The simulation of action disorganisation in complex activities of daily living

Action selection in everyday goal-directed tasks of moderate complexity is known to be subject to breakdown following extensive frontal brain injury. A model of action selection in such tasks is presented and used to explore three hypotheses concerning the origins of action disorganisation: that it is a consequence of reduced top-down excitation within a hierarchical action schema network coupled with increased bottom-up triggering of schemas from environmental sources, that it is a more general disturbance of schema activation modelled by excessive noise in the schema network, and that it results from a general disturbance of the triggering of schemas by object representations. Results suggest that the action disorganisation syndrome is best accounted for by a general disturbance to schema activation, while altering the balance between top-down and bottom-up activation provides an account of a related disorder - utilisation behaviour. It is further suggested that ideational apraxia (which may result from lesions to left temporoparietal areas and which has similar behavioural consequences to action disorganisation syndrome on tasks of moderate complexity) is a consequence of a generalised disturbance of the triggering of schemas by object representations. Several predictions regarding differences between action disorganisation syndrome and ideational apraxia that follow from this interpretation are detailed

Responsibility modelling for civil emergency planning

This paper presents a new approach to analysing and understanding civil emergency planning based on the notion of responsibility modelling combined with HAZOPS-style analysis of information requirements. Our goal is to represent complex contingency plans so that they can be more readily understood, so that inconsistencies can be highlighted and vulnerabilities discovered. In this paper, we outline the framework for contingency planning in the United Kingdom and introduce the notion of responsibility models as a means of representing the key features of contingency plans. Using a case study of a flooding emergency, we illustrate our approach to responsibility modelling and suggest how it adds value to current textual contingency plans

How can health care organisations make and justify decisions about risk reduction? Lessons from a cross-industry review and a health care stakeholder consensus development process

Interventions to reduce risk often have an associated cost. In UK industries decisions about risk reduction are made and justified within a shared regulatory framework that requires that risk be reduced as low as reasonably practicable. In health care no such regulatory framework exists, and the practice of making decisions about risk reduction is varied and lacks transparency. Can health care organisations learn from relevant industry experiences about making and justifying risk reduction decisions? This paper presents lessons from a qualitative study undertaken with 21 participants from five industries about how such decisions are made and justified in UK industry. Recommendations were developed based on a consensus development exercise undertaken with 20 health care stakeholders. The paper argues that there is a need in health care to develop a regulatory framework and an agreed process for managing explicitly the trade-off between risk reduction and cost. The framework should include guidance about a health care specific notion of acceptable levels of risk, guidance about standardised risk reduction interventions, it should include regulatory incentives for health care organisations to reduce risk, and it should encourage the adoption of an approach for documenting explicitly an organisation’s risk position

Students’ perceptions of patient safety during the transition from undergraduate to postgraduate training: an activity theory analysis

Evidence that medical error can cause harm to patients has raised the attention of the health care community towards patient safety and influenced how and what medical students learn about it. Patient safety is best taught when students are participating in clinical practice where they actually encounter patients at risk. This type of learning is referred to as workplace learning, a complex system in which various factors influence what is being learned and how. A theory that can highlight potential difficulties in this complex learning system about patient safety is activity theory. Thirty-four final year undergraduate medical students participated in four focus groups about their experiences concerning patient safety. Using activity theory as analytical framework, we performed constant comparative thematic analysis of the focus group transcripts to identify important themes. We found eight general themes relating to two activities: learning to be a doctor and delivering safe patient care. Simultaneous occurrence of these two activities can cause contradictions. Our results illustrate the complexity of learning about patient safety at the workplace. Students encounter contradictions when learning about patient safety, especially during a transitional phase of their training. These contradictions create potential learning opportunities which should be used in education about patient safety. Insight into the complexities of patient safety is essential to improve education in this important area of medicine

BMC Ophthalmol

BACKGROUND: This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment. METHODS: An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with >/=10 and >/= 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network). RESULTS: Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90-8.52 ETDRS letters), >/=15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12-4.20), and >/=10 ETDRS letter loss (OR 0.25, 95% CrI 0.05-0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26-10.61 ETDRS letters) (IPD and aggregate random-effects model). CONCLUSIONS: This NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA

Port of Weipa long‐term seagrass monitoring program, 2000‐2020

Monitoring in 2020 found seagrasses in the port of Weipa were in good condition overall. - Most monitoring meadows were in good or very good condition for all three indicators measured; biomass, area and species composition. - Total area of seagrass meadows in the region closest to the port (Intensive Monitoring Area (IMA)) was one of the highest recorded in the 20‐year monitoring program history. Seagrass cover across the broader port area (including Pine River Bay, Embley, Hey and Mission Rivers) was higher than any other survey since monitoring began in 2000. Light conditions were above the threshold for seagrass growth and survival throughout the year, with the exception of an expected period during the wet season. Favourable climate conditions for multiple years has led to greater seagrass cover across the port and the overall good condition of Weipa’s seagrass in 2020. The healthy state of Weipa’s seagrassin 2020 means they should be resilient to planned maintenance dredging activities in 2021 assuming that there are no major seagrass losses associated with the predicted La Nina weather conditions leading up to the 2021 maintenance dredging campaign

Port of Weipa long‐term seagrass monitoring program, 2000‐2020

Monitoring in 2020 found seagrasses in the port of Weipa were in good condition overall. - Most monitoring meadows were in good or very good condition for all three indicators measured; biomass, area and species composition. - Total area of seagrass meadows in the region closest to the port (Intensive Monitoring Area (IMA)) was one of the highest recorded in the 20‐year monitoring program history. Seagrass cover across the broader port area (including Pine River Bay, Embley, Hey and Mission Rivers) was higher than any other survey since monitoring began in 2000. Light conditions were above the threshold for seagrass growth and survival throughout the year, with the exception of an expected period during the wet season. Favourable climate conditions for multiple years has led to greater seagrass cover across the port and the overall good condition of Weipa’s seagrass in 2020. The healthy state of Weipa’s seagrassin 2020 means they should be resilient to planned maintenance dredging activities in 2021 assuming that there are no major seagrass losses associated with the predicted La Nina weather conditions leading up to the 2021 maintenance dredging campaign

1578. Treatments for complicated urinary tract infections (cUTI) caused by multidrug resistant (MDR) Gram-negative (GN) pathogens- a systematic review and network meta-analysis (NMA)

Abstract Background Antimicrobial resistance is a major and growing threat to global public health. Cefiderocol (CFDC) is a new siderophore-cephalosporin with a wide activity spectrum covering all aerobic GN pathogens including all WHO critical priority pathogens, that was recently approved by FDA for the treatment of GN cUTI in susceptible organisms. We aim to understand the relative efficacy and safety of current treatment options for cUTI caused by MDR GN pathogens. Methods We conducted a systematic review to identify all relevant trials that investigated the efficacy and safety of antimicrobial regimens, for the treatment of GN pathogens in cUTI. Outcomes of interest included clinical cure and microbiological eradication (ME) at time of cure (TOC) and sustained follow up (SFU), and safety. Evidence networks were constructed using data for outcomes of interest and analyses were conducted in a frequentist framework using NMA methods outlined by the NICE decision support unit using the netmeta package in R. Results A total of 5 studies, 6 interventions and 2,349 randomised patients were included in the final analysis. Interventions included CFDC, imipenem-cilastatin (IPM-CIL), ceftazidime-avibactam (CAZ/AVI), doripenem (DOR), levofloxacin and ceftolozane-tazobactam (CEF/TAZ). Trials included predominantly Enterobacterales, and Pseudomonas aeruginosa and very few Acinetobacter baumannii. The patient population presented some clinical differences across trials, which were not adjusted for the NMA. Overall, there were numerical differences (especially in endpoints at SFU favouring CFDC), but all treatments showed similar efficacy and safety, with exception of higher ME rate at TOC for CFDC vs IPM, Table 1, also observed at SFU, consistent with the data from the individual clinical trial. Table 1- Results for microbiological eradication Table 1- Results for microbiological eradication Conclusion This NMA, showed superiority of CFDC vs IPM-CIL in ME at TOC and SFU and similar efficacy and safety vs all other comparators, with numeric differences favouring CFDC for outcomes at SFU. These traditional methodologies for NMA, are only valid within a similar pathogens pool and population across the trials, and may not reflect the full value of breadth of coverage that new therapeutic options bring for the treatment of MDR GN pathogens. Disclosures Tim Reason, PhD, Shionogi (Consultant) Karan Gill, MSc, Shionogi BV (Employee) Christopher Longshaw, PhD, Shionogi B.V. (Employee) Rachael McCool, PhD, York Health Economics Consortium (Employee, YHEC was commissioned by Shionogi to conduct the systematic review) Katy Wilson, PhD, York Health Economics Consortium (Employee, Shionogi commissioned YHEC to conduct the systematic review) Sara Lopes, PharmD, Shionogi BV (Employee) </jats:sec

Indirect treatment comparison of the efficacy of olaparib 300 mg tablets BID and cabazitaxel 25 mg/m² every 3 weeks plus daily prednisolone and granulocyte colony-stimulating factor in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

5051 Background: In PROfound, olaparib demonstrated improved radiological PFS (rPFS) and overall survival (OS) versus new hormonal agent (NHA) in patients with homologous recombination repair mutated (HRRm) mCRPC that had progressed on prior NHA. This efficacy was observed across prespecified subgroups including patients treated with prior taxane therapy and for whom intravenous cabazitaxel is an alternative treatment option. The relative efficacy of olaparib versus cabazitaxel has not been assessed in head-to-head studies. An indirect treatment comparison (ITC) was performed to simulate the comparative efficacy of olaparib and cabazitaxel in patients with HRRm mCRPC after prior taxane and NHA. Methods: Fixed-effects frequentist ITCs were conducted using efficacy data from the prior taxane subgroup of PROfound (NCT02987543) and published data from the Phase IV CARD study of cabazitaxel versus NHA after prior NHA and taxane treatment (NCT02485691). Baseline variables feasible for comparison across studies were assessed for effect modification. Efficacy analyses were performed on the hazard ratios (HR) of rPFS by independent central review and OS. The OS analysis was performed using the final PROfound OS results, which included switching from NHA to olaparib after progression, and using results that were adjusted for switching. In the absence of biomarker subgroup data, the efficacy results of the overall population in CARD were assumed generalizable to the HRRm biomarker population of PROfound, such that mutation status is not a modifier of relative treatment effect for cabazitaxel versus NHA. Results were presented for the comparison of olaparib with cabazitaxel in the BRCA1-/BRCA2-mutated (BRCAm) and BRCAm/ATM populations. Results: The ITC HR for rPFS was 0.36 (95% confidence interval 0.20–0.64) in BRCAm and 0.51 (0.31–0.84) for the BRCAm/ATM population. Without adjustment for switching in PROfound, the ITC HRs for OS in the BRCAm population and BRCAm/ATM population were 0.99 (0.55–1.78) and 0.88 (0.52–1.47), respectively; after switch adjustment, the OS HRs were 0.47 (0.12–1.79) and 0.44 (0.17–1.10), respectively. Conclusions: The ITC results suggest that olaparib is associated with significantly improved rPFS versus cabazitaxel in the treatment of BRCAm and BRCAm/ATM patients who have progressed on taxane and NHA therapy. After removing the effect of switching from NHA to olaparib in PROfound, olaparib appears associated with a non-significant OS improvement versus cabazitaxel in both populations. The results require confirmation in comparative studies. Analysis limitations include uncertainty over the efficacy of cabazitaxel versus NHA in HRRm mCRPC patients, and heterogeneity in prior taxane and NHA therapy. Clinical trial information: NCT02987543. </jats:p