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Finbarr Foy,1 Giuseppe Luna,1 Jorge Martinez,1 Zach Nizich,2 Jason Seet,2 Katie Lie,2 Bruce Sunderland,1 Petra Czarniak11School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia; 2Sir Charles Gairdner Hospital, Department of Pharmacy, Nedlands, WA, AustraliaPurpose: To evaluate the stability of meropenem trihydrate in elastomeric infusion devices at a range of selected concentrations (6, 12, 20 and 25 mg/mL) at ambient, refrigeration and freezing temperatures.Methods: Meropenem Ranbaxy® (meropenem trihydrate equivalent to anhydrous meropenem 1 g) vials for injection were reconstituted with 0.9% sodium chloride and adjusted to pH 6.5 using 1 M hydrochloric acid. Following preparation, solutions were stored for 7 days at either 6.7°C in elastomeric infusion devices or at −19°C in glass vials; samples of each concentration were removed from the infusion devices at specific time-points and stored for 24 hrs at 22.5°C. All solutions were assayed at specific time-points using high-performance liquid chromatography. Forced degradation in hydrochloric acid, sodium hydroxide and hydrogen peroxide was carried out at 40°C.Results: The lowest concentration of meropenem (6 mg/mL) displayed the highest stability. It maintained >90% of its initial concentration for up to 144 hrs when stored at 6.7°C and 72 hrs following 24 hrs storage at 22.5°C, having been initially refrigerated for 48 hrs. Meropenem 20 mg/mL required immediate administration following preparation under ambient temperatures, whilst meropenem 25 mg/mL did not remain stable following 24 hrs storage at ambient temperatures. Frozen meropenem solutions displayed good stability in all concentrations but were physically unstable due to the formation of a precipitate.Conclusion: At lower concentrations, meropenem showed suitable stability for storage and administration in elastomeric infusion devices, at refrigerated temperatures. To enhance the stability of lower concentration solutions when exposed to ambient temperatures by ambulatory patients, a more adept method of maintaining lower temperatures that reflect refrigerated conditions for elastomeric infusion devices should be devised.Keywords: meropenem, stability, HPLC, elastomeric infusion device, OPAT

A 49-year-old Chinese woman was referred to our hospital for management of multiple lung nodules, which were incidentally detected on routine chest radiography. Chest computed tomography (CT) confirmed the presence of multiple pulmonary nodules and lung cysts. The lung cysts were located apart from the pulmonary nodules. CT-guided biopsy of the pulmonary nodule specimens confirmed the diagnosis of nodular pulmonary amyloidosis. While cavitation of existing pulmonary amyloid nodules is a well-recognised feature of nodular pulmonary amyloidosis, widespread lung cysts located apart from pulmonary nodules is rare. [ABSTRACT FROM AUTHOR]

Objective This study investigated antibiotic prophylaxis (AP) guideline adherence and the cardiac implantable electronic device (CIED) infection rate in two major Australian public teaching hospitals. Methods In a retrospective observational study, the medical records of patients who underwent CIED procedures between January and December 2017 were reviewed (Hospital A, n = 400 procedures; Hospital B, n = 198 procedures). Adherence to AP guidelines was assessed regarding drug, dose, timing, route and frequency. Infection was identified using follow-up documentation. Results AP was administered in 582 of 598 procedures (97.3%). Full guideline adherence was observed in 33.9% of procedures (203/598) and differed significantly between Hospitals A and B (47.3% vs 7.1%, respectively; P < 0.001). Common reasons for non-adherence were the timing of administration (42.3% vs 60.6% non-adherent in Hospitals A and B, respectively; P < 0.001) and repeat dosing (19.3% vs 78.8% non-adherent in Hospitals A and B, respectively; P < 0.001). Twenty infections were identified over 626.6 patient-years of follow-up (mean (±s.d.) follow-up 1.0 ± 0.3 years). The infection rate was 3.19 per 100 patient-years (P = 0.99 between hospitals). Two devices were removed due to infection; no patients died from CIED infection. Conclusions Although the rate of serious CIED infection was low, there was evidence of highly variable and suboptimal antibiotic use, and potential overuse of AP. What is known about the topic? Previous Australian studies have revealed high rates of inappropriate surgical AP. CIED infections are potentially life threatening, but can be avoided through effective use of AP. However, prolonged durations of AP in this setting may also result in complications, including Clostridioides difficile infection. What does this paper add? This study, the first to our knowledge to focus specifically on adherence to Australian guidelines for AP in CIED procedures, highlighted several common issues between AP in this setting and surgical and procedural AP more broadly. 'Early' and 'late' dose administration and extended post-procedural AP were common. Only 34% of prescriptions fully adhered to the guidelines; practices varied significantly between the two hospitals. What are the implications for practitioners? There is a clear need for institution-specific antimicrobial stewardship strategies to optimise AP in CIED procedures, aligned with the Antimicrobial Stewardship Clinical Care Standard. Patients are being placed at potentially avoidable risk of both complications of extended durations of AP and CIED infection, although the rate of serious CIED infection was low. A standardised approach to surveillance of CIED infections and prospective multisite audits of AP in CIED procedures using a validated tool, such as the Surgical National Antimicrobial Prescribing Survey, are recommended to better inform evidence-based practice. Potential strategies to optimise guideline adherence include prescribing support in patients with immediate penicillin hypersensitivity or methicillin-resistant Staphylococcus aureus colonisation, optimising the in-patient location of drug administration to promote timely dosing, limiting inappropriate post-procedural prophylaxis and routine S. aureus screening and decolonisation.

We describe the case of an 89-year old Caucasian woman admitted with confusion and severe clinical manifestations of acute hypercalcaemia. There was no history suggestive of any malignancy and initial management included correction of the hypercalcaemia with intravenous fluid therapy. Sestamibi parathyroid scintigraphy and neck ultrasonography demonstrated a 4cm left-sided thyroid lesion and a nearly 2cm right-sided thyroid lesion. The patient underwent a total thyroidectomy and parathyroidectomy. Histology confirmed a concomitant parathyroid adenoma, parathyroid carcinoma and follicular thyroid carcinoma. To our knowledge, this is the first reported case in the literature.

Starch nanoparticles (SNPs) were hydrophobically modified by using 1-pyrenebutyric acid (PyBA) with degrees of substitution (DS) between 0.0006 and 0.11. Fluorescence quenching studies were conducted on the pyrene-labeled starch nanoparticles (Py-SNPs) in dimethyl sulfoxide (DMSO) and water with nitromethane (NM), 4-mononitrotoluene (MNT), 2,6-dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT) to assess the mode of quenching of the pyrene labels in the two solvents. In DMSO where pyrene, starch, and the quenchers were soluble, a decrease in fluorescence signal was the result of dynamic encounters between the excited pyrene labels and the nitrated quenchers. In water where starch could be dispersed but pyrene and the nitroaromatic compounds (NACs) were sparingly soluble, quenching took place through the binding of NACs to pyrene aggregates. Py(11)-SNPs (Py-SNPs with a DS of 0.11)-coated filter papers (Py-CFPs) were prepared as fluorescence sensors. The fluorescence emitted by Py-CFPs was quenched to 25% of its original value within 10 ± 2, 72 ± 20, and 23 ± 4 s upon exposure to vapors of MNT, DNT, and TNT, respectively. When known amounts of NACs were deposited onto Py-CFPs, their limit of detection (LOD) when the fluorescence decreased by more than 3 standard deviations (3σ) from its original value equaled 9.2 ± 0.8, 3.3 ± 0.5, and 0.20 ± 0.02 ng/mm 2 for MNT, DNT, and TNT, respectively. These response times and LODs were among the best values reported to date in the scientific literature for fluorescence sensors. The selectivity of the Py-CFPs toward NACs was also investigated by comparing their response to the presence of non-nitrated aromatics, amines, and aromatic ketones. Quenching was only observed with the latter family of chemicals tested, but with much lower efficiency compared to TNT, thus reflecting some level of selectivity toward this specific NAC.

Background: Surgical site infections (SSIs) are a common complication following breast surgery procedures, despite being considered a clean surgery. The prevalence of SSIs can be minimised with the appropriate use of antibiotic prophylaxis as outlined in the Australian Therapeutic Guidelines (eTG). The aims of this study were to evaluate adherence to the eTG for antibiotic prophylaxis in breast surgery procedures at a Western Australian teaching hospital following an update of the guidelines in 2014 and examine the impact of prophylactic antibiotics on SSI incidence and length of hospital stay., Method: A retrospective cross-sectional study which reviewed medical records from a random sample of 250 patients selected from 973 patients who underwent breast surgical procedures between February 2015 and March 2017., Results: Overall adherence to current eTG occurred in 49.2% (123/250) of operations. Pre-operative and post-operative antibiotics were prescribed in 98.4% (246/250) and 11.2% (28/250) operations respectively. Adherence rates to three specific elements of the eTG (drug prescribed, drug dosage and timing of administration) were 91.6% (229/250), 53.6% (134/250) and 86.4% (216/250) respectively. For the 14.4% (36/250) patients with relevant drug allergies, there was zero adherence to the eTG. Overall recorded SSI prevalence was low at 5.2% (13/250). The mean length of stay in patients (2.3 ± 1.7 days) was not influenced by level of eTG adherence ( p  = 0.131) or SSIs ( p  = 0.306)., Conclusion: These data demonstrate a significant improvement in overall adherence to the eTG from 13.3% to 49.2% ( p  =  < 0.001). The level of detected SSIs in this study was low. Further improvement is necessary with respect to prescribing appropriate antibiotic dosages and for those with allergies., Competing Interests: The authors declare there are no competing interests.

Pseudogout, also known as calcium pyrophosphate deposition disease, is a rheumatological condition arising from accumulation of calcium pyrophosphate dihydrate crystals in connective tissues. We present a case of a 56-year-old Bangladeshi woman who underwent focused right inferior parathyroidectomy for primary hyperparathyroidism from a right inferior parathyroid adenoma. On the first post-operative day, she complained of left elbow painful swelling with redness and warmth. Arthrocentesis of left elbow was done due to suspicion of septic arthritis. Two weeks prior to this surgery, she had sudden bilateral knee swelling was diagnosed in her home country of bilateral knee osteoarthritis with effusion and arthrocentesis showed no crystals. Aspiration of left elbow showed calcium pyrophosphate crystals, associated with post parathyroidectomy hypocalcemia, hypomagnesemia confirming pseudogout. Her uric acid level was normal. Bilateral wrist x-rays showed triangular fibrocartilage complex chondrocalcinosis. The patient's condition improved with colchicine and naproxen, as well as calcium and magnesium replacement. Her left elbow swelling and pain resolved. Pseudogout flare is a rare but known sequelae after parathyroidectomy. Early recognition and expeditious treatment is essential.

Objective: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed., Data Sources: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed., Study Selection and Data Extraction: Relevant English-language studies or those conducted in humans were considered., Data Synthesis: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5'-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin., Conclusions: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.

Background Guidelines for the appropriate use of antibiotic prophylaxis are provided in the Therapeutic Guidelines: Antibiotics (eTG) in Australia. Inappropriate use of antibiotics is problematic. Objective To examine adherence with therapeutic guidelines (eTG) in breast surgery and trends in non-adherence dependent on the type of breast surgery performed. Setting Major Western Australian teaching hospital. Method A retrospective cross-sectional study reviewed a random sample of 150 from 1049 eligible medical records of patients who underwent a breast surgical procedure in 2013 or 2014. Main outcome measure Adherence to the eTG. Results Antibiotic prophylaxis was prescribed for 139 (92.7%) operations. Adherence to the eTG occurred in 20 (13.3%) operations, whilst 11 (7.3%) did not adhere to any element of the eTG. Appropriate timing was the main factor not adhered to. Postoperative antibiotics were prescribed following 35 (23.3%) operations, with 32 (91.4%) administered beyond 24 h. Length of stay was significantly different (p = 0.0036) between surgical groups. There was a tendency for risk of an infection to be decreased with adherence (odds ratio: 0.23; 95% CI: 0.05, 1.07; p = 0.06). Conclusion Adherence to the eTG was low (13.3%), despite a decreased risk of SSI when guidelines were followed.

The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of the HIV-infected patient. These issues include adherence, long- and short-term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs into sanctuary sites, such as the central nervous system, genital tract and small bowel, and drug-drug and drug-food interactions related to cytochrome P450 drug-metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug transporters, to name a few. There is future promise, as an increased understanding of the immunopathogenesis of HIV and global public health initiatives are driving novel treatment approaches with goals to prevent, control and, ultimately, eradicate HIV., (© 2014 The British Pharmacological Society.)

Aim: To evaluate the feasibility of magnetic resonance imaging (MRI) for the transformation of preserved organs and their disease entities into digital formats for medical education and creation of a virtual museum., Materials and Methods: MRI of selected 114 pathology specimen jars representing different organs and their diseases was performed using a 3 T MRI machine with two or more MRI sequences including three-dimensional (3D) T1-weighted (T1W), 3D-T2W, 3D-FLAIR (fluid attenuated inversion recovery), fat-water separation (DIXON), and gradient-recalled echo (GRE) sequences. Qualitative assessment of MRI for depiction of disease and internal anatomy was performed. Volume rendering was performed on commercially available workstations. The digital images, 3D models, and photographs of specimens were archived into a workstation serving as a virtual pathology museum., Results: MRI was successfully performed on all specimens. The 3D-T1W and 3D-T2W sequences demonstrated the best contrast between normal and pathological tissues. The digital material is a useful aid for understanding disease by giving insights into internal structural changes not apparent on visual inspection alone. Volume rendering produced vivid 3D models with better contrast between normal tissue and diseased tissue compared to real specimens or their photographs in some cases. The digital library provides good illustration material for radiological-pathological correlation by enhancing pathological anatomy and information on nature and signal characteristics of tissues. In some specimens, the MRI appearance may be different from corresponding organ and disease in vivo due to dead tissue and changes induced by prolonged contact with preservative fluid., Conclusions: MRI of pathology specimens is feasible and provides excellent images for education and creating a virtual pathology museum that can serve as permanent record of digital material for self-directed learning, improving teaching aids, and radiological-pathological correlation., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Acute respiratory distress syndrome, a severe form of acute lung injury (ALI), is a major cause of death during influenza pneumonia. We have provided evidence for the involvement of recruited neutrophils, their toxic enzymes such as myeloperoxidase and matrix metalloproteinases (MMPs), and neutrophil extracellular traps in aggravating alveolar-capillary damage. In this study, we investigated the effects of doxycycline (DOX), an inhibitor of MMPs, on influenza-induced ALI. BALB/c mice were infected with a sublethal dose of mouse-adapted virulent influenza A/Aichi/2/68 (H3N2) virus, and administered daily with 20mg/kg or 60 mg/kg DOX orally. The effects of DOX on ALI were determined by measuring inflammation, capillary leakage, and MMP activities. Furthermore, levels of T1-α (a membrane protein of alveolar type I epithelium) and thrombomodulin (an endothelial protein) in the bronchoalveolar lavage fluid were evaluated by Western blot analysis. Our results demonstrate significantly decreased inflammation and protein leakage in the lungs after DOX treatment. Levels of MMP-2 and MMP-9 activity, T1-α and thrombomodulin were also diminished in the DOX-treated group. These findings were corroborated by histopathologic analyses, which demonstrated significant reduction in lung damage. Although DOX treatment reduced ALI, there were no effects on virus titers and body weights. Taken together, these results demonstrate that DOX may be useful in ameliorating ALI during influenza pneumonia. Further studies are warranted to determine whether DOX can be used in combination with anti-viral agents to alleviate severe influenza pneumonia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The composition and protein quality of the two most important Western Australian export-quality pollens were investigated. Crude pollen protein content was 20.6% and 27.9% for Jarrah (Eucalyptus marginata) and Marri (Eucalyptus calophylla), respectively. Lysine was the limiting amino acid relative to the FAO protein scoring pattern (Food and Agriculture Organization of the United Nations), and the amino acid scores were 0.73 and 0.66 for Jarrah and Marri pollen, respectively. Apparent biological value (BV) was 61.7 for Jarrah pollen, 66.9 for Marri pollen and 71.4 for the casein controls. Adjusted protein efficiency ratio (PER) values were 2.5, 1.2 and 1.1 for casein and Jarrah and Marri pollens, respectively. Apparent net protein utilization (NPU) was significantly reduced for both pollens (32.8 for Jarrah and 39.5 for Marri) compared to casein (63.6). The low apparent NPU values result from the relatively low digestibility of pollens. Apparent digestibility was 52 and 59% for Jarrah and Marri pollen compared to 89% for casein. Although both Jarrah and Marri pollen are relatively high in protein and have favorable amino acid patterns, their relatively low digestibility will be a limiting factor in their usefulness as a food for humans and monogastric animals. The proximate analysis and mineral content of the pollens are also presented.