Low-dose Oral Thimerosal for the Treatment of Oral Herpes: Clinical Trial Results and Improved Outcome After Post-hoc Analysis.

BACKGROUND: Thimerosal (TML) is an organomercury antimicrobial. Low doses (1/250th of the amount in a typical vaccine dose) may promote an antiviral immune response. Low-dose TML (BTL-TML) was evaluated for safety and efficacy against herpes labialis in two FDA-approved, randomized, double blind, placebo-controlled clinical trials. METHODS: BTL-TML was evaluated in a Phase IIa trial for its ability to block progression to lesion in subjects with recurrent oral herpes caused by dental trauma. Subjects were administered BTL-TML or a saline control over a 7-day period. In a Phase IIb trial, BTL-TML was evaluated for its ability to block progression to lesion over a 7-day period in subjects with herpes lip infections induced by exposure to ultraviolet (UV) radiation. RESULTS: Progression to lesion post-dental procedure was prevented in 54.5% (12/22) TML subjects versus 22.2% (2/9) control subjects (p = 0.106). Progression to lesion post-UV irradiation was blocked in 47.8% (11/23) BTL-TML treatment subjects and 42.8% (6/14) control subjects. A post-hoc analysis yielded 52.2% (12/23) BTL-TML subjects with no progression to lesion versus 28.6% (6/21) control subjects with no progression (p = 0.099). There were no significant differences in adverse effects between treatment and control groups in either trial. CONCLUSIONS: Neither clinical trial showed a statistically significant effect of BTL-TML on progression to lesion. However, the post-hoc analysis suggested there is a 48-hour period following UV radiation exposure during which the anti-herpes activity of antivirals such as BTL-TML is reduced. Accordingly, BTL-TML may have promise in subsequent, properly designed and powered clinical trials.

Pharmacy students' readiness to use the electronic health record: A tale of two institutions.

INTRODUCTION: Despite widespread implementation of the electronic health record (EHR) in practice, the EHR curriculum in pharmacy schools is slow to emerge. This study used a single assessment tool to evaluate pharmacy students' perceived readiness to use an EHR after completion of two different curricula. METHODS: Pharmacy students at the University of Nebraska Medical Center (UNMC) and the University of California San Diego (UCSD) pharmacy schools voluntarily participated. A 14-item survey was administered asking students to rate their comfort on several different EHR skills. Baseline data on non-academic EHR exposure was also collected. RESULTS: Seventy students at UNMC and 69 students at UCSD participated in the survey (27.2% and 28.5% response rate, respectively). Gender and academic year were similar between institutions. Overall, students were more comfortable finding information compared to entering new information in the EHR. Students were most comfortable reviewing laboratory information, progress notes, and medication lists and less comfortable performing medication reconciliation and identifying clinical errors. There were no differences between institutions for overall comfort. Students with at least one month of extracurricular EHR experience rated themselves as more comfortable, but not all of those differences were statistically significant. CONCLUSIONS: This study demonstrated that two different EHR curricula in two different pharmacy schools can result in similar student confidence. The information and assessment tool from this study can be a helpful starting point for other schools to determine student preparedness to work with the EHR as well as provide information to inform EHR curricula design and assessment.

Self-Perceptions of Readiness to Use Electronic Health Records Among Medical Students: Survey Study.

BACKGROUND: Although several national organizations have declared the ability to work with electronic health records (EHRs) as a core competency of medical education, EHR education and use among medical students vary widely. Previous studies have reported EHR tasks performed by medical students, but students' self-perceived readiness and comfort with EHRs are relatively unknown. OBJECTIVE: This study aimed to better understand medical students' self-perceived readiness to use EHRs to identify potential curricular gaps and inform future training efforts based on students' perspectives. METHODS: The authors deployed a survey investigating self-perceived comfort with EHRs at 2 institutions in the United States in May 2019. Descriptive statistics were generated regarding demographics, comfort level with various EHR-related tasks, and cross-institutional comparisons. We also assessed the impact of extracurricular EHR experience on comfort level. RESULTS: In total, 147 medical students responded, of which 80 (54.4%) were female, with equal distribution across all 4 years of training. Overall confidence was generally higher for students with longer extracurricular EHR experience, even when adjusted for age, gender, year of training, and institution. Students were most comfortable with tasks related to looking up information in the EHR and felt less comfortable with tasks related to entering new information and managing medications. Fourth-year students at both schools reported similar levels of comfort with EHR use, despite differences in preclinical EHR training. Open-ended comments emphasized the value of experiential training over didactic formats. CONCLUSIONS: Information entry and medication management in the EHR represent areas for future curricular development. Experiential training via extracurricular activities and early clinical exposure may be high-yield approaches to help medical students achieve critical EHR competencies.

The safety and efficacy of transurethral microwave therapy in high-risk catheter-dependent men.

OBJECTIVE: Previous studies have demonstrated the efficacy of transurethral microwave therapy (TUMT) in the management of high-risk catheter-dependent men, although few have assessed safety in high-risk patients, including those continuing anticoagulation therapy during treatment. Our goal was to assess the safety and effectiveness of TUMT in a population of high-risk catheter-dependent men. MATERIAL AND METHODS: A retrospective analysis of patients who underwent TUMT at a single Veterans Affairs facility for the treatment of benign prostatic hyperplasia was completed. The primary outcome was 30-day postprocedural complications by Clavien-Dindo grade, including bleeding events. The secondary outcome was success in catheter removal. RESULTS: We performed TUMT in 157 men, 105 of whom had urinary retention-requiring an indwelling urethral catheter or clean intermittent catheterization. Overall, 86% of patients underwent TUMT while on anticoagulant therapy and 25% were treated while taking warfarin. The median age of the patients was 76.9 years (95% CI 74.9-78.8) median ASA-score was 3, and median follow-up was 26 months (range 1-65). Only two men experienced hematuria requiring treatment postoperatively and no transfusions were required. Only two patients (1.9%) required readmission within 30 days after treatment. There were 24 (22.9%) Clavien-Dindo grade I-II complications without grade III or higher complications. Urinary retention resolved in 63.7% of men after treatment. CONCLUSION: Our results suggest that TUMT is a safe and reasonably effective treatment for high-risk catheter-dependent men. Furthermore, the low incidence of adverse bleeding events suggests that TUMT is a safe treatment modality for men requiring uninterrupted anticoagulation.

The use of streptolysin O (SLO) as an adjunct therapy for Rhodococcus equi pneumonia in foals.

Rhodococcus equi is a soil borne bacterium that causes severe morbidity and death in young foals. The economic costs of the disease include loss of life, treatment expenses, veterinary monitoring expenses and, perhaps most importantly, potential reduction in future athletic performance in horses that suffer severe lung abscessations caused by R. equi. Current standard of care for pneumonia caused by R. equi is treatment with a macrolide antimicrobial and rifampicin. However, the hallmark of pneumonia caused by R. equi is severe formation of pyogranulomas and a walling off effect that can prevent systemic antibiotics from reaching antimicrobial concentrations in lung tissues. It is hypothesized that streptolysin O (SLO) used as an adjunct therapy with antibiotics will reduce the duration and severity of disease caused by R. equi pneumonia compared to antibiotic therapy alone. Addition of SLO to the antibiotic enhanced clinical responses compared to the other groups, including the antibiotic alone group. Of particular significance were lower bacterial counts in the lungs and longer survival time in those foals treated with SLO and antibiotics.

Chlamydia psittaci genetic variants differ in virulence by modulation of host immunity.

BACKGROUND: Psittacosis is a zoonosis caused by Chlamydia psittaci and is characterized by severe pneumonia and systemic infection. We sought to determine the basis of the 1000-fold difference in lethal dose of 2 C. psittaci 6BC strains in mice. METHODS: Genomes of the strains were sequenced. Mice were infected intraperitoneally and the growth kinetics, immune responses, and pathology were compared. RESULTS: The 2 strains differed by the presence of a 7.5-kb plasmid in the attenuated strain and 7 nonsynonomous single-nucleotide polymorphisms between the chromosomes, including a serine/threonine protein kinase gene pkn5. The plasmid was cured from the attenuated strain, but it remained nonlethal. Strains did not differ in growth kinetics in vitro or in vivo. Infection with the attenuated strain led to influx of activated macrophages with relatively minor organ damage. In contrast, the virulent strain caused an influx of nonactivated macrophages, neutrophils, and significant end organ damage. Mice infected with the virulent strain survived challenge when coinfected with either the plasmid-positive or plasmid-negative attenuated strain, indicating that an active process elicited by the attenuated strain reduces inflammation and disease. CONCLUSIONS: C. psittaci modulates virulence by alteration of host immunity, which is conferred by small differences in the chromosome.

Genome sequences of the zoonotic pathogens Chlamydia psittaci 6BC and Cal10.

Chlamydia psittaci is a highly prevalent avian pathogen and the cause of a potentially lethal zoonosis, causing life-threatening pneumonia in humans. We report the genome sequences of C. psittaci 6BC, the prototype strain of the species, and C. psittaci Cal10, a widely used laboratory strain.

Binding and activation of host plasminogen on the surface of Francisella tularensis.

BACKGROUND: Francisella tularensis (FT) is a gram-negative facultative intracellular coccobacillus and is the causal agent of a life-threatening zoonotic disease known as tularemia. Although FT preferentially infects phagocytic cells of the host, recent evidence suggests that a significant number of bacteria can be found extracellularly in the plasma fraction of the blood during active infection. This observation suggests that the interaction between FT and host plasma components may play an important role in survival and dissemination of the bacterium during the course of infection. Plasminogen (PLG) is a protein zymogen that is found in abundance in the blood of mammalian hosts. A number of both gram-positive and gram-negative bacterial pathogens have the ability to bind to PLG, giving them a survival advantage by increasing their ability to penetrate extracellular matrices and cross tissue barriers. RESULTS: We show that PLG binds to the surface of FT and that surface-bound PLG can be activated to plasmin in the presence of tissue PLG activator in vitro. In addition, using Far-Western blotting assays coupled with proteomic analyses of FT outer membrane preparations, we have identified several putative PLG-binding proteins of FT. CONCLUSIONS: The ability of FT to acquire surface bound PLG that can be activated on its surface may be an important virulence mechanism that results in an increase in initial infectivity, survival, and/or dissemination of this bacterium in vivo.

Global transcriptional upregulation in the absence of increased translation in Chlamydia during IFNgamma-mediated host cell tryptophan starvation.

The developmentally regulated intracellular pathogen Chlamydia pneumoniae is a natural tryptophan auxotroph. These organisms survive tryptophan starvation induced by host cell activation with IFNgamma by blocking maturation to the infectious form. In most bacteria, the stringent response is induced during amino acid starvation to promote survival. However, the response of obligate intracellular pathogens, which are predicted to lack stringent responses to amino acid starvation, is poorly characterized. Chlamydial transcription and translation were analysed during IFNgamma-mediated tryptophan starvation using genomic normalization methods, and the data revealed the novel findings that: (i) global chlamydial transcription was upregulated; and (ii) protein synthesis was dramatically reduced. These results indicate a dysregulation of developmental gene expression and an uncoupling of transcription from translation. These observations represent an alternative survival strategy for host-adapted obligate intracellular bacterial pathogens that have lost the genes for stringent control during reductive evolution.

Selective promoter recognition by chlamydial sigma28 holoenzyme.

The sigma transcription factor confers the promoter recognition specificity of RNA polymerase (RNAP) in eubacteria. Chlamydia trachomatis has three known sigma factors, sigma(66), sigma(54), and sigma(28). We developed two methods to facilitate the characterization of promoter sequences recognized by C. trachomatis sigma(28) (sigma(28)(Ct)). One involved the arabinose-induced expression of plasmid-encoded sigma(28)(Ct) in a strain of Escherichia coli defective in the sigma(28) structural gene, fliA. The second was an analysis of transcription in vitro with a hybrid holoenzyme reconstituted with E. coli RNAP core and recombinant sigma(28)(Ct). These approaches were used to investigate the interactions of sigma(28)(Ct) with the sigma(28)(Ct)-dependent hctB promoter and selected E. coli sigma(28) (sigma(28)(Ec))-dependent promoters, in parallel, compared with the promoter recognition properties of sigma(28)(EC). Our results indicate that RNAP containing sigma(28)(Ct) has at least three characteristics: (i) it is capable of recognizing some but not all sigma(28)(EC)-dependent promoters; (ii) it can distinguish different promoter structures, preferentially activating promoters with upstream AT-rich sequences; and (iii) it possesses a greater flexibility than sigma(28)(EC) in recognizing variants with different spacing lengths separating the -35 and -10 elements of the core promoter.

Health human resources in the United States of America

En el artículo se examinan de manera sintética los recursos humanos de salud en los Estados Unidos de América. Se señala que el tipo de provisión de servicios y de financiamiento ha cambiado y, por esta causa, también la práctica profesional y la utilización de las profesiones. Se indica que el número de personal que ejerce y de graduados en todas las profesiones de salud continuó aumentando en el decenio de 1980, aunque el ritmo fue más lento que en el decenio de 1970; la oferta refleja esa misma curva. En una sociedad tan desarrollada y compleja, que posee la mayor cantidad y variedad de información del mundo, cada factor de la sociedad tiene repercusiones múltiples sobre la oferta y la demanda del sector salud, que el autor menciona. Entre ellas se pueden citar las intervenciones del Gobierno Federal, la influencia del seguro de salud (Medicare), los cambios demográficos, las restricciones a la inmigración de profesionales, la presencia de grupos minoritarios, la participación creciente de la mujer en la fuerza de trabajo, etc