bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Blood Eosinophilia at Diagnosis of Inflammatory Bowel Disease Is Associated With Severe Disease Course: A Nationwide Study From the epi-IIRN Cohort
Authors: Yerushalmy-Feler Anat , Lujan Rona , Loewenberg Weisband Yiska , Greenfeld Shira , Ben-Tov Amir , Ledderman Natan , Matz Eran , Dotan Iris , Lev-Tzion Raffi , Goren Idan , Turner Dan , Cohen Shlomi 
Published: August 2024

Abstract

Background and Aims
We conducted this nationwide study to evaluate the association between peripheral blood eosinophilia (PBE) and long-term outcomes in children and adults with inflammatory bowel diseases (IBDs).

Methods
Data from the Epidemiology Group of the Israeli IBD Research Nucleus (epi-IIRN) cohort, a validated population-based IBD database, included patients diagnosed between 2005 and 2020, who had an eosinophil count recorded at diagnosis, and non-IBD controls. PBE was defined as an eosinophil count of &gt;0.5 × 109/L. Severe disease course was defined as corticosteroid dependency, use of ≥2 biologics from different classes, or surgery. Time-to-outcomes, including severe disease course, was determined by Cox proportional hazard models.

Results
This study included 28 133 patients (15 943 Crohn’s disease [CD] and 12 190 ulcerative colitis [UC]) and 28 724 non-IBD controls. The prevalence of PBE was 13% in the IBD group and 5% in the control group (p &lt; 0.001). PBE was more prevalent in UC (16.1%) compared to CD (10.6%, odds ratio [OR] = 1.52, 95% confidence interval [CI], 1.42-1.63; p &lt; 0.001) and in pediatric-onset (23.5%) compared to adult-onset (11%) IBD (OR = 2.14, 95% CI, 1.97-2.31; p &lt; 0.001). In a multivariate analysis, PBE was a predictor of severe disease course in IBD (hazard ratio [HR] = 1.49, 95% CI, 1.38-1.62, p &lt; 0.001). PBE also predicted time-to-hospitalization (HR = 1.24, 95% CI, 1.19-1.30), use of corticosteroids (HR = 1.32, 95% CI, 1.28-1.36), corticosteroid dependency (HR = 1.37, 95% CI, 1.31-1.43), and need for biologics (HR = 1.27, 95% CI, 1.21-1.33).

Conclusions
In this largest nationwide study, PBE predicted severe IBD course. These findings support the use of PBE as a marker of adverse outcomes of IBD and as a potential target for future therapies.
Diverticular disease and risk of incident major adverse cardiovascular events: a nationwide matched cohort study
Authors: Forss Anders , Ma Wenjie , Thuresson Marcus , Sun Jiangwei , Ebrahimi Fahim , Bergman David , Olén Ola , Sundström Johan , Ludvigsson Jonas F 
Published: August 2024

Abstract

Background
An increased risk of cardiovascular disease (CVD) has been reported in patients with diverticular disease (DD). However, there are knowledge gaps about specific risks of each major adverse cardiovascular event (MACE) component.

Methods and results
This nationwide cohort study included Swedish adults with DD (1987–2017, N = 52 468) without previous CVD. DD was defined through ICD codes in the National Patient Register and colorectal histopathology reports from the ESPRESSO study. DD cases were matched by age, sex, calendar year, and county of residence to ≤5 population reference individuals (N = 194 525). Multivariable-adjusted hazard ratios (aHRs) for MACE up until December 2021 were calculated using stratified Cox proportional hazard models. Median age at DD diagnosis was 62 years, and 61% were females. During a median follow-up of 8.6 years, 16 147 incident MACE occurred in individuals with DD and 48 134 in reference individuals [incidence rates (IRs)= 61.4 vs. 43.8/1000 person-years], corresponding to an aHR of 1.24 (95%CI = 1.22–1.27), equivalent to one extra case of MACE for every 6 DD patients followed for 10 years. The risk was increased for ischaemic heart disease (IR = 27.9 vs. 18.6; aHR = 1.36, 95%CI = 1.32–1.40), congestive heart failure (IR = 23.2 vs. 15.8; aHR = 1.26, 95%CI = 1.22–1.31), and stroke (IR = 18.0 vs. 13.7; aHR = 1.15, 95%CI = 1.11–1.19). DD was not associated with cardiovascular mortality (IR = 18.9 vs. 15.3; aHR = 1.01, 95%CI = 0.98–1.05). Results remained robust in sibling-controlled analyses.

Conclusions
Patients with DD had a 24% increased risk of MACE compared with reference individuals, but no increased cardiovascular mortality. Future research should confirm these data and examine underlying mechanisms and shared risk factors between DD and CVD.
The cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012–2019
Authors: Chen Dong-Yi , Chang Shu-Hao , Huang Wen-Kuan , Hsieh I Chang , See Lai-Chu 
Published: August 2024

Abstract

Aims
Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. We investigated the relationship between temperature and new-onset HF by risk strata.

Methods and results
This nationwide cohort study analysed daily data on ambient temperature, the dynamic status of risk factors (age, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease, hypertension, myocardial infarction, and atrial fibrillation), and new-onset HF among the Taiwan population from 2012 to 2019. Poisson regression, Austin’s algorithm, and classification and regression tree (CART) were used to determine risk strata and obtain the predicted HF rate. 148 708 patients developed new-onset HF over 152.52 million person-years. Three risk strata for HF were identified: Stratum 1 was predominantly those without any comorbidity (89.9%); Stratum 2 was those aged 60–69 with 2–3 comorbidities or aged 70+ with 1–2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more comorbidity (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The R2 of the Poisson regression with the three risk strata and the daily minimum temperature on the ln HF incidence rates was 77.99%. The risk of HF increased as temperatures decreased, and the slopes were 1.032, 1.040, and 1.034 for Strata 1–3, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1–3, respectively. Cross-validation reveals a good fit and predicted HF rates by ambient temperature for the three strata were provided.

Conclusion
Cold temperatures are associated with an increased risk of new-onset HF. Stratum 2 (aged 60–69 with 2–3 comorbidities or aged 70+ with 1–2 comorbidities) are particularly susceptible to cold-related new-onset HF.
Do sympatric catfish radiations in Lake Tanganyika show eco-morphological diversification?
Authors: Peart Claire R , Bills Roger , Newton Jason , Near Thomas J , Day Julia J 
Published: August 2024

Abstract
Adaptive radiation is characterized by eco-morphological differentiation, in which niche partitioning has been shown to be a central response to natural selection during the diversification of animal clades. This process is suggested to have generated the exceptional biodiversity in the East African rift lakes; however, aside from the cichlid fishes, the nature of the divergence, over time, or among species is less clear in the other radiations. To address this, we focus on two distantly related sympatric Lake Tanganyika catfish clades, the genus Synodontis, considered to be Müllerian mimics, and the subfamily Claroteinae. We investigate to what extent, if any, these radiations have undergone eco-morphological diversification. We place these radiations in a common phylogenetic context, and test for morphological divergence and trophic niche partitioning using novel trait data and stable isotope signatures. Diversification of both catfish clades was recent, with the Synodontis radiation synchronized in time with individual genera within the claroteine radiation, suggesting initial diversification was facilitated by lake basin dynamics and/or lake level fluctuations. There is evidence for eco-morphological diversification within the claroteine radiation, as inferred from observed morphological disparity and divergence in diet both between and within genera; however, several species show significant overlap in dietary isotopic signatures. In contrast, the Synodontis radiation has greater overlap between taxa both in morphology and in isotopic signatures potentially indicating niche conservatism, suggesting different selective forces may be driving these radiations.
Young people’s views and experience of diet-related inequalities in England (UK): a qualitative study
Authors: Er Vanessa , Crowder Mary , Holding Eleanor , Woodrow Nicholas , Griffin Naomi , Summerbell Carolyn , Egan Matt , Fairbrother Hannah 
Published: August 2024

Abstract
Inequalities in diets contribute to overall inequalities in health. Economic inequality and inequalities in access to healthy food are key drivers of poor diet and ill health among young people (YP). Despite mounting evidence of structural barriers to healthy eating, less is known about how YP view and experience these inequalities where they live, and how to address them. To explore YP’s perspectives on the drivers of diet-related health inequalities, we conducted three interlinked focus groups with YP aged 13–21 years from six youth groups across three geographical areas in England. We analysed the data inductively and deductively using reflexive thematic analysis and generated themes by examining how social structure, context and agency interact and impact YP’s diet. YP were aware of how inequalities in employment conditions impact their families’ income and ability to eat a healthy diet. They cited the high availability of hot food takeaways in their local areas as a significant barrier to healthy eating but did not support closing or restricting these outlets. They held strong views on policies to tackle diet inequality and showed a nuanced understanding of the strengths and limitations of universal and targeted approaches. Our study showed that YP have an awareness and understanding of food as important in relation to health, and of diet-related inequalities. However, further efforts are needed to shape and promote policies that resonate with YP and address both their health and wider social concerns.
O01 Antimicrobial resistance and death certification: are we there yet?
Authors: Baltas Ioannis , Rawson Timothy M , Houston Hamish , Grandjean Louis , Pollara Gabriele 
Published: August 2024

Abstract

Background
The impact of antimicrobial resistance (AMR) on death at the patient level remains challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK centre through death certification.

Methods
This was a retrospective study of all patients who died in University College London Hospitals NHS Foundation Trust in 2022 (N=758). Clinical records of participants with positive microbiological samples within 28 days of death were reviewed by two independent investigators. AMR-attributable deaths were defined using a newly proposed standardized patient-level definition after consensus agreement between the two investigators. A third investigator acted as a tiebreaker in cases of disagreement.

Results
Overall, infection was the underlying cause of death for 11.7% (89/758) of participants and was implicated in the pathway that led to death in 41.1% (357/758) of cases. The most common infection syndromes leading to death as documented on the medical certificate of confirmation of death (MCCD) were respiratory tract infections, sepsis and COVID-19. In total, 4.2% (32/758) of all deaths were AMR-attributable. AMR-attributable deaths were more commonly recorded in patients admitted under haematology (7.5%, 9/120) and in younger patients (median age 67 versus 72, P=0.01). The median time from the index sample collection until death was 4.5 days (IQR 2–10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were caused by treatment failure and subsequent treatment delay caused by intrinsic resistance mechanisms, primarily by Enterococcus faecium (38.9%, 7/18), Enterobacterales carrying repressed chromosomal AmpCs (27.7%, 5/18) and Pseudomonas aeruginosa (22.2%, 4/18). On the contrary, a minority of AMR-attributable deaths (43.7%, 14/32) were caused by acquired resistance mechanisms, primarily derepressed AmpCs (28.6%, 4/14) and ESBLs (21.4%, 3/14). The median time to effective treatment was 32 h 15 min and did not differ significantly between the two groups. Only 62.5% (20/32) of AMR-attributable deaths as judged by study investigators had infection recorded on the MCCD. AMR was not recorded as a cause of death in any of the patients, including the 14 patients who were deemed to have suffered deaths due to acquired resistance by the study investigators.

Conclusions
Infection and AMR were significant causes of death in this cohort, yet there significantly underreported during death certification. In a low incidence setting for AMR, delays in treatment and AMR-attributable mortality due to intrinsic resistance mechanisms (expected phenotypes) were more common compared with acquired resistance mechanisms.
P23 Advance market commitment for point of care diagnostic focused on neonatal sepsis: estimating costs and effectiveness
Authors: Bansal Akhil , Howes Adam , Arih Ilona 
Published: August 2024

Abstract

Background
Antimicrobial resistance (AMR) is a pressing global health concern, responsible for millions of deaths every year. Overuse and misuse of antimicrobials is a significant driver of AMR and is partly driven by a lack of decision-relevant and timely diagnostic tests to guide treatment. Point of care tests (POCT) would be of great public health benefit for neonatal sepsis, which refers to systemic life-threatening infections in newborns in their first 28 days of life. Neonatal sepsis, for which over- and inappropriate prescription of antibiotics are very high, affects 1.3 to 3.9 million neonates and accounts for nearly a quarter of all neonatal deaths. However, due to insufficient market incentives and revenue guarantee for developers, research and development pipelines are stagnant and no such POCT exists. One proposed solution is an advanced market commitment (AMC), a form of ‘pull incentive’ that would aim to ‘pull’ a new POCT to market. In an AMC, donors commit to a fund from which a specified subsidy is paid per unit purchased by low income countries until the fund is exhausted. This aims to strengthen suppliers’ incentives to invest in research, development and capacity.

Methods
This study modelled the costs and outcomes of an AMC for a neonatal sepsis POCT that would seek to identify the presence or absence of sepsis. Modelled for the Indian public healthcare system, the test was conceived as an adjunct to clinical judgement where there is diagnostic uncertainty if a neonate has sepsis. The POCT was compared with current best practice. Benefits of increased identification of neonatal sepsis and decreased burden of AMR were considered; cost of diagnostic tests and antibiotic treatment were considered. Cost-effectiveness and incremental cost-effectiveness were calculated in cost per disability adjusted life year (DALY), from both the perspective of the Indian healthcare system and investors to an AMC.

Results
From our cost-effectiveness model, a POCT would have an incremental cost-effectiveness of $93.56/DALY (compared with current clinical practice) for the Indian healthcare system, with a cost-effectiveness of $5.9/DALY for donors to an AMC. On sensitivity analysis, the cost benefit analysis is contingent on a test with sufficiently high specificity and sensitivity and varies depending on estimated AMR burden.

Conclusions
Although a novel market incentive with some uncertainty in model parameters, an AMC for a neonatal sepsis POCT may be highly effective and cost-effective from both a global health and AMR perspective.
P29 Understanding penicillin allergy assessment and delabelling massive open online community
Authors: Powell Neil , Quinn Alicia , Weaving Chris , Sandoe Jonathan ,   educational team, Bhogal Rashmeet , Elkhalifa Shuayb , Blumenthal Kimberly , Sneddon Jacqueline , Tonkin-Crine Sarah , Trubiano Jason , Stone Cosby , Stollings Joanna 
Published: August 2024

Abstract

Background
PenA records are associated with antibiotic prescribing that is potentially less effective and more harmful. The paucity of allergy specialists worldwide has prompted non-allergist delivered penicillin allergy delabelling (PADL). To facilitate non-allergist delivery of PADL, a massive open online course (MOOC) was developed with objectives to raise awareness and provide healthcare workers with the requisite knowledge and skills to deliver PADL.

Methods
Developmental support and funding for the MOOC was provided by BSAC. An educator panel was convened with topic experts from the USA, UK and Australia representing infectious diseases, allergy, pharmacy, medical microbiology and health psychology. Key learning objectives were defined, the course structure was agreed, and content was developed and peer reviewed by panel members and BSAC. The MOOC was launched and hosted on FutureLearn. Data on learner numbers, demographics and feedback were collected to measure course uptake and effectiveness in meeting the objectives.

Results
The 2 week course entitled ‘Understanding Penicillin Allergy Assessment and Delabelling’ with 6 h of learning was published 20 November 2023 on FutureLearn. The course was accredited by the Royal College of Pathologists for 6 CPD points. As of 10 April 2024, there were 1599 learners from 119 countries, which were: 16% medical doctors, 2% surgical doctors, 3% other doctors, 18% pharmacists, 11% nurses, 34% students, 1% physicians associate (PA), 1% nurses associate and 15% other. The top five countries by joiner count are UK (466), India (118), Pakistan (60), Italy (44) and Egypt (44). Of those that completed the course and responded to the end-of-course survey, 40/65 (62%) rated the course better than expected, 24 (37%) had their expectations met and 1 (1.5%) rated the course worse than expected. Overall, 61 (94%) gained new knowledge or skills, 29 (45%) applied their learnings and 49 (75%) reported sharing their learnings with others. Examples of learner comments:
“Truly, the best penicillin allergy explanation I have ever come across. So detailed and well illustrated. Thank you!”
“Fantastic course! I’m going to recommend every health care professional at my organisation complete this as part of my Antimicrobial Stewardship training. Thank you for putting it together.”

Conclusions
The MOOC has reached a broad range of learners from a variety of disciplines in a range of countries globally. The reception has been very positive, with comments stating that knowledge of penicillin allergies had improved and applied to improve local PADL services—a direct indication of meeting the learning outcomes.
P37 Molecular characterization of resistance and heteroresistance to cefiderocol in clinical Gram-negative isolates
Authors: Young Francesca , Watson Celeste , Rofael Sylvia , Wey Emmanuel , Balakrishnan Indran 
Published: August 2024

Abstract

Background
Treatment failure with cefiderocol has been attributed to heteroresistance, a phenomenon whereby clinically susceptible bacterial populations contain a minority resistant subpopulation.

Objectives
To compare three antimicrobial susceptibility tests (AST) for detecting cefiderocol resistance/heteroresistance; to investigate the population dynamics of heteroresistant isolates in response to antibiotic exposure; and to characterize the molecular mechanisms underlying resistance and heteroresistance to cefiderocol.

Methods
Forty-three Gram-negative clinical isolates were screened for cefiderocol susceptibility using disc diffusion, Etest and broth microdilution (BMD), according to EUCAST guidelines. Eleven isolates demonstrating heteroresistance were serially passaged in iron-depleted Mueller–Hinton II broth containing sub-inhibitory concentrations of cefiderocol (0.25xMIC) and then further passaged in the absence of antibiotic selection pressure. Changes in MIC and frequency of the heteroresistant phenotype were determined using Etests. Fourier transform infrared and MALDI-TOF spectroscopy were used to compare the molecular differences between resistant, heteroresistant and susceptible phenotypes.

Results
Etest assays significantly underestimated cefiderocol resistance (P&lt;0.001), with 32% categorical agreement, compared with 75% for disc diffusion, relative to the gold-standard BMD method. However, BMD is poor at detecting heteroresistance, identifying only 1/11 (9%), whilst Etests identified 3/11 (27%) (Figure 1). After passages under antibiotic selection pressure, 2/11 (18%) increased in MIC (mean: 3-fold). After subsequent antibiotic-free passages, 4/11 (36%) demonstrated increased MICs. Interestingly, this contrasted with isolates only passaged in antibiotic-free medium, in which 8/11 (72%) decreased in MIC, reverting to the more susceptible parental phenotypes. Molecular analyses highlighted characteristic differences between the spectra of parental populations and subpopulations, indicating complex mechanistic modifications in carbohydrate, lipid and protein complexes.

Conclusions
Detection of clinically significant heteroresistance indicates that resistant subpopulations may exist amongst a phenotypically susceptible population, underscoring the need for heteroresistance detection methods in clinical settings. The heteroresistant phenotype was unstable and reverted to susceptibility unless exposed to cefiderocol. Interestingly, isolates exposed to antibiotic pressure often exhibit increases in MIC only after antibiotic removal. These findings suggest that cefiderocol exposure primes isolates for later development of resistance. Spectroscopic analyses confirm the presence of characteristic molecular fingerprints associated with cefiderocol susceptibility, which may inform our understanding of resistance.