bluuebunny/crossref_metadata_2025 huggingface dataset:
P181 Assessing and improving mental health in axial spondyloarthritis through digital solutions
Authors: Chan Antoni , Rigler Kathryn , McDougall Arran
Published: April 2023

Background/Aims

Mental health issues in axial spondyloarthritis (AxSpA) such as anxiety and depression can affect up to two thirds of patients. We aimed to detect the prevalence of anxiety and depression in our AxSpA patients in order to provide interventions to improve the condition. This is part of our work in the National Axial Spondyloarthritis Society’s (NASS) Aspiring to Excellence programme to improve patient outcomes. We have provided an online mental health assessment and self-management video that signpost patients to psychological help and resources.

Methods

We used the Hospital Anxiety and Depression Score (HADS) for AxSpA patients attending the clinic in January to March 2020. We also collected the BASDAI, Spinal Pain, BASFI and BASG. The HADS scores are divided into three groups, 0-7 (normal), 8-10 (borderline abnormal) and 11-21 (abnormal). Patients were invited to watch a self-help video on managing anxiety and depression, which we produced in house with our clinical psychologist. Patients were directed to online mental health resources and self-management programmes. Follow up HADS were collected post watching the video.

Results

All patients met the ASAS criteria for AxSpA. 100 patients were assessed and invited to watch the video. 90/100 (90%) of patients completed the baseline and follow up score. The mean (SD) age was 44.7 (13.2) years. The male:female ratio was 3:1. The mean disease duration was 9 years. The number of patients on biologics was 36 (40%). At baseline, the mean (SD) HADS was 10 (6), BASDAI 4.4 (2.3), Spinal pain 4.2 (3), BASFI 3.7 (2.7) and BASG 4.3 (2.7). The number of patients with a HADS score 0-7 was 28 (31%), 8-10 was 18 (20%) and >11 was 44 (49%). All patients participated in the viewing of the video and used the self-management programme. 34 (38%) patients reported engaging with psychological services such as talking therapies. At follow up, the mean (SD) HADS score was 9 (6), BASDAI 3.7 (2.1), Spinal pain 3.8 (2.2), BASFI 3.4 (2) and BASG 3.9 (2.4). The number of patients with a HADS score 0-7 was 38 (42%), 8-10 was 28 (31%) and >11 reduced to 24 (27%). There was a reduction in the number of patients with HADS >11 (from 49% to 31%) and a trend towards lower HADS (HADS 0-7 increased from 31% to 42%) and AxSpA outcome scores (reduction in all four AS scores from baseline).

Conclusion

Mental health issues in AxSpA can be improved through the use of digital mental health assessment and self-management programmes. This study shows that this is a useful method of delivering care. There was a trend towards the improvement of the mental health and AS disease activity scores using the digital video.

Disclosure

A. Chan: None. K. Rigler: None. A. McDougall: None.
E012 An audit examining specialist referral for osteoporosis treatment for rheumatoid arthritis patients using new NOGG (National Osteoporosis Guideline Group) Guidelines 2022
Authors: Rauf Atif , Moss Kaite
Published: April 2023

Background/Aims

Major osteoporotic fractures remain an important cause of mortality and morbidity. Rheumatoid arthritis patients have significantly increased risk of fracture. New NOGG 2022 guidance recommends specialist referral for certain patients based on FRAX and other risk factors, to consider parenteral and anabolic treatment. Our aim was to assess how many rheumatoid arthritis patients would now require specialist referral.

Methods

We identified 38 patients with rheumatoid arthritis who had been referred for DEXA scanning in January 2022. FRAX was used to estimate fracture risk, this was then adjusted as per NOGG guidance to account for risk factors not included in FRAX. Intervention thresholds from new and old guidance were compared.

Results

90% of patients were female. Average age was 63.2 years. Mean major osteoporotic fracture risk is 15.6 and mean hip fracture risk is 4.7 over 10 years. 31.6% had previous fracture, 8% had recent fracture, and 8% had vertebral fractures. 26.3% were taking steroids, 10.5% were taking high dose steroids. 5% had received parenteral treatment at time of audit.

Conclusion

Rheumatoid arthritis patients have an increased fracture risk and therefore require robust bone protection/fracture risk reduction. This is because of a combination of disease pathogenesis, and concurrence of fracture risk factors. Our cohort reflected this; fracture risk was high and risk factors, particularly steroid use, and previous fracture, were common. Under previous guidance, some patients would eventually be referred to a specialist at the discretion of their physician. New NOGG guidance recommends referral as first line for certain patients. When applied to this cohort, we can see that a significant number of patients would be referred to a specialist. This represents a significant shift away from oral therapies and towards consideration of specialist treatment. Under new guidance, a significant number of rheumatoid arthritis patients need specialist referral. This requires a substantial number of resources and means that parenteral therapies will have a much larger place in osteoporosis management.

Disclosure

A. Rauf: None. K. Moss: None.
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

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

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

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

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

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 < 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 < 0.001). At 12 months, significant reductions in median anti-dsDNA titre (16.50-point reduction, n = 42, p < 0.001) and median daily prednisolone dose were evident (2.50mg reduction, n = 51, p < 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 >/= 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

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 < 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 < B < 4.30; 1.38 < s.e. < 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

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 < 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 < 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

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.
Adaptation of digital navigation training for integrated behavioral health providers: Interview and survey study
Authors: Emerson Margaret R , Dinkel Danae , Watanabe-Galloway Shinobu , Torous John , Johnson David J
Published: April 2023

Despite effective treatment options, people who experience mental health conditions often do not receive needed care. E-mental health, for instance the use of mobile apps, is emerging as a way to increase access to and extend care. However, little formal training is available to increase the digital literacy level among behavioral healthcare providers (BHPs), seeking to employ such technology. The purpose of this study was to explore the acceptability and usability of an adapted in-person Digital Navigation Training (DNT) curriculum into e-Learning modules focused on the integrated environment for BHPs. BHP confidence to serve as digital navigators was also explored. E-Learning modules were adapted from an existing in-person DNT. A purposeful sampling strategy was used to recruit BHPs (n = 8) to complete the modules. Acceptability, usability, and confidence were assessed via survey and semi-structured interviews. Descriptive statistics were calculated for survey data and qualitative data were analyzed using a directed content analysis approach. BHPs who completed the training (n = 8) felt the modules were usable, enjoyed the structure, and felt the amount of time to complete the modules was acceptable. All participants thought the structure of the training worked well and enjoyed learning new information. While participants’ confidence in their digital navigation skills increased, they desired more information and/or experience with screening apps prior to increasing their use of apps within their care. E-Learning modules were an acceptable method of educating BHPs with digital navigation skills. Future research is needed to explore incentives needed for training along with if participating in these modules can increase use of quality mobile apps to augment care within BHP treatment plans.
Effects of perfluorododecanoic acid on testicular function in mice
Authors: Liu Zhuo-jie , Liu Yong-hui , Huang Sheng-yu , Wu Cheng-lun , Zang Zhi-Jun
Published: April 2023

Perfluorodecanoic acid (PFDoA) is a widely distributed environmental pollutant that can affect the functions of many organs. However, systematic evaluations of the effects of PFDoA on testicular functions are lacking. The aim of this study was to investigate the effects of PFDoA on mouse testicular functions, including spermatogenesis, testosterone synthesis, and stem Leydig cells (SLCs) in the interstitial tissue of the testis. PFDoA (0, 2, 5, 10 mg/kg/d) was administered via gavage to 2-month-old mice for 4 weeks. Serum hormone levels and sperm quality were assayed. Furthermore, to investigate the mechanisms by which PFDoA affects testosterone synthesis and spermatogenesis in vivo, the expression of StAR and P450scc in testicular tissue was measured by immunofluorescence staining and quantitative real-time PCR. In addition, the levels of SLC markers, including nestin and CD51, were studied. PFDoA decreased the luteinizing hormone concentration and sperm quality. Although the difference was not statistically significant, mean testosterone levels showed a downward trend. The expression of StAR, P450scc, CD51, and nestin was also suppressed in the PFDoA-treated groups compared with the control group. Our study suggested that PFDoA exposure can decrease testosterone biosynthesis, and even reduce the number of SLCs. These results indicated that PFDoA suppressed the main functions of testis, and further researches are required to identify strategies for preventing or reducing the effect of PFDoA on testicular function.
Hepatoprotective effect of avicularin on lead-induced steatosis, oxidative stress, and inflammation in mice associated with the MAPK/HSP60/NLRP3 and SREBP1c pathway
Authors: Qiu Ting , Shi Jia-Xue , Cheng Chao , Jiang Hong , Ruan Hai-Nan , Li Jun , Liu Chan-Min
Published: April 2023

Lead (Pb), an environmental hazard, causes severe diseases in the liver, kidney, cardiovascular system, hematopoietic system, reproductive system, and nervous system. Avicularin (AVI), the main dietary flavonoid found in many citrus fruits, exhibited potential protective properties on organs. However, the molecular mechanisms of these protective actions are currently not clear. In our study, the effects of AVI on Pb-induced hepatotoxicity were evaluated using ICR mice. Changes in oxidative stress, inflammation, lipid metabolism, and related signaling were evaluated. We found for the first time that treatment with AVI significantly reduced hepatic steatosis, inflammation, and oxidative stress induced by Pb. AVI attenuated Pb-induced liver dysfunction and lipid metabolism disorder in mice. AVI decreased the serum biochemical indicators of lipid metabolism. AVI decreased the expression levels of lipid metabolism-related protein SREBP-1c, acetyl-CoA carboxylase (ACC), and FAS. AVI suppressed Pb-induced inflammation in livers, as indicated by decreasing the TNF-α and IL-1β levels. AVI suppressed oxidative stress by increasing the activation of SOD, CAT, and GPx. Furthermore, AVI inhibited the activities of JNK, ERK, p38, and NF-κB. AVI further decreased the levels of HSP60, NLRP3, p-IκBα, and p-p65 in the livers of mice. Collectively, this study indicated that AVI mitigated Pb-induced hepatic steatosis, oxidative stress, and inflammation by regulating the SREBP-1c and MAPK/HSP60/NLRP3 signaling pathways.
The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5
Authors: Zhang Yan , Wang Hanbin , Zhu Ye , Hou Xiaojing , Li Xing , Zhou Xiaomei , Ge Lili , Xu Juan , Su Yiping
Published: April 2023

Premature ovarian failure (POF) is a complication of ovarian dysfunction resulting from the depletion or dysfunction of primordial follicles (PFs) in the ovaries. However, residual follicles that have the potential to be activated are present in POF or aged women. Little is known about the mechanisms by which the remaining dormant PFs in POF patients are activated. Using mass spectrometry, we screened differentially generated peptides extracted from the ovarian cortical tissue biopsies of patients with or without POF, during which we identified PFAP1, a peptide that significantly promoted the activation of PFs in the ovaries of 3 dpp mice in vitro. PFAP1 reversed age‐related fertility damage in vivo to a certain extent, promoted estrogen (E2) and anti‐mullerian hormone (AMH) production (p < .05), and decreased the levels of follicle‐stimulating hormone (FSH) (p < .05). In newborn mouse ovaries, PFAP1 could bind to the protein minichromosome maintenance protein 5 (MCM5) and inhibit its ubiquitination and degradation. In addition, PFAP1 promoted the proliferation of GCs, probably by regulating the function and production of MCM5. In conclusion, PFAP1 could promote the activation of PFs in the ovaries of newborn mice, partially restore the ovarian function of aged mice, and increase the proliferation of primary granulosa cells (GCs) by regulating the function of MCM5. PFAP1 is a promising novel peptide that may be developed into a new therapeutic agent for POF and other ovarian diseases.
Necrotizing Fasciitis Due to Staphylococcus lugdunensis
Authors: Patel Amolee , Nadeem Iram
Published: April 2023

Necrotizing fasciitis is a complicated infection requiring surgical intervention, antimicrobial therapy, and extensive supportive care. Necrotizing fasciitis presents with a few key clinical features and surgical findings, even though it can be a monomicrobial or polymicrobial infection. Timely medical and surgical management is crucial to prevent mortality and achieve positive clinical outcomes. Although initial treatment includes broad-spectrum antibiotics, therapy is often targeted based on isolated cultures and susceptibilities. First identified in 1988, Staphylococcus lugdunensis has been isolated as a pathogen in an increasing number of invasive infections. We describe a rare case of necrotizing fasciitis associated with S. lugdunensis and review the current clinical and microbiological literature.
Assessment of atherosclerosis: should coronary calcium score and intima-media thickness be replaced by ultrasound measurement of carotid plaque burden and vessel wall volume?
Authors: Spence J. David
Published: April 2023

Purpose of review

To describe the uses of vessel wall volume (VWV) and measurement of carotid plaque burden, as total plaque area (TPA) and total plaque volume (TPV), and to contrast them with measurement of carotid intima-media thickness (IMT) and coronary calcium (CAC).

Recent findings

Measurement of carotid plaque burden (CPB) is useful for risk stratification, research into the genetics and biology of atherosclerosis, for measuring effects of new therapies for atherosclerosis, and for treatment of high-risk patients with severe atherosclerosis. It is as predictive of risk as CAC, with important advantages. IMT is only a weak predictor of risk and changes so little over time that it is not useful for assessing effects of therapy.

Measurement of CPB and VWV are far superior to measurement of carotid IMT in many ways, and should replace it. Vessel wall volume can be measured in persons with no plaque as an alternative to IMT. There are important advantages of CPB over coronary calcium; CPB should be more widely used in vascular prevention.
THE GLOBAL MACROECONOMIC BURDEN OF BURN INJURIES
Authors: Gerstl Jakob V. E. , Ehsan Anam N. , Lassarén Philipp , Yearley Alexander , Raykar Nakul P , Anderson Geoffrey A. , Smith Timothy R. , Sabapathy Raja , Ranganathan Kavitha
Published: April 2023

Background:

Standardized estimates of global economic losses of burn injuries are missing. The primary objective of this study was to determine the global macroeconomic consequences of burn injuries and their geographic distribution.

Methods:

Using the Institute of Health Metrics and Evaluation (2009 and 2019) database, mean and 95% uncertainty intervals (UI) data on incidence, mortality, and disability adjusted life year (DALY) from injuries caused by fire, heat and hot substances were collected. Gross domestic product (GDP) data were analyzed together with DALYs to estimate macroeconomic losses globally using a value of lost welfare approach.

Results:

There were 9.0 (95%UI 6.8-11.2) million global burn cases and 111,000 (95%UI 88,000-132,000) mortalities in 2019, representing a total of 7.5 (95%UI 5.8-9.5) million DALYs. This represented welfare losses of 112 (95%UI 78-161) billion USD or 0.09% (95%UI 0.06-0.13%) of GDP. Welfare losses as a share of GDP were highest in LMIC regions Oceania (0.24%; 95%UI 0.09-0.42%) and Eastern Europe (0.24%; 95%UI 0.19-0.30%) compared to high-income country regions such as Western Europe (0.06%; 95%UI 0.04-0.09%). Mortality-to-incidence ratios were highest in LMIC regions highlighting a lack of treatment access, with Southern Sub-Saharan Africa reporting a mortality-incidence-ratio of 40.1 per 1,000 people compared to 1.9 for Australasia.

Conclusion:

Burden of disease and resulting economic losses for burn injuries are substantial worldwide and are disproportionately higher in LMICs. Possible effective solutions include targeted education, advocacy, and legislation to decrease incidence and investing in existing burn centers to improve treatment access.
EXOSOMES AND MICROVESICLES FROM ADIPOSE-DERIVED MESENCHYMAL STEM CELLS PROTECTS THE ENDOTHELIAL GLYCOCALYX FROM LPS INJURY
Authors: Taghavi Sharven , Abdullah Sarah , Shaheen Farhana , Packer Jacob , Duchesne Juan , Braun Stephen E. , Steele Chad , Pociask Derek , Kolls Jay K. , Jackson-Weaver Olan
Published: April 2023

Introduction: Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASCs) have therapeutic potential in multiple disease states; however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. Methods: Exosomes and microvesicles were collected from ASC conditioned media by centrifugation (10,000g for microvesicles, 100,000g for exosomes). Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). LPS-injured cells (n = 578) were compared with HUVECS with concomitant LPS injury plus 1.0 μg/mL of exosomes (n = 540) or microvesicles (n = 510) for 24 hours. These two cohorts were compared with control HUVECs that received phosphate-buffered saline only (n = 786) and HUVECs exposed to exosomes (n = 505) or microvesicles (n = 500) alone. Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify EGX. Real-time quantitative reverse-transcription polymerase chain reaction was used on HUVECs cell lystate to quantify hyaluron synthase-1 (HAS1) expression. Results: Exosomes alone decreased endothelial glycocalyx staining intensity when compared with control (4.94 vs. 6.41 AU, P < 0.001), while microvesicles did not cause a change glycocalyx staining intensity (6.39 vs. 6.41, P = 0.99). LPS injury resulted in decreased glycocalyx intensity as compared with control (5.60 vs. 6.41, P < 0.001). Exosomes (6.85 vs. 5.60, P < 0.001) and microvesicles (6.35 vs. 5.60, P < 0.001) preserved endothelial glycocalyx staining intensity after LPS injury. HAS1 levels were found to be higher in the exosome (1.14 vs. 3.67 RE, P = 0.02) and microvesicle groups (1.14 vs. 3.59 RE, P = 0.02) when compared with LPS injury. Hyaluron synthase-2 and synthase-3 expressions were not different in the various experimental groups. Conclusions: Exosomes alone can damage the endothelial glycocalyx. However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect seems to be mediated by HAS1. Level of Evidence: Basic science study
Tahibacter soli sp. nov., isolated from soil and Tahibacter amnicola sp. nov., isolated from freshwater
Authors: Baek Ju Hye , Han Dong Min , Kim Jeong Min , Jia Baolei , Jung Ji Young , Jeon Che Ok
Published: April 2023

Two Gram-stain-negative, facultative aerobic, catalase- and oxidase-positive, and non-motile rod bacteria, strains BLT and W38T, that were isolated from soil and freshwater, respectively, were taxonomically characterized. Both strains optimally grew at 30 °C and pH 7.0 in Reasoner's 2A medium and contained ubiquinone-8 as the sole respiratory quinone. As major fatty acids (>10 %), strain BLT contained iso-C15 : 0 and summed features 3 and 9 (comprising iso-C15 : 0 2-OH and/or C16 : 1
 ω7c/ω6c and iso-C17 : 1
 ω9c and/or C16 : 0 10-methyl, respectively), whereas strain W38T contained iso-C15 : 0, iso-C16 : 0 and summed feature 9. Diphosphatidylglycerol and phosphatidylmonomethylethanolamine as major polar lipids and phosphatidylethanolamine and phosphatidylglycerol as minor polar lipids were detected in both strains. The DNA G+C contents of strains BLT and W38T were 68.3 and 65.3 %, respectively. Phylogenetic analyses based on 16S rRNA gene and genome sequences revealed that strains BLT and W38T formed a tight phylogenetic lineage with

Tahibacter

species, and they shared 98.8 % 16S rRNA gene sequence similarity and 75.5 % average nucleotide identity (ANI) and 16.6 % digital DNA–DNA hybridization (dDDH) values, indicating that they are different species. Strains BLT and W38T were most closely related to

Tahibacter caeni

BUT-6T and

Tahibacter aquaticus

PYM5-11T with 97.7 and 98.0 % 16S rRNA gene sequence similarities, respectively. ANI and dDDH values between strain BLT and

T. caeni

BUT-6T and between strain W38T and

T. aquaticus

DSM 21667T were 78.5 and 21.6% and 75.3 and 21.0 %, respectively. Based on their phenotypic, chemotaxonomic and genomic properties, strains BLT and W38T represent two different novel species of the genus

Tahibacter

, for which the names Tahibacter soli sp. nov. and Tahibacter amnicola sp. nov. are proposed. The type strains of T. soli and T. amnicola are BLT (=KACC 22831T=JCM 35402T) and W38T (=KACC 22832T=JCM 35749T), respectively.
Rapid realist review of virtual wards for people with frailty
Authors: Westby Maggie , Ijaz Sharea , Savović Jelena , McLeod Hugh , Dawson Sarah , Welsh Tomas , Roux Hein Le , Walsh Nicola , Bradley Natasha
Published: April 2023

Background

Virtual wards (VWs) deliver multidisciplinary care at home to people with frailty at high risk of a crisis or in-crisis, aiming to mitigate the risk of hospital admission. Different VWs models exist and evidence of effectiveness is inconsistent.

Aim

We conducted a rapid realist review to identify different types of VWs, and to develop explanations for how and why VWs could deliver effective frailty management.

Methods

We searched published and grey literature to identify evidence on VWs for frailty, based in Great Britain and Ireland. Information on how and why virtual wards might ‘work’ was extracted and synthesised in two rounds with input from clinicians and patient/public contributors, generating 12 hypothesised context-mechanism-outcome configurations.

Results

We included 17 published and 11 grey literature documents. VWs could be short-term and acute (1-21 days), or longer-term and preventative (3-7 months).

Effective VW operation requires common standards agreements, information sharing processes, an appropriate multidisciplinary team that plans patient care remotely, and good co-ordination. VWs may enable delivery of frailty interventions through appropriate selection of patients, comprehensive assessment including medication review, integrated case management, and proactive care. Important components for patients and caregivers are their communication with the VW, their experience of care at home, and feeling included, safe and empowered to manage their condition.

Conclusions

Insights gained from this review could inform implementation or evaluation of VWs for frailty. A combination of acute and longer-term VWs may be needed, within a whole system approach. An emphasis on proactive care is recommended.