bluuebunny/crossref_metadata_2025_split huggingface dataset:
E034 Rheumatology trainees’ experience of osteoporosis and metabolic bone disease: a UK-wide survey
Authors: Hardcastle Sarah A , Rutter Megan , Paskins Zoe 
Published: April 2023

Abstract

Background/Aims
The 2022 rheumatology curriculum requires trainees to achieve competence in the management of osteoporosis and a number of metabolic bone diseases by the end of their training. In addition, the recent 2022 NOGG guidance states that very high-risk osteoporosis patients should be considered for referral to specialist care. Hence there is a need to ensure high quality training in this area. We aimed to assess rheumatology trainees’ experience of osteoporosis and metabolic bone disease.

Methods
A Google form was designed, comprising questions relating to experience of and confidence in managing osteoporosis and other metabolic bone disease. A completion link was circulated to rheumatology trainees via regional trainee representatives. Reminders were sent at intervals during the survey period. Trainees completed the survey anonymously.

Results
41 trainees responded. Training grade ranged from ST4-ST7, with 1 specialty doctor and 1 individual who had completed training. Six regions in England, plus Wales and Northern Ireland were represented. 23 trainees (56.1%) reported having observed at least one osteoporosis clinic, and 18 (43.9%) reported having participated in an osteoporosis clinic on a weekly basis for at least 12 weeks. Fewer trainees (11, 26.8%) had observed a specialist metabolic bone disease clinic, and 9 (22%) had participated in one. In terms of exposure to individual conditions, 31 trainees (75.6%) reported clinical experience of managing postmenopausal osteoporosis and 29 (70.7%) reported experience of managing Paget’s disease. Exposure to rarer metabolic bone diseases was much lower, with over half reporting no clinical experience of: osteomalacia; osteonecrosis; bone marrow oedema syndromes; hypophosphatasia; osteogenesis imperfecta; fibrous dysplasia; or FGF-23 mediated osteomalacia. 12 trainees (29.3%) had experience reporting DXA scans. Table 1 summarises trainees’ confidence levels across a number of areas. Overall, 9 (22%) rated their confidence in assessing and managing patients with osteoporosis and metabolic bone disease as equal to or higher than for patients with inflammatory arthritis. 22% said they were likely or very likely to consider sub-specialising in osteoporosis/metabolic bone disease.

Conclusion
Our survey has identified significant variations in training, particularly for rarer metabolic bone diseases. However, despite this, the sub-specialty appears to remain an attractive career option.
Disclosure
S.A. Hardcastle: None. M. Rutter: Other; M.R. is a Versus Arthritis Clinical Research Fellow and Chair of the BSR trainee committee. Z. Paskins: Consultancies; Unpaid consultancy for non promotional activity with UCB.
E037 Rheumatic and musculoskeletal diseases among olive pickers: prevalence, characteristics, management, treatments expectations and beliefs
Authors: Giardulli Benedetto , Battista Simone , Testa Marco 
Published: April 2023

Abstract

Background/Aims
Olive oil is a core part of the Mediterranean diet, as its consumption is associated with increased longevity. Olive pickers are those in charge of the harvest of olives. They are exposed to ergonomic hazards that might lead to rheumatic and musculoskeletal diseases (RMDs). Therefore, it is crucial for them to adopt the correct strategies to prevent and treat RMDs. However, there is a lack of studies focusing on the prevalence, prevention and treatments of RMDs among this population. Hence, this study highlighted the prevalence, characteristics and management of RMDs in olives pickers, their expectations about the treatments, and beliefs about their job to the onset of RMDs.

Methods
A web-based cross-sectional survey was developed to collect data from an Italian olive pickers’ cohort in the Liguria region. The survey investigated the sample’s 1) prevalence and characteristics of RMDs, 2) preventive and treatment activities for RMDs, 3) expectations about RMD treatments, and 3) beliefs about their job and RMD onset.

Results
From January to July 2021, we collected data from 127 participants (99 males (78%); 28 females (22); mean age 52±13). Prevalence of RMDs over one month, over six months, and over one year was 61.6% (95% confidence interval [51.3%-71.2%]), 77.8% [68.3%-85.5%], and 84.8% [76.3%-91.2%], respectively. The most affected joints were the lumbar spine (61%), the shoulders (57%), and the cervical spine (46%). The pain was experienced by 63% of participants during the harvest time and by 30% at the end. To prevent the onset of RMDs, 44% of participants did nothing, and 94% of them never attended any physical activity preventive course for their profession. To reduce pain, 45% of participants took painkillers or anti-inflammatory drugs. Roughly 63% of participants reported avoiding specific movements, and 45% feared movement could enhance their pain. Due to the pain, 62% of participants were referred to health professionals. Participants expected to be educated on the right movements to perform (62%) and to receive manual treatments (46%) from health professionals. Participants believed that having a straight spine while working was crucial for their health (89%) and that physical activity was important for their joint wellness (82%).

Conclusion
RMDs strongly impact Ligurian olive pickers since one out of two experienced them. More attention should be given to the education of this population to provide them with preventive and managerial strategies for preventing and treating RMDs. Oliver pickers stressed the need to be educated on working ergonomics and the perceived importance of physical activity on health. Future studies should test the generalisability of these results to a broader sample and explore the efficacy of an educational programme focused on working ergonomics and preventive physical activity.
Disclosure
B. Giardulli: None. S. Battista: None. M. Testa: None.
E045 Clinical triage: Investing in the front door
Authors: MacPhie Elizabeth , Fish Sarah M , Madan Ayesha , Rao Chandini , Horton Sarah 
Published: April 2023

Abstract

Background/Aims
The processes and IT systems that support the referral pathway are complex. The focus on referral optimisation and out-patient transformation has provided an opportunity to do things differently. Getting It Right First Time recommendations highlight the importance of ensuring rheumatologists focus on conditions which require specialist rheumatology input. As part of an integrated musculoskeletal (MSK) service we are able to redirect referrals regarding non-inflammatory conditions to our MSK and Community Pain teams. This project evaluates the impact of clinical triage.

Methods
Consultant-led triage introduced in July 2021. Directory of services updated and met with primary care networks leads to inform them of the changes. Letter co-designed with GPs to send out to patients when referral responded to with immediate specialist advice. Triage job planned with an allocation of 45 minutes per day. Referrals are reviewed on the electronic referral system and accepted, returned or redirected to another service. Standard responses developed to ensure consistency. All triage outcomes recorded in a spreadsheet. Review undertaken of returned referrals to identify any patients who were re-referred. To ascertain the proportion of patients triaged to early inflammatory arthritis (EIA) appointments who were diagnosed with an EIA, National Early Inflammatory Arthritis Audit data was analysed before and after changes to triage.

Results
Between January and June 2022 we received 1194 referrals; 761 (64%) were accepted, 289 (24%) returned, 43 (4%) redirected to another service and 73 (6%) returned with immediate specialist advice. Of the 289 referrals that were returned, 74 (25%) were returned for more information, 61 (21%) with a request to examine the patient, 118 (41%) were deemed inappropriate, 14 (4%) were patients already under our care and 22 (8%) were returned for other reasons. We received a further referral for 46/74 of those returned for more information, 45/61 following the request to examine the patient, 13/118 of those returned as not felt appropriate and 3/73 of those returned with immediate specialist advice. In total, we saved 278 new patient appointments over a 6-month period. Allowing for the time job planned, this was a net gain of 6 new patient appointments a week. In 2019, 37% of patients seen in an EIA appointment were diagnosed with an EIA compared to 51% in 2022.

Conclusion
Investment in clinical triage has saved a considerable number of appointments. For some patients it has provided an immediate specialist opinion or redirected them to a more appropriate service. It has helped to ensure that we are seeing patients who require specialist rheumatology input. Next steps are to share this work more widely and develop resources for patients and primary care to help promote a different way of working and delivering specialist advice.
Disclosure
E. MacPhie: None. S.M. Fish: None. A. Madan: None. C. Rao: None. S. Horton: None.
E068 A systematic review assessing the comparative harms associated with opioids for musculoskeletal pain
Authors: McCarthy Craig 
Published: April 2023

Abstract

Background/Aims
Opioids are prescribed commonly for the management of musculoskeletal (MSK) pain, however they may be associated with several adverse events that vary between the type, drug dose and potency. The aim of this study was to systematically review the evidence to assess the comparative adverse events associated with opioids for both inflammatory and non-inflammatory MSK conditions.

Methods
A systematic review of the literature was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework (PRISMA). MEDLINE, OVID and Cochrane databases were searched up to 16th June 2022. Randomised controlled trials, open label trials and observational studies in patients who were aged 18 years and older, without cancer and on opioids for a musculoskeletal condition were included.

Results
Of the 1,091 studies extracted, 782 studies underwent titles and abstract review, 185 studies were assessed for full-text eligibility of which 11 studies were met inclusion criteria. These studies included 28,828 participants, of which 9,162 were male and 19,666 were female. The average age of participants was 69 years of age. Conditions in 10 studies were for chronic pain related to osteoarthritis (generalised, hip and knee). One study included a population with both osteoarthritis and rheumatoid arthritis. Using the Cochrane Collaboration’s risk of bias tool and the Newcastle-Ottawa scales the quality of the 11 articles ranged from low, moderate and high quality. The review highlighted a high risk of gastrointestinal (nausea, constipation, vomiting), neurological adverse events (dizziness, headache, fatigue and somnolence) and increased falls. Only one study quantified risk of adverse events comparing different drugs in the form of a relative risk or absolute risk. Whilst all opioids were associated with adverse events, oxycodone and buprenorphine were associated with a higher proportion of adverse events within the populations studied. There was insufficient evidence to conclude a differential risk with specific opioids with the available literature.

Conclusion
The systematic review highlighted a lack of scientific evidence quantifying the risk of potential harms of different opioids in patients with MSK conditions. There was also a large heterogenicity across the cohorts and poor methodological design that made comparisons difficult. It highlighted the need for high-quality studies to quantify the risk of adverse events that incorporate aspects of dose and potency, to better aid shared decision making with patients.
Disclosure
C. McCarthy: None.
E081 Effectiveness of intravenous belimumab in patients with systemic lupus erythematosus at a UK tertiary referral centre
Authors: Mallett Garry , Hession Charlie , Fernando Michelle 
Published: April 2023

Abstract

Background/Aims
Belimumab was approved in the United Kingdom (UK) in 2016 as add-on therapy for patients with auto-antibody positive systemic lupus erythematosus (SLE) and high disease activity refractory to standard treatment. Data regarding the effectiveness of belimumab outside clinical trials has been published in worldwide SLE cohorts but not the UK. Here, we describe the efficacy of add-on belimumab therapy in SLE patients from a large London tertiary centre.

Methods
We performed a retrospective, intention-to-treat analysis of clinical and biochemical outcomes, at 6 and 12 months, post receipt of at least 1 infusion of belimumab in SLE patients attending Guy’s and St Thomas’ NHS Trust (April 2013-November 2021). Outcomes assessed included: the Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), anti-dsDNA ELISA titre, complement C3 and C4 titres, urine protein:creatinine ratio (uPCR) and daily prednisolone dose. Analyses performed using SPSS statistics 27.

Results
63 patients (56 female [88.9%], median age 38 years, self-reported race/ ethnicity; 24 Black [38.1%], 24 White [38.1%], 13 Asian [20.6%]) with SLE as defined by the 1997 ACR criteria were included. An 8-point reduction in median SELENA-SLEDAI was evident at 6 months after commencing belimumab, which increased to 9 points at 12 months (n = 28, p &lt; 0.001)(Table 1). Improvements in C3/ C4 titres were also observed at 6 months (0.13-point and 0.04-point increase in median C3/ C4 titres respectively, n = 45, p &lt; 0.001). At 12 months, significant reductions in median anti-dsDNA titre (16.50-point reduction, n = 42, p &lt; 0.001) and median daily prednisolone dose were evident (2.50mg reduction, n = 51, p &lt; 0.001). No change in uPCR was noted (n = 23, p = 0.956). 40/47 (85%) patients with a SELENA-SLEDAI score recorded at 6 months achieved the National Institute for Health and Care Excellence (NICE) defined target for a &gt;/= 4-point reduction in SELENA-SLEDAI. No significant associations between baseline demographic variables and SELENA-SLEDAI score at 6 months, or prednisolone dose at 12 months, were evident.

Conclusion
We observed a significant improvement in SLE disease activity as determined by SELENA-SLEDAI score measured at 6 and 12 months after starting belimumab, and a significant steroid-sparing effect at 12 months. These findings are similar to published worldwide data.
Disclosure
G. Mallett: None. C. Hession: None. M. Fernando: Other; MF has received speaker fees from GlaxoSmithKline (GSK) and Union Chimique Belge (UCB), as well as conference fees from GSK.
Paranasal sinus occupancy assessed from magnetic resonance images—associations with clinical indicators in patients with systemic lupus erythematosus
Authors: Valdés Hernández Maria del C , Ferguson Karen J , Loon Pearlyn , Kirkwood Grant , Zhang Jun-Fang , Amft Nicole , Ralston Stuart H , Wu Yun-Cheng , Wardlaw Joanna M , Wiseman Stewart J 
Published: April 2023

Abstract

Objectives
Nasal, paranasal sinus and mucosal disorders are common symptoms in autoimmune rheumatic diseases. Soft tissue changes and fluid accumulation in the osteomeatal complexes and paranasal sinuses manifest as opaqueness on radiological images which can be assessed using visual scoring and computational methods on CT scans, but their results do not always correlate. Using MRI, we investigate the applicability of different image analysis methods in SLE.

Methods
We assessed paranasal sinus opaqueness on MRI from 51 SLE patients, using three visual scoring systems and expert-delineated computational volumes, and examined their association with markers of disease activity, inflammation, endothelial dysfunction and common small vessel disease (SVD) indicators, adjusting for age and sex-at-birth.

Results
The average paranasal sinus volume occupation was 4.55 (6.47%) [median (interquartile range) = 0.67 (0.25–2.65) ml], mainly in the maxillary and ethmoid sinuses. It was highly correlated with Lund–Mackay (LM) scores modified at 50% opaqueness cut-off (Spearman’s ρ: 0.71 maxillary and 0.618 ethmoids, P &lt; 0.001 in all), and with more granular variations of the LM system. The modified LM scores were associated with SVD scores (0: B = 5.078, s.e. = 1.69, P = 0.0026; 2: B = –0.066, s.e. = 0.023, P = 0.0045) and disease activity (anti-dsDNA: B = 4.59, s.e. = 2.22, P = 0.045; SLEDAI 3–7: 2.86 &lt; B &lt; 4.30; 1.38 &lt; s.e. &lt; 1.63; 0.0083 ≤ P ≤ 0.0375). Computationally derived percent opaqueness yielded similar results.

Conclusion
In patients with SLE, MRI computational assessment of sinuses opaqueness and LM scores modified at a 50% cut-off may be useful tools in understanding the relationships among paranasal sinus occupancy, disease activity and SVD markers.
Global trends in the consumption of benzodiazepines and Z-drugs in 67 countries and regions from 2008 to 2018: a sales data analysis
Authors: Ma Tian-Tian , Wang Zixuan , Qin Xiwen , Ju Chengsheng , Lau Wallis C Y , Man Kenneth K C , Castle David , Chung Chang Wing , Chan Adrienne Y L , Cheung Edmund C L , Chui Celine Sze Ling , Wong Ian C K 
Published: April 2023

Abstract

Study Objectives
To investigate the trends in the consumption of benzodiazepines (BZDs) and Z-drugs at global, regional, and national levels from 2008 to 2018, across 67 countries and regions.

Methods
This cross-sectional descriptive study investigated the consumption of BZDs and Z-drugs analyzed by global pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System database between 2008 and 2018. Consumption was measured in defined daily dose (DDD) per 1000 inhabitants per day (DDD/TID). The global, regional, and national trends were estimated using linear mixed models. Additional analyses were conducted by grouping countries by income level. The association between consumption and Gross Domestic Product (GDP) and the prevalence of different medical conditions was explored in univariable linear models.

Results
BZD consumption decreased annually by −1.88% (95% CI: −2.27%, −1.48%), and Z-drugs increased by + 3.28% (+2.55%, +4.01%). In 2008, the top ten countries for BZD and Z-drug consumption were all European, ranging from 63.69 to 128.24 DDD/TID. Very low levels were found in Russia, Kuwait, United Arab Emirates, Saudi Arabia, French West Africa, and the Philippines, with DDD/TID &lt; 1. The consumption in high-income countries was much higher than in middle-income countries. The results showed that increased consumption of BZDs and Z-drugs was statistically associated (p &lt; 0.05) with higher GDP and increased prevalence of anxiety, self-harm, neurological disorders, chronic respiratory diseases, cardiovascular diseases, and cancers.

Conclusions
Distinct differences in consumption and trends of BZDs and Z-drugs were found across different countries and regions. Further exploration is needed to understand the association and safety of the use of BZDs and Z-drugs in patients with comorbidities.
Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion
Authors: Kurenkova Anastasiia D , Li Lei , Usanova Anna P , Feng Xiaogang , Zhou Baoyi , Nedorubov Andrei A , Lychagin Alexey V , Chagin Andrei S 
Published: April 2023

Articular cartilage has a limited capacity for self-repair and clinical approaches to cartilage regeneration are needed. The only such approach developed to date involves an expansion of primary autologous chondrocytes in culture, followed by their reimplantation into a cartilage defect. However, because of the formation of fibrocartilage instead of hyaline cartilage, the outcome is often not satisfactory. It happens due to the de-differentiation of chondrocytes during the expansion step. Indeed, articular chondrocytes are non-proliferative and require partial or complete dedifferentiation before actively proliferating. In recent years stem/progenitor cells in articular cartilage (artSPCs) have been described. These cells maintain their own population and renew articular cartilage in sexually mature mice. artSPCs can, theoretically, be superior to chondrocytes, for repairing damaged cartilage.
Accordingly, here, we searched for conditions that allow rapid expansion of both artSPCs and chondrocytes with simultaneous preservation of their ability to form hyaline cartilage. Among the modulators of Wnt, Notch, and FGF signaling and of cell adhesion screened, only fibronectin and modulators of the Notch pathway promoted the rapid expansion of artSPCs. Surprisingly, both inhibition and activation of the pathway had this effect. However, only inhibition of Notch during expansion facilitated the chondrogenic potential of both artSPCs and primary chondrocytes, whereas activation of this pathway abrogated this potential entirely. This effect was the same for murine and human cells. Our present observations indicate that Notch signaling is the major regulator of the chondrogenic capacity of both artSPCs and chondrocytes during their expansion.
Extracellular Vesicles From Primed Adipose-Derived Stem Cells Enhance Achilles Tendon Repair by Reducing Inflammation and Promoting Intrinsic Healing
Authors: Shen Hua , Lane Ryan A 
Published: April 2023

Abstract
Achilles tendon rupture is a common sports-related injury. Even with advanced clinical treatments, many patients suffer from long-term pain and functional deficits. These unsatisfactory outcomes result primarily from an imbalanced injury response with excessive inflammation and inadequate tendon regeneration. Prior studies showed that extracellular vesicles from inflammation-primed adipose-derived stem cells (iEVs) can attenuate early tendon inflammatory response to injury. It remains to be determined if iEVs can both reduce inflammation and promote regeneration in the later phases of tendon healing and the underlying mechanism. Therefore, this study investigated the mechanistic roles of iEVs in regulating tendon injury response using a mouse Achilles tendon injury and repair model in vivo and iEV-macrophage and iEV-tendon cell coculture models in vitro. Results showed that iEVs promoted tendon anti-inflammatory gene expression and reduced mononuclear cell accumulation to the injury site in the remodeling phase of healing. iEVs also increased collagen deposition in the injury center and promoted tendon structural recovery. Accordingly, mice treated with iEVs showed less peritendinous scar formation, much lower incidence of postoperative tendon gap or rupture, and faster functional recovery compared to untreated mice. Further in vitro studies revealed that iEVs both inhibited macrophage M1 polarization and increased tendon cell proliferation and collagen production. The iEV effects were partially mediated by miR-147-3p, which blocked the toll-like receptor 4/NF-κB signaling pathway that activated the M1 phenotype of macrophages. The combined results demonstrate that iEVs are a promising therapeutic agent that can enhance tendon repair by attenuating inflammation and promoting intrinsic healing.