Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes.

Recent studies recognize a vast diversity of noncoding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated) DNA probes detects surprisingly abundant euchromatin-associated RNA comprised predominantly of repeat sequences (C0T-1 RNA), including LINE-1. C0T-1-hybridizing RNA strictly localizes to the interphase chromosome territory in cis and remains stably associated with the chromosome territory following prolonged transcriptional inhibition. The C0T-1 RNA territory resists mechanical disruption and fractionates with the nonchromatin scaffold but can be experimentally released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds to aberrant chromatin distribution and condensation. C0T-1 RNA has several properties similar to XIST chromosomal RNA but is excluded from chromatin condensed by XIST. These findings impact two "black boxes" of genome science: the poorly understood diversity of noncoding RNA and the unexplained abundance of repetitive elements.

Early-career general practitioners' antibiotic prescribing for acute infections: a systematic review.

BACKGROUND: Antimicrobial resistance is a worldwide threat, exacerbated by inappropriate prescribing. Most antibiotic prescribing occurs in primary care. Early-career GPs are important for the future of antibiotic prescribing and curbing antimicrobial resistance. OBJECTIVES: To determine antibiotic prescribing patterns by early-career GPs for common acute infections. METHODS: A systematic literature search was conducted using PubMed, Embase and Scopus. Two authors independently screened abstracts and full texts for inclusion. Primary outcomes were antibiotic prescribing rates for common acute infections by GPs with experience of 10 years or less. Secondary outcomes were any associations between working experience and antibiotic prescribing. RESULTS: Of 1483 records retrieved, we identified 41 relevant studies. Early-career GPs were less likely to prescribe antibiotics compared with their more experienced colleagues (OR range 0.23-0.67). Their antibiotic prescribing rates for 'any respiratory condition' ranged from 14.6% to 52%, and for upper respiratory tract infections from 13.5% to 33%. Prescribing for acute bronchitis varied by country, from 15.9% in Sweden to 26% in the USA and 63%-73% in Australia. Condition-specific data for all other included acute infections, such as sinusitis and acute otitis media, were limited to the Australian context. CONCLUSIONS: Early-career GPs prescribe fewer antibiotics than later-career GPs. However, there are still significant improvements to be made for common acute conditions, as their prescribing is higher than recommended benchmarks. Addressing antimicrobial resistance requires an ongoing worldwide effort and early-career GPs should be the target for long-term change.

Single-molecule analysis of solvent-responsive mechanically interlocked ring polymers and the effects of nanoconfinement from coarse-grained simulations.

In this study, we simulate mechanically interlocked semiflexible ring polymers inspired by the minicircles of kinetoplast DNA (kDNA) networks. Using coarse-grained molecular dynamics simulations, we investigate the impact of molecular topological linkage and nanoconfinement on the conformational properties of two- and three-ring polymer systems in varying solvent qualities. Under good-quality solvents, for two-ring systems, a higher number of crossing points lead to a more internally constrained structure, reducing their mean radius of gyration. In contrast, three-ring systems, which all had the same crossing number, exhibited more similar sizes. In unfavorable solvents, structures collapse, forming compact configurations with increased contacts. The morphological diversity of structures primarily arises from topological linkage rather than the number of rings. In three-ring systems with different topological conformations, structural uniformity varies based on link types. Extreme confinement induces isotropic and extended conformations for catenated polymers, aligning with experimental results for kDNA networks and influencing the crossing number and overall shape. Finally, the flat-to-collapse transition in extreme confinement occurs earlier (at relatively better solvent conditions) compared to non-confined systems. This study offers valuable insights into the conformational behavior of mechanically interlocked ring polymers, highlighting challenges in extrapolating single-molecule analyses to larger networks such as kDNA.

Inhaled Reliever Therapies for Asthma: A Systematic Review and Meta-Analysis.

Importance: The optimal inhaled reliever therapy for asthma remains unclear. Objective: To compare short-acting ß agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting ß agonist formoterol combined with ICS for asthma. Data Sources: The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Study Selection: Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Main Outcomes and Measures: Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. Results: A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). Conclusions and Relevance: In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

An overview of outputs of Aboriginal- and Torres Strait Islander-related publications from University Departments of Rural Health in Australia; 2010-2021.

INTRODUCTION: Disparities in the health of Indigenous people and in the health of rural populations are well described. University Departments of Rural Health (UDRHs) in Australia are federally funded under a program to address ongoing challenges with health workforce distribution for rural and remote areas. They have a significant role in research in regional, rural and remote areas, including research related to Indigenous health. However, a comprehensive analysis of their contributions to original Indigenous health related to Indigenous health is lacking. OBJECTIVE: This study examines the contributions of UDRHs to Indigenous issues through analysis of publications of UDRHs focused on Indigenous health during the period 2010-2021. DESIGN: This paper examines a database of UDRH Indigenous-related publications from 2010 to 2021. FINDINGS: A total of 493 publications to which UDRHs contributed were analysed, including 354 original research articles. Health services research was the most common category, followed by epidemiology and papers exploring Indigenous culture and health. While health services research substantially increased over the period, the numbers of original research papers specifically focused on Indigenous workforce issues, whether related to Indigenous people, students or existing workforce was relatively small. DISCUSSION: This broad overview shows the nature and trends in Indigenous health research by UDRHs and makes evident a substantial contribution to Indigenous health research, reflecting their commitment to improving the health and well-being of Indigenous communities. CONCLUSIONS: The analysis can help direct future efforts, and future analyses should delve deeper into the impact of this research and further engage Indigenous researchers.

Implementing paediatric appropriate use criteria for endotracheal suction to reduce complications in mechanically ventilated children with respiratory infections.

BACKGROUND: Endotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections. OBJECTIVE: The objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions. METHODS: A mixed-method, pre-implementation-post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models. RESULTS: Data from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use. CONCLUSIONS: Implementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections.

Surgical site infection prophylaxis: what have we learned and are we making progress?

PURPOSE OF REVIEW: This review aims to discuss the current state of surgical antimicrobial prophylaxis (SAP) evidence for surgical site infection prevention. Despite decades of research, knowledge gaps persist in identifying optimal SAP regimens. RECENT FINDINGS: Recent randomised controlled trials highlight ongoing heterogeneity in study design. Key new findings support the use of oral preoperative SAP for colorectal surgery and advise against the use of SAP for transperineal prostate biopsy. There is growing evidence for culture-based SAP over empiric use for transrectal prostate biopsy.Contentious issues remain regarding topical antimicrobials for cardiac procedures involving sternotomy, the necessity of SAP for wire lumpectomy and laparoscopic cholecystectomy for both mild or moderate acute cholecystitis. Procedures where SAP is not indicated, yet research is still being conducted on this topic include dental implants and clean orthopaedic procedures. SUMMARY: Research efforts continue with numerous trials published and registered to determine optimal SAP regimens. However, many efforts are suboptimal due to poor statistical design and redundant questions already answered by existing literature. To improve practice and influence surgeons prescribing behaviour future RCTs should be well powered, with large sample sizes across multiple sites, focusing on clinically relevant questions.

Coarse-grained modeling of polymers with end-on and side-on liquid crystal moieties: Effect of architecture.

Mesogens, which are typically stiff rodlike or disklike molecules, are able to self-organize into liquid crystal (LC) phases in a certain temperature range. Such mesogens, or LC groups, can be attached to polymer chains in various configurations including within the backbone (main-chain LC polymers) or at the ends of side-chains attached to the backbone in an end-on or side-on configuration (side-chain LC polymers or SCLCPs), which can display synergistic properties arising from both their LC and polymeric character. At lower temperatures, chain conformations may be significantly altered due to the mesoscale LC ordering; thus, when heated from the LC ordered state through the LC to isotropic phase transition, the chains return from a more stretched to a more random coil conformation. This can cause macroscopic shape changes, which depend significantly on the type of LC attachment and other architectural properties of the polymer. Here, to study the structure-property relationships for SCLCPs with a range of different architectures, we develop a coarse-grained model that includes torsional potentials along with LC interactions of a Gay-Berne form. We create systems of different side-chain lengths, chain stiffnesses, and LC attachment types and track their structural properties as a function of temperature. Our modeled systems indeed form a variety of well-organized mesophase structures at low temperatures, and we predict higher LC-to-isotropic transition temperatures for the end-on side-chain systems than for analogous side-on side-chain systems. Understanding these phase transitions and their dependence on polymer architecture can be useful in designing materials with reversible and controllable deformations.

"Handing out non-prescribed antibiotics is storing up trouble for the next generation!" Unpacking multistakeholder views of drivers and potential solutions in Ethiopia.

BACKGROUND: Antibiotic resistance is a global health crisis, with inappropriate antibiotic use often being linked to non-prescribed antibiotic dispensing practices. This study aimed to examine the perspectives of multiple stakeholders on the drivers and potential solutions for non-prescribed antibiotic dispensing in Ethiopian community drug retail outlets (CDROs). Despite the prescription only use policies, the practice remains prevalent in Ethiopia. Many factors are thought to contribute to this issue, although little research is available for non-urban settings. METHODS: A phenomenological qualitative study was conducted. Pharmacy professionals (owners or employees) working in non-urban towns CDROs were selected through a simulated client study, which identified CDROs that had dispensed antibiotics without a prescription. Some high-level decision makers in the Ethiopian health system were also purposively selected. Interviews were conducted in-person and over the phone or via Zoom. The interview data were transcribed verbatim, translated to English, and thematically analysed. NVivo 12 software was used to assist with coding. RESULTS: CDRO pharmacy professionals (n = 18) and five decision makers were interviewed. Most professionals (61%) were pharmacists working in drug stores, with one to 11 years of work experience. Several contributing factors were identified at the level of patients, CDRO staff, and the healthcare system. These included economic interests, inadequate knowledge and inappropriate attitudes about antibiotic use or supply, and issues within the healthcare system included inaccessibility and insufficient capacity, absence of or a weak enforcement of prescription-only regulations or service supervision. Additionally, patient-related factors included a lack of knowledge and inappropriate attitudes about antibiotics use and their supply, previous successful treatment experience and a culture of seeking out antibiotics. CONCLUSIONS: A complex set of modifiable factors related to patients, CDRO staff and healthcare system were identified that contribute to the non-prescribed supply of antibiotics. Due to this complexity, a single solution will not resolve the issues. Therefore, a range of multifaceted solutions have been suggested, including stricter regulation, increasing availability and accessibility of healthcare services, collaboration, and local consensus-building among CDROs, regular training for CDRO staff, and using community social events to educate the public about responsible use of antibiotics.

Improving difficult peripheral intravenous access requires thought, training and technology (DART3): a stepped-wedge, cluster randomised controlled trial protocol.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. METHODS: A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie's Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. DISCUSSION: Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. TRIAL REGISTRATION: Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).

Clinical stakeholder preferences for paediatric cardiac surgery outcome reporting in Australia and New Zealand.

BACKGROUND: Outcome reporting is an essential element of quality assurance. Evaluation of the information needs of stakeholders of outcome reporting is limited. This study aimed to examine stakeholder preferences for the content, format, and dissemination of paediatric cardiac surgery performance data in Australia and New Zealand. METHODS: Semi-structured interviews were completed with a purposive sample of Queensland stakeholders to evaluate their attitudes and expectations regarding reporting of paediatric cardiac surgery outcomes. The interviews were audio-recorded and transcribed. Two researchers used an interpretive description approach to analyse the transcripts qualitatively. RESULTS: Nineteen stakeholders were interviewed including fifteen clinicians, four parents, one hospital administrator, and one consumer advocate were interviewed. Mortality was highlighted as the area of greatest interest in reports by clinical and consumer groups. The majority preferred hospital rather than individual/clinician-level reporting. Annual reports were preferred by clinicians who requested reports be distributed electronically. CONCLUSIONS: The evidence generated from outcome reporting in paediatric cardiac surgery is highly desired by clinicians, administrators, parents, families, and advocacy groups. Clinical users prefer information to assist in clinical decision-making, while families seek personalised information at crucial time points in their clinical journey.

Quality measurement and surveillance platforms in critically ill children: A scoping review.

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin.

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A's role with repeat-rich C0T-1 hnRNA (repeat-rich heterogeneous nuclear RNA), shown recently to comprise mostly intronic sequences of pre-mRNAs and diverse long non-coding RNAs (lncRNAs). Our results show that SAF-A mutants cause dramatic changes to cytological chromatin condensation through dominant negative effects on C0T-1 RNA's association with euchromatin, and likely other nuclear scaffold factors. In contrast, depletion of SAF-A by RNA interference (RNAi) had no discernible impact on C0T-1 RNA, nor did it cause similarly marked chromatin changes as did three different SAF-A mutations. Overall results support the concept that repeat-rich, chromatin-associated RNAs interact with multiple RNA binding proteins (RBPs) in a complex dynamic meshwork that is integral to larger-scale chromatin architecture and collectively influences cytological-scale DNA condensation.

Magnitude of non-prescribed antibiotic dispensing in Ethiopia: a multicentre simulated client study with a focus on non-urban towns.

OBJECTIVES: Non-prescription dispensing of antibiotics significantly contributes to widespread antibiotic misuse, which in turn hastens the occurrence of antibiotic resistance. It is believed to be common in Ethiopia despite prescription-only regulations. We aimed to quantify non-prescription dispensing of antibiotics in community drug retail outlets (CDROs) with a focus on non-urban towns in the Amhara region of Ethiopia. METHODS: A multicentre simulated client (SC) study was conducted to measure the non-prescription provision of antibiotics in 225 consenting CDROs. Each CDRO was visited twice by two trained SCs, one to present pre-prepared clinical case scenarios and the other to directly request specific antibiotics. Descriptive statistical analysis was performed to report the findings. RESULTS: The study had 450 interactions across the two visits. Non-prescribed antibiotics were obtained in 198 (88%) of the 225 clinical case scenarios-based visits and in 205 (91%) of the 225 direct antibiotic request visits. Most of the supply was at the first level of demand: 84% of the 198 clinical case scenario visits and 95% of the 205 direct antibiotic request visits. CDRO staff requested further information about the patient or the case in 40% of the clinical case scenarios-based visits and 30% of the direct antibiotic request visits. CONCLUSIONS: It was possible to obtain antibiotics without prescription from a high proportion of CDROs, both in clinical scenario-based and direct antibiotic request interactions. Multifaceted interventions including stringent regulatory enforcement, frequent CDRO practice surveillance, CDRO staff training and community health education are needed with greater emphasis on rural areas.

Economic evaluation of antimicrobial stewardship in primary care: a systematic review and quality assessment.

BACKGROUND: Primary care accounts for 80%-90% of antimicrobial prescriptions, making this setting an important focus for antimicrobial stewardship (AMS) interventions. OBJECTIVES: To collate the findings and critically appraise the qualities of economic evaluation studies of AMS or related interventions aimed at reducing inappropriate antimicrobial prescribing in primary care. METHODS: A systematic review of economic evaluations of interventions aimed at reducing inappropriate antimicrobial prescribing in primary care was performed. Published literature were retrieved through a search of Medline, Embase, EconLit and Web of Science databases for the period 2010 to 2020. The quality of the studies was assessed using the Consensus on Health Economic Criteria checklist and Good Practice Guidelines for Decision-Analytic Modelling in Health Technology Assessment. RESULTS: Of the 2722 records identified, 12 studies were included in the review (8 trial-based and 4 modelled evaluations). The most common AMS interventions were communication skills training for health professionals and C-reactive protein point-of-care testing (CRP-POCT). Types of economic evaluations included in the review were cost-effectiveness (7 studies), cost-utility (1), cost-benefit (2), cost-effectiveness and cost-utility (1) and cost analysis (1). While six of the studies found AMS interventions to be cost-effective, the other six reported them as not cost-effective or inconclusive. The quality of the studies ranged from good to low. CONCLUSIONS: There were significant variations in cost-effectiveness of AMS interventions across studies and depending on the inclusion of cost components such as the cost of antimicrobial resistance. However, communication skills training and CRP-POCT were frequently cost-effective or cost-beneficial for reducing inappropriate antimicrobial prescribing.

Developing a framework for implementing opioid stewardship programmes in Australian hospital settings.

There is growing interest in strategies to improve patient safety with prescription opioids, collectively known as opioid stewardship (OS). This study aimed to develop a framework to facilitate the implementation of OS in the Australian acute hospital setting. Using a Modified Delphi Technique, a diverse stakeholder panel (including patient representatives and multidisciplinary healthcare professionals) was selected. A survey based on the results of a literature review was sent to the panel for appraisal. In line with standard Delphi methodology, the primary outcome for each element was reaching consensus of at least 70% of the participants on the importance of its inclusion in the framework. The survey allowed the participants to suggest new items for inclusion in subsequent rounds or rephrase existing items. Of the 29 participants who completed the survey, the majority (23/29) were regularly involved in providing direct patient care. Twenty-six of 27 items reached the 70% threshold for agreement for importance after the first round. The remaining item not agreed on in the initial round was modified based on comments received and reached 100% agreement on importance at the second round. There was greater than 85% agreement on importance of 24 of 27 items for inclusion in a framework with 8 of 27 reaching a 100% level of agreement. We have developed a framework for OS in the Australian acute hospital settings that may be used to guide health services to prioritise and plan strategies to improve opioid use.

Use of a Victorian statewide surveillance programme to evaluate the burden of healthcare-associated Staphylococcus aureus bacteraemia and Clostridioides difficile infection in patients with cancer.

BACKGROUND: Patients with cancer are at high risk for infection, but the epidemiology of healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) and Clostridioides difficile infection (HA-CDI) in Australian cancer patients has not previously been reported. AIMS: To compare the cumulative aggregate incidence and time trends of HA-SAB and HA-CDI in a predefined cancer cohort with a mixed statewide patient population in Victoria, Australia. METHODS: All SAB and CDI events in patients admitted to Victorian healthcare facilities between 1 July 2010 and 31 December 2018 were submitted to the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Descriptive analyses and multilevel mixed-effects Poisson regression modelling were applied to a standardised data extract. RESULTS: In total, 10 608 and 13 118 SAB and CDI events were reported across 139 Victorian healthcare facilities, respectively. Of these, 89 (85%) and 279 (88%) were healthcare-associated in the cancer cohort compared with 34% (3561/10 503) and 66% (8403/12 802) in the statewide cohort. The aggregate incidence was more than twofold higher in the cancer cohort compared with the statewide cohort for HA-SAB (2.25 (95% confidence interval (CI): 1.74-2.77) vs 1.11 (95% CI: 1.07-1.15) HA-SAB/10 000 occupied bed-days) and threefold higher for HA-CDI (6.26 (95% CI: 5.12-7.41) vs 2.31 (95% CI: 2.21-2.42) HA-CDI/10 000 occupied bed-days). Higher quarterly diminishing rates were observed in the cancer cohort than the statewide data for both infections. CONCLUSIONS: Our findings demonstrate a higher burden of HA-SAB and HA-CDI in a cancer cohort when compared with state data and highlight the need for cancer-specific targets and benchmarks to meaningfully support quality improvement.

Appropriate use criteria for endotracheal suction interventions in mechanically ventilated children: The RAND/UCLA development process.

OBJECTIVES: Endotracheal suction is an invasive airway clearance technique used in mechanically ventilated children. This article outlines the methods used to develop appropriate use criteria for endotracheal suction interventions in mechanically ventilated paediatric patients. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop paediatric appropriate use criteria. This included the following sequential phases of defining scope and key terms, a literature review and synthesis, expert multidisciplinary panel selection, case scenario development, and appropriateness ratings by an interdisciplinary expert panel over two rounds. The panel comprised experts in the fields of paediatric and neonatal intensive care, respiratory medicine, infectious diseases, critical care nursing, implementation science, retrieval medicine, and education. Case scenarios were developed iteratively by interdisciplinary experts and derived from common applications or anticipated intervention uses, as well as from current clinical practice guidelines and results of studies examining interventions efficacy and safety. Scenarios were rated on a scale of 1 (harm outweighs benefit) to 9 (benefit outweighs harm), to define appropriate use (median: 7 to 9), uncertain use (median: 4 to 6), and inappropriate use (median: 1 to 3) of endotracheal suction interventions. Scenarios were than classified as a level of appropriateness. CONCLUSIONS: The RAND Corporation/University of California, Los Angeles Appropriateness Method provides a thorough and transparent method to inform development of the first appropriate use criteria for endotracheal suction interventions in paediatric patients.

The Paediatric AirWay Suction (PAWS) appropriateness guide for endotracheal suction interventions.

BACKGROUND/OBJECTIVE: Endotracheal suction is an invasive and potentially harmful technique used for airway clearance in mechanically ventilated children. Choice of suction intervention remains a complex and variable process. We sought to develop appropriate use criteria for endotracheal suction interventions used in paediatric populations. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop the Paediatric AirWay Suction appropriateness guide. This included defining key terms, synthesising current evidence, engaging an expert multidisciplinary panel, case scenario development, and two rounds of appropriateness ratings (weighing harm with benefit). Indications (clinical scenarios) were developed from common applications or anticipated use, current practice guidelines, clinical trial results, and expert consultation. RESULTS: Overall, 148 (19%) scenarios were rated as appropriate (benefit outweighs harm), 542 (67%) as uncertain, and 94 (11%) as inappropriate (harm outweighs benefit). Disagreement occurred in 24 (3%) clinical scenarios, namely presuction and postsuction bagging across populations and age groups. In general, the use of closed suction was rated as appropriate, particularly in the subspecialty population 'patients with highly infectious respiratory disease'. Routine application of 0.9% saline for nonrespiratory indications was more likely to be inappropriate/uncertain than appropriate. Panellists preferred clinically indicated suction versus routine suction in most circumstances. CONCLUSION: Appropriate use criteria for endotracheal suction in the paediatric intensive care have the potential to impact clinical decision-making, reduce practice variability, and improve patient outcomes. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.

Factors associated with pyomyositis: A systematic review and meta-analysis.

OBJECTIVES: Pyomyositis, an acute bacterial infection of skeletal muscle usually resulting in abscess formation, is well recognised in tropical regions where it can account for up to 4% of adult surgical admissions. It is increasingly being reported from high-income temperate countries. Pyomyositis occurs across all ages and in both sexes. Mortality ranges from 1% to 23%. Many risk factors have been suggested. We aimed to identify factors associated with pyomyositis. METHODS: We undertook a systematic review and meta-analysis, using PubMed, EMBASE, Scopus and the Cochran Library and hand-searching published papers. The random-effects model meta-analysis was used to calculate pooled estimated odd ratios with the corresponding 95% confidence interval. RESULTS: All studies in the systematic review (n = 25) and the meta-analysis (n = 12) were hospital-based. Seven only included children. Relatively few studies have been published in the last decade, the majority of which are from high-income temperate settings. Staphylococcus aureus was the main organism isolated. Males under the age of 20 predominated, and mortality of up to 20% was reported. Factors associated with pyomyositis were HIV infection (OR = 4.82; 95% CI: 1.67-13.92) and fulfilling an AIDS surveillance definition (OR = 6.08; 95% CI: 2.79-13.23). CONCLUSIONS: Our meta-analysis indicated significant associations between pyomyositis infection and HIV/AIDS. Major gaps in our understanding of the epidemiology, pathogenesis, clinical presentation, and outcome remain, highlighting the need for further research and more systematic studies. Pyomyositis merits consideration as a neglected tropical disease.