The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

A functional genomics approach reveals suggestive quantitative trait loci associated with combined TLR4 and BCP crystal-induced inflammation and osteoarthritis.

OBJECTIVE: Basic calcium phosphate (BCP) crystals can activate the NLRP3 inflammasome and are potentially involved in the pathogenesis of osteoarthritis (OA). In order to elucidate relevant inflammatory mechanisms in OA, we used a functional genomics approach to assess genetic variation influencing BCP crystal-induced cytokine production. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers who were previously genotyped and stimulated with BCP crystals and/or lipopolysaccharide (LPS) after which cytokines release was assessed. Cytokine quantitative trait locus (cQTL) mapping was performed. For in vitro validation of the cQTL located in anoctamin 3 (ANO3), PBMCs were incubated with Tamoxifen and Benzbromarone prior to stimulation. Additionally, we performed co-localisation analysis of our top cQTLs with the most recent OA meta-analysis of genome-wide association studies (GWAS). RESULTS: We observed that BCP crystals and LPS synergistically induce IL-1ß in human PBMCs. cQTL analysis revealed several suggestive loci influencing cytokine release upon stimulation, among which are quantitative trait locus annotated to ANO3 and GLIS3. As functional validation, anoctamin inhibitors reduced IL-1ß release in PBMCs after stimulation. Co-localisation analysis showed that the GLIS3 locus was shared between LPS/BCP crystal-induced IL-1ß and genetic association with Knee OA. CONCLUSIONS: We identified and functionally validated a new locus, ANO3, associated with LPS/BCP crystal-induced inflammation in PBMCs. Moreover, the cQTL in the GLIS3 locus co-localises with the previously found locus associated with Knee OA, suggesting that this Knee OA locus might be explained through an inflammatory mechanism. These results form a basis for further exploration of inflammatory mechanisms in OA.

Basic calcium phosphate crystals induce the expression of extracellular matrix remodelling enzymes in tenocytes.

OBJECTIVES: Basic calcium phosphate (BCP) crystals contribute to several syndromes associated with tendon disease, including acute calcific tendinitis and Milwaukee shoulder syndrome. Interactions between BCP crystals and tenocytes (tendon cells) may contribute to these clinical syndromes. This study aimed to determine the direct effects of BCP crystals on tenocyte function and viability. METHODS: In vitro assays were used to assess changes in human tenocytes cultured with BCP crystals. Real-time PCR was used to determine changes in the expression of tendon-related genes and extracellular matrix remodelling enzymes (MMPs; a disintegrin and metalloproteases, ADAMTS; and tissue inhibitor of metalloproteinases, TIMPs). ELISA was used to measure protein concentrations in tenocyte supernatants. MTT and alamarBlue™ assays were used to determine changes in cell viability. RESULTS: BCP crystals upregulated tenocyte gene expression of MMP-1, MMP-3, ADAMTS-4 and TIMP-1 after 24 h. Time-course experiments showed expression peaked at 8 h for TIMP-1 and 48 h for MMP-1 and ADAMTS-4. Cyclooxygenase (COX)-1 gene expression was upregulated after 48 h. Tenocytes did not alter expression of scleraxis and tendon collagens, and expression of pro-inflammatory cytokines was not induced with BCP crystals. BCP crystals increased tenocyte release of prostaglandin E2 (PGE2) and MMP-1 protein after 24 h. However, neither COX-1 inhibition nor COX-2 inhibition led to consistent change in BCP crystal-induced tenocyte gene expression of extracellular matrix remodelling enzymes. BCP crystals had no effect on tenocyte viability. CONCLUSION: BCP crystals induce extracellular matrix remodelling enzymes, but not inflammatory cytokines, in tenocytes.

A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.

AIMS: Type 2 diabetes is a risk factor for late-life dementia, but dementia prevention strategies have yet to be comprehensively evaluated in people with diabetes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated cognitive benefits of a 2-year multidomain lifestyle intervention. However, given the intensive nature of FINGER, there is uncertainty about whether it can be implemented in other high-risk populations. Our aim was to explore attitudes towards dementia risk, and barriers to an intervention based on the FINGER model in older adults with type 2 diabetes living in rural areas of Ireland. METHODS: Focus groups were conducted with 21 adults (11 men and 10 women) aged 60+ years with type 2 diabetes living in border regions of north and south Ireland. Data were analysed using thematic analysis. RESULTS: There was limited understanding of diabetes as a risk factor for late-life dementia. The main barriers to engagement with the multidomain intervention were eating foods that were not compatible with cultural norms, time and travel constraints, and perceived lack of self-efficacy and self-motivation for adopting the desired diet, exercise and computerised cognitive training (CCT) behaviours. Facilitators for intervention acceptability included the provision of culturally tailored and personalised education, support from a trusted source, and inclusion of goal setting and self-monitoring behavioural strategies. CONCLUSIONS: While there was high acceptability for a brain health intervention, several barriers including cultural food norms and low self-efficacy for adopting the diet, exercise and CCT components would need to be considered in the intervention design. Findings from this study will be used to inform local decisions regarding the adaptation of FINGER for people with type 2 diabetes. The feasibility of the adapted multidomain intervention will then be evaluated in a future pilot trial.

An Update on the Diagnosis and Management of Calcium Crystal Disease.

PURPOSE OF REVIEW: This article aims to review the challenges to diagnosis and management of calcium crystal deposition diseases and evaluate the literature published over the past 3 years. RECENT FINDINGS: The awaited development of classification criteria is an essential step in the progression of calcium crystal deposition disease clinical research. There have been recent improvements in the accuracy of imaging for the diagnosis of crystal deposition diseases with published definitions of characteristic features. Factors associated with acute flares of disease have been identified and an association with increased cardiovascular risk has been demonstrated. Targeted treatment options for calcium crystal diseases remain elusive. However, there have been advances in understanding the molecular mechanisms of disease revealing potential targets for future drug development. Calcium-crystal deposition diseases are increasing in incidence and prevalence as populations age and continue to associate with a high burden of disability. Despite this, calcium crystal deposition disease remains under-studied with a paucity of evidence-based treatment guidelines.

Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry.

OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.

Clinical pathways for the management of low back pain from primary to specialised care: a systematic review.

PURPOSE: Clinical pathways for low back pain (LBP) have potential to improve clinical outcomes and health service efficiency. This systematic review aimed to synthesise the evidence for clinical pathways for LBP and/or radicular leg pain from primary to specialised care and to describe key pathway components. METHODS: Electronic database searches (CINAHL, MEDLINE, Cochrane Library, EMBASE) from 2006 onwards were conducted with further manual and citation searching. Two independent reviewers conducted eligibility assessment, data extraction and quality appraisal. A narrative synthesis of findings is presented. RESULTS: From 18,443 identified studies, 28 papers met inclusion criteria. Pathways were developed primarily to address over-burdened secondary care services in high-income countries and almost universally used interface services with a triage remit at the primary-secondary care boundary. Accordingly, evaluation of healthcare resource use and patient flow predominated, with interface services associated with enhanced service efficiency through decreased wait times and appropriate use of consultant appointments. Low quality study designs, heterogeneous outcomes and insufficient comparative data precluded definitive conclusions regarding clinical- and cost-effectiveness. Pathways demonstrated basic levels of care integration across the primary-secondary care boundary. CONCLUSIONS: The limited volume of research evaluating clinical pathways for LBP/radicular leg pain and spanning primary and specialised care predominantly used interface services to ensure appropriate specialised care referrals with associated increased efficiency of care delivery. Pathways demonstrated basic levels of care integration across healthcare boundaries. Well-designed randomised controlled trials to explore the potential of clinical pathways to improve clinical outcomes, deliver cost-effective, guideline-concordant care and enhance care integration are required.

Towards understanding the nature and need of delirium guidelines across nations and cultures.

BACKGROUND: Delirium is associated with a variety of adverse healthcare outcomes but is highly predictable, preventable and treatable. For this reason, numerous guidelines have been developed for delirium recognition, prevention and management across different countries and disciplines. Although research is adduced as evidence for these guidelines, a constant finding is the lack of implementation if they exist at all. Implementation is a human behaviour that can be influenced by various factors including culture at a micro- and macro-level. Hofstede's model proposes that national cultures vary along six consistent dimensions. AIM: Using this model, we examined the nature of delirium guidelines across countries in relation to Hofstede's six cultural dimensions. METHODS: Data collected for each country on: the six dimensions of Hofstede's model, number of delirium guidelines approved by a National professional body of each country (through searching databases), the annual old-age dependency ratio for each country. RESULTS: Sixty-four countries had the completed six dimensions of Hofstede's model. Twenty of them (31%) had one or more delirium guidelines. The total number of different delirium guidelines was 45. Countries with formal delirium guidelines have significantly lower power distance among their members, are more individualistic societies, have lower levels of uncertainty avoidance and higher old-age dependency ratio compared to those without delirium guidelines. DISCUSSION/CONCLUSION: The development and implementation of delirium guidelines vary across countries. Specific combinations of cultural dimensions influence the production of delirium guidelines. Understanding these important cultural differences can facilitate more widespread acceptance and implementation of guidelines.

Comparison of verbal and computerised months backwards tests in a hospitalized older population.

BACKGROUND: Delirium is extremely prevalent, yet underdiagnosed, in older patients and is associated with prolonged length of hospital stay and higher mortality rates. Impaired attention is the cardinal deficit in delirium and is a required feature in diagnostic criteria. The verbal months backwards test (MBT) is the most sensitive bedside test of attention, however, hospital staff occasionally have difficulty with its administration and interpretation. We hypothesise that the MBT on an electronic tablet may be easier and more consistent to use for both experienced and unexperienced medical professionals and, if the diagnostic efficacy was similar, aid delirium diagnosis. AIM: We aim to investigate the correlation of the verbal MBT with a computerised MBT application. METHODS: Participants recruited (age > 65, n = 75) were allocated to different cohorts (Dementia and Delirium (DMDL), Dementia (DM), Delirium (DL), No Neurocognitive Disorder (NNCD)) and were administered both the verbal and electronic versions. RESULTS: Correlation between measurements were: overall Spearman's rho = 0.772 (p < 0.0001); DMDL rho = 0.666 (p < 0.0001); DL rho = 0.778 (p = 0.039); DM rho = 0.378 (p = 0.203); NNCD rho = 0.143 (p = 0.559). DISCUSSION: Overall, and for the delirious subset, statistically significant agreement was present. Poor inter-test correlation existed in the groups without delirium (DM, NNCD). CONCLUSIONS: The MBTc correlates well with the MBTv in patients who are clinically suspected to have delirium but has poor correlation in patients without delirium. Visuospatial cognition and psychomotor deficits in a dementia cohort and mechanical factors (such as tremor, poor fingernail hygiene and visual impairment) in a group with no neurocognitive disorder may limit the utility of the MBTc in a hospitalised older population.

Which factors predict discordance between a patient and physician on a gout flare?

OBJECTIVE: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare. METHODS: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups-patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed-were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis. RESULTS: Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0-10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]. CONCLUSION: Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints.

Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus.

OBJECTIVE: The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout. METHODS: Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n = 704) and Ardea (n = 755), and data were meta-analysed. RESULTS: In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83). CONCLUSION: In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout.

Telehealth in Psychiatry of Old Age: Ordinary Care in Extraordinary Times in Rural North-West Ireland.

The COVID-19 pandemic has required a rapid evolution of services to maintain routine care in Ireland. Services which had been previously slow to adapt technology in their practices are suddenly integrating various telehealth measures to continue routine practice where possible. In this article, we discuss the challenges we face in rapidly implementing telehealth in a rural Psychiatry of Old Age service in the North-West of Ireland.

Plasma levels of the soluble form of the FcγRIIa receptor vary with receptor polymorphisms and are elevated in rheumatoid arthritis.

Soluble forms of the low-affinity immunoglobulin receptor FcγRIIa (sFcγRIIa) lacking the cytoplasmic tail have been reported in plasma however the mechanism and functional consequences are unknown. This study aimed to evaluate mechanisms of FcγRIIa release compared to GPVI release from platelets, and examine whether genetic polymorphisms at positions 27 and 131 within FcγRIIa correlate with platelet FcγRIIa stability and function. Enzyme-linked immunosorbent assays (ELISAs) were used to measure plasma sFcγRIIa and sGPVI levels. FcγRIIa genotype at positions 27 and 131 was evaluated. sFcγRIIa levels were not significantly different between non-131HH and 131HH but were significantly lower in 27W than non-27W. Treatment of platelets with aggregated immunoglobulin (Ig) G induced release of FcγRIIa and GPVI, but only sGPVI release was statistically significant, required functional FcγRIIa, and was blocked by inhibitors of signaling pathways and metalloproteinases. This indicated that sFcγRIIa was not released from platelets by metalloproteolysis. sFcγRIIa levels were not correlated with sGPVI levels in healthy individuals however levels of sFcγRIIa and sGPVI in plasma from patients with rheumatoid arthritis (RA) were significantly elevated above levels found in healthy individuals. Elevated level of sFcγRIIa in RA patients may reflect active immune-based arthritis and be predictive of active inflammation.

Development and validation of the Spirituality Instrument-27© (SpI-27©) in individuals with chronic illness.

AIM: To develop and validate the Spirituality Instrument 27 (SpI-27©) in individuals with chronic illness (n = 249). BACKGROUND: A need for a rigorously developed spirituality instrument that can be used with people who are religious and non-religious was identified. METHODS: The initial 46-item instrument was developed from a concept analysis, a review of theoretical and empirical literature, and an appraisal of instruments measuring spirituality. Content validity was established with user focus groups and an expert panel review. A pilot study evaluated the online mode of administration and a descriptive correlational design assessed the reliability and validity of the instrument. RESULTS: Results of exploratory factor analysis concluded a five-factor solution with 27 items: Connectedness with Others, Self-Transcendence, Self-Cognisance, Conservationism, and Connectedness with a Higher Power. Cronbach's alpha coefficients ranged from 0.823 to 0.911 for the five factors, and 0.904 for the overall scale. Paired t-tests, intra-class correlations, and weighted kappa values supported the temporal stability of the instrument. A significant and positive correlation was found between the SpI-27© and the Spirituality Index of Well-Being (p < 0.01), supporting convergent validity. CONCLUSIONS: Findings support the validity and reliability of the SpI-27©, which was developed with patient input and is underpinned by theoretical and empirical literature. The SpI-27© should be validated for use with other samples. The conceptual framework that guided the study can be used to enhance healthcare professionals' understanding of spirituality and its core dimensions.

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

OBJECTIVE: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Basic Calcium Phosphate Crystals Induce Osteoarthritis-Associated Changes in Phenotype Markers in Primary Human Chondrocytes by a Calcium/Calmodulin Kinase 2-Dependent Mechanism.

Chondrocytes in osteoarthritis undergo a phenotype shift leading to increased production of cartilage-degrading enzymes. There are similarities between the phenotype of osteoarthritic chondrocytes and those of growth plate chondrocytes. Hydroxyapatite can promote chondrocyte differentiation in the growth plate. Basic calcium phosphate (BCP) crystals (which consist of hydroxyapatite, octacalcium apatite and tricalcium phosphate) are frequently found in osteoarthritic joints. The objective of this study was to determine whether BCP crystals induce disease-associated changes in phenotypic marker expression in chondrocytes. Primary human chondrocytes isolated from macroscopically normal cartilage were treated with BCP for up to 48 h. Expression of indian hedgehog (IHH), matrix metalloproteinase 13 (MMP13), interleukin-6 (IL-6) and type X collagen (COLX) were higher, and expression of sry-box 9 (SOX9) lower, in BCP-treated chondrocytes (50 µg/mL) compared to untreated controls. COLX protein was also present in BCP-treated chondrocytes. Intracellular calcium and levels of phosphorylated and total calcium/calmodulin kinase 2 (CaMK2) were elevated following BCP treatment due to BCP-induced release of calcium from intracellular stores. CaMK2 inhibition or knockdown ameliorated the BCP-induced changes in SOX9, IHH, COLX, IL-6 and MMP13 expression. BCP crystals induce osteoarthritis-associated changes in phenotypic marker expression in chondrocytes by calcium-mediated activation of CaMK2. The presence of BCP crystals in osteoarthritic joints may contribute to disease progression.

Performance characteristics and predictors of temporal artery ultrasound for the diagnosis of giant cell arteritis in routine clinical practice in a prospective cohort.

OBJECTIVES: The diagnosis of giant cell arteritis (GCA) is primarily a clinical one. Temporal artery (TA) ultrasound (US) has been proposed as a new diagnostic tool. We aimed to assess the performance characteristics of TA US in routine clinical practice. METHODS: All patients presenting with suspected GCA to our institution are recruited to a prospective registry. Patients who had both a TA US and biopsy (TAB) performed at the time of presentation were included in the current study. The performance characteristics of TA US was compared to physician diagnosis at six months following presentation. Predictive factors for a positive TA US were explored in univariate and multivariable logistic regression analyses. RESULTS: 162 patients were included, 123 (76%) with GCA. Mean (SD) duration of glucocorticoid therapy was 6.6 days (19.4) at the time of TA US. TA US had a sensitivity of 52.8% (95%CI 43.7, 61.9) and specificity of 71.8% (95%CI 54.9, 84.5) for the diagnosis of GCA. Glucocorticoid duration did not significantly impact the results. A sequential strategy of TA US followed by TAB in the case of a negative US had a sensitivity of 78.9% (95%CI 70.1, 85.5) and specificity of 71.8% (95%CI 54.9, 84.5), equivalent to a simultaneous testing strategy. The only factor independently predictive of a positive TA US was male sex (OR 5.53, 95% CI 2.72 to 11.22, p<0.001). CONCLUSIONS: TA US is potentially useful in the diagnosis of GCA; however, interpretation of its results requires knowledge of the performance characteristics in the target population.

Cancer-related fatigue and self-care agency: A multicentre survey of patients receiving chemotherapy.

AIMS AND OBJECTIVES: To measure cancer-related fatigue (CRF), self-care agency (SCA) and fatigue self-care strategies, and to explore the relationship between CRF and SCA. BACKGROUND: Cancer-related fatigue has been consistently rated as the most elusive, common and severe of symptoms that patients with cancer undergoing chemotherapy experience. Despite its frequency and severity, CRF is poorly managed. A renewed focus on supporting self-care among patients with cancer has been found to reduce symptom burden, empower patients and improve patient satisfaction. Understanding the link between self-care agency (i.e. capability and willingness to self-care) and CRF levels will help practitioners to better support individuals on the cancer journey. DESIGN: A descriptive, correlational survey design was employed. METHODS: Patients (n = 362) undergoing chemotherapy with a primary diagnosis of breast, colorectal, Hodgkin's and non-Hodgkin's lymphoma cancers were recruited from four oncology centres in one city in the South of Ireland. Participants completed the Piper Fatigue Scale-Revised, Appraisal of Self-care Agency Scale and a researcher-developed Fatigue Self-Care Survey. Multivariate logistic regression was used to examine the relationship between CRF and self-care agency using a dichotomous dependent variable score of four as the cut-off between those deemed to be fatigued (≥4) and those not fatigued (<4). As recommended by the EQUATOR Network, the STROBE checklist of items for cross-sectional studies is used to report the study. RESULTS: The incidence of CRF was high with 75% of participants scoring clinically relevant CRF. Higher SCA (OR = 0.96, 95% CI = 0.93-0.99, p = .011) was associated with decreased odds of developing CRF. Having non-Hodgkin's lymphoma (OR = 3.02, 95% CI = 1.29-7.07, p = .011) was associated with increased odds of developing CRF. CONCLUSIONS: Patient's undergoing chemotherapy experience significant fatigue. Higher capability for self-care is associated with lower fatigue. The promotion of SCA and self-care strategies can impact on CRF. RELEVANCE TO CLINICAL PRACTICE: Understanding the link between self-care abilities and fatigue can lead to more individualised and tailored approaches to CRF.

Interleukin 12 and interleukin 23 play key pathogenic roles in inflammatory and proliferative pathways in giant cell arteritis.

OBJECTIVES: The pathogenesis of giant cell arteritis (GCA) remains unclear. TH1 and TH17 pathways are implicated, but the proximal initiators and effector cytokines are unknown. Our aim was to assess the role of interleukin 12 (IL-12) and interleukin 23 (IL-23) in GCA pathogenesis. METHODS: IL-12 and IL-23 expression were quantified by immunohistochemistry in temporal artery biopsies (TABs). Temporal artery (TA) explant, peripheral blood mononuclear cell (PBMC) and myofibroblast outgrowth culture models were established. PBMCs and TA explants were cultured for 24 hours in the presence or absence of IL-12 (50 ng/mL) or IL-23 (10 ng/mL). Gene expression in TA was quantified by real-time PCR and cytokine secretion by ELISA. Myofibroblast outgrowths were quantified following 28-day culture. RESULTS: Immunohistochemistry demonstrated increased expression of interleukin 12p35 (IL-12p35) and interleukin 23p19 (IL-23p19) in biopsy-positive TAs, localised to inflammatory cells. IL-12p35 TA expression was significantly increased in those with cranial ischaemic complications (p=0.026) and large vessel vasculitis (p=0.006). IL-23p19 TA expression was increased in those with two or more relapses (p=0.007). In PBMC cultures, exogenous IL-12 significantly increased interleukin 6 (IL-6) (p=0.009), interleukin 22 (IL-22) (p=0.003) and interferon γ (IFN-γ) (p=0.0001) and decreased interleukin 8 (IL-8) (p=0.0006) secretion, while exogenous IL-23 significantly increased IL-6 (p=0.029), IL-22 (p=0.001), interleukin 17A (IL-17A) (p=0.0003) and interleukin 17F (IL-17F) (p=0.012) secretion. In ex vivo TA explants, IL-23 significantly increased gene expression of IL-8 (p=0.0001) and CCL-20 (p=0.027) and protein expression of IL-6 (p=0.002) and IL-8 (p=0.004). IL-12 (p=0.0005) and IL-23 (p<0.0001) stimulation increased the quantity of myofibroblast outgrowths from TABs. CONCLUSION: IL-12 and IL-23 play central and distinct roles in stimulating inflammatory and proliferative pathways relevant to GCA pathogenesis.