The effect of single-dose tramadol on oxycodone clearance.

We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance

Ahmed vs Baerveldt Glaucoma Drainage Device in Uveitic Glaucoma

Introduction: Uveitis is an inflammatory eye disorder which may elevate intraocular pressure (IOP), causing sight-threatening glaucoma. Treatment of refractory uveitic glaucoma involves implantation of a glaucoma drainage device (GDD). Uveitic glaucoma has been a minority diagnosis in prior studies comparing the valved Ahmed GDD and non-valved Baerveldt GDD. Here we compare the safety and efficacy of the Ahmed and Baerveldt GDD in uveitic glaucoma. Methods: This retrospective comparative study was conducted on patients with uveitic glaucoma (≥14 years old) who underwent Ahmed or Baerveldt GDD implantation between 2006–2018 with a minimum follow-up of 3 months. Success was defined as IOP of 6-21 mmHg with (complete success) or without (qualified success) medications, with at least light perception vision and no further glaucoma surgery. Pearson Chi-squared test, independent t test, and Kaplan-Meier survival model were utilized for statistical analysis. Results: 137 eyes of 122 patients (67 Ahmed and 70 Baerveldt) were included. Baseline characteristics were comparable in both groups. The Baerveldt group experienced greater IOP reduction (60.3% vs. 44.5%), higher complete success rate (28.6% vs. 10.4%), higher complication rate (44.3% vs. 20.9%), and higher hypotony rate (10% vs. 0%) than the Ahmed group (all p values \u3c0.05). Discussion: Our results are in line with pooled analysis of previous GDD comparison studies on various types of glaucoma. For patients with uveitic glaucoma, the Baerveldt implant provided a significantly higher success rate and greater IOP reduction with fewer medications, but was associated with a higher complication rate, compared to the Ahmed implant

African Bush Viper Envenomation: A Case Report

Atheris squamigera envenomation is an infrequently documented occurrence in the United States (US). Cases of envenomation may induce severe coagulopathies, renal failure, and potentially life-threatening hemorrhage. Currently, there are no antivenoms specific to the Atheris genus, but there have been documented cases of the use of antivenoms for other species. A 26-year-old man presented to the emergency department (ED) complaining of swelling and discomfort in his left foot after being bitten by an Atheris squamigera that he kept as a pet.After performing a physical exam, it was noted that the patient’s envenomation was likely mild. Throughout his hospital stay, he developed lab abnormalities, most notably an elevated D-dimer and low fibrinogen. His clinical symptoms improved after a short stay, and he did not require antivenom treatment. This case highlights a rare, but potentially life-threatening envenomation that may be encountered in the US due to the continued practice of exotic pet ownership and sales. Moreover, procurement of antivenom for non-native species poses a unique challenge to US physicians responsible for treating these patients

Influence of Pennsylvania liquor store closures during the COVID-19 pandemic on alcohol withdrawal consultations.

INTRODUCTION: Alcohol withdrawal syndrome (AWS) is a serious consequence of alcohol use disorder (AUD). Due to the current COVID-19 pandemic there was a closure of Pennsylvania (PA) liquor stores on March 17, 2020. METHODS: This is a retrospective, observational study of AWS patients presenting to a tertiary care hospital. We used descriptive statistics for continuous and categorical variables and compared AWS consults placed to the medical toxicology service for six months preceding liquor store closure to those placed between March 17, 2020 and August 31, 2020. We compared this to consults placed to the medical toxicology service placed from October 1, 2019 through March 16, 2020. Charts were identified based on consults placed to the medical toxicology service, and alcohol withdrawal was determined via chart review by a medical toxicologist. This study did not require IRB approval. We evaluated Emergency Department (ED) length of stay (LOS), weekly and monthly consultation rate, rate of admission and ED recidivism, both pre- and post-liquor store closure. RESULTS: A total of 324 AWS consults were placed during the ten month period. 142 (43.8%) and 182 (56.2%) consults were pre- and post-liquor store closure. The number of consults was not statistically significant comparing these two time frames. There was no significant difference by patient age, gender, or race or by weekly or monthly consultation rate when comparing pre- and post-liquor store periods. The median ED LOS was 7 h (95% Confidence Interval (CI) Larson et al. (2012), Pollard et al. (2020) [5, 11]) and did not significantly differ between pre- and post-liquor store periods (p = 0.78). 92.9% of AWS patients required admission without significant difference between the pre- and post-liquor store closure periods (94.4% vs. 91.8%, p = 0.36). There was a significant increase in the number of AWS patients requiring a return ED visit (Odds Ratio 2.49; 95% CI [1.38, 4.49]) post closure. CONCLUSION: There were nearly 2.5 times greater odds of ED recidivism among post-liquor store closure AWS patients compared with pre-closure AWS patients

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Optically levitated nanoparticle as a model system for stochastic bistable dynamics

Nano-mechanical resonators have gained an increasing importance in nanotechnology owing to their contributions to both fundamental and applied science. Yet, their small dimensions and mass raises some challenges as their dynamics gets dominated by nonlinearities that degrade their performance, for instance in sensing applications. Here, we report on the precise control of the nonlinear and stochastic bistable dynamics of a levitated nanoparticle in high vacuum. We demonstrate how it can lead to efficient signal amplification schemes, including stochastic resonance. This work contributes to showing the use of levitated nanoparticles as a model system for stochastic bistable dynamics, with applications to a wide variety of fields.inancial support from the ERC- QnanoMECA (Grant No. 64790), the Spanish Ministry of Economy and Competitiveness, under grant FIS2016-80293-R and through the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (SEV-2015-0522), Fundació Privada CELLEX and from the CERCA Programme/Generalitat de Catalunya. J.G. has been supported by H2020-MSCA-IF-2014 under REA grant Agreement No. 655369. L.R. acknowledges support from an ETH Marie Curie Cofund Fellowship

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases

Background: The secondary structure and complexity of mRNA influences its accessibility to regulatory molecules (proteins, micro-RNAs), its stability and its level of expression. The mobile elements of the RNA sequence, the wobble bases, are expected to regulate the formation of structures encompassing coding sequences. Results: The sequence/folding energy (FE) relationship was studied by statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found that the FE (dG) associated with coding sequences is significant and negative (407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able to form structures. However, the FE has only a small free component, less than 10% of the total. The contribution of the 1st and 3rd codon bases to the FE is larger than the contribution of the 2nd (central) bases. It is possible to achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous codons. The sequence/FE relationship can be described with a simple algorithm, and the total FE can be predicted solely from the sequence composition of the nucleic acid. The contributions of different synonymous codons to the FE are additive and one codon cannot replace another. The accumulated contributions of synonymous codons of an amino acid to the total folding energy of an mRNA is strongly correlated to the relative amount of that amino acid in the translated protein. Conclusion: Synonymous codons are not interchangable with regard to their role in determining the mRNA FE and the relative amounts of amino acids in the translated protein, even if they are indistinguishable in respect of amino acid coding.Comment: 14 pages including 6 figures and 1 tabl