bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of protein tertiary and quaternary structure predictions using the ReFOLD refinement method and the AlphaFold2 recycling process
Authors: Adiyaman Recep , Edmunds Nicholas S , Genc Ahmet G , Alharbi Shuaa M A , McGuffin Liam J
Published: June 2023

Motivation

The accuracy gap between predicted and experimental structures has been significantly reduced following the development of AlphaFold2 (AF2). However, for many targets, AF2 models still have room for improvement. In previous CASP experiments, highly computationally intensive MD simulation-based methods have been widely used to improve the accuracy of single 3D models. Here, our ReFOLD pipeline was adapted to refine AF2 predictions while maintaining high model accuracy at a modest computational cost. Furthermore, the AF2 recycling process was utilized to improve 3D models by using them as custom template inputs for tertiary and quaternary structure predictions.

Results

According to the Molprobity score, 94% of the generated 3D models by ReFOLD were improved. AF2 recycling showed an improvement rate of 87.5% (using MSAs) and 81.25% (using single sequences) for monomeric AF2 models and 100% (MSA) and 97.8% (single sequence) for monomeric non-AF2 models, as measured by the average change in lDDT. By the same measure, the recycling of multimeric models showed an improvement rate of as much as 80% for AF2-Multimer (AF2M) models and 94% for non-AF2M models.

Availability and implementation

Refinement using AlphaFold2-Multimer recycling is available as part of the MultiFOLD docker package (https://hub.docker.com/r/mcguffin/multifold). The ReFOLD server is available at https://www.reading.ac.uk/bioinf/ReFOLD/ and the modified scripts can be downloaded from https://www.reading.ac.uk/bioinf/downloads/.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Revelation, Revolution and Utopia, c.1770–1820
Authors: Jones P M
Published: June 2023

The philosophes and France’s revolutionaries are often held jointly responsible for the attack on revealed religion in the course of the eighteenth century. This article suggests that the culture of belief among the laity of Protestant and Catholic Europe was not seriously undermined or even radically altered by the ralliement of State churches to the rationalistic and utilitarian values of the Enlightenment. Scepticism remained a narrowly confined phenomenon and religious ‘enthusiasm’, including literal belief in biblical prophecy, recovered strongly towards the century’s end. Traumatic public events (including the destruction of the Jesuit Order, the war in America, the revolution in France, the rise of Napoleon) were capable of triggering a latent millenarian reflex in nearly all social milieus. Although frequently played down by researchers, biblical literalism, prophetic witness and the quest for spiritual utopia should be considered an integral part of the tumultuous politics of the 1790 and 1800s. The article focuses particularly on the outlook and behaviour of England’s Rational Dissenters, French and Italian Jansenists and German Pietists in order to illustrate this contention. It concludes that, even at elite levels, detachment from religion was superficial and mainly doctrinal in nature. God, in one form or another, survived both the Enlightenment and the French Revolution.
Burden of mood symptoms and disorders in implantable cardioverter defibrillator patients: a systematic review and meta-analysis of 39 954 patients
Authors: Ghezzi Erica S , Sharman Rhianna L S , Selvanayagam Joseph B , Psaltis Peter J , Sanders Prashanthan , Astley Jack M , Knayfati Sara , Batra Vrinda , Keage Hannah A D
Published: June 2023

Aims

Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. Anxiety, depression, and post-traumatic stress disorder (PTSD) are underappreciated symptoms. We aimed to systematically synthesize prevalence estimates of mood disorders and symptom severities, pre- and post-ICD insertions. Comparisons were made with control groups, as well as within ICD patients by indication (primary vs. secondary), sex, shock status, and over time.

Methods

Databases (Medline, PsycINFO, PubMed, and Embase) were searched without limits from inception to 31 August 2022; 4661 articles were identified, 109 (39 954 patients) of which met criteria.

Results

Random-effects meta-analyses revealed clinically relevant anxiety in 22.58% (95%CI 18.26–26.91%) of ICD patients across all timepoints following insertion and depression in 15.42% (95%CI 11.90–18.94%). Post-traumatic stress disorder was seen in 12.43% (95%CI 6.90–17.96%). Rates did not vary relative to indication group. Clinically relevant anxiety and depression were more likely in ICD patients who experienced shocks [anxiety odds ratio (OR) = 3.92 (95%CI 1.67–9.19); depression OR = 1.87 (95%CI 1.34–2.59)]. Higher symptoms of anxiety were seen in females than males post-insertion [Hedges’ g = 0.39 (95%CI 0.15–0.62)]. Depression symptoms decreased in the first 5 months post-insertion [Hedges’ g = 0.13 (95%CI 0.03–0.23)] and anxiety symptoms after 6 months [Hedges’ g = 0.07 (95%CI 0–0.14)].

Conclusion

Depression and anxiety are highly prevalent in ICD patients, especially in those who experience shocks. Of particular concern is the prevalence of PTSD following ICD implantation. Psychological assessment, monitoring, and therapy should be offered to ICD patients and their partners as part of routine care.
Additional coils mitigate elevated defibrillation threshold in right-sided implantable cardioverter defibrillator generator placement: a simulation study
Authors: Qian Shuang , Monaci Sofia , Mendonca-Costa Caroline , Campos Fernando , Gemmell Philip , Zaidi Hassan A , Rajani Ronak , Whitaker John , Rinaldi Christopher A , Bishop Martin J
Published: June 2023

Aims

The standard implantable cardioverter defibrillator (ICD) generator (can) is placed in the left pectoral area; however, in certain circumstances, right-sided cans may be required which may increase defibrillation threshold (DFT) due to suboptimal shock vectors. We aim to quantitatively assess whether the potential increase in DFT of right-sided can configurations may be mitigated by alternate positioning of the right ventricular (RV) shocking coil or adding coils in the superior vena cava (SVC) and coronary sinus (CS).

Methods and results

A cohort of CT-derived torso models was used to assess DFT of ICD configurations with right-sided cans and alternate positioning of RV shock coils. Efficacy changes with additional coils in the SVC and CS were evaluated. A right-sided can with an apical RV shock coil significantly increased DFT compared to a left-sided can [19.5 (16.4, 27.1) J vs. 13.3 (11.7, 19.9) J, P < 0.001]. Septal positioning of the RV coil led to a further DFT increase when using a right-sided can [26.7 (18.1, 36.1) J vs. 19.5 (16.4, 27.1) J, P < 0.001], but not a left-sided can [12.1 (8.1, 17.6) J vs. 13.3 (11.7, 19.9) J, P = 0.099). Defibrillation threshold of a right-sided can with apical or septal coil was reduced the most by adding both SVC and CS coils [19.5 (16.4, 27.1) J vs. 6.6 (3.9, 9.9) J, P < 0.001, and 26.7 (18.1, 36.1) J vs. 12.1 (5.7, 13.5) J, P < 0.001].

Conclusion

Right-sided, compared to left-sided, can positioning results in a 50% increase in DFT. For right-sided cans, apical shock coil positioning produces a lower DFT than septal positions. Elevated right-sided can DFTs may be mitigated by utilizing additional coils in SVC and CS.
Fast-track virtual reality software to facilitate 3-dimensional reconstruction in congenital heart disease
Authors: Bertelli Francesco , Raimondi Francesca , Godard Charlotte , Bergonzoni Emma , Cattapan Claudia , Gastino Elisa , Galliotto Francesco , Boddaert Nathalie , El Beheiry Mohamed , Masson Jean-Baptiste , Guariento Alvise , Vida Vladimiro L
Published: June 2023

OBJECTIVES

Two limitations of the clinical use of 3-dimensional (3D) reconstruction and virtual reality systems are the relatively high cost and the amount of experience required to use hardware and software to effectively explore medical images. We have tried to simplify the process and validate a new tool developed for this purpose with a novel software package.

METHODS

Five patients with right partial anomalous pulmonary venous return with adequate preoperative images acquired with magnetic resonance imaging were enrolled. Five volunteers with no previous experience in the field of 3D reconstruction were instructed to use the software after viewing a short video tutorial. Users were then asked to create a 3D model of each patient's heart using DIVA software. Their results were compared quantitatively and qualitatively with a benchmark reconstruction performed by an experienced user.

RESULTS

All our participants recreated 3D models in a relatively short time, maintaining a good overall quality (average quality score ≥ 3 on a scale of 1–5). The overall trend of all the parameters analysed showed a statistical improvement between case 1 and case 5, as users became more and more experienced.

CONCLUSIONS

DIVA is a simple software program that allows accurate 3D reconstruction in a relatively short time (“fast-track” virtual reality). In this study, we demonstrated the potential use of DIVA by inexperienced users, with a significant improvement in quality and time after a few cases were performed. Further studies are needed to confirm the potential application of this technology on a larger scale.
Exergetic-energetic effectiveness of a simple H2O-LiBr absorption chiller operated by solar energy collected using a direct flow evacuated tube collector
Authors: Al-Tahaineh Hamza A
Published: June 2023

A comprehensive examination of a 10-kW simple H2O/LiBr absorption system energized by an evacuated tube solar collector of the single-ended glass direct flow type has been conducted. For various operating conditions, the thermal and exergetic performance coefficients (COP, ECOP respectively), and exergy destruction (ΔE) through each system component are determined. At evaporator temperatures of 1°C, 5°C, and 10°C, COP around 0.75, 0.77, and 0.81, respectively, was achieved, and the maximum ECOP values of approximately 0.36, 0.35, and 0.342, respectively, could be attained. The highest values of COP and ECOP were seen at a desorber temperature of around 90°C. Around 41% of the system’s exergy destructed were attributed to the desorber. The lowest absorber exergy losses occur at a desorber temperature of 90°C for various evaporator temperatures. Increasing the desorber temperature by a factor of two reduces the system’s efficiency from 0.45 to 0.20. In addition, 65.88% solar collector exegetic efficiency was achieved when its differential temperature surpasses 50°C.
O02 Patterns of GP and nurse-independent prescriber prescriptions for antibiotics dispensed in the community in England: a retrospective analysis
Authors: Courtenay Molly , Gillespie David , Lim Rosemary
Published: June 2023

Background

The substitution of nurses for doctors is a strategy used in primary care to improve access to, and efficiency and quality of, care. Many of these nurses prescribe medicines including antibiotics.

Objectives

To identify nurse-independent prescriber (NIP) and GP numbers in England, the proportions and types of NIPs and GP antibiotic prescriptions dispensed in the community, and the impact of COVID-19 on the volume, rate and types of antibiotic prescriptions dispensed.

Methods

A descriptive population-based retrospective cohort study using data obtained from the National Health Service Business Service Authority (under a Freedom of Information request) on GP and nurse-independent prescriber prescriptions for antibiotics dispensed in the community in England between January 2014 and October 2021.

Results

Between 2014 and 2021, the number of NIPs (headcount) in England almost doubled from 24 457 to 41 649. Of the 41 649 NIPs in 2021, the prescriptions of 34 997 (84%) were dispensed in the community, i.e. a rise of 146% over this 6-year period. By contrast, GP numbers (headcount) rose by 10% to 44 681. Of the 25.373 million antibiotic prescriptions dispensed between 2014 and 2021, NIPs were responsible for 8.6%. The rate of dispensed antibiotic prescriptions decreased (NIPs by 50% and GPs by 21%) between 2014 and 2020 (where data across the full year were available). This decreasing trend continued following the onset of the pandemic across both groups. In line with guidance for the treatment of minor infections, narrow-spectrum antibiotics (penicillins, macrolides and tetracyclines) were the most frequently dispensed across both NIPs and GPs. Trends in prescription of antibiotics during the pandemic were reflected in the use of individual classes of antibiotics prescribed for RTIs.

Conclusions

Given the rising numbers of nurse prescribers and their increasing contributory influence on total antibiotic prescribing, it is important that this group is included in antimicrobial stewardship efforts. NIPs prescribe fewer antibiotics than GPs but work under different conditions (e.g. longer consultations and less complex patients), and so, interventions should also be tailored to this group and the population and context in which they are delivered.
O04 Understanding the key role of accessory genes in AMR phenotype through interpretable machine learning techniques
Authors: Dillon Lucy , Dimonaco Nicholas J , Creevey Christopher J
Published: June 2023

Background

Antimicrobial resistance (AMR) genes are found to be ubiquitous within the microbiome, even when antimicrobial usage is absent. To identify the AMR phenotype, the most common method is to use a laboratory-based assay. Yet, when dealing with samples from the microbiome, many species are difficult to culture within the laboratory. The vast quantity of strains would be time-consuming to culture. To avoid this, a computational approach may be a more favourable choice. AMR gene finder tools are efficient at determining the AMR genotype. Despite this, how a genotype relates to the AMR phenotype is still an open question.

Methods

To evaluate the relationship between the AMR phenotype and the AMR genotype, 16 950 genomes from BV-BRC which had corresponding MIC values were analysed. Using Weka’s J48 decision tree model, the relationship between the AMR phenotype and the AMR genotype was analysed. The role of accessory genes in relation to the AMR phenotype was analysed in the same way.

Results

The J48 models could predict the AMR phenotype accurately using AMR genes and accessory genes; the average accuracy was 91.7% and 92.2%, respectively. The results found that gene co-occurrence, presence and absence of genes are key factors to analyse when identifying the AMR phenotype from genomic data. These factors are not evaluated by commonly used AMR gene finder tools, which could miss vital information to determine the correct phenotype.

Conclusions

Our results highlight why we should continue to research the relationship between the AMR phenotype and genomic data.
P01 Antibiotic efficacy treatment of community-acquired pneumonia among CMV-infected individuals
Authors: Chichirelo-Konstantynovych Kiarina , Konstantynovych Tetyana
Published: June 2023

Background

The investigation is devoted to possible antibiotic resistance formation and its adverse event prognostic influence among young patients with community-acquired pneumonia (CAP) with cytomegalovirus (CMV) persistence and absence of other comorbid pathology.

Subjects and methods

The observation included 105 patients (average age 34.1 ± 0.8 years), which had been examined by epidemiological, clinical (including PORT prognostic scale) according to European Respiratory Society requirements, serological test for CMV IgM, IgG detection and antibiotic usage questionnaire for a 3-month period prior CAP.

Results

76.2% (n = 80) CAP patients had positive CMV IgG. CMV-positive patients were characterized by higher severity outcome risk in the nearest future versus CMV-negative ones (P < 0.0001): third risk class—14.9 times higher, fourth risk class—10.5 times higher. CMV IgG–positive results correlated with the CAP severity level (r (Spearman) = 0.472). In total, 51.4% (n = 54, among them 47 CMV-positive patients) mentioned antibiotic use during the last 3 months prior to CAP. During the CAP treatment, 75.0% (n = 60) of CMV-positive patients and 20.0% (n = 5) of CMV-negative ones did not respond to antibiotic treatment by cephalosporin and quinolone lines and needed changes in aetiology prescription according to antibiotic susceptibility microbial test. 61.3% (n = 47) of CAP patients (everybody was after medication replacement) got adverse events like antibiotic-associated diarrhoea (16 cases), QT prolongation in ECG (17 cases), creatinine, urea elevation (11 cases) and alanine/aminotransferase elevation (5 cases).

Conclusions

CMV persistence is associated with higher risk of severe CAP among young patients without comorbid pathologies and contributes to the antibiotic resistance creation as well as related side effects.
P03 A retrospective review of the safety and efficacy of dalbavancin at Ireland’s largest acute medical hospital
Authors: Conlon Peter , Murphy Aisling , McKernan Sarah , Williamson Clare , Kelly Mary , Bannan Ciaran
Published: June 2023

Background

Dalbavancin is a second-generation lipoglycopeptide antibiotic. It is licensed in Ireland and the United Kingdom for the management of acute skin and soft tissue infections. International colleagues report treatment success in its use for patients who are unable to stay in hospital for prolonged periods and not suitable for OPAT.1 We reviewed the use of dalbavancin at St. James’s Hospital, Dublin, which is the largest hospital in Ireland with over 700 acute beds. We are located in Dublin’s inner city which experiences significant socio-economic deprivation.

Methods

We used the electronic patient records at St. James’s Hospital to capture all uses of dalbavancin from August 2018 to September 2022. We established baseline demographics, indication, microbiological characteristics, if there was oversight by ID/micro, safety and treatment outcomes. We considered how many hospital days were saved if a patient was changed to dalbavancin and discharged home compared with how long they would have required to stay in hospital to pursue conventional treatment. One hospital day in an acute bed is estimated to cost 800€.

Results

We identified 23 patients who met the inclusion criteria. Baseline demographics are shown in Table 1. The most common indication was endovascular infection (35%) and skin and soft tissue infection (35%) (Figure 1). Most patients were not bacteraemic. Staphylococcus aureus was the most common organism identified on blood culture (Figure 2). In total, 322 hospital beds were saved, which equates to 257 600 EUR. No patients had an adverse drug reaction. 100% of cases were discussed with micro or ID.

Conclusions

Dalbavancin is a safe and effective drug. It is another tool that can be used when caring for patients who are experiencing unstable housing and challenging social circumstances. Our experience has found 0 adverse events, 69% of patients experienced treatment success (this increases to 88.8% if we exclude those lost to follow up). This is an important finding considering 17% of indications were considered ‘on label’. Dalbavancin can save money on hospital beds and also reduces non-recyclable plastic associated with repeated doses of IV antibiotics.
P05 Introducing new laboratory equipment for blood culture tests to improve the timeliness of antimicrobial susceptibility results in sepsis patients: a quality improvement project
Authors: Paul Rachel , Rajendran Rajesh , Eccles Simon , Worsley Michelle
Published: June 2023

Background

Blood culture tests are crucial for identifying microorganisms causing sepsis and planning targeted antimicrobial therapy based on susceptibility results. However, the traditional testing method has remained unchanged for the last 60 years, resulting in a delay of approximately four days for final antimicrobial susceptibility results. This delay contributes to increased antimicrobial resistance, broad-spectrum antimicrobial use and healthcare costs. This project aims to reduce the time taken for antimicrobial susceptibility results.

Methods

An initial pilot study trial of 100 samples with a new system will be conducted, followed by a qualitative and quantitative evaluation strategy, keeping the existing system as a gold standard. The project scope was defined to avoid scope creep, and a detailed SWOT analysis was conducted to identify the best equipment available on the market.

Interventions

A process map was created, and a detailed fish bone (Ishikawa) problem analysis was done to identify key issues and potential bottlenecks. A robust stakeholder analysis has been planned, and a detailed GANTT chart has been prepared. Implementing effective communication, leadership and nudge theory can engage stakeholders and mitigate risks. A cost-benefit analysis predicted a cost savings of nearly a million pounds within one hospital of seven within the Trust.

Conclusions

The introduction of new laboratory equipment for blood culture tests has the potential to reduce the turnaround time for antimicrobial susceptibility results significantly to less than 24 h, leading to early diagnosis and treatment of sepsis with targeted antimicrobial therapy. This initiative also counters various problems, including antimicrobial resistance, broad-spectrum antimicrobial use and healthcare costs. This project proposal is an important step towards improving blood culture testing and the timeliness of antimicrobial susceptibility results. Organizations like the NHS must seek to improve continuously for long-term effectiveness, and this project is one such change that will reap many long-term benefits.
P12 Partial implementation of procalcitonin measurement as an antibiotic stewardship in the ICU
Authors: Gill Simon , Phillips Ryan , Cain David , Powell Neil
Published: June 2023

Background

Procalcitonin (PCT) was introduced to the Royal Cornwall Hospital ICU in April 2020. A local PCT testing and decision support algorithm was developed using published consensus guidelines. We report our adherence to this algorithm in the ICU.

Methods

This retrospective observational study included all patients discharged from ICU from 1 February 2022 to 28 February 2022. Patients who received antibiotics during their admission were identified. Data on antibiotic indication, antibiotic course length in the ICU and pre-ICU and PCT testing were collected and compared with local PCT-based antibiotic prescribing guideline.

Results

Of 50 patients discharged, 34 (68%) received antibiotics and 26 for acute infections and 8 for deep-seated infections or surgical prophylaxis. A baseline PCT was sent in 10 (38%) patients with acute infections, with 4 having repeat PCT testing. Of four patients with a low baseline PCT, three were repeated and remained low. Two of these patients had antibiotics stopped as per PCT algorithm. A further patient with a low PCT was not initiated on antibiotics. Six patients had a high baseline PCT (>0.5) and one had a repeat PCT which remained high. Antibiotics were continued in all 6 patients. 16 patients with acute infections did not have baseline PCT testing with one having a random PCT during the antibiotic course. Five patients had deep-seated infections, and therefore, PCT testing was not indicated. However, 2 had baseline and repeat PCTs, with repeat PCTs low (<0.5) and antibiotics continued. Median course lengths were 5 days in the ICU and 6 days when pre-ICU antibiotics were included.

Conclusions

PCT testing in our ICU is low with only a third of eligible patients having a baseline PCT test with repeat PCT testing in accordance with local guidelines in the minority of these. There is some limited evidence that PCT testing is impacting antibiotic decision making in our ICU. We have identified that antibiotic course lengths in our ICU are relatively short. We have introduced PCT measurement as part of antimicrobial stewardship in our ICU. Fully embedding PCT testing, and PCT-guided antibiotic decision making, may further reduce antibiotic use. How to achieve this is challenging—there is a paucity of published PCT implementation studies.
P15 Direct provocation test for penicillin allergy delabelling: a 4-year retrospective review
Authors: Sugrue Ellen , McKee Edward D H , Sutherland Rebecca K
Published: June 2023

Background

Penicillin allergy is the most commonly reported drug allergy.1 Over 90% of these are mislabelled1. Labelled penicillin allergy is associated with increased broad-spectrum antibiotic use, increased antibiotic costs, and increased length of admission. A recent meta-analysis of delabelling studies showed that drug provocation test (DPT) is a low-risk procedure in patients with multiple clinical and financial benefits.2

Methods

Retrospective analysis of all patients who had DPT in hospital across one health trust 2019–2022. Hospital and GP electronic records of drug allergies were reviewed. GPs of patients who retained an allergy status post-DPT were contacted.

Results

46 DPTs were documented during this time. The PENFAST3 score was used to identify those suitable for DPT. One delayed reaction was recorded. No anaphylaxis was recorded. Infectious diseases were the primary specialty for DPT (67%). In total, 78% were carried out on medical patients. ID consult service was responsible for 100% of DPTs in surgical specialties. Seven patients who received DPT had been relabelled penicillin allergic post-DPT. Two were self-reported on presentation to hospital. Five were from physician review of historic documentation in hospital settings. In total, 56% of patients had not had GP documentation regarding allergy status updated.

Conclusions

This review concludes that DPT is safe in an inpatient population and inpatient review of reported penicillin allergy is an opportunity to identify mislabelled allergy. Infection specialists were the primary teams for DPT however given the safety profile of the DPT non-infection, and allergy specialists should be encouraged to use the protocol. Enhanced communication is needed with GPs to ensure the correct status is known in the community. Relabelling of penicillin allergy is a risk, and further education must be given to patients and healthcare providers post-DPT to ensure continuation of delabelled status.
P26 Epidemiology and risk factors associated with and clinical approach to Staphylococcus aureus bacteraemia at North West Anglia Foundation Trust (NWAFT)
Authors: Katherine Wong Wai Ying , Mlangeni Dennis
Published: June 2023

Background

Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and morbidity. Certain patient groups are predisposed to developing SAB. Careful monitoring of these patients for persistence of bacteraemia and development of complications is important to improve prognosis. There is international consensus on (i) treating patients with at least 2 weeks of IV antibiotics, (ii) performing echocardiography to evaluate for infective endocarditis and (iii) repeating blood cultures 2–4 days after initiating empirical treatment. Adherence to trust antimicrobial guidelines is also imperative to national antimicrobial stewardship.

Objectives

To characterize patients at risk of SAB and make recommendations to reduce the incidence and complications of SAB.

Methods

Retrospective review of case notes of patients whose blood culture results were positive for S. aureus from April to September 2022 in NWAFT. 57 results from 51 patients aged 0 to 96 years were included. The four audit standards were compliance with (i) trust empirical antimicrobial guidelines, (ii) 2-week duration of IV therapy, (iii) echocardiography evaluation for endocarditis, and (iv) repeat blood cultures 48–96 hours after initiating empirical treatment. Patients who were on palliative pathway were excluded from analysis of standards two to four. Prognostic outcomes were examined in terms of hospital readmission, recurrence and mortality.

Results

36 patients (70.6%) were found to harbour known risk factors, with the presence of indwelling prosthetic devices (83.3%) and type 2 diabetes (25.0%) being the most common. The most frequent sources of infection were unknown (27.5%) as well as the skin or soft tissue (17.6%). MRSA bacteraemia accounted for 10.5% of all cases. The compliances with (i) trust empirical antimicrobial guidelines, (ii) 2-week duration of IV therapy, (iii) echocardiography evaluation of endocarditis and (iv) repeat blood cultures 48–96 hours after initial blood culture were 52.8%, 75.0%, 57.8% and 66.0%, respectively. Rates of hospital readmission, recurrence and mortality were 39.5%, 11.4% and 35.3%, respectively.

Conclusions

The incidence of SAB correlates with the presence of risk factors, and SAB is associated with adverse outcomes. There was partial compliance with the audited outcomes. Introduction of trust SAB guidelines to guide clinical approach and adherence to local antimicrobial prescribing guidelines are imperative to improving patient outcomes.
P27 Rezafungin treatment of candidaemia and invasive candidiasis: outcomes stratified by baseline renal function—analysis of the Phase 2 + Phase 3 trials
Authors: Sandison Taylor , Vazquez Jose A , Honore Patrick M , Soriano Alex , Horcajada Juan P , Slavin Monica
Published: June 2023

Background

Rezafungin (RZF) once weekly (QWk) is a next-generation echinocandin in development for treatment of candidaemia and invasive candidiasis (IC) and prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in BMT. RZF QWk was compared with caspofungin (CAS) QD in two double-blind, randomized, controlled trials of treatment of candidaemia and/or IC: STRIVE (Phase 2, NCT02734862) and ReSTORE (NCT03667690).

Objectives

Trial data (Phase 2 + Phase 3) were analysed to evaluate outcomes stratified by renal function at baseline: CrCl ≥ 60 mL/min (normal/mild impairment [Norm/Mild]) and <60 mL/min (moderate/severe impairment [Mod/Sev]).

Methods

Outcomes were evaluated for differences between CrCl categories and between treatment groups: RZF QWk 400 mg on Wk 1 then 200 mg versus CAS QD 70 mg on Day (D)1 then 50 mg, for ≥14 days (≤4 Wks) w/optional oral fluconazole stepdown for CAS.

Results

D30 all-cause mortality (ACM)—Mod/Sev: RZF, 13% (7/54); CAS, 30.5% (18/59); Norm/Mild: RZF, 22.7% (17/75); CAS, 10.8% (9/83). Mycological eradication (ME) at D5—Mod/Sev: RZF, 75.9% (41/54); CAS, 61.0% (36/59); Norm/Mild: RZF, 74.7% (56/75); CAS, 66.3% (55/83). ME at D14—Mod/Sev: RZF, 75.9% (41/54); CAS, 57.6% (34/59); Norm/Mild: RZF, 69.3% (52/75); CAS, 74.7% (62/83). ≥1 treatment-emergent AE—Mod/Sev: RZF, 93.2% (55/59); CAS, 88.9% (56/63); Norm/Mild: RZF, 88.9% (72/81); CAS, 76.7% (69/90).

Conclusions

RZF efficacy was comparable across CrCl categories, with higher ME and lower D30 ACM in the Mod/Sev group. Further analyses are needed to evaluate the observed differences between treatment groups.
P31 Frequency, resistance pattern and antibiogram of bacterial pathogens isolated in Yastebsheron Hospital, Khartoum, Sudan
Authors: Altahir Mihad , Saeed Mohammed
Published: June 2023

Background

This study focused on providing a report about the current situation of AMR in Yastebsheron Hospital in Khartoum, Sudan, monitoring and identifying the resistant trends in clinical isolates, highlighting the gaps in the IPC and ASP through antibiogram analysis, and implementing its data to improve antibiogram-guided empirical antibiotic therapy selection.

Method

A retrospective longitudinal study. The study retrieved data from microbiology laboratory records from 1 January 2022 to 31 December 2022, at Yastebsheron Hospital. A total of 1182 clinical specimens were processed in 2022.

Results

The most frequent samples were urine, with a prevalence rate of 59.3%, of which 69.8% were female and 30.2% were male. The total Gram-positives were 52.6%, with Staphylococcus aureus accounted for 98%; out of the total specimens, MRSA accounted for 48.6%, and MSSA accounted for 11.8%. The total Gram-negative isolates were 48.3%, of which Escherichia coli Enterobacter, Proteus mirabilis, Pseudomonas aeruginosa and Klebsiella pneumoniae represented 25.4%, 21.8%, 9.8%, 9.4% and 3.8%, respectively. MSSA were highly susceptible to meropenem (97%) and vancomycin (95%), and luckily, MRSA isolates were susceptible to levofloxacin and colistin at 86% and to meropenem (84%), with minimal susceptibility to clindamycin (37%) and nalidixic acid (12%). Meropenem, colistin and nitrofurantoin were the most effective antibiotics against E. coli with more than 80% susceptibility rates, while cephalosporins and nalidixic acid showed minimal efficacy. Meropenem and levofloxacin were highly effective against Enterobacter, P. mirabilis, while the susceptibility rates for second-, third- and fourth-generation cephalosporins were less than 50% for both of them, and less than 30% for P. aeruginosa, P. aeruginosa was 100% susceptible to colistin.

Conclusions

Among infections, UTIs had the highest incidence rates. The majority of the isolates were S. aureus, then came Enterobacteriaceae, particularly E. coli, and then P. aeruginosa. Contrary to ciprofloxacin and norfloxacin, meropenem showed high efficacy against G-positive and G-negative isolates, while levofloxacin displayed moderately high results. Except for MSSA, the effectiveness of second-, third- and fourth-generation cephalosporins against G-positive and G-negative organisms was compromised. In order to stop the deterioration of the AMR status, it is crucial to implement the ASP strategies and tools effectively, as the emergence of MDR strains is alarming. Antibiogram’s formulation is essential for directing empirical antibiotic therapy and tracking the emergence of resistance.
P34 Gentamicin labels: improving the timing of gentamicin levels and reducing delay in dose administrations
Authors: Zakariya Muhammad Zakwan , Palenzuela Esperanza , Sutherland Rebekah , Lockman Khalida Ann
Published: June 2023

Background

Due to its narrow therapeutic index and significant risks of ototoxicity and nephrotoxicity, gentamicin requires meticulous prescribing, administration and monitoring. Despite readily available guidelines, gentamicin use continues to be associated with errors, with recent Datix reports within NHS Lothian recording incidents such as incorrectly prescribed doses or frequencies, missed levels, and delayed or omitted doses. In response to this, an audit was undertaken to investigate errors in gentamicin use within the Acute Medical Unit (AMU) at the Royal Infirmary of Edinburgh and evaluate the barriers to adherence to guidelines to unearth possible areas for improvement.

Methods

The initial audit studied patients prescribed gentamicin in AMU within a 3-week period, excluding those who received prophylactic or single one-off doses of gentamicin. The following parameters were examined both on their paper and electronic prescribing charts: (i) dose, (ii) dosing interval/frequency, (iii) time of level sampling, and (iv) administration times of the first and second gentamicin doses. After identifying issues with delayed gentamicin levels and subsequent dose administration times, we introduced the use of gentamicin labels in each AMU bay, in hopes of increasing staff awareness towards patients on gentamicin, thereby promoting timely level sampling and dose administration. The aforementioned parameters were re-audited for a further 3 weeks following this intervention.

Results

The baseline audit highlighted that only 23/31 (74%) patients had levels taken within the recommended window, and 23/31 (74%) received their second gentamicin doses at the right time. Following the introduction of the gentamicin labels, the second audit observed a slight improvement, with 31/40 (78%) patients having their levels taken within the recommended window, and 30/40 (75%) patients receiving their subsequent doses at the right interval. Noteworthily, in both the pre- and post-intervention groups, the majority of patients who had their second doses delayed received their first doses in the emergency department (ED) prior to admission to AMU.

Conclusions

In addition to improving staff awareness towards patients on gentamicin, a further overarching issue needs to be addressed: the delays in gentamicin administration which more commonly occurs for patients who transition from ED into AMU. Further interventions should therefore target improving the handover of time-critical medicines between ED and AMU.
P39 A qualitative study investigating the views of nurses and doctors on the management of urinary tract infections in long-term care facilities
Authors: Fleming Aoife , Monaghan Áine , Benjamin-Payne Natasha , Shah Mala , Barbosa Teresa M
Published: June 2023

Background

The most commonly reported infections in older persons’ long-term care facilities (LTCFs) are urinary tract infections (UTIs). UTIs contribute to high rates of antimicrobial prescribing, for the treatment and prophylaxis of UTI. Antimicrobials are often inappropriately prescribed and can increase the risk of antimicrobial resistance and other negative outcomes in LTCF populations.1

Objectives

To explore the views and experiences of nurses and doctors working in LTCF on the management of UTIs.

Methods

Qualitative, semi-structured interviews were conducted with nurses and GPs who work in or provide medical service in LTCFs in November 2022. Interviews were conducted online or by telephone, and recordings transcribed. Thematic analysis was conducted, and the themes were mapped to the Theoretical Domains Framework (TDF)1.2

Results

Seven nurses and eight GPs were interviewed. Key domains such as knowledge, memory, attention and decision making and beliefs about consequences had an influential role on UTI management as reported by participants. Contextual factors such as the time taken to obtain urine culture results, and social factors such as the key role of the LTCF nurse, were reported as key issues. Variability in practice and inconsistent knowledge of urine dipstick and UTI management guidelines were acknowledged in the management of UTIs and urine dipstick practices between participants.

Conclusions

This study identified social factors, contextual LTCF factors and variability in the management of UTI and urine dipstick practices across the participants. LTCFs require improved access to urine culture results, improved communication between all healthcare professionals involved and increased implementation of dipstick and UTI management guidelines.
P41 Use of delafloxacin in osteomyelitis: a case report
Authors: Vidwans Madhuri , Mitria Andra , Kandil Hala
Published: June 2023

Background

Data and experience with delafloxacin use in osteomyelitis (OM) and other deep-seated infections are limited, yet the burden of OM on healthcare systems is significant. We hereby describe the first case, to our knowledge, of delafloxacin use in OM.

Case description

A 94-year-old male with a history of prostate cancer, hypertension and heart failure was admitted to hospital in June 2022 with grade 4 bilateral heel ulcers. Empirical IV co-amoxiclav was started and then escalated to IV piperacillin/tazobactam. MRI scans confirmed the diagnosis of OM, and tissue and bone samples grew MDR Pseudomonas aeruginosa (piperacillin/tazobactam-resistant and ciprofloxacin intermediate), an additional challenge. Due to this result and poor clinical response, IV meropenem was prescribed. Off-label use of delafloxacin was discussed within the multidisciplinary team (MDT) to switch to oral administration, decrease length of hospital stay and account for the patient’s age and co-morbidities. Minimum inhibitory concentration of the MDR P. aeruginosa using EUCAST guidelines demonstrated delafloxacin susceptibility (0.125 mg/L). Delafloxacin also has good bioavailability and does not require therapeutic drug monitoring. The patient was started on 450 mg delafloxacin twice daily with monitoring of clinical response. After 10 days of initial in-hospital clinical monitoring, the patient was discharged home with 450 mg twice daily delafloxacin to complete 28 days of therapy. Follow-up imaging was not planned given his age and co-morbidities. District nurses reported improvement in his heel ulcers. On follow-up telephone consultation with the treating consultant in November 2022, the patient reported feeling well and noted improvement in his ulcers. Readmission and adverse events have not been reported to date and the ulcers continue to improve.

Conclusions

This case presents the first successful use of delafloxacin in osteomyelitis, with good tolerability and clinical response against MDR P. aeruginosa. Delafloxacin enabled our patient to be discharged 3 weeks earlier than planned which would otherwise not have been possible, improving his quality of life and reducing risk of hospital-acquired infections with associated costs. Delafloxacin also enables early IV to oral switch in support of the antimicrobial stewardship agenda.
Outcome, risk factors and therapeutic strategies in carbapenem-resistant Gram-negative bacteraemia from Pakistan
Authors: Fatima Mehreen , Dodani Sunil Kumar , Babar Zaheer Udin , Badlani Sanjay , Rani Beena , Mushtaq Maryam , Nadeem Ali , Nasim Asma
Published: June 2023

Background

Carbapenem-resistant Gram-negative (CRGN) bacteraemia has high mortality and limited therapeutic options. We assessed the risk factors and outcome of CRGN bacteraemia treated with limited options.

Methods

A prospective cohort study done at a tertiary care hospital in Pakistan, from October 2021 to August 2022. All patients >18 years with CRGN bacteraemia were assessed for demographics, source, risk factors and treatment received. Outcome was assessed as bacterial clearance and all-cause mortality at Day 14 of bacteraemia.

Results

We included 175 patients. Median age was 45 years (IQR 30–58) and the majority of our patients were on haemodialysis (75%). We found 14 day mortality in 26.8% of our patients; in addition, microbiological clearance was achieved in 95%. The central line (49.7%) was the most common source and Klebsiella spp. (47%) the most common organism. On multivariate analysis, risk factors for mortality were Foley’s catheter [aOR 2.7 (95% CI 1.1–6.5)], mechanical ventilation [aOR 5.1 (95% CI 1.6–15.8)] and Pitt bacteraemia score >4 [aOR 3.48 (95% CI 1.1–10.5)]. Source control was a significant protective factor [aOR 0.251 (95% CI 0.09–0.6)]. The majority received a colistin-based regimen with no difference in mortality between monotherapy and combination therapy.

Conclusions

Our cohort of CRGN bacteraemia is unique, comprising younger patients mostly on haemodialysis with a central line as the source of bacteraemia and we have found 14 day mortality of 27%. Colistin with various combinations can be an effective option in patients with renal failure having prompt source control.
Memories without Survival: Personal Identity and the Ascending Reticular Activating System
Authors: Meier Lukas J
Published: June 2023

Lockean views of personal identity maintain that we are essentially persons who persist diachronically by virtue of being psychologically continuous with our former selves. In this article, I present a novel objection to this variant of psychological accounts, which is based on neurophysiological characteristics of the brain. While the mental states that constitute said psychological continuity reside in the cerebral hemispheres, so that for the former to persist only the upper brain must remain intact, being conscious additionally requires that a structure originating in the brainstem—the ascending reticular activating system—be functional. Hence, there can be situations in which even small brainstem lesions render individuals irreversibly comatose and thus forever preclude access to their mental states, while the neural correlates of the states themselves are retained. In these situations, Lockeans are forced to regard as fulfilled their criterion of diachronic persistence since psychological continuity, as they construe it, is not disrupted. Deeming an entity that is never again going to have any mental experiences to be a person, however, is an untenable position for a psychological account to adopt. In their current form, Lockean views of personal identity are therefore incompatible with human neurophysiology.
Public Secrets: The Dynamics of Publicity and Secrecy in Offensive Cyber Operations
Authors: Baram Gil
Published: June 2023

Historically, offensive cyber operations (OCOs) have been considered a practice that states could carry out covertly, away from the public eye, with both perpetrators and defenders having incentives to remain silent. Over the past few years, however, perpetrators and defenders have publicly acknowledged their involvement in OCOs. How common is this strategic choice among states? What are its characteristics? In this research note I show that this is not a binary choice, and that there is variance in the strategies available to either side. I then examine what state behavior patterns can be identified by using compiled data of OCOs between 1996 and 2019. I show that this phenomenon of giving up secrecy is occurring and point out on states’ characteristics and probabilities of choosing each strategy. Initial findings show significant use of public strategies by perpetrators (20 percent) and more so by defenders (50 percent), and that democracies tend toward public credit claiming and attribution, while less democratic countries tend toward public denial. As governments increasingly engage in OCOs, the implications of this research note are of interest to scholars and practitioners alike.
Comparative network analysis as a new approach to the editorship profiling task: A case study of the Mishnah and Tosefta from Rabbinic literature
Authors: Zadok Avital , Zhitomirsky-Geffet Maayan , Schler Jonathan , Katzoff Binyamin
Published: June 2023

Social network analysis of characters in historical works is a popular research methodology in the study of historical literature. This article proposes using this methodology to characterize and comparatively analyze editing styles of similar historical literary works to determine whether they were edited by the same hand. To that end, the study proposes constructing a network of characters for each of the works being studied and to compute standard statistical measures for these networks, thus producing a network-based profile for the editing style of each work, which can be compared to the profiles of various other works. To determine the effectiveness of this new approach, it was tested on two similar works from the realm of Rabbinic literature—the Mishnah and the Tosefta. Our findings show that despite the abundant structural, thematic, and linguistic similarities of the works, their network-based profiles demonstrated clear differences between them with respect to various parameters, like the degree of connectivity, density, and centrality of the networks and their communities, and also with respect to the usage of different types of relationships in each network. These differences are reflected in the network features of the works, rather than in their texts, and so it would be difficult to identify them using direct stylometric analysis on the texts of the works, especially given the stylistic and thematic similarity between them. The approach presented in this article forms a basis for developing automatic classifiers to identify different editors and editing styles based on works’ network-based profiles.