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Objectives The Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) has developed a calcium pyrophosphate deposition (CPPD) nomenclature project. This systematic literature review constituted its first step and aimed to provide a state-of-the-art analysis of the medical literature of the last 20 years.Methods A systematic literature search was undertaken in the PubMed, Cochrane and Embase databases between 2000 and 2022, restricted to studies on humans and in the English language. Eight reviewers independently and manually extracted labels related to CPPD concepts, according to an a priori list generated by the authors: pathogenic conditions and pathogenic crystal labels, elementary imaging condition elements and asymptomatic and symptomatic condition states. For each concept, labels were analysed to determine their frequency.Results Among the 2375 articles identified, 886 articles were included, of which 394 (44.5%) were case reports and 169 (19.0%) were scoping reviews. Overall, the most common labels used to designate the pathogenic condition were ‘pseudogout’ in 365/783 (46.6%), ‘chondrocalcinosis’ in 207/783 (26.4%) and ‘calcium pyrophosphate deposition disease’ in 181/783 (23.1%) occurrences. The most common abbreviation was ‘CPPD’ in 312/390 (80.0%), but with different meanings. CPPD clinical phenotypes were often described as ‘pseudo-form’ labels.Conclusion Those results demonstrate the heterogeneity of labels used to describe CPPD condition concepts, with wide variation in condition labels in the medical literature. This work provides the rationale and basis to achieve agreement about CPPD technical nomenclature.

Introduction The central biochemical cause of gout is hyperuricemia (elevated serum urate levels). Ultrasound features of monosodium urate (MSU) crystal deposition are common in people with asymptomatic hyperuricemia. However, it is unclear whether this is a precondition for the development of gout. This study aims to determine whether ultrasound imaging evidence of MSU crystal deposition predicts development of symptomatic gout over 5 years, in people who already have an increased risk of gout due to elevated serum urate concentrations (≥8 mg/dL).Methods and analysis This is a prospective, international, multicentre study. The study population comprises over 250 participants with asymptomatic hyperuricemia (serum urate ≥8.0 mg/dL). After the baseline assessments, participants are followed for 5 years or until the development of gout, defined by the 2015 American College of Rheumatology/European Alliance of Associations for Rheumatology gout classification criteria. Baseline assessments include anthropomorphic measures, laboratory tests, questionnaires, blood and urine specimen collection, plain radiographs of the feet and standardised ultrasound scans of the lower limbs, scored according to the Outcomes in Rheumatology (OMERACT) gout ultrasound scoring system. The primary outcomes are the development of gout and time course for development of gout in people with and without ultrasound evidence of MSU crystal deposition. Exploratory analyses will examine clinical, genetic and biological factors associated with development of MSU crystal deposition and gout.Ethics and dissemination This study protocol was approved by the New Zealand Ministry of Health Southern Health and Disability Ethics Committee (MEC/05/10/130/AM16) on 18 December 2018. The findings from this study will be published in peer-reviewed journals and will be presented at national and international conferences.Trial registration number ACTRN12619000915156.

Introduction Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to

Objective Previous research has identified that gout impacts various domains of daily life. However, there have been no qualitative studies focusing on employment. This study aimed to understand the impact of gout on employment.Methods Semistructured interviews were conducted in Spain and Aotearoa/New Zealand, in people with gout (according to the 2015 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria) who had experienced a gout flare during their employment. The interviews were guided by questions exploring the impact on employment, job changes, disclosure and co-workers’ reactions. Data were analysed thematically.Results Eighteen participants were interviewed (89% male, mean age 52.9 years). Six themes were identified. The characteristics of the disease (pain intensity, tophi and joints affected) and the job itself (including physical job requirement and workplace flexibility) determined the experience of working with gout. The experiences were divided into physical (from total incapacity to working despite pain), emotional (feeling responsible, embarrassment, guilt and depression) and social (including disclosure responses and financial impact). Gout management strategies including rapid gout flare management and urate-lowering therapy reduced the number of flares and the intensity of pain, and allowed work attendance and participation.Conclusion Both gout and work characteristics influence the employment experience for people with gout. Effective management of gout led to improved work experiences in all its domains.

Objective Transitions to biosimilars are common to reduce the cost burden of biologics. While brand changes can be daunting for patients, few studies have explored patients’ experiences with the transitioning process. This study examined rheumatology patients’ experiences with a mandatory nationwide brand change to an adalimumab biosimilar. Methods People with rheumatic diseases involved in the adalimumab transition in Aotearoa New Zealand completed a nationwide online survey. Participants (n = 117, 48% with rheumatoid arthritis) reported their satisfaction with the biosimilar, logistics and supply, information and communication, and availability of support. They also reported what did and did not go well during the transition and provided recommendations for future transitions. Results The mean [SD] satisfaction score with the transition was 6.2 [3.2] on a 0‐10 scale, with 10 indicating high satisfaction. Participants were the least satisfied with the support and information from patient support organizations, and training for the device during the transition. Participants were most satisfied with the biosimilar supply, support from pharmacists, and how early they were informed before the transition occurred. After the transition, participants were less satisfied with the device quality, patient support program, biosimilar safety and efficacy, and the provision of alcohol wipes and sharps bins (p

Abstract Background Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout. Methods This research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses. Results Alcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the ADH1B locus (P = 3.0 × 10−44) and rs6460047 at the MLXIPL locus (P = 1.4 × 10−4). ADH1B also demonstrated interaction with alcohol consumption for hyperuricaemia (P = 7.9 × 10−13) and gout (P = 8.2 × 10−9). Beer intake had the most significant interaction with ADH1B for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses, ADH1B and MLXIPL were associated with serum urate level and ADH1B was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers. Conclusions In this large study of European participants, novel interactions with alcohol consumption were identified at ADH1B and MLXIPL for association with serum urate level and at ADH1B for association with hyperuricaemia and gout. The association of ADH1B with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.

Objective Transitioning patients to biosimilars has become common to reduce costs and improve access. However, it is unclear how the transition process impacts health care providers at the frontline of the brand change. This study explores health care providers’ experiences of a mandatory brand change to an adalimumab biosimilar. Methods A cross‐sectional study was conducted in Aotearoa New Zealand with 164 providers involved in the nationwide adalimumab brand change. Rheumatologists (n = 39), rheumatology nurses (n = 16), and pharmacists (n = 109) completed a survey that assessed their satisfaction with logistics and supply, information and education, support, and administrative workload and reported what did and did not go well during the transition. Results The mean satisfaction score (0‐10) with the transition was 5.7 (SD = 2.6). Providers were the least satisfied with training for the biosimilar device, information from government agencies, and administrative workload during the transition. Satisfaction with adalimumab safety, efficacy and device quality, and the availability of sharps bins, alcohol wipes, and patient support was lower following the transition. Satisfaction with administrative workload (B = 0.37, P

Abstract Background While xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia. Methods A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA

Abstract Background Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. Objectives This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. Methods A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. Results Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p

Objective Preliminary remission criteria for gout have been developed. However, the patient experience of gout remission has not been described. This qualitative study aimed to understand the patient experience of gout remission and views about the preliminary gout remission criteria. Methods Semistructured interviews were conducted. All participants had gout, had not had a gout flare in the preceding 6 months, and were on urate‐lowering medication. Participants were asked to discuss their experience of gout remission and views about the preliminary remission criteria. Interviews were audio recorded and transcribed verbatim. Data were analyzed using a reflexive thematic approach. Results Twenty participants with gout (17 male participants, median age 63 years) were interviewed. Four key themes of the patient experience of remission were identified: 1) minimal or no gout symptoms (absence of pain due to gout flares, good physical function, smaller or no tophi), 2) freedom from dietary restrictions, 3) gout is “not on the mind”, and 4) multifaceted management strategies to maintain remission (regular urate‐lowering therapy, exercise, healthy eating). Participants believed that the preliminary remission criteria contained all relevant domains but considered that the pain and patient global assessment domains overlapped with the gout flares domain. Participants regarded 12 months as a more suitable time frame than 6 months to measure remission. Conclusion Patients experience gout remission as a return to normality with minimal or no gout symptoms, dietary freedom, and absence of mental load. Patients use a range of management strategies to maintain gout remission.

Abstract Efforts to develop effective disease-modifying drugs to treat osteoarthritis have so far proved unsuccessful with a number of promising drug candidates from pre-clinical studies failing to show efficacy in clinical trials. It is therefore timely to re-evaluate our current understanding of osteoarthritis pathogenesis and the similarities and differences in disease development between commonly used pre-clinical mouse models and human patients. There is substantial heterogeneity between patients presenting with osteoarthritis and mounting evidence that the pathways involved in osteoarthritis (e.g. Wnt signalling) differ between patient sub-groups. There is also emerging evidence that the pathways involved in osteoarthritis differ between the STR/ort mouse model (the most extensively studied mouse model of spontaneously occurring osteoarthritis) and injury-induced osteoarthritis mouse models. For instance, while canonical Wnt signalling is upregulated in the synovium and cartilage at an early stage of disease in injury-induced osteoarthritis mouse models, this does not appear to be the case in the STR/ort mouse. Such findings may prove insightful for understanding the heterogeneity in mechanisms involved in osteoarthritis pathogenesis in human disease. However, it is important to recognise that there are differences between mice and humans in osteoarthritis pathogenesis. A much more extensive array of pathological changes are evident in osteoarthritic joints in individual mice with osteoarthritis compared to individual patients. There are also specified differences in the pathways involved in disease development. For instance, although increased TGF-β signalling is implicated in osteoarthritis development in both mouse models of osteoarthritis and human disease, in mice, this is mainly mediated through TGF-β3 whereas in humans, it is through TGF-β1. Studies in other tissues have shown TGF-β1 is more potent than TGF-β3 in inducing the switch to SMAD1/5 signalling that occurs in osteoarthritic cartilage and that TGF-β1 and TGF-β3 have opposing effects on fibrosis. It is therefore possible that the relative contribution of TGF-β signalling to joint pathology in osteoarthritis differs between murine models and humans. Understanding the similarities and differences in osteoarthritis pathogenesis between mouse models and humans is critical for understanding the translational potential of findings from pre-clinical studies.

Abstract The genetic determinants of the allopurinol dose‐concentration relationship have not been extensively studied. We aimed to clarify what factors, including genetic variation in urate transporters, influence oxypurinol pharmacokinetics (PKs). A population PK model for oxypurinol was developed with NONMEM (version 7.3). The influence of urate transporter genetic variants for ABCG2 (rs2231142 and rs10011796), SLC2A9/GLUT9 (rs11942223), SLC17A1/NPT1 (rs1183201), SLC22A12/URAT1 (rs3825018), SLC22A11/OAT4 (rs17300741), and ABCC4/MRP4 (rs4148500), as well as other participant factors on oxypurinol PKs was assessed. Data from 325 people with gout were available. The presence of the T allele for ABCG2 (rs2231142) and SLC17A1/NPT1 (rs1183201) was associated with a 24% and 22% increase in oxypurinol clearance, respectively, in univariate analysis. This effect was not significant in the multivariate analysis. In the final model, oxypurinol PKs were predicted by creatinine clearance, diuretic use, ethnicity, and body weight. We have found that genetic variability in the transporters examined does not appear to influence oxypurinol PKs.

Abstract Background Aotearoa New Zealand (AoNZ) has no agreed models for rheumatology service provision in government-funded health care. We aimed to describe what people with inflammatory rheumatic diseases who have used rheumatology services view as being important in those services, and map these views to previously collated statements describing best practice components of rheumatology services from international recommendations. If these statements did not capture all service aspects that people with inflammatory rheumatic diseases considered important, we aimed to co-create new statements with our patient-participants. Methods We conducted one focus group and an interview with people with inflammatory rheumatic disease who had used a government-funded rheumatology service in the previous 5 years (patient-participants) and analysed data using thematic analysis. The research team mapped subthemes to previously collated best practice recommendations that had been included in a Delphi consensus exercise with rheumatologists in AoNZ and proposed new statements, based on patient-participant data. Patient-participant feedback on thematic analysis and the new statements led to a refining of statements. A patient-partner in the research team informed research design and data analysis. Results Patient-participants viewed it as highly valuable for rheumatology services to respect and value their experiences as people and patients, and those of their whānau (Māori word for family). They expected rheumatology services to provide the right care, at the right time. Many of the subthemes mapped to the best-practice statements. However, three new principles and three new statements were developed and refined by patient-participants. The three principles addressed valuing individuals, and their whānau (family) and their experiences, and providing a patient-focused health system that supports patient participation in decision-making and self-management, and patient education. New statements related to having a specific rheumatologist and other staff for comprehensive care, having adequate nurse staffing, and active provision of outside services and support. Conclusion It was important to patients that rheumatology services demonstrated that patients and their whānau (family) were valued. The inclusion of people with rheumatic diseases who are users of rheumatology services in service development can provide valuable insights to inform how services should be delivered.

Introduction Gout in Aotearoa New Zealand (NZ) remains an equity issue. The prevalence in Pacific and Māori people is one of the highest internationally. Although Pacific and Māori experience earlier onset and higher burden of gout, which can severely impact their quality of life, their management of it is often sub-optimal. Aim To conduct a scoping review of the NZ literature for interventions to improve the uptake/management of allopurinol for gout and their evaluation. Methods Databases Medline, Scopus, Embase, and CINAHL Plus and the grey literature were searched systematically to identify all NZ intervention studies aiming to improve allopurinol uptake for gout treatment. Interventions included: if they were delivered in NZ, aimed to improve allopurinol uptake, and were provided in English. A narrative approach was used to extract and synthesise data. Results Eighteen peer-reviewed and grey literature publications met the search criteria. Interventions clustered into three domains: multifaceted or multi-practitioner; gout app; and online booklets or fact sheets. Serum urate levels improved in multi-faceted or multi-practitioner interventions only, whereas the gout app only improved patients’ awareness and understanding of gout and medications. Online fact sheets and booklets need more active utilisation from health professionals to improve gout health literacy. Discussion Most gout interventions in NZ use multifaceted or multi-practitioner approaches. Although most interventions successfully controlled serum urate levels and improved equitable access for gout patients to urate-lowering therapy, these interventions did not sustain retention, completion, and engagement for certain population groups, particularly Pacific and Māori, who experience a higher burden of gout.

Summary: Background: Due to geographic isolation and border controls Aotearoa New Zealand (AoNZ) attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread transmission of COVID-19. We describe outcomes of SARS-CoV-2 infection (Omicron variant) in people with inflammatory rheumatic diseases in this unique setting. Methods: This observational study included people with inflammatory rheumatic disease and SARS-CoV-2 infection in AoNZ between 1 February and 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry including demographic and rheumatic disease characteristics, and COVID-19 vaccination status and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death. Findings: Of the 1599 cases included, 96% were from three hospitals that systematically identified people with inflammatory rheumatic disease and COVID-19. At time of COVID-19, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases and 10 (0.6%) patients died. Lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to the unvaccinated (20.6%) or those with a single vaccine dose (10.7%). In multivariable adjusted models, people with gout or connective tissue diseases (CTD) had increased risk of the combined outcome of hospitalisation/death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with increased rates of hospitalisation/death. All patients who died had three or more co-morbidities or were over 60 years old. Interpretation: In this cohort with inflammatory rheumatic diseases and high vaccination rates, severe outcomes from SARS-CoV-2 Omicron variant were relatively infrequent. The outcome of Omicron variant infection among vaccinated but SARS-CoV-2 infection-naive people with inflammatory rheumatic disease without other known risk factors were favourable. Funding: Financial support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) included management of COVID-19 Global Rheumatology Alliance funds.

Abstract Background Tophi are lesions commonly present at sites of bone erosion in gout-affected joints. The tophus comprises a core of monosodium urate (MSU) crystals surrounded by soft tissue that contains macrophages and other immune cells. Previous studies found that MSU crystals directly reduce osteoblast viability and function. The aim of the current study was to determine the indirect, macrophage-mediated effects of MSU crystals on osteoblasts. Methods Conditioned medium from the RAW264.7 mouse macrophage cell line cultured with MSU crystals was added to the MC3T3-E1 mouse osteoblastic cell line. Conditioned medium from the THP-1 human monocytic cell line cultured with MSU crystals was added to primary human osteoblasts (HOBs). Matrix mineralization was assessed by von Kossa staining. Gene expression was determined by real-time PCR, and concentrations of secreted factors were determined by enzyme-linked immunosorbent assay. Results In MC3T3-E1 cells cultured for 13 days in an osteogenic medium, the expression of the osteoblast marker genes Col1a1, Runx2, Sp7, Bglap, Ibsp, and Dmp1 was inhibited by a conditioned medium from MSU crystal-stimulated RAW264.7 macrophages. Mineral staining of MC3T3-E1 cultures on day 21 confirmed the inhibition of osteoblast differentiation. In HOB cultures, the effect of 20 h incubation with a conditioned medium from MSU crystal-stimulated THP-1 monocytes on osteoblast gene expression was less consistent. Expression of the genes encoding cyclooxygenase-2 and IL-6 and secretion of the proinflammatory mediators PGE2 and IL-6 were induced in MC3T3-E1 and HOBs incubated with conditioned medium from MSU crystal-stimulated macrophages/monocytes. However, inhibition of cyclooxygenase-2 activity and PGE2 secretion from HOBs indicated that this pathway does not play a major role in mediating the indirect effects of MSU crystals in HOBs. Conclusions Factors secreted from macrophages stimulated by MSU crystals attenuate osteoblast differentiation and induce the expression and secretion of proinflammatory mediators from osteoblasts. We suggest that bone erosion in joints affected by gout results from a combination of direct and indirect effects of MSU crystals.

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

Abstract In observational studies, serum urate positively associates with cardiometabolic and kidney diseases. We analyzed data from a randomised placebo-controlled trial to determine whether moderate hyperuricemia induced by inosine affects cardiometabolic and kidney function markers. One hundred and twenty post-menopausal women were recruited into a 6-month randomised, double-blind, placebo-controlled trial of inosine for bone health. Change from baseline in the following pre-specified endpoints was analyzed: body mass index; blood pressure; lipid profile; C-reactive protein; fasting glucose; insulin; HbA1c; serum creatinine; and estimated glomerular filtration rate (eGFR). Despite increases in serum urate levels (+ 0.17 mmol/L at week 6, P

Abstract Background Pharmacists play a key role in community gout education. We investigated pharmacist knowledge of gout management and developed an educational intervention which was assessed in a cohort of Irish pharmacists. Methods A ten-question questionnaire about gout management was developed to assess pharmacists’ knowledge. A 14 min 26 s video educational intervention was co-designed by a rheumatologist, a pharmacist, and designer of pharmacy education resources. The effectiveness of this pharmacy-specific intervention was assessed using the same questionnaire in 53 pharmacists (25 in the intervention group; 28 in the control group). Contingency tables were used to analyse differences between groups. Results There were 173 pharmacist respondents to the initial survey; 35.3% answered that first-line therapy for gout involves a combination of a xanthine oxidase inhibitor (e.g., allopurinol) combined with a prophylactic agent (e.g., colchicine), and 28.9% of respondents answered that colchicine prophylaxis should be used when initiating urate-lowering therapy. Following the educational intervention, pharmacist’s knowledge about gout management increased across many domains, including serum urate targets when using urate-lowering therapy (p = 0.006), use of colchicine prophylaxis (p = 0.011), and duration of colchicine use (p

Abstract Introduction Tranexamic acid (TXA) has been shown to be effective at reducing peri-operative blood loss and haemarthrosis in arthroplasty and arthroscopic soft tissue reconstructions. Intra-articular application, as an injection or peri-articular wash, is becoming increasingly common. Recent studies have shown TXA has the potential to be cytotoxic to cartilage, but its effects on human tendon and bone remain poorly understood. The aim of this study was to investigate whether TXA has any detrimental effects on tendon-derived cells and osteoblast-like cells and determine whether there is a safe dosage for clinical application. Materials and methods Primary tendon-derived cells and osteoblast-like cells were harvested from hamstring tendons and trabecular bone explants, respectively, and analysed in vitro with a range of TXA concentrations (0 to 100 mg/ml) at time points: 3 and 24 h. The in vitro toxic effect of TXA was investigated using viability assays (alamarBlue), functional assays (collagen deposition), fluorescent microscopy and live/apoptosis/necrosis staining for cell death mechanisms in 2D monolayer and 3D collagen gel cell culture. Results There was a significant (P 35 mg/ml resulted in significantly (P

Abstract Objectives The objective of this study was to develop and validate a prediction model for renal urate underexcretion (RUE) in male gout patients. Methods Men with gout enrolled from multicenter cohorts in China were analyzed as the development and validation data sets. The RUE phenotype was defined as fractional excretion of uric acid (FEUA)

AimsMonogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Māori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes.MethodsTargeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Māori and Pacific peoples with BMI of 37.9 ± 8.6 kg/m2 who had been diagnosed with type 2 diabetes between 3 and 40 years of age. A triple-screen combined autoantibody assay was used to test for GAD, IA-2, and ZnT8. MODY probability calculator score was generated in those with sufficient clinical information (55/199).ResultsNo genetic variants curated as likely pathogenic or pathogenic were found. One individual (1/199) tested positive for GAD/IA-2/ZnT8 antibodies. The pre-test probability of monogenic diabetes was calculated in 55 individuals with 17/55 (31%) scoring above the 20% threshold considered for diagnostic testing referral.DiscussionOur findings suggest that monogenic diabetes is rare in Māori and Pacific people with clinical age, and the MODY probability calculator likely overestimates the likelihood of a monogenic cause for diabetes in this population.

Abstract Background Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood. Methods A 2016–2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have “primary gout”, based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 6.9), aligning with the clinical significance of urine pH. Results Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria. Conclusions Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

Abstract Background Gout is a painful chronic disease which disrupts work and family life and can lead to chronic joint damage. Pacific people in Aotearoa/New Zealand experience significant inequities, with over three times the gout prevalence of the non-Pacific non-Māori populations. Pacific people receive less regular urate-lowering drugs to prevent gout flare-ups, and have nine times the hospitalisation from gout compared with non-Pacific non-Māori people. Rates for Indigenous Māori lie between Pacific and non-Pacific non-Māori. A long-established Collective comprising community members from the Pacific People’s Health Advisory Group, clinical staff from the Pacific Practice-Based Research Network, and University of Auckland researchers have identified that improving Pacific urate-lowering therapy use as the research question of prime importance for improved health outcomes of Pacific people in South Auckland. Building on the existing knowledge, this study aims to develop, implement and evaluate a novel innovative intervention to improve the uptake of urate-lowering therapy by Pacific patients with gout. Methods Three-phase mixed methods co-design study using the Fa’afaletui research framework following the STROBE statement. Phase1 is observational times series of prevalence of patients with gout, proportion with urate blood-level monitoring and use of urate-lowering medication over past 5 years. In Phase 2 the Collective will workshop new interventions to address previous uptake barriers, using culturally-appropriate Talanga communications with results synthesised in line with Kakala principles. The designed intervention will be implemented and process and outcome evaluations conducted. Finally, an implementation framework will be produced to facilitate further roll-out. Discussion The study aims to enhance health and reduce inequities for Pacific people, contribute to creation of Pacific health knowledge and translation of research findings into Pacific health gains. Potential longer-term impact is a gout-management pathway for use throughout Aotearoa/New Zealand. Māori have similar issues with high gout prevalence and low urate-lowering therapy use hence the intervention is likely to translate to Māori healthcare. The project will contribute to Pacific research capacity and capability-building as well as general upskilling of community and practice members involved in the co-design processes. Trial registration The Australian New Zealand Clinical Trial Registry is in process, request number 38206, 1-09-2021.

Abstract Background Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout. Methods Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over 2 years from an additional 25 patients. Inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system). Results Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76–0.89) for sclerosis and 0.81 (0.72–0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (r = 0.65–0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90–0.98) for sclerosis score and 0.76 (0.65–0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (r = 0.87 and 0.71 respectively), but not with change in erosion scores over 2 years (r = −0.04–0.15). Conclusion A semi-quantitative plain radiographic scoring method for the assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.

Summary: Current understanding of lipid genetics has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history and high prevalence of dyslipidemia may provide insight into the biological foundations of variation in lipid levels. Here, we performed an association study to fine map a suggestive association on 5q35 with high-density lipoprotein cholesterol (HDL-C) seen in Micronesian and Polynesian populations. Fine-mapping analyses in a cohort of 2,851 Samoan adults highlighted an association between a stop-gain variant (rs200884524; c.652C>T, p.R218∗; posterior probability = 0.9987) in BTNL9 and both lower HDL-C and greater triglycerides (TGs). Meta-analysis across this and several other cohorts of Polynesian ancestry from Samoa, American Samoa, and Aotearoa New Zealand confirmed the presence of this association (βHDL-C = −1.60 mg/dL, pHDL-C = 7.63 × 10−10; βTG = 12.00 mg/dL, pTG = 3.82 × 10−7). While this variant appears to be Polynesian specific, there is also evidence of association from other multiancestry analyses in this region. This work provides evidence of a previously unexplored contributor to the genetic architecture of lipid levels and underscores the importance of genetic analyses in understudied populations.

Objective To examine the association of gout with cardiovascular outcomes using linked administrative health data in Aotearoa New Zealand.Design Data linkage study.Setting National registries of pharmaceutical dispensing, hospital admission, and deaths linked to the Auckland/Northland regional repository of laboratory results to create a regional health contact population as of 31 December 2011.Participants 942 416 residents of the Auckland/Northland region, aged 20-79 years with no history of cardiovascular disease.Main outcome measures Time to first fatal or non-fatal cardiovascular event, identified from national datasets on hospital admissions and mortality, between 1 January 2012 and 31 December 2016. Cardiovascular disease was broadly defined as comprising ischaemic heart disease, ischaemic or haemorrhagic stroke, transient ischaemic attack, peripheral vascular disease, and heart failure.Interventions A history of gout identified from a discharge diagnosis of gout from a public hospital admission or previous dispensing of gout specific drug treatments. The cohort was then linked to national hospital admissions and deaths through to 31 December 2016 (ie, 5 years' follow-up). Multivariable Cox proportional hazard models were constructed to assess the associations between gout, other risk factors, and cardiovascular outcomes.Results Of 942 416 people included in the study, 31 907 (3.4%) had gout (6261 women and 25 646 men). After adjustment for multiple risk factors for cardiovascular disease, gout was associated with increased cardiovascular events (adjusted hazard ratio 1.34 (95% confidence interval 1.23 to 1.45) in women; 1.18 (1.12 to 1.24) in men). For men with gout, there was an increased risk of cardiovascular disease in those who were not dispensed regular allopurinol (1.15 (1.05 to 1.25)) and those with a serum urate above the treatment target of 0.36 mmol/L (1.16 (1.04 to 1.30)). Risk of cardiovascular events was lower for men with gout who were not dispensed colchicine compared with those who were (0.84 (0.77 to 0.92)). These findings were not observed in women.Conclusion These results indicate that gout is associated with an increased risk of cardiovascular events. In men with gout without history of cardiovascular disease, the cardiovascular risk was lower in those regularly dispensed allopurinol and those with serum urate levels at the recommended treatment target. By contrast, colchicine dispensing was associated with an increased risk of cardiovascular events in men with gout without a cardiovascular history. The potential causal mechanisms of these associations require further exploration, including casual inference modelling in future studies.

Abstract Background Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at “mid-pass” 1-7x coverage. Results Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with high recall (98%) and precision (97.5%). Conclusion Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications.

Abstract Introduction Elevated serum urate (SU) concentration is the central risk factor for the development of gout. The aim of this study was to examine the incidence of gout in people with low and normal SU levels ( 7.00 mg/dL was 12.2%. In an adjusted Cox proportional hazards model, compared to the referent baseline SU 7.00 mg/dL (HR 18.62). Conclusion A baseline SU of 5.50 mg/dL or more is a risk factor for development of gout over 15 years. However, incident gout does occur over time in a small proportion of people with lower baseline SU levels.

Abstract Background In clinical trials, good quality athletic shoes offer short-term improvements (two-months) in foot pain and disability in people with gout, but these improvements are not sustained over time. This may be due to wear and subsequent changes to the structural integrity of the shoe. The aim of this study was to examine the effects of wear on plantar pressures and footwear characteristics in shoes over six-months in people with gout. Methods Forty people with gout participated in a cross-sectional repeated measures study. Participants wore a pair of commercially available athletic footwear for six-months. Participants then attended a study visit where the worn footwear was compared with a new pair of the same model and size of footwear. Wear characteristics (upper, midsole, outsole) and plantar pressure were measured in the two footwear conditions. Wear characteristics were analysed using paired t-tests and Fisher’s exact tests. Plantar pressure data were analysed using linear mixed models. Results Increases in medial midsole (P

Objectives The objectives for this study were to assess whether gout and/or rheumatoid arthritis (RA) are risk factors for coronavirus disease 2019 (COVID‐19) diagnosis and to assess whether gout and/or RA are risk factors for death from COVID‐19. Methods We used data from the UK Biobank. Multivariable‐adjusted logistic regression was employed in the following analyses: analysis A, to test for association between gout and/or RA and COVID‐19 diagnosis (n = 473,139); analysis B, to test for association between gout and/or RA and death from COVID‐19 in a case‐control cohort of people who died of or survived COVID‐19 (n = 2059); analysis C, to test for association between gout and/or RA and death from COVID‐19 in the entire UK Biobank cohort (n = 473,139). Results RA, but not gout, was associated with COVID‐19 diagnosis in analysis A. Neither RA nor gout was associated with risk of death in the group diagnosed with COVID‐19 in analysis B. However, RA was associated with risk of death related to COVID‐19 by using the UK Biobank cohort in analysis C, independent of comorbidities and other measured risk factors (odds ratio [OR] 1.9; 95% confidence interval CI 1.2–3.0). Gout was not associated with death related to COVID‐19 in the same UK Biobank analysis (OR 1.2; 95% CI 0.8–1.7). Conclusion RA is a risk factor for death from COVID‐19 by using the UK Biobank cohort. These findings require replication in larger data sets that also allow for inclusion of a wider range of factors.

Abstract Background Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU. We use Mendelian randomisation to test for the causality of diet in urate levels. Methods Four European-ancestry sample sets, three from the general population (n = 419,060) and one of people with gout (n = 6781) were derived from the Database of Genotypes and Phenotypes (ARIC, FHS, CARDIA, CHS) and UK Biobank. Dichotomised exposures to diet, genetic risk variants, BMI, alcohol, diuretic treatment, sex and age were used to calculate adjusted population and average attributable fractions (PAF/AAF) for HU (≥0.42 mmol/L [≥7 mg/dL]). Exposure to ULT was also assessed in the gout cohort. Two sample Mendelian randomisation was done in the UK Biobank using dietary pattern-associated genetic variants as exposure and serum urate levels as outcome. Results Adherence to dietary recommendations, BMI (

Gout is characterized by monosodium urate (MSU) crystal deposits in and within joints. These deposits result from persistent hyperuricaemia and most typically lead to recurrent acute inflammatory episodes (gout flares). Even though some aspects of gout are well characterized, uncertainties remain; this upcoming decade should provide further insights into many of these uncertainties. Synovial fluid analysis allows for the identification of MSU crystals and unequivocal diagnosis. Non-invasive methods for diagnosis are being explored, such as Raman spectroscopy and imaging modalities. Both ultrasound and dual-energy computed tomography (DECT) allow the detection of MSU crystals; this not only provides a mean of diagnosis, but also has furthered gout knowledge defining the presence of a preclinical deposition in asymptomatic hyperuricaemia. Scientific consensus establishes the beginning of gout as the beginning of symptoms (usually the first flare), but the concept is currently under review. For effective long-term gout management, the main goal is to promote crystal dissolution treatment by reducing serum urate below 6 mg/dL (or 5 mg/dL if faster crystal dissolution is required). Current urate-lowering therapies’ (ULTs) options are limited, with allopurinol and febuxostat being widely available, and probenecid, benzbromarone, and pegloticase available in some regions. New xanthine oxidase inhibitors and, especially, uricosurics inhibiting urate transporter URAT1 are under development; it is probable that the new decade will see a welcomed increase in the gout therapeutic armamentarium. Cardiovascular and renal comorbidities are common in gout patients. Studies determining whether optimal treatment of gout will positively impact these comorbidities are currently lacking, but will hopefully be forthcoming. Overall, the single change that will most impact gout management is greater uptake of international rheumatology society recommendations. Innovative strategies, such as nurse-led interventions based on these recommendations have recently demonstrated treatment success for people with gout.

Abstract Background Fictional portrayals of illness and medical management in film and television can reflect and perpetuate cultural stereotypes about illness. The aim of this study was to analyse fictional depictions of gout in contemporary film and television. Methods We conducted a search for English language depictions of gout in film and television since 1990 using the Internet Movie Database (IMDb), other internet media databases, and member suggestions from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). Film and television episodes with gout content were analysed for depictions of characters with gout, causal factors, and management strategies (n=44). Results Gout was used to denote royalty or nobility in historical settings, and as a plot device to explain the absence of characters from key events. The most commonly depicted causes of gout were overindulgence of food and alcohol (61%), and portrayals of biological causes were infrequent (12%). Common management strategies were change in diet (36%) and short-term pain relief (32%), with only one mention of urate-lowering therapy (5%). The majority of films and television episodes depicted gout as humorous (59%) and embarrassing (50%). Conclusions In contemporary film and television, gout is portrayed as a humorous and embarrassing condition, caused by dietary indulgence. These depictions may reinforce inaccurate beliefs about the causes of gout and its management.

Abstract Background High body mass index (BMI) is strongly associated with hyperuricaemia. It is unknown whether overweight and obesity influences serum urate primarily through increased urate production or reduced renal clearance of uric acid. The aim of this study was to determine the influence of BMI on the response to inosine, a purine nucleoside that functions as an intermediate in the purine salvage and degradation pathways. Methods Following an overnight fast, 100 healthy participants without gout attended a study visit. Blood and urine samples were taken prior to and over 180 min after 1.5 g oral inosine. Serum urate and fractional excretion of uric acid (FEUA) were analysed according to high BMI (≥ 25 kg/m2) and low/normal BMI (

Abstract Background Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. Methods Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmö Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. Results Five clusters (C1–C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2–C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. Conclusions Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.

Abstract Background The International Classification of Functioning, Disability and Health (ICF) aims to comprehensively describe the ways in which a person’s health condition affects their life. This study aimed to contribute to the development of an ICF core set for gout through patient opinion derived from focus groups and interviews. Methods We conducted a secondary qualitative analysis of data from three studies investigating the patient experience of gout. In total there were 30 individual interviews and 2 focus groups (N = 17) comprising 47 participants. We conducted thematic analysis of the textual data to extract meaning units, which were then linked to the ICF. Results A large number of ICF categories were relevant to patients with gout. Participants mentioned 93 third level categories, 17 of which were mentioned by more than 50% of patients. The most references for a single category was for b280, Sensation of pain, followed by personal factors (not yet categorised by the ICF). The most participants mentioned the environmental factor e355, Health professional support, followed by b280, Sensation of pain. Conclusion The categories identified in this study as relevant to patients with gout highlight the severe pain associated with this disease, the impact on mobility and corresponding life areas. The roles of health professional support, medication, and personal attitudes to disease management are also reflected in the data. These results will contribute to the development of the ICF core set for gout.

The common ABCG2 variant Q141K contributes to hyperuricemia and gout risk. Here, using a human interventional study and a new orthologous mouse model, the authors report a tissue specific pathobiology of the Q141K variant, and support a significant role for ABCG2 in urate excretion in both the kidney and intestine.

Abstract Background Despite contemporary advances in understanding pathogenesis and effective management of gout, beliefs about the disease continue to be focused on gout as a self-inflicted illness. The illness label itself may contribute to inaccurate perceptions of the disease and its management. In Aotearoa/New Zealand, Māori (Indigenous New Zealanders) have high prevalence of severe gout. The aim of this study was to examine the impact of the illness label ‘gout’ on perceptions of the disease and its management for Māori. Methods Māori supermarket shoppers (n = 172) in rural and urban locations were recruited into a study examining the perceptions about arthritis. Participants were randomised 1:1 to complete a questionnaire examining the perceptions of the same illness description labelled as either ‘gout’ or ‘urate crystal arthritis’. Differences between the two illness labels were tested using independent sample t-tests. Results ‘Gout’ was most likely to be viewed as caused by diet, whereas ‘urate crystal arthritis’ was most likely to be viewed as caused by aging. ‘Urate crystal arthritis’ was seen as having a wider range of factors responsible for the illness, including stress or worry, hereditary factors and chance. ‘Gout’ was less likely to be viewed as having a chronic timeline, and was perceived as being better understood. Dietary management strategies were seen as more helpful for management of the gout-labelled illness. Conclusions This study has demonstrated that for Māori, Indigenous New Zealanders who are disproportionately affected by gout, the illness label influences perceptions about gout and beliefs about management.

Abstract Background The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls. Methods We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables. Results In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E− 21 and ORmeta = 1.85, P = 1.3E− 03, respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E− 18) but not in Polynesian (ORmeta = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E− 06), however significantly weaker than ABCG2 rs2231142 141K (P Het = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E− 06). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (P meta = 2.5E− 03). Conclusion These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.

Urate-lowering therapies for the management of gout lead to a reduction in serum urate levels, monosodium urate crystal deposition, and the clinical features of gout, including painful and disabling gout flares, chronic gouty arthritis, and tophi. Thus, disease remission is a potential goal of urate-lowering therapy. In 2016, preliminary gout remission criteria were developed by a large group of rheumatologists and researchers with expertise in gout. The preliminary gout remission criteria were defined as: serum urate < 0.36 mmol/L (6 mg/dL); an absence of gout flares; an absence of tophi; pain due to gout < 2 on a 0–10 scale; and a patient global assessment < 2 on a 0–10 scale over a 12-month period. In this critical review, we describe the development of the preliminary gout remission criteria, the properties of the preliminary gout remission criteria, and clinical studies of gout remission in people taking urate-lowering therapy. We also describe a future research agenda for gout remission.

Tendinopathy is characterised by pathological changes in tendon matrix composition, architecture, and stiffness, alterations in tendon resident cell characteristics, and fibrosis, with inflammation also emerging as an important factor in tendinopathy progression. The sequence of pathological changes in tendinopathy and the cellular effects of the deteriorating matrix are largely unknown. This study investigated the effects of substrate stiffness on tendon-derived cells (TDCs) and THP-1 macrophages using PDMS substrates representing physiological tendon stiffness (1.88 MPa), a stiff gel (3.17 MPa) and a soft gel (0.61 MPa). Human TDCs were cultured on the different gel substrates and on tissue culture plastic. Cell growth was determined by alamarBlue™ assay, cell morphology was analysed in f-actin labelled cells, and phenotypic markers were analysed by real-time PCR. We found that in comparison to TDCs growing on gels with physiological stiffness, cell growth increased on soft gels at 48 h (23%, p = 0.003). Cell morphology was similar on all three gels. SCX expression was slightly reduced on the soft gels (1.4-fold lower, p = 0.026) and COL1A1 expression increased on the stiff gels (2.2-fold, p = 0.041). Culturing THP-1 macrophages on soft gels induced increased expression of IL1B (2-fold, p = 0.018), and IL8 expression was inhibited on the stiffer gels (1.9-fold, p = 0.012). We also found that culturing TDCs on plastic increased cell growth, altered cell morphology, and inhibited the expression of SCX, SOX9, MMP3, and COL3. We conclude that TDCs and macrophages respond to changes in matrix stiffness. The magnitude of responses measured in TDCs were minor on the range of substrate stiffness tested by the gels. Changes in THP-1 macrophages suggested a more inflammatory phenotype on substrates with non-physiological stiffness. Although cell response to subtle variations in matrix stiffness was moderate, it is possible that these alterations may contribute to the onset and progression of tendinopathy.

Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3-5 years apart, followed by an assessment of gout incidence 5-6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9-10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 μmol/L (5.42 mg/dL) vs. 340 μmol/L (5.71 mg/dL), P

Abstract Background Foot problems, including foot pain, structural deformities, skin and nail lesions, and footwear difficulties, are common in people with inflammatory rheumatic diseases. However, dedicated podiatry services are limited, including in Aotearoa New Zealand. This study aimed to evaluate the podiatry service use for people with inflammatory rheumatic diseases who attended a specialist podiatric rheumatology clinic in Aotearoa New Zealand. Methods This retrospective review included people with an inflammatory rheumatic disease who attended the Auckland University of Technology Podiatric Rheumatology Clinic between 2010 and 2021. Data were extracted manually from patients' clinical records, including variables relating to patient characteristics, appointment details, presenting complaint, assessments performed, and treatments provided. Results From 2010 to 2021, 157 people with inflammatory rheumatic diseases attended 1570 appointments. The most common presenting concern was foot pain (reported by n = 121, 77.1% patients during at least one appointment), followed by skin/nail lesions (n = 98, 62.4%) and footwear/orthotic needs (n = 90, 57.3%). A range of podiatric interventions were provided to address foot‐care needs, in which education (n = 151, 96.2%) and general skin/nail care (n = 107, 68.2%) were the most common treatments provided. The majority of patients also received footwear interventions at some point during their period of service provision (n = 96, 61.1%), followed by orthoses, other padding/offloading devices, wound care, exercise prescription and referrals to other health professionals. Conclusions This is the first study to review podiatric service provision for people with inflammatory rheumatic diseases attending a specialist podiatric rheumatology clinic in Aotearoa New Zealand. The results of this study have shown that a podiatry clinic dedicated to people with inflammatory rheumatic diseases addresses the wide range of foot problems through an extensive provision of treatment services.

Abstract Background Colchicine is a widely used drug to treat inflammatory diseases. Due to its long historical use in medicine, controlled clinical trials have been small and there remains some caution with the use of this drug in patients with co-morbidities. The aim of the study is to systematically examine the side effect profile of colchicine in controlled clinical trials across all published indications. Methods A systematic review was conducted in accordance with PRISMA methodology. The Cochrane Library, MEDLINE and EMBASE were searched for double-blind controlled trials of oral colchicine in adult patients that reported adverse event data. Meta-analyses were used to determine the relative risk (RR) of adverse events in colchicine users compared to comparator groups. Results A total of 4915 studies were initially identified and after exclusions, 35 randomised controlled trials with placebo (n = 30) or active comparators (n = 5) were included. The most common diseases studied were gout, liver cirrhosis and pericarditis. There were a total of 8659 pooled participants, 4225 participants were randomised to receive colchicine, 3956 to placebo and 411 to an active comparator. Diarrhoea was reported in 17.9% of colchicine users versus 13.1% in comparator groups (RR 2.4, 95% confidence interval (CI) 1.6, 3.7). Any gastrointestinal event was reported in 17.6% of colchicine users and 13.1% of comparators (RR 1.7, 95% CI 1.3, 2.3). Adverse liver events were reported in 1.9% of colchicine users versus 1.1% in the comparator groups (RR 1.6, 95% CI 0.9, 3.0). Muscle events were reported in 4.2% of colchicine users and 3.3% in the comparator groups (RR 1.3, 95% CI 0.8, 1.9). Haematology events were reported in 0.6% of colchicine users and 0.4% of comparator groups (RR 1.34 (0.64, 2.82). No study reported neuropathy events. Other sensory events were reported in 1.1% of colchicine users and 1.5% of comparator groups (RR 1.4, 95% CI 0.3, 6.7). Infectious events were reported in 0.4% of colchicine users and 2.1% of comparator groups (RR 1.0, 95% CI 0.7, 1.5). No study reported death as an adverse event. Conclusion Colchicine increases the rate of diarrhoea and gastrointestinal adverse events but does not increase the rate of liver, sensory, muscle, infectious or haematology adverse events or death.

Abstract Background Injuries to tendons and ligaments make up a large portion of musculoskeletal injuries, and contribute to significant morbidity and healthcare costs. However, there is currently a poor understanding of the burden of these injuries at a population level. The purpose of this study was to quantify the burden and distribution of tendon and ligament injuries in the Aotearoa/New Zealand population. Methods Using the Accident Compensation Corporation (ACC, a no fault comprehensive compensation scheme encompassing all of Aotearoa/New Zealand; population in 2013 4.4 million) database, data specific to tendon and ligament injuries were identified between July 2010 and June 2016. The total number of claims made and the total cost of these claims per financial year were analyzed. Injuries were categorized by anatomical site, gender, ethnicity and age of the claimant. Results During the 6-year study period, the total number of tendon and ligament injury claims was 1,112,077, with a total cost of over $1.4 billion NZD. There was a 16.2% increase in the number of claims, and a 40% increase in the total cost of these injuries during this period. The majority of claims were made by people of European ethnicity, whilst the number of claims made by people of Asian ethnicity increased at the greatest rate; 52% (from 9047 claims in 2011) during the 6-year study period. Interestingly, Māori (Indigenous New Zealanders) maintained the highest average cost per claim ($1614.05 NZD); 13% more than the overall average cost per claim ($1262.12 NZD). The most common sites of injury were the shoulder and knee; these injuries were also the greatest contributors to overall cost. The total costs of injuries peaked in claimants aged 40–54, irrespective of the number of claims made for that age group. Conclusions Health and economic burdens of tendon and ligament injuries in Aotearoa/New Zealand are rising. The high healthcare costs underscore the urgent need for multifaceted interventions to reduce the incidence and improve clinical outcomes of tendon and ligament injuries.

The aims of this study were to determine factors that predict serum urate (SU) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24‐month open, randomized, controlled, parallel‐group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and SU was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (ROC) curves were used to identify a minimum oxypurinol concentration predictive of SU

Objective To investigate the relationship between stigma perception and demographic, clinical, and psychosocial variables. Methods A sample of 50 patients with gout and prescribed urate‐lowering medication (84% were males, mean serum urate 0.34 mmol/l) completed questionnaires on internalized and anticipated stigma, demographics, clinical gout‐related variables, and psychosocial variables (illness perceptions, illness‐related disability, illness‐related body satisfaction, intentional nonadherence). Serum urate level was obtained from the most recent blood test. Results In this sample, 26% experienced internalized stigma, 26% expected to be stigmatized by friends or family members, and 14% by health care workers. Univariate regression analyses showed that younger age, ethnicity other than New Zealand European, increased severity of gout pain, cognitive and emotional illness perceptions, greater illness‐related disability, and increased intentional nonadherence to urate‐lowering medication were associated with increased internalized and anticipated stigma. Younger age, emotional illness response, and intentional nonadherence were the only variables explaining incremental variance of the experience of anticipated stigma in a multivariate regression model. Conclusion Internalized and anticipated illness‐related stigma was reported by a subgroup of patients with gout. The experience of stigma is associated with younger age, a negative emotional illness response, and intentions to not adhere with a medical treatment.

Abstract Background Reduced renal clearance of uric acid is a major contributor to hyperuricemia. The aim of this study was to examine clinical and genetic variables associated with fractional excretion of uric acid (FEUA). Methods Participants (with and without gout) in the Genetics of Gout in Aotearoa study with available genotyping and FEUA data were included (n = 1713). Ten FEUA-associated loci detected within a genome-wide association study for serum urate in a European population were analysed. A polygenic score for FEUA was calculated in each ancestry group to model the cumulative effects of the genetic variants on FEUA. Associations between FEUA and both clinical variables and polygenic score were tested using linear regression models. Results The mean (SD) FEUA was 5.13 (2.70) % in Eastern Polynesian participants, 4.70 (5.89) % in Western Polynesian participants, and 5.89 (2.73) % in New Zealand European participants. Although association with FEUA was observed for SLC2A9 rs11942223 in New Zealand European participants (P = 2.39 × 10− 8), this association was not observed in Eastern or Western Polynesian participants. The polygenic score was positively associated with FEUA in all ancestry groups. In New Zealand European participants, body mass index, diuretic use, polygenic score, and male sex were associated with FEUA and explained 22% of FEUA variance in the regression model. In Eastern and Western Polynesian participants, the tested variables explained 10% and 4% of FEUA variance respectively. Conclusions Both clinical and genetic variables contribute to renal clearance of uric acid. SLC2A9 exerts effects on FEUA variance in people of European ancestry, but not in those of Polynesian ancestry. There is a large unexplained variance in FEUA, particularly in people of Polynesian ancestry.