What information can the lay public find about osteoporosis treatment? A descriptive study coding the content and quality of bisphosphonate information on the internet.

Despite its effectiveness, bisphosphonate use for osteoporosis is low. We assessed bisphosphonate information on the internet and found the most commonly listed benefits/risks were bone density loss, gastrointestinal issues, and jaw necrosis, that risk quantification was rare, and information quality varied. Findings underscore the importance of clinical communication about bisphosphonates. INTRODUCTION: The US Preventative Services Task Force recommends osteoporosis screening and treatment with bisphosphonates in high-risk populations. However, bisphosphonate use among individuals with osteoporosis remains low. The content and quality of information from outside sources may influence individuals' bisphosphonate decisions. Therefore, we sought to assess the content and quality of osteoporosis treatment information available to the public by conducting an internet search and coding available bisphosphonate information. METHODS: Eleven search terms about osteoporosis and bisphosphonates were entered into four search engines. Two raters assessed websites for information about bisphosphonates, whether and how benefits and side effects were described and quantified, contraindications, and dosing instructions. Coders also assessed website interface and slant/balance of information. RESULTS: One thousand four hundred seventy-three websites were identified. Two hundred twenty-seven websites met inclusion criteria and were coded. The most common bisphosphonate benefit described was prevention of bone density loss (77.1% of websites). The most common side effects described were gastrointestinal problems (66.1%) and jaw osteonecrosis (58.6%). Most websites did not quantify bisphosphonate benefits (78.0%) or side effects (82.4%). Complementary/integrative health websites (p < .001) and pharmaceutical litigation websites (p < .001) were more often slanted against taking bisphosphonates, compared to all websites coded. General medical knowledge websites were more balanced than other websites (p = .023). CONCLUSIONS: The quality of bisphosphonate information on the internet varies substantially. Providers counseling patients about osteoporosis treatment should inquire about patients' baseline bisphosphonate knowledge. Providers can complement accurate information and address potential bisphosphonate misconceptions.

Carbapenemase-producing Enterobacteriaceae in Australian hospitals: outcome of point-prevalence screening in high-risk wards.

Carbapenemase-producing Enterobacteriaceae (CPE) infections are increasingly reported in Australian hospitals, but prevalence is unknown. In 2016, Victorian hospitals conducted CPE point-prevalence surveys in high-risk wards (intensive care, haematology, transplant). Forty-three hospitals performed 134 surveys, with 1839/2342 (79%) high-risk patients screened. Twenty-four surveys were also performed in other wards. Inability to obtain patient consent was the leading reason for non-participation. In high-risk wards, no CPE cases were detected; three cases were identified in other wards. Since there is low prevalence in high-risk wards, continuous screening is not recommended. Targeted screening may be enhanced by review of patient consent processes.

Central and peripheral line-associated bloodstream infections in Australian neonatal and paediatric intensive care units: findings from a comprehensive Victorian surveillance network, 2008-2016.

BACKGROUND: Healthcare-associated infections in neonatal and paediatric populations are associated with poorer outcomes and healthcare costs, and surveillance is a necessary component of prevention programmes. AIM: To evaluate burden of illness, aetiology, and time-trends for central and peripheral line-associated bloodstream infection (CLABSI and PLABSI) in Australian neonatal and paediatric intensive care units (ICUs) between July 1st, 2008 and December 31st, 2016. METHODS: Using National Healthcare Safety Network methods, surveillance in neonatal and paediatric units was performed by hospitals participating in the Victorian Healthcare Associated Infection Surveillance System. Mixed effects Poisson regression was used to model infections over time. FINDINGS: Overall, 82 paediatric CLABSI events were reported during 37,125 CVC-days (2.21 per 1000 CVC-days), 203 neonatal CLABSI events were reported during 92,169 CVC-days (2.20 per 1000 CVC-days), and 95 neonatal PLABSI events were reported during 142,240 peripheral line-days (0.67 per 1000 peripheral line-days). Over time, a significant decrease in quarterly risk for neonatal CLABSI events was observed (risk ratio (RR): 0.98; 95% confidence interval: 0.97-0.99; P = 0.023) and this reduction was significant for the 751-1000 g birth weight cohort (RR: 0.97; P = 0.015). Most frequently, coagulase-negative Staphylococcus spp. (24.2%) and Staphylococcus aureus (16.1%) were responsible for CLABSI events. A significant reduction in Gram-negative neonatal infections was observed (annual RR: 0.85; P < 0.001). CONCLUSION: CLABSI rates in neonatal and paediatric ICUs in our region are low, and neonatal infections have significantly diminished over time. Evaluation of infection prevention programmes is required to determine whether specific strategies can be implemented to further reduce infection risk.

Validation of healthcare-associated infection surveillance in smaller Australian hospitals.

A validation study was conducted in smaller (<100 acute beds) Victorian hospitals to evaluate case detection for Staphylococcus aureus bloodstream (SAB), meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) infections. Overall, 142 infections were identified in 20 hospitals. For routine surveillance of SAB events, sensitivity was 74.4% and specificity was 100.0%. For MRSA infections, sensitivity was 47.5% and specificity was 90.9%. All confirmed VRE infections were reported correctly. Of unreported SAB and MRSA infections, 80% (N = 16) and 83.9% (N = 26) were community-associated infections, respectively. Future programme refinements include targeted education to ensure appropriate application of case definitions, particularly those including community onset.

Central line-associated bloodstream infections in Australian ICUs: evaluating modifiable and non-modifiable risks in Victorian healthcare facilities.

Central line-associated bloodstream infections (CLABSIs) in intensive care units (ICUs) result in poor clinical outcomes and increased costs. Although frequently regarded as preventable, infection risk may be influenced by non-modifiable factors. The objectives of this study were to evaluate organisational factors associated with CLABSI in Victorian ICUs to determine the nature and relative contribution of modifiable and non-modifiable risk factors. Data captured by the Australian and New Zealand Intensive Care Society regarding ICU-admitted patients and resources were linked to CLABSI surveillance data collated by the Victorian Healthcare Associated Infection Surveillance System between 1 January 2010 and 31 December 2013. Accepted CLABSI surveillance methods were applied and hospital/patient characteristics were classified as 'modifiable' and 'non-modifiable', enabling longitudinal Poisson regression modelling of CLABSI risk. In total, 26 ICUs were studied. Annual CLABSI rates were 1·72, 1·37, 1·00 and 0·93/1000 CVC days for 2010-2013. Of non-modifiable factors, the number of non-invasively ventilated patients standardised to total ICU bed days was found to be independently associated with infection (RR 1·07; 95% CI 1·01-1·13; P = 0·030). Modelling of modifiable risk factors demonstrated the existence of a policy for mandatory ultrasound guidance for central venous catheter (CVC) localisation (RR 0·51; 95% CI 0·37-0·70; P < 0·001) and increased number of sessional specialist full-time equivalents (RR 0·52; 95% CI 0·29-0·93; P = 0·027) to be independently associated with protection against infection. Modifiable factors associated with reduced CLABSI risk include ultrasound guidance for CVC localisation and increased availability of sessional medical specialists.

Epidemiology of infections and antimicrobial use in Australian haemodialysis outpatients: findings from a Victorian surveillance network, 2008-2015.

BACKGROUND: Patients with chronic renal failure who require haemodialysis are at high risk for infections. AIM: To determine the burden of bloodstream and local access-related infections and the prescribing patterns for intravenous antibiotics in Australian haemodialysis outpatients. METHODS: A surveillance network was established following stakeholder consultation, with voluntary participation by haemodialysis centres and data collation by the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Definitions for infection and intravenous antimicrobial starts were based upon methods employed by the Centers for Disease Control and Prevention. Longitudinal mixed-effects Poisson regression was used to model time-trends for the period 2008-2015. FINDINGS: Forty-eight of 78 Victorian dialysis centres participated in the network, with 3449 events reported over 78,826 patient-months. Rates of bloodstream infection, local infection and intravenous antimicrobial starts were much higher for patients with tunnelled central lines (2.60, 1.41, and 3.37 per 100 patient-months, respectively), compared to those with arteriovenous fistulae (0.27, 0.23, and 0.73 per 100 patient-months, respectively) and arteriovenous grafts (0.76, 1.08, 1.50 per 100 patient-months, respectively). Staphylococcus aureus was the most frequent pathogen, with meticillin-resistant isolates (MRSA) responsible for 14.0%. Access-related infections diminished significantly across all vascular-access modalities over time. Vancomycin contributed nearly half of all antimicrobial starts consistently throughout the study period. CONCLUSION: Risk for bloodstream and local access-related infections is highest in Australian haemodialysis patients with tunnelled central lines. S. aureus is the most frequent cause of infection, with a low incidence of MRSA. Future programmes should evaluate infection prevention practices and appropriateness of antibiotic prescribing in this population.

Epidemiology of Clostridium difficile infections in Australia: enhanced surveillance to evaluate time trends and severity of illness in Victoria, 2010-2014.

BACKGROUND: With epidemic strains of Clostridium difficile posing a substantial healthcare burden internationally, there is a need for longitudinal evaluation of Clostridium difficile infection (CDI) events in Australia. AIM: To evaluate time trends and severity of illness for CDI events in Australian healthcare facilities. METHODS: All CDI events in patients admitted to Victorian public hospitals between 1(st) October 2010 and 31(st) December 2014 were reported to the Victorian Healthcare Associated Infection Surveillance System. CDI was defined as the isolation of a toxin-producing C. difficile organism in a diarrhoeal specimen, and classified as community-associated (CA-CDI) or healthcare-associated (HA-CDI). Severe disease was defined as admission to an intensive care unit, requirement for surgery and/or death due to infection. Time trends were examined using a mixed-effects Poisson regression model, and the Walter and Edward test of seasonality was applied to evaluate potential cyclical patterns. FINDINGS: In total, 6736 CDI events were reported across 89 healthcare facilities. Of these, 4826 (71.6%) were HA-CDI, corresponding to a rate of 2.49/10,000 occupied bed days (OBDs). The incidence of HA-CDI was highest in the fifth quarter of surveillance (3.6/10,000 OBDs), followed by a reduction. Severe disease was reported in 1.66% of events, with the proportion being significantly higher for CA-CDI compared with HA-CDI (2.21 vs 1.45%, P = 0.03). The highest and lowest incidence of HA-CDI occurred in March and October, respectively. CONCLUSIONS: A low incidence of HA-CDI was reported in Victoria compared with US/European surveillance reports. Seasonality was evident, together with diminishing HA-CDI rates in 2012-2014. Severe infections were more common in CA-CDI, supporting future enhanced surveillance in community settings.

Implementation of standardised surveillance for Clostridium difficile infections in Australia: initial report from the Victorian Healthcare Associated Infection Surveillance System.

Detection of a hypervirulent strain of Clostridium difficile in Victoria led to commencement of targeted surveillance for C. difficile infection in 2010. Cases were reported through the Victorian Healthcare Associated Infection Surveillance System. Between 1 October 2010 and 31 March 2011, 477 cases of C. difficile infection were identified; 11 (2.3%) secondary to a hypervirulent strain. Three hundred and seventy (1.7 per 10,000 occupied bed days) were healthcare associated. Data reflect successful implementation of continuous surveillance for C. difficile infection. With hypervirulent C. difficile infection now reported in other Australian states, development of a national data repository for C. difficile infection is necessary.

Development and application of a flow cytometric potency assay for DNA vaccines.

We have developed a rapid, reliable, and sensitive quantitative flow cytometric assay to measure the in vitro potency and stability of DNA vaccines to be delivered either by particle-mediated epidermal delivery (PMED) or by electroporation. The method involves transfecting cells with test DNA and comparing the measured antigen expression to that generated with expression from known quantities of reference material DNA. The assay was adapted for performance under Good Laboratory Practice (GLP) guidelines and was successfully utilized to perform potency testing in support of a Phase I study for two hantavirus DNA vaccines delivered by gene gun. The results from the potency assays conducted over a 24-month period using this method proved to be highly reproducible with high signal-to-noise ratios. The assay was also adapted to assess the in vitro potency and stability of a DNA vaccine for Venezuelan equine encephalitis virus that will be delivered by electroporation. Our results indicate that this assay can be readily applied to support potency and stability testing of numerous DNA vaccines delivered by various methods, including multiagent vaccines.

Electronic antibiotic stewardship--reduced consumption of broad-spectrum antibiotics using a computerized antimicrobial approval system in a hospital setting.

OBJECTIVES: Antibiotic stewardship is important, but the ideal strategy for providing stewardship in a hospital setting is unknown. A practical, sustainable and transferable strategy is needed. This study evaluates the impact of a novel computerized antimicrobial approval system on antibiotic-prescribing behaviour in a hospital. Effects on drug consumption, antibiotic resistance patterns of local bacteria and patient outcomes were monitored. METHODS: The study was conducted at a tertiary referral teaching hospital in Melbourne, Australia. The system was deployed in January 2005 and guided the use of 28 restricted antimicrobials. Data were collected over 7 years: 5 years before and 2 years after deployment. Uptake of the system was evaluated using an in-built audit trail. Drug utilization was prospectively monitored using pharmacy data (as defined daily doses per 1000 bed-days) and analysed via time-series analysis with segmental linear regression. Antibiograms of local bacteria were prospectively evaluated. In-hospital mortality and length of stay for patients with Gram-negative bacteraemia were also reported. RESULTS: Between 250 and 300 approvals were registered per month during 2006. The gradients in the use of third- and fourth-generation cephalosporins (+0.52, -0.05, -0.39; P < 0.01), glycopeptides (+0.27, -0.53; P = 0.09), carbapenems (+0.12, -0.24; P = 0.21), aminoglycosides (+0.15, -0.27; P < 0.01) and quinolones (+0.76, +0.11; P = 0.08) all fell after deployment, while extended-spectrum penicillin use increased. Trends in increased susceptibility of Staphylococcus aureus to methicillin and improved susceptibility of Pseudomonas spp. to many antibiotics were observed. No increase in adverse outcomes for patients with Gram-negative bacteraemia was observed. CONCLUSIONS: The system was successfully adopted and significant changes in antimicrobial usage were demonstrated.

Interhospital comparisons of coronary artery bypass graft surgical site infection rates differ if donor sites are excluded.

The advent of public reporting of hospital-acquired infection rates has sparked ongoing discussion about the most appropriate surveillance data to present. When we used different numerators to calculate rates of surgical site infection following coronary artery bypass graft surgery, we found that some hospitals' rates and their rankings were notably affected.

Compliance with surgical antibiotic prophylaxis--reporting from a statewide surveillance programme in Victoria, Australia.

A statewide assessment of the compliance of surgical antibiotic prophylaxis (SAP) with guidelines was undertaken for large public hospitals in Victoria, Australia. This was carried out using data collected as part of a surveillance system for hospital-acquired infections. The study population comprised patients in Victorian public hospitals with >100 beds (N=27) undergoing cardiac surgical procedures, hip or knee arthroplasty, cholecystectomy, appendectomy, colon surgery or hysterectomy over a 21-month period. Australian guidelines recommend SAP for all 10 643 surgical procedures included in this study. Combining all procedures, 87% received SAP, the choice of antibiotic was concordant with guidelines for 53.3% of procedures, and the choice of antibiotic was considered to be 'adequate but not concordant' for 23.9% of procedures. SAP was considered to be inadequate for 18.9% of procedures. A large number of antibiotic regimens were utilized for cardiac and orthopaedic surgery. Documentation of timing of administration was not submitted for more than half of all procedures. Timing was concordant with guidelines for 76.4% of procedures when documented. Prophylactic antibiotic choice was generally more concordant with guidelines for cardiac and orthopaedic procedures than for other types of surgery. However, even for these procedures, where infections carry high morbidity, SAP was sometimes inadequate. Regular reporting on SAP compliance from data collected during surveillance for hospital-acquired infections is achievable. This should lead to improvements in both compliance and documentation.

The efficacy of continuous infusion flucloxacillin in home therapy for serious staphylococcal infections and cellulitis.

The efficacy and safety of continuous infusion flucloxacillin as home-based treatment was assessed in 62 consecutive patients with proven serious methicillin-susceptible Staphylococcus aureus (MSSA) infections (n = 36) and cellulitis (n = 26). The treatment was well tolerated and resulted in cure or adequate suppression of infection in 27 of 28 (96%) patients in the serious MSSA infection group, and in 24 of 26 (92%) patients in the cellulitis group.

Nosocomial infections in combined medical-surgical intensive care units in the United States.

OBJECTIVE: To describe the epidemiology of nosocomial infections in combined medical-surgical (MS) intensive care units (ICUs) participating in the National Nosocomial Infection Surveillance (NNIS) System. DESIGN: Analysis of surveillance data on 498,998 patients with 1,554,070 patient-days, collected between 1992 and 1998 from 205 MS ICUs following the NNIS Intensive Care Unit protocol, representing 152 participating NNIS hospitals in the United States. RESULTS: Infections at three major sites represented 68% of all reported infections (nosocomial pneumonia, 31%; urinary tract infections (UTIs), 23%; and primary bloodstream infections (BSIs), 14%: 83% of episodes of nosocomial pneumonia were associated with mechanical ventilation, 97% of UTIs occurred in catheterized patients, and 87% of primary BSIs in patients with a central line. In patients with primary BSIs, coagulase-negative staphylococci (39%) were the most common pathogens reported; Staphylococcus aureus (12%) was as frequently reported as enterococci (11%). Coagulase-negative staphylococcal BSIs were increasingly reported over the 6 years, but no increase was seen in candidemia or enterococcal bacteremia. In patients with pneumonia, S. aureus (17%) was the most frequently reported isolate. Of reported isolates, 59% were gram-negative bacilli. In patients with UTIs, Escherichia coli (19%) was the most frequently reported isolate. Of reported isolates, 31% were fungi. In patients with surgical-site infections, Enterococcus (17%) was the single most frequently reported pathogen. Device-associated nosocomial infection rates for BSIs, pneumonia, and UTIs did not correlate with length of ICU stay, hospital bed size, number of beds in the ICU, or season. Combined MS ICUs in major teaching hospitals had higher device-associated infection rates compared to all other hospitals with combined medical-surgical units. CONCLUSIONS: Nosocomial infections in MS ICUs at the most frequent infection sites (bloodstream, urinary, and respiratory tract) almost always were associated with use of an invasive device. Device-associated infection rates were the best available comparative rates between combined MS ICUs, but the distribution of device-associated rates should be stratified by a hospital's major teaching affiliation status.

Retinal structure and function in an animal model that replicates the biochemical hallmarks of desmosterolosis.

Desmosterolosis is a rare, autosomal recessive, human disease characterized by multiple congenital anomalies in conjunction with grossly elevated levels of desmosterol and markedly reduced levels of cholesterol in all bodily tissues. Herein, we evaluated retinal sterol composition, histology, and electrophysiological function in an animal model that exhibited the biochemical features of desmosterolosis, produced by treating pregnant rats and their progeny with U18666A, an inhibitor of desmosterol reductase. Treated rats had cataracts, were substantially smaller, and had markedly high levels of desmosterol and profoundly low levels of cholesterol in their retinas and other tissues compared to age-matched controls. However, their retinas were histologically normal and electrophysiologically functional. These results suggest that desmosterol may be able to replace cholesterol in the retina, both structurally and functionally. These findings are discussed in the context of "sterol synergism".