Drug-drug interaction between dexamethasone and direct-acting oral anticoagulants: a nested case-control study in the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE. DESIGN: We used nested case-control study design. SETTING: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA. PARTICIPANTS: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban. RESULTS: McNemar's Χ2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ2=0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18). CONCLUSION: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out.

Falls prediction using the nursing home minimum dataset.

OBJECTIVE: The purpose of the study was to develop and validate a model to predict the risk of experiencing a fall for nursing home residents utilizing data that are electronically available at the more than 15 000 facilities in the United States. MATERIALS AND METHODS: The fall prediction model was built and tested using 2 extracts of data (2011 through 2013 and 2016 through 2018) from the Long-term Care Minimum Dataset (MDS) combined with drug data from 5 skilled nursing facilities. The model was created using a hybrid Classification and Regression Tree (CART)-logistic approach. RESULTS: The combined dataset consisted of 3985 residents with mean age of 77 years and 64% female. The model's area under the ROC curve was 0.668 (95% confidence interval: 0.643-0.693) on the validation subsample of the merged data. DISCUSSION: Inspection of the model showed that antidepressant medications have a significant protective association where the resident has a fall history prior to admission, requires assistance to balance while walking, and some functional range of motion impairment in the lower body; even if the patient exhibits behavioral issues, unstable behaviors, and/or are exposed to multiple psychotropic drugs. CONCLUSION: The novel hybrid CART-logit algorithm is an advance over the 22 fall risk assessment tools previously evaluated in the nursing home setting because it has a better performance characteristic for the fall prediction window of ≤90 days and it is the only model designed to use features that are easily obtainable at nearly every facility in the United States.

Photobleaching of Erythrosine B in Aqueous Environment Investigation Beyond pH.

In the scientific literature, the term aqueous environment is loosely employed as it encompasses a broad range of different buffering agents. While there is an increasing number of experimental evidence that point toward specific buffer effects extending far beyond pH, the impact of the chemical nature of the buffering ions is often disregarded, especially in photochemical studies. Herein, we highlighted the importance of buffer specific effects on both the photobleaching and the singlet oxygen quantum yields of a dye in aqueous environments. For this study, we chose erythrosine B (EB) as our model photosensitizer as its photochemistry and photobleaching are well documented in the literature. We followed EB's photobleaching via absorption spectroscopy in four different aqueous solvents, including pure water, phosphate, Tris and HEPES buffer. These buffer systems were selected because they are commonly used in biochemical and biological applications. Our results show that specific buffer effects cannot be neglected. Indeed, the singlet oxygen quantum yield for EB is significantly different in HEPES compared to the other solvents. Furthermore, we showed that EB's photoproduct is highly dependent on the nature of the chemical buffer being used.

Testing the face validity and inter-rater agreement of a simple approach to drug-drug interaction evidence assessment.

Low concordance between drug-drug interaction (DDI) knowledge bases is a well-documented concern. One potential cause of inconsistency is variability between drug experts in approach to assessing evidence about potential DDIs. In this study, we examined the face validity and inter-rater reliability of a novel DDI evidence evaluation instrument designed to be simple and easy to use. METHODS: A convenience sample of participants with professional experience evaluating DDI evidence was recruited. Participants independently evaluated pre-selected evidence items for 5 drug pairs using the new instrument. For each drug pair, participants labeled each evidence item as sufficient or insufficient to establish the existence of a DDI based on the evidence categories provided by the instrument. Participants also decided if the overall body of evidence supported a DDI involving the drug pair. Agreement was computed both at the evidence item and drug pair levels. A cut-off of ≥ 70% was chosen as the agreement threshold for percent agreement, while a coefficient > 0.6 was used as the cut-off for chance-corrected agreement. Open ended comments were collected and coded to identify themes related to the participants' experience using the novel approach. RESULTS: The face validity of the new instrument was established by two rounds of evaluation involving a total of 6 experts. Fifteen experts agreed to participate in the reliability assessment, and 14 completed the study. Participant agreement on the sufficiency of 22 of the 34 evidence items (65%) did not exceed the a priori agreement threshold. Similarly, agreement on the sufficiency of evidence for 3 of the 5 drug pairs (60%) was poor. Chance-corrected agreement at the drug pair level further confirmed the poor interrater reliability of the instrument (Gwet's AC1 = 0.24, Conger's Kappa = 0.24). Participant comments suggested several possible reasons for the disagreements including unaddressed subjectivity in assessing an evidence item's type and study design, an infeasible separation of evidence evaluation from the consideration of clinical relevance, and potential issues related to the evaluation of DDI case reports. CONCLUSIONS: Even though the key findings were negative, the study's results shed light on how experts approach DDI evidence assessment, including the importance situating evidence assessment within the context of consideration of clinical relevance. Analysis of participant comments within the context of the negative findings identified several promising future research directions including: novel computer-based support for evidence assessment; formal evaluation of a more comprehensive evidence assessment approach that requires consideration of specific, explicitly stated, clinical consequences; and more formal investigation of DDI case report assessment instruments.

Gaucher Disease Involving Virchow's Lymph Node: a Case Report.

Gaucher disease is a metabolic storage disorder caused by a mutation in the lysosomal enzyme B-glucocerebrosidase. This disease is usually manifested in new born infants, however, an exceptional case of this disease in adult has been recently reported. A 21-year-old Caucasian patient was diagnosed with Gaucher disease, demonstrating Virchow's lymphatic node enlargement and mild splenomegaly. A familial link to this disease was also found. Macrophage infiltration was observed in the aff ected Virchow's lymph node which is not a classic sign of Gaucher disease. DNA analysis and a whole blood count also suggested a manifestation of this disease. In summary, this is the first study to report such case of Gaucher disease in an adult female patient, which may suggest an asymptomatic characteristic of this condition and an importance of the presence of Gaucher cells in the enlarged Virchow's lymph node.

Transport properties of the rough hard sphere fluid.

Results are presented of a systematic study of the transport properties of the rough hard sphere fluid. The rough hard sphere fluid is a simple model consisting of spherical particles that exchange linear and angular momenta, and energy upon collision. This allows a study of the sole effect of particle rotation upon fluid properties. Molecular dynamics simulations have been used to conduct extensive benchmark calculations of self-diffusion, shear and bulk viscosity, and thermal conductivity coefficients. As well, the validity of several kinetic theory equations have been examined at various levels of approximation as a function of density and translational-rotational coupling. In particular, expressions from Enskog theory using different numbers of basis sets in the representation of the distribution function were tested. Generally Enskog theory performs well at low density but deviates at larger densities, as expected. The dependence of these expressions upon translational-rotational coupling was also examined. Interestingly, even at low densities, the agreement with simulation results was sometimes not even qualitatively correct. Compared with smooth hard sphere behaviour, the transport coefficients can change significantly due to translational-rotational coupling and this effect becomes stronger the greater the coupling. Overall, the rough hard sphere fluid provides an excellent model for understanding the effects of translational-rotational coupling upon transport coefficients.

The effect of rotational and translational energy exchange on tracer diffusion in rough hard sphere fluids.

A study is presented of tracer diffusion in a rough hard sphere fluid. Unlike smooth hard spheres, collisions between rough hard spheres can exchange rotational and translational energy and momentum. It is expected that as tracer particles become larger, their diffusion constants will tend toward the Stokes-Einstein hydrodynamic result. It has already been shown that in this limit, smooth hard spheres adopt "slip" boundary conditions. The current results show that rough hard spheres adopt boundary conditions proportional to the degree of translational-rotational energy exchange. Spheres for which this exchange is the largest adopt "stick" boundary conditions while those with more intermediate exchange adopt values between the "slip" and "stick" limits. This dependence is found to be almost linear. As well, changes in the diffusion constants as a function of this exchange are examined and it is found that the dependence is stronger than that suggested by the low-density, Boltzmann result. Compared with smooth hard spheres, real molecules undergo inelastic collisions and have attractive wells. Rough hard spheres model the effect of inelasticity and show that even without the presence of attractive forces, the boundary conditions for large particles can deviate from "slip" and approach "stick."

Molecular epidemiology of HIV Type 1 in Ukraine: birthplace of an epidemic.

During the 1990s, HIV-1 spread rapidly through drug networks in Ukraine and from there throughout the former Soviet Union. To examine the origins of this epidemic, the genetics of HIV-1 in Ukraine were studied. Proviral DNA from PBMC was extracted and PCR amplified. Part of pol and nearly full genomes of HIV-1 were sequenced and characterized. The predominant genetic form in 163 strains was subtype A (66%), followed by subtypes B (30%), C (2%), D (1%), and a new AB recombinant form (1%). HIV strains from Kiev were diverse having subtypes A, B, C, and D. In Crimea, Donetsk, Poltava, and Odessa, however, the strains were overwhelmingly subtype A, while in Nikolaev subtype B predominated. After the near simultaneous introduction of subtypes A and B in Ukraine, subtype B remained where it was introduced while subtype A spread widely, creating the fastest growing epidemic in the world.

Simultaneous introduction of HIV type 1 subtype A and B viruses into injecting drug users in southern Ukraine at the beginning of the epidemic in the former Soviet Union.

The vast majority of HIV-1 strains from the epidemic in the former Soviet Union (FSU) belong to subtype A (IDU-A) and CRF03_AB (IDU-A/B), for which IDU-A is one of parental strains; no epidemic by another parental virus, belonging to subtype B (IDU-B), has yet been identified. To characterize viruses present during the early stage of the epidemic in southern Ukraine, where the first outbreaks in the FSU were registered, we obtained partial env and pol sequences from IDUs from Odessa and Nikolaev and compared them with viruses from other outbreaks. All viruses from Odessa belonged to the IDU-A type, which is in accord with previous studies. At the same time, we found that the outbreak in Nikolaev was caused by IDU-B viruses, indicating that this outbreak is the result of an independent virus introduction. Phylogenetic analysis of viruses from the FSU supported the epidemiological data suggesting that the HIV-1 epidemic in the FSU started in southern Ukraine.