Background
Effective risk communication is essential for informed decision making. Unfortunately, many people struggle to understand typical risk communications because they lack essential ...decision-making skills.
Objective
The aim of this study was to review the literature on the effect of numeracy on risk literacy, decision making, and health outcomes, and to evaluate the benefits of visual aids in risk communication.
Method
We present a conceptual framework describing the influence of numeracy on risk literacy, decision making, and health outcomes, followed by a systematic review of the benefits of visual aids in risk communication for people with different levels of numeracy and graph literacy. The systematic review covers scientific research published between January 1995 and April 2016, drawn from the following databases: Web of Science, PubMed, PsycINFO, ERIC, Medline, and Google Scholar. Inclusion criteria were investigation of the effect of numeracy and/or graph literacy, and investigation of the effect of visual aids or comparison of their effect with that of numerical information. Thirty-six publications met the criteria, providing data on 27,885 diverse participants from 60 countries.
Results
Transparent visual aids robustly improved risk understanding in diverse individuals by encouraging thorough deliberation, enhancing cognitive self-assessment, and reducing conceptual biases in memory. Improvements in risk understanding consistently produced beneficial changes in attitudes, behavioral intentions, trust, and healthy behaviors. Visual aids were found to be particularly beneficial for vulnerable and less skilled individuals.
Conclusion
Well-designed visual aids tend to be highly effective tools for improving informed decision making among diverse decision makers. We identify five categories of practical, evidence-based guidelines for heuristic evaluation and design of effective visual aids.
OA is the most common joint disorder in the world, but there are no approved therapeutics to prevent disease progression. Historically, OA has been considered a wear-and-tear joint disease, and ...efforts to identify and develop disease-modifying therapeutics have predominantly focused on direct inhibition of cartilage degeneration. However, there is now increasing evidence that inflammation is a key mediator of OA joint pathology, and also that the link between obesity and OA is not solely due to excessive load-bearing, suggesting therefore that targeting inflammation in OA could be a rewarding therapeutic strategy. In this review we therefore re-evaluate historical clinical trial data on anti-inflammatory therapeutics in OA patients, highlight some of the more promising emerging therapeutic targets and discuss the implications for future clinical trial design.
Objective
To identify long noncoding RNAs (lncRNAs), including long intergenic noncoding RNAs (lincRNAs), antisense RNAs, and pseudogenes, associated with the inflammatory response in human primary ...osteoarthritis (OA) chondrocytes and to explore their expression and function in OA.
Methods
OA cartilage was obtained from patients with hip or knee OA following joint replacement surgery. Non‐OA cartilage was obtained from postmortem donors and patients with fracture of the neck of the femur. Primary OA chondrocytes were isolated by collagenase digestion. LncRNA expression analysis was performed by RNA sequencing (RNAseq) and quantitative reverse transcriptase–polymerase chain reaction. Modulation of lncRNA chondrocyte expression was achieved using LNA longRNA GapmeRs (Exiqon). Cytokine production was measured with Luminex.
Results
RNAseq identified 983 lncRNAs in primary human hip OA chondrocytes, 183 of which had not previously been identified. Following interleukin‐1β (IL‐1β) stimulation, we identified 125 lincRNAs that were differentially expressed. The lincRNA p50‐associated cyclooxygenase 2–extragenic RNA (PACER) and 2 novel chondrocyte inflammation–associated lincRNAs (CILinc01 and CILinc02) were differentially expressed in both knee and hip OA cartilage compared to non‐OA cartilage. In primary OA chondrocytes, these lincRNAs were rapidly and transiently induced in response to multiple proinflammatory cytokines. Knockdown of CILinc01 and CILinc02 expression in human chondrocytes significantly enhanced the IL‐1–stimulated secretion of proinflammatory cytokines.
Conclusion
The inflammatory response in human OA chondrocytes is associated with widespread changes in the profile of lncRNAs, including PACER, CILinc01, and CILinc02. Differential expression of CILinc01 and CIinc02 in hip and knee OA cartilage, and their role in modulating cytokine production during the chondrocyte inflammatory response, suggest that they may play an important role in mediating inflammation‐driven cartilage degeneration in OA.
Studies of psychiatric disorders have traditionally focused on emotional symptoms such as depression, anxiety and hallucinations. However, poorly controlled cognitive deficits are equally prominent ...and severely compromise quality of life, including social and professional integration. Consequently, intensive efforts are being made to characterize the cellular and cerebral circuits underpinning cognitive function, define the nature and causes of cognitive impairment in psychiatric disorders and identify more effective treatments. Successful development will depend on rigorous validation in animal models as well as in patients, including measures of real-world cognitive functioning. This article critically discusses these issues, highlighting the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders.
Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased ...adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients.
Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of ...IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.
Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas ...associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets.
Patients with early knee OA (n = 29) and end-stage knee OA (n = 22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. Fibroblast single cell RNA sequencing was performed using Chromium 10X and analysed using Seurat. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis and the effect of fibroblast secretome on neuronal growth assessed using rat DRGN.
Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced greater survival and neurite outgrowth in dissociated adult rodent dorsal root ganglion neurons.
Sites of patient-reported pain in knee OA exhibit a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients.
This study was funded by Versus Arthritis, UK (21530; 21812)
The aim of our study was to investigate the effect of asymmetric crosslinked polyethylene liner use on the risk of revision of cementless and hybrid total hip arthroplasties (THAs).
We undertook a ...registry study combining the National Joint Registry dataset with polyethylene manufacturing characteristics as supplied by the manufacturers. The primary endpoint was revision for any reason. We performed further analyses on other reasons including instability, aseptic loosening, wear, and liner dissociation. The primary analytic approach was Cox proportional hazard regression.
A total of 213,146 THAs were included in the analysis. Overall, 2,997 revisions were recorded, 1,569 in THAs with a flat liner and 1,428 in THAs using an asymmetric liner. Flat liner THAs had a higher risk of revision for any reason than asymmetric liner THAs when implanted through a Hardinge/anterolateral approach (hazard ratio (HR) 1.169, 95% confidence interval (CI) 1.022 to 1.337) and through a posterior approach (HR 1.122, 95% CI 1.108 to 1.346). There was no increased risk of revision for aseptic loosening when asymmetric liners were used for any surgical approach. A separate analysis of the three most frequently used crosslinked polyethylene liners was in agreement with this finding. When analyzing THAs with flat liners only, THAs implanted through a Hardinge/anterolateral approach were associated with a reduced risk of revision for instability compared to posterior approach THAs (HR 0.561 (95% CI 0.446 to 0.706)). When analyzing THAs with an asymmetric liner, there was no significant difference in the risk of revision for instability between the two approaches (HR 0.838 (95% CI 0.633 to 1.110)).
For THAs implanted through the posterior approach, the use of asymmetric liners reduces the risk of revision for instability and revision for any reason. In THAs implanted through a Hardinge/anterolateral approach, the use of an asymmetric liner was associated with a reduced risk of revision. The effect on revision for instability was less pronounced than in the posterior approach. Cite this article:
2021;103-B(9):1479-1487.
Background
Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in ...pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations.
Aims
The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement.
Methods
Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes.
Results
A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance.
Conclusions
Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other.
Review Registration:
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699
Objective
To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and ...function of these lncRNAs.
Methods
Synovium was collected from normal‐weight patients with hip fracture (non‐OA; n = 6) and from normal‐weight (n = 8) and obese (n = 8) patients with hip OA. Expression of RNA was determined by RNA‐sequencing and quantitative reverse transcription–polymerase chain reaction. Knockdown of lncRNA was performed using LNA‐based GapmeRs. Synovial fibroblast cytokine production was measured by enzyme‐linked immunosorbent assay.
Results
Synovial fibroblasts from obese patients with OA secreted greater levels of interleukin‐6 (IL‐6) (mean ± SEM 162 ± 21 pg/ml; P < 0.001) and CXCL8 (262 ± 67 pg/ml; P < 0.05) compared to fibroblasts from normal‐weight patients with OA (IL‐6, 51 ± 4 pg/ml; CXCL8, 78 ± 11 pg/ml) or non‐OA patients (IL‐6, 35 ± 3 pg/ml; CXCL8, 56 ± 6 pg/ml) (n = 6 patients per group). RNA‐sequencing revealed that fibroblasts from obese OA patients exhibited an inflammatory transcriptome, with increased expression of proinflammatory messenger RNAs (mRNAs) as compared to that in fibroblasts from normal‐weight OA or non‐OA patients (>2‐fold change, P < 0.05; n = 4 patients per group). A total of 19 lncRNAs were differentially expressed between normal‐weight OA and non‐OA patient fibroblasts, and a further 19 lncRNAs were differentially expressed in fibroblasts from obese OA patients compared to normal‐weight OA patients (>2‐fold change, P < 0.05 for each), which included the lncRNA for metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1 was rapidly induced upon stimulation of OA synovial fibroblasts with proinflammatory cytokines, and was up‐regulated in the synovium from obese OA patients as compared to normal‐weight OA patients (1.6‐fold change, P < 0.001) or non‐OA patients (6‐fold change, P < 0.001). MALAT1 knockdown in OA synovial fibroblasts (n = 4 patients) decreased the levels of mRNA expression and protein secretion of CXCL8 (>1.5‐fold change, P < 0.01), whereas it increased expression of mRNAs for TRIM6 (>2‐fold change, P < 0.01), IL7R (<2‐fold change, P < 0.01), HIST1H1C (>1.5‐fold change, P < 0.001), and MAML3 (>1.5‐fold change, P < 0.001). In addition, MALAT1 knockdown inhibited the proliferation of synovial fibroblasts from obese patients with OA.
Conclusion
Synovial fibroblasts from obese patients with hip OA exhibit an inflammatory phenotype. MALAT1 lncRNA may mediate joint inflammation in obese OA patients.
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