Impact of point-of-care gonorrhea and chlamydia testing in the emergency department on reducing overtreatment rates.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections continue to increase in the United States. Advancement in technology with point-of-care (POC) testing can improve the overall treatment of sexually transmitted infections (STI) in the emergency department (ED) by shortening the time to test result and administration of accurate treatment. The purpose of this study was to assess if the POC test reduced the rate of overtreatment for CT and/or NG compared to the standard-of-care (SOC) test. METHODS: This retrospective cohort study included adult patients tested for CT and NG at two urban EDs between August 2020 and October 2022. This cohort excluded hospital admissions, elopement, pregnancy, rectal and oral samples, victims of sexual assault, and diagnoses for which antimicrobial treatment overlapped that of CT/NG. The primary outcome assessed overtreatment, defined as receiving treatment in the ED or a prescription prior to discharge for patients who tested negative for CT and/or NG. Secondary outcomes included undertreatment rates, overtreatment rates in select populations, test turnaround time, and ED length of stay (LOS). RESULTS: Of 327 patients screened, 97 patients were included in the SOC group and 100 in POC. Overtreatment for CT was provided in zero POC patients and 29 (29.9%) SOC patients (p < 0.001). NG was overtreated in 1 (1%) POC and 23 (23.7%) SOC (p < 0.001). POC was associated with undertreatment of CT and/or NG in two patients, compared to four patients tested with SOC. Overall, treatment was deemed inappropriate for 5 (5%) of those tested with POC, compared to 35 (36%) tested with SOC (p < 0.001). There was no difference in ED LOS (2.7 vs 3.01 h, p = 0.41). CONCLUSIONS: POC testing facilitated the return of results prior to patients being discharged from the ED. Compared to standard testing, POC improved appropriateness of CT and NG treatment by reducing the rates of overtreatment.

Radiographic localization and isometry of the origin and insertion of the canine cranial cruciate ligament.

OBJECTIVE: To radiographically define the anatomic origin and insertion of the cranial cruciate ligament translated to the lateral radiographic projection of the stifle (CrCL-Lo and CrCL-Li, respectively), to correlate these landmarks for identification of the CrCL-Lo intraoperatively, and to compare the isometry of the CrCL-Lo to the lateral fabella. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Pelvic limbs (n = 12) from dogs weighing 13-26 kg. METHODS: A radiographic quadrant method was used to localize the CrCL-Lo. Mediolateral radiographic projections of each stifle were taken through a range of motion. Maximum percent change in length between each tibial marker and femoral marker during range of motion determined isometry. RESULTS: The CrCL-Lo is located at the caudal 33% and distal 50% of the lateral femoral condyle using Blumensaat's line or a line from the origin of the long digital extensor (LDE) to the lateral fabella, with no significant difference (P = .766) between the 2 reference lines. The CrCL-Li is located at the proximal 20% of the tibial plateau. No significant difference (P < .05) in isometry was found between the CrCL-Lo and lateral fabella. CONCLUSION: The CrCL-Lo is located at the caudal 1/3 and distal ½ of the lateral femoral condyle. The CrCL-Lo and lateral fabella are not significantly different in isometry when used as a proximal anchor point in extracapsular stifle stabilization.

Evaluating reduction in medical costs associated with pharmacists' presence in the emergency department using a novel cost avoidance framework.

PURPOSE: The purpose of this study was to evaluate the cost avoidance associated with emergency medicine pharmacist (EMP) presence in the emergency department (ED) using a novel cost avoidance framework. SUMMARY: This single-center, retrospective, observational study examined EMP interventions from November 1, 2021, through March 31, 2022. EMPs prospectively selected up to 10 shifts in which to log interventions during the study period. Interventions were categorized into 25 cost avoidance categories, 10 of which incorporated recently proposed probability variables. All categories were organized into 4 broad cost avoidance domains, including resource utilization, individualization of patient care, adverse drug event prevention, and hands-on care. During the study period, 894 interventions were logged, which accounted for $143,132 in cost avoidance (lower probability value of $124,186, upper probability value of $168,858), with a median cost avoidance per shift of $1,671 (interquartile range, $1,025 to $2,451). On the basis of 240 shifts, the estimated annual total cost avoidance per pharmacist was extrapolated to be $401,040. CONCLUSION: While the mean cost avoidance of $161.10 per intervention observed in our study was less than that in prior cost avoidance studies due to the conservative and potentially more realistic estimates used, implementation of this cost avoidance framework still showed substantial cost avoidance associated with EMP presence in the ED.

Identification of cis-acting elements in the 3'-untranslated region of the dengue virus type 2 RNA that modulate translation and replication.

Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3'-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5'- and 3'-DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3'-DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by ∼60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation.

Piperacillin/Tazobactam versus Tobramycin-Based Antibiotic Prophylaxis for Type III Open Fractures.

Background: Type III open fractures are associated with an infection rate as high as 50%. The optimal antibiotic for open fracture prophylaxis remains unclear, and the literature comparing the safety and efficacy of different antibiotic regimens is limited. The aim of this study was to compare the composite adverse events (AEs) in patients before and after a change in prophylactic antibiotic management for these injuries from a tobramycin- to a piperacillin/tazobactam-based regimen. Methods: This was a retrospective single-center cohort study of patients with Type III open fractures admitted from January 2010 to December 2016. Patients were included if they received either tobramycin plus cefazolin or clindamycin or piperacillin/tazobactam for fracture prophylaxis. The primary outcome was the rate of composite AEs, which included nephrotoxicity, surgical site infection (SSI), and hospital re-admission with surgical intervention. Secondary outcomes included the rate of SSI within 30 and 60 days after injury. Data were analyzed using the Student t-, Mann-Whitney U, and Fisher exact tests. Results: Eighty-five patients were included. There were 29 events in the tobramycin group compared with three in the piperacillin/tazobactam group. At 30 days, SSI had occurred in 17 patients (27.5%) in the tobramycin group and 1 patient (4.3%) in the piperacillin/tazobactam group (p = 0.033). At 60 days, SSI had occurred in three additional patients in the tobramycin group (p = 0.009). Conclusion: There was no difference in the composite AEs in the piperacillin/tazobactam compared with the tobramycin group. However, SSI within 30 and 60 days was significantly more common with tobramycin.

Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity.

Dengue virus serotypes 1-4 (DENV1-4) are transmitted by mosquitoes which cause most frequent arboviral infections in the world resulting in ∼390 million cases with ∼25,000 deaths annually. There is no vaccine or antiviral drug currently available for human use. Compounds containing quinoline scaffold were shown to inhibit flavivirus NS2B-NS3 protease (NS2B-NS3pro) with good potencies. In this study, we screened quinoline derivatives, which are known antimalarial drugs for inhibition of DENV2 and West Nile virus (WNV) replication using the corresponding replicon expressing cell-based assays. Amodiaquine (AQ), one of the 4-aminoquinoline drugs, inhibited DENV2 infectivity measured by plaque assays, with EC50 and EC90 values of 1.08±0.09µM and 2.69±0.47 µM, respectively, and DENV2 RNA replication measured by Renilla luciferase reporter assay, with EC50 value of 7.41±1.09µM in the replicon expressing cells. Cytotoxic concentration (CC50) in BHK-21 cells was 52.09±4.25µM. The replication inhibition was confirmed by plaque assay of the extracellular virions as well as by qRT-PCR of the intracellular and extracellular viral RNA levels. AQ was stable for at least 96h and had minor inhibitory effect on entry, translation, and post-replication stages in the viral life cycle. DENV protease, 5'-methyltransferase, and RNA-dependent RNA polymerase do not seem to be targets of AQ. Both p-hydroxyanilino and diethylaminomethyl moieties are important for AQ to inhibit DENV2 replication and infectivity. Our results support AQ as a promising candidate for anti-flaviviral therapy.

Construction of self-replicating subgenomic West Nile virus replicons for screening antiviral compounds.

Mosquito-borne flavivirus RNA genomes encode one long open reading frame flanking 5'- and 3'-untranslated regions (5'- and 3'-UTRs) which contain cis-acting RNA elements playing important roles for viral RNA translation and replication. The viral RNA encodes a single polyprotein, which is processed into three structural proteins and seven nonstructural (NS) proteins. The regions coding for the seven NS proteins are sufficient for replication of the RNA. The sequences encoding the structural genes can be deleted except for two short regions. The first one encompasses 32 amino acid (aa) residues from the N-terminal coding sequence of capsid (C) and the second, 27 aa region from the C-terminus of envelope (E) protein. The deleted region can be substituted with a gene coding for a readily quantifiable reporter to give rise to a subgenomic reporter replicon. Replicons containing a variety of reporter genes and marker genes for construction of stable mammalian cell lines are valuable reagents for studying the effects of mutations in translation and/or replication in isolation from processes like the entry and assembly of the virus particles. Here we describe the construction of two West Nile virus (WNV) replicons by overlap extension PCR and standard recombinant DNA techniques. One has a Renilla luciferase (Rluc) reporter gene followed by an internal ribosome entry site (element) for cap-independent translation of the open reading frame encompassing the carboxy-terminal sequence of E to NS5. The second replicon has in tandem the Rluc gene, foot and mouth disease virus 2A, and neomycin phosphotransferase gene that allows establishment of a stable mammalian cell line expressing the Rluc reporter in the presence of the neomycin analog, G418. The stable replicon-expressing Vero cell line has been used for cell-based screening and determination of EC50 values for antiviral compounds that inhibited WNV replication.

Effect of barcode-assisted medication administration on emergency department medication errors.

OBJECTIVES: Barcode-assisted medication administration (BCMA) is technology with demonstrated benefit in reducing medication administration errors in hospitalized patients; however, it is not routinely used in emergency departments (EDs). EDs may benefit from BCMA, because ED medication administration is complex and error-prone. METHODS: A naïve observational study was conducted at an academic medical center implementing BCMA in the ED. The rate of medication administration errors was measured before and after implementing an integrated electronic medical record (EMR) with BCMA capacity. Errors were classified as wrong drug, wrong dose, wrong route of administration, or a medication administration with no physician order. The error type, severity of error, and medications associated with errors were also quantified. RESULTS: A total of 1,978 medication administrations were observed (996 pre-BCMA and 982 post-BCMA). The baseline medication administration error rate was 6.3%, with wrong dose errors representing 66.7% of observed errors. BCMA was associated with a reduction in the medication administration error rate to 1.2%, a relative rate reduction of 80.7% (p < 0.0001). Wrong dose errors decreased by 90.4% (p < 0.0001), and medication administrations with no physician order decreased by 72.4% (p = 0.057). Most errors discovered were of minor severity. Antihistamine medications were associated with the highest error rate. CONCLUSIONS: Implementing BCMA in the ED was associated with significant reductions in the medication administration error rate and specifically wrong dose errors. The results of this study suggest a benefit of BCMA on reducing medication administration errors in the ED.

Alphavirus antiviral drug development: scientific gap analysis and prospective research areas.

The New World alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) pose a significant threat to human health as the etiological agents of serious viral encephalitis through natural infection as well as through their potential use as a biological weapon. At present, there is no FDA-approved medical treatment for infection with these viruses. The Defense Threat Reduction Agency, Joint Science and Technology Office for Chemical and Biological Defense (DTRA/JSTO), is currently funding research aimed at developing antiviral drugs and vaccines against VEEV, EEEV, and WEEV. A review of antiviral drug discovery efforts for these viruses revealed significant gaps in the data, assays, and models required for successful drug development. This review provides a description of these gaps and highlights specific critical research areas for the development of a target-based drug discovery program for the VEEV, EEEV, and WEEV nonstructural proteins. These efforts will increase the probability of the successful development of a pharmaceutical intervention against these viral threat agents.

Spore cortex formation in Bacillus subtilis is regulated by accumulation of peptidoglycan precursors under the control of sigma K.

The bacterial endospore cortex peptidoglycan is synthesized between the double membranes of the developing forespore and is required for attainment of spore dehydration and dormancy. The Bacillus subtilis spoVB, spoVD and spoVE gene products are expressed in the mother cell compartment early during sporulation and play roles in cortex synthesis. Here we show that mutations in these genes block synthesis of cortex peptidoglycan and cause accumulation of peptidoglycan precursors, indicating a defect at the earliest steps of peptidoglycan polymerization. Loss of spoIV gene products involved in activation of later, sigma(K)-dependent mother cell gene expression results in decreased synthesis of cortex peptidoglycan, even in the presence of the SpoV proteins that were synthesized earlier, apparently due to decreased precursor production. Data show that activation of sigma(K) is required for increased synthesis of the soluble peptidoglycan precursors, and Western blot analyses show that increases in the precursor synthesis enzymes MurAA, MurB, MurC and MurF are dependent on sigma(K) activation. Overall, our results indicate that a decrease in peptidoglycan precursor synthesis during early sporulation, followed by renewed precursor synthesis upon sigma(K) activation, serves as a regulatory mechanism for the timing of spore cortex synthesis.