bluuebunny/crossref_metadata_2025 huggingface dataset:
A method for unmasking incomplete astronomical signals: Application to the CO Multi-line Imaging of Nearby Galaxies project
Authors: Cooray Suchetha , Takeuchi Tsutomu T , Yoda Moe , Sorai Kazuo
Published: April 2020

Photometric surveys have provided incredible amounts of astronomical information in the form of images. However, astronomical images often contain artifacts that can critically hinder scientific analysis by misrepresenting intensities or contaminating catalogs as artificial objects. These affected pixels need to be masked and dealt with in any data reduction pipeline. We present a flexible, iterative algorithm to recover (unmask) astronomical images where some pixels are lacking. We demonstrate the application of the method on some intensity calibration source images in the CO Multi-line Imaging of Nearby Galaxies (COMING) project conducted using the 45 m telescope at Nobeyama Radio Observatory. The proposed algorithm restored artifacts due to a detector error in the intensity calibration source images. The restored images were used to calibrate 11 out of 147 observed galaxy maps in the survey. The tests show that the algorithm can restore measured intensities at sub 1% error even for noisy images (S/N = 2.4), despite lacking a significant part of the image. We present the formulation of the reconstruction algorithm, discuss its possibilities and limitations for extensions to other astronomical signals, and examine the results of the COMING application.
Dissecting the statistical properties of the linear extrapolation method of determining protein stability
Authors: Lindorff-Larsen Kresten
Published: April 2020

The linear extrapolation method to determine protein stability from denaturant-induced unfolding experiments is based on the observation that the free energy of unfolding is often a linear function of the denaturant concentration. The value in the absence of denaturant is then estimated by extrapolation from this linear relationship. Parameters and their confidence intervals are typically estimated by nonlinear least-squares regression. We have compared different methods for calculating confidence intervals and found that a simple method based on linear theory gives accurate results. We have also compared three different parameterizations of the linear extrapolation method and show that the most commonly used form is problematic since the stability and m-value are correlated in the nonlinear least-squares analysis. Parameter correlation can in some cases causes problems in the estimation of confidence intervals and regions and should be avoided when possible. Two alternative parameterizations show much less correlation between parameters.
EP32 Seamless transition to a biosimilar
Authors: Wood Katherine , Pickersgill Gemma , Khoffash Mahmoud Al , Stevens Robert , Coote Annabel , Sekyrynskaya Helen , Mackenzie Felicity , Yee Chee-Seng
Published: April 2020

Background

As adalimumab biosimilars were about to be launched in the UK, our trust was looking for ways to simplify and streamline the process to make it an efficient and seamless transition from originator to biosimilar. Consultations took place between all the stakeholders (clinical commissioning groups, pharmacy department, rheumatology department, home-care provider and biosimilar manufacturer) and an agreement was reached as follows: letters were sent to patients explaining what a biosimilar is and the process of transition. A helpline was established whereby patients were advised to contact if they had any questions or concerns. The home-care provider provided pre-populated prescriptions for the biosimilar. Latex allergy was determined for each patient and transition was made at next delivery (patients with a latex allergy stayed on originator as biosimilar pen contains latex). There was no additional clinic visit required. This is a descriptive analysis of our experience using this seamless transition to the biosimilar adalimumab.

Methods

From our database, we collected demographic data on the rheumatology patients who were on the originator and those who transitioned to the biosimilar. The success of the transition was determined if patients remained on the biosimilar six months later. In patients who did not remain on the biosimilar at six months, we analysed if the patient had switched back to originator, to a different targeted therapy or no longer on a targeted therapy.

Results

There were 262 rheumatology patients on the originator and 2 patients had a latex allergy. Therefore 260 patients were transitioned during a two month period. They were 50.4% female with mean age of 54 years (range 22 to 86 years) and the majority were Caucasians (99%). The diagnoses for this population were axial spondyloarthropathy (45%), rheumatoid arthritis (33%), psoriatic arthritis (21%) and juvenile idiopathic arthritis (1%). At six months post transition, 18 patients (6.9%) were no longer on the biosimilar: 57.1% female, mean age 50 (range 23 to 73), 85.7% axial spondyloarthropathy and all Caucasian. Of these, 11 had switched back to the originator, 3 were switched to a different targeted therapy and 4 were no longer on targeted therapy. The reasons for switching back to the originator were worsening symptoms (6 patients), side effects (4 patients) and difficulty using the pen device (1 patient).

Conclusion

This seamless transition with minimal impact on clinical time was very successful (93.1% success). It will be the model to be used for the future transition of other biosimilars.

Disclosures

K. Wood None. G. Pickersgill None. M. Al Khoffash None. R. Stevens None. A. Coote None. H. Sekyrynskaya None. F. Mackenzie None. C. Yee None.
EP43 Biologic retention in psoriatic arthritis: a real world study
Authors: Jawad Issrah , Nisar Muhammad K
Published: April 2020

Background

Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse. Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment.

Methods

We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management.

Results

335 patients were identified with PsA. 58% were female with mean age 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%). 35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy.

Conclusion

To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy.

Disclosures: I. Jawad: None. M.K. Nisar: None.
O35 Efficacy & safety of tocilizumab in GCA: a multi-centre experience of NHS clinical practice
Authors: Sebastian Alwin , Kayani Abdul , Ranasinghe Chavini , Hall Frances , Ransom Colin , Jayne David , Quick Vanessa , Hughes Mark , Stack John , Mukhtyar Chetan , Coath Fiona , Bharadwaj Anurag , Hajela Vijay , Butler Stephanie , Lwin May , Edwards Christopher , Whitlock Madeline , Dasgupta Bhaskar
Published: April 2020

Background

Giant cell arteritis (GCA) has a relapsing, remitting course with ischemic/vascular damage in a number of cases. Glucocorticoids (GC) remain mainstay of treatment with SAEs e.g. diabetes and fractures commonly seen. The GiACTA trial of tocilizumab (TCZ) in GCA led to NICE approval for 12 month’s therapy in relapsing/ refractory disease. We report real life experience in 51 cases.

Methods

Multicentre retrospective data collected through ENRAD and individual centres across England (Table 1). Outcomes were as assessed by supervising clinicians.

Results

Fifty-one patients were treated with TCZ (26 cranial, 13 LVV, 11 both). 11 (22.0%) had prior permanent sight loss due to AION, CRAO or both. One died prior to TCZ, from recurrent cerebral infarcts. Mean age was 71 years with 66.7% females. Ultrasound (US) was used for diagnosis in 28 (56.0%), exclusively or in combination with other tests such as biopsy, PET-CT or CTA. 70% had prior DMARD (LEF/MTX/AZT/MMF/CYC, mean duration 58 weeks). MTX was used in 50% alone or combination. Initial TCZ was given as subcutaneous or intravenous (85.4% and 14.6%). TCZ indication in 89.8% was relapsing, refractory or ischemic disease. Steroid AEs that prevented optimal GC dosing constituted 10% of TCZ indication. Mean follow up was 31 weeks, 30 (58.8%) continuing TCZ uninterrupted, 4 completed 12 months, 4 discontinued due to SAEs. Ten had brief interruptions due to minor AEs. One restarted after 12 months due to flare but died 12 weeks later from abdominal aortic aneurysm rupture. At follow up, 37(74%) were in remission with a mean GC dose of 6.97 mg (mean GC dose pre-TCZ 33.2 mg), Thirty-two (65.3%) ≤ 5mg. In 4 (8%) outcome could not be assessed as either they started TCZ recently or about to start. In 53% lipids were not checked after commencing TCZ. AEs seen were 37.0%.

Conclusion

In clinical practice, TCZ is efficacious and safe in relapsing/refractory/ischemic GCA. I.V. route is an option awaiting NHSE approval in refractory visual symptoms. Infections and other AEs do occur but overall safety profile is acceptable. US is excellent in identifying patients at need and is a useful disease activity monitoring tool.

Disclosures

A. Sebastian: None. A. Kayani: None. C. Ranasinghe: None. F. Hall: Consultancies; Sobi, S. Grants/research support; Actelion. C. Ransom: None. D. Jayne: None. V. Quick: Honoraria; Roche. M. Hughes: None. J. Stack: Member of speakers’ bureau; Roche. C. Mukhtyar: None. F. Coath: None. A. Bharadwaj: None. V. Hajela: None. S. Butler: Consultancies; Lily. M. Lwin: None. C. Edwards: Consultancies; Roche, Chugai. Grants/research support; Roche, Chugai. M. Whitlock: None. B. Dasgupta: Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.
O41 Percentage body fat as a predictor for fragility fracture: an observational study
Authors: Beith Dominic T , Bukhari Marwan
Published: April 2020

Background

A body mass index (BMI) of less than 19 is a known risk factor for the development of osteoporosis and thus increases the propensity of one having a fragility fracture. Bone mineral density (BMD) referrals are aided by the FRAX™ tool, which contains BMI in order to calculate the ten-year fracture risk. We aimed to investigate the effect of percentage body fat on risk of fracture referred for BMD estimation.

Methods

Between June 2004 and October 2015, patients were referred for bone mineral density (BMD) estimation in a scanner in the North West of England. All patients were referred with all FRAX™ indications including rheumatoid arthritis, excess alcohol, steroids, family history of fracture and secondary osteoporosis. The cohort was divided into quintiles of ascending body mass percentage. Logistical regression was then applied before adjusting for age at scan, gender and total left BMD comparing patients with a fracture and those that had not.

Results

35,759 patients were referred for scanning during the period. 22,765 (63.66%) were referred for BMD estimation and had body fat percentage measured. Mean age at scan was 63.16 (SD 12.86) and 18,961 (88.29%) of the cohort were females. 8,072 (35.46%) had a fracture. More fractures were seen in higher quintiles of percentage body fat, 1,693 (20.97%) compared to 1,580 (19.57%) in females (p = <0.05). Predictors shown in the Table 1 below adjusted for age at scan, gender and total left BMD. Logistical regression of the quintiles after adjustment shows statistical significance in quintiles 3, 4 and 5 as well as for age at scan and total left BMD. Other predictors did not shows statistical significance p > 0.05.

Conclusion

Our study of 22,765 patients referred for BMD estimations opposes current literature on the effect of BMI on fragility fractures. The data shows that increasing percentage body fat in associated with an increased propensity of fragility fractures in those with BMI as a FRAX™ indicator. Currently percentage body fact is not featured in the FRAX™ tool and further work needs to be done to show the relationship between fracture risk and percentage body fat.

Disclosures

D.T. Beith: None. M. Bukhari: None.
P14 Using NHS resources wisely: A Snapshot of biologic and small molecule agent prescribing at the Peter Maddison Rheumatology Centre
Authors: Jones Alaw R , Batty Ann , Lloyd Lois A , Breslin Anne , Owen Catherine , Ahmad Yasmeen
Published: April 2020

Background

Pharmacological management of rheumatological conditions has transformed in the past two decades. A range of targeted therapies are available to manage conditions such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Careful governance and management is required to ensure patients receive the most appropriate drug and dose for their condition.

Methods

Patients diagnosed with RA, PsA and SpA/AS treated with a biologic or small molecule agent during the period of April 2018 - March 2019 for >6 months duration were eligible for inclusion. Patients were identified using biologic patient registers maintained by the Rheumatology department.

Results

One hundred and eighty-one patients were eligible for inclusion. Ninety-two patients (51%) were female, age range: 21 - 85 years, median = 54 years. The most prescribed biologic was etanercept (n = 71, 39.2%) followed by rituximab (n = 31, 17.1%) and adalimumab (n = 23, 12.7%) of which 98.4% were prescribed a biosimilar formulation. A breakdown of prescribing is illustrated below.

Over a third of patients were maintained on a reduced dose of biologic, resulting in significant cost efficiencies (£20,000 cost avoidance with etanercept dose reduction). Twenty-eight patients in the RA cohort were not on a DMARD; of these 25 patients (89.2%) had achieved remission/ low disease activity. Average annual drug cost per patient was higher for psoriatic arthritis (£6,719.33 vs. £4731.00 for RA and £3,417.27 for SpA). Patients treated with rituximab had a dosing interval of 12 months or longer between cycles, as dosing was influenced by clinical symptoms. As a result, the percentage of patients in low disease activity is lower.

Conclusion

This study has shown marked variance in cost per head (range= £1,769- £9,303) depending on the disease, type of targeted therapy and disease response rate. The PMRC multidisciplinary team approach to introducing biosimilar medicine prescribing and actively maintaining patients in remission/low disease activity on reduced biologic therapy, has enabled patients to access medicines and deliver value-based healthcare with positive patient outcomes in line with NICE guidelines and clinical reasoning.

Disclosures

A.R. Jones None. A. Batty None. L.A. Lloyd None. A. Breslin None. C. Owen None. Y. Ahmad: None.
P32 Should we continue to test for latent tuberculosis infection in patients treated with biologics?
Authors: Sidhu Arslan A , Nandagudi Anupama
Published: April 2020

Background

Timely diagnosis of tuberculosis (TB) infection is important in patients receiving biologics. Current BSR guidelines on biologic safety in inflammatory arthritis (2018) advise to screen all patients for TB before starting treatment. Due to limitations of tuberculin skin test (TST), IFN-γ release assay (IGRA) is frequently used in addition to clinical examination, risk assessment and chest x-ray (CXR). There are no clear guidelines whether IGRA should be part of follow up assessments. The Royal College of Nursing suggest patients on biologics should have repeat CXR in 3 months after starting biologics and then annually. The American College of Rheumatology suggest an annual TST or IGRA for high-risk individuals receiving biologics. Centers for disease control and prevention guidelines allows to use TST and IGRA for surveillance in selected population.

Methods

We present two cases in which patients developed TB after starting biologics. Both patients had negative IGRA, normal CXR and low risk of developing TB on prebiologic screening.

Results

First patient was a 64-year-old female with rheumatoid arthritis diagnosed in 2001. She failed multiple conventional DMARDs and was started on Certolizumab in 2014. Prebiologic screen showed a negative IGRA (T Spot) and CXR was clear. She was a smoker and her mother had pulmonary TB when she was a child. After 4 years she presented with weight loss and cough. CXR showed 1.4 cm round opacity in right upper lobe. She underwent surgical resection and histology showed acid fast bacilli on ZN stain with superimposed aspergilloma. She was started on quadruple therapy and we switched Certolizumab to Etanercept due to its shorter half-life. Second patient was a 27-year-old man with ankylosing spondylitis diagnosed in 2015. He was a smoker and had no past medical history. He was started on Adalimumab in 2016. T Spot was negative and CXR was clear. There were no risk factors for TB. Two years later he presented with multiple tender subcutaneous nodules over thighs and lower abdomen. Skin biopsy after dermatology assessment showed superficial and deep perivascular inflammation with lymphocytes and small number of eosinophils. Differential were granulomatous infection or panniculitis due to injection site reaction. TB cultures came back negative but repeat T Spot was positive. He was treated as latent TB infection for 3 months and Adalimumab was restarted without any problems.

Conclusion

Current BSR guidelines advise to monitor patient clinically for any signs of TB while receiving biologics. We suggest that there is a need to review whether TST or IGRA should be done annually on high risk patients along with CXR.

Disclosures

A.A. Sidhu None. A. Nandagudi None.
P45 Interstitial pneumonitis induced by secukinumab therapy in a patient with psoriatic arthritis
Authors: Saleh Christopher , Bilgrami Syed , Gatheral Timothy , Ottewell Lesley
Published: April 2020

Background

Inhibition of pro-inflammatory interleukin-17A (IL-17A) with secukinumab (an anti-IL-17A antibody) has been utilised in patients with chronic autoimmune disease such as psoriasis seronegative spondyloarthopathies. In mouse models, IL-17A was involved in the development of pulmonary inflammation and progression of fibrosis, with blockade of IL-17A implicated as a potential therapeutic target in such conditions. Here we report a case of, seemingly paradoxical, interstitial lung disease (ILD) secondary to secukinumab therapy in a 61-year-old patient with psoriatic arthritis.

Methods

Please refer to the results section.

Results

Initial therapy was with adalimumab achieving good disease control for 9 years, at which point his arthritis began to progress. Secukinumab was commenced with good clinical response from his arthritis, however he developed a persistent cough with blood-stained secretions, and shortness of breath on exertion. A CT thorax was arranged at 21 weeks after initiation of secukinumab, and showed florid bibasal, lingula and middle lobe ground glass density air space opacification. He went on to have bronchoscopy with bronchoalveolar lavage (BAL) and differential cell count. BAL was negative for atypical infection including P. jirovecii, growing upper respiratory tract flora only. Microscopy of BAL showed lymphocytosis in keeping with the diagnosis of drug induced ILD, with no atypical cells. The patient made a significant improvement on withdrawal of secukinumab therapy within 7-8 weeks of cessation - both clinically and radiologically.

Conclusion

A review of the current literature at this time indicates this is now a third case of secukinumab induced ILD. Given this potentially idiosyncratic reaction we suggest further work may be necessary to understand the underlying immunogenic potential of secukinumab, and an increased awareness as well as vigilance in reporting, to determine those at-risk populations of this phenomenon.

Disclosures

C. Saleh None. S. Bilgrami None. T. Gatheral None. L. Ottewell None.
P61 Trajectories of foot pain severity over seven years and relationship to potential prognostic factors: the clinical assessment study of the foot
Authors: Marshall Michelle , Blagojevic-Bucknall Milica , Rathod-Mistry Trishna , Thomas Martin J , Edwards John J , Peat George , Menz Hylton B , Roddy Edward
Published: April 2020

Background

Foot pain is common and disabling in older adults however little is known about its course. The objective of this study was to identify foot pain trajectories over seven years and examine the associations between progressive symptom trajectories and potential prognostic factors.

Methods

All adults aged ≥50 years registered with four general practices in North Staffordshire, UK were mailed a health survey at baseline. Those reporting foot pain in the previous 12 months were invited to attend a research clinic that included a standardised interview, physical examination, and plain radiographs of the feet. Follow-up was by repeated postal surveys at 18 months, three years, 54 months, and seven years. Trajectories of repeated measures of foot pain severity in the previous month (10-point numerical rating scale) were identified using Latent Class Growth Analysis (LCGA). Logistic regression was undertaken to explore the relationship between these trajectories and both person-level and foot-level prognostic factors adjusted for covariates (age, gender, and body mass index).

Results

Of 560 adults with foot pain attending baseline research clinics, 425 (76%) provided data at baseline and ≥two follow-up time-points and were included in the analysis. The optimum LGCA model for foot pain severity was a 4-class model with the following trajectories: mild improving pain (n = 109, 26%); moderate improving pain (n = 179, 42%); moderate persistent pain (n = 122, 29%); severe persistent pain (n = 15, 4%). Compared with individuals with mild/moderate improving pain trajectories, those with moderate/severe persistent pain trajectories over 7 years did not differ significantly by age, sex, foot posture or radiographic foot OA phenotype at baseline, but were more likely to be overweight/obese. After adjustment for covariates, these less favourable long-term trajectories were associated with lower socioeconomic position, poorer physical and mental health, catastrophising, greater foot-specific functional limitation (Manchester Foot Pain and Disability Index), and self-reported hallux valgus at baseline (Table 1).

Conclusion

Over a 7-year period, one-third of individuals had persistent moderate to severe pain. Targeting interventions to modifiable prognostic factors such as obesity and hallux valgus may have the potential to improve long-term outcomes in people with foot pain.

Disclosures

M. Marshall None. M. Blagojevic-Bucknall None. T. Rathod-Mistry None. M.J. Thomas None. J.J. Edwards Other; JJE is part of The Keele Academic General Practice which has received funding from Bristol-Myers Squibb to develop and evaluate a quality improvement tool in anticoagulation. G. Peat None. H.B. Menz None. E. Roddy None.
P80 Value of the clinical nurse specialist role in the care of patients with systemic lupus erythematosus: the patient experience
Authors: Culshaw Alison N , Roychowdhury Dr. Bijaya
Published: April 2020

Background

Systemic lupus erythematosus (SLE) is a complex, multi-system, chronic disease that is predominantly managed by rheumatologists in a clinical setting. Clinical Nurse Specialist (CNS) access and support for patients can be variable and mostly lacking. The value of the CNS role in supporting patients with SLE has not previously been explored in depth from the patient’s perspective. This service evaluation investigates the role of the SLE CNS in supporting patients with SLE, with the aim to further develop the CNS role in SLE care to support patients locally in North Wales.

Methods

Seven SLE participants, who had access to a dedicated SLE CNS, were selected from connective tissue disease clinics at a district general hospital. The age range was 33-69 years with a disease duration from 4-20 years. Participants took part in a one to one semi-structured interview using open ended questions. Interviews were digitally recorded, transcribed verbatim, and analysed using thematic analysis.

Results

The analysis of the interviews highlighted the value of a specific SLE CNS role to SLE patients. Overall, responses were positive with participants feeling reassured knowing they could contact the CNS for support via the telephone nurse advice line during flares of disease activity: “It’s like a lifeline”. Owing to the complex nature of SLE, participants valued having a nurse to monitor their condition, enabling them to feel supported between routine appointments: “I think of the nurse as my safety blanket”. Validation of symptoms led participants to feel in control, as they appreciated having a nurse to discuss their concerns with, who took the time to listen: “It’s about not putting it all down to lupus”. All respondents valued receiving information about SLE from the CNS, who was perceived as having specialist knowledge of SLE: “The specialist nurse knows the ins and outs”. This expert knowledge of SLE was fundamental to participants at diagnosis and throughout their disease trajectory, as those without support from a CNS soon after diagnosis felt isolated and ill informed: “I didn't even know what I had”. The majority of participants reported a lack of empathy and understanding of SLE among primary care specialists, and experiences of misdiagnosis were not uncommon: ‘“They said I had scarlet fever, psoriasis and various other things”.

Conclusion

Though the number of participants was small, the study has revealed that the SLE CNS provides an important and unique role in the care of patients with SLE. Continued support from SLE CNS roles, and improved knowledge of SLE within primary care, is fundamental so that SLE patients have enhanced support soon after diagnosis and throughout their journey with SLE.

Disclosures

A.N. Culshaw None. D. Roychowdhury None.
P131 Patients with hand osteoarthritis have a long duration of symptoms and significant pain scores at the time of referral to rheumatology services
Authors: Ghaffar Muhammad Tauseef , O'Sullivan Miriam , Silke Carmel , Whelan Bryan
Published: April 2020

Background

Osteoarthritis is the most common arthritic condition worldwide affecting 9.6% of men and 18% of women aged >60 years with an Irish prevalence >50 years of age is 17.3% for women and 9.4% for men. It can occur in any joint but is most common in the hip, knee and spine. It is also prevalent in the hand and can lead to significant pain and disability. The aim of this study was to examine the pattern and severity of hand osteoarthritis in patients referred to a regional rheumatology service.

Methods

Consecutive patients seen in general rheumatology clinics of all ages and gender who had confirmed diagnosis of hand osteoarthritis based on the ACR criteria were recruited (patients with RA, psoriatic arthritis, gout and haemochromatosis were excluded). All gave written informed consent to participate and had a single assessment performed including demographic details, symptom assessment using the AUSCAN Osteoarthritis Hand Index. In addition, measures of functional ability, grip strength and pincer strength were performed in the OT department. All patients also had an up to date hand X-ray performed. For the purposes of this paper we will report the initial assessments including the demographic details and pain scores.

Results

103 consecutive patients were included in this analysis. M:F ratio 1:5.25. Mean age was 66.13 years. Mean duration of symptoms 74.63 months (8-422). At assessment the mean pain scores (0-10 VAS) were 4.53 (at rest), 6.09 (when gripping), 6.06 (when lifting) and 6.42 (when turning objects). The mean tender joint count was 7.14 and the mean score for objective soft tissue swelling in the joints was 1.36.

Subject Average VAS (0-10) Pain Score at presentation by Gender

Conclusion

From these analyses, we can see that patients are referred very late with no one being seen within 6 months of symptoms onset. This is despite patients having pain scores which are comparable to those with inflammatory arthritis and in a small minority evidence of soft tissue swelling in joints at the time of presentation. In addition, it is noticeable that men are under-represented in the cohort of referred patients based on estimates of prevalence.

Disclosures

M. Ghaffar None. M. O'Sullivan None. C. Silke None. B. Whelan None.
P134 Collaborating with the National Congenital Anomaly and Rare Disease Registration Service to estimate national incidence of Kawasaki disease in England
Authors: Rutter Megan , Lanyon Peter C , Bythell Mary , Stevens Sarah , Aston Jeanette , Pearce Fiona A
Published: April 2020

Background

The true incidence of Kawasaki disease (KD) in England is unknown. In KD treatment with intravenous immunoglobulin (IVIG) can be lifesaving, but it is both expensive and in limited supply. In collaboration with Public Health England’s National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) we aimed to determine the incidence of KD in England.

Methods

We worked within NCARDRS to access patient-identifiable Hospital Episode Statistics (HES) data, enabled by their legal permissions (CAG 10-02(d)/2015). We extracted all patients receiving a primary or additional diagnostic code for KD between April 2003 -March 2017. For patients identified in Nottingham University Hospitals Trust, we reviewed the coding accuracy in their medical records. We calculated incidence with 95% Poisson confidence intervals among children in England using the total number of cases newly diagnosed in the study period. We used the ONS mid-year estimates for 2016 for the denominator.

Results

37 patients were coded as having KD in our Trust. All had a clinical diagnosis of KD (positive predictive value 100%). 32 patients were paediatric cases treated for KD; the remaining 5 patients were diagnosed in adult life on the basis of pathognomonic angiogram findings. It was not possible to apply classification criteria because the required information was not always available. During the 13-year study period we identified 3345 cases in children aged <5, and 4234 cases in children <16 in England. The incidence in children aged <5 years was 7.50 (95% CI: 7.25-7.76)/100,000 person-years, and 40.7% of cases were female. Incidence in children aged <16 was 3.09 (95% CI: 3.00-3.19)/100,000 person-years, and 41% of cases were female.

Conclusion

Analysis of HES data within NCARDRS has provided population-based estimates of incidence of KD for the whole of England. Our estimates are higher than in previous studies. Validation of coding accuracy has shown our methods were specific, and they are likely to be sensitive given KD is always treated in hospital. Accurate incidence estimates are essential for appropriate resource allocation, given the limited availability of lifesaving IVIG treatment.

Disclosures

M. Rutter None. P.C. Lanyon None. M. Bythell None. S. Stevens None. J. Aston None. F.A. Pearce None.
P150 Influence of patient reported arthritis activity in determining sHAQ, HAQ-DI and Cochin scores in systemic sclerosis
Authors: Gjeloshi Klodian , Danzo Fiammetta , Abignano Giuseppina , Dean Anne-Maree , Masini Francesco , Cuomo Giovanna , del Galdo Francesco
Published: April 2020

Background

Arthritic involvement is a common manifestation in systemic sclerosis (SSc). The aim of this study is to assess the weight of patient reported arthritis activity in determining Patient Reported Outcome Measures (PROMs) in an observational cohort of SSc patients.

Methods

We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with SSc according to EULAR/ACR 2013 classification criteria, in annual follow-up (for a total of 165 patients/year) with Pulmonary Function Tests (PFTs), Health Assessment Questionnaire - Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ) and Cochin Hand Function Score (CHFS). Hand disability index was assessed by CHFS and global disability index was assessed by HAQ and sHAQ. Patient reported arthritis activity was assessed by Visual Analogical Scale for Arthritis Activity (VAS3). Based on the median of VAS3, patients were classified in two groups and the evaluation of global and hand disability index was performed for each group. Furthermore, we assessed the correlation between the change of VAS3 and the modification of disability scores (ΔHAQ, ΔSHAQ, ΔCHFS) over 12 months of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropriate (Prism 7).

Results

The median disease duration was 5 years (IQR 3-10). The median of VAS3 was 35 (IQR 2 - 66). In patients with VAS3 <35 and VAS ≥35 the HAQ-DI medians were 0.625 (IQR 0.25 - 1.5) and 1.75 (IQR 1.125-2.25) respectively, (p < 0.0001); the sHAQ medians were 0.628 (IQR 0.255 - 1.114) and 1.701 (IQR 1.234-2.059), respectively, (p < 0.0001); and the CHFS medians were 4 (IQR 0 - 19) and 28 (IQR 10 - 46) respectively, (p < 0.0001). A significant correlation was observed between VAS3 and HAQ (r = 0.463, p < 0.0001), SHAQ (r = 0.651, p < 0.0001), CHFS (r = 0.497, p < 0.0001); between ΔVAS3 and ΔSHAQ (r = 0.493, p < 0.0001).

Conclusion

This analysis of a monocentric non-selected population supports the key role of joint involvement in determining global patient reported functional and hand disability in SSc. Severity of musculoskeletal involvement should be carefully considered when interpreting PROs in patients with SSc.

Disclosures

K. Gjeloshi: None. F. Danzo: None. G. Abignano: None. A. Dean: None. F. Masini: None. G. Cuomo: None. F. del Galdo: None.
P162 Cross-validation and complementary value of optical coherence tomography and high frequency ultrasound for the assessment of skin disease in systemic sclerosis
Authors: Karadag Duygu Temiz , Lettieri Giovanni , Picerno Valentina , Gundogdu Ozcan , Padula Maria Carmela , Mennillo Gianna A , Padula Angela A , Galdo Francesco Del , D'Angelo Salvatore , Abignano Giuseppina
Published: April 2020

Background

The modified Rodnan skin score (mRSS) is the current gold standard for skin assessment in systemic sclerosis (SSc) both in clinical trials and practice. Several studies have reported that skin high frequency ultrasound (HFUS) and, more recently, optical coherence tomography (OCT) are able to reflect the severity of the skin disease in SSc. Aim of the study was to compare OCT and HFUS in the assessment of skin involvement in SSc.

Methods

Dorsal forearm skin of consecutive diffuse cutaneous SSc (dcSSc) patients and matched-healthy controls (HC) were scanned using OCT and HFUS by investigators blinded to the clinical details using Vivosight scanner (1 assessor) and Esaote MyLab70 equipped with a 22 MHZ probe (2 assessors) respectively. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) (OCT) and skin thickness (HFUS) were measured. Clinical involvement was assessed by a blinded operator using the mRSS and results were cross matched with imaging data. Statistical analysis was performed using GraphPad Prism software V.7.0.

Results

A total of 88 OCT images and 176 HFUS images were obtained from 22 dcSSc patients [20 Female, mean age 49 (±11) years, 12 with < 5 years disease duration) and 22 HC (20 Female, mean age 50.7 (±6.7) years]. All OCT measures (MinOD, MaxOD and OD300) were significantly lower in SSc patients than in HC (p = 0.011, p < 0.0001, p < 0.0001 respectively). HFUS showed a lower performance in discriminating SSc skin vs HC compared to OCT (overall AUC 0.6 vs 0.72, 0.8 and 0.89 for MinOD, MaxOD and OD300 respectively). Nevertheless, mean HFUS skin thickness significantly correlated with mRSS at site of analysis (r = 0.47, p = 0.0013) and showed overall excellent interobserver reliability between assessors (ICC >0.8). Importantly, MaxOD and OD300 negatively correlated with HFUS skin thickness (r=-0.32, p = 0.035; r=-0.31, p = 0.039).

Conclusion

OCT of the skin has been previously validated against skin biopsy in SSc. Our results validate HFUS against OCT and indicate that HFUS of the skin is a reliable measure of skin involvement. Further, here we show that HFUS and OCT outperform each other in measuring different aspects of skin involvement in SSc and they offer complementary surrogate outcome measures of disease.

Disclosures

D. Temiz Karadag None. G. Lettieri None. V. Picerno None. O. Gundogdu None. M. Padula None. G.A. Mennillo None. A.A. Padula None. F. Del Galdo None. S. D'Angelo None. G. Abignano None.
P163 Biosamples from at risk SSc patients show classic pathological signs of scleroderma: opportunity for a diagnosis of pre-clinical SSc
Authors: Ross Rebecca L , Georgiou Ioanna , Carriero Antonio , Abignano Giuseppina , Wasson Chris , Migneco Gemma , Herrick Ariane , Denton Chris , Galdo Francesco Del
Published: April 2020

Background

The VEDOSS study has recently indicated that more than 80% of patients affected by Raynaud’s phenomenon (RP) and specific SSc auto-antibodies + capillaroscopy changes satisfied ACR/EULAR 2013 criteria within 5 years.These data suggest that there is a window of opportunity for early detection of SSc in these patients. Here we aimed to determine whether sera, skin biopsies and skin fibroblasts cultured from these patients showed any biomarker sign of SSc.

Methods

Fifty-nine at risk patients identified by having RP and SSc auto-antibodies or capillaroscopy pattern (or both) were enrolled in the national inception cohort (Kennedy Cohort). Sera were tested for IFN inducible chemokines (CXCL-9,10 and 11 and CCL2, 8 and 19) and biomarker of extracellular matrix turnover (ELF test), all previously shown to be increased in SSc. Further, two 3mm skin biopsies were taken from the forearms from 3 ACA+ve (anti-centromere antibodies), 3 SCL70+ve patients. One biopsy was subjected to histology analysis, including haematoxylin and eosin staining and immunohistological staining for Collagen Type 1, alpha-SMA, Caveolin 1 and CD31 as endothelial marker. The other biopsy was used to explant fibroblasts cultures. mRNA and protein were isolated from primary fibroblasts and processed for RT-qPCR and western blotting analyses.

Results

Sera from at risk patients showed overall higher IFN inducible chemokines and ELF test (P < 0.05) with bimodal distribution among patients. Skin biopsies from both ACA or SCL70+ve patients showed decreased number of CD31+ cells, increased number of myofibroblasts and increased collagen bundles within the dermis, as usually seen in SSc, compared to healthy controls. In vitro, fibroblasts from both ACA or SCL70+ve patients showed average 10-fold higher collagen mRNA levels and 31-fold increased collagen protein levels compared to healthy control fibroblasts. Furthermore, fibroblasts from ACA or SCL70+ve patients showed limited TGF-beta induced increase in collagen and SMA expression, similar to SSc fibroblasts.

Conclusion

Although pilot in nature, this study suggests that patients “at risk” already show biomarker signs of SSc both in their sera and at skin biopsy and fibroblast level. Longitudinal studies on patients at this stage of pre-clinical disease may inform on the stratification strategies for imminent progression to clinical manifestations and offer both insights on pathogenesis of clinical signs and a window of opportunity for delaying the onset clinical intervention trials.

Disclosures

R.L. Ross None. I. Georgiou None. A. Carriero None. G. Abignano None. C. Wasson None. G. Migneco None. A. Herrick None. C. Denton None. F. Del Galdo None.
P176 A retrospective analysis of aortitis cases from radiology reports in a London teaching hospital: implications for screening and management
Authors: Townsend Katherine , Cattini Geoff , Moss Katie , Stenson Kate , Holt Peter , Morgan Robert , Sofat Nidhi
Published: April 2020

Background

Aortitis is a heterogeneous rare condition causing aortic inflammation, often due to infectious or autoimmune aetiology. Its presentation, diagnosis and optimal management remain poorly understood, often requiring multidisciplinary input. With the advent of improved imaging techniques, an increasing number of radiology reports are identifying features of vasculitis necessitating clinical investigation. We investigated how cases identified on imaging with features of aortitis reflected clinical diagnosis and treatment. We further examined whether radiological detection of aortitis enables more rapid management decisions to improve outcomes.

Methods

A search was conducted of all radiology reports from St George’s Hospital between 2008 and 2018 for key words indicating “aortitis”, including ‘hyperintense vessel uptake’ and ‘periaortic inflammation.’ From 15,963 initial results, 80 reports were identified with radiological suspicion of aortitis.

Results

Of 80 cases, 36/80 were diagnosed with autoimmune or idiopathic inflammatory pathology: 9 retroperitoneal fibrosis, 8 idiopathic, 7 Takayasu’s, 4 giant cell arteritis, 2 inflammatory aneurysms, 2 Behçet's, 2 IgG4 disease, 1 lupus, 1 granulomatosis with polyangiitis. Diagnosis of autoimmune or idiopathic aortitis was based on symptomatology, imaging, serology, vessel biopsy, and treatment response. 14/80 had infective aortitis: 11 had positive microbiology and 3 demonstrated empirical antibiotic response. Table 1 shows demographics. 12/80 had atheromatous disease. 18/80 were not further investigated due to comorbidity, lack of correlation with symptoms, or absence of follow-up. Initial imaging modalities with the highest yield were computed tomography (CTs) with aorta protocols and CTs of thorax/abdomen/pelvis. The most useful radiology report terms included: aortitis, periaortic inflammation, Takayasu’s, and hyperintense vessel uptake.

Conclusion

Our study is the first retrospective case analysis, to our knowledge, of more than 15,000 radiology reports used as a starting point to evaluate for aortitis, identifying a large dataset with a broad case-mix. It contrasts with current literature identifying cases histologically and post-operatively. We found that radiology can be a useful early alert for possible diagnoses which require further assessment. Consequently, we developed an alerting system within our radiology department based on the search terms and imaging modalities identified. This links to a multidisciplinary meeting including vascular and rheumatology, so highlighted cases are discussed early.

Disclosures

K. Townsend: None. G. Cattini: None. K. Moss: None. K. Stenson: None. P. Holt: None. R. Morgan: None. N. Sofat: None.
P178 Maintenance treatment for ANCA-associated vasculitis in real world practice in the UK: reality of vasculitis remission and relapse and burden of disease
Authors: Worthington David , Rutherford Peter
Published: April 2020

Background

AAV is a relapsing remitting condition and patients are at risk of organ damage from active AAV and therapy especially glucocorticoids (GC). The maintenance phase of AAV is critical for good long-term outcomes. This retrospective study examined maintenance definition, therapy and outcomes in patients in routine clinical practice.

Methods

300 AAV patients managed by 100 UK physicians (40% rheumatologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance between 2014-16 were studied. Data were collected at time maintenance was determined to begin by the physician and at 6, 12, 18 and 36 months.

Results

56% had granulomatosis with polyangiitis; mean age 55.4 years 54% male. 61% had incident AAV and 39% relapsed. Physicians defined time of start of maintenance from treatment start with mean of 4.5 months, on basis of fixed time point 47%, starting new maintenance drug 27%, reaching full remission 16% and no specific criteria 9%. At this time 45% were in full remission vs 49% in partial and 6% refractory. Various maintenance regimes were used, 11% received rituximab (84% 6 monthly and 16% 12 monthly) at varying planned doses 61% 1g, 19% 500 mg and 16% 375 mg/m2, 4% not recorded. Remission rates varied and many patients experienced adverse events (AE) and infections, prolonged GC use was common. At most recent review patients had been followed for a mean of 49.2 months - 6% had died, 30% relapsed at least once, and 10% required renal replacement therapy. 62% had no vasculitis activity and were ANCA negative with 14% still experiencing active disease. 35% still received GCs - 19% > 5mg/ day. There was negative impact on functional status with 13% reducing working hours, 13% restricted social life, 4% leaving employment, 3% registered as disabled and 2% leaving full time education.

Conclusion

Maintenance therapy is variably defined at 4-5 months from start of remission induction therapy. Achieving full remission and preventing relapse are still problems and many patients require GC therapy to maintain remission. Infectious complications are a problem and there is significant negative impact on patient functional status.

Disclosures

D. Worthington Corporate appointments; Employee of Vifor Pharma. P. Rutherford Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.