bluuebunny/crossref_metadata_2025 huggingface dataset:
P218 Drug repurposing screen of Food and Drug Administration-approved medicines identifies novel anti-inflammatory and NF-kB inhibitory activity of the tyrosine kinase inhibitor sunitinib malate
Authors: Bowman Amelia C , Chaffey Laura , Greaves David
Published: April 2022

Background/Aims

Macrophage-mediated inflammation is a driver of both acute inflammatory responses and chronic inflammatory conditions such as rheumatoid arthritis. Drug repurposing is an attractive strategy for the development of novel anti-inflammatory therapeutics. Currently used anti-inflammatories for rheumatoid arthritis have their own risk factors, the development of small molecule anti-inflammatory drugs with decreased side effect profiles is thus an ongoing process. The aim of this study was to identify FDA-approved medicines with novel anti-inflammatory effects in macrophages.

Methods

A murine macrophage NF-κB reporter cell-line was used to screen a library of 159 FDA-approved medicines for NF-κB inhibition upon LPS stimulation. To investigate sunitinib malate in vitro, cytokine production in LPS-stimulated bone marrow derived macrophages treated with sunitinib malate was measured (n = 5-7) and IC50 values were calculated from resulting concentration response curves. To investigate NF-κB inhibitory effects of sunitinib malate in vivo, mice (n = 10-11 per group) dosed orally with vehicle or sunitinib malate (30mg kg-1) were exposed to a model of acute endotoxemia (1-hour intraperitoneal injection with LPS, 10mg kg-1). Statistical significance was assessed by one-way ANOVA followed by Tukey’s post-hoc test.

Results

Our initial screen identified 18 medicines with NF-κB inhibitory activity. Among these, the type III tyrosine kinase inhibitor sunitinib malate was further investigated and found to reduce pro-inflammatory mediator production in BMDMs (TNFα IC50=0.97μM, IL-1β IC50= 1.74μM, IL-6 IC50=1.14μM, CCL2 IC50=1.19μM, Nitrite IC50=0.59μM; n = 5-7) without compromising cell viability. In vivo, sunitinib malate significantly reduces serum TNFα (p < 0.05; one-way ANOVA; n = 10) and liver tnf mRNA expression (p < 0.01; one-way ANOVA; n = 10) in a murine model of acute endotoxemia, and reduces nuclear translocation of NF-κB compared to vehicle-treated mice (p < 0.01; one-way ANOVA; n = 7).

Conclusion

Screening of existing medicines in macrophages allows previously unexplored anti-inflammatory properties to be identified. Here, we have found that the tyrosine kinase inhibitor sunitinib malate has potent anti-inflammatory activity in macrophages in vitro and in vivo, mediated via an NF-κB-dependent mechanism. These results justify further exploration of sunitinib malate in macrophages and its potential as a repurposed anti-inflammatory therapeutic in arthritis.

Disclosure

A.C. Bowman: None. L. Chaffey: None. D. Greaves: None.
P226 Bortezomib-induced muscle toxicity mimicking myositis
Authors: Ansari Ghazal , Alkutobi Ziad , Nandagudi Anupama
Published: April 2022

Background/Aims

Novel drugs such as bortezomib are proteasome inhibitors that are used to treat multiple myeloma. Bortezomib induces apoptosis of rapidly dividing, metabolically active cells with extensive protein synthesis. Literature review shows two case reports of bortezomib-induced reversible muscle toxicity and motor neuropathy, used to treat multiple myeloma (MM) with persistently normal creatine kinase. In a single-centre prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, seven developed proximal lower limb weakness with complete resolution of symptoms after discontinuation of bortezomib as depicted in our case.

We present a case of myositis mimic which was triggered by the use of immunotherapy Bortezomib to treat multiple myeloma.

Methods

An 81-year-old Caucasian gentleman was admitted with proximal lower limb weakness. He had a background history of multiple myeloma, treated with melphalan, prednisolone and bortezomib commenced in September 2019. Following his fourth cycle in January 2020, he noted proximal lower limb weakness and was referred to Rheumatology. He had MRI of the spine which did not reveal any cord compression. His prednisolone was stopped. On further questioning, there were no features to suggest connective tissue disease, inflammatory arthritis or vasculitis. On examination power was reduced to 4/5 in the proximal muscles of lower limb affecting his mobility. Rest of the examination was unremarkable.

Results

All bloods including creatinine kinase, autoimmune profile and inflammatory markers were normal. Magnetic resonance imaging (MRI) of the thighs showed diffuse fatty atrophy within all muscle groups of the thighs with low grade oedema within the vastus lateralis and intermedius particularly of the left thigh when compared to the right. The appearances were in keeping with inflammatory myositis, without any abscess formation. Electromyography showed abnormal signals with neurogenic and myopathic changes. Nerve conduction studies showed moderate length-dependent axonal peripheral neuropathy. Following his review, investigations and discussion between Rheumatology and Haematology, it was believed that his lower limb weakness was likely related to his bortezomib and the decision was made to stop bortezomib therapy. He was followed up in Rheumatology and Haematology clinic after stopping bortezomib with improvement of lower limb weakness and mobility. His creatinine kinase and inflammatory markers remained persistently normal. Muscle biopsy was not considered as there was enough evidence to suggest it was bortezomib induced muscle toxicity.

Conclusion

We present a case of myositis mimic whose symptoms completely resolved on stopping bortezomib. As this is one of the rare and early complications of bortezomib we suggest that patients treated with bortezomib should be monitored for muscle weakness.

Disclosure

G. Ansari: None. Z. Alkutobi: None. A. Nandagudi: None.
P227 Molecular and functional characterisation of distinct resident and migratory skin fibroblast populations in systemic sclerosis
Authors: Clark Kristina E. N , Cole Alice , Xu Shiwen , Ong Voon H , Buckley Christopher D , Denton Christopher P
Published: April 2022

Background/Aims

Modern single-cell analysis has confirmed functional heterogeneity amongst fibroblast populations within normal and diseased skin. To better understand differences between fibroblast subpopulations, we have developed a novel technique to selectively isolate “migratory” fibroblasts, and non-migratory “resident” fibroblasts from heathy control (HC) and systemic sclerosis (SSc) skin and used functional assays of fibrotic potential, and gene expression to compare these novel fibroblasts populations.

Methods

Forearm skin punch biopsies were collected from dcSSc (n = 3), and HC skin (n = 3). Migratory fibroblasts were isolated by standard explant culture. The remaining biopsy fragments then underwent collagenase digestion to yield a population of resident fibroblasts. These populations were expanded and used at passage 3-6. Functional characterisation included 3-D collagen gel contraction, and migratory scratch-wound assays. Expression of pro-collagen I, CTGF and alphaSMA was compared by western blot. Bulk RNAseq on each fibroblast population was performed. Statistical analysis was carried out using Rsoftware “tidyverse”. Significant differences in gene expression were those with a fold change of ≥ 1.5, and adjusted p-value (FDR) of < 0.05.

Results

SSc fibroblasts showed a hallmark fibrotic phenotype with increased gel contraction, faster migration, and overexpression of Col1, CTGF and alphaSMA compared with HC. Conversely, resident fibroblasts showed reduced contraction, migration, and reduced secretion of alphaSMA compared to migratory fibroblasts in both SSc and HCs. RNAseq confirmed 1483 significantly differentially expressed genes between SSc resident and migratory fibroblasts, whereas no genes were significantly differentially expressed between HC resident and migratory fibroblasts. To further understand disease-related differences between the two fibroblast populations, we compared gene expression between SSc and HC migratory fibroblasts, and resident fibroblasts. 644 genes were upregulated in the migratory fibroblasts of SSc compared to HC (including ACTA2, C1QTNF3). 914 genes were upregulated in SSc resident fibroblasts compared to HC (including IL6, CCL2). Of these 375 genes were upregulated in both SSc fibroblast populations compared to HC (Table 1) including IL11 and COMP.

Conclusion

There are clear functional and transcriptional differences between migratory and resident fibroblasts, which is more marked in SSc compared to HC. Further work is required to understand their role in SSc pathogenesis and contribution to disease phenotype that may facilitate a more targeted approach to treatment

Disclosure

K.E.N. Clark: None. A. Cole: None. S. Xu: None. V.H. Ong: None. C.D. Buckley: Corporate appointments; founder of Mestag Therapeutics. C.P. Denton: None.
P280 Maternal use of hydroxychloroquine with anti-Ro and or anti-La during pregnancy: a systematic review
Authors: Nokhatha Shamma A. Al , Maguire Sinead , Harrington Robert
Published: April 2022

Background/Aims

Anti-Ro antibody and, to a lesser extent, anti-La antibody have been associated with fetal heart block during pregnancy. Use of hydroxychloroquine has previously been shown to reduce this risk in pregnancy. According to ACR 2020, all women with positive anti-Ro and or anti-La antibodies are conditionally advised to commence HCQ during pregnancy, but this is based on limited data. We performed a systematic review to evaluate the prevalence of hydroxychloroquine prescription in women with anti-Ro or La antibodies and examine the prevalence of congenital heart block.

Methods

This was a systematic review of case controlled and observational studies. A PICO model was used to design the research question. Literature searches were initiated based on five keywords: hydroxychloroquine, pregnancy(antenatal), maternal, anti-Ro(SSA), anti-La(SSB). Studies were retrieved from Pubmed, MEDLINE, Mendeley, Cochrane, University College Dublin Library using relevant search strategies from inception to May 2021. The search was restricted to English language articles only. Data were extracted and cross-checked by two reviewers.

Results

Sixteen studies involving 1,706 anti-Ro and 454 anti-La positive females, resulting in 2,279 pregnancies, were eligible for inclusion in this review. Mean age was 30.7 years at gestation. The prevalence of HCQ prescription in pregnancy in Ro+ women was 32.7%. The most common diagnoses were systemic lupus erythematosus (n = 990) and Sjögren’s syndrome (n = 452), while the remaining women had rheumatoid arthritis, antiphospholipid syndrome, undifferentiated connective tissue disease, scleroderma, autoimmune thyroiditis, dermatomyositis, polychondritis and overlap conditions. Eight studies included asymptomatic antibody carriers (n = 192). The prevalence of congenital heart block in neonates of women on HCQ in pregnancy was 1.8%. Due to issues with data reporting in the included studies, it was not possible to separate out Ro+ women on HCQ from those not on HCQ. For this reason, we could not compare and draw conclusions on the prevalence of CHB in pregnancies of Ro+ women.

Conclusion

This systematic review highlights the need for additional studies to examine use of HCQ in women positive for Ro or La antibodies. While these antibodies are commonly encountered in SLE and Sjögren’s syndrome, they can occur in other rheumatic diseases and should be screened for to limit risk of CHB.

Disclosure

S.A. Al Nokhatha: None. S. Maguire: None. R. Harrington: None.
P281 In vitro evaluation of the response of human tendon-derived stromal cells to a novel electrospun suture
Authors: Nezhentsev Andrey , Abhari Roxanna E , Baldwin Mathew J , Mimpen Jolet Y , Augustyniak Edyta , Isaacs Mark , Mouthuy Pierre-Alexis , Carr Andrew J , Snelling Sarah J. B
Published: April 2022

Background/Aims

Recurrent tears after surgical tendon repair remain common, with 40% of rotator cuff repairs failing within one year. Repair failures can be partly attributed to the use of sutures not designed for the tendon cellular niche nor designed for the promotion of repair processes. Clinically-used sutures have high tensile strength to mechanically support injured tendon. However, these sutures do not support cell integration into the material, but instead can stimulate a chronic inflammatory response. Synthetic electrospun materials can mechanically support the tendon while providing topographical cues that modulate the immune response to promote wound healing. Electrospun material has an increased surface area and porosity which can mimic that of tendon tissue, thus promoting tendon cell infiltration and proliferation. Here, a novel electrospun suture made from twisted polydioxanone (PDO) polymer filaments is compared to PDS II, a clinically used PDO suture currently utilised in tendon repair.

Methods

We evaluated the ability of electrospun suture and PDS II to support the attachment and proliferation of human tendon-derived stromal cells using PrestoBlue cell viability assays and scanning electron microscopy. Suture surface chemistry was analysed using X-ray photoelectron spectroscopy. Bulk RNA-Seq interrogated the transcriptional response of primary tendon-derived stromal cells to sutures after 14 days.

Results

The electrospun suture showed increased initial cell attachment compared to PDS II. X-ray photoelectron spectroscopy revealed that the local surface chemistry of electrospun suture and PDS II is similar, indicating that the tendon-like architecture of electrospun suture was responsible for the greater cell attachment. Furthermore, electrospun suture elicited a stronger transcriptional response compared with PDS II, with relative enrichment of pathways including mTorc1 signalling and depletion of epithelial-to-mesenchymal transition and extracellular matrix gene sets. When compared to baseline, neither suture induced transcriptional upregulation of inflammatory pathways such as IL6-JAK-STAT3 signalling and TNF-α signalling via NF-κB.

Conclusion

Twisted electrospun sutures demonstrated a tendon-derived stromal cell response indicative of cell proliferation and wound healing, without significant fibrosis, when compared to clinically-used and safe PDS II suture. Twisted electrospun sutures therefore show promise in improving outcomes in surgical tendon repair by allowing increased cell attachment while maintaining an appropriate tissue response.

Disclosure

A. Nezhentsev: None. R.E. Abhari: None. M.J. Baldwin: None. J.Y. Mimpen: None. E. Augustyniak: None. M. Isaacs: None. P. Mouthuy: None. A.J. Carr: None. S.J.B. Snelling: None.
P297 Takayasu arteritis presents at an older age in a northern European population
Authors: Ecclestone Tegwen , Coath Fiona , Ducker Georgina , Fordham Sarah , Mukhtyar Chetan
Published: April 2022

Background/Aims

The definition of Takayasu arteritis includes the age of onset of disease as being <50 years. It has been reported most frequently in young females from Asian populations. We investigated whether the epidemiological features are the same in Norfolk, where the population is predominantly of northern European ancestry.

Methods

n our centre, cases are classified using validated international criteria. The electronic records of our vasculitis clinic were reviewed to identify all individuals with a new diagnosis of large vessel vasculitis from 2011-2020 who met a modified ACR 1990 criteria for Takayasu arteritis. The original criteria include decreased brachial artery pulse, bruit over subclavian arteries or aorta, and arteriogram abnormality. The respective modifications of these three criteria were to accept decreased radial pulse as well as the brachial pulse, bruit over the axillary artery as well as the subclavian artery, and abnormality of positron emission tomography and/or ultrasonography instead of arteriograms.

Results

14 individuals met the modified ACR 1990 criteria for Takayasu arteritis. 13 were female. The mean (standard deviation) age at diagnosis was 68.2 (7.7) years. None of the individuals were <40 years old. On presentation, 8 had upper limb claudication, 8 had pulse discrepancy, 4 had a blood pressure difference >10 mm Hg systolic, and 8 had an audible bruit over either subclavian or axillary artery. The diagnosis was confirmed on positron emission tomography in 7, ultrasonography of extracranial arteries in 5, and 2 by both modalities. The mean (standard deviation) ESR was 66.7 (48.1) and CRP was 49.2 (33.8). 2/14 also met the ACR 1990 criteria for GCA.

Conclusion

Takayasu arteritis can present at an older age in Norfolk where the population predominantly has northern European ancestry. Some of these individuals also fulfil the criteria for GCA. This has implications for treatment, identification of immunogenetic factors and disease classification.

Disclosure

T. Ecclestone: None. F. Coath: None. G. Ducker: None. S. Fordham: None. C. Mukhtyar: None.
Fungicide Efficacy During a Severe Epidemic of Tar Spot on Corn in the United States and Canada in 2021
Authors: Telenko Darcy E. P. , Chilvers Martin I. , Ames Keith , Byrne Adam M. , Check Jill C. , Da Silva Camila R. , Jay W. Scott , Mueller Brian , Ross Tiffanna J. , Smith Damon L. , Tenuta Albert U.
Published: April 2022

A 2021 epidemic of tar spot of corn caused by Phyllachora maydis led to significant yield losses in the midwestern United States and Ontario, Canada. Uniform fungicides trials consisting of nine foliar fungicides applied at the tassel (VT) or silk (R1) growth stage were evaluated for tar spot management in five field trials in the midwestern United States and Ontario, Canada, in 2021. All nine foliar fungicide treatments significantly reduced tar spot severity, but only Delaro Complete (prothioconazole + fluopyram + trifloxystrobin), Revytek (mefentrifluconazole + pyraclostrobin + fluxapyroxad), and Veltyma (mefentrifluconazole + pyraclostrobin) protected yield compared with the nontreated control.
Impact of NP follow-up calls on reducing 30-day readmissions in patients with stroke
Authors: Hwang Pauline J.
Published: April 2022

Hospital readmissions are major contributors to increased healthcare costs and lower quality of life. Despite advanced stroke care, patients who have experienced a stroke require ongoing follow-up care to prevent complications and hospital readmissions. We evaluated the impact of NP follow-up calls, providing another level of expertise to promptly identify new symptoms and complications, on readmission rates in patients who have experienced stroke.
Early Postoperative Opioid Requirement Is Associated With Later Pain Control Needs After Supratentorial Craniotomies
Authors: Wilson Bayard R. , Grogan Tristan R. , Schulman Nathan J. , Kim Won , Gabel Eilon , Wang Anthony C.
Published: April 2022

Background:

Despite a renewed focus in recent years on pain management in the inpatient hospital setting, postoperative pain after elective craniotomy remains under investigated. This study aims to identify which perioperative factors associate most strongly with postoperative pain and opioid medication requirements after inpatient craniotomy.

Materials and Methods:

Using an existing dataset, we selected a restricted cohort of patients who underwent elective craniotomy surgery requiring an inpatient postoperative stay during a 7-year period at our institution (n=1832). We examined pain scores and opioid medication usage and analyzed the relative contribution of specific perioperative risk factors to postoperative pain and opioid medication intake (morphine milligram equivalents).

Results:

Postoperative pain was found to be highest on postoperative day 1 and decreased thereafter (up to day 5). Factors associated with greater postoperative opioid medication requirement were preoperative opioid medication use, duration of anesthesia, degree of pain in the preoperative setting, and patient age. Notably, the most significant factor associated with a higher postoperative pain score and Morphine milligram equivalents requirement was the time elapsed between the end of general anesthesia and a patient’s first intravenous opioid medication.

Conclusion:

Postcraniotomy patients are at higher risk for requiring opioid pain medications if they have a history of preoperative opioid use, are of younger age, or undergo a longer surgery. Moreover, early requirement of intravenous opioid medications in the postoperative period should alert treating physicians that a patient’s pain may require additional or alternative methods of pain control than routinely administered, to avoid over-reliance on opioid medications.
Designing Immersive Virtual Reality Environments for Supporting Patients at Home
Authors: Goldsmith Denise M. , Flash Sara , Holdnack Jim , Brennan Patricia Flatley
Published: April 2022

Immersive virtual reality computer programs provide new experimental and treatment interventions that hold great promise for nursing. Immersive virtual reality uses sensory cues to represent real-world environments in a way that makes participants feel as if they are in a physical space different from the one in which they currently exist. As the acceptance of immersive virtual reality as a clinical and experimental tool has grown, so has the need to ensure that the context depicted in the environment mirrors both the sensory and the task requirements of the real-world situation. Here, we describe the use of nurse expert key informant group interviews to generate requirements that must be fulfilled in immersive virtual reality environments designed to evoke and engage participants in self-management tasks. An expert panel of four home care nurses participated in three sessions designed to elicit details of common home care challenges, frequency of variation, and typical participants. More than 20 potential scenarios were identified. The design team later used this information to create design requirements for two key scenarios and subsequently develop immersive virtual reality environments for use in research studies, mapping sensory and functional expectations to immersive virtual reality implementations. Challenges in mapping from key informant group findings to requirements are addressed.
Neonatal Intensive Care Workflow Analysis Informing NEC-Zero Clinical Decision Support Design
Authors: Gephart Sheila M. , Tolentino D. Anthony , Quinn Megan C. , Wyles Christina
Published: April 2022

Decision support in neonatal ICUs is needed, especially for prevention and risk awareness of the devastating complication of necrotizing enterocolitis, a major cause of emergency surgery among fragile infants. The purpose of this study was to describe the current clinical workflow and sociotechnical processes among clinicians for necrotizing enterocolitis risk awareness, timely recognition of symptoms, and treatment to inform decision support design. A qualitative descriptive study was conducted. Focus groups were held in two neonatal ICUs (five groups in Unit A and six in Unit B). Transcripts were analyzed using content analysis and compared with field notes. Clinicians (N = 27) included nurses (37%), physicians (30%), neonatal nurse practitioners (19%), and other staff (16%). Workflow processes differed for nurses (who see necrotizing enterocolitis signs and notify providers to order diagnostic tests and treatments) and providers (who receive notification of necrotizing enterocolitis concern and then decide how to act). Clinicians desired (1) a necrotizing enterocolitis-relevant dashboard to support nutrition tracking and necrotizing enterocolitis recognition; (2) features to support decision-making (eg, necrotizing enterocolitis risk and adherence scoring); (3) breast milk tracking and feeding clinical decision support; (4) tools for necrotizing enterocolitis surveillance and quality reporting; and (5) general EHR optimizations to improve user experience.
A Meta-Analysis Comparing Endoscopic Ultrasound-guided Fine-needle Aspiration With Endoscopic Ultrasound-guided Fine-needle Biopsy
Authors: Li Zhiwang , Liu Wei , Xu Xiaoda , Li Peiyu
Published: April 2022

Background:

The superiority between endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is still a debate. The purpose of this meta-analysis was to compare the diagnostic value and safety of these 2 needles in sampling of all solid lesions and separately pancreatic lesions.

Materials and Methods:

PubMed, EMBASE, and the Cochrane library were searched for randomized controlled studies that reported the comparison of FNA and FNB in solid mass. Outcome measures included diagnostic accuracy, number of needle passes, diagnostic adequacy, presence of tissue cores, and adverse events. Standard error, upper and lower confidence intervals at 95% confidence interval for the risk were obtained using Review Manager Version 5.3 which was also used to generate forest plots for pooled analysis. The random or fixed effect model was applied depending on the heterogeneity (I
2).

Results:

Eighteen randomized control trial studies with a total of 2718 patients (1141 patients with EUS-FNA, 1108 with EUS-FNB, and remaining 469 patients were sampled with both needles alternatively) were included in the meta-analysis.

FNB group has relatively good diagnostic accuracy relative risk (RR): 0.94, 0.92-0.97; P=0.0002), diagnostic adequacy (RR: 0.95, 0.9-1.0; P=0.04) and high quality histologic yield compared (RR: 0.77, 0.64-0.93; P=0.007) with the FNA group in solid gastrointestinal lesions, and the number of needle passes to obtain sufficient tissue (mean difference: 0.54, 0.45-0.64; P<0.00001) was lower in the FNB group. For solid pancreatic disease only, there was no difference in diagnostic accuracy (RR: 0.97, 0.93-1.01, P=0.13) or quality histologic yield (RR: 0.60, 0.29-1.23; P=0.16). The rate of adverse events (RR: 1.04, 0.48-2.29; P=0.92) did not significantly differ between FNA and FNB groups.

Conclusions:

In solid gastrointestinal lesions, FNB is associated with a relatively better diagnostic adequacy, diagnostic adequacy and tissue cores rates, and less number of needle passes. For solid pancreatic disease only, there is no difference in diagnostic accuracy or tissue cores rates.
Alzheimer Disease Occurs More Frequently In Patients With Inflammatory Bowel Disease
Authors: Aggarwal Manik , Alkhayyat Motasem , Abou Saleh Mohannad , Sarmini Muhammad T. , Singh Amandeep , Garg Rajat , Garg Palakshi , Mansoor Emad , Padival Ruthvik , Cohen Benjamin L.
Published: April 2022

Alzheimer disease (AD) affects 5 million Americans and early recognition improves cognitive function. Chronic inflammation and gut microbiome alteration are linked to cognitive decline which are common in inflammatory bowel disease (IBD). We investigated the association of IBD with development of AD. A commercial database (Explorys Inc., Cleveland, OH), an aggregate of electronic health records from 26 major US health care systems, was surveyed. Cohorts of patients with Systematized Nomenclature of Medicine—Clinical Terms (SNOMED-CT) diagnoses of Crohn’s disease (CD), ulcerative colitis (UC), and AD were identified. IBD patients with new diagnosis of AD were characterized based on demographic and traditional AD risk factors and IBD-related features. Among 342,740 IBD patients in the database, AD developed in 5750 IBD patients (1.55%). After adjusting for traditional AD risk factors, IBD was identified as an independent risk factor for development of AD [odds ratio (OR)=2.30, 95% confidence interval (CI)=2.10-2.51]. IBD patients with AD were younger in comparison to AD patients without IBD. On sub-group analysis, patients with CD had higher odds of developing AD (adjusted OR=3.34, 95% CI=3.25-3.42) than UC (adjusted OR=1.09, 95% CI=1.06-1.14). Use of tumor necrosis factor (TNF-α) inhibitors in IBD was associated with significantly lower odds of developing AD in both CD and UC. In this population based study, IBD was independently associated with development of AD. Among IBD; the association was stronger in patients with CD in comparison with UC. Use of TNF-α inhibitors was associated with lower odds of developing AD.
Outcomes of a COVID Mobility Team
Authors: Girardot Kellie , Pancake LeAnn
Published: April 2022

The detrimental effects of immobility are well documented in the literature, yet immobility still plagues the hospitalized adult. As the influx of COVID-19 patients began, patient mobility was further compromised. The purpose of this quality improvement project was to assess the impact of COVID mobility teams, composed of deployed coworkers, on COVID-19–positive and person under investigation patient outcomes. Using mobility teams improved mobility in COVID-positive and person under investigation patients. Increasing patient mobility results in improved patient outcomes by preventing hospital-acquired functional decline, preventing intensive care unit transfers, and decreasing length of stay.
Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review
Authors: Alruwaii Zainab I. , Montgomery Elizabeth A.
Published: April 2022

Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.
In-Hospital Cardiac Arrest in Adult Patients Admitted to a Quaternary Children's Center
Authors: O'Halloran Amanda J. , Callif Charles G. , Romano Jane C. , Ross Catherine E. , Kleinman Monica E.
Published: April 2022

Objective

This study aimed to describe baseline and event characteristics and outcomes for adult patients who experience in-hospital cardiac arrest (IHCA) in a quaternary children's hospital and compare IHCA outcomes in younger (18–24 years) versus older (≥25 years) adults. We hypothesized that the rate of survival to hospital discharge would be lower in the older adult group.

Methods

We performed a retrospective single-center cohort study of inpatient areas of a quaternary children's center. Adult patients (≥18 years of age) with an index pulseless IHCA requiring at least 1 minute of cardiopulmonary resuscitation or defibrillation were included.

Results

Thirty-three events met the inclusion criteria with a median patient age of 23.9 years (interquartile range, 20.2–33.3 years). Twenty-one (64%) patients had congenital heart disease, and 25 (76%) patients had comorbidities involving ≥2 organ systems. The most common prearrest interventions were invasive mechanical ventilation (76%) and vasoactive infusions (55%). Seventeen patients (52%) survived to hospital discharge.

Survival to discharge was lower in patients 25 years or older compared with patients aged 18 to 24 years old (3 of 15 [20%] vs 14 of 18 [78%], respectively; P = 0.002).

Conclusions

The majority of adult patients with IHCA in our pediatric hospital had preexisting multisystem comorbidities, the most common of which was congenital heart disease. Overall survival to discharge after IHCA was 52%, similar to that reported for the general pediatric population. Survival to discharge was significantly lower in the subgroup of patients 25 years or older when compared with those between the ages of 18 and 24 years.
Bounds on heat flux for Rayleigh–Bénard convection between Navier-slip fixed-temperature boundaries
Authors: Drivas Theodore D. , Nguyen Huy Q. , Nobili Camilla
Published: April 2022

We study two-dimensional Rayleigh–Bénard convection with Navier-slip, fixed temperature boundary conditions and establish bounds on the Nusselt number. As the slip-length varies with Rayleigh number

R
a

, this estimate interpolates between the Whitehead–Doering bound by

R
a

5
12

for free-slip conditions (Whitehead & Doering. 2011 Ultimate state of two-dimensional Rayleigh–Bénard convection between free-slip fixed-temperature boundaries.
Phys. Rev. Lett.
106
, 244501) and the classical Doering–Constantin

R
a

1
2

bound (Doering & Constantin. 1996 Variational bounds on energy dissipation in incompressible flows. III. Convection.
Phys. Rev. E
53
, 5957–5981).

This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 1)’.
Silver cities: planning for an ageing population in Singapore. An urban planning policy case study of Kampung Admiralty
Authors: Azzali Simona , Yew André Siew Yeong , Wong Caroline , Chaiechi Taha
Published: April 2022

Purpose

This paper explores ways in which Singapore adapts its planning policy and practices to meet the needs of its growing silver population, particularly the relationship between ageing related policies and its urban development strategies.

Design/methodology/approach

The research assesses Singapore's urban planning policies for the ageing population against the WHO framework for age-friendly cities using Kampung Admiralty (KA) (a pioneering project of integrated housing cum community for the ageing population) as a case study for the analysis. The methodology adopted includes a post-occupancy evaluation and a walking tour of the selected case study (Kampung Admiralty), and an analysis of Singapore's ageing policies in relation to urban planning governance.

Findings

The study examines the role and significance of a multi-agency collaborative governance structure in ageing planning policies with diverse stakeholders in the project. The evaluation carried out on KA reveals the challenges and opportunities in urbanisation planning for the ageing population. This paper concludes by emphasising the potential of multi-collaborative governance and policymaking in creating an inclusive, liveable built environment for the ageing population in Singapore, particularly but also potential implications for other ASEAN tropical cities.

Practical implications

The case study identified key issues in Singapore's urban planning for betterment in ageing and highlighted the requirement for enhancing urban planning strategies.

Originality/value

This article fulfils an identified need for the Singapore government to address the issue of ageing by providing affordable and silver-friendly housing to its ageing population.
Relationship trend of energy consumption and economic growth studies: a global examination based on bibliometric and visualization analysis
Authors: Singh Kamaljit , Vashishtha Simmi
Published: April 2022

Purpose

The evidence on the causality of energy consumption and economic growth nexus is plentiful in energy economics studies. The empirical research results documented are dissimilar because different methodologies, variables, time or data sources have been used. This study aims to examine and evaluate the existing literature to reveal the research inclinations, including future research directions. Therefore, from an application perspective, this study performed a bibliometric analysis that can serve as a basis for understanding research trend in relation to nexus of energy consumption and economic growth, its comprehensive research outcomes and the growing research inclination.

Design/methodology/approach

Using keyword search and delimiting criteria, 969 articles are selected for bibliometric analysis. Citation analysis, author keyword co-occurrence analysis, co-authorship and co-citation analysis are performed to assess the productive countries, authors, journals, articles, energy research trends, collaborating scholars and more frequently cited together articles.

Findings

Research results of the paper present a comprehensive research understanding of energy consumption and economic growth nexus studies. In terms of trending research topics, sustainable development, population density, urbanization, energy efficiency, energy intensity and carbon emission constitute a distinguished association that indicates the growth of these diverse fields’ study about energy.

Practical implications

As a policy implication and direction, the trade openness, natural gas/ resources, environmental kuznets curve, fossil-fuel consumption, agricultural land, financial development and foreign investments can be studied along with energy usage and economic growth nexus studies.

Social implications

The results provide valuable insight for the researchers selecting their potential disciplines for study, combining various techniques to deal with complex problems, identifying prospective co-authors and identifying the appropriate institutes for accompanying academic studies or collaborative research.

Originality/value

To the best of the author’s knowledge, this study is one of its kind regarding investigating the trend of energy consumption and economic growth relationship-related research published from 2001 to 2020 on the Scopus database.
Determinants of indebtedness and institutional credit to rural agricultural households: an empirical evidence from South India
Authors: R.L. Manogna , Mishra Aswini Kumar
Published: April 2022

Purpose

This article attempts to understand the pattern of credit (loan) among agricultural households and identify the correlates of their access to institutional credit for policy imperatives. It also focuses on the inclusivity of institutional credit and debt pattern in terms of outstanding loan in the southern region of India.

Design/methodology/approach

This study employs the Tobit model along with the Heckman selection model to study the impact of various factors on the institutional borrowing and the amount outstanding.

Findings

The findings reveal that the access to credit is strongly associated with the socio-economic and demographic characteristics of agricultural households in South India. Asset position of households and size of holding are positively related with the probability of household having access to institutional credit. Education and family size are also found to be associated with higher access to formal credit. On the other hand, the socially disadvantaged households have lower access to formal credit. Similarly, other variables – assets, holding size and education – are associated with higher credit per household.

Research limitations/implications

The findings indicate that the strategies to develop agriculture in southern India must encompass efforts to bring the small and marginal farmers under the coverage of institutional credit.

Originality/value

There are very few studies that have explored the credit access in South India from the perspective of land class despite the government’s attempts to include small and marginal farmers in the ambit of formal financial services.
Meaningful engagement with a gamified knowledge management system: theoretical conceptualization and empirical validation
Authors: Suh Ayoung , Cheung Christy M.K. , Lin Yongqian
Published: April 2022

Purpose

In light of the recent increase in the scholarly attention given to meaningful engagement with gamified information systems (IS), this research explores the definition and measurement of meaningful engagement as well as its role in predicting employees’ knowledge contributions via gamified knowledge management systems (KMSs).

Design/methodology/approach

The authors conducted two empirical studies. Study 1 develops a measure of meaningful engagement and evaluates its validity and reliability. Drawing on the literature on user engagement and work gamification theory, Study 2 places meaningful engagement in a nomological network and assesses the construct’s utility for predicting the quantity and quality of knowledge contributions via a gamified KMS.

Findings

The results show that meaningful engagement encompasses five specific dimensions: intense involvement, sense of meaning, self-discovery, pursuit of excellence, and personal expressiveness. The results also indicate that fostering meaningful engagement, which goes beyond hedonic and instrumental engagement, is essential to enhance the quality and quantity of knowledge contribution.

Research limitations/implications

This research contributes to the literature on gamification by drawing scholarly attention to meaningful engagement as a parsimonious yet powerful construct that complements the notions of hedonic and instrumental engagement with KMSs. Although previous studies have highlighted the significance of meaningful engagement with gamified IS, little effort has been made to develop a scale to measure meaningful engagement. The scale the authors have developed will help researchers precisely measure users’ meaningful engagement and systematically examine its role in gamified systems compared to that of other forms of engagement. The study also has practical implications, as the results can inform future design strategies to enable the successful implementation of gamified KMSs that facilitate knowledge contribution in the workplace.

Originality/value

The development of new constructs is the starting point for theoretical development. This research responds to the call to conceptualize meaningful engagement with gamified IS.
Gender differences in the entrepreneurial ladder: evidence for Latin America
Authors: Bernat Luisa Fernanda , Lambardi German , Palacios Paola
Published: April 2022

Purpose

The main objective of this paper is to identify the factors associated with a successful transition through the entrepreneurial ladder for both men and women in a sample of nine Latin American countries.

Design/methodology/approach

The authors classify individuals according to five categories of increasing entrepreneurial engagement and estimate separate generalized ordered logit models to account for possible gender differences. Compared to previous literature, this is a more efficient methodology that allows us to identify the factors that have a significant and persistent relationship across stages and those that are only significant to specific engagement levels.

Findings

The authors find that factors such as parent business ownership, access to loans and autonomy increase the probability of progressing in the entrepreneurial ladder for both men and women and through all the stages. The authors also find that span of activity and the proxy for income increase the likelihood of moving to the next stages only for men, while higher education and autonomy do so only for women.

Originality/value

To the best of the authors’ knowledge, this is the first study to identify the factors promoting progress through the different stages of the entrepreneurial ladder in Latin America. Separate regressions for women and men provide insight into the differential role of each variable by gender. Results from this study suggest that the gender dimension, currently absent in most policies, should be incorporated or strengthened in the design of entrepreneurship promotion programs in Latin America.
Blockchain technology: a troubleshooter for blood cold chains
Authors: Asokan Dinith , Sunny Justin , Pillai V. Madhusudanan , Nath Hiran V.
Published: April 2022

Purpose

Blood cold chain (BCC) represents a system for preserving the blood during its journey from the donor to the ultimate transfusion site. Existing BCCs have many drawbacks related to information transparency and information security. Secured and real-time information sharing in BCC can bring several benefits. The purpose of this paper is to summarise the issues in typical BCCs and to explore the scope of blockchain in the management of BCCs.

Design/methodology/approach

Issues in the existing BCCs are identified through a narrative review. To explain the potential of blockchain in mitigating these issues, a blockchain-based traceability solution is demonstrated with respect to a particular BCC scenario. The BCC management system discussed in this study makes use of the Ethereum blockchain’s smart contract feature and internet of things (IoT) technology. The smart contract is written in the solidity programming language and tested and validated using the Remix integrated development environment.

Findings

BCCs are concerned with several issues both from technical and non-technical perspectives. Blockchain technology is capable of troubleshooting the issues in the existing BCCs. Combining blockchain and IoT technology enables real-time information sharing among the entities. The demonstration presented in this work depicts how the blockchain-based smart contract can support operations in a typical BCC.

Research limitations/implications

This paper explores the scope of blockchain in BCCs through a demonstration. To get insights into its technical and economical feasibilities, further investigations are needed.

Originality/value

Blockchain-based traceability system presented in this work can be adopted in BCCs to ensure the quality of blood or blood products. Blockchain-based smart contracts can aid the BCCs to achieve a proper balance between blood shortage and outdating.
Measuring the effect of GST towards performances of Malaysian takaful operators
Authors: Che Mohd Salleh Marhanum , Chowdhury Mohammad Abdul Matin , Cahyono Eko Fajar , Widiastuti Tika
Published: April 2022

Purpose

The main purpose of this study is to evaluate the performance of takaful operators in Malaysia.

Design/methodology/approach

The study applied the data envelopment analysis (DEA) technique and the ratio analysis, using secondary data available on Malaysian Takaful operators’ annual reports. The study period for the analysis ranged from 2013 to 2016.

Findings

Based on both analyses, the performance of Takaful operators was affected due to the additional cost imposed by the goods and services tax (GST) implementation. Results showed a decline in average technical efficiency for takaful operators upon GST implementation.

Research limitations/implications

The data were taken from the annual audited reports for selected firms that were available on the firm’s website only, which was limited. The data were taken till 2016, even though the GST is omitted from Malaysia on 1 June 2018. This study has applied Ratio analysis and DEA constant returns to scale (CRS) technique; the future study may adopt both DEA CRS and DEA carrying returns to scale model to evaluate along with other methods to identify the specific factors.

Practical implications

These findings may associate policymakers in identifying the shortcomings of GST or new tax implementation in a new and emerging industry. So, the policymakers and central banks may adopt necessary initiatives to support the industry. Because the Malaysian government is trying to push the takaful industry along with Islamic banking and finance in the competitive market, takaful operators may be exempted from the current sales and service tax (SST). In addition, takaful operators may use these findings to enhance their operational activities efficiently to improve performance. This paper might help the researchers and practitioners to learn the impact of GST. Even though GST seems not relevant anymore as the government has replaced it with SST, the trick is still the same as it is a kind of tax or costs incurred by the Takaful operators in running their business. Takaful managers may identify their efficient level in managerial aspects as well as the optimal scale of resources by the findings of this study.

Originality/value

To the best of the authors’ knowledge, this research is original in terms of data that is gathered directly from the annual report of the company during the GST period.