bluuebunny/crossref_metadata_2025 huggingface dataset:
Macroprudential policy implementation in a heterogeneous monetary union
Authors: Rubio Margarita
Published: April 2023

In this article, I develop a two-country new Keynesian general equilibrium model with housing and collateral constraints to explore how macroprudential policies should be conducted in a heterogeneous monetary union. I consider several types of cross-country heterogeneity: asymmetric shocks, different leveraged countries, and mortgage contract heterogeneity (fixed and variable rates). As a macroprudential tool, I propose a Taylor-type rule for the loan-to-value ratio, which responds to deviations in output and house prices. This policy can be applied at a national or union level. Results show that structural asymmetries matter for the implementation of macroprudential policies, especially when the heterogeneity delivers differences in economic and financial volatilities. It seems then adequate to delegate macroprudential policies to national authorities. However, a supranational institution could also help stabilize the whole union when there are asymmetric shocks.
Lineage diversity in a widely distributed New World passerine bird, the House Wren
Authors: Klicka John , Epperly Kevin , Smith Brian Tilston , Spellman Garth M , Chaves Jaime A , Escalante Patricia , Witt Christopher C , Canales-del-Castillo Ricardo , Zink Robert M
Published: April 2023

We explored the evolutionary radiation in the House Wren complex (Troglodytes aedon and allies), the New World’s most widely distributed passerine species. The complex has been the source of ongoing taxonomic debate. To evaluate phenotypic variation in the House Wren complex, we collected 81,182 single-nucleotide polymorphisms (SNPs) from restriction site associated loci (RADseq) and mitochondrial DNA (mtDNA) from samples representing the taxonomic and geographic diversity of the complex. Both datasets reveal deep phylogeographic structuring, with several topological discrepancies. The trees highlight the evolutionary distinctiveness of eastern and western T. aedon, which were sister taxa in the SNP tree and paraphyletic on the mtDNA tree. The RADseq data reveal a distinct T. a. brunneicollis group, although STRUCTURE plots suggest admixture between western T. aedon and northern Mexican samples of T. a. brunneicollis. MtDNA data show a paraphyletic arrangement of T. a. musculus on the tree, whereas the SNP tree portrays them as monophyletic. Island taxa are distinct in both datasets, including T. a. beani (Isla Cozumel), which appears derived from T. a. musculus in eastern Mexico, and T. sissonii (Isla Socorro) and T. tanneri (Isla Clarión) although the 2 datasets disagree on their overall phylogenetic placement. Although we had only mtDNA data for T. a. martinicensis from the Lesser Antilles, we found at least 4 distinct and paraphyletic taxa from Trinidad, Granada, St. Vincent islands, and Dominica. The House Wren complex showed strong differentiation in mtDNA and RADseq datasets, with conflicting patterns likely arising from some combination of sex-biased dispersal, incomplete lineage sorting, or selection on mtDNA. The most glaring discrepancies between these 2 datasets, such as the paraphyly of eastern and western North American House Wrens in the mtDNA tree, present excellent opportunities for follow-up studies on evolutionary mechanisms that underpin phylogeographic patterns.
A multifunctional true caffeoyl coenzyme A O-methyltransferase enzyme participates in the biosynthesis of polymethoxylated flavones in citrus
Authors: Liao Zhenkun , Liu Xiaojuan , Zheng Juan , Zhao Chenning , Wang Dengliang , Xu Yang , Sun Chongde
Published: April 2023

Polymethoxylated flavones (PMFs) have received extensive attention due to their abundant bioactivities. Citrus peels specifically accumulate abundant PMFs, and methylation modification is a key step in PMF biosynthesis; however, the function of reported O-methyltransferase (OMT) in citrus is insufficient to elucidate the complete methylation process of PMFs. In this study, we analyzed the accumulation pattern of PMFs in the flavedo of the sweet orange (Citrus sinensis) cultivar “Bingtangcheng” at different developmental stages. We found that accumulation of PMFs was completed at the early stage of fruit development (60-d after flowering). Furthermore, we characterized a true caffeoyl-CoA O-methyltransferase (named CsCCoAOMT1) from C. sinensis. Functional analysis in vitro showed that CsCCoAOMT1 preferred flavonoids to caffeoyl-CoA and esculetin. This enzyme efficiently methylated the 6-, 7- 8-, and 3′-OH of a wide array of flavonoids with vicinal hydroxyl groups with a strong preference for quercetin (flavonol) and flavones. The transient overexpression and virus-induced gene silencing experiments verified that CsCCoAOMT1 could promote the accumulation of PMFs in citrus. These results reveal the function of true CCoAOMTs and indicate that CsCCoAOMT1 is a highly efficient multifunctional O-methyltransferase involved in the biosynthesis of PMFs in citrus.
The First- and Second-Nature Geographic Correlates of Federal Budget Transfers and Fiscal Dependence—Evidence from Russia and the United States
Authors: White Allison C , Kim Youngsung
Published: April 2023

This study examines fiscal federalism by interrogating the relationship between first- and second-nature geographic features—most notably distance as well as various economic/infrastructural indicators—and intergovernmental transfers and subnational fiscal dependence in Russia and the United States from 2003 to 2015. Our findings reveal stark differences in the role that geographic factors play in these two federations. While first- and second-nature factors influenced both transfers and reliance in Russia, only second-nature indicators had an effect in the U.S. case. Economic development and infrastructural improvements do not cause the influence of first-nature indicators to evaporate altogether, but they do attenuate the effects of those considerations.
OA01 No difference in risk of myocardial infarction among patients receiving either IL6 or TNF inhibitors for rheumatoid arthritis
Authors: Tian Zixing , Kearsley-Fleet Lianne , Lauper Kim , Haughton Sally , Watson Kath , Lunt Mark , Mclaughlin John , Verma Arpana , Hyrich Kimme L
Published: April 2023

Background/Aims

Interleukin 6 inhibitors (IL-6i) can increase LDL cholesterol levels, which raises concerns about the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) receiving this therapy. This study aims to compare the risk of MI between people with RA in the UK clinical setting receiving IL-6i or tumour necrosis factor inhibitors (TNFi) overall or by line of therapy (LoT).

Methods

Patients with RA registered between 01/10/2001 and 27/05/2022 with BSRBR-RA starting IL-6i or TNFi treatments were included. Occurrence of MI was identified from clinical follow-up forms and through cause of death reported by the national UK death register. Only those MIs occurring whilst the patient was actively receiving drug were included. The risk of MI in patients receiving IL6i compared to TNFi was compared using Cox regression, adjusted for baseline co-variates using propensity scores (PS, see Table 1). Follow-up commenced at the start of the drug of interest and patients were censored at occurrence of MI, death, discontinuation of therapy or last follow-up visit, whichever came first. Multiple imputation was used for missing data. To account for known differences in LoT use of TNFi and IL6i (with IL6i more likely as a later line bDMARD), overall analyses adjusted for LoT in PS and secondary analyses by LoT were conducted. Direct switches between originator to biosimilars were considered the same treatment.

Results

A total of 29,596 IL6i or TNFi treatments in 20,725 patients were included (3,098 IL-6i; 26,498 TNFi), representing 153,913 person-years of exposure. Compared to patients receiving TNFi, patients starting IL-6i treatment were older, had longer disease duration, less likely to use methotrexate and steroids, and had more comorbidities. During follow-up, 372 MIs occurred, 27 on IL-6i and 345 on TNFi, with an overall lower crude rate of MI in patients receiving IL6i compared to TNFi. After PS adjustment, the risk of MI was not significantly different between the two treatment overall (HR 0.77, 95% CI 0.48-1.24) or when stratified by LoT (Table 1).

Conclusion

This study could not identify any difference in risk of MI between IL-6i and TNFi treatment after patient characteristics and LoT were considered.

Disclosure

Z. Tian: None. L. Kearsley-Fleet: None. K. Lauper: Honoraria; Celltrion, Pfizer, Viatris, Galapagos. S. Haughton: None. K. Watson: None. M. Lunt: None. J. Mclaughlin: None. A. Verma: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.
P007 Automating blood monitoring and handover for patients with rheumatic diseases commencing disease-modifying anti-rheumatic drugs (DMARDs)
Authors: Mirza Maria , Lang David , Escudero Alexa , Soni Anushka , Shine Brian , Paddon Kevin , Luqmani Raashid
Published: April 2023

Background/Aims

Approximately 100 patients a month are commenced on DMARD therapy and until recently required manual monitoring and handover to primary care. We aimed to improve this process using a system implementing automated algorithms.

Methods

We designed a system to automate analysis using algorithms based on BSR guidance. Clinician endorsement was required for individual missing and abnormal results. Group endorsement was enabled for normal and mildly abnormal results. Handover to primary care was facilitated by patients completing a Microsoft form providing details of efficacy, side-effects, and compliance. All reports are imported into our bespoke system to generate automatic reports which constituted as a handover letter to primary care

Results

We have analysed 5,483 blood tests using the new system. All normal results can be endorsed at once without scrutiny. Missing records occurred chiefly due to the laboratory providing blood results in sections. The new system has been tested against the manual method for blood monitoring highlighting improved accuracy and efficiency of the new system. To date, 69% of patients have been handed over to the GP successfully without a need for further out-patient appointment.

Conclusion

We have introduced an efficient method for semi-automating DMARD monitoring and handover in 5,483 sets equivalent to assessing 200-250 records per 4-hour session and could efficiently oversee handover in 69% of cases without necessitating direct clinical review. The efficiency is almost 80% reduction in workforce required.

Disclosure

M. Mirza: None. D. Lang: None. A. Escudero: None. A. Soni: Grants/research support; Oxford ucb grant. B. Shine: None. K. Paddon: None. R. Luqmani: Grants/research support; Pfizer global grant.
P039 The association between gout and psychological co-morbidity: a five-year prospective cohort study
Authors: Higgs Jordan J R , Clarson Lorna , Bajpai Ram , Muller Sara , Roddy Edward
Published: April 2023

Background/Aims

Gout is associated with physical co-morbidities and a reduction in physical health-related quality of life. However, the association between gout and psychological comorbidity (depression and anxiety) has received less attention. A secondary analysis of data from a five-year prospective cohort study was performed to determine the prevalence and incidence of anxiety and depression in people with gout, and gout characteristics associated with psychological co-morbidity.

Methods

Adults aged ≥18 years with gout were identified via Read codes or allopurinol prescriptions from 20 general practices across the West Midlands. Questionnaires were mailed at baseline and at 12-, 36- and 60-months. Questionnaire data included socio-demographics, gout-related characteristics (flare frequency, oligo- or poly-articular gout, gout duration and allopurinol use) and validated anxiety (GAD-7) and depression (PHQ-9) questionnaires. Current anxiety and depression were defined as scores>10 on the GAD-7 and PHQ-9 respectively. The prevalence and incidence of new-onset anxiety or depression were described at 12, 36 and 60 months in those without anxiety and depression at baseline. Binary logistic regression used to determine baseline gout characteristics associated with developing new-onset anxiety or depression at each time point (odds ratios (OR), 95% confidence intervals (CI), adjusted for age, gender and deprivation).

Results

Of 1184 baseline responders, 721, 605 and 411 responded at 12-, 36- and 60-months, respectively. The peak prevalence of both depression and anxiety was at baseline at 12.6% and 10.0%, respectively. Responders with anxiety (GAD-7 ≥10) or depression (PHQ-9 ≥10) at baseline were excluded from new-onset analysis. Over five years, one in thirteen (7.5%) developed new-onset anxiety, and one in eleven (9.2%) developed new-onset depression at any future time point. Developing anxiety was associated with a history of oligo- or poly-articular gout flares at baseline (OR 2.31, 95% CI:1.26 to 4.23) but not flare frequency, gout duration, or allopurinol use. New-onset depression was associated with allopurinol use at baseline (OR 1.93, 95% CI: 1.01 to 3.69) but not flare frequency, gout duration, or oligo- or poly-articular gout flares.

Conclusion

Psychological co-morbidity is common in people living with gout; clinicians should be aware of this when assessing and treating people with gout.

Disclosure

J.J.R. Higgs: None. L. Clarson: None. R. Bajpai: None. S. Muller: None. E. Roddy: None.
P055 Giant Cell Arteritis Diagnosis: Metadiagnosis by robust Bayesian estimate of strength of belief
Authors: Clearkin Louis
Published: April 2023

Background/Aims

Metadiagnosis expresses diagnostic belief as: (i) a numeric probability, (ii) degree of confidence in the probability estimate and (iii) defines the derived information as decision thresholds. We use this approach to stratify suspected GCA patients, by disease probability, into three classes. (a) Likely to have GCA, (b) Unlikely to have GCA, and (c) Uncertain GCA status.

Methods

We developed a Bayesian algorithm that computes a patient’s disease probability based on their signs, symptoms and reference-standard tests. This algorithm forms the computational engine of the first iteration of an online APP. The computational engine incorporated statistical weights (likelihood ratios) from a meta-analysis of 68 unique studies (14 037 unique patients with suspected GCA). The algorithm requires the specification of a disease prevalence. This is the “prior” probability any patient has GCA. We then update this probability incrementally with each additional item of information elicited from the questionnaire proforma (e.g. female? headache? visual abnormality? …) by incremental evidence aggregation. Finally, the outcome of the patient's reference standard test is incorporated (e.g. positive, negative, indeterminate) and a final posterior GCA probability is computed for each patient.

Results

Quantitative GCA risk estimate for each individual patient, and how that was altered by the result of reference standard test, produces three distinct groups: a) Low probability group - estimated risk of GCA is significantly lower than the prevalence in the cohort. The reference standard test in this group was uniformly negative.b) intermediate probability group - estimated risk of GCA is around the same as the prevalence in the cohort. The reference standard test (TAB) is almost always negative in this group, but not exclusively.c) high probability group - estimated risk of GCA far exceeds the base or population risk level, and the reference standard test (TAB) is typically confirmatory in this group.

Conclusion

Applying Bayesian algorithmic metadiagnosis, based on established values of how indicators of disease impact on diagnosis, allows numerical disease prediction and non-mathematically communicating the precision of diagnosis may enhance informed patient choice leading to personalised, targeted intervention. An inbuilt artificial neural network (a deep learning method feedback-loop) trains the algorithm to identify the value of all relevant indicators and so improves predictive accuracy. We plan further studies to establish how this approach could impact on patient well-being and resource utilisation.

Disclosure

L. Clearkin: None.
P059 A review of intra-articular corticosteroid injection safety and clinical effectiveness during COVID-19
Authors: McCall Gary J
Published: April 2023

Background/Aims

Intraarticular corticosteroid injections (CSI) are used as a short-term treatment for inflammatory arthritis and osteoarthritis. At the outset of the COVID-19 pandemic there was concern regarding the immunosuppressive effect of steroids and the potential risk of COVID-19 infection in patients treated with CSI. There is no universal evidence-based consensus on the optimum dosing of CSI.

Nationally there was a mixed response to CSI use during the COVID-19 pandemic. Early during the pandemic, our Trust advised using only the lowest BNF indicated steroid dose to minimize any potential side effects. Large joints (knees and shoulders) were injected with 40mg of Kenalog compared to 80mg pre pandemic.

No previous survey has reported the incidence of covid infection post CSI. The primary aim of this project was to address this gap. A secondary aim was to review the clinical effectiveness of a ‘larger’ versus ‘smaller’ steroid dose in CSI.

Methods

Retrospective data collection was carried out for 107 patients who received CSI during the pandemic. All patients who received CSI within the Trust rheumatology department were followed up with a six-week phone call. During this consultation the effectiveness of the CSI was considered by asking them to score the effectiveness of the CSI out of 10 (10 being maximum improvement). The incidence of COVID-19 infection was also recorded.

This data was compared to the same data from a group of patients injected with a larger dose of CSI pre-pandemic (n = 114).

Results

The patient reported incidence of COVID-19 infection within 6 weeks of CSI was 1.87%.

Patient reported outcomes showed a mean improvement in joint symptoms of 6.97 using 80mg of kenalog, versus 5.02 improvement using the smaller 40mg dose at six week follow up.

Interestingly 56% of people injected with a larger dose reported a minimum 8/10 improvement compared to 22% of patients injected with a smaller dose.

Conclusion

The low incidence of COVID-19 infections following CSI indicates that there is no significant correlation with increased in risk of contracting COVID-19. This study did not collect any data on outcomes of infection but at the time of the phone calls no patients had been hospitalized or died.

The incidence of COVID-19 infection was below the national average. Some of the Rheumatology patients injected may have been advised to shield which may have contributed to the lower-than-expected figure.

The significantly increased benefit consistently reported by patients supports the use of a higher dose steroid (Kenalog 80mg) versus lower dose (40mg) when injecting large joints in patients with arthritis. It is important to weight up the risks and benefits of CSI but this suggests that we should use the higher dose in clinical practice.

Disclosure

G.J. McCall: None.
P075 Mendelian randomization studies of lifestyle-related risk factors for osteoarthritis: a PRISMA review and meta-analysis
Authors: Ho Justin , Mak Christopher
Published: April 2023

Background/Aims

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors.

Methods

We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines.

Results

A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA.

Conclusion

Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.

Disclosure

J. Ho: None. C. Mak: None.
P077 Bone mineral density predicts fractures when measured in more than one area: results from a large observational cohort
Authors: Nadeem Ummaz , Bukhari Marwan , Sultan Zain
Published: April 2023

Background/Aims

Osteoporosis is characterised by a reduction in bone mineral density (BMD). Low BMD is correlated with increased fracture risk. It is unclear whether a BMD value at a specific site is superior for predicting fracture. The Fracture Risk Assessment (FRAX™) tool is used to evaluate fracture risk, using the BMD at the non-dominant hip; focussing on the neck mean and neck total. This is despite a T score of -2.5 or below in the lumbar spine defining a patient as osteoporotic. This study aimed to determine whether the other measures of BMD that are noted are as predictive of fracture.

Methods

Patients referred for routine dual-energy x-ray absorptiometry (DEXA) scans at the Royal Lancaster Infirmary from 2004 to 2019 were studied. BMD data from lumbar vertebrae (L1-L4) and anatomical regions of the left and right femur were collected from DEXA images. A logistic regression model was fitted using fracture as a dependent variable and BMD values from the lumbar vertebrae, right and left femur as predictors, adjusted for age at scan and sex. Goodness of fit was assessed using a receiver operating characteristic (ROC) curve.

Results

A total of 31,546 patients were included in the analysis (82.9% female), of whom 37.6% had sustained a fracture, and the mean age of the cohort was 64.9 (standard deviation 12.9). Table 1 shows the results of the logistic models. Areas under the receiver operating characteristic curve (AUC) demonstrated the positive predictive ability of a reduction in BMD in the lumbar vertebrae and regions of the femur and fracture risk. BMD data from the four lumbar vertebrae were just as predictive of fracture as the right and left femur.

Conclusion

The study findings demonstrate that low BMD in all areas measured were equally predictive of fracture. When the non-dominant hip is not measurable, using other areas from a DEXA scan could be used to predict fracture risk. Research evaluating change in BMD over time could alter this observation.

Disclosure

U. Nadeem: None. M. Bukhari: None. Z. Sultan: None.
P079 Use of an electronic text messaging service to improve efficiency in initial Fracture Liaison Service Patient Assessment
Authors: Reid Rosie , Lever Elliott , Davis Diana
Published: April 2023

Background/Aims

Fracture Liaison Service (FLS) is labour intensive. It aims to identify all patients aged over 50 years presenting with a new fragility fracture and assess for treatment, in order to prevent future fractures and associated morbidity and mortality. According to the Royal Osteoporosis Society published Standards (2015), patients should have a comprehensive bone assessment within 3 months of the incident fracture. However, such assessments are time consuming, typically taking up to 40 minutes of an FLS practitioner's time. Understaffing led to designing an approach to gather information and streamline the Fracture Liaison service.

Methods

We approached an electronics communication company who generated a secure form containing the information required for FLS initial assessment. As a trial, all patients identified by the FLS as having a new fragility fracture between 15th November 2021 and 15th December 2021 were sent a text link to this questionnaire. A follow-up message was sent 1 day and 1 week later (3 messages in total). The questionnaires were then exported to the patient's electronic clinical record. Data collected included information allowing prediction of risk for future fractures. Following assessment of this data, action letters could be sent to the GP advising on a treatment plan, for example, to start an oral bisphosphonate or referral for parenteral treatment. We analysed the results and performed cost analysis based on comparison to normal practice where the initial assessment would have been undertaken as a clinic appointment.

Results

43 out of 103 patients (42%) responded to the questionnaire. Of these 43 patients, 32 (74%) were female and the majority aged 60 to 79 years. Our cost analysis showed that allowing for a 30-minute face to face appointment for each of 43 patients would have taken 22.5 hours. By comparison, virtual assessment of the data from each questionnaire took only 8 minutes ie a total of 5.7 hours. This saved 16.8 hours of the FLS practitioner's time with a calculated cost saving of £352, based on professional time cost of £21 per hour. Face to face attendances would have cost £120 per patient ie £5160 for 43 patients. The total amount saved using the electronic questionnaire for 43 patients was £5512.

Conclusion

We were able to capture the initial FLS bone assessment data using an electronic questionnaire in 43 out of 103 patents. This resulted in a significant cost saving from outpatient clinics of £5512 over a 1-month period. Downstream processing of the data was much shorter. Further action will be to modify the text messages to increase yield of patients. Electronic fracture liaison is effective at reducing demands on the service and coordinating activity. We have demonstrated a significant cost saving on a small number of patients.

Disclosure

R. Reid: None. E. Lever: None. D. Davis: None.
P085 First ever Juvenile Idiopathic Arthritis Awareness Week
Authors: Wilson Debbie
Published: April 2023

Background/Aims

During conversations with parents, children and adults living with JIA, a common theme kept coming up which is ‘why can’t people understand that JIA is a fluctuating condition?’ It can be very frustrating to keep explaining this. Some days, those living with JIA are able to do most things e.g. play football, cook, go for a run. However other days it can be a struggle to even get out of bed or climb the stairs at school/work. Due to the lack of understanding of this disease some children have had people asking them if they are faking it. They have said, ‘We need to help teachers to understand how diverse and fluctuating the disease is from day to day, I’m not lying about my symptoms, they change’. Therefore, following the success of NRAS’s RA awareness weeks, it was decided we would run the first ever JIA Awareness Week on the theme that no two days are the same living with JIA, and the hashtag #SameJIADifferentDay was created.

Methods

NRAS does not have the resources to do major TV adverts, so we decided to make this a social media campaign. We wanted to have films/photos and content to educate and inform people of what it is like to live with JIA and how no two days are the same. Six films were created, three were from a teenager and three from an adult, both living with JIA. This helps to highlight that adults can be living with JIA as well; it is does not become RA when you are an adult. We launched a different film each day that week (https://jia.org.uk/youtube) Throughout the week, events took place, including: JoinTogether JIA Parent/Carer online group meeting, a Facebook Live Session in which Chloe Umpleby and Ellie Farr from NRAS’s Young Voices Panel shared their experiences of what a good day and bad day looks like for them. Pam Duncan-Glancy MSP living with JIA, put in a motion to the Scottish Government and she helped raise awareness throughout the week.

Results

On average, NRAS’s social media platforms’ engagements went up by 189%. The highest was Facebook which had a 386.5% increase in profile visits. Some of the feedback we received included: “This is important recognition that a condition diagnosed in early childhood can continue to impact on your life as an adult.” “Simple video that speaks volumes.” “I’m loving the social media post for #SameJIADifferentDay, that is exactly what my child is like.”

Conclusion

This was a successful campaign, not only in terms of post engagement and website visits but, as seen in the feedback above, in using video as a powerful tool to get across common misconceptions about JIA.

Disclosure

D. Wilson: None.
P087 Predictors of long-term functional outcomes of juvenile idiopathic arthritis-enthesitis-related arthritis: a single-centre experience
Authors: Ravichandran Naveen , Guleria Shivika , Mohindra Namita , Aggarwal Amita
Published: April 2023

Background/Aims

Long-term functional outcomes in enthesitis-related arthritis (ERA), is limited from developing countries. We assessed the clinical and genetic factors that predicted the long-term functional outcome in ERA.

Methods

Patients with ERA having >5 years of disease and > 16 years of age were included in this cross-sectional study. Data on clinical features within 6 months of disease onset was collected from hospital records. Bath indices, HAQ-DI, and WHO-QOL were assessed at last visit. Poor functional outcome (PFO) was defined as BASFI>1.5 or HAQ-DI>1. Persistent disease activity (PDA) was defined as BASDAI>4. ERAP-1 and IL23R SNP genotyping was done by TaqMan method and HLA-B27 by PCR.

Results

181 patients [170-male, age of disease onset 12.5 (10-15) years, disease duration 7 (5-11) years] were recruited. There was delay in diagnosis of 3 (1-5) years. The median ASDAS-ESR, BASDAI, HAQ-DI, and BASFI at inclusion were 2.6 (1.8-3.6), 2.6 (1-5.2), 0.5 (0-0.5) and 1.6 (0.3-3.2) respectively. BASFI and HAQ-DI correlated with ASDAS-ESR, ASDAS-CRP and WHO-QOL-BREF. Those with PFO (n = 98) had a longer delay in diagnosis (4 vs 2 years, p < 0.001), lower prevalence of arthritis at onset (OR = 0.3, 95%CI:0.1-0.8), higher prevalence of ERAP1(rs27044) allele C (OR = 7.2, 95%CI:1.5-33.7), and higher disease activity currently. Delay in diagnosis (OR = 1.2; 95%CI:1.08-1.4) was the sole predictors of PFO in multivariate analysis. One-third of patients had PDA. Tarsitis at disease onset was the sole predictor of PDA (OR = 2.3; 95%CI:1.009-5.4).

Conclusion

Poor functional outcome was seen in one-half of JIA-ERA in the long-term and was associated with active disease with delay in diagnosis as its sole predictor.

Disclosure

N. Ravichandran: None. S. Guleria: None. N. Mohindra: None. A. Aggarwal: None.
P105 Mode of hospital rheumatology appointments in people with rheumatoid arthritis: the impact of the pandemic in England
Authors: Costello Ruth E , Hollick Rosemary J , Parker Michael , Kennedy Jonathan , Mackenna Brian , Brophy Sinead , Tomlinson Laurie , Humphreys Jenny H
Published: April 2023

Background/Aims

During the COVID-19 pandemic rheumatology services were advised to limit face to face contact, with remote telemedicine used instead. Although suitable for some people, issues have been highlighted with telemedicine. The frequency and proportion of remote appointments during the pandemic has not been described, or the socio-demographic characteristics of those accessing remote or in-person rheumatology care. This study aims to describe rheumatology healthcare utilisation and mode of appointment (remote/in-person) in people with rheumatoid arthritis (RA), prior to, and during the pandemic in England.

Methods

A retrospective prevalent cohort study of people with RA, identified using a validated algorithm, as of 1st April 2019 using electronic health record data (OpenSAFELY). Outpatient rheumatology appointments between 1st April 2019 and 31st March 2022 were identified. For each year, the number of outpatient appointments, mode of appointment (remote/in-person) and patient socio-demographic characteristics were described.

Results

130,884 people with RA were identified. Since the start of the pandemic, the proportion of people without any appointments in a 12-month period increased from 28.5% in 2019/20 to 33.3% in 2020/21 and has not recovered. Older people were most frequently not seen (51% of people >80 years in 2020/21 and 2021/22). Of appointments where mode was known, 54.4% of people with appointments in the year from April 2020 were only seen remotely, reducing to 35.1% in the year from April 2021 (Table 1). The proportion with all remote appointments increased with increasing age, comprising 62% of people >80 years in 2020. This age gradient persisted in 2021, though proportions of those >80 years with all-remote appointments was lower (44%). Compared to urban dwellers, a higher proportion of those living in rural areas had all remote appointments in 2020 (58% vs 53%) and 2021 (38% vs 34%).

Conclusion

During the pandemic, one third of people with RA were not seen at all over a 12-month period and these were more frequently older people. Over half of people were only seen remotely in 2020, decreasing to one-third in 2021. Given the limitations of remote appointments it is unknown whether this increased frequency of remote appointments will impact long-term outcomes.

Disclosure

R.E. Costello: Shareholder/stock ownership; AstraZeneca. R.J. Hollick: None. M. Parker: None. J. Kennedy: None. B. Mackenna: None. S. Brophy: None. L. Tomlinson: None. J.H. Humphreys: None.
P113 Attitudes to Technology supported Rheumatoid Arthritis care Questionnaire study: Barriers to People with RA & their clinicians using Technology in the care pathway
Authors: MacBrayne Amy , Soyel Hamit , Marsh William , Fenton Norman , Pitzalis Costantino , Curzon Paul , Humby Frances
Published: April 2023

Background/Aims

Rheumatoid arthritis (RA) outcomes have significantly improved with the treat-to-target paradigm, however, this necessitates intensive monitoring. Demand outstrips capacity in rheumatology services, making Mobile Health (mHealth) an attractive prospect. However, software developers often design without understanding the needs of ultimate users, solving non-existent problems. EULAR’s ‘Points to Consider’ for remote care specifies that interventions “should be developed in collaboration with all stakeholders including the healthcare team … and people with RMDs” as an overarching principle. This study sought to understand the barriers to end-users utilising technology within RA care.

Methods

Questionnaires were devised collaboratively between Rheumatologists and Computer scientists, informed by discussions with an RA patient group. Patients >18 with a diagnosis of RA completed paper surveys (utilising likert scales, ranking preferences, and tick-box answers) whilst awaiting appointments at Mile End Hospital (Barts Health NHS Trust). Clinicians were recruited to complete an online survey via mailing lists from multiple centres across London & South-East England, from October 2019-March 2020. The study was registered (CMPS ID [43816]). Ethical approval was obtained through the Bloomsbury Research and Ethics Committee (19/LO/1345). This work forms part of a larger mixed-methods study funded by the PAMBAYESIAN project grant.

Results

109 people with RA returned paper questionnaires, 41 clinicians completed the online survey. Most used technology daily (87.2% patients; 100% clinicians), but few used RA apps (75.3% patients never used). Whilst clinician use was higher (54.8%), only 2/31 (6.4%) recommended Rheumatology apps to patients. People with RA were willing to share & record monitoring data, with only 8.3% unwilling to share via technology, 53.8% preferring monthly submissions. Clinical data, e.g. pain scores & joint counts, was preferred to sharing personal data. Sharing with clinicians was preferred to self-monitoring. 83.9% clinicians responded positively to using technology, but cited NHS technical capabilities, cost, need for clinical trials, and concerns for data saturation as the most significant barriers.

Conclusion

In spite of reasonable tech-literacy, willing to use, and many existing apps, people with RA and their clinicians do not utilise technology in RA care. Clinicians identified data saturation and insufficient evidence as barriers, in addition to systemic healthcare system barriers.

Disclosure

A. MacBrayne: None. H. Soyel: None. W. Marsh: None. N. Fenton: None. C. Pitzalis: None. P. Curzon: None. F. Humby: None.
P122 Changes in Serum Levels of Cytokines with Methotrexate Monotherapy in Active Rheumatoid Arthritis: Results from a Multicentre, Randomized Controlled Trial on Methotrexate Escalation In Rheumatoid Arthritis
Authors: Jain Siddharth , Dhir Varun , Aggarwal Amita , Gupta Ranjan , Maurya Supriya , Leishangthem Bidyalaxmi , Khullar Aastha , Naidu Shankar , Sharma Shefali K , Sharma Aman , Jain Sanjay
Published: April 2023

Background/Aims

Identification of novel biomarkers of disease activity and prediction of treatment response in rheumatoid arthritis (RA) is an area of active research. Reliable biomarkers of methotrexate (MTX) response in RA are yet to be identified. We sought to study the change in serum levels of IL-6, MMP-3, and TNF-α with MTX monotherapy in patients with active RA.

Methods

Patients with active RA (SJC≥2 and TJC≥4) not on DMARDs (except HCQ and low-dose prednisolone) who had been enrolled in the multicentre, parallel-group RCT comparing two different MTX escalation strategies in RA (MEIRA) were included. All these patients received MTX monotherapy started at 15 mg/week and escalated to 25 mg/week by 4-8 weeks. Serum levels of IL-6, MMP-3, and TNF-α were measured by ELISA before starting MTX and after 16 weeks of MTX therapy. Responders were defined as patients who achieved a EULAR good or moderate response (based on DAS28ESR-3v) at 16 weeks. Analyses were intention-to-treat.

Results

16 weeks of MTX therapy led to a decline in serum levels of both MMP-3 (p = 0.03, n = 129) and IL-6 (p = 0.048, n = 151). The decline in IL-6 levels was seen only in MTX responders (p = 0.003), but not in non-responders, while the decline in MMP-3 levels was seen in both MTX non-responders (p = 0.015) and responders (p = 0.44) (Table 1). Baseline (pre-treatment) serum levels of both IL-6 and MMP-3 were similar between MTX responders and non-responders. Correlations of serum levels of IL-6 (but not MMP-3) with measures of disease activity (DAS28, tender joint count) were weak but significant at 16 weeks. Serum TNF-α levels (n = 137) were undetectable in a majority of patients (93%). Serum IL-6 was not detectable in 67 (44%) patients at baseline.

Conclusion

Although serum levels of both MMP-3 and IL-6 reduced significantly with MTX therapy, the decline of IL-6 was seen only in MTX responders but not in non-responders. Pre-treatment serum levels did not predict future MTX response or non-response. IL-6 levels also correlated weakly but significantly with disease activity. Serial measurement of serum IL-6 merits further exploration in larger studies as a potential biomarker of MTX response in RA.

Disclosure

S. Jain: None. V. Dhir: None. A. Aggarwal: None. R. Gupta: None. S. Maurya: None. B. Leishangthem: None. A. Khullar: None. S. Naidu: None. S.K. Sharma: None. A. Sharma: None. S. Jain: None.
P136 T-cell-Specific Biomarkers of Early Treatment Response in Patients with Rheumatoid Arthritis Treated with a Tumour Necrosis Factor Inhibitor
Authors: Sutcliffe Megan A , Ling Stephanie , Banyard Antonia , Rumker Laurie , Viatte Sebastien , Morris Andrew , Barton Anne , Raychaudhuri Soumya , Plant Darren
Published: April 2023

Background/Aims

The use of tumour necrosis factor inhibitors (TNFi) has advanced the clinical management of rheumatoid arthritis (RA). However, only 30-40% of patients who receive initial treatment with a TNFi experience a beneficial response. The discovery of reliable biomarkers of TNFi response is, therefore, a priority. Whilst T-cell dysfunction is documented in RA pathophysiology, T-cell involvement in TNFi treatment response is unclear. We aimed to phenotype peripheral blood-derived T-cells in RA patients over a number of time-points through the first 12-weeks of TNFi treatment; and to apply a cluster-free association testing method developed on single-cell CITE-seq data—co-varying neighbourhood analysis (CNA)—to high-dimensional single-cell CyTOF data.

Methods

16 TNFi-naïve RA patients commenced treatment with a TNFi (10 on Adalimumab, 6 on Etanercept) and peripheral blood samples were collected at 6-7 time-points between pre-treatment and 12-weeks. Peripheral blood mononuclear cells were extracted, and stained with a 35-marker CyTOF panel. Treatment response was classified using the EULAR response criteria, and patients were characterised as good, moderate or non-responders. Data were cleaned in FlowJo and analysed using both i) a cluster-based approach, where data were clustered into 12 populations, and linear mixed models were fitted per cluster to test for significant differences in population abundance and ii) a cluster-free approach called CNA where association testing is purely data-driven. Both analyses controlled for age, sex, type of TNFi and TNFi concentration.

Results

Cluster-based analysis showed at 12-weeks, 1 of the 12 clusters (CD4+CD39+HLA-DR+) significantly increased in abundance in the non-responder cohort compared to the good and moderate responders (adjusted p = 0.037). Interestingly, HLA-DR and CD39 genetic effects have previously been associated with TNFi response. No significant differences were observed with CNA.

Conclusion

These results demonstrate that significant differences in T-cell abundance can be seen as early as 12-weeks after commencing treatment with a TNFi. Validation of these findings is required before the predictive value of this T-cell population can be tested.

Disclosure

M.A. Sutcliffe: None. S. Ling: None. A. Banyard: None. L. Rumker: None. S. Viatte: None. A. Morris: None. A. Barton: None. S. Raychaudhuri: None. D. Plant: None.
P147 Predictors of interstitial lung involvement in systemic sclerosis
Authors: Santos Cristiana Sieiro , Rego Salgueiro Rúben , Morales Clara Moriano , Castro Carolina Álvarez , Álvarez Elvira Díez
Published: April 2023

Background/Aims

Interstitial lung disease (ILD) and pulmonary hypertension are the leading cause of death in patients with systemic sclerosis (SSc). Identifying SSc-ILD development and initiating treatment is essential to optimize therapeutic benefit. We aimed to identify predictors of SSc-ILD and compared early (<5 years from diagnosis) versus late (>5 years from diagnosis) onset.

Methods

We conducted a retrospective cohort study by including patients diagnosed with SSc from 1980 to 2020 followed in our unit and compared the clinical profile of patients with SSc-ILD to control SSc-non-ILD patients. Demographic features, clinical and immunological characteristics and baseline pulmonary function were retrieved. Logistic regression modelling was run to identify factors associated with SSc-ILD development. Factors associated with ILD were determined as factors associated with early or late onset. Bonferroni correction was used to limit Type I errors.

Results

We have included 103 patients from our patient registry from 1980 to 2021 (42% with SSc-ILD). Logistic regression identified risk factors associated with increased or decreased odds ratio for developing ILD is summarized in table 1: smoking history, male sex, the presence of myositis, anti-Scl70 and anti-Ro52 positivity, baseline pulmonary function including FVC and DLCO, mMRC (modified medical research council) dyspnea scale>2, mMSS (modified rodnan skin score)>3 and late pattern in capillaroscopy. Older age at SSc diagnosis, the presence of telangiectasias and smoking status was associated with increased odds of SSc-ILD onset before 5 years, while male gender, the presence of myositis and antiphospholid antibodies were associated with late-onset SSc-ILD.

Conclusion

We identified 11 factors significantly associated with risk of developing SSc-ILD. We identified early and late-onset predictors for ILD-SSc.

Disclosure

C. Sieiro Santos: None. R. Rego Salgueiro: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None.
P168 Factors associated with adverse outcomes in uveitis related to spondylarthritis (SpA-U) - development of a prognostic outcome score in patients with SpA-U
Authors: Santos Cristiana Sieiro , Sendino Tenorio Isabel , Castro Carolina Álvarez , Díez Álvarez Elvira
Published: April 2023

Background/Aims

Uveitis is the most frequent extra-articular manifestation of spondylarthritis (SpA), characterised by a sudden onset, often unilateral, anterior and recurrent, and may be the first clinical manifestation of the disease. The lack of standardised and validated outcome measures in uveitis makes it difficult to evaluate the efficacy of and refractoriness to treatment and determine factors associated with adverse outcomes. The objective of our study was to develop a prognostic outcome score for patients with uveitis associated with spondylarthritis (SpA-U) and determine factors associated with adverse outcomes in uveitis associated with SpA-U in patients under systemic treatment.

Methods

The outcome score was defined by best-corrected visual acuity (BCVA), anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their standard errors are displayed together with linear regression coefficients with 95% confidence intervals (CI). For continuous factors, averages and standard deviations are reported in addition to linear regression coefficients with 95% CI. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex.

Results

250 uveitis outbreaks were included. 62 uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history (β = 0.34), axial and peripheral involvement (β = 0.43), a BASDAI>4 (β = 0.32), positive HLA-B27 (β = 0.29), female sex (β = 0.19), patients with CRP elevation (β = 0.002) and bilateral ocular involvement (β = 0.32). At the same time, shorter disease evolution (β=-0.02) was associated with less severe uveitis activity.

Conclusion

We have determined factors associated with adverse outcomes in SpA-U by developing an outcome score that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.

Disclosure

C. Sieiro Santos: None. I. Sendino Tenorio: None. C. Álvarez Castro: None. E. Díez Álvarez: None.