Impact of a prospective feedback loop aimed at reducing non-beneficial treatments in older people admitted to hospital and potentially nearing the end of life. A cluster stepped-wedge randomised controlled trial.

OBJECTIVES: To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life. DESIGN: Prospective stepped-wedge cluster randomised trial with usual care and intervention phases. SETTING: Three large tertiary public hospitals in south-east Queensland, Australia. PARTICIPANTS: 14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84 years) who were potentially near the end of life and flagged at risk of non-beneficial treatment. INTERVENTION: The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35 weeks across the three hospitals. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk. RESULTS: There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03). CONCLUSIONS: This nudge intervention was not sufficient to reduce the trial's non-beneficial treatment outcomes in older hospital patients. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

Enhancing gestational diabetes mellitus risk assessment and treatment through GDMPredictor: a machine learning approach.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious health concern that affects pregnant women worldwide and can lead to adverse pregnancy outcomes. Early detection of high-risk individuals and the implementation of appropriate treatment can enhance these outcomes. METHODS: We conducted a study on a cohort of 3467 pregnant women during their pregnancy, with a total of 5649 clinical and biochemical records collected. We utilized this dataset as our training dataset to develop a web server called GDMPredictor. The GDMPredictor utilizes advanced machine learning techniques to predict the risk of GDM in pregnant women. We also personalize treatment recommendations based on essential biochemical indicators, such as A1MG, BMG, CysC, CO2, TBA, FPG, and CREA. Our assessment of GDMPredictor's effectiveness involved training it on the dataset of 3467 pregnant women and measuring its ability to predict GDM risk using an AUC and auPRC. RESULTS: GDMPredictor demonstrated an impressive level of precision by achieving an AUC score of 0.967. To tailor our treatment recommendations, we use the GDM risk level to identify higher risk candidates who require more intensive care. The GDMPredictor can accept biochemical indicators for predicting the risk of GDM at any period from 1 to 24 weeks, providing healthcare professionals with an intuitive interface to identify high-risk patients and give optimal treatment recommendations. CONCLUSIONS: The GDMPredictor presents a valuable asset for clinical practice, with the potential to change the management of GDM in pregnant women. Its high accuracy and efficiency make it a reliable tool for doctors to improve patient outcomes. Early identification of high-risk individuals and tailored treatment can improve maternal and fetal health outcomes http://www.bioinfogenetics.info/GDM/ .

Process evaluation of a tailored nudge intervention to promote appropriate care and treatment of older patients at the end-of-life.

BACKGROUND: Non-beneficial treatment affects a considerable proportion of older people in hospital, and some will choose to decline invasive treatments when they are approaching the end of their life. The Intervention for Appropriate Care and Treatment (InterACT) intervention was a 12-month stepped wedge randomised controlled trial with an embedded process evaluation in three hospitals in Brisbane, Australia. The aim was to increase appropriate care and treatment decisions for older people at the end-of-life, through implementing a nudge intervention in the form of a prospective feedback loop. However, the trial results indicated that the expected practice change did not occur. The process evaluation aimed to assess implementation using the Consolidated Framework for Implementation Research, identify barriers and enablers to implementation and provide insights into the lack of effect of the InterACT intervention. METHODS: Qualitative data collection involved 38 semi-structured interviews with participating clinicians, members of the executive advisory groups overseeing the intervention at a site level, clinical auditors, and project leads. Online interviews were conducted at two times: implementation onset and completion. Data were coded to the Consolidated Framework for Implementation Research and deductively analysed. RESULTS: Overall, clinicians felt the premise and clinical reasoning behind InterACT were strong and could improve patient management. However, several prominent barriers affected implementation. These related to the potency of the nudge intervention and its integration into routine clinical practice, clinician beliefs and perceived self-efficacy, and wider contextual factors at the health system level. CONCLUSIONS: An intervention designed to change clinical practice for patients at or near to end-of-life did not have the intended effect. Future interventions targeting this area of care should consider using multi-component strategies that address the identified barriers to implementation and clinician change of practice. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619000675123p (approved 06/05/2019).

From pilot to a multi-site trial: refining the Early Detection of Deterioration in Elderly Residents (EDDIE +) intervention.

BACKGROUND: Early Detection of Deterioration in Elderly Residents (EDDIE +) is a multi-modal intervention focused on empowering nursing and personal care workers to identify and proactively manage deterioration of residents living in residential aged care (RAC) homes. Building on successful pilot trials conducted between 2014 and 2017, the intervention was refined for implementation in a stepped-wedge cluster randomised trial in 12 RAC homes from March 2021 to May 2022. We report the process used to transition from a small-scale pilot intervention to a multi-site intervention, detailing the intervention to enable future replication. METHODS: The EDDIE + intervention used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide the intervention development and refinement process. We conducted an environmental scan; multi-level context assessments; convened an intervention working group (IWG) to develop the program logic, conducted a sustainability assessment and deconstructed the intervention components into fixed and adaptable elements; and subsequently refined the intervention for trial. RESULTS: The original EDDIE pilot intervention included four components: nurse and personal care worker education; decision support tools; diagnostic equipment; and facilitation and clinical support. Deconstructing the intervention into core components and what could be flexibly tailored to context was essential for refining the intervention and informing future implementation across multiple sites. Intervention elements considered unsustainable were updated and refined to enable their scalability. Refinements included: an enhanced educational component with a greater focus on personal care workers and interactive learning; decision support tools that were based on updated evidence; equipment that aligned with recipient needs and available organisational support; and updated facilitation model with local and external facilitation. CONCLUSION: By using the i-PARIHS framework in the scale-up process, the EDDIE + intervention was tailored to fit the needs of intended recipients and contexts, enabling flexibility for local adaptation. The process of transitioning from a pilot to larger scale implementation in practice is vastly underreported yet vital for better development and implementation of multi-component interventions across multiple sites. We provide an example using an implementation framework and show it can be advantageous to researchers and health practitioners from pilot stage to refinement, through to larger scale implementation. TRIAL REGISTRATION: The trial was prospectively registered with the Australia New Zealand Clinical Trial Registry (ACTRN12620000507987, registered 23/04/2020).

Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.

Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.

Design and optical performance research of a fully customizable collimating lens based on total internal reflection.

An optical design method of a fully customizable collimating lens is proposed. The initial model of the complete lens is constructed by two parts. One part is calculated by the total internal reflection algorithm; the other part is constructed by trial-and-error method. The lens is further optimized by normal vector correction and high- and low-angle compensation. The optical performance of the fully customizable collimating lens is studied. It is proven to have good collimation performance with a divergence angle of 1.8° at 50% of the maximum luminous intensity; the uniformity is as high as 98.4%.

Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections.

Ganodermataceae is one of the main families of macrofungi since species in the family are both ecologically and economically important. The double-walled basidiospores with ornamented endospore walls are the characteristic features of Ganodermataceae. It is a large and complex family; although many studies have focused on Ganodermataceae, the global diversity, geographic distribution, taxonomy and molecular phylogeny of Ganodermataceae still remained incompletely understood. In this work, taxonomic and phylogenetic studies on worldwide species of Ganodermataceae were carried out by morphological examination and molecular phylogenetic analyses inferred from six gene loci including the internal transcribed spacer regions (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), the second largest subunit of RNA polymerase II gene (rpb2), the translation elongation factor 1-α gene (tef1), the small subunit mitochondrial rRNA gene (mtSSU) and the small subunit nuclear ribosomal RNA gene (nSSU). A total of 1 382 sequences were used in the phylogenetic analyses, of which 817 were newly generated, including 132 sequences of ITS, 139 sequences of nLSU, 83 sequences of rpb2, 124 sequences of tef1, 150 sequences of mtSSU and 189 sequences of nSSU. The combined six-gene dataset included sequences from 391 specimens representing 146 taxa from Ganodermataceae. Based on morphological and phylogenetic analyses, 14 genera were confirmed in Ganodermataceae: Amauroderma, Amaurodermellus, Cristataspora, Foraminispora, Furtadoella, Ganoderma, Haddowia, Humphreya, Magoderna, Neoganoderma, Sanguinoderma, Sinoganoderma, Tomophagus and Trachydermella. Among these genera, Neoganoderma gen. nov. is proposed for Ganoderma neurosporum; Sinoganoderma gen. nov. is proposed for Ganoderma shandongense; Furtadoella gen. nov. is proposed to include taxa previously belonging to Furtadoa since Furtadoa is a homonym of a plant genus in the Araceae; Trachydermella gen. nov. is proposed to include Trachyderma tsunodae since Trachyderma is a homonym of a lichen genus in the Pannariaceae. Twenty-three new species, viz., Ganoderma acaciicola, G. acontextum, G. alpinum, G. bubalinomarginatum, G. castaneum, G. chuxiongense, G. cocoicola, G. fallax, G. guangxiense, G. puerense, G. subangustisporum, G. subellipsoideum, G. subflexipes, G. sublobatum, G. tongshanense, G. yunlingense, Haddowia macropora, Sanguinoderma guangdongense, Sa. infundibulare, Sa. longistipitum, Sa. melanocarpum, Sa. microsporum and Sa. tricolor are described. In addition, another 33 known species are also described in detail for comparison. Scanning electron micrographs of basidiospores of 10 genera in Ganodermataceae are provided. A key to the accepted genera of Ganodermataceae and keys to the accepted species of Ganoderma, Haddowia, Humphreya, Magoderna, Sanguinoderma and Tomophagus are also provided. In total, 278 species are accepted as members of Ganodermataceae including 59 species distributed in China. Taxonomic novelties: New genera: Furtadoella B.K. Cui & Y.F. Sun, Neoganoderma B.K. Cui & Y.F. Sun, Sinoganoderma B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella B.K. Cui & Y.F. Sun; New species: Ganoderma acaciicola B.K. Cui, J.H. Xing & Y.F. Sun, G. acontextum B.K. Cui, J.H. Xing & Vlasák, G. alpinum B.K. Cui, J.H. Xing & Y.F. Sun, G. bubalinomarginatum B.K. Cui, J.H. Xing & Y.F. Sun, G. castaneum B.K. Cui, J.H. Xing & Y.F. Sun, G. chuxiongense B.K. Cui, J.H. Xing & Y.F. Sun, G. cocoicola B.K. Cui, J.H. Xing & Y.F. Sun, G. fallax B.K. Cui, J.H. Xing & Vlasák, G. guangxiense B.K. Cui, J.H. Xing & Y.F. Sun, G. puerense B.K. Cui, J.H. Xing & Y.F. Sun, G. subangustisporum B.K. Cui, J.H. Xing & Y.F. Sun, G. subellipsoideum B.K. Cui, J.H. Xing & Y.F. Sun, G. subflexipes B.K. Cui, J.H. Xing & Y.F. Sun, G. sublobatum B.K. Cui, J.H. Xing & Y.F. Sun, G. tongshanense B.K. Cui, J.H. Xing & Y.F. Sun, G. yunlingense B.K. Cui, J.H. Xing & Y.F. Sun, Haddowia macropora B.K. Cui, Vlasák & Y.F. Sun, Sanguinoderma guangdongense B.K. Cui & Y.F. Sun, Sa. infundibulare B.K. Cui & Y.F. Sun, Sa. longistipitum B.K. Cui & Y.F. Sun, Sa. melanocarpum B.K. Cui & Y.F. Sun, Sa. microsporum B.K. Cui & Y.F. Sun and Sa. tricolor B.K. Cui & Y.F. Sun; New combinations: Furtadoella biseptata (Costa-Rezende et al.) B.K. Cui & Y.F. Sun, Fu. brasiliensis (Singer) B.K. Cui & Y.F. Sun, Fu. corneri (Gulaid & Ryvarden) B.K. Cui & Y.F. Sun, Neoganoderma neurosporum (J.S. Furtado) B.K. Cui & Y.F. Sun, Sinoganoderma shandongense (J.D. Zhao & L.W. Xu) B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella tsunodae (Yasuda ex Lloyd) B.K. Cui & Y.F. Sun. Citation: Sun Y-F, Xing J-H, He X-L, Wu D-M, Song C-G, Liu S, Vlasák J, Gates G, Gibertoni TB, Cui B-K (2022). Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections. Studies in Mycology 101: 287-415. doi: 10.3114/sim.2022.101.05.

Impact of a prospective feedback loop on care review activities in older patients at the end of life. A stepped-wedge randomised trial.

BACKGROUND: Hospitalisation rates for older people are increasing, with end-of-life care becoming a more medicalised experience. Innovative approaches are warranted to support early identification of the end-of-life phase, communicate prognosis, provide care consistent with people's preferences, and improve the use of healthcare resources. The Intervention for Appropriate Care and Treatment (InterACT) trial aimed to increase appropriate care and treatment decisions for older people at the end of life, through implementation of a prospective feedback loop. This paper reports on the care review outcomes. METHODS: A stepped-wedge randomised controlled trial was conducted in three large acute hospitals in Queensland, Australia between May 2020 and June 2021. The trial identified older people nearing the end of life using two validated tools for detecting deterioration and short-term death. Admitting clinical teams were provided with details of patients identified as at-risk with the goal of increasing awareness that end of life was approaching to facilitate appropriate patient centred care and avoid non-beneficial treatment. We examined the time between when the patient was identified as 'at-risk' and three outcomes: clinician-led care review discussions, review of care directive measures and palliative care referrals. These were considered useful indicators of appropriate care at the end of life. RESULTS: In two hospitals there was a reduction in the review of care directive measures during the intervention compared with usual care at 21 days (reduced probability of - 0.08; 95% CI: - 0.12 to - 0.04 and - 0.14; 95% CI: - 0.21 to - 0.06). In one hospital there was a large reduction in clinician-led care review discussions at 21 days during the intervention (reduced probability of - 0.20; 95% CI: - 0.28 to - 0.13). There was little change in palliative care referrals in any hospital, with average probability differences at 21 days of - 0.01, 0.02 and 0.04. DISCUSSION: The results are disappointing as an intervention designed to improve care of hospitalised older people appeared to have the opposite effect on care review outcomes. The reasons for this may be a combination of the intervention design and health system challenges due to the pandemic that highlight the complexity of providing more appropriate care at the end of life. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

[A multicenter retrospective study on the efficacy of different anti-reflux reconstruction methods after proximal gastrectomy for gastric cancer].

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ2 test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ2 test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ2=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m2, P<0.01; mean difference=2.429 kg/m2, P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m2, P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ2=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ2=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.

A stepped-wedge randomised controlled trial assessing the implementation, effectiveness and cost-consequences of the EDDIE+ hospital avoidance program in 12 residential aged care homes: study protocol.

BACKGROUND: Older people living in residential aged care homes experience frequent emergency transfers to hospital. These events are associated with risks of hospital acquired complications and invasive treatments or interventions. Evidence suggests that some hospital transfers may be unnecessary or avoidable. The Early Detection of Deterioration in Elderly residents (EDDIE) program is a multi-component intervention aimed at reducing unnecessary hospital admissions from residential aged care homes by empowering nursing and care staff to detect and manage early signs of resident deterioration. This study aims to implement and evaluate the program in a multi-site randomised study in Queensland, Australia. METHODS: A stepped-wedge randomised controlled trial will be conducted at 12 residential aged care homes over 58 weeks. The program has four components: education and training, decision support tools, diagnostic equipment, and implementation facilitation with clinical systems support. The integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework will be used to guide the program implementation and process evaluation. The primary outcome measure will be the number of hospital bed days used by residents, with secondary outcomes assessing emergency department transfer rates, admission rates, length of stay, family awareness and experience, staff self-efficacy and costs of both implementation and health service use. A process evaluation will assess the extent and fidelity of program implementation, mechanisms of impact and the contextual barriers and enablers. DISCUSSION: The intervention is expected to improve outcomes by reducing unnecessary hospital transfers. Fewer hospital transfers and admissions will release resources for other patients with potentially greater needs. Residential aged care home staff might benefit from feelings of empowerment in their ability to proactively manage early signs of resident deterioration. The process evaluation will be useful for supporting wider implementation of this intervention and other similar initiatives. TRIAL REGISTRATION: The trial is prospectively registered with the Australia New Zealand Clinical Trial Registry ( ACTRN12620000507987 , registered 23/04/2020).

[Comparative study of CT relative enhancement value and subjective visual evaluation for intestinal ischemia in patients with closed loop obstruction].

Objective: To compare and evaluate the diagnostic performance of visual evaluation and CT maximal density relative enhancement value in the diagnosis of intestinal ischemia complication in patients with closed loop obstruction and to explore the feasibility of CT maximal density relative enhancement value in quantifying the degrees of intestinal ischemia. Methods: The clinical and CT imaging data of 82 patients, 46 males and 36 females, aged from 19 to 78(52±18) years, with closed loop obstruction were retrospectively analyzed in the First Affiliated Hospital of Zhengzhou University from July 2017 to July 2019. All patients were classified into three groups: necrosis group (28 cases), ischemia group (22 cases), non-ischemia group(32 cases) using clinicopathologic results as reference standard. CT visual evaluation was performed by two experienced radiologists. The sensitivity, specificity, positive and negative predictive values and accuracy of the two observers were calculated respectively. The inter-observer agreement was analyzed by kappa analysis. Maximal density relative enhancement value was defined as the difference CT value of an ROI at dilated obstructed loops between contrast-enhanced and unenhanced CT images. The differences among groups were compared by one-way analysis of variance. Diagnostic performances were evaluated by receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, positive and negative predictive values and accuracy of observer1 were 62.0%, 87.5%, 88.6%, 59.6%, 72.0%, and 58.0%, 93.8%, 93.5%, 58.8%, 72.0%for observer2, respectively. The kappa value of inter-observer agreement was 0.747. The unenhanced CT value of necrosis group, ischemia group and non-ischemia group was (53.7±9.7), (45.7±7.2) and (44.7±7.0) HU, enhanced CT value was (60.5±10.1), (65.0±11.6) and (87.0±15.8) HU, relative enhancement value was(6.8±8.4), (19.2±12.4) and(44.7±16.2)HU, respectively. All had a statistical difference among three groups (all P<0.05). The unenhanced CT value of necrosis group was higher than that of ischemia group and un-ischemia group (both P<0.05). The enhanced CT value of non-ischemia group was higher than that of ischemia group and necrosis (both P<0.05). The relative enhancement value all had a significant difference between groups (all P<0.05). Taking maximal density relative enhancement value below 19.5 HU as diagnosis threshold, the sensitivity, specificity and area under curve(AUC) were 96.9%, 74.0% and 0.947, respectively. Taking enhanced CT value below 66.5 HU as diagnosis threshold, the sensitivity, specificity and AUC were 93.8%, 60.0% and 0.903, respectively; the sensitivity was higher than that of objective visual evaluation. Conclusion: Maximal density relative enhancement value can quantize the bowel wall enhancement, and is a more reliable way in the diagnosis of intestinal ischemia than visual evaluation.

Clinical and Economic Outcomes of Genome Sequencing Availability on Containing a Hospital Outbreak of Resistant Escherichia coli in Australia.

OBJECTIVES: To evaluate the outbreak size and hospital cost effects of bacterial whole-genome sequencing availability in managing a large-scale hospital outbreak. METHODS: We built a hybrid discrete event/agent-based simulation model to replicate a serious bacterial outbreak of resistant Escherichia coli in a large metropolitan public hospital during 2017. We tested the 3 strategies of using whole-genome sequencing early, late (actual outbreak), or not using it and assessed their associated outbreak size and hospital cost. The model included ward dynamics, pathogen transmission, and associated hospital costs during a 5-month outbreak. Model parameters were determined using data from the Queensland Hospital Admitted Patient Data Collection (N = 4809 patient admissions) and local clinical knowledge. Sensitivity analyses were performed to address model and parameter uncertainty. RESULTS: An estimated 197 patients were colonized during the outbreak, with 75 patients detected. The total outbreak cost was A$460 137 (US$317 117), with 6.1% spent on sequencing. Without sequencing, the outbreak was estimated to result in 352 colonized patients, costing A$766 921 (US$528 547). With earlier detection from use of routine sequencing, the estimated outbreak size was 3 patients and cost A$65 374 (US$45 054). CONCLUSIONS: Using whole-genome sequencing in hospital outbreak management was associated with smaller outbreaks and cost savings, with sequencing costs as a small fraction of total hospital costs, supporting the further investigation of the use of routine whole-genome sequencing in hospitals.

A hybrid simulation model approach to examine bacterial genome sequencing during a hospital outbreak.

BACKGROUND: Hospital infection control requires timely detection and identification of organisms, and their antimicrobial susceptibility. We describe a hybrid modeling approach to evaluate whole genome sequencing of pathogens for improving clinical decisions during a 2017 hospital outbreak of OXA-181 carbapenemase-producing Escherichia coli and the associated economic effects. METHODS: Combining agent-based and discrete-event paradigms, we built a hybrid simulation model to assess hospital ward dynamics, pathogen transmission and colonizations. The model was calibrated to exactly replicate the real-life outcomes of the outbreak at the ward-level. Seven scenarios were assessed including genome sequencing (early or late) and no sequencing (usual care). Model inputs included extent of microbiology and sequencing tests, patient-level data on length of stay, hospital ward movement, cost data and local clinical knowledge. The main outcomes were outbreak size and hospital costs. Model validation and sensitivity analyses were performed to address uncertainty around data inputs and calibration. RESULTS: An estimated 197 patients were colonized during the outbreak with 75 patients detected. The total outbreak cost was US$318,654 with 6.1% of total costs spent on sequencing. Without sequencing, the outbreak was estimated to result in 352 colonized patients costing US$531,109. Microbiology tests were the largest cost component across all scenarios. CONCLUSION: A hybrid simulation approach using the advantages of both agent-based and discrete-event modeling successfully replicated a real-life bacterial hospital outbreak as a foundation for evaluating clinical outcomes and efficiency of outbreak management. Whole genome sequencing of a potentially serious pathogen appears effective in containing an outbreak and minimizing hospital costs.

A stepped-wedge randomised-controlled trial assessing the implementation, impact and costs of a prospective feedback loop to promote appropriate care and treatment for older patients in acute hospitals at the end of life: study protocol.

BACKGROUND: Hospitalisation rates for the older population have been increasing with end-of-life care becoming a more medicalised and costly experience. There is evidence that some of these patients received non-beneficial treatment during their final hospitalisation with a third of the non-beneficial treatment duration spent in intensive care units. This study aims to increase appropriate care and treatment decisions and pathways for older patients at the end of life in Australia. This study will implement and evaluate a prospective feedback loop and tailored clinical response intervention at three hospitals in Queensland, Australia. METHODS: A stepped-wedge cluster randomised trial will be conducted with up to 21 clinical teams in three acute hospitals over 70 weeks. The study involves clinical teams providing care to patients aged 75 years or older, who are prospectively identified to be at risk of non-beneficial treatment using two validated tools for detecting death and deterioration risks. The intervention's feedback loop will provide the teams with a summary of these patients' risk profiles as a stimulus for a tailored clinical response in the intervention phase. The Consolidated Framework for Implementation Research will be used to inform the intervention's implementation and process evaluation. The study will determine the impact of the intervention on patient outcomes related to appropriate care and treatment at the end of life in hospitals, as well as the associated healthcare resource use and costs. The primary outcome is the proportion of patients who are admitted to intensive care units. A process evaluation will be carried out to assess the implementation, mechanisms of impact, and contextual barriers and enablers of the intervention. DISCUSSION: This intervention is expected to have a positive impact on the care of older patients near the end of life, specifically to improve clinical decision-making about treatment pathways and what constitutes appropriate care for these patients. These will reduce the incidence of non-beneficial treatment, and improve the efficiency of hospital resources and quality of care. The process evaluation results will be useful to inform subsequent intervention implementation at other hospitals. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619000675123p (approved 6 May 2019).

The effectiveness and cost effectiveness of a hospital avoidance program in a residential aged care facility: a prospective cohort study and modelled decision analysis.

BACKGROUND: Residential aged care facility residents experience high rates of hospital admissions which are stressful, costly and often preventable. The EDDIE program is a hospital avoidance initiative designed to enable nursing and care staff to detect, refer and quickly respond to early signals of a deteriorating resident. The program was implemented in a 96-bed residential aged care facility in regional Australia. METHODS: A prospective pre-post cohort study design was used to collect data on costs of program delivery, hospital admission rates and length of stay for the 12 months prior to, and following, the intervention. A Markov decision model was developed to synthesize study data with published literature in order to estimate the cost-effectiveness of the program. Quality adjusted life years (QALYs) were adopted as the measure of effectiveness. RESULTS: The EDDIE program was associated with a 19% reduction in annual hospital admissions and a 31% reduction in the average length of stay. The cost-effectiveness analysis found the program to be both more effective and less costly than usual care, with 0.06 QALYs gained and $249,000 health system costs saved in a modelled cohort of 96 residents. A probabilistic sensitivity analysis estimated that there was an 86% probability that the program was cost-effective after taking the uncertainty of the model inputs into account. CONCLUSIONS: This study provides promising evidence for the effectiveness and cost-effectiveness of a nurse led, early intervention program in preventing unnecessary hospital admissions within a residential aged care facility. Further research in multi-site randomised studies is needed to confirm the generalisability of these results.

Estimating the costs of genomic sequencing in cancer control.

BACKGROUND: Despite the rapid uptake of genomic technologies within cancer care, few studies provide detailed information on the costs of sequencing across different applications. The objective of the study was to examine and categorise the complete costs involved in genomic sequencing for a range of applications within cancer settings. METHODS: We performed a cost-analysis using gross and micro-costing approaches for genomic sequencing performed during 2017/2018 across different settings in Brisbane, Australia. Sequencing was undertaken for patients with lung, breast, oesophageal cancers, melanoma or mesothelioma. Aggregated resource data were captured for a total of 1433 patients and point estimates of per patient costs were generated. Deterministic sensitivity analyses addressed the uncertainty in the estimates. Estimated costs to the public health system for resources were categorised into seven distinct activities in the sequencing process: sampling, extraction, library preparation, sequencing, analysis, data storage and clinical reporting. Costs were also aggregated according to labour, consumables, testing, equipment and 'other' categories. RESULTS: The per person costs were AU$347-429 (2018 US$240-297) for targeted panels, AU$871-$2788 (2018 US$604-1932) for exome sequencing, and AU$2895-4830 (2018 US$2006-3347) for whole genome sequencing. Cost proportions were highest for library preparation/sequencing materials (average 76.8% of total costs), sample extraction (8.1%), data analysis (9.2%) and data storage (2.6%). Capital costs for the sequencers were an additional AU$34-197 (2018 US$24-67) per person. CONCLUSIONS: Total costs were most sensitive to consumables and sequencing activities driven by commercial prices. Per person sequencing costs for cancer are high when tumour/blood pairs require testing. Using the natural steps involved in sequencing and categorising resources accordingly, future evaluations of costs or cost-effectiveness of clinical genomics across cancer projects could be more standardised and facilitate easier comparison of cost drivers.

Multi-gene phylogeny and taxonomy of Amauroderma s.lat. (Ganodermataceae).

Amauroderma s.lat. has been defined mainly by the morphological features of non-truncate and double-walled basidiospores with a distinctly ornamented endospore wall. In this work, taxonomic and phylogenetic studies on species of Amauroderma s.lat. are carried out by morphological examination together with ultrastructural observations, and molecular phylogenetic analyses of multiple loci including the internal transcribed spacer regions (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), the largest subunit of RNA polymerase II (RPB1) and the second largest subunit of RNA polymerase II (RPB2), the translation elongation factor 1-α gene (TEF) and the ß-tubulin gene (TUB). The results demonstrate that species of Ganodermataceae formed ten clades. Species previously placed in Amauroderma s.lat. are divided into four clades: Amauroderma s.str., Foraminispora, Furtadoa and a new genus Sanguinoderma. The classification of Amauroderma s.lat. is thus revised, six new species are described and illustrated, and eight new combinations are proposed. SEM micrographs of basidiospores of Foraminispora and Sanguinoderma are provided, and the importance of SEM in delimitation of taxa in this study is briefly discussed. Keys to species of Amauroderma s.str., Foraminispora, Furtadoa, and Sanguinoderma are also provided.

NGS-based profiling reveals a critical contributing role of somatic D-loop mtDNA mutations in HBV-related hepatocarcinogenesis.

BACKGROUND: Somatic mutations of mitochondrial DNA (mtDNA) have been extensively identified mainly by traditional Sanger sequencing technology in various cancer types. However, low detection sensitivity of traditional methods greatly limits the comprehensive profiling of mtDNA somatic mutations in cancers, especially in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Moreover, the functional roles of mtDNA mutation in HBV-related hepatocarcinogenesis have not been systematically revealed. PATIENTS AND METHODS: Next-generation sequencing (NGS) platform was applied to profile the somatic mtDNA mutations of HCC and paired paratumor (non-HCC) tissues from a large cohort of 156 HBV-HCC patients. RESULTS: Our data revealed the common existence of mtDNA mutation in both inflammatory and cancer tissues with significantly different mutation pattern. The mutation density (mutation number/region length) of D-loop region was much higher than that of other regions in both HCC and non-HCC tissues. Unexpectedly, the average mutation number in D-loop region of HCC tissues was significantly less than that of non-HCC tissues. In contrast, the heteroplasmy level of D-loop region mutations was significantly increased in HCC tissues, implying that the D-loop mutations might be positively selected in HCC tissues. Furthermore, our results indicated that the patients with D-loop mutations had a significantly lower mtDNA copy number and were more likely to relapse. In vitro experiments demonstrated that proliferation, invasion and metastasis ability of HCC cells with D-loop region mutations were significantly higher than those without D-loop region mutations. CONCLUSION: These results emphasize the critical contributing role of somatic mtDNA D-loop mutations in HBV-related hepatocarcinogenesis.

The PNKD gene is associated with Tourette Disorder or Tic disorder in a multiplex family.

Tourette Disorder (TD) is a childhood-onset neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. The genetic architecture of TD is believed to be complex and heterogeneous. Nevertheless, DNA sequence variants co-segregating with TD phenotypes within multiplex families have been identified. This report examines whole exomes of affected and unaffected individuals in a multiplex TD family to discover genes involved in the TD etiology. We performed whole exome sequencing on six out of nine members in a three-generation TD multiplex family. Putative deleterious sequence variants co-segregating with TD patients were identified by our in-house bioinformatics pipeline. Induced pluripotent stem cells (iPSCs) were generated from one unaffected and two TD affected individuals. Neurons were derived from the iPSCs and biochemical assays were conducted to evaluate possible molecular differences between affected and unaffected. A rare heterozygous nonsense mutation in PNKD was co-segregated with TD in this multiplex family. Transcript and protein levels of the PNKD long isoform were reduced in neurons derived from the individuals with TD due to the nonsense mutation, indicating nonsense-mediated mRNA decay. We demonstrated that the PNKD long isoform monomer oligomerizes with itself as well as interacts with the synaptic active zone protein RIMS1α. We concluded that reduced PNKD long isoform levels are detected in all affected individuals and we provide evidence for a mechanism whereby this might contribute to the TD phenotype.

Comparison of EQ-5D-5L and SPVU-5D for measuring quality of life in patients with venous leg ulcers in an Australian setting.

PURPOSE: Given the importance of measuring health-related quality of life (HRQoL) for cost-utility studies, this study aimed to determine the validity and responsiveness of two preference-based HRQoL instruments, the EuroQol-five dimensions-five levels questionnaire (EQ-5D-5L) and the Sheffield Preference-based Venous Ulcer questionnaire (SPVU-5D) in patients with venous leg ulcers (VLUs) in an Australian setting. METHODS: This study analysed de-identified data collected from 80 patients with VLUs recruited by a prospective study in Brisbane, Queensland, Australia. Patients were asked to complete EQ-5D-5L and SPVU-5D surveys at baseline, 1-month, 3-month and 6-month follow-up as part of the prospective study. Baseline data and follow-up data were pooled to test the construct validity and level of agreement of the two instruments. Follow-up data were used to test the responsiveness. RESULTS: The ceiling effects were negligible for EQ-5D-5L and SPVU-5D utility scores. Both instruments were able to discriminate between healed VLU and unhealed VLU and showed great responsiveness when healing status changed over time. Weak to strong correlations were found between dimensions of EQ-5D-5L and SPVU-5D. The utility scores produced from EQ-5D-5L were generally lower. CONCLUSIONS: This study found that both EQ-5D-5L and SPVU-5D were valid and responsive in detecting change of VLU healing status among a small Australian population. Both instruments may be used in economic evaluation studies that involve patients with healed or unhealed VLUs. However, given the limitations presented in this study, further research is necessary to make sound recommendations on the preferred instrument in economic evaluation of VLU-related interventions.