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RMD Open Jul 2024To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references.
OBJECTIVES
To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references.
METHODS
Cohort study using prospectively collected healthcare data from the Skåne region, Sweden (~1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model.
RESULTS
We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4.
CONCLUSIONS
Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.
Topics: Humans; Female; Male; Osteoarthritis; Aged; Sweden; Middle Aged; Multimorbidity; Adult; Morbidity; Incidence; Chronic Disease; Prospective Studies; Comorbidity
PubMed: 38955511
DOI: 10.1136/rmdopen-2024-004164 -
Annals of the Rheumatic Diseases Jul 2024To report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled...
OBJECTIVE
To report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled data from three randomised clinical trials (RCT) followed by open-label extension (OLE) study.
METHODS
Cumulative data from three phase 3 core trials and their OLE were analysed. Safety variables assessed included treatment-emergent adverse events (AEs), serious AEs (SAEs), AEs of special interest and laboratory results. Efficacy assessments included ACR20/50/70 responses, Disease Activity Score 28 (C-reactive protein) <3.2, CDAI remission and low disease activity (LDA), SDAI remission and LDA, HAQ-DI decrease of 0.22 unit and Boolean 2.0 remission.
RESULTS
A total of 2304 patients received OKZ in combination with MTX either once every 2 weeks or once every 4 weeks. Event rates per 100 patient-years in OKZ every 2 weeks and OKZ every 4 weeks, respectively, were 9.57 and 9.13 for SAEs; 2.95 and 2.34 for serious infections; 0.09 and 0.05 for gastrointestinal perforations; 0.58 and 0.83 for major adverse cardiovascular events; and 0.45 and 0.50 for malignancies. No increase in the rate of any AE was observed over 106 weeks of treatment. The evaluation of laboratory variables demonstrated the expected changes, like neutropenia, elevation of liver enzymes and blood lipids. Clinical response rates remained stable during the OLE.
CONCLUSION
The long-term safety and tolerability of OKZ in combination with MTX remained stable. The efficacy of OKZ was maintained through week 106. These findings support OKZ as a treatment option for patients with active RA.
PubMed: 38955475
DOI: 10.1136/ard-2023-225473 -
Bone & Joint Open Jul 2024Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors...
AIMS
Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients' decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research.
METHODS
Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached.
RESULTS
Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants' symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care.
CONCLUSION
Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands.
PubMed: 38955355
DOI: 10.1302/2633-1462.57.BJO-2024-0009.R1 -
Talanta Jun 2024Accurate and sensitive determination of human immunoglobulin G (HIgG) level is critical for diagnosis and treatment of various diseases, including rheumatoid arthritis,...
Accurate and sensitive determination of human immunoglobulin G (HIgG) level is critical for diagnosis and treatment of various diseases, including rheumatoid arthritis, humoral immunodeficiencies, and infectious disease. In this study, versatile tri-signal probes were developed by preparing CdS@SiO nanorods that integrate photoluminescence (PL), multi-phonon resonant Raman scattering (MRRS) and infrared absorption (IRA) properties. Through the coating of multiple CdS nanoparticles as cores within SiO shells, the PL and MRRS properties of CdS were improved, resulting in a significantly lowered limit of detection (LOD), with the lowest LOD of 12.37 ag mL. Integration with the distinctive IRA property of SiO shells widened the detection range towards higher concentrations, establishing a final linear range of 50 ag mL to 10 μg mL. The remarkable consistency among the three signals highlighted the robust internal verification capability for accurate detection. This approach enhances flexibility in selecting detection methodologies to suit diverse scenarios, facilitating HIgG detection. The tri-signal nanoprobes also exhibited excellent detection selectivity, specificity and repeatability. This study presents a fresh idea for developing high-performance detection strategies.
PubMed: 38955105
DOI: 10.1016/j.talanta.2024.126495 -
Talanta Jun 2024Dysregulation of peptidyl arginine deiminase 4 (PAD4) is involved in a variety of diseases including rheumatoid arthritis (RA) and Alzheimer's disease (AD), and it has...
Dysregulation of peptidyl arginine deiminase 4 (PAD4) is involved in a variety of diseases including rheumatoid arthritis (RA) and Alzheimer's disease (AD), and it has emerged as potential and promising therapeutic target. However, no PAD4 inhibitor is ready for clinical use. Immobilized enzyme screening technology has gained increasing attention due to its low cost, reusability, easy separation from the reaction mixture, and resistance to changes in environmental conditions. In this study, PAD4 was immobilized on the magnetic nanoparticles (MNP) to prolong its activity stability, and a simple and rapid screening strategy of traditional Chinese medicine inhibitors based on immobilized PAD4 was established. The PAD4 enzyme was immobilized on magnetic nanoparticles (MNP) via Schiff base reaction using glutaraldehyde (GA) as crosslinking agent. Compared with free PAD4, the resulting MNP@GA@PAD4 exhibited an enhanced tolerance to temperature and storage stability, and its reusability was greatly improved with 66 % of initial enzyme activity after being recycled 10 times. The inhibitory activity of the immobilized PAD4 was assessed using two known PAD4 inhibitors GSK484 and BB-Cl-amidine. The semi-maximum inhibitory concentrations (IC) of GSK484 and BB-Cl-amidine for MNP@GA@PAD4 were 1.00 and 0.97 μM, respectively, for free PAD4 were 0.64 and 0.85 μM, respectively. Finally, the MNP@GA@PAD4 was employed to rapid screen of natural PAD4 inhibitors from forty traditional Chinese medicines (TCMs). Under the same conditions, the controlled experiment was conducted with free PAD4. The screening results of TCMs inhibitors on MNP@GA@PAD4 and free PAD4 were similar, the alcohol extracts of Cinnamomi Cortex and Caryophylli Flos had significant inhibitory effects on PAD4 enzyme activity. The IC values of Cinnamomi Cortex extract for MNP@GA@PAD4 and free PAD4 were determined as 27 and 48 μg/mL, respectively. The IC values of Caryophylli Flos extracts for MNP@GA@PAD4 and free PAD4 were determined as 48 and 32 μg/mL, respectively. For the first time, this study proposed a method to immobilize PAD4 on magnetic materials, and developed a rapid, reusable and feasible strategy to screening natural PAD4 inhibitors from TCMs.
PubMed: 38955099
DOI: 10.1016/j.talanta.2024.126492 -
Seminars in Arthritis and Rheumatism Jun 2024Systemic sclerosis (SSc) is a heterogenous, multi-system autoimmune disease that causes progressive fibrosis of the skin and internal organs, resulting in high morbidity... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a heterogenous, multi-system autoimmune disease that causes progressive fibrosis of the skin and internal organs, resulting in high morbidity and mortality. Intravenous Immunoglobulin (IVIG) is a therapeutic option for SSc; however, reports of its efficacy have been variable, and its use across multiple organ manifestations of SSc has not been comprehensively reviewed.
AIM
The aim of this study was to systematically assess the existing literature on the role of IVIG use across a range of SSc manifestations.
METHODS
Medline, Embase, Cochrane, Web of Science and Scopus were searched from 01/01/2003-15/04/2024 using terms related to SSc and IVIG. Included studies were English-language full texts, where ≥5 adults with SSc received IVIG, and where a reportable outcome was documented.
RESULTS
Of 418 potentially relevant records, 12 were included in this review, comprising 266 patients across one randomised control trial, two pilot studies, one open label study, seven retrospective studies and one case control study. Eighteen outcomes were documented across five different organ systems: cutaneous, respiratory, musculoskeletal, gastrointestinal, and other (clinical improvement and corticosteroid sparing benefit). Results showed a favourable effect of IVIG in reducing the extent of skin thickening, muscle and joint pain, gastrointestinal symptoms, steroid dosing and improving patient/physician reported quality of life. Whilst IVIG may appear to be less beneficial for respiratory disease, the stabilisation in pulmonary function tests and radiological features may be considered a positive outcome in itself. Limitations included a lack of high-quality studies, and the use of concomitant therapies in many studies, rendering the efficacy of IVIG alone difficult to ascertain.
CONCLUSION
IVIG showed benefit in treating some manifestations of SSc, however there was a lack of convincing evidence for the efficacy in others. The lack of high-quality data highlights the need for further well-designed clinical trials to confirm these findings and inform guidelines for IVIG use.
PubMed: 38954999
DOI: 10.1016/j.semarthrit.2024.152471 -
Seminars in Arthritis and Rheumatism Jul 2024
PubMed: 38954998
DOI: 10.1016/j.semarthrit.2024.152496 -
Plastic and Reconstructive Surgery Feb 2024Silicone metacarpophalangeal joint arthroplasty (SMPA) can reconstruct metacarpophalangeal (MCP) joint deformities in the rheumatoid hand, but patient selection criteria...
BACKGROUND
Silicone metacarpophalangeal joint arthroplasty (SMPA) can reconstruct metacarpophalangeal (MCP) joint deformities in the rheumatoid hand, but patient selection criteria for the procedure remains unclear. We used statistical learning to elucidate patient selection criteria that will enhance long-term patient-reported and functional outcomes in patients with severe hand rheumatoid arthritis (RA).
METHODS
This is a secondary analysis of a prospective study of 169 adults with severe hand RA (average combined ulnar deviation (UD) and extensor lag (EL) at the MCP joint ≥ 50 degrees, per finger) with one-year follow-up, conducted at three centers in the United States and England from January 1, 2004, to December 31, 2011. Primary outcomes were Michigan Hand Outcomes Questionnaire (MHQ) pain sub-score, changes in EL, UD, and Arthritis Impact Measurement Scale (AIMS2) score. A tree-based reinforcement learning (T-RL) model was used to estimate clinical decision rules for treatment.
RESULTS
132 patients (mean[SD], 61[9] years; 108[72%] female) were included in the SMPA (n=50) and non-SMPA (n=82) cohorts. To minimize EL and UD, patients should undergo SMPA. To minimize pain, patients older than 55 should undergo SMPA. To increase hand-related quality-of-life (QOL), patients with grip strength <12 kg should undergo SMPA. Estimations with imputed missing data were similar, aside from a lower grip strength (<8 kg) threshold for hand-related QOL.
CONCLUSION
Unless there is significant comorbidity that precludes surgery, most patients older than 55 with severe hand RA will have improved QOL, pain, and function after SMPA. Patients with preserved grip strength may benefit from continued medical management.
PubMed: 38954654
DOI: 10.1097/PRS.0000000000011340 -
The Journal of Bone and Joint Surgery.... Jul 2024There is increasing evidence that musculoskeletal tissues are differentiallys regulated by sex hormones in males and females. The influence of sex hormones, in addition...
There is increasing evidence that musculoskeletal tissues are differentiallys regulated by sex hormones in males and females. The influence of sex hormones, in addition to other sex-based differences such as in anatomical alignment and immune-system function, impact the prevalence and severity of disease as well as the types of injuries that affect the musculoskeletal system and the outcomes of prevention measures and treatment. Literature specifically addressing sex differences related to the musculoskeletal system is limited, underscoring the imperative for both basic and clinical research on this topic. This review highlights areas of research that have implications for bone and cartilage health, including growth and development, sports injuries, osteoarthritis, osteoporosis, and bone frailty. It is clear that important aspects of the musculoskeletal system have been understudied. Consideration of how sex hormone therapy will affect musculoskeletal tissues in prepuberty, during puberty, and in adults is vital, yet little is known. The purpose of this article is to foster awareness and interest in advancing our understanding of how sex differences influence orthopaedic practice.
PubMed: 38954642
DOI: 10.2106/JBJS.24.00194 -
The Journal of Bone and Joint Surgery.... Jul 2024The influence of sex and gender-related factors on health and disease at all levels of scale, across all health conditions, and throughout the entire life course is...
The influence of sex and gender-related factors on health and disease at all levels of scale, across all health conditions, and throughout the entire life course is increasingly clear. A series of policies instituted by the National Institutes of Health (NIH) that require researchers to include appropriate populations and to analyze the data accordingly have strengthened the evidence base around the health of women. Translating these advances to the entire research ecosystem can catalyze rigorous biomedical discovery that can improve health. We encourage journals, publishers, and funders to align their policies and expectations regarding sex and gender considerations in research with those of the NIH and other international funding agencies.
PubMed: 38954641
DOI: 10.2106/JBJS.24.00172