Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

OBJECTIVES: Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. METHODS: We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. RESULTS: From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. CONCLUSION: People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink.

OBJECTIVES: To determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout. METHODS: We conducted two matched retrospective cohort studies in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with (1) colchicine or (2) NSAID prophylaxis were compared with those initiating without prophylaxis, individually matched by age, sex and propensity to receive the relevant prophylaxis. Weighted Cox proportional hazards models investigated associations between colchicine/NSAID and specified adverse events. RESULTS: 13 945 individuals prescribed colchicine were matched to 13 945 with no prophylaxis and 25 980 prescribed NSAID to 25 980 with no prophylaxis. Adverse event incidence rates were <200/10 000 patient-years except diarrhoea (784.4; 95% CI 694.0 to 886.5) and nausea (208.1; 95% CI 165.4 to 261.7) for colchicine and angina for NSAID (466.6; 95% CI 417.2 to 521.8). Diarrhoea (HR 2.22; 95% CI 1.83 to 2.69), myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17), neuropathy (4.75; 95% CI 1.20 to 18.76), myalgia (2.64; 95% CI 1.45 to 4.81), bone marrow suppression (3.29; 95% CI 1.43 to 7.58) and any adverse event (1.91, 95% CI 1.65 to 2.20) were more common with colchicine than no prophylaxis, but not nausea/vomiting (1.34; 95% CI 0.97 to 1.85). Angina (1.60; 95% CI 1.37 to 1.86), acute kidney injury (1.56; 95% CI 1.20 to 2.03), MI (1.89; 95% CI 1.44 to 2.48), peptic ulcer disease (1.67; 95% CI 1.14 to 2.44) and any adverse event (1.63; 95% CI 1.44 to 1.85) were more common with NSAID than without. CONCLUSIONS: Adverse events were more common when allopurinol was initiated with prophylaxis, particularly diarrhoea with colchicine. Other events were uncommon, providing reassurance for patients and clinicians to enable shared decision-making.

Treat-to-target urate-lowering therapy and hospitalizations for gout: results from a nationwide cohort study in England.

OBJECTIVE: To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout. METHODS: Using linked Clinical Practice Research Datalink and NHS Digital Hospital Episode Statistics data, we described the incidence and timing of hospitalizations for flares in people with index gout diagnoses in England from 2004-2020. Using Cox proportional hazards and propensity models, we investigated associations between ULT initiation, serum urate target attainment, colchicine prophylaxis, and the risk of hospitalizations for gout. RESULTS: Of 292 270 people with incident gout, 7719 (2.64%) had one or more hospitalizations for gout, with an incidence rate of 4.64 hospitalizations per 1000 person-years (95% CI 4.54, 4.73). There was an associated increased risk of hospitalizations within the first 6 months after ULT initiation, when compared with people who did not initiate ULT [adjusted Hazard Ratio (aHR) 4.54; 95% CI 3.70, 5.58; P < 0.001]. Hospitalizations did not differ significantly between people prescribed vs not prescribed colchicine prophylaxis in fully adjusted models. From 12 months after initiation, ULT associated with a reduced risk of hospitalizations (aHR 0.77; 95% CI 0.71, 0.83; P < 0.001). In ULT initiators, attainment of a serum urate <360 micromol/l within 12 months of initiation associated with a reduced risk of hospitalizations (aHR 0.57; 95% CI 0.49, 0.67; P < 0.001) when compared with people initiating ULT but not attaining this target. CONCLUSION: ULT associates with an increased risk of hospitalizations within the first 6 months of initiation but reduces hospitalizations in the long term, particularly when serum urate targets are achieved.

The effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome: 24-month follow-up of a randomized trial.

OBJECTIVES: This follow-up study of the INSTinCTS (INjection vs SplinTing in Carpal Tunnel Syndrome) trial compared the effects of corticosteroid injection (CSI) and night splinting (NS) for the initial management of mild-to-moderate CTS on symptoms, resource use and carpal tunnel surgery, over 24 months. METHODS: Adults with mild-to-moderate CTS were randomized 1:1 to a local corticosteroid injection or a night splint worn for 6 weeks. Outcomes at 12 and 24 months included the Boston Carpal Tunnel Questionnaire (BCTQ), hand/wrist pain intensity numeric rating scale (NRS), the number of patients referred for and undergoing CTS surgery, and healthcare utilization. A cost-utility analysis was conducted. RESULTS: One hundred and sixteen participants received a CSI and 118 a NS. The response rate at 24 months was 73% in the CSI arm and 71% in the NS arm. By 24 months, a greater proportion of the CSI group had been referred for (28% vs 20%) and undergone (22% vs 16%) CTS surgery compared with the NS group. There were no statistically significant between-group differences in BCTQ score or pain NRS at 12 or 24 months. CSI was more costly [mean difference £68.59 (95% CI: -120.84, 291.24)] with fewer quality-adjusted life-years than NS over 24 months [mean difference -0.022 (95% CI: -0.093, 0.045)]. CONCLUSION: Over 24 months, surgical intervention rates were low in both groups, but less frequent in the NS group. While there were no differences in the clinical effectiveness of CSI and NS, initial treatment with CSI may not be cost-effective in the long-term compared with NS.

Factors associated with change in health-related quality of life in people with gout: a 3-year prospective cohort study in primary care.

OBJECTIVE: To describe factors associated with change in health-related quality of life (HRQOL) in people living with gout in primary care. METHODS: In a UK prospective cohort study, adults with a diagnosis of gout registered with 20 general practices completed the Gout Impact Scale (GIS; scale 0-100), 36-item Short Form Physical Function subscale (PF-10; 0-100) and HAQ Disability Index (HAQ-DI; 0-3) via postal questionnaires at baseline and 6, 12, 24 and 36 months. Linear mixed modelling was used to investigate factors associated with changes in HRQOL over 3 years. RESULTS: A total of 1184 participants responded at baseline (adjusted response 65.6%); 990 (83.6%) were male, with a mean age of 65.6 years (s.d. 12.5). A total of 818, 721, 696 and 605 responded at 6, 12, 24 and 36 months, respectively. Factors associated with worse disease-specific and generic HRQOL over 3 years were flare frequency (five or more flares; GIS subscales, PF-10), oligo/polyarticular flares (GIS subscales, PF-10, HAQ-DI), worse pain (GIS subscales, PF-10, HAQ-DI), body pain (GIS subscales, PF-10, HAQ-DI) and more severe depression (GIS subscales, PF-10, HAQ-DI) (P ≤ 0.05). More severe anxiety was associated with worse disease-specific HRQOL only (GIS subscales). Older age (PF-10), being female (PF-10, HAQ-DI) and BMI (HAQ-DI) were associated with worse generic HRQOL (P ≤ 0.05). CONCLUSION: Gout-specific, comorbid and sociodemographic factors were associated with change in HRQOL over a 3-year period, highlighting people at risk of worse outcomes who could be targeted for interventions.

The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis.

OBJECTIVES: Evidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT) comprising advice and education plus a single ultrasound-guided intra-articular hip injection (USGI) of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T) versus BCT alone. METHODS: A trial-based cost-utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a United Kingdom (UK) National Health Service (NHS) perspective. RESULTS: BCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: £-161.6, 95% CI: £-583.95 to £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487, 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists, and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T. CONCLUSION: Intra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone. TRIAL REGISTRATION: EudraCT: 2014-003412-37 (August 8, 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (July 28, 2015). TRIAL PROTOCOL: Full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0#citeas. DOI: doi.org/10.1186/s12891-018-2153-0.

Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares.

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations for gout flares. METHODS: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment, and re-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and a retrospective cohort of hospitalised patients from 12 months pre-implementation. RESULTS: 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio (aOR) 11.5; 95% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/L within 6 months of discharge (10.6% pre-implementation vs. 26.8% post-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients re-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed.

Improving outcomes for patients hospitalized with gout: a systematic review.

OBJECTIVES: Hospital admissions for gout flares have increased dramatically in recent years, despite widely available, effective medications for the treatment and prevention of flares. We conducted a systematic review to evaluate the effectiveness and implementation of interventions in patients hospitalized for gout flares. METHODS: A search was conducted in MEDLINE, Embase and the Cochrane library, from database inception to 8 April 2021, using the terms 'gout' and 'hospital' and their synonyms. Studies were included if they evaluated the effectiveness and/or implementation of interventions during hospital admissions or emergency department attendances for gout flares. Risk of bias assessments were performed for included studies. RESULTS: Nineteen articles were included. Most studies were small, retrospective analyses performed in single centres, with concerns for bias. Eleven studies (including five randomized controlled trials) reported improved patient outcomes following pharmacological interventions with known efficacy in gout, including allopurinol, prednisolone, NSAIDs and anakinra. Eight studies reported improved outcomes associated with non-pharmacological interventions: inpatient rheumatology consultation and a hospital gout management protocol. No studies to date have prospectively evaluated strategies designed to prevent re-admissions of patients hospitalized for gout flares. CONCLUSION: There is an urgent need for high-quality, prospective studies of strategies for improving uptake of urate-lowering therapies in hospitalized patients, incorporating prophylaxis against flares and treat-to-target optimization of serum urate levels. Such studies are essential if the epidemic of hospital admissions from this treatable condition is to be countered.

Onset of comorbidities and flare patterns within pre-existing morbidity clusters in people with gout: 5-year primary care cohort study.

OBJECTIVE: To investigate the onset of comorbidities and pattern of flares over 5 years according to baseline comorbidity clusters in people with gout. METHODS: In a prospective primary care-based cohort study, adults aged ≥18 years with gout were identified from primary care medical records in 20 general practices across the West Midlands, UK and followed up over 5 years. Four clusters of participants have been defined previously according to baseline comorbidity status. The associations of (i) incident comorbidities and (ii) gout flares with baseline cluster membership were estimated using age and sex-adjusted Poisson regression and mixed effects ordinal logistic regression, respectively. RESULTS: The comorbidity with the highest incidence was coronary artery disease (39.2%), followed by hypertension (36.7%), chronic kidney disease stage ≥3 (18.1%), obesity (16.0%), hyperlipidaemia (11.7%), diabetes (8.8%) and cancer (8.4%). There were statistically significant associations observed between cluster membership and incidence of coronary artery disease, hyperlipidaemia, heart failure and hypertension. In each cluster, nearly one-third of participants reported two or more gout flares at each time-point. History of oligo/polyarticular flares (odds ratio [OR]= 2.16, 95% confidence interval [CI]: 1.73, 2.70) and obesity (1.66, 95% CI: 1.21, 2.25) were associated with increasing flares whereas current use of allopurinol was associated with lower risk (0.42, 95% CI: 0.34-0.53). Cluster membership was not associated with flares. CONCLUSION: Substantial numbers of people in each cluster developed new comorbidities that varies by cluster membership. People also experienced multiple flares over time, but these did not differ between clusters. Clinicians should be vigilant for the development of new comorbidities in people with gout.

The cost-effectiveness of different approaches to exercise and corticosteroid injection for subacromial pain (impingement) syndrome.

OBJECTIVES: To determine whether physiotherapist-led exercise intervention and US-guided subacromial CS injection is cost-effective when compared with standard advice and exercise leaflet and unguided injection in patients with subacromial pain (impingement) syndrome. METHODS: An incremental cost-utility analysis using patient responses to the five-level EuroQoL-5D (EQ-5D-5L) questionnaire was undertaken from a healthcare perspective alongside a 2 × 2 factorial randomized trial with 256 participants over a 12-month follow-up period. Uncertainty was explored through the use of cost-effectiveness acceptability curves. RESULTS: The cost-utility analysis indicated that physiotherapist-led exercise was associated with an incremental cost of £155.99 (95% CI 69.02, 241.93) and 0.031 (95% CI -0.01, 0.07) additional quality-adjusted life-years (QALYs), an incremental cost-effectiveness ratio (ICER) of £5031 per QALY gained and an 85% chance of being cost-effective at a threshold of £20 000 per QALY gained compared with the advice and exercise leaflet. US-guided injection was associated with an incremental cost of £15.89 (95% CI -59.36, 109.86) and 0.024 (95% CI -0.02, 0.07) additional QALYs, an ICER of £662 per QALY gained and a 83% chance of being cost-effective at a threshold of £20 000 per QALY gained compared with unguided injection. CONCLUSION: Physiotherapist-led exercise was cost-effective compared with the advice and exercise leaflet, and US-guided injection was cost-effective when compared with unguided injection. CLINICAL TRIAL REGISTRATION: ISRCTN, http://www.isrctn.com, ISRCTN42399123.

Optimising outcomes of exercise and corticosteroid injection in patients with subacromial pain (impingement) syndrome: a factorial randomised trial.

OBJECTIVES: To compare the clinical effectiveness of (1) physiotherapist-led exercise versus an exercise leaflet, and (2) ultrasound-guided subacromial corticosteroid injection versus unguided injection for pain and function in subacromial pain (formerly impingement) syndrome (SAPS). METHODS: This was a single-blind 2×2 factorial randomised trial. Adults with SAPS were randomised equally to one of four treatment groups: (1) ultrasound-guided corticosteroid injection and physiotherapist-led exercise, (2) ultrasound-guided corticosteroid injection and an exercise leaflet, (3) unguided corticosteroid injection and physiotherapist-led exercise and (4) unguided corticosteroid injection and an exercise leaflet. The primary outcome was the Shoulder Pain and Disability Index (SPADI), collected at 6 weeks, 6 and 12 months and compared at 6 weeks for the injection interventions and 6 months for the exercise interventions by intention to treat. RESULTS: We recruited 256 participants (64 treatment per group). Response rates for the primary outcome were 94% at 6 weeks, 88% at 6 months and 80% at 12 months. Greater improvement in total SPADI score was seen with physiotherapist-led exercise than with the exercise leaflet at 6 months (adjusted mean difference -8.23; 95% CI -14.14 to -2.32). There were no significant differences between the injection groups at 6 weeks (-2.04; -7.29 to 3.22), 6 months (-2.36; -8.16 to 3.44) or 12 months (1.59; -5.54 to 8.72). CONCLUSIONS: In patients with SAPS, physiotherapist-led exercise leads to greater improvements in pain and function than an exercise leaflet. Ultrasound guidance confers no additional benefit over unguided corticosteroid injection. TRIAL REGISTRATION NUMBER: ISRCTN42399123.

Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care.

OBJECTIVES: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care. METHODS: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat. RESULTS: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54). CONCLUSION: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications. TRIAL REGISTRATION NUMBER: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95).

Percutaneous coronary intervention outcomes in patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: Patients with autoimmune rheumatic disease (AIRD) are at an increased risk of coronary artery disease. The present study sought to examine the prevalence and outcomes of AIRD patients undergoing percutaneous coronary intervention (PCI) from a national perspective. METHODS: All PCI-related hospitalizations recorded in the US National Inpatient Sample (2004-2014) were included, stratified into four groups: no AIRD, RA, SLE and SSc. We examined the prevalence of AIRD subtypes and assessed their association with in-hospital adverse events using multivariable logistic regression [odds ratios (OR) (95% CI)]. RESULTS: Patients with AIRD represented 1.4% (n = 90 469) of PCI hospitalizations. The prevalence of RA increased from 0.8% in 2004 to 1.4% in 2014, but other AIRD subtypes remained stable. In multivariable analysis, the adjusted odds ratio (aOR) of in-hospital complications [aOR any complication 1.13 (95% CI 1.01, 1.26), all-cause mortality 1.32 (1.03, 1.71), bleeding 1.50 (1.30, 1.74), stroke 1.36 (1.14, 1.62)] were significantly higher in patients with SSc compared with those without AIRD. There was no difference in complications between the SLE and RA groups and those without AIRD, except higher odds of bleeding in SLE patients [aOR 1.19 (95% CI 1.09, 1.29)] and reduced odds of all-cause mortality in RA patients [aOR 0.79 (95% CI 0.70, 0.88)]. CONCLUSION: In a nationwide cohort of US hospitalizations, we demonstrate increased rates of all adverse clinical outcomes following PCI in people with SSc and increased bleeding in SLE. Management of such patients should involve a multiteam approach with rheumatologists.

The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial.

BACKGROUND: To our knowledge, the comparative effectiveness of commonly used conservative treatments for carpal tunnel syndrome has not been evaluated previously in primary care. We aimed to compare the clinical and cost-effectiveness of night splints with a corticosteroid injection with regards to reducing symptoms and improving hand function in patients with mild or moderate carpal tunnel syndrome. METHODS: We did this randomised, open-label, pragmatic trial in adults (≥18 years) with mild or moderate carpal tunnel syndrome recruited from 25 primary and community musculoskeletal clinics and services. Patients with a new episode of idiopathic mild or moderate carpal tunnel syndrome of at least 6 weeks' duration were eligible. We randomly assigned (1:1) patients (permutated blocks of two and four by site) with an online web or third party telephone service to receive either a single injection of 20 mg methylprednisolone acetate (from 40 mg/mL) or a night-resting splint to be worn for 6 weeks. Patients and clinicians could not be masked to the intervention. The primary outcome was the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. We used intention-to-treat analysis, with multiple imputation for missing data, which was concealed to treatment group allocation. The trial is registered with the European Clinical Trials Database, number 2013-001435-48, and ClinicalTrial.gov, number NCT02038452. FINDINGS: Between April 17, 2014, and Dec 31, 2016, 234 participants were randomly assigned (118 to the night splint group and 116 to the corticosteroid injection group), of whom 212 (91%) completed the BCTQ at 6 weeks. The BCTQ score was significantly better at 6 weeks in the corticosteroid injection group (mean 2·02 [SD 0·81]) than the night splint group (2·29 [0·75]; adjusted mean difference -0·32; 95% CI -0·48 to -0·16; p=0·0001). No adverse events were reported. INTERPRETATION: A single corticosteroid injection shows superior clinical effectiveness at 6 weeks compared with night-resting splints, making it the treatment of choice for rapid symptom response in mild or moderate carpal tunnel syndrome presenting in primary care. FUNDING: Arthritis Research UK.

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.

Coexistence of plantar calcaneal spurs and plantar fascial thickening in individuals with plantar heel pain.

Objectives: To examine associations between plantar calcaneal spurs, plantar fascia thickening and plantar heel pain (PHP), and to determine whether tenderness on palpation of the heel differentiates between these presentations. Methods: Adults aged ⩾50 years registered with four general practices were mailed a Health Survey. Responders reporting foot pain within the last 12 months underwent a detailed clinical assessment. PHP in the past month was documented using a foot manikin. Plantar calcaneal spurs were identified from weight-bearing lateral radiographs and plantar fascia thickening (defined as >4 mm) from ultrasound. Tenderness on palpation of the plantar fascia insertion was documented. Associations between these factors and PHP were explored using generalized estimating equations. Results: Clinical and radiographic data were available from 530 participants (296 women, mean [s.d.] age 64.9 [8.4] years), 117 (22.1%) of whom reported PHP. Plantar calcaneal spurs and plantar fascia thickening were identified in 281 (26.5%) and 501 (47.3%) feet, respectively, but frequently coexisted (n = 217, 20.4%). Isolated plantar calcaneal spurs were rare (n = 64, 6.0%). Participants with PHP were more likely to have a combination of these features compared with those without PHP (odds ratio 2.16, 95% CI 1.24, 3.77, P = 0.007). Tenderness on palpation of the heel was not associated with plantar calcaneal spurs or plantar fascia thickening, either in isolation or in combination, in those with PHP. Conclusion: Plantar calcaneal spurs and plantar fascial thickening are associated with PHP, but frequently coexist. Tenderness on palpation of the heel does not appear to differentiate between clinical presentations of PHP.

Venous thromboembolism in patients with gout and the impact of hospital admission, disease duration and urate-lowering therapy.

BACKGROUND: Systemic inflammatory diseases have been associated with increased risk of venous thromboembolism. We aimed to quantify the risk of venous thromboembolism in patients with gout, the most common inflammatory arthritis, and to assess how disease duration, hospital admission and urate-lowering therapy affect this risk. METHODS: We used data from the population-representative, England-based Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify incident gout cases between 1998 and 2017. We matched cases individually to 1 control without gout on age, gender, general practice and follow-up time. We calculated absolute and relative risks of venous thromboembolism, stratified by age, gender and hospital admission. Among those with gout, we assessed the risk of venous thromboembolism by exposure to urate-lowering therapy. RESULTS: We identified 62 234 patients with incident gout matched to 62 234 controls. Gout was associated with higher risk of venous thromboembolism compared with controls (absolute rate 37.3 [95% confidence interval (CI) 35.5-39.3] v. 27.0 [95% CI 25.5-28.9] per 10 000 person-years, adjusted hazard ratio [HR] 1.25, 95% CI 1.15-1.35). The excess risk in patients with gout, which was sustained up to a decade after diagnosis, was present during the time outside hospital stay (adjusted HR 1.30, 95% CI 1.18-1.42), but not during it (adjusted HR 1.01, 95% CI 0.83-1.24). The risk of venous thromboembolism was similar among patients prescribed versus not prescribed urate-lowering therapy (incidence rate ratio 1.04, 95% CI 0.89-1.23). INTERPRETATION: Gout was associated with higher risk of venous thromboembolism, particularly when the patient was not in hospital and regardless of exposure to urate-lowering therapy. Although the observed excess risk may not be sufficient to warrant preventive intervention, clinical vigilance may be required when caring for these patients.

Plantar heel pain in middle-aged and older adults: population prevalence, associations with health status and lifestyle factors, and frequency of healthcare use.

BACKGROUND: The objectives of this study were to estimate the population prevalence and distribution of plantar heel pain in mid-to-older age groups, examine associations with selected health status and lifestyle factors, and report the frequency of healthcare use. METHODS: Adults aged ≥50 years registered with four general practices were mailed a health survey (n = 5109 responders). Plantar heel pain in the last month was defined by self-reported shading on a foot manikin, and was defined as disabling if at least one of the function items of the Manchester Foot Pain and Disability Index were also reported. Population prevalence estimates and associations between plantar heel pain and demographic characteristics, health status measures and lifestyle factors were estimated using multiple imputation and weighted logistic regression. Healthcare professional consultation was summarised as the 12-month period prevalence of foot pain-related consultation. RESULTS: The population prevalence of plantar heel pain was 9.6% (95% CI: 8.8, 10.5) and 7.9% (7.1, 8.7) for disabling plantar heel pain. Occurrence was slightly higher in females, comparable across age-groups, and significantly higher in those with intermediate/routine and manual occupations. Plantar heel pain was associated with physical and mental impairment, more anxiety and depression, being overweight, a low previous use of high-heeled footwear, and lower levels of physical activity and participation. The 12-month period prevalence of foot pain-related consultation with a general practitioner, physiotherapist or podiatrist/chiropodist was 43.0, 15.1 and 32.8%, respectively. CONCLUSIONS: Plantar heel pain is a common, disabling symptom among adults aged 50 years and over. Observed patterns of association indicate that in addition to focused foot-specific management, primary care interventions should also target more general physical and psychological factors that could potentially act as barriers to treatment adherence and recovery.

Comparative effectiveness of treatment options for plantar heel pain: a systematic review with network meta-analysis.

OBJECTIVE: To evaluate the comparative effectiveness of current treatment options for plantar heel pain (PHP). DESIGN: Systematic review and network meta-analysis (NMA). DATA SOURCES: Medline, EMBASE, CINAHL, AMED, PEDro, Cochrane Database, Web of Science and WHO Clinical Trials Platform were searched from their inception until January 2018. STUDY SELECTION: Randomised controlled trials (RCTs) of adults with PHP investigating common treatments (ie, corticosteroid injection, non-steroidal anti-inflammatory drugs, therapeutic exercise, orthoses and/or extracorporeal shockwave therapy (ESWT)) compared with each other or a no treatment, placebo/sham control. DATA EXTRACTION AND ANALYSIS: Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random effects NMA in the short term, medium term and long term. Relative ranking of treatments was assessed by surface under the cumulative ranking probabilities (0-100 scale). RESULTS: Thirty-one RCTs (total n=2450 patients) were included. There was no evidence of inconsistency detected between direct and indirect treatment comparisons in the networks, but sparse data led to frequently wide CIs. Available evidence does not suggest that any of the commonly used treatments for the management of PHP are better than any other, although corticosteroid injections, alone or in combination with exercise, and ESWT were ranked most likely to be effective for the management of short-term, medium-term and long-term pain or function; placebo/sham/control appeared least likely to be effective; and exercise appeared to only be beneficial for long-term pain or function. CONCLUSIONS: Current evidence is equivocal regarding which treatment is the most effective for the management of PHP. Given limited understanding of long-term effects, there is need for large, methodologically robust multicentre RCTs investigating and directly comparing commonly used treatments for the management of PHP. PROSPERO REGISTRATION NUMBER: CRD42016046963.

Risk of fracture among patients with polymyalgia rheumatica and giant cell arteritis: a population-based study.

BACKGROUND: Glucocorticoids are associated with increased fracture risk and are the mainstay of treatment in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). However, fracture risk in these conditions has not been previously quantified. The aim of this study was to quantify the risk of fracture among patients with PMR and GCA. METHODS: A retrospective cohort study was conducted using primary care records from the UK-based Clinical Practice Research Datalink. Individuals aged 40 years and over, with incident diagnoses of PMR or GCA were separately identified from 1990-2004 and followed up until 2015. For each exposed individual, four age-, sex- and practice-matched controls were randomly selected. Incidence rates of fracture per 10,000 person-years were calculated for each disease group and hazard rates were compared to the unexposed using Cox regression models. RESULTS: Overall, 12,136 and 2673 cases of PMR and GCA, respectively, were identified. The incidence rate of fracture was 148.05 (95% CI 141.16-155.28) in PMR and 147.15 (132.91-162.91) in GCA per 10,000 person-years. Risk of fracture was increased by 63% in PMR (adjusted hazard ratio 1.63, 95% CI 1.54-1.73) and 67% in GCA (1.67, 1.49-1.88) compared to the control populations. Fewer than 13% of glucocorticoid-treated cases were prescribed bisphosphonates. CONCLUSIONS: This study reports, for the first time, a similar increase in fracture risk for patients with PMR and GCA. More needs to be done to improve adherence to guidelines to co-prescribe bisphosphonates. Further research needs to identify whether lower glucocorticoid starting doses and/or aggressive dose reduction reduces fracture risk.