Oseltamivir induced sinus bradycardia: an area of potential concern

Oseltamivir was approved for the prevention and treatment of influenza in 1999 by the USFDA (US Food and Drug Administration). The use of Oseltamivir is increasing rapidly all over the world, especially after the 2009 “Swine Flu” pandemic. Less data is published as far as the cardiovascular side effects of Oseltamivir are concerned, but it could be associated with some serious cardiovascular side effects. This study presented a case series of 5 cases suspected to be suffering from seasonal influenza H1N1 (“Swine Flu”), who developed sinus bradycardia while they were on Oseltamivir therapy

Analysis of drug related electrolyte disturbances in emergency medicine department

Background: Electrolytes play an important role in various physiological functions of the body. Electrolyte disturbances are one of the most common problems encountered in critically ill patients. Drugs are also known to cause adverse electrolyte consequences. These drugs could be anti-hypertensive agents, hormones, antipsychotics or steroids. There is paucity of published literature on electrolyte disturbances caused by drugs. The purpose of our study was to evaluate the electrolyte disturbances caused by various drugs in critically ill patients.Methods: Following approval of the Institutional Ethics Committee, data collection was started. Adverse Drug Reactions (ADRs) presenting as an electrolyte disturbance in emergency medicine department or occurring in hospitalized patients in the Intensive care unit (ICU) of our hospital was be collected. ADRs resulting into electrolyte disturbances were identified and analysed in detail for demographic details, types of electrolyte disturbances, seriousness, severity, causality and preventability of ADRs. Fisher's exact test was done to find out the statistical difference between the electrolyte disturbances and different drugs.Results: Total 58 ADRs were reported as an electrolyte disturbance. Mean age of the patients affected was 52.48 years. Highest number of ADRs were observed in the age group of 61 to 70 years. Hypokalemia constituted 32 cases (55.2%) followed by hyponatremia (25.9%), hyperkalemia (6.9%), hypernatremia (6.9%), hypocalcemia (1.7%), hypomagnesemia (1.7%) and hypophosphatemia (1.7%). Insulin was associated with maximum cases of ADRs (27.6%).Conclusions: Electrolyte disturbances constitutes a major chunk of ADRs especially in critically ill patients. The physicians must be well-versed with the dynamics of fluid-electrolyte balance

Precession of timelike bound orbits in Kerr spacetime

Astrometric observations of S-stars provide a unique opportunity to probe the nature of Sagittarius-A* (Sgr-A*). In view of this, it has become important to understand the nature and behavior of timelike bound trajectories of particles around a massive central object. It is known now that whereas the Schwarzschild black hole does not allow the negative precession for the S-stars, the naked singularity spacetimes can admit the positive as well as negative precession for the bound timelike orbits. In this context, we study the perihelion precession of a test particle in the Kerr spacetime geometry. Considering some approximations, we investigate whether the timelike bound orbits of a test particle in Kerr spacetime can have negative precession. In this paper, we only consider low eccentric timelike equatorial orbits. With these considerations, we find that in Kerr spacetimes, negative precession of timelike bound orbits is not allowed.Comment: 12 pages, 18 figure

Results of Posterior Dislocation of Elbow Associated with Bony and Soft Tissue Injury

Elbow trauma is challenging to manage by virtue of its complex articular structure and capsuloligamentous and musculotendinous arrangements. We included 17 patients with elbow dislocation and associated injuries in this study. The study protocol included early elbow reduction and planned fixation of the medial or lateral condyle, coronoid and radial head. The sample was 73% male and 27% female with mean duration follow-up of 8 months, and mean age of 37 years. The mean Mayo Elbow Performance Score was 96 points at conclusion of follow-up, indicating an excellent result in 14 patients. Whenever the radial head was excised, we performed a strong transosseous ligamentous repair of the medial and lateral collateral ligaments. Fixation of the coronoid is essential for elbow stability. A small avulsed fragment can be fixed using an ACL jig. We found this technique very useful. Early planned intervention, stable fixation, and repair provide sufficient stability and enhance functional outcomes

Estimated size of the clinical medical imaging physics workforce in the United States

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United States in 2019 consisted of approximately 1794 physicists supporting diagnostic X-ray (1073 board-certified) and 934 physicists supporting nuclear medicine (460 board-certified), with a number of individuals practicing in both subfields. There were an estimated 235 physicists supporting nuclear medicine exclusively (150 board-certified). The estimated total workforce, accounting for overlap, was 2029 medical physicists. These estimates are in approximate agreement with other published studies of segments of the workforce

Preclinical Pharmacokinetic Evaluation to Facilitate Repurposing of Tyrosine Kinase Inhibitors Nilotinib and Imatinib as Antiviral Agents

Background Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for “repurposing” as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the “Animal Rule” to facilitate use of validated animal models for conducting anti-viral efficacy studies. Methods To enable such efficacy studies of two clinically approved TKIs, nilotinib, and imatinib, we first conducted comprehensive pharmacokinetic (PK) studies in relevant rodent and non-rodent animal models. PK of these agents following intravenous and oral dosing were evaluated in C57BL/6 mice, prairie dogs, guinea pigs and Cynomolgus monkeys. Plasma samples were analyzed using an LC-MS/MS method. Secondarily, we evaluated the utility of allometry-based inter-species scaling derived from previously published data to predict the PK parameters, systemic clearance (CL) and the steady state volume of distribution (Vss) of these two drugs in prairie dogs, an animal model not tested thus far. Results Marked inter-species variability in PK parameters and resulting oral bioavailability was observed. In general, elimination half-lives of these agents in mice and guinea pigs were much shorter (1–3 h) relative to those in larger species such as prairie dogs and monkeys. The longer nilotinib elimination half-life in prairie dogs (i.v., 6.5 h and oral, 7.5 h), facilitated multiple dosing PK and safety assessment. The allometry-based predicted values of the Vss and CL were within 2.0 and 2.5-fold, respectively, of the observed values. Conclusions Our results suggest that prairie dogs and monkeys may be suitable rodent and non-rodent species to perform further efficacy testing of these TKIs against orthopoxvirus infections. The use of rodent models such as C57BL/6 mice and guinea pigs for assessing pre-clinical anti-viral efficacy of these two TKIs may be limited due to short elimination and/or low oral bioavailability. Allometry-based correlations, derived from existing literature data, may provide initial estimates, which may serve as a useful guide for pre-clinical PK studies in untested animal models

b-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression

Glutamate is the principal excitatory neurotransmitter in the nervous system. Inactivation of synaptic glutamate is handled by the glutamate transporter GLT1 (also known as EAAT2; refs 1, 2), the physiologically dominant astroglial protein. In spite of its critical importance in normal and abnormal synaptic activity, no practical pharmaceutical can positively modulate this protein. Animal studies show that the protein is important for normal excitatory synaptic transmission, while its dysfunction is implicated in acute and chronic neurological disorders, including amyotrophic lateral sclerosis (ALS) 3 , stroke 4 , brain tumours 5 and epilepsy To identify compounds capable of increasing rodent GLT1 expression, a structurally diverse library of 1,040 FDA-approved drugs and nutritionals were individually added to organotypic spinal cord slice cultures prepared from postnatal day 9 rats To better understand the mechanism of action, the effect of the drugs on the GLT1 promoter was examined in cell lines fro

How to screen for non-adherence to antihypertensive therapy

The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians’ perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography–tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere

Defining the Middle Corona

International audienceAbstract The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment