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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.
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Introduction: Monitoring healthcare quality is challenging in paediatric critical care due to measure variability, data collection burden, and uncertainty regarding consumer and clinician priorities. Objective: We sought to establish a core quality measure set that (i) is meaningful to consumers and clinicians and (ii) promotes alignment of measure use and collection across paediatric critical care. Design: We conducted a multi-stakeholder Delphi study with embedded consumer prioritisation survey. The Delphi involved two surveys, followed by a consensus meeting. Triangulation methods were used to integrate survey findings prior tobefore the consensus meeting. In the consensus panel, broad agreement was reached on a core measure set, and recommendations were made for future measurement directions in paediatric critical care. Setting and participants: Australian and New Zealand paediatric critical care survivors (aged >18 years) and families were invited to rank measure priorities in an online survey distributed via social media and consumer groups. A concurrent Delphi study was undertaken with paediatric critical care clinicians, policy makers, and a consumer representative. Interventions: None. Main outcome measures: Priorities for quality measures. Results: Respondents to the consumer survey (n = 117) identified (i) nurse-patient ratios; (ii) visible patient goals; and (iii) long-term follow-up as their quality measure priorities. In the Delphi process, clinicians (Round 1 n = 191; Round 2 n = 117 [61% retention]; Round 3 n = 14) and a consumer representative reached broad agreement on a 51-item (61% of 83 initial measures) core measure set. Clinician priorities were (i) nurse-patient ratio; (ii) staff turnover; and (iii) long term-follow up. Measure feasibility was rated low due to a perceived lack of standardised case definitions or data collection burden. Five recommendations were generated. Conclusions: We defined a 51-item core measurement set for paediatric critical care, aligned with clinician and consumer priorities. Next steps are implementation and methodological evaluation in quality programs, and where appropriate, retirement of redundant measures.
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BACKGROUND: Skin and soft tissue infections (SSTIs) are among the most common indications for antimicrobial prescribing in hospitals. Inappropriate antimicrobial use can lead to increased morbidity, unnecessary hospital readmission and increased antimicrobial resistance. This study aims to assess the quality of antimicrobial prescribing practices in SSTI management within Australian hospitals to provide guidance for future practice. METHODS: A retrospective analysis was conducted with data from the National Antimicrobial Prescribing Survey (NAPS). SSTI prescribing data from Hospital NAPS (2013-2022) and surgical site infection data from Surgical NAPS (2016-2022) datasets were analysed. Variables assessed included guideline compliance, appropriateness as per the structured NAPS algorithm and reasons for inappropriateness. RESULTS: From the Hospital NAPS dataset, 40,535 antimicrobial prescriptions for SSTIs were analysed. The most common indication was cellulitis (34.1%; n=13,822), and the most prescribed antimicrobial was flucloxacillin (18.8%; n=7,638). SSTI indications had a lower rate of guideline compliance, but a higher rate of appropriateness compared to all other indications for antimicrobial prescriptions (guideline compliance 66.3%, n=21,035 vs 67.4%, n=156,285 appropriateness 75.6%, n=30,639 vs 72.7%, n=209,383). The most common reason for inappropriateness was incorrect dose or frequency (29.3%; n=2,367). From the Surgical NAPS dataset, 5,674 prescriptions for surgical site infections were analysed. 68.2% (n=3,867) were deemed appropriate. The most common reason for inappropriateness was incorrect dose or frequency (27.7%; n=350). CONCLUSIONS: As SSTIs are a common indication for prescribing an antimicrobial in Australian hospitals, identifying effective antimicrobial stewardship strategies to optimise antimicrobial use for SSTI management is therefore recommended to improve patient outcomes.
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OBJECTIVES: This systematic literature review aimed to explore experiences worldwide of societal preferences integration into health technology assessments (HTAs) for rare diseases (RDs) and orphan drugs (ODs) through the implementation of multicriteria decision analysis (MCDA), discrete choice experiments (DCEs), and person trade-off (PTO) methods, among others. METHODS: A systematic search of the literature was conducted in April 2021 using PubMed, Cochrane, Embase, and Scopus databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach was used for the review phases. Finally, the Promoting Action on Research Implementation in Health Services framework was used to discuss the implementation of these instruments in the RD context. RESULTS: A total of 33 articles met the inclusion criteria. The studies measured societal preferences for RD and OD as part of HTA using MCDA (n = 17), DCE (n = 8), and PTO (n = 4), among other methods (n = 4). These found that patients and clinicians do not prioritize funding based on rarity. The public is willing to allocate funds only if the OD demonstrates effectiveness and improves the quality of life, considering as relevant factors disease severity, unmet health needs, and quality of life. Conversely, HTA agency experts preferred their current approach, placing more weight on cost-effectiveness and evidence quality, even though they expressed concern about the fairness of the drug review process. CONCLUSIONS: MCDA, PTO, and DCE are helpful and transparent methods for assessing societal preferences in HTA for RD and OD. However, their methodological limitations, such as arbitrary criteria selection, subjective scoring methods, framing effects, weighting adaptation, and value measurement models, could make implementation challenging.
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BACKGROUND AND OBJECTIVE: Biosimilars represent an opportunity to realise savings against the costs of innovative medicines. Despite efforts made by stakeholders, there are numerous barriers to the uptake of biosimilars. To realise the promise of biosimilars reducing costs, barriers must be identified, understood, and overcome, and enablers magnified. The aim of this systematic review is to summarise the enablers and barriers affecting uptake of biosimilars through the application of a classification system to organise them into healthcare professional (HCP), patient, or systemic categories. METHODS: A systematic literature search was performed in PubMed, Scopus, CINAHL, eConlit, and Embase. Included were primary research studies published in English between Jan 2017 through June 2023 focused on enablers and barriers affecting uptake of biosimilars. Excluded studies comprised comparisons of biosimilar efficacy and safety versus the reference biologic. One reviewer extracted data that included classification of barriers or enablers, the sub-classification, and the identification of the degree of agency associated with the actor through their role and associations as a mediator within their network, through the application of Actor Network Theory. The data were validated by a second reviewer (PV). RESULTS: Of the 94 studies included, 59 were cross-sectional, 20 were qualitative research, 12 were cohort studies, and three were economic evaluations. Within the review, 51 of the studies included HCP populations and 35 included patients. Policies and guidelines were the most cited group of enablers, overall. Systemic enablers were addressed in 29 studies. For patients, the most frequently cited enabler was positive framing of a biosimilar, while for HCPs, cost benefit was the most frequently noted enabler. The most frequently discussed systemic barrier to biosimilar acceptance was lack of effective policies or guidelines, followed by lack of financial incentives, while the most significant barriers for HCPs and patients, respectively, were their lack of general knowledge about biosimilars and concerns about safety and efficacy. Systemic actors and HCPs most frequently acted with broad degree of agency as mediators, while patient most frequently acted with a narrow degree of agency as mediators within their networks. CONCLUSIONS: Barriers and enablers affecting uptake of biosimilars are interconnected within networks, and can be divided into systemic, HCP, and patient categories. Understanding the agency of actors within networks may allow for more comprehensive and effective approaches. Systemic enablers in the form of policies appear to be the most effective overall levers in affecting uptake of biosimilars, with policy makers advised to give careful consideration to appropriately educating HCPs and positively framing biosimilars for patients.
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Biosimilares Farmacéuticos , Biosimilares Farmacéuticos/economíaRESUMEN
Our qualitative analysis of interviews with remote Australian healthcare professionals found that they require reliable, local antimicrobial resistance (AMR) data reflecting the geographical diversity of the population they serve. The optimal use of AMR data must consider challenges within this setting, including high staff turnover, limited diagnostic capacity, and antibiotic shortages.
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RNA labeled in young mice is detected 2 years later in adult mouse brains.
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ARN Nuclear , ARN , Animales , Ratones , ARN Nuclear/genética , ARN/genética , EncéfaloRESUMEN
Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.
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Terapia de Protones , Radiocirugia , Radioterapia de Intensidad Modulada , Adolescente , Humanos , Niño , Lactante , Adulto Joven , Adulto , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
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.
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Proton-beam therapy (PBT) is a cutting-edge radiation therapy modality that is currently not available in Australia. Comparative photon-proton (CPP) planning is required for the medical treatment overseas programme (MTOP) and will be required for access to PBT in Australia in the future. Comparative planning brings professional development benefits to all members of the radiation therapy team. This service was also created to support future proposals for a PBT facility in Victoria. We report our experience developing an in-house CPP service at Peter MacCallum Cancer Centre. A set of resources to support CPP planning was established. Training of relevant staff was undertaken after which an in-house training programme was developed. A standard protocol for PBT planning parameters was established. All CPP plans were reviewed. Future goals for the CPP planning programme were described. In total, 62 cases were comparatively planned over 54 months. Of these, 60% were paediatric cases, 14% were adolescents and young adults (15-25 years) and 26% were adults. The vast majority (over 75%) of patients comparatively planned required irradiation to the central nervous system including brain and cranio-spinal irradiation. A variety of proton plans were reviewed by international PBT experts to confirm their deliverability. Our team at Peter MacCallum Cancer Centre has gained significant experience in CPP planning and will continue to develop this further. Local expertise will help support decentralisation of patient selection for proton treatments in the near future and the PBT business case in Victoria.
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Neoplasias , Terapia de Protones , Humanos , Niño , Adolescente , Protones , Victoria , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
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 10â 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.
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Médicos Generales , Infecciones del Sistema Respiratorio , Sinusitis , Humanos , Enfermedad Aguda , Antibacterianos/uso terapéutico , Australia , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Pautas de la Práctica en MedicinaRESUMEN
Bolus is commonly used to improve dose distributions in radiotherapy in particular if dose to skin must be optimised such as in breast or head and neck cancer. We are documenting four years of experience with 3D printed bolus at a large cancer centre. In addition to this we review the quality assurance (QA) program developed to support it. More than 2000 boluses were produced between Nov 2018 and Feb 2023 using fused deposition modelling (FDM) printing with polylactic acid (PLA) on up to five Raise 3D printers. Bolus is designed in the radiotherapy treatment planning system (Varian Eclipse), exported to an STL file followed by pre-processing. After checking each bolus with CT scanning initially we now produce standard quality control (QC) wedges every month and whenever a major change in printing processes occurs. A database records every bolus printed and manufacturing details. It takes about 3 days from designing the bolus in the planning system to delivering it to treatment. A 'premium' PLA material (Spidermaker) was found to be best in terms of homogeneity and CT number consistency (80 HU +/- 8HU). Most boluses were produced for photon beams (93.6%) with the rest used for electrons. We process about 120 kg of PLA per year with a typical bolus weighing less than 500 g and the majority of boluses 5 mm thick. Print times are proportional to bolus weight with about 24 h required for 500 g material deposited. 3D printing using FDM produces smooth and reproducible boluses. Quality control is essential but can be streamlined.
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Impresión Tridimensional , Humanos , Garantía de la Calidad de Atención de Salud/normas , Control de Calidad , Planificación de la Radioterapia Asistida por Computador , Tomografía Computarizada por Rayos X , Dosificación Radioterapéutica , Poliésteres/químicaRESUMEN
The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built. We examine two models of large-scale chromatin condensation: X-chromosome inactivation and formation of senescence-associated heterochromatin foci (SAHFs). XIST RNA triggers gene silencing but also formation of the condensed Barr Body (BB), thought to reflect cumulative gene silencing. However, we find Alu-rich regions are depleted from the L1-rich BB, supporting it is a dense core but not the entire chromosome. Alu-rich bands are also gene-rich, affirming our earlier findings that genes localize at the outer periphery of the BB. SAHFs similarly form within each territory by coalescence of syntenic L1 regions depleted for highly Alu-rich DNA. Analysis of senescent cell Hi-C data also shows large contiguous blocks of G-band and R-band DNA remodel as a segmental unit. Entire dark-bands gain distal intrachromosomal interactions as L1-rich regions form the SAHF. Most striking is that sharp Alu peaks within R-bands resist these changes in condensation. We further show that Chr19, which is exceptionally Alu rich, fails to form a SAHF. Collective results show regulation of genome architecture corresponding to large blocks of DNA and demonstrate resistance of segments with high Alu to chromosome condensation.
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BACKGROUND: The health and economic burden of antimicrobial resistance (in Australia is significant. Interventions that help guide and improve appropriate prescribing for acute respiratory tract infections in the community represent an opportunity to slow the spread of resistant bacteria. Clinicians who work in primary care are potentially the most influential health care professionals to address the problem of antimicrobial resistance, because this is where most antibiotics are prescribed. METHODS: A cluster randomised trial was conducted comparing two parallel groups of 27 urban general practices in Queensland, Australia: 13 intervention and 14 control practices, with 56 and 54 general practitioners (GPs), respectively. This study evaluated an integrated, multifaceted evidence-based package of interventions implemented over a 6-month period. The evaluation included quantitative and qualitative components, and an economic analysis. RESULTS: A multimodal package of interventions resulted in a reduction of 3.81 prescriptions per GP per month. This equates to 1280.16 prescriptions for the 56GPs in the intervention practices over the 6-month period. The cost per prescription avoided was A$148. The qualitative feedback showed that the interventions were well received by the GPs and did not impact on consultation time. Providing GPs with a choice of tools might enhance their uptake and support for antimicrobial stewardship in the community. CONCLUSIONS: A multimodal package of interventions to enhance rational prescribing of antibiotics is effective, feasible and acceptable in general practice. Investment in antimicrobial stewardship strategies in primary care may ultimately provide the important returns for public health into the future.
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Antibacterianos , Medicina General , Humanos , Antibacterianos/uso terapéutico , Pautas de la Práctica en Medicina , Medicina Familiar y Comunitaria , AustraliaRESUMEN
BACKGROUND: The use of telehealth has increased dramatically since the beginning of the COVID-19 pandemic. Little is known about how GPs manage acute infections during telehealth, and the potential impact on antimicrobial stewardship. AIM: To explore the experiences and perceptions of GP trainees' and supervisors' use of telehealth, and how it influences their management of acute infections. DESIGN & SETTING: Australian GP registrars (trainees) and supervisors were recruited via email through their training organisations. Semi-structured interviews with 18 participants were conducted between July and August 2022. METHOD: Interviews were transcribed verbatim and analysed using a reflexive thematic approach. RESULTS: We identified six overall themes. 1. Participants experienced impaired diagnostic capacity during telehealth consultations. 2. Attempts to improve diagnostic acuity included various methods, such as having patients self-examine. 3. The management of clinical uncertainty frequently entailed referring patients for in-person assessment, overinvestigating, or overtreating. 4. Antibiotic prescribing decisions during telehealth were informed by less information than were in-person consults, with varying impact. 5. Participants believed that other GPs improperly prescribed antibiotics during telehealth. 6. Supervisors believed that registrars hadn't developed the knowledge or skills to determine when conditions could be managed appropriately via telehealth. CONCLUSION: Telehealth has potential for reducing transmission of acute infections and increasing access to healthcare. However, the implications of GPs, especially less experienced GPs, making diagnoses with less certainty, and consequently compromising antimicrobial stewardship, are a concern. Patient self-assessment tools may improve outcomes of telehealth consultations for acute infections.
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BACKGROUND: The Stewardship Framework (Framework) was developed by an expert clinician group and was designed to provide a mechanism for continuous monitoring of improvement in opioid prescribing in acute hospitals. The aim of this study was to modify the Framework into an Opioid Stewardship Self-Assessment Tool (Self-Assessment Tool), and pilot test the acceptability and its use in a variety of acute hospital settings. METHODS: The Framework was converted into the Self-Assessment Tool to allow hospitals to undertake a gap analysis of their current opioid stewardship activities. To participate hospitals were required to establish a small team and complete the Self-Assessment Tool. Participating sites were recruited using purposive sampling. Responses were tabulated and coded to enable assessment. 'Acceptability' was defined as the completion of the Self-Assessment Tool (response rate, proportion of questions answered) and responder feedback relating to its content. The use of the Tool was categorised based on the level of detail of responses. RESULTS: Nineteen of the 20 facilities approached, agreed to participate. The 16 sites which established a small team to facilitate survey completion are included in the final analysis. The overall response rate was 96 % (413/432) for the (27 survey questions across 16 participating sites), 4 % (19/432) of questions were left unanswered or were not interpretable by the study team. Opportunities were identified to enhance the use of the Self-Assessment Tool, particularly to support its potential to assist reflection and planning of local strategies. CONCLUSION: This study demonstrated that the Self-Assessment Tool was an acceptable method of assessing a facility's opioid stewardship capabilities in a real-world setting. The next iteration will be modified using the insights on how the Tool was used by study participants.
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Analgésicos Opioides , Autoevaluación (Psicología) , Humanos , Analgésicos Opioides/uso terapéutico , Pautas de la Práctica en Medicina , Hospitales , Proyectos de InvestigaciónRESUMEN
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.
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Respiración Artificial , Infecciones del Sistema Respiratorio , Niño , Humanos , Succión/métodos , Intubación Intratraqueal/efectos adversos , Cloruro de SodioRESUMEN
In side-chain liquid crystal polymers (SCLCPs), short side chains are attached on a flexible polymer backbone, and each side chain can have a liquid crystal (LC) group attached at the final bead in either an end-on or a side-on configuration. SCLCPs with random sequences of end-on and side-on LC moieties exhibit nonmonotonic thermal behavior as a function of composition, with some mixed sequences having a lower isotropic to LC phase transition than either purely end-on or side-on configurations. The origin of this nonmonotonic thermal trend lies in the disruption of molecular-level positional ordering and alignment due to the different preferred types of ordering of the different LC attachment types. We compare coarse-grained molecular dynamics (MD) simulations and experiments on SCLCP systems with only one type of LC moiety and demonstrate qualitative agreement in the observed mesophases of end-on and side-on SCLCP systems. Specifically, end-on SCLCPs display a smectic B-like mesophase, with layers of polymer between LC layers, while side-on SCLCPs exhibit a quasi-hexagonal columnar structure of polymer and a nematic surrounding the LC mesophase. Detailed analysis of SCLCP systems with various compositions of these types of LC attachments via MD reveals structural disruption in systems with intermediate compositions. Simulation snapshots and anisotropy ratio measurements show how random SCLCP systems deviate from the expected behavior of prolate or oblate systems in terms of their conformation. This molecular disruption in random SCLCP systems, particularly with a high composition of side-on LC moieties, also significantly impacts the relaxation dynamics. Modifying the composition of the LC type of attachment (molecular structure) is a possible route to tuning both the phase behavior and mechanical response of these systems.
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BACKGROUND: Metronidazole is a commonly prescribed antimicrobial in Australian hospitals. Inappropriate use may increase risks to patient care, such as toxicities and antimicrobial resistance. To date, there is limited information on the quality of metronidazole prescriptions to inform antimicrobial stewardship and quality improvement initiatives. This study aims to describe the quality of metronidazole prescribing practices in Australian hospitals. METHODS: Retrospective data analysis of the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS). Data were collected by auditors at each participating hospital using a standardised auditing tool. All data from 2013 to 2021 were de-identified and analysed descriptively. Variables included were antimicrobial prescribed, indication, guideline compliance and appropriateness. RESULTS: Metronidazole was the fifth most prescribed antimicrobial in the Hospital NAPS dataset (2013-2021), accounting for 5.7 % (n = 14,197) of all antimicrobial prescriptions (n = 250,863). The proportion of metronidazole prescriptions declined by 2 % from 2013 to 2021 (p < 0.001). The most common indications were surgical prophylaxis (15.3 %), diverticulitis (9.4 %), aspiration pneumonia (7.3 %). Over half (53.5 %) of metronidazole prescriptions were deemed compliant with prescribing guidelines and 67.8 % were deemed appropriate. These rates were comparatively lower than the overall results of all antimicrobials. The primary documented reason for inappropriateness was that the spectrum was too broad (34.2 %). Surgical prophylaxis had the lowest rates of guideline compliance (53.8 %) and appropriateness (54.3 %). CONCLUSIONS: Metronidazole remains widely used in Australian hospitals with suboptimal rates of guideline compliance and appropriateness. A noted area for improvement that we identified was using metronidazole when its spectrum was too broad, possibly when anaerobic therapy is unnecessary. With increasing international adoption of the Hospital NAPS programme, future comparative studies will be critical to identify global trends of antimicrobial prescribing quality. Antimicrobial stewardship (AMS) programmes have proven to be effective in improving prescribing quality and should be considered to specifically target improvements in metronidazole prescribing.