronger effect on target detection when the space between them was filled with other flankers, indicating that the detection threshold is caused by dynamics of large neuronal populations in the neocortex, with a major interplay between excitation and inhibition. We considered a model of the primary visual cortex as a network consisting of excitatory and inhibitory cell populations, with both short- and long-range interactions. The model exhibited a behavior similar to the experimental results throughout a range of parameters. Experimental and modeling results indicated that long-range connections play an important role in visual perception, possibly mediating the effects of context.     

Role of color Doppler imaging in diagnosing and managing pregnancies complicated by placental chorioangioma

PURPOSE: The purpose of this study was to evaluate the role of color Doppler imaging in the diagnosis and management of placental chorioangioma. METHODS: The medical records, sonographic reports, and sonograms of all pregnant women who had placental masses diagnosed in our sonography unit during the years 1992 through 2000 and had been evaluated using both gray-scale and color Doppler sonography were included in this study. Subjective evaluation of the amount and distribution of intralesional vascularity by color Doppler imaging was made in all cases. Cases of chorioangioma of the placenta were compared with cases of placental hemorrhage or subchorionic hematoma. The outcomes of the pregnancies were also recorded. RESULTS: Fifteen cases of placental masses were evaluated; 8 of them were identified as placental hemorrhage or subchorionic hematoma on the basis of the sonographic findings. The other 7 cases were identified prenatally as placental chorioangioma, at a mean menstrual age of 23 weeks and a mean maternal age of 29 years. The mean size of the tumor was 6.5 cm (range, 4-13 cm). All cases of chorioangioma showed either substantial internal vascularity or a large feeding vessel within the tumor. Three infants were delivered at term with favorable outcome; 2 of them demonstrated reduction of the intratumoral blood flow during follow-up. The other 4 cases were delivered at or before 32 weeks' menstrual age (1 intrauterine fetal death, 2 terminated pregnancies, and 1 normal infant). No case of placental hematoma demonstrated blood flow within the lesion or was associated with complications of the pregnancy. CONCLUSIONS: Color Doppler imaging helps differentiate placental chorioangioma from other placental lesions and may be useful in the prenatal follow-up of chorioangioma.     

Earlier detection of public health risks – Health policy lessons for better compliance with the International Health Regulations (IHR 2005): Insights from low-, mid- and high-income countries

The International Health Regulations (IHR 2005) require all Member States to build and maintain the capacities to prevent, detect and respond to public health emergencies. Early detection of public health risks is one of the core functions. In order to improve surveillance and detection, a better understanding of the health system conditions and their influencing factors are needed. The Israeli Ministry of Health/IHR National Focal Point held a workshop to elucidate health system conditions and their influencing factors that enable earlier detection. The workshop methodology employed a stepwise, small working group analysis approach to elucidate the conditions and their influencing factors affecting each stage of recognition, assessment, and reporting of infectious disease outbreaks, at the local, regional and national levels. In order to detect public health risks earlier, the detection process needs to be moved closer to the local communities and start with building capacity within communities. Building capacity and engaging with local and diverse communities requires significant changes in the governance approach and include information sharing, multi-sectoral communication and coordination across various levels before, during and after public health emergencies. Across the regions, low-, mid- and high-income countries seem to struggle more with governance and information sharing rather than with technical capacities and capabilities.     

The common prothrombotic factors in nulliparous women do not compromise blood flow in the feto-maternal circulation and are not associated with preeclampsia or intrauterine growth restriction

OBJECTIVE: In this study we evaluated the associations between common prothrombotic factors and increased blood flow resistance in the feto-maternal circulation, intrauterine growth restriction, small for gestational age, or preeclampsia. STUDY DESIGN: A prospective study was conducted in healthy nulliparous women with spontaneous singleton pregnancy. Blood was tested for the common prothrombotic factors, i.e., factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase C677T, anticardiolipin, and lupus anticoagulant. Blood flow resistance in the uterine, placental, and umbilical arteries were assessed by multigate Doppler and compared between women with and without prothrombotic factors. The maternal, fetal, and neonatal clinical courses were also compared among these subgroups. RESULTS: Prothrombotic factors were detected in 191 of 637 (30%) subjects. No significant difference in resistance to blood flow in the feto-maternal unit was discernible between women with and without prothrombotic factors. Pregnancy-induced hypertension or preeclampsia occurred in 10 of 191 (5.2%) and in 19 of 446 (4.3%) of women with and without a prothrombotic factor respectively ( P = .59). Intrauterine growth restriction was detected at 31 weeks in 13 of 164 (7.9%) and in 42 of 377 (11.1%) fetuses of women with and without a prothrombotic factor ( P = .26), and small for gestational age at delivery was observed in 19 of 187 (10.2%) and in 41 of 413 (9.9%) of mothers with and without prothrombotic markers, respectively. CONCLUSION: The presence of prothrombotic factors in healthy nulliparous women does not compromise blood flow in the feto-maternal unit, nor is it associated with preeclampsia, intrauterine growth restriction, or small for gestational age .     

Decision to evacuate a hospital during an emergency: the safe way or the leader's way?

Hospitals have frequently been evacuated because of natural or man-made disasters. In this article, we identify elements to be considered when confronted with the possibility of hospital evacuation. Hospital evacuation may have a significant impact on the surrounding community and the overall population. When the patients in a hospital are placed at risk, hospital leadership often decides to evacuate the facility to safeguard the well-being of both patients and staff. Such a decision is not likely to be criticized. We present various considerations. The effect of evacuation on patients, hospital staff, family members, the community, and even the nation as a whole, as well as repercussions affecting potential patients should be integral to the decision-making process and parallel to the risk assessment.     

Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers

Journal of Thrombosis and Thrombolysis - Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to...