The impact of cerebrospinal fluid viral polymerase chain reaction testing on the management of adults with viral meningitis: A multi-center retrospective study.

The aim of this study was to evaluate the role of viral polymerase chain reaction (PCR) testing in patients with aseptic meningitis and identify opportunities for improvement in clinical management. All cerebrospinal fluid samples collected in 1 year from four teaching hospitals in Sydney, Australia, were reviewed. Patients with aseptic meningitis were selected, and clinical and diagnostic features, hospital length of stay (LOS), and treatment were analyzed. Identifying a cause by viral PCR did not reduce hospital LOS (median 3 days) or antibiotic use (median 2 days), but the turnaround time of the PCR test correlated with LOS (Rs = 0.3822, p = 0.0003). Forty-one percent of patients received intravenous acyclovir treatment, which was more frequent in patients admitted under neurologists than infectious diseases physicians (56% vs. 24%; p = 0.013). The majority of patients did not have investigations for alternative causes of aseptic meningitis such as human immunodeficiency virus and syphilis if the viral PCR panel was negative. The benefit of PCR testing in aseptic meningitis in adults in reducing LOS and antibiotic use is unclear. The reasons for unnecessary aciclovir use in meningitis syndromes require further assessment.

Clinical variation in the early assessment and management of suspected community-acquired meningitis: a multicentre retrospective study.

BACKGROUND: Bacterial meningitis is a medical emergency and timely management has been shown to improve outcomes. The aim of this study was to compare the early assessment and management of adults with suspected community-onset meningitis between hospitals and identify opportunities for clinical practice improvement. METHODS: This retrospective cohort study was conducted at three principal referral hospitals in Sydney, Australia. Adult patients with suspected meningitis undergoing cerebrospinal fluid sampling between 1 July 2018 and 31 June 2019 were included. Relevant clinical and laboratory data were extracted from the medical record. Differences between sites were analysed and factors associated with time to antimicrobial therapy were assessed by Cox regression. RESULTS: In 260 patients, the median time from triage to antibiotic administration was 332 min with a difference of up to 147 min between hospitals. Median time from triage to lumbar puncture (LP) was 366 min with an inter-hospital difference of up to 198 min. Seventy per cent of patients had neuroimaging prior to LP, and this group had a significantly longer median time to antibiotic administration (367 vs 231 min; P = 0.001). Guideline concordant antibiotics were administered in 84% of patients, with only 39% of those administered adjunctive corticosteroids. Seven (3%) patients had confirmed bacterial meningitis. Modifiable factors associated with earlier antimicrobial administration included infectious diseases involvement (adjusted hazard ratio [aHR], 1.50 [95% confidence interval (CI), 1.01-2.24]) and computed tomography (CT) scanning (aHR, 0.67 [95% CI, 0.46-0.98]). CONCLUSION: Opportunities for improvement include reducing the time to LP and antibiotic administration, improving coadministration of corticosteroids and avoiding potentially unnecessary CT scanning.

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association with Climate Conditions, Australia.

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.

Concomitant Marked Decline in Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Other Respiratory Viruses Among Symptomatic Patients Following Public Health Interventions in Australia: Data from St Vincent's Hospital and Associated Screening Clinics, Sydney, NSW.

Our Australian hospital tested almost 22 000 symptomatic people over 11 weeks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multiplex polymerase chain reaction (PCR) assay. Following travel bans and physical distancing, SARS-CoV-2 and other respiratory viruses diagnoses fell dramatically. Increasing rhinovirus diagnoses as social control measures were relaxed may indirectly indicate an elevated risk of coronavirus disease 2019 (COVID-19) resurgence.

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.

OBJECTIVE: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. DESIGN: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RESULTS: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. CONCLUSIONS: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.

A retrospective study to determine the cefepime-induced neurotoxicity threshold in hospitalized patients.

OBJECTIVES: Cefepime-induced neurotoxicity (CIN) has been demonstrated to be associated with cefepime plasma concentrations; however, the toxicity threshold remains unclear. The primary objective of this study was to identify the cefepime plasma trough concentration at which neurotoxicity occurs. Secondary objectives were to determine the incidence of CIN at a large tertiary institution and to identify patient factors associated with the development of CIN. METHODS: A retrospective review of all adult patients administered cefepime between October 2017 and May 2018 in a tertiary hospital was conducted to determine total incidence of CIN. A receiver operating characteristic (ROC) curve was constructed to review the sensitivity and specificity of using various cefepime trough plasma concentrations to predict the development of neurotoxicity. Cefepime plasma concentrations were measured using ultra-HPLC. A regression was conducted to identify patient factors associated with CIN. RESULTS: In total, 206 patients were administered 259 courses of cefepime, with an overall CIN incidence of 6% (16/259 courses). A total of 64 courses had a cefepime trough concentration measured (24.7%). A cefepime trough concentration of 36 mg/L provided the best differentiation between patients who experienced neurotoxicity and those who did not. No other patient covariates were identified to be significantly associated with neurotoxicity occurring. CONCLUSIONS: A cefepime trough plasma concentration ≥36 mg/L appears to be the most sensitive and specific cut-off to predict CIN occurring. No patient factors were associated with the development of CIN when accounting for cefepime trough plasma concentrations.

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Can dogs use vocal intonation as a social referencing cue in an object choice task?

Evidence from the literature indicates that dogs' choices can be influenced by human-delivered social cues, such as pointing, and pointing combined with facial expression, intonation (i.e., rising and falling voice pitch), and/or words. The present study used an object choice task to investigate whether intonation conveys unique information in the absence of other salient cues. We removed facial expression cues and speech information by delivering cues with the experimenter's back to the dog and by using nonword vocalizations. During each trial, the dog was presented with pairs of the following three vocal cues: Positive (happy-sounding), Negative (sad-sounding), and Breath (neutral control). In Experiment 1, where dogs received only these vocal cue pairings, dogs preferred the Positive intonation, and there was no difference in choice behavior between Negative or Breath. In Experiment 2, we included a point cue with one of the two vocal cues in each pairing. Here, dogs preferred containers receiving pointing cues as well as Negative intonation, and preference was greatest when both of these cues were presented together. Taken together, these findings indicate that dogs can indeed extract information from vocal intonation alone, and may use intonation as a social referencing cue. However, the effect of intonation on behavior appears to be strongly influenced by the presence of pointing, which is known to be a highly salient visual cue for dogs. It is possible that in the presence of a point cue, intonation may shift from informative to instructive.

Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward.

We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. © 2016 Wiley Periodicals, Inc.

Metal-Organic Framework Glass as a Functional Filler Enables Enhanced Performance of Solid-State Polymer Electrolytes for Lithium Metal Batteries.

Polymers are promising candidates as solid-state electrolytes due to their performance and processability, but fillers play a critical role in adjusting the polymer network structure and electrochemical, thermal, and mechanical properties. Most fillers studied so far are anisotropic, limiting the possibility of homogeneous ion transport. Here, applying metal-organic framework (MOF) glass as an isotropic functional filler, solid-state polyethylene oxide (PEO) electrolytes are prepared. Calorimetric and diffusion kinetics tests show that the MOF glass addition reduces the glass transition temperature of the polymer phase, improving the mobility of the polymer chains, and thereby facilitating lithium (Li) ion transport. By also incorporating the lithium salt and ionic liquid (IL), Li-Li symmetric cell tests of the PEO-lithium salt-MOF glass-IL electrolyte reveal low overpotential, indicating low interfacial impedance. Simulations show that the isotropic structure of the MOF glass facilitates the wettability of the IL by enhancing interfacial interactions, leading to a less confined IL structure that promotes Li-ion mobility. Finally, the obtained electrolyte is used to construct Li-lithium iron phosphate full batteries that feature high cycle stability and rate capability. This work therefore demonstrates how an isotropic functional filler can be used to enhance the electrochemical performance of solid-state polymer electrolytes.

Paediatric community-associated Staphylococcus aureus: a retrospective cohort study.

AIM: We aimed to characterise the demographic and clinical features of paediatric community-associated Staphylococcus aureus (CA-SA) infection. We aimed to identify factors associated with methicillin-resistant S.aureus (MRSA) infection evident at the point of care with the potential to guide antibiotic choice. METHODS: A retrospective chart review in 2008 of CA-SA infections at the Children's Hospital at Westmead (CHW), a 300-bed tertiary paediatric hospital in western Sydney, Australia. We calculate rates of MRSA and perform univariate and multivariate analysis for predictors of MRSA. RESULTS: Of 431 patients with CA-SA infections, 19.3% were MRSA. In univariate analysis, MRSA was predicted by age greater than 1 year, Aboriginal race, rural/regional residence, previous history of skin and soft tissue infection (SSTI) or a family history of SSTI, at least 48 h of antibiotics active against methicillin-sensitive S.aureus (MSSA), invasive infection and abscess formation. In a multivariate analysis factors that independently predicted MRSA in the entire cohort, and in the non-invasive subgroup included abscess formation, a family history of staphylococcal infection or SSTI, Aboriginal ethnicity, at least 48 h of anti-MSSA antibiotics at presentation, presentation during spring and age greater than 1 year. CONCLUSIONS: One fifth of CA-SA infections at our tertiary paediatric hospital in 2008 were MRSA. Several clinical and demographic factors evident at the point of care were highly significant predictors of CA-MRSA infection.

Comparison of human metapneumovirus and respiratory syncytial virus in children admitted to a paediatric intensive care unit.

AIM: To describe the clinical presentation and course of children admitted to the paediatric intensive care unit (PICU) with human metapneumovirus (hMPV) infection, and compare them with children admitted to the PICU with respiratory syncytial virus (RSV) infection. METHODS: hMPV was identified by immunofluorescence in 22 children admitted to the PICU over a 16-month period. The medical records of these children were reviewed retrospectively, and their clinical and laboratory data were compared with 66 children admitted to the PICU with positive tests for RSV over the same period. RESULTS: Children admitted to the PICU with hMPV were significantly older than children with RSV (P= 0.003). Children with hMPV presented more commonly with pneumonia or pneumonitis (29% vs. 16%), and less commonly with bronchiolitis (43% vs. 68%) than RSV (P= 0.13). Invasive ventilation was required in 10 patients (48%) with hMPV, and non-invasive ventilation was required in a further 5 (28%), similar to patients with RSV. Children with hMPV were more likely to have an underlying co-morbidity (P= 0.11). CONCLUSIONS: Children admitted to the PICU with hMPV have a similar disease presentation and severity as children admitted with RSV, including some with extremely severe disease who require additional ventilatory or cardiovascular support. Children with hMPV are likely to be older than those with RSV, and more likely to present with pneumonia and less likely to present with bronchiolitis.

Coronary artery embolism and culture-negative endocarditis post Bentall's procedure.

Infective endocarditis is an important cause of morbidity and mortality, which classically presents with fevers and nonspecific symptoms. Afebrile infective endocarditis with negative blood cultures makes diagnosis more challenging and delays in treatment can occur increasing the likelihood of complications. The presence of prosthetic heart valves places patients at an increased risk of infective endocarditis and the case described below highlights the importance of considering this diagnosis even if classic clinical features such as fever and raised inflammatory markers are not present, as well as discussing an unusual complication of infective endocarditis; coronary artery embolism leading to myocardial infarction.

Assessment of cefepime toxicodynamics: comprehensive examination of pharmacokinetic/pharmacodynamic targets for cefepime-induced neurotoxicity and evaluation of current dosing guidelines.

BACKGROUND: Cefepime-induced neurotoxicity (CIN) is an increasingly reported adverse event; however, the toxicity threshold remains unclear. This study was conducted to provide a comprehensive examination of the most appropriate threshold for CIN, and evaluate the ability of current dosing regimens to attain therapeutic targets. METHODS: Data of the incidence of CIN and cefepime plasma concentrations were collected retrospectively from patients administered cefepime. Population pharmacokinetic modelling was used to determine daily cefepime trough concentration (Cmin), maximum serum concentration and area under the concentration-time curve. The ability of each pharmacokinetic parameter to predict CIN was evaluated using receiver operating characteristic (ROC) curves, from which optimal toxicity thresholds were determined. Pharmacokinetic simulation was used to evaluate the ability of cefepime dosing guidelines to meet established efficacy targets, whilst maintaining exposure below the determined CIN threshold. RESULTS: In total, 102 cefepime courses were evaluated, with CIN reported in 10. ROC analyses showed that all cefepime pharmacokinetic parameters were strongly predictive of CIN. Cmin of 49 mg/L was identified as the optimal toxicity target, based on its predictive ability (0.88, 95% confidence interval 0.758-0.999, P<0.001) and ease of clinical use. Assessment of cefepime dosing regimens predicted that only 29% of simulated patients achieve therapeutic targets, with patients with impaired renal function more likely to exhibit subtherapeutic concentrations (89%), and patients with normal renal function likely to have potentially toxic exposure (64%). CONCLUSIONS: The findings from this study provide evidence that cefepime exposure is highly predictive of CIN, with Cmin of 49 mg/L being the most appropriate toxicity threshold. Further research is required to optimize cefepime dosing in the context of this therapeutic target.

Medical Errors in Iowa: Prevalence and Patients' Perspectives.

OBJECTIVES: The following primary objectives of this study were to: (1) establish baselines of prevalence and causes of medical errors experienced by Iowans in medical settings, (2) determine whether Iowa patients were informed of the errors by the responsible healthcare providers, (3) understand reasons why Iowans who experienced medical errors did or did not report the errors, and (4) discover how Iowans view mandatory reporting of medical errors. METHODS: A total of 1010 Iowa adults took part in a telephone survey in summer 2017. Interviews were completed via random landlines and random digit dialing of cell phone numbers. RESULTS: Nearly one fifth of surveyed Iowa adults (18.8%) reported being involved in a medical error in their own care or in the care of someone close to them, and yet only four in 10 (39.1%) were notified of the error by the responsible provider. Most Iowans strongly agree that Iowa hospitals (79.5%), physicians (74.1%), and nursing homes (82.2%) should be required to report all medical errors to the patient and to a state agency. CONCLUSIONS: A significant proportion of Iowans will experience a medical error. They also desire full transparency from healthcare providers with respect to medical errors, including notifying the patient when an error occurs and mandating that providers report errors to a state-based agency. Iowa regulators should carefully assess and initiate stringent regulatory guidelines for mandatory reporting of medical errors.

Revisiting the important role of magnetic resonance imaging (MRI) in long bone acute osteomyelitis: A case report of methicillin resistant Staphylococcus aureus acute tibial osteomyelitis with conventional radiography, computed tomography, and MRI.

The tibia is an atypical site of osteomyelitis (OM) in adults, and patients with this infection experience a significant degree of morbidity as well as the need for prolonged aggressive antibiotic therapy. The early diagnosis of OM remains challenging, and often relies on imaging modalities which are of variable sensitivity. We present a case of a 49-year-old male with a methicillin resistant Staphylococcus aureus (MRSa) left tibial OM, contiguous left knee septic arthritis, and concurrent bacteraemia. Eight days after the onset of pain in the left knee and lower limb, conventional radiography and computed tomography (CT) imaging had only subtleties of a soft tissue collection and a knee effusion. A MRI demonstrated significant involvement of his tibial bone with a collection, from which surgical specimens confirmed MRSa. This case demonstrates the difficulty of diagnosing early acute OM with conventional radiography and CT imaging, even after a week of symptoms in the affected limb. Given the poor sensitivity of conventional radiography and CT in the diagnosis of early acute OM, this case report illustrates how MRI is the imaging modality of choice in this setting.

The representation of object viewpoint in human visual cortex.

Understanding the nature of object representations in the human brain is critical for understanding the neural basis of invariant object recognition. However, the degree to which object representations are sensitive to object viewpoint is unknown. Using fMRI we employed a parametric approach to examine the sensitivity to object view as a function of rotation (0 degrees-180 degrees ), category (animal/vehicle) and fMRI-adaptation paradigm (short or long-lagged). For both categories and fMRI-adaptation paradigms, object-selective regions recovered from adaptation when a rotated view of an object was shown after adaptation to a specific view of that object, suggesting that representations are sensitive to object rotation. However, we found evidence for differential representations across categories and ventral stream regions. Rotation cross-adaptation was larger for animals than vehicles, suggesting higher sensitivity to vehicle than animal rotation, and was largest in the left fusiform/occipito-temporal sulcus (pFUS/OTS), suggesting that this region has low sensitivity to rotation. Moreover, right pFUS/OTS and FFA responded more strongly to front than back views of animals (without adaptation) and rotation cross-adaptation depended both on the level of rotation and the adapting view. This result suggests a prevalence of neurons that prefer frontal views of animals in fusiform regions. Using a computational model of view-tuned neurons, we demonstrate that differential neural view tuning widths and relative distributions of neural-tuned populations in fMRI voxels can explain the fMRI results. Overall, our findings underscore the utility of parametric approaches for studying the neural basis of object invariance and suggest that there is no complete invariance to object view in the human ventral stream.

Infections following lawnmower and farm machinery-related injuries in children.

AIMS: Because of the paucity of previous data, we report the organisms causing infection in children with injuries from lawnmowers and farm machinery. METHODS: Retrospective study of children admitted to the Children's Hospital at Westmead for lawnmower and farm machinery-related injuries from 1998 to 2007. RESULTS: Twenty-four patients were admitted for lawnmower-related injuries. They had a bimodal age distribution, with peaks at 2-4 years and 14 years. Twenty-one (87.5%) were boys. Positive wound cultures were obtained in 16.7% and included Gram-positive and Gram-negative organisms. Eight patients were admitted for farm machinery-related injuries. Two patients (25%) returned positive wound cultures with multiple organisms including bacteria, fungi and mycobacteria and were diagnosed with osteomyelitis caused by Stenotrophomonas maltophilia and Scedosporium prolificans, respectively. CONCLUSION: The rate of infection in our small series of children with lawnmower and farm machinery-related injuries was comparable to previous reports. We found a wide range of causative organisms, often inherently antibiotic resistant, and we add a case of invasive fungal infection to previous case reports. Because of the wide range of organisms, empirical antibiotic therapy is difficult and our data emphasise the need for cultures to direct ongoing therapy.