bluuebunny/crossref_metadata_2025_split huggingface dataset:
E032 Deficiency of Adenosine Deaminase 2: a rare diagnosis in a case of suspected vasculitis
Authors: Xenophontos Mikalena , Gan Jasmine , Seneviratne Anoushka C 
Published: April 2023

Abstract

Background/Aims
Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive condition first described in 2014 which is characterised by vasculitis, systemic inflammation, immunodeficiency and cytopenias. The vasculitis is difficult to differentiate from polyarteritis nodosa and typically presents with recurrent strokes. It can also affect the skin and present with livedo racemosa. Clinical presentation varies widely; from vasculitic manifestations which tend to present later in life to severe haematological abnormalities such as bone marrow failure which tend to present earlier in life. Treatment with TNF inhibitors reduces the risk of additional strokes and controls inflammation in the presence of vasculitis but is not very effective against bone marrow failure.

Methods
We present the case of a 44-year-old gentleman who was being investigated for possible vasculitis by the rheumatology team in view of a history of Raynaud’s, 20-year history of recurrent leg ulcers and a previous pontine infarct. He presented acutely to the emergency department with numbness below the midthoracic level, weakness of his lower limbs and hands and urinary retention. His symptoms had progressed over a period of a few hours. On examination power was 4/5 on the MRC power scale for shoulder abduction and elbow flexion, 2/5 for elbow extension, 3/5 for wrist extension and 1/5 for finger extension. Power was 1/5 on his lower limbs. Sensation to pain was reduced with a T6 sensory level. Proprioception and vibration sense were intact. Upper limb reflexes were brisk. Knee jerks and left ankle jerk were difficult to elicit. Plantars were downgoing. Cranial nerves were normal.

Results
Bloods showed a white cell count of 6.7x109/l, haemoglobin of 96g/l (microcytic), platelets of 243x109/l, creatinine 119μmol/l (baseline 85μmol/l) and CRP of 42.9mg/l. Vitamin B12 was 200ng/l and folate levels were 2.2μg/L. ANA, ANCA, cryoglobulins and hepatitis serology were negative. MRI brain showed a 4mm area of hyper-density in the left pons. MRI whole spine was unremarkable. CSF showed normal protein, white cell count and glucose level. The patient was transferred to a tertiary neurology centre and a diagnosis of anterior spinal cord infarction was made. A nerve biopsy was performed which showed evidence of vasculitis and he was pulsed with methylprednisolone and commenced on high dose oral steroids. Genetic testing showed a pathogenic mutation in the adenosine deaminase 2 gene. He is currently awaiting to commence treatment with TNF inhibitors.

Conclusion
We conclude that DADA2 is an important differential in a young patient with suspected vasculitis especially in the presence of infarction. Identification of DADA2 allows initiation of treatment with TNF inhibitors which reduces the risk of additional strokes.
Disclosure
M. Xenophontos: None. J. Gan: None. A.C. Seneviratne: None.
E051 A systematic review of audit and feedback tools to reduce opioid prescribing for chronic non-cancer pain
Authors: Feldman Joshua , Jani Meghna 
Published: April 2023

Abstract

Background/Aims
Opioid prescribing has increased considerably over the 15 years for chronic non-cancer pain in the UK, including for musculoskeletal conditions. Whilst there are national and international guidelines to reduce inappropriate opioid prescribing, these are not always adhered to in practice. Audit and feedback is a common intervention for supporting clinical behaviour change. Little is known if such tools have been used to support safer opioid prescribing to date. This systematic review aimed to describe audit and feedback tools that were designed, implemented and led to changes in opioid prescribing practices.

Methods
A systematic review of the literature was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework (PRISMA). Both Embase and MEDLINE were searched to identify studies that included audit and feedback tools in patients prescribed opioids with chronic non-cancer pain until the 31st of May 2021.

Results
Of the 539 studies imported, following removal of duplicates, 497 studies were screened. Following title and abstract review 6 full-text studies were assessed for eligibility. A total of three studies were deemed to meet inclusion criteria. Approaches found included: The Controlled Medication Advisory Board (CMAB), Systems Consultation and the Opioid Safety Initiative (OSI). CMAB involved the use of a dashboard to provide feedback to clinicians on referred patients. As a result the opioid prescribing rate per 100 patient visits decreased by 31% and the rate of co-prescription of benzodiazepines and opioids decreased by 56%. Systems Consultation involved the use of audit and feedback, academic detailing and external facilitation to reduce opioid prescribing. Systems consultation resulted in a statistically significant reduction in the morphine equivalent daily doses. The OSI used automatic electronic medical records auditing to enable clinic leaders to identify physician prescribing patterns via a dashboard. OSI enabled a 9.9% reduction in opioid prescriptions from 571,476 to 514,883.

Conclusion
Computerised audit and feedback tools may be effective interventions to support opioid stewardship initiative and promote safer opioid prescribing. Such approaches being used internationally could pave the way for similar initiatives in the UK and future research evaluating their impact on patient safety.
Disclosure
J. Feldman: None. M. Jani: Grants/research support; National Institute for Health and Care Research Advanced Fellowship (NIHR301413).
E055 COVID-19 in male elite Irish-based athletes at a national sports institute
Authors: McLarnon Michael , Rankin Alan T , Heron Neil 
Published: April 2023

Abstract

Background/Aims
The impact of COVID-19 has not been previously documented in an elite sporting population. Previous reports have documented cardiorespiratory sequelae in athletes, and expert opinion-based guidance is generally employed in their rehabilitation. However, there still persists a lack of information on how COVID-19 affects elite athletes, and a standardised approach to graduated return to play (GRTP). This case series describes a cohort of six elite Irish-based athletes diagnosed with COVID-19.

Methods
Six athletes were followed from symptom onset until their GRTP. A retrospective case series was performed using a standardised audit form for COVID-19 among elite athletes.

Results
Headache and fatigue (6/6) were the commonest presenting symptoms, with mean duration 4.5 days; all athletes experienced mild illness, none required further investigation. 3/6 athletes supplemented vitamin D. Mean rest period was 11.5 days and mean GRTP 19.2 days. All athletes had an unremarkable screening electrocardiogram.

Conclusion
This case series presents the first clinical summary of COVID-19 illness in elite athletes based in Ireland. Treatment is largely supportive although further consideration should be given to implementing supplementation, such as vitamin D, in the management of COVID-19. Larger, longer term studies are required to better understand the impact of COVID-19 in athletes and across different sports.
Disclosure
M. McLarnon: None. A.T. Rankin: None. N. Heron: None.
E075 Predictive factors for successful biologic disease-modifying anti-rheumatic drugs dose tapering in rheumatoid arthritis
Authors: Loh Min Yi , Jones Claire J , Peall Adrian , Trickey Jeanette 
Published: April 2023

Abstract

Background/Aims
Use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionised the management of rheumatoid arthritis (RA). However, their use is not without side effects including infection and malignancy risk. Recent EULAR and ACR guidelines support consideration of dose tapering in patients in sustained remission. This study looks at identifying predictive factors for successful bDMARD dose tapering, to help select patients who may benefit from it, whilst minimising the risk of flare.

Methods
We searched our local biologic database retrospectively for RA patients who were dose tapered in line with our local guideline, between June 2015 and December 2021. 91 patients were identified, 17 patients were excluded due to death or cessation of bDMARD for unrelated reasons. Clinical and demographic data collected included: age, gender, rheumatoid factor and/or anti-cyclic citrullinated peptide antibody positivity, biologic choice, concurrent use of conventional synthetic DMARD (csDMARD), number of previous bDMARDs, and overall annual cost-saving.
Incidence of flares after tapering and outcome after resuming original dose of biologic were noted.

Results
Of the 74 patients included, 39 (53%) were on rituximab, 14 (19%) were on etanercept , 11 (15%) were on certolizumab pegol, 9 (12%) were on adalimumab, and 1 (1%) was on tocilizumab.
The incidence of flare is highest in the first 6 months after being tapered (47%; n = 18). Of those who flared (n = 38), 84% regained control following re-introduction of original dose.
After tapering, 67% (n = 18/27) of patients aged 70-89 remained in remission whilst more than 50% (n = 29/47) flared in younger age groups. Patients on rituximab were more likely to remain in remission.
There were no notable differences in gender, seropositivity and concurrent csDMARD use.
Despite reduced cost of biologics through use of biosimilars, we are estimated to save £68,783 per annum from dose tapering.

Conclusion
We find that patients in older age group or on rituximab have a higher chance of remaining in remission following bDMARD dose tapering. The risk of flare is not affected by gender, seropositivity or concurrent csDMARDs use. If patients were to flare post dose tapering, this is more likely to occur within the first 6 months after tapering.
Disclosure
M. Loh: None. C.J. Jones: Other; Received payment from Fresenius Kabi for participation in a focus group regarding publication of NICE TA 715. A. Peall: None. J. Trickey: None.
Effect of type I interferon on engineered pediatric skeletal muscle: a promising model for juvenile dermatomyositis
Authors: Covert Lauren T , Patel Hailee , Osman Alaa , Duncan Lavonia , Dvergsten Jeffrey , Truskey George A 
Published: April 2023

Abstract

Objective
To investigate pathogenic mechanisms underlying JDM, we defined the effect of type I IFN, IFN-α and IFN-β, on pediatric skeletal muscle function and expression of myositis-related proteins using an in vitro engineered human skeletal muscle model (myobundle).

Methods
Primary myoblasts were isolated from three healthy pediatric donors and used to create myobundles that mimic functioning skeletal muscle in structural architecture and physiologic function. Myobundles were exposed to 0, 5, 10 or 20 ng/ml IFN-α or IFN-β for 7 days and then functionally tested under electrical stimulation and analyzed immunohistochemically for structural and myositis-related proteins. Additionally, IFN-β-exposed myobundles were treated with Janus kinase inhibitors (JAKis) tofacitinib and baricitinib. These myobundles were also analyzed for contractile force and immunohistochemistry.

Results
IFN-β, but not IFN-α, was associated with decreased contractile tetanus force and slowed twitch kinetics. These effects were reversed by tofacitinib and baricitinib. Type I IFN paradoxically reduced myobundle fatigue, which did not reverse after JAKi. Additionally, type I IFN correlated with MHC I upregulation, which normalized after JAKi treatment, but expression of myositis-specific autoantigens Mi-2, melanocyte differentiation-associated protein 5 and the endoplasmic reticulum stress marker GRP78 were variable and donor specific after type I IFN exposure.

Conclusion
IFN-α and IFN-β have distinct effects on pediatric skeletal muscle and these effects can partially be reversed by JAKi treatment. This is the first study illustrating effective use of a three-dimensional human skeletal muscle model to investigate JDM pathogenesis and test novel therapeutics.
Regulatory Sandboxes and Fintech Funding: Evidence from the UK
Authors: Cornelli Giulio , Doerr Sebastian , Gambacorta Leonardo , Merrouche Ouarda 
Published: April 2023

Abstract
Over fifty countries have introduced regulatory sandboxes to foster financial innovation. This article conducts the first evaluation of their ability to improve fintechs’ access to capital and attendant real effects. Exploiting the staggered introduction of the UK sandbox, we establish that firms entering the sandbox see an increase of 15% in capital raised post-entry. Their probability of raising capital increases by 50%. Sandbox entry also has a significant positive effect on survival rates and patenting. Investigating the mechanism, we present evidence consistent with lower asymmetric information and regulatory costs.
Course Transformation to Enhance Student Learning in Undergraduate Nursing Course
Authors: Cho Hyun Jin , Hannigan Elaine , Davis Jan E. , Levesque-Bristol Chantal 
Published: April 2023

Abstract

AIM
The purpose of the study was to investigate whether course transformation teaching strategies using repetitive quizzing and peer-tutor supplemental instruction help enhance students' learning experiences and learning outcomes based on self-determination theory.

BACKGROUND
Undergraduate baccalaureate pharmacology and pathophysiology courses were redesigned as part of a campus-wide course transformation program to promote students' perceptions of learning and academic achievement.

METHOD
Students in the nursing pathopharmacology course participated in the two-time online perception survey (pretest and posttest) and knowledge-based exams.

RESULTS
Results revealed that the course transformation implemented to support students' basic psychological needs was significantly associated with both learning outcomes and students' feelings of competence while also decreasing attrition rates.

CONCLUSION
Considering the depth and breadth of pathopharmacology content, the teaching intervention using repetitive quizzing and peer-tutor supplemental instruction may contribute to improving students' understanding of the course content while promoting their competence.
Methylprednisolone Following Minimally Invasive Lumbar Decompression
Authors: Florence TJ , Say Irene , Rivera Joshua , Kim Jiyoon , Li Gang , Holly Langston T. , Lu Daniel C. 
Published: April 2023

Study Design.
Prospective randomized.

Objective.
Intraoperative methylprednisolone is a common adjunct following microscopic laminectomy/microdiscectomy. The goal of epidural instillation is a rapid symptomatic reduction in irritation of neural elements. There is inconsistent data supporting its use intraoperatively. To understand whether this maneuver results in any clinical effect, we performed a multiyear prospective study.

Summary of Background Data.
Previous work has demonstrated equivocal effects on pain with a suggestion of an increased risk of complication. These studies tend to suffer from small sample sizes and short follow-ups.

Materials and Methods.
Study obtained IRB approval. During the study period from 2013 to 2019, nearly equivalent numbers of patients who had received steroids during MIS decompressions were followed. Primary outcomes included pain (visual analog scale) and disability [Oswestry Disability Index (ODI)] at 2 weeks and 4 months. Secondary outcomes included complications, readmissions, and reoperation rates during the study period.

Results.
Four hundred eighty-six patients were followed for a mean follow-up of 5.17 years. The index case was more likely to be a revision surgery in the steroid group. Across all patients, there was no difference in pain at 2 weeks or 4 months. Disability was reduced at 2 weeks in the steroid group (ODI: 16.71 vs. 21.02, P = 0.04) but not at 4 months. By subgroup analysis, this is largely explained by ODI reduction in patients with high preoperative ODI (13.00 vs. 43.43, P = 0.03). Patients in the steroid cohort were more likely to undergo subsequent spinal surgery during the study period.

Conclusion.
Methylprednisolone instillation is associated with a large, transient reduction in ODI for patients with high preoperative ODI; there is no measurable effect on pain. There is equivocal effect on risk of subsequent reoperation. This issue was clarified in peer review but changes did not make it to the abstract. Therefore, the technique is likely best reserved for patients with significant preoperative disability.
Novel Monitoring and Dose Adjustment of Argatroban, a Direct Thrombin Inhibitor, to Maintain Therapeutic Anticoagulation in a Patient With Antiphospholipid Antibody Syndrome, Heparin-Induced Thrombocytopenia, and COVID-19 Pneumonia
Authors: Ryan Christine E. , Newman Kelly A. , Roberts Russel J. , Frydman Galit H. , Rosovsky Rachel P. 
Published: April 2023

BACKGROUND:
In patients who require systemic anticoagulation, a reliable monitoring method is required to ensure anticoagulation is maintained within the correct therapeutic window and patients are treated appropriately. When titrating direct thrombin inhibitors (DTIs), dilute thrombin time (dTT) measurements have been demonstrated to be more reliable and accurate than activated partial thromboplastin time (aPTT) measurements and thus often the preferred DTI assessment. However, a clinical need arises when both dTT measurements are not readily available and aPTT measurements are unreliable.

CASE SUMMARY:
A 57-year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. However, the patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. A multidisciplinary team of hematology and pharmacy clinicians created a modified patient-specific aPTT target range and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient blood samples were additionally evaluated retrospectively using an investigational novel point-of-care test that detected and quantified the argatroban anticoagulant effect.

CONCLUSIONS:
Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements can be achieved with use of a modified patient-specific aPTT target range. Early validation of an investigational rapid testing alternative for DTI monitoring is promising.
Temporalis Myofascial Flap and Conchal Bowl Cartilage Grafting for Temporomandibular Joint Arthritis
Authors: DeLeonibus Anthony , Swanson Marco , Coombs Demetrius M. , Maasarani Samantha , Papay Francis , Bassiri Gharb Bahar , Rampazzo Antonio 
Published: April 2023

Summary:
Temporomandibular joint (TMJ) arthritis arises from a multitude of etiologies; however, there is no consensus definitive treatment. The complication profile of artificial TMJs is well known, and outcomes are variable and are reserved for salvage attempts. This case details a patient with persistent traumatic TMJ pain, arthritis, and single-photon emission computed tomography scan of potential nonunion. The present study reports on the first novel use of an alternative composite myofascial flap to help arthritic TMJ pain. This study details the successful use of a temporalis myofascial flap and conchal bowl autologous cartilage graft in posttraumatic TMJ degeneration.
Assessing a Virtual Education Intervention for Patients With Atrial Fibrillation
Authors: Mihas Paul , Rosman Lindsey , Armbruster Tiffany , Walker Jennifer , Deyo Zack , Gehi Anil 
Published: April 2023

Background
Authors of studies of patients with atrial fibrillation (AF) have identified several knowledge gaps and misconceptions regarding the condition and its management. The COVID-19 pandemic heightened isolation of patients and underscored the need for education and knowledge building in order for patients to effectively manage AF during times of increased health risk.

Objective
The aim of this study was to assess, using a qualitative approach, the experiences and perceived benefits of patients with AF regarding an 8-session virtual education intervention (AF-at-Home) during the early months of the COVID-19 pandemic.

Methods
A qualitative study with 3 focus groups using a semistructured focus group guide was conducted and recorded online with the same trained moderator.

Results
We identified 7 primary themes emerging from patients' experiences: (1) building knowledge beyond information available in clinic visits, (2) managing anxiety, (3) generating self-efficacy, (4) providing social comparison, (5) perceived benefits of both experiential and informational content, (6) facilitating self-management behaviors, and (7) facilitating communication with providers.

Conclusions
The analysis of the focus groups shows the benefits of a virtual education program in building knowledge, skills, and self-efficacy as well as reducing anxiety and normalizing one's experience by attending a program alongside other patients with AF.
The Effectiveness of Mind-Body Therapies for Women With Gynecological Cancer
Authors: Ong Jing Wen , Ong Qian-Er Oriana , Metsävainio Tea , Vaajoki Anne , Tian Jing Ling , He Hong-Gu 
Published: April 2023

Background
Mind-body therapies (MBTs) have gained popularity among patients with cancer as a supportive therapy. To date, no systematic reviews have assessed the effect of MBTs on the health outcomes in women with gynecological cancer.

Objective
This systematic review and meta-analysis aimed to synthesize the effectiveness of MBTs on quality of life, anxiety, depression, cancer-related pain, and fatigue among women with gynecological cancer.

Methods
We searched and screened randomized controlled trials in 7 databases, trial registries, and gray literature from the databases’ inception to December 2021. Data were extracted from eligible studies, with each study’s quality assessed using the Cochrane risk-of-bias tool. Meta-analyses were conducted using RevMan 5.4. Sensitivity and subgroup analyses were performed. The quality of evidence across the studies was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results
Nine trials were included. Statistically significant effects of MBTs on depression (standardized mean difference, −0.56; 95% confidence interval, −1.01 to −0.11; P = .01), pain (standardized mean difference, −1.60; 95% confidence interval, −3.14 to −0.07; P = .04), and fatigue (standardized mean difference, −1.17; 95% confidence interval, −2.16 to −0.18; P = .02) were observed, but not on quality of life and anxiety. The quality of evidence was low due to the high risks of bias and high heterogeneity among the studies.

Conclusions
Mind-body therapies were effective in reducing depression, pain, and fatigue of women with gynecological cancer. However, the low quality of the evidence implies the need for more future studies with better methodologies.

Implications for Practice
Mind-body therapies may be used as an additional strategy to help manage depressive mood, pain, and fatigue among women with gynecological cancer.