bluuebunny/crossref_metadata_2025_split huggingface dataset:
O02 Is vitamin D testing essential in elderly patients with a hip fracture?
Authors: Mehta Serena N , Omar Mohd K , Sapkota Hem 
Published: April 2020

Abstract

Background
Elderly patients with hip fractures are likely to be vitamin D deficient. As per some studies, a vitamin D level above 75nmol/L is considered to be sufficient for this cohort. The majority of these patients will require treatment for their osteoporosis. Prior to treatment, vitamin D levels need to be sufficient, however there is often a delay to obtain vitamin D test results and this can postpone the initiation of osteoporosis management. In this retrospective study, we hypothesised whether empirical, high dose vitamin D treatment can be given to patients with hip fractures, regardless of their vitamin D level, who are not currently on vitamin D supplementation.

Methods
We obtained a list of 917 patients with a hip fracture, aged over 50, from the Trust National Hip Fracture Database from January 2017 to December 2018. We accessed patients’ electronic hospital and GP records to collect patient demographics, vitamin D levels, and medication history.

Results
The mean age in this study was 82.7 years, and 69.8% were female. Vitamin D levels were available for 666 patients. Of this, 69.9% of patients had a below adequate level (50 nmol/L) and 88.4% of patients had a below sufficient level (75 nmol/L) of vitamin D. Electronic records for vitamin D supplementation were only available for 434 patients. Of this, 300 patients (69.1%) were not on any form of vitamin D supplementation. In this cohort, only 7 patients had a vitamin D level above sufficient levels (75 nmol/L). Upon contacting these 7 patients; 3 were taking some form of vitamin D supplementation, 3 died and no information was available for 1.

Conclusion
Our study demonstrates all patients with a hip fracture, who are not taking any form of vitamin D supplementation will have subtherapeutic vitamin D levels. Thus, patients presenting with a hip fracture, can be treated empirically with high dose vitamin D treatment, without prior vitamin D testing. This would reduce the number of vitamin D tests conducted by 69.1% which will enable patients to receive prompt osteoporosis treatment and will reduce costs.

Disclosures
S.N. Mehta None. M.K. Omar None. H. Sapkota None.
O22 Assessing the role of tendon T cell interactions in the development of chronicity in PsA
Authors: Garcia-Melchor Emma , Cafaro Giacomo , Sood Shatakshi , Crowe Lindsay A. N , McLean Michael , McInnes Iain B , Akbar Moeed , Millar Neal L 
Published: April 2020

Abstract

Background
Mechanical stress or damage is a well-known inducer of inflammation in both psoriasis and psoriatic arthritis (PsA). The occurrence of microtrauma at enthesial sites, areas subjected to high mechanic stress, could explain the development of local inflammation (enthesitis) that further extends to the synovial tissue through what it is known synovio-entheseal complex. Current treatment strategies mainly target the immune compartment, however there is growing evidence for the role of the stroma in the development of chronic inflammation. Increasing attention has focused on the interaction between the stroma and immune system and its role in the initiation/development of tissue inflammatory chronicity. Our hypothesis is that stromal cells in the tendon or tenocytes, once activated, are able to recruit and activate T cells into the tendon, which in turn may have an effect on the stroma, altogether leading to chronicity.

Methods
We assessed the effect of damage on healthy tenocytes after stimulation with conditioned media from tendon explants or IL-1β by qPCR and ELISA. A transwell membrane system was used to test the impact of conditioned media from tenocytes on T cell migration. T cells and tenocytes were co-cultured with or without the presence of a transwell membrane to quantify T cell activation (CD69 by FACS and IFN-γ by ELISA). Changes in gene expression on tenocytes after co-culture with activated T cells were analysed by qPCR.

Results
In the presence of damage, tenocytes upregulated inflammatory cytokines (IL-1β, IL-6), chemokines (IL-8, CCL2, CCL5, CXCL10) and adhesion molecules (ICAM-1). Of interest, we observed an upregulation of CCL20, both at transcript and protein level. Conditioned media from tenocytes induced T cell migration, especially after stimulation. Co-culture of tenocytes and T cells resulted in contact dependant activation of T cells. These activated T cells also had an effect on tenocytes, further upregulating the production of inflammatory mediators.

Conclusion
These results support the role of the tendon stromal compartment in the recruitment and activation of T cells, creating a feedback loop that could be involved in the maintenance of the inflammatory process and the development of chronicity in the context of PsA. Moreover, the production of CCL20 by tenocytes after damage could explain the preferential recruitment of Th17 or gamma delta T cells into the tendon. We are further investigating the mechanisms that govern this relationship that could be targeted therapeutically in the future.

Disclosures
E. Garcia-Melchor None. G. Cafaro None. S. Sood None. L.A.N. Crowe None. M. McLean None. I.B. McInnes None. M. Akbar None. N.L. Millar None.
O26 Non-serious infections in patients with RA: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis
Authors: Bechman Katie , Halai Kapil , Norton Sam , Cope Andrew P , Hyrich Kimme L , Galloway James B 
Published: April 2020

Abstract

Background
Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA).

Methods
The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number.

Results
There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1).

Conclusion
These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life.

Disclosures
K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.
O32 Digital artery volume index (DAVIX©) predicts the onset of future digital ulcers in patients with SSc
Authors: Gjeloshi Klodian , Danzo Fiammetta , Lettieri Giovanni , Abignano Giuseppina , Hinton Mark , Dean Anne-Maree , Cuomo Giovanna , Kubassova Olga , del Galdo Francesco 
Published: April 2020

Abstract

Background
Digital Ulcer Disease is a main vascular manifestation of Systemic Sclerosis (SSc) caused by progressive narrowing of digital arteries with consequent tissue ischemia. Time of flight angiography (TOF) is an MRI technique based on flow-related enhancement of spins entering into an imaging slice. It can visualise flow within vessels, without the need to administer contrast. Here we measured Digital Artery Volume index (DAVIX ©) as an MRI TOF quantitative score of digital arteries flow and determined its value in predicting the onset of digital ulcers (DUs) in patients with SSc.

Methods
We studied 91 consecutive patients, 63 of which fulfilled the 2013 ACR/EULAR classification criteria for SSc and 28 had a score &lt;9. The data collected included: clinical examination, pulmonary function tests (PFTs), echocardiography, nailfold capillaroscopy. DAVIX of the dominant hand was calculated as % mean of the 4 fingers, employing MeVisLab software. The distribution was analysed with D’Agostino-Pearson normality test. Correlation with clinical parameters was performed using Spearman’s or Pearson test, as appropriate (Prism 7).

Results
78/91 patients were females and median disease duration was 4 years (IQR 1.91-9). Complete historical and prospective follow-up data were available for 68 patients. At baseline 7 patients had DUs (5 with a positive history for DUs). 12 patients developed DUs within 12 months, 3 of them had DUs at baseline. 38 patients did not have either previous or current DUs, neither did they develop new DUs within 12 months. The median of DAVIX in this population was 0.65 (IQR 0.46-0.82). DAVIX of patients with current DUs was 3-fold lower than DAVIX of patients without DUs (0.18 vs 0.63 p = 0.0093). Further, DAVIX of patients with positive history of DUs was 50% lower than in patient with a negative history (median 0.34 vs 0.64, p = 0.0052). In patients without current DUs who developed new DUs within 12 months of follow-up the DAVIX was 3-fold lower than in patients who didn’t develop (0.21 vs 0.65, p = 0.0156). Most importantly in patients with no current DUs a DAVIX &lt;0.47 gave a 35% risk of developing DUs ( vs 15% overall risk).

Conclusion
Outcome measures of vascular involvement in SSc are scanty. We demonstrated that DAVIX© is a promising and feasible surrogate outcome measure of neointima proliferation in SSc. Furthermore, the predictive value of DAVIX for the future onset of DUs could be employed as a useful stratification tool in Clinical trials.

Disclosures
K. Gjeloshi None. F. Danzo None. G. Lettieri None. G. Abignano None. M. Hinton None. A. Dean None. G. Cuomo None. O. Kubassova None. F. del Galdo None.
O33 Earlier cancer diagnosis after myositis onset is associated with improved long term survival: results from UK, French and Czech cohorts
Authors: Oldroyd Alexander , New Paul , Lamb Janine , Ollier William , Cooper Robert , Mariampillai Kuberaka , Benveniste Olivier , Vencovský Jiří , Mann Heřman , Chinoy Hector 
Published: April 2020

Abstract

Background
The idiopathic inflammatory myopathies (IIMs) are associated with cancer. Cancer screening is advocated in new IIM cases; however no study has investigated if this confers improved long-term survival. This study aimed to investigate if a shorter time between IIM onset and cancer diagnosis is associated with improved survival.

Methods
Verified adult-onset IIM (dermatomyositis, polymyositis, anti-synthetase syndrome) cases, according to the International Myositis Classification Criteria, were recruited from three separate UK (UKMYONET), France and Czech-based cohort studies. Only cases with cancer diagnosis following IIM onset were included in analysis. The time between IIM onset and cancer diagnosis was calculated for each case. The relationship between survival at the end of follow up and time between IIM onset and cancer diagnosis was quantified via calculation of hazard ratios using a Cox-proportional hazard model, adjusted for age and gender.

Results
A total of 193 (66% female) IIM cases with a total of 1,395 person-years follow up were included in the analysis (Table 1). Data of 120 UK, 45 Czech and 28 French participants were analysed. Breast was the most common site of cancer (16%), followed by lung (9%) and bowel (6%). Forty six (24%) deaths occurred within the follow up period. The IIM onset to cancer diagnosis time was shorter for those that survived at the end of follow up, compared to those that died: 4.6 years (IQR 1.2, 10.7), vs 5.8 years (IQR 1.6, 13.8), respectively. Cox-proportional hazard modelling, indicated that a longer time between IIM onset and cancer diagnosis was significantly associated with death (HR 1.06 [95% CI 1.02, 1.10]). This significant relationship was only demonstrated in the female cohort when analysed separately: female HR 1.06 (95% CI 1.01, 1.10), male HR 1.08 (95% CI 0.98, 1.18).

Conclusion
Using data from three international cohorts, this study has, for the first time, identified that earlier cancer diagnosis after IIM onset is associated with improved long term survival. This finding was observed in the female cohort only. This study therefore indicate that cancer screening in newly diagnosed IIM cases without a preceding cancer history should be carried out, especially in female cases.

Disclosures
A. Oldroyd None. P. New None. J. Lamb None. W. Ollier None. R. Cooper None. K. Mariampillai None. O. Benveniste None. J. Vencovský None. H. Mann None. H. Chinoy None.
O36 Validation of methods to enable national registration for rare autoimmune rheumatic diseases
Authors: Pearce Fiona A , Rutter Megan , Griffiths Bridget , Mukhtyar Chetan , Al-Jayoussi Reem , Watts Richard A , Aston Jeanette , Bythell Mary , Stevens Sarah , Lanyon Peter C 
Published: April 2020

Abstract

Background
The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) records those people with congenital anomalies and rare diseases across the whole of England. The NCARDRS Rare Rheumatology Project is establishing methodologies to identify and register people with rare rheumatic diseases. Hospital Episode Statistics (HES), comprising data from all admitted-patient NHS care in England, provides a promising source for case ascertainment. We aimed to confirm the reliability of diagnostic ICD codes for rare autoimmune rheumatic diseases within HES.

Methods
We used NCARDRS’ legal permissions (CAG 10-02(d)/2015) to extract cases who had at least one inpatient or daycase admission recorded in HES during 2003 to 2017 with a primary or additional diagnostic code for Kawasaki disease, Takayasu’s arteritis, Adult-onset Still’s disease, Relapsing polychondritis, Polyarteritis nodosa, Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA) or Eosinophilic granulomatosis with polyangiitis (EGPA). Using Data Sharing Agreements between NCARDRS and NHS Trusts, we reviewed medical records for all cases admitted to one NHS Trust to confirm diagnoses. For ANCA-associated vasculitis (AAV), up to 20 randomly selected cases admitted to 5 Trusts with a diagnostic code of GPA, MPA and EGPA were reviewed.

Results
Table 1 shows the positive predictive value (PPV) of each diagnosis at one Trust: Kawasaki disease 100%, Takayasu’s arteritis 91.7%, Adult-onset Still’s disease 42.8%, Relapsing polychondritis 40.0%, and Polyarteritis nodosa 5.0%. For AAV, which had a PPV at the index Trust of 92.0%, the PPV across the 5 Trusts varied from 92.9% to 74.0%. Combining all 5 Trusts PPV for AAV was 85.9%. It was higher in MPA (PPV=98.4%) than in GPA (PPV=83.3%) and EGPA (PPV=77.4).

Conclusion
This is the first study to validate the coding of rare rheumatic disease diagnoses within HES data. Our results highlight heterogeneity in coding accuracy both between conditions and between NHS Trusts. Further work is needed to develop and validate algorithms for conditions where HES coding alone has poor positive predictive value, and test sensitivity. National rare disease registration will enable robust, cost-effective and reproducible population-based epidemiology of rare rheumatic diseases across England which is needed to inform service provision and aid development of new treatments.

Disclosures
F.A. Pearce None. M. Rutter None. B. Griffiths None. C. Mukhtyar None. R. Al-Jayoussi None. R.A. Watts None. J. Aston None. M. Bythell None. S. Stevens None. P.C. Lanyon None.
O39 VTE risk in the general population: applying context to the impact of JAK inhibition
Authors: Baroncini Serena , Yates Mark , Bechman Katie , Patel Sanjeev , Rutherford Andrew , Kleymann Alexander , Galloway James 
Published: April 2020

Abstract

Background
Trial data indicate an increased risk of VTE with JAK inhibition. The EMA and FDA have given regulatory advice for their use as a result. To understand the context of any association, we need to understand VTE risk in the background population. Our objective was to describe the changing epidemiology of VTE risk including a breakdown of DVT and PE in the general population in England, over a 20-year period.

Methods
We utilised hospital episodes statistics data to study all patients presenting for hospital care in England between 1 January 1998 and 31 December 2017. We identified VTE events using ICD10 codes I26.0, I26.9, I80.1, I80.2 and I80.3. To estimate annualised event rates, we used the number of finished consultant episodes for admitted care where the primary diagnosis was VTE for the numerator; the denominator was the whole population estimate, from the office for National Statistics, for the relevant year for England. Rates were calculated per 100,000 population, and the Cochrane Armitage test was used to evaluate statistical significance of trends over time. Linear regression allowed modelling of estimates over time, with model assumptions tested using residual versus fitted plots. To explore non-linearity, we used a cubic spline model.

Results
The average VTE rate across the 20 years was 127/100,000. VTE rates have increased over time, climbing from 108/100,000 in 1998, to 151/100,000 in 2017. The relative frequency of DVTs and PEs has changed over this time: in 1998 DVT was more frequent than PE (rates 68/100,000 and 40/100,000 respectively). By 2018 this ratio had reversed (DVT 52/100,000: PE 98/100,000). This change was statistically significant (p &lt; 0.0001). DVT rates declined in a linear manner over time. PE rates increased with a non-linear pattern, with a sharp rise apparent between 2008 and 2010.

Conclusion
The inversion in the frequency of DVTs and PEs is consistent with previous findings using European data. One possible explanation is changing diagnostics (CTPA replacing V/Q), capturing previously subclinical PE events. Limitations include our ecologic design as well as lack of linkage to mortality records. The presumed VTE risk associated with JAK inhibition is small. It is plausible that future shifts in population wide patterns of VTE could obscure or amplify any effect attributable to JAK inhibitors. As longer-term observational data become available, it is crucial they are interpreted in the context of background population trends.

Disclosures
S. Baroncini: None. M. Yates: None. K. Bechman: None. S. Patel: None. A. Rutherford: None. A. Kleymann: None. J. Galloway: None.
P02 Osteoporosis management when denosumab therapy ends: an audit of current practice
Authors: Zhang Jean , Clynes Michael A , Cooper Cyrus , Dennison Elaine M 
Published: April 2020

Abstract

Background
In recent years denosumab therapy has been widely used in the treatment of osteoporosis. However, since its first introduction to clinical practice, evidence has demonstrated discontinuation leads to rebound bone loss and risk of vertebral fracture. In view of this, guidance has been updated recommending transition to an alternative osteoporosis therapy. Given that osteoporosis management is largely managed in primary care, we performed this audit to investigate whether this educational message was being effectively relayed to primary care clinicians.

Methods
In this study, we closed the audit loop of a previous study of the first 50 patients commenced on denosumab at University Hospital Southampton in 2013; we explored the percentage of patients remaining on denosumab 6 years later, using the hospital electronic system, which is linked to the general practice electronic system, to confirm prescriptions for osteoporosis therapy. In cases where it was unclear, letters were written, or telephone calls were made to general practices for clarification. Continuation of denosumab or use of an alternative agent was then recorded.

Results
Nineteen (38%) patients had died since the initial audit, reflecting the use of the agent in later life post hip fracture. Of 15 patients no longer on denosumab, 9 (60%) were found not to be on alternative bone protection without other information recorded, 1 (7%) had denosumab suspended by the GP (with the presumption it may be restarted at a later date), 1 (7%) had denosumab suspended due to recurrent cellulitis with the view to reassess in a year and 3 (20%) were on alternative therapy. One patient was recorded as being on a ‘drug holiday’. Of 16 patients remaining on denosumab, 13 (81%) had pre-injection calcium level checks, and 12 (75%) had a recorded pre-injection renal function check.

Conclusion
These data reflect inappropriate widespread discontinuation of denosumab without follow-on with an alternative osteoporosis therapy, suggesting that targeted education of primary care physicians is necessary. A high proportion of patients on denosumab are having the relevant blood tests in primary care as per clinical guidelines.

Disclosures
J. Zhang None. M.A. Clynes None. C. Cooper None. E.M. Dennison None.