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Ching Jou Lim,1 David CM Kong,1 Rhonda L Stuart2,31Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia; 2Monash Infectious Diseases, Monash Health, Clayton, VIC, Australia; 3Department of Medicine, Monash University, Clayton, VIC, AustraliaAbstract: Residential aged care facilities are increasingly identified as having a high burden of infection, resulting in subsequent antibiotic use, compounded by the complexity of patient demographics and medical care. Of particular concern is the recent emergence of multidrug-resistant organisms among this vulnerable population. Accordingly, antimicrobial stewardship (AMS) programs have started to be introduced into the residential aged care facilities setting to promote judicious antimicrobial use. However, to successfully implement AMS programs, there are unique challenges pertaining to this resource-limited setting that need to be addressed. In this review, we summarize the epidemiology of infections in this population and review studies that explore antibiotic use and prescribing patterns. Specific attention is paid to issues relating to inappropriate or suboptimal antibiotic prescribing to guide future AMS interventions.Keywords: residential aged care, health care-associated infection, surveillance, multidrug-resistant, antibiotic prescribing, antimicrobial stewardship

The aim of the study was to quantify clinical pharmacists’ workload in Australia. Specific objectives were to perform a direct observation of the pattern of clinical activities in two acute hospitals and compare that with previously documented self-reported patterns. We were also interested in identifying what records kept by pharmacists would capture all the activities they perform.Methods: An observer recorded the activities of clinical pharmacists on six separate days in the medical and surgical wards of two Melbourne metropolitan hospitals. We examined resultant data to determine suitable records by which clinical pharmacists could capture all the activities they perform. To compare the observed pattern of clinical activities with those earlier self-reported by pharmacists, we categorised our data using the Pharmacy Activity Codes present in the penultimate version of the ICD-10-AM classification system.Results: The observer recorded the performance of 807 workload ‘events’, representing 28 separate types of activities. When compressed into the Pharmacy Activity Codes formerly used in the ICD-10-AM classification system, the pattern of activities identified by direct observation matched that which had previously been self-reported by pharmacists. The majority of the activities performed could be captured by completion of a Pharmaceutical Care Plan and by recording pharmacists’ interventions to a database. The remaining activities may be recorded for departmental workload purposes in a simple template format.Conclusion: The pattern of clinical pharmacist activity at the two hospitals was confirmed by direct observation as similar to that previously reported in other Australian hospitals. A Pharmaceutical Care Plan, a database for intervention recording and a simple workload template provide the means to record all activities that clinical pharmacists perform.

Piezocatalysis is considered to be a favorable catalytic technology by utilizing external mechanical stimulation to promote the specific redox reactions. The application of piezocatalysis in batteries is promising but faces formidable challenges. Herein, the operation principles of piezocatalysis were successfully demonstrated by constructing solid-state Li-Se and Li-S battery models with interfacial stress accumulation. Lead zirconate titanate with an ultra-high piezoelectric coefficient was applied as the piezoelectric catalyst. The uniformity of the dipole orientation in materials was essential for achieving piezocatalysis in batteries. The accumulated high-stress converts to piezopotential for catalyzing most reaction processes in batteries, while the rapid stress change prevents the internal charge reorganization, ensuring continuous efficient catalysis. The internal stress change alters the internal polarisation strength, driving excess screening charge to participate in the electrochemical reaction. Under piezocatalysis, solid-state Li-Se batteries exhibited a initial discharge capacity of 670.9 mAh g -1 (99.4 % of the theoretical value) at 0.1 C, and Li-S batteries showed a capacity of 1463 mAh g -1 at 0.2 C, which was still maintained up to 1084 mAh g -1 at an elevated rate of 0.5 C. This piezocatalysis strategy provides a strong theoretical basis and design specification for enhancing Li-Se and Li-S battery reaction kinetics., (© 2024 Wiley-VCH GmbH.)

IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis., (© 2024. The Author(s).)

Aprotic lithium-oxygen (Li-O 2 ) batteries are considered to be a promising alternative option to lithium-ion batteries for high gravimetric energy storage devices. However, the sluggish electrochemical kinetics, the passivation, and the structural damage to the cathode caused by the solid discharge products have greatly hindered the practical application of Li-O 2 batteries. Herein, the nonsolid-state discharge products of the off-stoichiometric Li 1- x O 2 in the electrolyte solutions are achieved by iridium (Ir) single-atom-based porous organic polymers (termed as Ir/AP-POP) as a homogeneous, soluble electrocatalyst for Li-O 2 batteries. In particular, the numerous atomic active sites act as the main nucleation sites of O 2 -related discharge reactions, which are favorable to interacting with O 2 - /LiO 2 intermediates in the electrolyte solutions, owing to the highly similar lattice-matching effect between the in situ-formed Ir 3 Li and LiO 2 , achieving a nonsolid LiO 2 as the final discharge product in the electrolyte solutions for Li-O 2 batteries. Consequently, the Li-O 2 battery with a soluble Ir/AP-POP electrocatalyst exhibits an ultrahigh discharge capacity of 12.8 mAh, an ultralow overpotential of 0.03 V, and a long cyclic life of 700 h with the carbon cloth cathode. The manipulation of nonsolid discharge products in aprotic Li-O 2 batteries breaks the traditional growth mode of Li 2 O 2 , bringing Li-O 2 batteries closer to being a viable technology.

Stroke poses a critical global health challenge, leading to substantial morbidity and mortality. Existing treatments often miss vital timeframes and encounter limitations due to adverse effects, prompting the pursuit of innovative approaches to restore compromised brain function. This review explores the potential of filamentous phages in enhancing stroke recovery. Initially antimicrobial-centric, bacteriophage therapy has evolved into a regenerative solution. We explore the diverse role of filamentous phages in post-stroke neurological restoration, emphasizing their ability to integrate peptides into phage coat proteins, thereby facilitating recovery. Experimental evidence supports their efficacy in alleviating post-stroke complications, immune modulation, and tissue regeneration. However, rigorous clinical validation is essential to address challenges like dosing and administration routes. Additionally, genetic modification enhances their potential as injectable biomaterials for complex brain tissue issues. This review emphasizes innovative strategies and the capacity of filamentous phages to contribute to enhanced stroke recovery, as opposed to serving as standalone treatment, particularly in addressing stroke-induced brain tissue damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Yang, Kong, Li, Duan and Ye.)

Cholera, a persistent global public health concern, continues to cause outbreaks in approximately 30 countries and territories this year. The imperative to safeguard water sources and food from Vibrio cholerae, the causative pathogen, remains urgent. The bacterium is mainly disseminated via ingestion of contaminated water or food. Despite the plate method's gold standard status for detection, its time-consuming nature, taking several days to provide results, remains a challenge. The emergence of novel virulence serotypes raises public health concerns, potentially compromising existing detection methods. Hence, exploiting Vibrio cholerae toxin testing holds promise due to its inherent stability. Immunobiosensors, leveraging antibody specificity and sensitivity, present formidable tools for detecting diverse small molecules, encompassing drugs, hormones, toxins, and environmental pollutants. This review explores cholera toxin detection, highlighting phage display-based nano immunosensors' potential. Engineered bacteriophages exhibit exceptional cholera toxin affinity, through specific antibody fragments or mimotopes, enabling precise quantification. This innovative approach promises to reshape cholera toxin detection, offering an alternative to animal-derived methods. Harnessing engineered bacteriophages aligns with ethical detection and emphasizes sensitivity and accuracy, a pivotal stride in the evolution of detection strategies. This review primarily introduces recent advancements in phage display-based nano immunosensors for cholera toxin, encompassing technical aspects, current challenges, and future prospects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Yang, Kong and Ye.)

Background: Periampullary diverticulum (PAD) may make the performance of endoscopic retrograde cholangiopancreatography (ERCP) in patients with choledocholithiasis more difficult and may increase complication rates. The present study evaluated the effects of PAD on first-time ERCP in patients with choledocholithiasis., Methods: Outcomes were compared in patients with and without PAD and in those with four types of PAD: papilla located completely inside the diverticulum (type I), papilla located in the inner (type II a) and outer (type II b) margins of the diverticulum; and papilla located outside the diverticulum (type III). Parameters compared included cannulation time and rates of difficult cannulation, post-ERCP pancreatitis (PEP) and perforation., Results: The median cannulation times in patients with types I, II a, II b, III PAD and in those without PAD were 2.0 min, 5.0 min, 0.67 min, 3.5 min, and 3.5 min, respectively, with difficult cannulation rates in these groups of 7.4%, 31.4%, 8.3%, 18.9%, and 23.2%, respectively. The rates of PEP in patients with and without PAD were 5.3% and 5.1%, respectively. Four patients with and one without PAD experienced perforation., Conclusions: The division of PAD into four types may be more appropriate than the traditional division into three types. Cannulation of type I and II b PAD was easier than cannulation of patients without PAD, whereas cannulation of type II a PAD was more challenging. PAD may not increase the rates of PEP., (© 2023. The Author(s).)

Introduction: Over the last two decades, we have experienced pressing needs for new additions to the antifungal armamentarium given the emergence of resistant fungi, the growth of at-risk patient populations for invasive fungal diseases (IFD), the high morbidity and mortality associated with IFD., Areas Covered: The current review will discuss the five promising antifungal agents for IFD (i.e. fosmanogepix, ibrexafungerp, olorofim, rezafungin, and opelconazole), now in the late-phase clinical studies, and likely to be available for clinical use in the near future. For each agent, we describe its mechanism of action, pharmacokinetic and pharmacodynamic properties, spectrum of activity as well as the safety and efficacy data, including findings from ongoing clinical trials. The potential roles of these novel antifungals in clinical practice and the key considerations for clinical use will also be discussed., Expert Opinion: There are unmet needs of these novel agents that should be addressed in the future studies. These include defining their indications and benefits, how to best target them appropriately, surveillance and stewardship of their use.

The demand for high-energy sustainable rechargeable batteries has motivated the development of lithium-oxygen (Li-O 2 ) batteries. However, the inherent safety issues of liquid electrolytes and the sluggish reaction kinetics of existing cathodes remain fundamental challenges. Herein, we demonstrate a promising photo-assisted solid-state Li-O 2 battery based on metal-organic framework-derived mixed ionic/electronic conductors, which simultaneously serve as the solid-state electrolytes (SSEs) and the cathode. The mixed conductors could effectively harvest ultraviolet-visible light to generate numerous photoelectrons and holes, which is favorable to participate in the electrochemical reaction, contributing to greatly improved reaction kinetics. According to the study on conduction behavior, we discover that the mixed conductors as SSEs possess outstanding Li + conductivity (1.52 × 10 -4 S cm -1 at 25 °C) and superior chemical/electrochemical stability (especially toward H 2 O, O 2 - , etc.). Application of mixed ionic electronic conductors in photo-assisted solid-state Li-O 2 batteries further reveals that a high energy efficiency (94.2%) and a long life (320 cycles) can be achieved with a simultaneous design of SSEs and cathodes. The achievements present the widespread universality in accelerating the development of safe and high-performance solid-state batteries.

Mono-ubiquitination of histone H2B plays a critical role in the regulation of gene transcription, DNA replication, and DNA damage repair. In Schizosaccharomyces pombe, Brl2 is an E3 ubiquitin ligase and required for the ubiquitination of H2B at lysine residue 119. Currently, there are few studies related to the function of Brl2 in DNA damage repair. Using camptothecin (CPT) to induce DNA double-strand breaks (DSBs) in S. pombe, we investigated the effect of Brl2 on DSB repair, and found that brl2-null mutants showed greater sensitivity to CPT when compared with wild-type (WT) cells, as well as having a drastically reduced spontaneous recombinant frequency. The fluorescent analysis demonstrated that Brl2 was co-localized with the recombination factor Rad52 at DSBs. Moreover, Brl2 promoted the recruitment of Rad52 to DSBs. Under CPT-induced DSBs, Brl2 was phosphorylated. These findings indicate that Brl2 plays a critical role in DNA homologous recombination and its mediated repair of DSBs.

Objective: To understand the epidemiological and pathogenic characteristics of Legionella in artificial water environment of public places in Shanghai from 2011 to 2018, and to provide scientific basis for the prevention and control of Legionellosis. Methods: A total of 4 817 samples of artificial water environment were collected from 31 public places in Huangpu, Jing'an, Xuhui and Songjiang districts of Shanghai from 2011 to 2108. Epidemiological characteristics of the collected years and months, regional and site types, and sample types were analyzed. After treatment, culture and isolation of the collected water samples, the positive samples were analyzed for Legionella typing characteristics. Results: The positive rate of Legionella pneumophila was 21.57% (1 039/4 817), of which 96.25% (1 000/1 039) was single type, 84.31% (876/1 039) was Legionella pneumophila type 1, followed by Legionella pneumophila type 7 and 6, which accounted for 4.72% (49/1 039) and 3.75% (39/1 039), respectively, and 29 (29/1 039) were multi-type positive. Further typing. From May to October, the highest positive rates were found in July and August, 27.61%(222/804)and 28.61% (230/804)respectively. There were significant differences between different months ( P <0.001); the highest positive rates were found in central air-conditioning cooling water and chilled water (32.40%) and there were significant differences among different water samples ( P <0.001). Legionella pneumophila type 1, type 7 and type 6 were the main diversity distribution characteristics in artificial water environment of different regions, different time, different places and different types of public places. Legionella pneumophila type 1 accounted for the highest proportion, and the proportion of positive samples under different epidemiological characteristics was more than 71.64%. Conclusion: There is relatively serious pollution of Legionella pneumophila type 1 in the artificial water environment of public places in Shanghai. It is necessary to strengthen the disinfection of cooling water/freezing water of central air conditioning in public places in July and August every year.

Introduction: Variegate porphyria (VP; OMIM 176200) is one of the acute hepatic porphyrias, and it is characterized by the partial deficiency of protoporphyrinogen oxidase (PPOX). The unusual homozygous variant with mutations on both alleles of PPOX is distinguished with general heterozygous VP by several typical points such as severe defect in PPOX enzyme activity, early onset of photosensitivity before puberty, and skeletal deformity., Material and Method: In this study, we describe a very rare case of autosomal recessive form of true homozygous VP found in a Chinese patient with consanguineous parents. Sanger sequencing of the PPOX gene showed a novel homozygous variant located at the first base of exon 8 of the gene, i.e., NM&#95;000309.3c.808G > T. To investigate aberrant splicing induced by the mutant, wild-type exon 8 and mutant exon 8 were expressed in pET01 vector as minigene in cultured-cells and analyzed by RT-PCR., Results: The wildtype PPOX showed an expected band in the gel electrophoresis after RT-PCR. The PPOX c.808G > T only showed a band similar to the band size of the vector only control. This result suggested c.808G > T mutant is an exonic mutation inducing aberrant splicing of pre-mRNA of the PPOX gene., Conclusion: This study showed a very rare case of homozygous VP with autosomal recessive homoallelic pattern. In comparison with previous cases of homozygous VP presenting brachydactyly, it is notable that our patient did not have any skeletal deformities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Shanghai Municipal Center for Disease Control and Prevention has implemented an active comprehensive surveillance project of acute respiratory infections in adults in Shanghai, including influenza like illness (ILI) and severe acute respiratory infection (SARI). By testing and identifying a variety of respiratory pathogens, it was found that influenza viruses were the main pathogens in 172 ILI cases in 2019. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 30.81%, 14.53% and 30.55%, respectively. The positive detection of influenza A (H1N1) pdm09 virus peaked in the first quarter. The positive rate of enterovirus/human rhinovirus was 6.40%, with a positive detection peak in the third quarter, while the positive rate of adenovirus was 4.65% with a positive detection peak in the second quarter of the year. Two human coronavirus (HCoV)-OC43 positive samples, 1 HCoV-HKU1 positive sample and 1 HCoV-NL63 positive sample were detected, respectively, and no HCoV-229E positive sample was detected. The detection rate of Staphylococcus aureus was 17.44%, and the detection rate of Klebsiella pneumoniae was 9.88%. Influenza viruses were also the main pathogens in 1 447 SARI cases. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 5.46%, 1.73% and 0.30%, respectively. The positive detection of influenza A (H1N1) pdm09 virus (17.50%) peaked in the first quarter. The total positive detection rate of enterovirus/human rhinovirus was 2.97%, the positive detection peaked in the first quarter. The positive rate of Mycoplasma pneumoniae was 3.25% and the positive rate of Legionella was 1.04%. 5 HCoV-229E positive samples, 10 HCoV-OC43 positive samples, 7 HCoV-HKU1 positive samples and 6 HCoV-NL63 positive samples were detected. Eight strains of Staphylococcus aureus , 4 strains of Pseudomonas aeruginosa and 3 strains of Klebsiella pneumoniae were detected after cultures. By implementing the active surveillance, we not only detected a case of human infection with avian influenza A(H7N9) virus in time, but also preliminary understood the pathogenic spectrum characteristics and seasonality of ILI and SARI in Shanghai. In recent years, the surveillance methods have been continuously improved and the number of sentinel hospitals has increased gradually. In particular, for the response to COVID-19, the Surveillance Information Reporting System of Acute Respiratory Infection based on HIS system has been promoted to cover the whole city, which might lay a foundation for the active surveillance and early warning of emerging infectious diseases in the future.

Objective: To analyze the epidemiological characteristics of imported COVID-19 cases in early phase in Shanghai, introduce measures and provide reference for prevention and control of imported COVID-19 cases. Methods: Data of imported COVID-19 cases in Shanghai reported as of 30 March, 2020 were obtained from National Notifiable Disease Report System of China CDC and field epidemiological investigation reports by CDCs in Shanghai. The information about measures of prevention and control was collected from official websites and platforms of the governments. Data cleaning and statistical analysis were performed with softwares of EpiData 3.1, Excel 2019 and SAS 9.4. Results: A total of 171 imported COVID-19 cases had been reported as of 30 March, 2020 in Shanghai, including 170 confirmed cases and 1 asymptomatic infection case. Among them, cases of Chinese nationality accounted for 71.3% (122/171) and cases of foreign nationality accounted for 28.7% (49/171). The median age of the cases was 23 years ( P(25) , P(75) : 18, 35 years), and the male to female ratio of the cases was 1.3∶1. Students accounted for 56.6% (97/171). About 45.6% (78/171) of the cases fell ill before arriving in Shanghai. The cases with mild or common clinical manifestation accounted for 96.5% (165/171) and no significant difference in clinical type was observed between overseas Chinese cases and foreign cases. The epidemic curve by diagnosis date reached peak on March 24, and the number of the cases gradually declined due to the closed-loop management process of joint port prevention and control mechanism. The 171 imported COVID-19 cases were mainly from 24 countries and regions, including the United Kingdom (64 cases, 37.3%), the United States (32 cases, 18.6%), France (19 cases, 11.0%) and Italy (16 cases, 9.4%). About 40.4% of the cases (69/171) planned to continue travelling to 21 other provinces and municipalities in China. Customs quarantine and community observation/detection points identified 43.9% (75/171) cases and 31.0% (53/171) cases, respectively. Conclusions: The imported COVID-19 cases in early phase in Shanghai were mainly young population and students accounted for high proportion. The imported risk of COVID-19 was consistent with the severity of the epidemic in foreign countries. The closed-loop management model of the joint port prevention and control mechanism plays an important role in the identification and management of the imported COVID-19 cases.

Objective: To study the epidemiological characteristics and mixed infection of adenovirus in acute respiratory tract infections in Shanghai from 2015 to 2019, and to provide scientific basis for the prevention and control of adenovirus. Methods: Acute respiratory tract infections were collected from 3 hospitals in Shanghai from 2015 to 2019. Relevant information was registered and respiratory specimens were sampled for detection of respiratory pathogens by multiplex PCR. Results: A total of 1 543 cases of acute respiratory tract infection were included. The positive rate of adenovirus was 2.92%(45/1 543), the positive rates of influenza like illness (ILI) and severe acute respiratory illness (SARI) were 2.74%(29/1 058) and 3.30%(16/485), respectively. The positive rate of ILI during January-May 2019 was 5.43%(7/129), higher than that in the same period of 2015- 2018 (0.52%-4.48%) (Fisher's exact test value=8.92, P =0.036). The incidence of adenovirus-positive cases was mainly distributed in the first and second quarters, accounting for 62.22% (28/45). The difference of the incidence of adenovirus-positive cases in each quarter was significant ( χ (2)= 12.52, P =0.006). The positive rate in the second quarter was highest (6.03%), which was higher than that in other quarters (1.89%-2.93%). There were significant differences among different age groups ( χ (2)=16.94, P =0.001), and the positive rate decreased with age ( χ (2)=10.16, P =0.001). The positive rate of 13-19 years old group (9.43%) was higher than that of other age groups (1.48%-4.81%). The positive rate of student group (12.07%) was higher than that of other occupations (2.61%). The difference was systematic ( χ (2)=11.53, P =0.001). Mixed infection accounted for 31.11% (14/45) of 45 adenovirus positive cases. The mixed infection rates of ILI and SARI were 34.48% (10/29) and 25.00% (4/16), respectively. Among 14 cases of mixed infection, the main mixed infection pathogens of adenovirus were influenza A virus and coronavirus. Conclusion: Adenovirus surveillance should be further strengthened in adolescents with a focus on students and other key groups in the second quarter.

The annual Aged Care National Antimicrobial Prescribing Survey aims to identify local and national prescribing issues and guide antimicrobial stewardship goals In the 2018 point prevalence survey, medication charts of over 20,000 residents were reviewed from 407 participating facilities across Australia On the day of the survey, almost 10% of residents were prescribed an antimicrobial Nearly two-thirds of recently prescribed antimicrobials were for residents who had no documented signs or symptoms of infection Over a quarter of antimicrobials had been prescribed for longer than six months Incomplete documentation was a prominent barrier to proper review of antimicrobial therapy, with the indication, review date or stop date not documented for many prescriptions Recommendations include using appropriate microbiological testing to guide prescribing, following national antimicrobial prescribing guidelines, documenting the indication for the antimicrobial, and its start, stop and review dates, and monitoring and re-evaluating long-term antimicrobial use, ((c) NPS MedicineWise 2019.)

Objective: To analyze the etiologic and epidemiological characteristics of adult acute respiratory infections in Shanghai during 2015-2017. Methods: Data was collected from outpatients with acute respiratory infections who visited the Fever Clinics in three hospitals of different levels in three administrative regions of Shanghai, from 2015 to 2017. Basic information and nasopharyngeal swabs were collected from cases in line with the inclusion criteria. Multiplex RT-PCR and bacterial cultures were performed to detect the respiratory pathogens. Results: A total of 806 individuals were enrolled from 2015 to 2017. Respiratory pathogens were identified in 73.45% (592/806) of the cases, with the virus detection rate as 66.75% (538/806). It was found that the major respiratory pathogens for virus detection were influenza A in 326 (40.45%), influenza B in 116 (14.39%), rhinovirus/enterovirus in 39 (4.84%) of the cases. The overall detection rate of bacteria was 16.13% (130/806), including Klebsiella pneumoniae in 90 (11.17%) cases, Staphylococcus Aureus in 46 (5.71%) cases. Other kind of bacteria were not detected in our study. The detection rates on Mycoplasma pneumoniae was 5.33% (43/806) and on Chlamydia pneumonia was 0.37% (3/806). Co-infection with multiple pathogens was detected in 18.61% (150/806) of the cases, including 135 with double infection (accounting for 90.00%), 14 with triple infection and 1 with quadruple infection (accounted for 9.33% and 0.67%, respectively). Among the 150 cases with co-infections, the main identified pathogens were influenza A, Klebsiella pneumoniae, Staphylococcus aureus, and Mycoplasma pneumoniae. Pathogens of acute respiratory infections that identified among the outpatients from the Fever Clinics at different time, region or population, the characteristics were different ( P <0.001). Conclusions: In 2015-2017, outpatients with acute respiratory infections in Shanghai were mainly caused by influenza virus or other viruses, however dynamically with its composition, time, region and characteristics of the population. It is necessary to strengthen and combine related medical and preventive services and to develop the appropriate strategies regarding clinical diagnosis and treatment.

Objective: To understand the epidemiological and pathogenic characteristics of hospitalized severe acute respiratory infections (SARI) in Shanghai, China. Methods: From 2015 to 2017, one Tertiary hospital and one Secondary hospital were chosen as the surveillance sites. Two respiratory tract specimens per case were collected from SARI cases aged 15 years and older. One specimen was tested for 22 respiratory pathogens by RT-PCR, and the other specimen was cultured for 6 respiratory bacteria. Results: A total of 287 SARI cases were enrolled for sampling and lab testing. 70.73% of the cases were aged 60 years and older, with 41.46% (119/287) were positive for at least one pathogen. Influenza virus was the predominant pathogen, accounting for 17.77% (51/287) of all SARI cases. Human rhinovirus/Enterovirus and Coronavirus were both accounting for 7.32% (21/287), followed by Mycoplasma pneumoniae (5.57%, 16/287). The positive rates of parainfluenza virus, bocavirus, adenovirus, respiratory syncytial virus and human metapneumo virus were all less than 5%. Bacterial strains were identified in seven SARI cases, including Klebsiella pneumoniae (3 strains), Staphylococcus aureus (2 strains), Streptococcus pneumoniae (1 strain) and Pseudomonas aeruginosa (1 strain). Two or Three pathogens were co-detected from 40 cases, accounting for 33.61% of 119 positive cases. The most common co-detected pathogens were influenza virus and Mycoplasma pneumoniae (10 cases). Influenza cases peaked in winter-spring and summer. Mycoplasma pneumoniae peaked in winter-spring season and overlapped with influenza. The positive rates of pathogens were not significantly different between different age groups. Conclusions: Various respiratory pathogens can be detected from SARI cases aged 15 years and older. Influenza virus was the predominant pathogen and the co-detection of influenza virus with Mycoplasma pneumoniae the most common one.

The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Antimicrobial resistance (AMR) has been recognised as an urgent health priority, both nationally and internationally. Australian hospitals are required to have an antimicrobial stewardship (AMS) program, yet the necessary resources may not be available in regional, rural or remote hospitals. This review will describe models for AMS programs that have been introduced in regional, rural or remote hospitals internationally and showcase achievements and key considerations that may guide Australian hospitals in establishing or sustaining AMS programs in the regional, rural or remote hospital setting., Methods: A narrative review was undertaken based on literature retrieved from searches in Ovid Medline, Scopus, Web of Science and the grey literature. 'Cited' and 'cited by' searches were undertaken to identify additional articles. Articles were included if they described an AMS program in the regional, rural or remote hospital setting (defined as a bed size less than 300 and located in a non-metropolitan setting)., Results: Eighteen articles were selected for inclusion. The AMS initiatives described were categorised into models designed to address two different challenges relating to AMS program delivery in regional, rural and remote hospitals. This included models to enable regional, rural and remote hospital staff to manage AMS programs in the absence of on-site infectious diseases (ID) trained experts. Non-ID doctor-led, pharmacist-led and externally led initiatives were identified. Lack of pharmacist resources was recognised as a core barrier to the further development of a pharmacist-led model. The second challenge was access to timely off-site expert ID clinical advice when required. Examples where this had been overcome included models utilising visiting ID specialists, telehealth and hospital network structures. Formalisation of such arrangements is important to clarify the accountabilities of all parties and enhance the quality of the service. Information technology was identified as a facilitator to a number of these models. The variance in availability of information technology between hospitals and cost limits the adoption of uniform programs to support AMS., Conclusion: Despite known barriers, regional, rural and remote hospitals have implemented AMS programs. The examples highlighted show that difficulty recruiting ID specialists should not inhibit AMS programs in regional, rural and remote hospitals, as much of the day-to-day work of AMS can be done by non-experts. Capacity building and the strengthening of networks are core features of these programs. Descriptions of how Australian regional, rural and remote hospitals have structured and supported their AMS programs would add to the existing body of knowledge sourced from international examples. Research into AMS programs predominantly led by GPs and nursing staff will provide further possible models for regional, rural and remote hospitals.

2,4-dichlorophenol(2,4-DCP), a highly toxic and refractory organic compound, was commonly used in pesticide production and thus widely distributed in water and soil. Goethite, magnetite and gypsum were added into the anaerobic system which simulated the natural anaerobic process to evaluate their effects on the anaerobic degradation of 2,4-DCP. It indicated that goethite, magnetite and gypsum had no appreciable adsorption ability toward 2,4-DCP under anaerobic condition. Mass balance analysis showed that only the transformation of 2,4-DCP to 4-chlorophenol(4-CP) occurred in all experimental groups. The addition of sodium acetate doubled the reductive dechlorination rate of 2,4-DCP in comparison with the groups without exogenous carbon source. The reductive dechlorination rate of 2,4-DCP was enhanced by the addition of goethite and magnetite, which was caused by the improved metabolic activity of dechlorination bacteria that played an important role in the anaerobic degradation of 2,4-DCP. Gypsum greatly inhibited or even stopped the degradation process of 2,4-DCP through restraining the growth and activity of dechlorination bacteria. This study will shed light on the migration and degradation of refractory chlorinated organic contaminants in anaerobic sedimentary environment, and the treatment of such matters in environmental technology.

Objectives: This study describes the safety, clinical effectiveness and trough plasma concentration (C min ) of intravenous (iv) posaconazole, provided as part of Merck Sharp and Dohme Australia's Named Patient Programme (NPP) in non-clinical trial settings., Methods: A multicentre, retrospective study on the NPP use of iv posaconazole between July 2014 and March 2015 across seven Australian hospitals., Results: Seventy courses of iv posaconazole were prescribed and evaluated in 61 patients receiving treatment for haematological malignancy. Sixty-one courses were prescribed for prophylaxis against invasive fungal disease (IFD), the majority of which (59) were initiated in patients with gastrointestinal disturbances and/or intolerance to previous antifungals. The median (IQR) duration for prophylaxis was 10 (6-15) days. No breakthrough IFD was observed during or at cessation of iv posaconazole. Nine courses of iv posaconazole were prescribed for treatment of IFD with a median (IQR) duration of 19 (7-30) days. Improvement in signs and symptoms of IFD was observed in five cases at cessation of, and six cases at 30 days post-iv posaconazole. C min was measured in 39 courses of iv posaconazole, with the initial level taken [median (IQR)] 4 (3-7) days after commencing iv posaconazole. The median (IQR) of initial C min was 1.16 (0.69-2.06) mg/L. No severe adverse events specifically attributed to iv posaconazole were documented, although six courses were curtailed due to potential toxicity., Conclusions: This non-clinical trial experience suggests that iv posaconazole appeared to be safe and clinically effective for prophylaxis or treatment of IFD in patients receiving treatment for haematological malignancies., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than in vitro MIC 90 values for typical fungi that cause keratitis., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Access to hearing health care is limited in many parts of the world, creating a lack of prompt diagnosis, which further complicates treatment. The use of portable audiometry for hearing loss testing can improve access to diagnostics in marginalized populations. Our study objectives were twofold: (1) to determine the prevalence of hearing loss in children aged 4 to 11 years in Iqaluit, Nunavut, and (2) to test and demonstrate the use of our tablet audiometer as a portable hearing-testing device in a remote location., Study Design: Prospective cross-sectional observational., Setting: Remote elementary schools in 3 Canadian Northern communities., Subjects and Methods: Tablet audiometers were used to test hearing in 218 children. Air conduction pure tones thresholds were obtained at 500, 1000, 2000, and 4000 Hz. Children with hearing loss ≥30 dB in either ear were referred for audiology services., Results: Tablet audiometry screening testing revealed abnormal results in 14.8% of the study participants. No significant difference in the rate of hearing loss was seen by sex; however, the rate of hearing loss decreased significantly with increasing age. The median duration of the hearing test was 5 minutes 30 seconds., Conclusions: Of the study population, 14.8% tested positive for hearing loss based on our interactive tablet audiometer. In this setting, the tablet audiometer was both time efficient and largely language independent. This type of testing is valuable for providing much-needed hearing health care for high-risk populations in rural and remote areas where audiology services are often unavailable., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objectives: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD., Methods: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective., Results: Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars; P < 0.001) compared with patients without IFD., Conclusions: This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The efficacy of infection control interventions against Acinetobacter baumannii remains unclear, despite such information being critical for effective prevention of the transmission of this pathogen. Mathematical modeling offers an alternative to clinical trials, which may be prohibitively expensive, unfeasible or unethical, in predicting the impact of interventions. Furthermore, it allows the ability to ask key "what if" questions to evaluate which interventions have the most impact. We constructed a transmission dynamic model to quantify the effects of interventions on reducing A. baumannii prevalence and the basic reproduction ratio (R0) in intensive care units (ICUs). We distinguished between colonization and infection, and incorporated antibiotic exposure and transmission from free-living bacteria in the environment. Under the assumptions and parameterization in our model, 25% and 18% of patients are colonized and infected with A. baumannii, respectively; and R0 is 1.4. Improved compliance with hand hygiene (≥87%), enhanced environmental cleaning, reduced length of ICU stay of colonized patients (≤ 10 days), shorter durations of antibiotic treatment of A. baumannii (≤6 days), and isolation of infected patients combined with cleaning of isolation rooms are effective, reducing R0 to below unity. In contrast, expediting the recovery of the intestinal microbiota (e.g. use of probiotics) is not effective. This study represents a biologically realistic model of the transmission dynamics of A. baumannii, and the most comprehensive analysis of the effectiveness of interventions against this pathogen. Our study provides important data for designing effective infection control interventions.

Background: Little is known about the use of sedation drugs for the management of acute agitation in Hong Kong's Accident and Emergency Departments (AEDs) and how it compares with Australasian practice., Objective: The aim of this study was to determine drug preferences, clinicians' perceived confidence in management, barriers/gaps in training and perceived usefulness of existing clinical practice guidelines (CPGs) in Hong Kong., Method: A validated questionnaire was used, with case vignettes typical of patients presenting to AEDs with acute agitation. The questionnaire was distributed by hand to all trainees and fellows of the Hong Kong College of Emergency Medicine (HKCEM). Two reminders were sent., Results: Of 483 HKCEM members, 280 (58.0% [95% CI 53.5-62.3]) responded. For monotherapy, 46.8% (95% CI 41.0-52.6) of respondents chose haloperidol to manage the undifferentiated patient, followed by midazolam (33.9%, 95% CI 28.6-39.7) and diazepam (13.9%, 95% CI 10.4-18.5). Most respondents (83.6%, 95% CI 78.8-87.5) would not administer combination therapy. Respondents were confident in managing agitation overall. The lack of local/institutional CPGs (55.7%, 95% CI 49.9-61.4) was perceived as an important barrier. Institutional guidelines were considered the most useful CPGs (66.4%, 95% CI 60.7-71.7). Most respondents (72.9%, 95% CI 67.4-77.7) perceived a HKCEM endorsed CPG would be useful., Conclusion: Haloperidol and benzodiazepines are frequently used as monotherapy for the management of acute agitation in Hong Kong's AEDs. Management in Hong Kong differs from Australasian practice in that combination therapy is less common and clinicians' choice of sedation drugs are less variable overall. Results suggest that future work on CPG development and training regarding the safe use of combination therapy would be well received., (© 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Introduction: Studies exploring the appropriateness of therapeutic antibiotic use among surgical patients are limited, particularly in developing countries. Therefore, the aim of our study was to determine the appropriateness of antibiotics prescribed in a surgical setting in Malaysia., Methodology: A prospective observational study was conducted in two surgical wards at a tertiary hospital in Malaysia from November 2012-July 2013. Data was collected using a case report form. The appropriateness of antibiotic therapy was based on compliance with either the Malaysian National Antibiotic Guidelines 2008 or International Clinical Practice Guidelines and determined by an expert panel (consisting of two infectious disease consultants and a pharmacist)., Results: Over the study period, a total of 593 antibiotic courses were prescribed for 129 patients (4.6±3.4 antibiotics/patient). Only 34 (26.4%) patients received appropriate antibiotic therapy, whilst 95 (73.6%) patients received at least one course of inappropriate antibiotic therapy. The prevalence of inappropriate antibiotic use was 214 (66.3%) and 55 (42.0%) for prophylactic and therapeutic purposes, respectively. The most common causes of inappropriate prophylactic antibiotics were inappropriate timing 20 (36.4%) and inappropriate duration of prophylaxis 19 (34.5%). In cases of inappropriate timing, 9 (45%) were administered too late while 6 (30%) were too early. In contrast, inappropriate choice of antibiotics (42.1%) and inappropriate indication (40.7%) were the most common reasons encountered for inappropriate therapeutic antibiotics., Conclusion: Our study suggests considerable inappropriate use of both prophylactic and therapeutic antibiotics in the surgical wards; highlighting an urgent need for antibiotic stewardship initiatives in this setting.

Objectives: No previous studies have investigated patients' expectations of, or interest in, using primary care pharmacy services in the UAE. The study investigated primary care services that patients would use if they were provided through community pharmacies., Methods: A questionnaire was developed in English and translated to Arabic. Participants were asked to rate their likelihood of using future primary care services on a three-point Likert-type scale (very likely-unlikely). Services included screening for disease, monitoring of disease control, health advice and referral, lifestyle and preventive care, supply of printed information, counselling on medication use and side effects, patient record keeping, and pharmacist intervention in chronic disease. The questionnaire was distributed to patrons of public places by hand to eligible participants: ≥21 years, taking at least one scheduled prescription medication and having adequate Arabic or English proficiency., Key Findings: Areas of most interest were as follows: the pharmacist explaining how to use medications (Median = 3, interquartile range (IQR) = 1), the pharmacist advising on side effects of medications (Median = 3, IQR = 1), receiving advice on how to use devices (Median = 3, IQR = 1) and receiving printed information about medications (Median = 3, IQR = 1). Participants were least supportive of pharmacists keeping medication records (Median = 2, IQR = 1) and intervening in chronic disease management (Median = 2, IQR = 1). Participants anticipated a caring professional service by pharmacists and a pharmacy layout that allows private communication., Conclusions: Participants were interested in accessing enhanced primary care services by community pharmacists. Participants were more supportive of receiving information about medications, help in self-management and monitoring, and advice about disease prevention than management of chronic disease., (© 2015 Royal Pharmaceutical Society.)

Little is known about the transmission dynamics of Acinetobacter baumannii in hospitals, despite such information being critical for designing effective infection control measures. In the absence of comprehensive epidemiological data, mathematical modelling is an attractive approach to understanding transmission process. The statistical challenge in estimating transmission parameters from infection data arises from the fact that most patients are colonised asymptomatically and therefore the transmission process is not fully observed. Hidden Markov models (HMMs) can overcome this problem. We developed a continuous-time structured HMM to characterise the transmission dynamics, and to quantify the relative importance of different acquisition sources of A. baumannii in intensive care units (ICUs) in three hospitals in Melbourne, Australia. The hidden states were the total number of patients colonised with A. baumannii (both detected and undetected). The model input was monthly incidence data of the number of detected colonised patients (observations). A Bayesian framework with Markov chain Monte Carlo algorithm was used for parameter estimations. We estimated that 96-98% of acquisition in Hospital 1 and 3 was due to cross-transmission between patients; whereas most colonisation in Hospital 2 was due to other sources (sporadic acquisition). On average, it takes 20 and 31 days for each susceptible individual in Hospital 1 and Hospital 3 to become colonised as a result of cross-transmission, respectively; whereas it takes 17 days to observe one new colonisation from sporadic acquisition in Hospital 2. The basic reproduction ratio (R0) for Hospital 1, 2 and 3 was 1.5, 0.02 and 1.6, respectively. Our study is the first to characterise the transmission dynamics of A. baumannii using mathematical modelling. We showed that HMMs can be applied to sparse hospital infection data to estimate transmission parameters despite unobserved events and imperfect detection of the organism. Our results highlight the need to optimise infection control in ICUs.

The National Return and Disposal of Unwanted Medicines Program provides a free and safe method for the disposal of unwanted and expired medicines. This stops drugs being dumped in landfill and waterways. An audit showed that over 600 tonnes of medicines are returned through the program. A substantial proportion of these medicines were still within their expiry dates. Salbutamol, insulin and frusemide are the most commonly discarded medicines. More than $2 million of public money is wasted each year. Hoarding and non-adherence to treatment contribute to waste. Health professionals may be able to help minimise waste by informing patients about the importance of completing prescribed courses of treatment, and discouraging them from hoarding medicines after reaching the safety net threshold on the Pharmaceutical Benefits Scheme. Prescribe no more than the required quantity of medicines. When starting a new therapy, prescribe a minimal quantity in case the drug is unsuitable for the patient. Advise patients to return all unwanted medicines to a pharmacy for disposal.

Background: High infection burden among the residential aged care facility (RACF) population has long been recognised; however, existing infection prevention effort is often limited to infection surveillance activity. There is a scarcity of evidence to guide antimicrobial stewardship in the Australian RACF setting., Objective: This review summarises the current trends in antibiotic use and multi-drug resistant (MDR) organisms, challenges related to antibiotic prescribing and areas of suboptimal antibiotic prescribing for further improvement, particularly in the Australian RACF setting., Discussion: There is widespread antibiotic prescribing in RACF, which may lead to the emergence of antibiotic resistance. Accordingly, there is an immediate need for judicious antibiotic use in this high-risk population to curb the rapid emergence of MDR organisms and other adverse consequences associated with inappropriate antibiotic use, as well as to reduce healthcare costs.

Background: The clinical utility of bronchoalveolar lavage (BAL) fluid galactomannan (GM) for the early diagnosis of invasive aspergillosis (IA) varies widely across studies mainly due to heterogeneity of the studied populations., Methods: We conducted a systematic review and meta-analysis of 16 studies involving 783 adults with hematological malignancies to derive summary estimates of the overall accuracy of BAL-GM for diagnosing IA., Findings: Summary estimates of BAL-GM using an optical density (OD) index cutoff value of 1.5 for proven and probable IA were: sensitivity 0.92 (95% CI = 0.48-0.99), specificity 0.98 (95% CI = 0.78-1.00), positive likelihood ratio 53.7 (95% CI = 3.7-771.8), and negative likelihood ratio 0.08 (95% CI = 0.01-0.83). Comparing serum GM and Aspergillus PCR testing on BAL fluid, BAL-GM conferred greater sensitivity, but lower specificity than the serum GM test, and similar specificity as the PCR assay. The use of BAL-GM with serum GM or BAL-PCR tests increased the sensitivity moderately when a positive result was defined by either assay., Interpretation: GM quantification in BAL fluid at an OD index cutoff value of 1.5 has excellent sensitivity and specificity to assist clinical decision-making in confirming or excluding a diagnosis of IA when results are interpreted with clinical findings. Additional research investigating the effects of antifungal agents, optimal timing and processing of BAL sampling are needed to improve the diagnostic accuracy of BAL-GM testing.

Four kinds of amendments including humus, ammonium sulfate, lime, superphosphate and their complex combination were added to rapid immobilize the heavy metals in contaminated soils. The best material was chosen according to the heavy metals' immobilization efficiency and the Capacity Values of the fixative in stabilizing soil heavy metals. The redistributions of heavy metals were determined by the European Communities Bureau of Referent(BCR) fraction distribution experiment before and after treatment. The results were as follows: (1) In the single material treatment, lime worked best with the dosage of 2% compared to the control group. In the compound amendment treatments, 2% humus combined with 2% lime worked best, and the immobilization efficiency of Pb, Cu, Cd, Zn reached 98.49%, 99.40%, 95.86%, 99.21%, respectively. (2) The order of Capacity Values was lime > humus + lime > ammonium sulfate + lime > superphosphate > ammonium sulfate + superphosphate > humus + superphosphate > humus > superphosphate. (3) BCR sequential extraction procedure results indicated that 2% humus combined with 2% lime treatment were very effective in immobilizing heavy metals, better than 2% lime treatment alone. Besides, Cd was activated firstly by 2% humus treatment then it could be easily changed into the organic fraction and residual fraction after the subsequent addition of 2% lime.

The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length of stay (LOS) in hospital, after adjusting for the time-varying nature of enterococcal bacteraemia (variable onset of bacteraemia post-admission), is unknown. Survival analyses (time-varying Cox and competing risks regression) were performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin-susceptible enterococci bacteraemia patients to determine the factors associated with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia, intensive-care-unit admission, Charlson co-morbidity index score ⩾4, and an increase in the time to receive appropriate antibiotics were associated with prolonged LOS. Competing risks regression which accounts for the influence of in-patient mortality on the ability to observe the event discharge alive from hospital suggests that, vanB VRE bacteraemia was not significantly associated with prolonged LOS. For the first time, the rate of discharge from hospital in patients with vanB VRE bacteraemia has been quantified.

Antifungal agents may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non-compliance, non-linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)