A genome-wide association analysis reveals new pathogenic pathways in gout.

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.

Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE: Versus Arthritis.

Effectiveness of footwear and foot orthoses in reducing medial metatarsophalangeal joint pressure in women with hallux valgus.

BACKGROUND: Hallux valgus is a common condition where the subluxation of the first metatarsophalangeal joint and lateral deviation of the hallux at the interphalangeal joint creates difficulty with footwear fit. Footwear and foot orthoses are commonly prescribed nonsurgical treatments for hallux valgus. RESEARCH QUESTION: Do extra-width footwear and foot orthoses influence peak pressure at the medial aspect of the metatarsophalangeal and interphalangeal joints in women with hallux valgus? METHODS: Community-dwelling women with symptomatic hallux valgus underwent gait testing when wearing their own shoes and when wearing extra-width footwear fitted with three-quarter length, arch-contouring prefabricated foot orthoses. Peak pressure (kPa) on the medial aspect of the metatarsophalangeal and medial interphalangeal joints and on the plantar surface of the foot (hallux, lesser toes, metatarsophalangeal joint 1, metatarsophalangeal joints 2-5, midfoot and heel) were measured using the novel pedar®-X system with the pedar® pad and pedar® insole, respectively (Novel, GmbH, Munich, Germany). Paired samples t-tests were used to calculate the differences between the two conditions, and the magnitude of observed differences was calculated using Cohen's d. RESULTS: We tested 28 participants (aged 44-80 years, mean 60.7, standard deviation 10.7). Compared to their own footwear, wearing the intervention footwear and orthoses was associated with a statistically significant decrease in pressure on the medial aspect of the metatarsophalangeal joint (58.3 ± 32.8 versus 42.6 ± 32.8, p=0.026, d=0.49), increased pressure under the midfoot (70.7 ± 25.7 versus 78.7 ± 23.6, p=0.029, d=0.33) and decreased pressure underneath the heel (137.3 ± 39.0 versus 121.3 ± 34.8, p=0.019, d=0.45). SIGNIFICANCE: The intervention footwear and orthoses significantly decreased peak pressure on the medial aspect of the first metatarsophalangeal joint but had no significant effect on the interphalangeal joint. Further studies are required to determine whether these changes are associated with improvements in symptoms associated with hallux valgus.

Health literacy and gout characteristics in a primary care cohort.

Objectives: To examine the cross-sectional association between health literacy and gout characteristics. Methods: In a primary care cohort of adults living with gout, the prevalence of poor health literacy was defined using the Single-Item Literacy Screener (SILS). Multiple logistic regression was used to obtain adjusted odds ratios (ORs) for the cross-sectional associations between health literacy and individual gout characteristics (frequency of flares, age at gout onset, history of oligo-/polyarticular flares, allopurinol use, allopurinol dose and serum urate level) with 95% CIs and adjustment for age, sex, deprivation and further education. Results: Of 551 participants [mean age 54.4 years (s.d. 11.2), 498 (90.4%) male], 163 (30.1%) reported two or more flares in the previous 12 months. Fifty-one (9.4%) had poor health literacy. Poor health literacy was associated with having two or more flares in the preceding 12 months [adjusted OR 4.10 (95% CI 2.04, 8.19)] and a history of oligo-/polyarticular flares [OR 1.93 (95% CI 1.06, 3.55)]. No associations were identified between health literacy and age at gout onset [OR 0.99 (95% CI 0.96, 1.01)], allopurinol use [OR 0.88 (95% CI 0.46, 1.65)] or dose [OR 1.00 OR (95% CI 1.00, 1.00)] or serum urate [most recent serum urate OR 1.0 (95% CI 1.00, 1.00)]. Conclusions: Frequent flares and a history of oligo-/polyarticular flares were associated with poor health literacy. Since health literacy is an important determinant of health outcomes, it is important to consider health literacy when providing information and education to people with gout.

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.

How common are side effects of treatment to prevent gout flares when starting allopurinol?

The studyRoddy E, Bajpai R, Forrester H, et al. 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. Ann Rheum Dis 2023;82:1618-25.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/.

Structural Foot Characteristics in People With Midfoot Osteoarthritis: Cross-Sectional Findings From the Clinical Assessment Study of the Foot.

OBJECTIVE: This study compared radiographic measures of foot structure between people with and without symptomatic radiographic midfoot osteoarthritis (OA). METHODS: This was a cross-sectional study of adults aged 50 years and older registered with four UK general practices who reported foot pain in the past year. Bilateral weightbearing dorsoplantar and lateral radiographs were obtained. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last 4 weeks, combined with radiographic OA in one or more midfoot joints (first cuneometatarsal, second cuneometatarsal, navicular-first cuneiform, and talonavicular). Midfoot OA cases were matched 1:1 for sex and age to controls with a 5-year age tolerance. Eleven radiographic measures were extracted and compared between the groups using independent sample t-tests and effect sizes (Cohen's d). RESULTS: We identified 63 midfoot OA cases (mean ± SD age was 66.8 ± 8.0 years, with 32 male and 31 female participants) and matched these to 63 controls (mean ± SD age was 65.9 ± 7.8 years). There were no differences in metatarsal lengths between the groups. However, those with midfoot OA had a higher calcaneal-first metatarsal angle (d = 0.43, small effect size, P = 0.018) and lower calcaneal inclination angle (d = 0.46, small effect size, P = 0.011) compared with controls. CONCLUSIONS: People with midfoot OA have a flatter foot posture compared with controls. Although caution is required when inferring causation from cross-sectional data, these findings are consistent with a pathomechanical pathway linking foot structure to the development of midfoot OA. Prospective studies are required to determine the temporal relationships between foot structure, function, and the development of this common and disabling condition.

Association of Bone Shape and Alignment Analyzed Using Statistical Shape Modeling With Severity of First Metatarsophalangeal Joint Osteoarthritis.

OBJECTIVE: We aimed to explore the relationship between bone shape and radiographic severity in individuals with first metatarsophalangeal joint osteoarthritis (first MTP joint OA). METHODS: Weightbearing lateral and dorsoplantar radiographs were obtained for the symptomatic foot of 185 participants (105 females, aged 22 to 85 years) with clinically diagnosed first MTP joint OA. Participants were classified into none/mild, moderate, or severe categories using a standardized atlas. An 80-point model for lateral radiographs and 77-point model for dorsoplantar radiographs was used to define independent modes of variation using statistical shape modeling software. Odds ratios adjusted for confounders were calculated using ordinal regression to determine the association between radiographic severity and mode scores. RESULTS: After assessment and grading of radiographs, 35 participants (18.9%) were included in the none/mild first MTP joint OA severity category, 69 (37.2%) in the moderate severity category, and 81 (43.7%) in the severe category. For lateral-view radiographs, 16 modes of variation were included, which collectively represented 83.2% of total shape variance. Of these, four modes were associated with radiographic severity. For dorsoplantar-view radiographs, 15 modes of variation were included, representing 82.6% of total shape variance. Of these, six modes were associated with radiographic severity. CONCLUSIONS: Variations in the shape and alignment of the medial cuneiform, first metatarsal, and proximal and distal phalanx of the hallux are significantly associated with radiographic severity of first MTP joint OA. Prospective studies are required to determine whether bone shape characteristics are associated with the development and/or progression of this condition.

Plantar pressures in people with midfoot osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

BACKGROUND: Midfoot osteoarthritis (OA) is a common condition, however its aetiology is not well understood. Understanding how plantar pressures differ between people with and without midfoot OA may provide insight into the aetiology and how best to manage this condition. RESEARCH QUESTION: To compare plantar pressures between people with and without symptomatic radiographic midfoot OA. METHODS: This was a cross-sectional study of adults aged ≥ 50 years registered with four UK general practices who reported foot pain in the past year. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last four weeks, combined with radiographic OA in one or more midfoot joints. Cases were matched 1:1 for sex and age ( ± 5 years) to controls. Peak plantar pressure and maximum force in 10 regions of the foot were determined using a pressure platform (RSscan International, Olen, Belgium) and compared between the groups using independent samples t-tests and effect sizes (Cohen's d). RESULTS: We included 61 midfoot OA cases (mean age 67.0, SD 8.1, 31 males, 30 females) and matched these to 61 controls (mean age 66.0, SD 7.9). Midfoot OA cases displayed greater force (d=0.79, medium effect size, p = <0.001) and pressure at the midfoot (d=0.70, medium effect size, p = <0.001), greater force at the fourth metatarsophalangeal (MTP) joint (d=0.28, small effect size, p = 0.13), and fifth MTP joint (d=0.37, small effect size, p = 0.10) and greater pressure at the fifth MTP joint (d=0.34, small effect size, p = 0.13). They also displayed lower force (d=0.40, small effect size, p = 0.02) and pressure at the hallux (d=0.50, medium effect size, p = <0.001) and lower force (d=0.54, medium effect size, p = <0.001) and pressure at the lesser toes (d=0.48, small effect size, p = <0.001) compared with controls. SIGNIFICANCE: Midfoot OA appears to be associated with lowering of the medial longitudinal arch, greater lateral push off and less propulsion at toe off. Longitudinal studies are needed to establish causal relationships.

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.

Ankle osteoarthritis: an online survey of current treatment practices of UK-based podiatrists and physiotherapists.

BACKGROUND: Patients with painful ankle osteoarthritis (OA) have a mixed experience of non-surgical management which they may attribute to a lack of guidance for clinicians on usual care treatment. Therefore, the purpose of this study was to survey the current clinical practices of UK-based physiotherapists and podiatrists for the treatment of painful ankle osteoarthritis (OA). METHODS: UK-based physiotherapists and podiatrists who treat patients with ankle OA completed a self-administered online questionnaire about their professional and clinical service characteristics, diagnostic criteria, treatment aims, preferred treatment options, and treatment outcome measures. Data were collected anonymously and stored on JISC online survey. 'Usual care' was defined as a combination of 'Always', and 'Frequently', and 'Not usual care' was defined as 'Sometimes' 'Rarely,' 'Never', and 'not applicable' combined. Statistically significant differences in responses between the physiotherapists and podiatrists were analysed using X2 tests for each treatment modality. Statistical significance was set at p < 0.05. RESULTS: Between 1st June 2021 and 31st August 2021, 100 responses were received; 2 were invalid. Of the 98 valid responses, 63 were from physiotherapists and 35 from podiatrists. The most common treatment aims in both professions were to reduce pain (n = 87, 89%) and improve quality of life (n = 82, 84%). 50 respondents (51%) offered 3 or 4 treatment sessions and 53 respondents (54%) saw patients for 30-40 min at the first treatment session. The five most common modalities used by physiotherapists were patient education (n = 63, 100%), teaching self-management (n = 58, 92%), lifestyle modification (n = 54, 86%), ankle strengthening (n = 55, 87%), and proprioception exercises (n = 54, 86%). For podiatrists, these were patient education (n = 35, 100%), ankle strengthening (n = 31, 89%), activity pacing (n = 28, 80%), lifestyle modification (n = 27, 77%), and gait training (n = 27, 77%). CONCLUSIONS: This first-ever survey revealed physiotherapists' and podiatrists' current practices to treat painful ankle OA. This study provides a better understanding of how ankle OA is treated in UK current clinical practice and can inform future clinical trials to compare current practice with new treatment modalities.

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.

Nonsurgical management of hallux valgus: findings of a randomised pilot and feasibility trial.

BACKGROUND: Hallux valgus is a common and disabling condition. This randomised pilot and feasibility trial aimed to determine the feasibility of conducting a parallel group randomised trial to evaluate the effectiveness of a nonsurgical intervention for reducing pain associated with hallux valgus. METHODS: Twenty-eight community-dwelling women with painful hallux valgus were randomised to receive either a multifaceted, nonsurgical intervention (footwear, foot orthoses, foot exercises, advice, and self-management) or usual care (advice and self-management alone). Outcome measures were obtained at baseline, 4, 8 and 12 weeks. The primary outcome was feasibility, evaluated according to demand (recruitment rate and conversion rate), acceptability, adherence, adverse events, and retention rate. Limited efficacy testing was conducted on secondary outcome measures including foot pain, foot muscle strength, general health-related quality of life, use of cointerventions, and participants' perception of overall treatment effect. RESULTS: Between July 8, 2021, and April 22, 2022, we recruited and tested 28 participants (aged 44 to 80 years, mean 60.7, standard deviation 10.7). This period encompassed two COVID-related stay-at-home orders (July 16 to July 27, and August 5 to October 21, 2021). The predetermined feasibility thresholds were met for retention rate, foot pain, mental health-related quality of life, and use of cointerventions, partly met for acceptability, adverse events, and muscle strength, and not met for demand (recruitment rate or conversion rate), adherence, physical health-related quality of life and perception of overall treatment effect. CONCLUSION: In its current form, a randomised trial of footwear, foot orthoses, foot exercises, advice and self-management for relieving pain associated with hallux valgus is not feasible, particularly due to the low adherence with the intervention. However, it is difficult to determine whether the trial would be feasible under different circumstances, particularly due to COVID-19 stay-at-home orders. Future trials will need to consider improving the aesthetics of the footwear and making the exercise program less burdensome. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ACTRN12621000645853).

Cohort study investigating gout flares and management in UK general practice.

BACKGROUND: Gout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT. METHODS: Using the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression. RESULTS: Fifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5-36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1-17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03-5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3-28.0%): 5.7% (95%CI 5.5-5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares. CONCLUSION: Approximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought.

A multi-professional survey of UK practice in the use of intra-articular corticosteroid injection for symptomatic first metatarsophalangeal joint osteoarthritis.

BACKGROUND: The first metatarsophalangeal joint is the most common site of osteoarthritis (OA) in the foot and ankle. Intra-articular corticosteroid injections are widely used for this condition, but little is known about their use in practice. This study explored current practice within the UK National Health Service (NHS) relating to the administration of intra-articular corticosteroids for people with painful first metatarsophalangeal joint (MTPJ) OA. METHODS: A cross-sectional survey using Qualtrics online survey platform (Qualtrics, Provo, UT, USA), distributed through professional bodies, special interest groups, and social media. RESULTS: One hundred forty-four healthcare professionals responded, including podiatrists (53/144; 39%), orthopaedic surgeons (28/144; 19%), podiatric surgeons (26/144; 17%) and physiotherapists (24/144; 16%). Half of respondents administered up to 25 corticosteroid injections per year (67/136; 49%) but some administered more than fifty (21/136; 15%). Injections were administered across the healthcare system but were most common in hospital settings (64/136; 44%) followed by community (38/136; 26%), with less delivered in primary care (11/136; 8%). Half of respondents routinely used image-guidance, either ultrasound or x-ray/fluoroscopy (65/136; 48%) although over one third used none (52/136; 38%). Imaging guidance was more common amongst medical professionals (21/31; 68%) compared to non-medical health professionals (45/105; 43%). Overall, methylprednisolone acetate was the most common corticosteroid used. Medical professionals mostly injected methylprednisolone acetate (n = 15/27; 56%) or triamcinolone acetonide (n = 11/27; 41%), whereas premixed methylprednisolone acetate with lidocaine hydrochloride was the most common preparation used by non-medical health professionals (41/85; 48%). When injecting non premixed steroid, lidocaine hydrochloride (15/35; 43%) was the most common choice of local anaesthetic for non-medical health professionals but medical professionals showed more variation between lidocaine hydrochloride (8/23; 35%) levobupivacaine hydrochloride (9/23; 39%) and bupivacaine hydrochloride (5/23; 22%). CONCLUSIONS: Multiple professional groups regularly administer intra-articular corticosteroids for symptomatic first MTPJ OA across a range of NHS healthcare settings. Overall, methylprednisolone acetate was the most commonly administered steroid and lidocaine hydrochloride the most common local anaesthetic. There was large variation in the use of imaging guidance, type and dose of steroid, local anaesthetic, and clinical pathways used in the intra-articular injection of corticosteroids for people with first MTPJ OA.

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.

Experiences of living with hip osteoarthritis and of receiving advice, education and ultrasound-guided intra-articular hip injection in the hip injection trial. A qualitative study.

OBJECTIVES: The Hip Injection Trial (HIT) compared the effectiveness of adding a single ultrasound-guided intra-articular injection of either corticosteroid and local anaesthetic or local anaesthetic alone to advice and education among people with hip osteoarthritis (OA). This nested qualitative study explored participants' experiences of living with hip OA and of the trial treatment they received. METHOD: Semi-structured telephone interviews were undertaken with a purposeful sample of trial participants after a 2-month trial follow-up. Interviewers were blinded to which injection participants had received. Thematic analysis using constant comparison was undertaken prior to knowing the trial results. RESULTS: 34 trial participants were interviewed across all arms. OA causes pain, physical limitations, difficulties at work, lowered mood, and disrupted sleep. Those who received advice and education alone felt that they had not received 'treatment' and described little/no benefit. Participants in both injection groups described marked improvements in pain, physical function, and other aspects of life (e.g., sleep, confidence). The perceived magnitude of benefit appeared greater among those who received the corticosteroid injection; however, the length of benefit varied in both injection groups. There was uncertainty about the longer-term benefits of injection and repeated injections. CONCLUSION: Hip OA is highly burdensome. Participants perceived little/no benefit from advice and education alone but reported marked improvements when combined with either injection. However, the magnitude of benefit was greater among those who received corticosteroid. The varying duration of response to injection and uncertainty regarding longer-term benefits of injection and repeated injections suggests that these areas are important for future research. TRIAL REGISTRATION: EudraCT 2014-003412-37; ISRCTN50550256.

Impact of Frailty on Emergency Department Encounters for Cardiovascular Disease: A Retrospective Cohort Study.

Data are limited on whether the causes of emergency department (ED) encounters for cardiovascular diseases (CVDs) and associated clinical outcomes vary by frailty status. Using the United States Nationwide ED Sample, selected CVD encounters (acute myocardial infarction [AMI], ischemic stroke, atrial fibrillation [AF], heart failure [HF], pulmonary embolism, cardiac arrest, and hemorrhagic stroke) were stratified by hospital frailty risk score (HFRS). Logistic regression was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ED mortality among the different frailty groups. A total of 8,577,028 selected CVD ED encounters were included. A total of 5,120,843 (59.7%) had a low HFRS (<5), 3,041,699 (35.5%) had an intermediate HFRS (5 to 15), and 414,485 (4.8%) had a high HFRS (>15). Ischemic stroke was the most common reason for the encounter in the high HFRS group (66.9%), followed by hemorrhagic stroke (11.7%) and AMI (7.2%). For the low HFRS group, AF was the most common reason for the encounter (30.2%), followed by AMI (23.6%) and HF (16.8%). Compared with the low-risk group, high-risk patients had a decreased ED mortality and an increased overall mortality across most CVD encounters (p <0.001). The strongest association with overall mortality was observed among patients with a high HFRS admitted for AF (aOR 27.14, 95% CI 25.03 to 29.43) and HF (aOR 13.71, 95% CI 12.95 to 14.51) compared with their low-risk counterparts. In conclusion, patients presenting to the ED with acute CVD have a significant frailty burden, with different patterns of CVD according to frailty status. Frailty is associated with an increased all-cause mortality in patients for most CVD encounters.