bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidetector‐row CT features and histopathological analysis of pericardial recesses in dogs
Authors: Negro Linda , Cordella Alessia , Costa Arianna , Nordio Laura , Bertolini Giovanna
Published: May 2023

At the level of pericardial reflections and near the great thoracic vessels, pericardial recesses (PRs) are present, where fluid can collect to increase the pericardial reserve volume. To date, these structures have not been described in vivo in veterinary patients. The aims of this observational and descriptive study were to describe the location and appearance of PRs in dogs, as seen with multidetector‐row CT (MDCT), and to develop a dedicated imaging technique for their best visualization. Dogs who underwent MDCT examination of the whole body were included in the study and CT data were retrospectively evaluated. Dogs with any thoracic abnormality were excluded. MDCT analysis of the PR's was compared with the pathological features of PRs. PRs were identified as fluid‐attenuating (10‐30 HU), non‐enhancing structures showing varied appearance. Two types of PRs were identified at the level of the transverse sinus of the pericardium and classified on the basis of their anatomic location: the aortic recess and the pulmonic recess. A third pericardial fluid‐containing structure was seen in a little number of cases, at the level of the termination of the caudal vena cava into the right atrium. A dorsal, slight oblique multiplanar section through the aortic bulb resulted the best technique for visualization of all the recesses. Anatomo‐pathological evaluation confirmed the location and the presence of pocket‐like reflections of the pericardium identified with 3D‐CT models. Knowledge of the CT appearance of the pericardial recesses is necessary in order to avoid their misinterpretation and subsequent unnecessary invasive investigations.
Mechanical Response of Trapezoidal Cage on Cervical 6–Cervical 7 Level
Authors: Balamurugan S. , Chhatoi Rushav Kumar , Dixit Vallabh , Manickam Pechimuthu Susai
Published: May 2023

The human cervical spine is the most essential support system of the whole body. It consists of vertebras, tissues, facet joints, intervertebral disks and ligaments. The problems in the cervical spine is more frequent, it can be due to accident or increase with the age. The objective of this study is to develop the interbody fusion cage with different porosity size and study the behavior of the cage for the compression loads. The bone graft introduced in the cage will provide osteointegration with the adjacent vertebra. For the biomechanical analysis we created the cervical level C6–C7 and inserted the cage in the functional spine unit and analyzed using finite element analysis for compression loadings. In this study, by introducing the semispherical shape porosity in the inferior and superior surface of the cage will reduce the cage stress and in the same porosity we introduced the bone graft for the better osteointegration. So, the reduced stress in the cage structure will reduce the occurrence of the subsidence and migration of the cage.
Co-Optimization of the Spooling and Cross-Current Trajectories of an Energy Harvesting Marine Hydrokinetic Kite
Authors: Bhattacharjee Debapriya , Tiburcio Miguel Alvarez , Opila Daniel F. , Vermillion Christopher , Fathy Hosam K.
Published: May 2023

This paper examines the problem of simultaneously optimizing the spooling and cross-current flight trajectory of a tethered marine hydrokinetic kite using an analytic solution of its inverse dynamics. Tethered kites hold considerable promise for energy production, especially when undergoing cross-current motion. The novelty of this work lies in the use of an analytic solution of the inverse dynamics of the kite to solve the trajectory optimization problem. The term “inverse dynamics” refer to the process of obtaining an exact solution for the actuator inputs from the position, velocity, and acceleration of the kite. While the literature on tethered kites explores trajectory optimization in great detail, most of the work exploits the forward dynamics of the kite, and does not simultaneously optimize the spooling motion and cross-current trajectory. This paper formulates the co-optimization of the kite spooling and cross-current trajectory using a three degrees-of-freedom kite model, paired with an inelastic tether model. The analytic solution of the inverse dynamics is solved in terms of the roots of a fourth-order polynomial in terms of the angle of attack. A simulation study validates the optimization approach and shows that the kite is able to achieve significant energy production.
Experimental and Probability-Based Approaches to Estimate Leakage Rates in Plugged and Abandoned Wells in CO2-Enhanced Oil Recovery Fields
Authors: On Thinh , Nguyen Tan , Balch Robert
Published: May 2023

When a well is at the end of its lifetime, it must be permanently plugged and abandoned to prevent fluid migration. Federal and local governmental authorities in different regions regulate plug and abandonment activities by setting minimum requirements for oil and gas operators. The regulatory requirements should be informed by an understanding of how wellbore damage occurs. Near-wellbore environments may experience long-term and complex coupled hydro-mechanical-chemical processes, such as those at CO2-enhanced oil recovery fields, where internal pressure loading on the casing varies greatly and essentially unpredictably due to changing injection operations, production operations, and/or reservoir flow conditions. The time-varying loading inside the wellbore may result in damage to the wellbore cement, especially the bond between casing and cement. We present results of an experimental setup that simulates the representative cement, casing, and internal casing pressure for field conditions, including measurement of evolving cement permeability and X-ray computed tomography to quantify near-wellbore damage and potentially identify damage mechanisms due to time-dependent and cyclic loading. Findings include an increase in cement permeability due to cyclic loading and the chloride ion’s effects on steel corrosion. We include a case study for a well in the Farnsworth Unit, Texas, where the cement plug was designed based on the minimum requirements of U.S. regulations. Based on the experimental results of permeability increase due to cyclic loading, we develop a probability-based approach for well-integrity using a normal distribution and rejection sampling to estimate potential leakage rates through the cement plug.
Generality-oriented optimization of enantioselective aminoxyl radical catalysis
Authors: Rein Jonas , Rozema Soren D. , Langner Olivia C. , Zacate Samson B. , Hardy Melissa A. , Siu Juno C. , Mercado Brandon Q. , Sigman Matthew S. , Miller Scott J. , Lin Song
Published: May 2023

Catalytic enantioselective methods that are generally applicable to a broad range of substrates are rare. We report a strategy for the oxidative desymmetrization of
meso
-diols predicated on a nontraditional catalyst optimization protocol by using a panel of screening substrates rather than a singular model substrate. Critical to this approach was rational modulation of a peptide sequence in the catalyst incorporating a distinct aminoxyl-based active residue. A general catalyst emerged, providing high selectivity in the delivery of enantioenriched lactones across a broad range of diols, while also achieving up to ~100,000 turnovers.
Braiding Indigenous rights and endangered species law
Authors: Lamb Clayton T. , Willson Roland , Menzies Allyson K. , Owens-Beek Naomi , Price Michael , McNay Scott , Otto Sarah P. , Hessami Mateen , Popp Jesse N. , Hebblewhite Mark , Ford Adam T.
Published: May 2023

Recovery targets fall short of culturally meaningful abundance
Don’t let the Court disrupt science
Authors: Falk Adam F. , Espinosa Lorelle L.
Published: May 2023

It is widely expected that by this summer, the United States Supreme Court will overturn long-standing precedents allowing the consideration of race as one factor among many in university admissions. The current legal regime goes back to the Court’s decision (
Regents of University of California
v.
Bakke
) in 1978 that banned racial quotas while allowing consideration of race for the purpose of creating a diverse educational environment. Although the law has evolved since then, almost all universities have relied on the
Bakke
framework to support their strategies to educate a diverse citizenry. If the Court upends those practices, the implications for the scientific enterprise will be far-reaching. It is essential that the process of science continue to become more diverse, equitable, and inclusive. Studies show that the best science is done when teams are diverse. Moreover, the very questions scientists address can change substantially when those scientists come from a variety of racial, ethnic, and other backgrounds.
Human genomic ‘bycatch’ threatens privacy
Authors: Vogel Gretchen
Published: May 2023

Environmental and microbe studies net human DNA that can reveal health, identity
Authorship listing for a harasser roils astronomy
Authors: Langin Katie
Published: May 2023

After outcry, Geoff Marcy was removed from a recent manuscript. Will policy changes be next?
Damage sidelines Virgo gravitational wave detector
Authors: Cho Adrian
Published: May 2023

The hunt for sources resumes this month with just the twin LIGO detectors and a limited science reach
Viral Capsid, Antibody, and Receptor Interactions: Experimental Analysis of the Antibody Escape Evolution of Canine Parvovirus
Authors: López-Astacio Robert A. , Adu Oluwafemi F. , Goetschius Daniel J. , Lee Hyunwook , Weichert Wendy S. , Wasik Brian R. , Frueh Simon P. , Alford Brynn K. , Voorhees Ian E. H. , Flint Joseph F. , Saddoris Sarah , Goodman Laura B. , Holmes Edward C. , Hafenstein Susan L. , Parrish Colin R.
Published: May 2023

Antibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system.
Interaction of EXA1 and eIF4E Family Members Facilitates Potexvirus Infection in Arabidopsis thaliana
Authors: Nishikawa Masanobu , Katsu Kosuke , Koinuma Hiroaki , Hashimoto Masayoshi , Neriya Yutaro , Matsuyama Juri , Yamamoto Toya , Suzuki Masato , Matsumoto Oki , Matsui Hidenori , Nakagami Hirofumi , Maejima Kensaku , Namba Shigetou , Yamaji Yasuyuki
Published: May 2023

The genus
Potexvirus
comprises a group of plant RNA viruses, including viruses that cause serious damage to agricultural crops. We previously showed that loss of
Essential for poteXvirus Accumulation 1
(
EXA1
) in
Arabidopsis thaliana
confers resistance to potexviruses.
Vesicular Stomatitis Virus (VSV) G Glycoprotein Can Be Modified to Create a Her2/Neu-Targeted VSV That Eliminates Large Implanted Mammary Tumors
Authors: Gao Yanhua , Bergman Ira
Published: May 2023

A new form of vesicular stomatitis virus (VSV) was created that specifically targets and destroys cancer cells that express the Her2/neu receptor. This receptor is commonly found in human breast cancer and is associated with a poor prognosis.
Worldwide transmission of ST11-KL64 carbapenem-resistant
Klebsiella pneumoniae
: an analysis of publicly available genomes
Authors: Wang Junna , Feng Yu , Zong Zhiyong
Published: May 2023

ST11-KL64 is an internationally distributed lineage of carbapenem-resistant
Klebsiella pneumoniae
and is the most common type in China. The international and interprovincial (in China) transmission of ST11-KL64 CRKP remains to be elucidated. We used both static clusters defined based on a fixed cutoff of ≤21 pairwise single-nucleotide polymorphisms and dynamic groups defined by modeling the likelihood to be linked by a transmission threshold to investigate the transmission of ST11-KL64 strains based on genome sequences mining. We analyzed all publicly available genomes (
n
= 730) of ST11-KL64 strains, almost all of which had known carbapenemase genes with KPC-2 being dominant. We identified 4 clusters of international transmission and 14 clusters of interprovincial transmission across China of ST11-KL64 strains. We found that dynamic grouping could provide further resolution for determining clonal relatedness in addition to the widely adopted static clustering and therefore increases the confidence for inferring transmission.

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) is a serious challenge for clinical management and is prone to spread in and between healthcare settings. ST11-KL64 is the dominant CRKP type in China with a worldwide distribution. Here, we used two different methods, the widely used clustering based on a fixed single-nucleotide polymorphism (SNP) cutoff and the recently developed grouping by modeling transmission likelihood, to mine all 730 publicly available ST11-KL64 genomes. We identified international transmission of several strains and interprovincial transmission in China of a few, which warrants further investigations to uncover the mechanisms for their spread. We found that static clustering based on ≤21 fixed SNPs is sensitive to detect transmission and dynamic grouping has higher resolutions to provide complementary information. We suggest the use of the two methods in combination for analyzing transmission of bacterial strains. Our findings highlight the need of coordinated actions at both international and interprovincial levels for tackling multi-drug resistant organisms.
Porphyromonas gingivalis Gingipains Destroy the Vascular Barrier and Reduce CD99 and CD99L2 Expression To Regulate Transendothelial Migration
Authors: Zou Zhaolei , Fang Juan , Ma Wanting , Guo Junyi , Shan Zhongyan , Ma Da , Hu Qiannan , Wen Liling , Wang Zhi
Published: May 2023

P. gingivalis
is associated with a variety of systemic diseases and colonizes in distal locations in the body. Here, we found that
P. gingivalis
gingipains degrade PECAM-1 to promote bacterial penetration while simultaneously reducing leukocyte TEM capacity.
Supplemental Material: Crustal structure of the Lazufre volcanic complex and the Southern Puna from 3-D inversion of magnetotelluric data: Im-plications for surface uplift and evidence for melt storage and hydrothermal fluids
Authors: Unsworth Martyn , al. et
Published: May 2023

Additional details of the magnetotelluric data and resulting 3-D resistivity models.
13 Feasibility of the pragmatic PBPK modelling approach – towards model-informed dosing in paediatric clinical care
Authors: van der Heijden Joyce , Freriksen Jolien , de Hoop-Sommen Marika , Greupink Rick , de Wildt Saskia
Published: May 2023

Introduction

More than half of all drugs are still prescribed off-label to children. To support off-label dosing, pharmacokinetic (PK) data are needed. Physiologically-based pharmacokinetic (PBPK) models are increasingly used to study PK and guide dosing decisions. We hypothesize that combining existing compound models with a paediatric population model can be used to pragmatically predict paediatric exposure.

Methods

Seven drugs, with various pharmacokinetic characteristics, were selected (i.e. meropenem, ceftazidime, azithromycin, propofol, midazolam, lorazepam, and caffeine). Simcyp v20 was used to predict exposure in adults, paediatrics and preterm neonates by combining an existing compound file with various virtual populations. Predictive performance was evaluated by calculating the ratio of predicted-to-observed PK parameter values (0.5 to 2-fold acceptance range) and by a visual predictive check.

Results

Overall, model predictions in adults were able to capture clinical observed PK data and confidence in PBPK model performance for predicting PK in this population was therefore considered high. However, predictive performance decreased when predicting PK in the paediatric population, even more so in preterm neonates.

Conclusions

Pragmatic PBPK modelling in paediatrics is feasible, though the approach is not straight forward as limitations, such as inadequate parameterization with respect to paediatric-specific ADME properties, have been observed. A thorough understanding of the models assumptions and limitations is required, before dose recommendations can be generated for use in clinical practice.

This abstract is based on research funded by the Bill & Melinda Gates Foundation.
14 A comparison of age-banded and weight-based oral paracetamol dosing in hospitalised children
Authors: Wright Kirstie , Craske Jennie , Gill Andrea , Jenson John , Arnold Philip
Published: May 2023

The British National Formulary for Children contains two dosing strategies for oral paracetamol: age-banded and weight-based. Weight-based is used in our hospital. This study compares dosing strategies in inpatients.

Retrospective analysis over 4 years was undertaken in a single tertiary paediatric hospital. Data was collected from electronic patient records. Patients 3 months to 18 years were included. One measurement per admission was allowed. This was compared the Health Survey England (HSE) and National Child Measurement Programme (NCMP).

Of 161150 admissions it was possible to match weight to 115466 (58287 patients) and height to 18806 (4892 patients). Of 95598 paracetamol prescriptions, doses <10mg/kg occurred in 5427(5.7%) prescriptions and doses >20mg/kg in 691(0.72%) prescriptions. Of the doses <10mg/kg, 1003 were in patients >66.7kg. Applying age-banded doses to all admissions would result in doses <10mg/kg in 20748 (18%) of admissions (13111 patients) and doses >20 mg/kg would occur in 4420 (3.8%) of admissions (2054 patients), most commonly in teenagers. Weight-based dosing (maximum 1g/dose) would lead to doses <10mg/kg in 931 admissions (395 patients).

The potential for inadequate or excessive paracetamol dosing is greater with age-banded doses compared with weight-based doses in hospitalised children. Compared to NCMP and HSE data, obesity is more common in hospitalised children across all ages. Compared to NCMP data, underweight is more common in reception aged hospitalised children but not in year 6. Therefore, atypical body weights are more common in hospitalised children than the general population. A higher proportion of low body weight is seen in young children and teenagers. As a result, age-banded dosing should not be used in hospitalised children
18 In vitro investigation of vancomycin-induced kidney injury: development of a 2D cellular model
Authors: Rhodes Lawrence , McWilliam Stephen , Chadwick Amy
Published: May 2023

Introduction

Vancomycin is a glycopeptide antibiotic that targets gram-positive bacteria and is the recommended treatment against MRSA infections. However, it is known to cause kidney injury in children. Vancomycin accumulates in proximal tubule cells but relatively little is known regarding the mechanism of this. We conducted a multiparameter assessment of vancomycin toxicity in a novel human renal cell line, Conditionally immortalised proximal tubule epithelial cells (ciPTECs), to determine if these cells recapitulate vancomycin-induced kidney injury (VIKI) in vitro.

Methods

Three ciPTEC lines were used (parent ciPTEC, and ciPTECs with upregulated expression of organic anion transporters 1 (ciPTEC OAT1) or 3 (ciPTEC OAT3), to assess the respective involvement of these transporters in vancomycin accumulation. ciPTECs were cultured at 33°c and seeded in 96-well plates at 1x104 cells/well. Vancomycin stocks were prepared in distilled water and administered between 1mM and 10mM for 24hr incubations before cell viability (ATP) and cell cytotoxicity (LDH) assays were performed.

Results

ATP data showed a dose-dependent increase in vancomycin toxicity with 17% cell viability observed at10mM. (EC50=5.6mM) Membrane permeabilization was only observed at 10mM (60% LDH retention), with no change observed at lower concentrations administered. There was no difference in vancomycin toxicity observed between each cell type.

Conclusions

Our results suggest that ciPTECs recapitulate the nephrotoxicity induced by vancomycin and indicates that OATs are not involved in vancomycin uptake. Here, we established a proof of concept for the use of ciPTECs as a 2D cellular model for VIKI as toxicity was observed after vancomycin administration.
2 Pitfalls and opportunities for centralized TDM services: a Belgian singe-centre experience
Authors: De Cock Pieter
Published: May 2023

Therapeutic drug monitoring (TDM) requires a multidisciplinary approach with different stakeholders (nurse, bio-analyst, pharmacist, pharmacologist, pharmacometrician, physician). In recent years, a pharmacist-guided TDM dosing advice service, mainly for anti-infective therapy, has been installed at the Ghent University Hospital, a tertiary hospital in Flanders, Belgium. From this experience, advantages, pitfalls and opportunities for centralized TDM services are being summarized. Together with the previous talk, this talk will serve as a basis for discussion with the audience.
23 Plasma renin activity in young children with heart failure: influence of age, disease and ACE inhibitor treatment
Authors: Steichert Melina , Cawello Willi , Breur Johannes MPJ , Male Christoph , de Wildt Saskia N , Läer Stephanie
Published: May 2023

Introduction

Increased plasma renin activity (PRA) levels may have various causes: PRA has gained importance as prognostic marker for patients with heart failure; age may have an influence on endogenous PRA levels; and ACE inhibitor (ACEi) treatment can also interfere with PRA levels. We aimed to investigate PRA levels in very young children with heart failure, with and without ACEi treatment.

Methods

As part of a PK-PD study of enalapril for pediatric heart failure (LENA studies), blood samples were collected and analyzed for PRA levels before, 4 hours after and within the first week of enalapril treatment. In addition, a literature search was conducted according to the PRISMA concept in MEDLINE to identify studies on PRA levels in healthy children as well as in children with heart failure in the age range from 1 day up to 2 years. Comparison was performed with LENA study data and with data from 9 healthy volunteers.

Results

Infants from LENA studies with heart failure (n= 35, aged 25 days – 2.1 years) had median PRA levels of 19.7 (n=35) before, 29.0 (n=34, p>0.05) 4 hours after enalapril dose, and 89.1 ng/mL/h (n=29, p<0.01) after 5 days of treatment. Literature search revealed mean PRA levels in healthy children between 2.3 to 29.8 (n= 14 studies) and 10.0 to 87.1 ng/mL/h in ACEi naïve heart failure children (n= 4 studies). PRA levels of 9 healthy adults ranged between 0.13 to 1.85 ng/mL/h.

Conclusions

Very young children had higher endogenous PRA levels compared to adults. Heart failure at this age was associated with even higher PRA levels and ACEi treatment further increased PRA levels. These results indicate that patients appear to respond to ACEi treatment but question the value of PRA levels as prognostic marker in this population.
24 Antipsychotics use and weight gain in children compared to adults: analysis of spontaneous adverse drug reaction reports
Authors: Kaguelidou Florentia , Lieber Zaba , Montastruc Francois , Durrieu Genevieve , Treluyer Jean-Marc , Chouchana Laurent
Published: May 2023

Introduction

Weight gain and obesity are common adverse effects of antipsychotics (APs). We aimed to assess AP-induced weight gain in pediatrics compared to adults.

Methods

In a case-non case study using the WHO global database of individual case safety reports (ICSRs), VigiBase®, we evaluated the existence of disproportionality in weight gain reporting under antipsychotic treatment in children and adolescents compared to adults. Disproportionality of weight gain reporting was evaluated using the reporting odds ratio (ROR) with corresponding 95% confidence intervals (95%CI). Analysis was adjusted for sex, reporting country, year of notification, reporter qualification and concomitant use of antidepressants (ADs) and lithium.

Results

A total of 282,224 ICSRs reported with an AP were retrieved: 6,446 (2.3%) in children, 14,112 (5%) in adolescents and 261,666 (92.7%) in adults. In children, 1,544 (24%) of ICSRs reported weight gain, 1,831 (13%) in adolescents and 13,506 (5.6%) in adults. Most weight gain cases concerned male patients (55%) and were reported by health professionals (47%) in North America (54%) and Europe (27%). Concomitant use of ADs and lithium was reported in 36% and 3.5% of weight gain cases overall. Disproportionality of weight gain reporting associated with APs was found in adolescents (adjusted ROR: 2.3 [95%CI 2.1–2.4]) and in children (aROR: 3.6 [95%CI 3.3–3.8]) compared to adults. Use of risperidone was associated with the highest increase in weight gain reporting in children (aROR 4.9, 95%CI 3.9–6.1) and adolescents (aROR 3.6, 95%CI 3.1–4.1).

Conclusions

Children and adolescents are at higher risk of reporting weight gain under APs than adults.
25 Point prevalence study of paediatric polypharmacy
Authors: Moss James , Rashed Asia , Jensen John , Wilson John , Walker Lauren , Hawcutt Daniel
Published: May 2023

Introduction

Paediatric polypharmacy is defined as two or more medicines, which is lower than the definition in adults (>5 medicines). A recent scoping review of paediatric polypharmacy found a mean prevalence of 39.7% with a large range from 0.9% to 98.4%.

Methods

Prescribing data from 85 active practices across Liverpool Clinical Commissioning Group (CCG), was extracted on the 6th January 2021 to include all patients below 18 years of age. Prescribing data was also obtained for Alder Hey Children’s Hospital from the electronic prescribing system, Meditech on the 12th January 2021. Descriptive analysis was performed.

Results

Of the 110,097 CYP registered in primary care, 17,271 (16%) were prescribed >2 medications, 3,507 (3·2%) >5, 715 (0·7%) ≥10, and 202 (0·2%) ≥15. The median number of CYP prescribed ≥10 and ≥15 medications per primary care practice was 7 (range 0–34) and 2 (range 0–11), respectively.

Within Alder Hey Children’s Hospital, 139 inpatients were identified, with 126 patients (91%) prescribed two or more medicines. The most frequently prescribed medicine was paracetamol. When ‘as required’ and ‘one off’ medicines were removed, omeprazole was the most frequently prescribed medicine.

Conclusions

Many children within Liverpool CCG meet the definition for paediatric polypharmacy. Further research is required to assess the consequences of paediatric polypharmacy and address its management which is under recognised and underrepresented in the literature to date.
27 Risk factors of augmented renal clearance in critically ill children using iohexol clearance for renal function assessment
Authors: Dhont Evelyn , Heggen Tatjana Van Der , Snauwaert Evelien , Willems Jef , Walle Johan Vande , de Cock Pieter
Published: May 2023

Introduction

Augmented renal clearance(ARC) of hydrophilic drugs is frequent in PICU patients and warrants adjustment of standard dosing regimens to prevent therapeutic failure. Knowledge of patient-, disease- and therapy-related factors associated with ARC, would allow to predict before the start of treatment, which patients would benefit from higher drug doses. We aimed to identify predictors of ARC in critically ill children with normal serum creatinine(Scr) using iohexol plasma clearance (CLiohexol) to quantify renal function.

Methods

We performed a post hoc analysis of data collected from an interventional study conducted at our academic PICU, which measured glomerular filtration rate (GFR) by CLiohexol in patients with normal Scr. ARC was defined as GFR exceeding normal values for age plus 2 standard deviations. Multivariable logistic regression analysis was performed to identify predictors of ARC.

Results

GFR was measured in 85 patients, median age was 16 [IQR 5;89] months, 59% had a surgical profile. Median CLiohexol was 122[IQR 75;152] ml/min/1.73m2. Fourthy patients out of 85 (47%) expressed ARC. Postoperative status was identified as independent predictor of ARC (p=0.014, OR 4.253, 95%CI 1.338–13.517). However, in patients after cardiac surgery the odds of developing ARC were significantly lower (p=0.010, OR 0.163, 95%CI 0.041 –0.644). There was a trend suggesting more ARC in male patients and in those without need for vaso-active drugs, however, this was not statistically significant.

Conclusion

Our findings raise clinicians’ awareness about ARC potentially being present in children after major surgery. This knowledge allows to anticipate on enhanced elimination of drugs by using empirically adjusted dosing regimens immediately from the start of treatment.
29 What domains related to medicines were measured in studies of burden of care for paediatric patients? A systematic review
Authors: Thatparan Tharshiya , Marro Julien , Hawcutt Daniel
Published: May 2023

Introduction

Medicines are becoming increasingly common for all populations and polypharmacy has been shown to have numerous risks. Although primary studies and reviews have explored the impact of medical conditions on patients and caregivers, there are no known reviews on the impact of medicines on paediatric patients. This systematic review therefore aimed to determine the domains commonly assessed in studies assessing treatment burden in different conditions for paediatric patients and their caregivers.

Methods

Searches were conducted on Medline, CINAHL, EMBASE, Web of Science and Cochrane Database of Systematic Reviews to find relevant papers. Two reviewers independently screened the papers based on the chosen inclusion and exclusion criteria. The quality of the papers was assessed independently by two reviewers using the Newcastle Ottawa Scale. This review was registered with PROSPERO (PROSPERO registration number: CRD42021285097) and conducted according to PRISMA methodology.

Results

6 papers with 8276 participants were identified in this review. The domains most commonly assessed were the perceived effectiveness of medications (4/6 studies), psychosocial impact (3/6 studies) and the impact on work and school (3/6 studies). Other domains included the ease of use of medicines, side effects from medicines, adherence to medicines, time requirements, costs, using healthcare resources and support from family/friends/organisations.

Conclusions

Studies assessing the burden of care due to medicines assessed a range of domains related to the impact of medicines on patients and caregivers. The results from this review will be used create a questionnaire for a cohort study that aims to determine the impact of polypharmacy on paediatric patients and their parents.
30 Utilization of and barriers to individual treatment trials in mucopolysaccharidosis – interim results of an expert survey
Authors: Wiesinger Anna-Maria , Lagler Florian , Scarpa Maurizio , Giugliani Roberto , Lampe Christina , Kampmann Christoph
Published: May 2023

Introduction

Mucopolysaccharidoses (MPS), comprise a group of rare chronically debilitating metabolic diseases and associated with reduced life expectancy and a substantial unmet clinical need. Current research directs towards a number of new treatment targets and strategies. Individual treatment trials (ITT) could make these options rapidly available to patients. Based on scientific publication, this is hardly used. We assess the utilization of and relevant barriers to ITT in MPS as well as potential solutions.

Methods

Phase 1 was done with 5 international top experts. After this interim analysis, the survey will be rolled out to a broader group of experts.

Results

Five MPS experts from Austria, Brazil, Germany and Italy have been enrolled. In total these clinicians manage about 350 MPS patients. Only three experts ever ran 1–3 numbers of ITT in MPS patients, solely MPS type II (n=2) and VI (n=1), summing up to a total of five ITTs, which is about 1.4% of their patients. The treatments used in ITTs comprise Montelukast, THC, Curcuma and a viral vector with transgene. As barriers for a wider use of ITTs, the im-practicability for implementation (n=1) and the insufficient training in ITT (n=1) have been indicated. All experts consider it highly likely that a decision analysis tool increases the use of ITT in MPS.

Conclusions

ITT are used in about 1% of MPS patients. This seems extremely low, considering the commonness of off label use in children with severe conditions, the high unmet medical need in MPS and the number of research results, which indicate various promising repurposing strategies. This interim analysis already demonstrates several relevant barriers and high potential of the planned decision framework tool to overcome this.
34 Attitudes of children and young people and their parents towards polypharmacy – pilot study
Authors: Moss James , Rashed Asia , Walker Lauren , Hawcutt Daniel
Published: May 2023

Introduction

A recent survey of healthcare professionals found that healthcare professionals concerns about patient and family anxiety was the main barrier to deprescribing. However, the attitudes of families, children and young people (CYP) have not previously been sought.

Methods

A questionnaire was designed to assess the attitudes of CYP and their parents towards polypharmacy and deprescribing based on a previously validated adult questionnaire (rPATD). Initial review and modification took place following input from a young person patient and public involvement group and a content evaluation panel of experts. Ethics approval was obtained, and a maximum of 22 participants (10% of the total study population) were to be recruited for the pilot. Inclusion criteria were CYP taking >2 for 28 days or more. The questionnaire was completed online using Microsoft Forms. Descriptive analysis was undertaken.

Results

Twenty participants completed the piloting process (12 parents, 5 CYP aged 10–15 years and 3 CYP aged 16–17 years), as saturation was achieved. The mean number of medicines taken was six. Most parents (67%) thought their children were taking many medicines, whereas only 38% of CYP agreed with this. Only one CYP in the 10–15yrs stated they wanted to be involved in decisions about their medicines, whereas all of the CYP in the 16–17yrs cohort, and 92% of parents, said they liked to be involved. Overall, 83% of parents and 63% of CYP stated they would like to try stopping one of their medicines if it was advised by a doctor.

Conclusions

The pilot data would suggest that CYP and their parents would be happy to consider stopping one of their medicines if advised to do so but data from the full study, which is currently recruiting, and statistically powered is awaited.
38 Innovative high-fidelity simulation for vaccination training of pharmacist including emergency cases - a randomised controlled study
Authors: Sayyed Shahzad , Reda Sharkas Ahmed , Ali Sherazi Bushra , Dabidian Armin , Schwender Holger , Läer Stephanie
Published: May 2023

Introduction

Recently, pharmacists in Germany were allowed to administer influenza and COVID-19 vaccines for people aged 12 years and older in order to increase vaccination coverage rates. To adapt pharmacy curriculum for clinical practice, an innovative, high level vaccination training course comprising clinical skills, techniques required for level of competence was developed with participants interacting either with a high-fidelity simulator or low-fidelity injection pad. Clinical scenarios to manage adverse events were also implemented.

Methods

A randomized controlled trial using a pre-post-design with pharmacy undergraduates alongside with a theoretical part was performed. The intervention group interacted with a high-fidelity simulator, while the control group was trained with low-fidelity injection pads. Before and after the respective training each participant went through an objective structured clinical examination (OSCE) and each participant completed a self-assessment questionnaire and knowledge quiz.

Results

OSCE Score were raised through an analytical checklist examining skills in anamnesis, patient information, vaccination process, and handling emergency case. Both training methods showed a significant (p<0,01) increase of skills but a significant (p<0,01) greater increase in the intervention group compared to the control group, particularly in vaccination process (p=0,007). Both Groups showed a similar increase of self-assessment score raised through a 6-point-Likert scale, and no significant differences were observed in the quizzes.

Conclusions

High fidelity simulation proves to be an appropriate tool to train pharmacy students for vaccine administration, as a new pharmaceutical service and enable the students to recognize and manage adverse events.
Oculomotor nerve palsy as an extraintestinal manifestation of Crohn’s disease
Authors: Papadopoulou Marianna , Tzortsou Sofia , Chatzi Ioanna , Baltogiannis Christos
Published: May 2023

Patients with inflammatory bowel disease (IBD) may present with extraintestinal manifestations. Neurological symptoms associated with IBD are infrequent. Thus, any unexplained neurological symptom that occurs in patients with IBD should raise the suspicion of a link between the two disorders. We report a case of a man in his 60s, who was diagnosed with Crohn’s disease and developed ptosis and diplopia. Neurological examination revealed oculomotor nerve palsy, sparing the pupil. MRI and magnetic resonance angiography of the brain were insignificant and no other cause was determined. He was treated with oral corticosteroids and symptoms gradually subsided. Cranial nerve palsies associated with IBD have been rarely reported. They usually involve the optic and acoustic nerve and are attributed to a common dysimmune base. This is the first reported case of oculomotor nerve palsy (III cranial nerve) associated with IBD. Clinicians treating patients with IBD should be alert for unusual neurological complications and treat them appropriately.
Disseminated tuberculosis presenting as cutaneous leucocytoclastic vasculitis
Authors: Verma Abhishek , Aggarwal Sunita , Singh Ranvijay , Mittal Tushar
Published: May 2023

Cutaneous leucocytoclastic vasculitis (CLV) is a type of small vessel vasculitis, predominantly presenting with palpable purpuras and sometimes with systemic manifestations. The following report describes the case of a woman, who presented with fever, anorexia and maculopapular lesions over both lower limbs. Skin biopsy revealed CLV. CT scan demonstrated bilateral pulmonary nodules, ileocecal wall thickening and generalised lymphadenopathy. Colonoscopy guided biopsy obtained from ileocecal valve ulcer showed epitheloid cell granuloma with Langhans-type giant cells and caseous necrosis. Rapid clinical improvement was seen with anti-tubercular therapy. Among infectious causes, although rare and an uncommon presentation,Mycobacterium tuberculosisshould be considered as an important cause of CLV.
Increasing uptake of FIT colorectal screening: protocol for the TEMPO randomised controlled trial testing a suggested deadline and a planning tool
Authors: Robb Kathyrn A , Kotzur Marie , Young Ben , McCowan Colin , Hollands Gareth J , Irvine Audrey , Macdonald Sara , McConnachie Alex , O'Carroll Ronan E , O'Connor Rory C , Steele Robert J C
Published: May 2023

Introduction

Screening can reduce deaths from colorectal cancer (CRC). Despite high levels of public enthusiasm, participation rates in population CRC screening programmes internationally remain persistently below target levels. Simple behavioural interventions such as completion goals and planning tools may support participation among those inclined to be screened but who fail to act on their intentions. This study aims to evaluate the impact of: (a) a suggested deadline for return of the test; (b) a planning tool and (c) the combination of a deadline and planning tool on return of faecal immunochemical tests (FITs) for CRC screening.

Methods and analysis

A randomised controlled trial of 40 000 adults invited to participate in the Scottish Bowel Screening Programme will assess the individual and combined impact of the interventions. Trial delivery will be integrated into the existing CRC screening process. The Scottish Bowel Screening Programme mails FITs to people aged 50–74 with brief instructions for completion and return. Participants will be randomised to one of eight groups: (1) no intervention; (2) suggested deadline (1 week); (3) suggested deadline (2 weeks); (4) suggested deadline (4 weeks); (5) planning tool; (6) planning tool plus suggested deadline (1 week); (7) planning tool plus suggested deadline (2 weeks); (8) planning tool plus suggested deadline (4 weeks). The primary outcome is return of the correctly completed FIT at 3 months. To understand the cognitive and behavioural mechanisms and to explore the acceptability of both interventions, we will survey (n=2000) and interview (n=40) a subgroup of trial participants.

Ethics and dissemination

The study has been approved by the National Health Service South Central—Hampshire B Research Ethics Committee (ref. 19/SC/0369). The findings will be disseminated through conference presentations and publication in peer-reviewed journals. Participants can request a summary of the results.

Trial registration number

clinicaltrials.govNCT05408169
‘A Unique opportunity to test things out’: a qualitative study of broad-based training in Scotland
Authors: Wakeling Judy , Cleland Jennifer , Stirling Suzanne Anderson , Johnston Peter
Published: May 2023

Objectives

A recent review recommended UK postgraduate medical education should produce doctors capable of providing general care in broad specialties across a range of different settings. Responding to this, broad-based training (BBT) was introduced in Scotland in 2018 to provide postgraduate trainees with a grounding in four specialties. Introduced as an option for trainees after initial postgraduate ‘Foundation’ training, it comprises 6 months in general medicine, general practice, paediatrics and psychiatry.

This study addresses two key BBT outcomes. It examines how successful BBT is in developing trainees who perceive they are able to work beyond traditional specialty boundaries to care for patients with complex, multifactorial healthcare needs. Second, it explores how well BBT prepares trainees for their next stage in training.

Design

A longitudinal qualitative study using semistructured interviews to collect data from BBT trainees, trainers and ‘programme architects’. Fifty-one interviews were conducted, 31 with trainees (with up to three interviews per trainee across BBT and immediately afterwards (post-BBT)) and 20 with trainers. Data were subject to thematic analysis.

Results

Two overarching themes were identified: (1) trainees able to work beyond specialty boundaries and (2) preparation for the next stage in training. BBT trainees were able to see the links and overlap between different specialties and understand the interface between primary and secondary care. They did not perceive that BBT (as compared with single-specialty early-stage training) disadvantaged them, other than in terms of specialty examination preparation. BBT was seen as a way to keep career options open in a system where it is difficult to switch training pathway.

Conclusions

BBT has the capacity to create doctors who will carry on using their generalist skills to care for patients more holistically, even if they end up working in focused practice areas. BBT helps to keep options open for longer, which is beneficial in a highly structured training environment.
Protocol for evaluating quality and safety for the public through home care nursing in Italy: a multicentre cross-sectional descriptive observational study (AIDOMUS-IT)
Authors: Bagnasco Annamaria , Alvaro Rosaria , Lancia Loreto , Manara Duilio Fiorenzo , Zega Maurizio , Rocco Gennaro , Rasero Laura , Mazzoleni Beatrice , Sasso Loredana
Published: May 2023

Introduction

Considering the increasing complexity of care and workload for home care nurses due to the ageing of the population, it is crucial to describe the work environment and the community care setting. The aim of this study protocol is to map the characteristics and identify gaps of home care in the community to design future interventions aimed at ensuring quality and safety.

Methods and analysis

This is a national cross-sectional descriptive observational study using the survey method. Nurses from all participating community care centres will be recruited through convenience sampling by the coordinators of each centre, who will act as facilitators for this study. All community care recipients and their informal carers during the study period will be invited to complete a survey.

To map the characteristics and identify gaps of home care in the community, three sources of data will be collected: (1) organisational characteristics, professional satisfaction, intention to leave and burn-out; (2) experience of care recipients and their informal carers and (3) improper access to the emergency department, readmission to hospital, comorbidities, services offered and users’ level of autonomy, and main and secondary diagnoses.

Considering the total Italian nursing population of approximately 450 000 registered nurses, a sample size of 1% of this population, equal to approximately 4600 nurses, was hypothesised.

This study started in July 2022 and is planned to end in December 2023.

Data will be analysed using descriptive and inferential statistics.

Ethics and dissemination

This study protocol was approved by the Liguria Regional Ethics Committee in November 2022. Informed consent will be obtained from participants and confidentiality will be ensured. Data collected for this study will be kept anonymised in a protected database.

The results of the study will be disseminated mainly through conferences, publications and meetings with government representatives.
Managing Canadian freshwater fisheries: persistent challenges and emerging opportunities
Authors: Howarth Andrew , Nguyen Vivian M. , Cooke Steven J.
Published: May 2023

Freshwater fisheries and biodiversity have substantial economic, socio-cultural, and ecological value, but face severe and mounting anthropogenic threats. Canada's freshwater fisheries are not exempt from this, and provide excellent opportunities to better understand these overlooked and undervalued systems. Using expert and chain-referral sampling, we surveyed practitioners from across Canada about the management of freshwater fisheries. We used a mixed methods approach to identify and describe in detail many important aspects of the above processes, including 10 persistent and innate challenges in (1) bureaucratic sprawl, (2) lack of priority, (3) scope, (4) competing interests, (5) political inconstancy, (6) socio-ecological complexity, (7) limited tools, (8) geographies and scale, (9) reactivity, and (10) intersectoral frictions. Many of these challenges defy conventional problem solving (e.g., advocacy, basic science), leading to chronic incapacity and triage management in some freshwater fisheries. We highlight opportunities to increase management capacity, using innovation where conventional solutions fall short (e.g., using novel technologies to increase management scope). Achieving sustainability in Canadian freshwater fisheries will require ingenuity and supportive contributions beyond those that currently exist.