Minimal effect of scanning parameters on ultrasound shear wave elastography variability in tendons.

PURPOSE: Ultrasound shear wave elastography has potential use in assessing tendon tissue; however, reducing measurement variability remains challenging. The primary purpose of this study was to identify the amount of variability accounted for by ultrasound parameter (frequency, harmonics and CrossXBeam) settings on shear wave speed at two testing sites. METHODS: Shear wave elastography images of the Achilles tendon were obtained from individuals with healthy tendons (n = 28) at two testing sites with standardised image acquisition/postprocessing protocols. Images were acquired at a range of frequencies (7-15 MHz) with CrossXBeam (a filtering technique) and harmonics settings toggled on and off. Variance decomposition analysis was performed to identify the amount of variability in shear wave speed accounted for by scan acquisition settings and testing sites. RESULTS: Shear wave speed variance was primarily attributed to participants (56.87% of variance; residual error: 35%). All scanning parameters, testing site and interaction terms each accounted for less than 2.5% of the variance. A statistically significant, negative relationship was observed between shear wave speed and image quality (p = 0.001) suggesting poor image quality yields higher shear wave speed estimates. CONCLUSION: The findings of this study suggest that natural variation in Achilles tendon mechanics between individuals without tendon pathology accounts for most of the shear wave speed variability. Optimising image quality, which may be observed in higher frequencies, should be considered to improve shear wave speed estimation. Clinically, this study highlights the need to take multiple images, maintain consistent ultrasound settings when tracking patient progress over time and use caution when comparing raw values from tendon scans performed in different clinics with shear wave elastography. LEVEL OF EVIDENCE: Level III.

Implementation of pharmacist targeted discharge prescription review in an emergency department.

BACKGROUND/PURPOSE: Little data has been published regarding emergency medicine pharmacist (EMP) review of discharge prescriptions. An internal retrospective review of a limited sample size of emergency department (ED) discharge prescriptions demonstrated a 13.6% potential intervention rate by EMPs. With this information, it was postulated that EMPs could provide a valuable service via a process of targeted review of ED discharge prescriptions that would yield intervention rates higher than the internal audit. The aim of this project was therefore to develop a real-time notification system within the electronic health record (EHR) for targeted discharge prescription review, to establish an associated EMP workflow, and to evaluate the intervention rate achieved through targeted discharge prescription review. METHODS: This was a single-center, retrospective review of the implementation of a new pharmacist-driven clinical service over a 12 week period from February 19th, 2018 to May 14th, 2018. Criteria for prescription review were determined after an internal audit by the EMPs and included an assessment of established high-alert medications. Discharge prescriptions that met the inclusion criteria were filtered into a real-time work queue in the EHR for EMP review. When necessary, EMPs discussed recommendations with prescribers, or adjusted prescriptions according to institutional pharmacist privileges. Interventions were reviewed and categorized to assess rate of intervention and the types of medication-related problems (MRPs) identified. RESULTS: EMPs reviewed 378 discharge prescriptions and a total of 158 prescriptions were identified as having at least one MRP. Of these, 70 prescriptions were intervened upon thereby resulting in an 18.5% intervention rate. The most common interventions included a change in the dose/frequency, duration/refills of the medication, and patient education. The highest number of interventions were made for anticoagulant and antiinfective agents. CONCLUSION: Utilization of a real-time notification system for prospective ED discharge prescription review is feasible. Using targeted criteria for review, pharmacists intervened on 18.5% of prescriptions reviewed. Prospective discharge prescription review by EMPs using a real-time notification system within the electronic health record identified opportunities for the pharmacist to ensure safe and optimal prescribing.

Cycloaddition Strategies for the Synthesis of Diverse Heterocyclic Spirocycles for Fragment-Based Drug Discovery.

In recent years the pharmaceutical industry has benefited from the advances made in fragment-based drug discovery (FBDD) with more than 30 fragment-derived drugs currently marketed or progressing through clinical trials. The success of fragment-based drug discovery is entirely dependent upon the composition of the fragment screening libraries used. Heterocycles are prevalent within marketed drugs due to the role they play in providing binding interactions; consequently, heterocyclic fragments are important components of FBDD libraries. Current screening libraries are dominated by flat, sp2-rich compounds, primarily owing to their synthetic tractability, despite the superior physicochemical properties displayed by more three-dimensional scaffolds. Herein, we report step-efficient routes to a number of biologically relevant, fragment-like heterocyclic spirocycles. The use of both electron-deficient and electron-rich 2-atom donors was explored in complexity-generating [3+2]-cycloadditions to furnish products in 3 steps from commercially available starting materials. The resulting compounds were primed for further fragment elaboration through the inclusion of synthetic handles from the outset of the syntheses.

Novel non-ATP competitive small molecules targeting the CK2 α/ß interface.

Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2α and CK2ß at the α-ß interface of the holoenzyme. A fragment, CAM187, with an IC50 of 44 µM and a molecular weight of only 257 gmol-1 has been identified as the most promising compound. Importantly, the lead fragment only bound at the interface and was not observed in the ATP binding site of the protein when co-crystallised with CK2α. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.

A Case of Metronidazole Injection Infiltration Without Sequelae.

Purpose: This report describes a case of metronidazole injection infiltration which contrasts the sole other case report in the literature at this time, as the patient described herein experienced mild signs and symptoms with prompt resolution and no significant sequelae. Summary: The patient experienced metronidazole injection infiltration during administration open to gravity via an 18-gauge peripheral catheter in the left brachial vein. The site was examined at bedside within approximately 30 minutes of the incident and was noted to be slightly edematous, erythemic, and painful in terms of a 5.5 × 6.6-cm area. No blanching, blister formation, induration, skin discoloration, or diminished capillary refill were observed. The event was conservatively managed in the form of catheter discontinuation and marking of the affected area with a patient skin marker, as hyaluronidase was not administered due to a product osmolarity of ~314 mOsM/L and pH of 5.8. A bedside evaluation the next morning revealed full resolution of the previously described symptoms. The patient was discharged from the facility 11 days later without further complications from the infiltration event. Conclusion: We describe a case of metronidazole injection infiltration which did not require pharmacologic or nonpharmacologic interventions and resulted in complete resolution. This case supplements the current literature by contrasting the sole other case report which resulted in profound necrosis near the intravenous access site. This case suggests metronidazole infiltrations may not require clinician alarm or treatment if events occur under circumstances similar to that which is presented.

Spirocycles as Rigidified sp3-Rich Scaffolds for a Fragment Collection.

Novel divergent methodology to access sp3-rich spirocyclic fragments is reported. First, a robust modular synthesis of bis-alkene amino ester building blocks was developed. Three different carbocycles and six heterocycles were then constructed to assemble eight spirocycles. Importantly, strategic exit vectors were incorporated within each scaffold to aid fragment growth and were elaborated via chemical modifications. Finally, computational methods demonstrate higher levels of rigidity, three-dimensionality, and structural diversity of the library compared to a commercial collection.

The development and performance of a perforated plate burner to produce vitiated flow with negligible swirl under engine-relevant gas turbine conditions.

The development and performance of a perforated plate burner (PPB) operating using premixed natural gas and air at engine-relevant inlet temperatures and combustor pressures with thermal powers up to 1 MW is discussed. A significant benefit of using burners with simplified flow fields, such as the PPB, for experimental studies in the laboratory is the potential for decoupling the complex fluid dynamics in typical combustors from the chemical kinetics. The primary motivation for developing this burner was to use it as a source of vitiated flow with negligible swirl for reacting jet in vitiated crossflow experiments. The design methodology for the PPB is described, including plate geometry selection and flashback mitigation features. The stable operation of the PPB within a high-pressure test rig was validated: successful ignition, effective use of red-lines for flashback mitigation, and long duration steady-state operation in both piloted and nonpiloted modes were all observed. Exhaust gas emissions measured using a Fourier-transform infrared (FTIR) spectrometer showed very good performance of the PPB in terms of the combustion efficiency (based on measured CO and UHC), and a stability diagram of the PPB was developed as a function of the equivalence ratio and the PPB hole velocity. FTIR measurements also showed very low levels of NOX in nonpiloted operation that were generally within 3 ppm (reported dry and referenced to 15% O2). The capability for steady-state operation, high combustion efficiency, and low levels of NOX makes this PPB an excellent burner candidate for combustion experiments in the laboratory.

Assessing pharmacy students' ability to accurately measure blood pressure using a blood pressure simulator arm.

OBJECTIVE: To compare student accuracy in measuring normal and high blood pressures using a simulator arm. METHODS: In this prospective, single-blind, study involving third-year pharmacy students, simulator arms were programmed with prespecified normal and high blood pressures. Students measured preset normal and high diastolic and systolic blood pressure using a crossover design. RESULTS: One hundred sixteen students completed both blood pressure measurements. There was a significant difference between the accuracy of high systolic blood pressure (HSBP) measurement and normal systolic blood pressure (NSBP) measurement (mean HSBP difference 8.4 ± 10.9 mmHg vs NSBP 3.6 ± 6.4 mmHg; p<0.001). However, there was no difference between the accuracy of high diastolic blood pressure (HDBP) measurement and normal diastolic blood pressure (NDBP) measurement (mean HDBP difference 6.8 ± 9.6 mmHg vs. mean NDBP difference 4.6 ± 4.5 mmHg; p=0.089). CONCLUSIONS: Pharmacy students may need additional instruction and experience with taking high blood pressure measurements to ensure they are able to accurately assess this important vital sign.