Sex and country differences in gout: cross-country comparison between Sweden and the UK.

OBJECTIVE: Compare characteristics, sex differences, and management of gout in Sweden and the UK. METHOD: The results from two separate primary care gout surveys from Sweden and the UK were compared. Participants aged ≥18 years with gout were sent a questionnaire asking about lifestyle, gout characteristics, uratelowering therapy (ULT), comorbidities, disability, and disease impact. For sex comparison, participants were pooled across countries. RESULTS: In total, 784 (80% male) participants from Sweden and 500 (87% male) from the UK were included. Swedish patients were significantly older at gout onset, mean (SD) age 72 (12) versus 63 (13) years, (p<0.0001), with more comorbidities, and more frequent use of ULT (48% vs 35%, p=0.0005, age-adjusted). Use of alcohol and diuretics was significantly more common among UK patients, who also reported a higher number of gout flares, mean (SD) 2.2 (1.7) versus 1.6 (3.6), (p=0.003) age-adjusted. Females with gout were older at gout onset, mean (SD) age 67 (13) versus 56 (15), (p<0.0001), more often obese, and reported higher use of diuretics. Furthermore, females reported greater impact of gout, more pain and physical limitations, whereas no sex differences were seen in ULT or flares. CONCLUSIONS: In the UK, gout was more frequently associated with modifiable risk factors. People with gout in Sweden were more commonly taking ULT and had lower frequency of gout flares and impact of gout. Females with gout more commonly took diuretics, had higher body mass index, and reported greater physical disability, which should be considered when managing gout in women.

International Foot and Ankle Osteoarthritis Consortium review and research agenda for diagnosis, epidemiology, burden, outcome assessment and treatment.

OBJECTIVE: To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research. METHOD: Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0 = not at all important to 100 = extremely important). Items scoring a mean of 70 or above were selected for inclusion. RESULTS: Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold: three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment. CONCLUSIONS: Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Shoe-stiffening inserts for first metatarsophalangeal joint osteoarthritis: a randomised trial.

OBJECTIVE: To evaluate the efficacy of carbon-fibre shoe-stiffening inserts in individuals with first metatarsophalangeal joint osteoarthritis. DESIGN: This was a randomised, sham-controlled, participant- and assessor-blinded trial. One hundred participants with first metatarsophalangeal joint osteoarthritis received rehabilitation therapy and were randomised to receive either carbon fibre shoe-stiffening inserts (n = 49) or sham inserts (n = 51). The primary outcome measure was the Foot Health Status Questionnaire (FHSQ) pain domain assessed at 12 weeks. RESULTS: All 100 randomised participants (mean age 57.5 (SD 10.3) years; 55 (55%) women) were included in the analysis of the primary outcome. At the 12 week primary endpoint, there were 13 drop-outs (7 in the sham insert group and 6 in the shoe-stiffening insert group), giving completion rates of 86 and 88%, respectively. Both groups demonstrated improvements in the FHSQ pain domain score at each follow-up period, and there was a significant between-group difference in favour of the shoe-stiffening insert group (adjusted mean difference of 6.66 points, 95% CI 0.65 to 12.67, P = 0.030). There were no between-group differences for the secondary outcomes, although global improvement was more common in the shoe-stiffening insert group compared to the sham insert group (61 vs 34%, RR 1.73, 95% CI 1.05 to 2.88, P = 0.033; number needed to treat 4, 95% CI 2 to 16). CONCLUSION: Carbon-fibre shoe-stiffening inserts were more effective at reducing foot pain than sham inserts at 12 weeks. These results support the use of shoe-stiffening inserts for the management of this condition, although due to the uncertainty around the effect on the primary outcome, some individuals may not experience a clinically worthwhile improvement.

Midfoot osteoarthritis: potential phenotypes and their associations with demographic, symptomatic and clinical characteristics.

OBJECTIVE: To investigate the demographic, symptomatic, clinical and structural foot characteristics associated with potential phenotypes of midfoot osteoarthritis (OA). DESIGN: Cross-sectional study of 533 community-dwelling adults aged ≥50 years with foot pain in the past year. Health questionnaires and clinical assessments of symptoms, foot structure and function were undertaken. Potential midfoot OA phenotypes were defined by the pattern of radiographic joint involvement affecting either the medial midfoot (talonavicular, navicular-1st cuneiform, or cuneiform-1st metatarsal joint), central midfoot (2nd cuneiform-metatarsal joint), or both medial and central midfoot joints. Multivariable regression models with generalised estimating equations were used to investigate the associations between patterns of midfoot joint involvement and symptomatic, clinical and structural characteristics compared to those with no or minimal midfoot OA. RESULTS: Of 879 eligible feet, 168 had medial midfoot OA, 103 central midfoot OA, 76 both medial and central midfoot OA and 532 no/minimal OA. Having both medial and central midfoot OA was associated with higher pain scores, dorsally-located midfoot pain (OR 2.54, 95%CI 1.45, 4.45), hallux valgus (OR 1.76, 95%CI 1.02, 3.05), flatter foot posture (ß 0.44, 95%CI 0.12, 0.77), lower medial arch height (ß 0.02, 95%CI 0.01, 0.03) and less subtalar inversion and 1st MTPJ dorsiflexion. Isolated medial midfoot OA and central midfoot OA had few distinguishing clinical characteristics. CONCLUSIONS: Distinct phenotypes of midfoot OA appear challenging to identify, with substantial overlap in symptoms and clinical characteristics. Phenotypic differences in symptoms, foot posture and function were apparent in this study only when both the medial and central midfoot were involved.

A comparison of drug substance predicted chemical stability with ICH compliant stability studies.

OBJECTIVE: The aim of this study is to demonstrate the applicability of predictive stability studies to the degradation of drug substances. SIGNIFICANCE: The use of predicted stability studies during pharmaceutical development and in regulatory submissions is increasing, particularly in early phase to support an initial retest period/shelf life claim in the absence of standard stability data. These studies offer an alternative to standard stability testing and can facilitate clinical trials to be started earlier and medicines to reach patients faster. They involve a short-term stressed stability study, typically designed to degrade a drug substance or product to the specification level of the shelf life limiting attribute. The results are used to predict degradation under long-term storage conditions and enable stability understanding to be gained over a short time frame, using limited amounts of material. METHODS: In this work, Accelerated Stability Assessment Program (ASAP) studies were performed for 10 different drug substances and the predictions obtained for chemical degradation were compared to ICH compliant stability data. RESULTS: Across the studies good agreement was achieved, with the initial retest period predictions from the ASAP studies being conservative by design. When minimal degradation was observed during an ASAP study, it was demonstrated that at least a 12-month initial retest period could be supported. CONCLUSION: This comparison of ASAP predictions and ICH compliant stability data has demonstrated the ability of well-designed ASAP studies to predict the long-term chemical stability of drug substances.

Risk of fragility fracture among patients with late-onset psoriasis: a UK population-based study.

This study aimed to examine fracture risk in patients with late-onset psoriasis. A cohort study was conducted using primary care records from the Clinical Practice Research Datalink. Psoriasis patients had a 10% increased risk of fracture compared to matched controls (hazard ratio (HR) = 1.10; 95% confidence interval (CI) 1.04, 1.16). INTRODUCTION: This study aimed to examine fracture risk in patients with late-onset psoriasis and investigate the effect of methotrexate on fracture risk. METHODS: A cohort study was conducted using primary care records from the UK-based Clinical Practice Research Datalink. Individuals aged 40 years and over, with incident (new onset) diagnoses of psoriasis, were identified from 1990 to 2004 and followed up until 2015. For each exposed individual, up to four age-, gender-, and practice-matched controls were randomly selected. Incidence rates of fragility fracture (hip, vertebral, spine, radius or unspecified site) per 10,000 person-years were calculated and hazard rates were compared to the unexposed using Cox regression models. The risk of fracture was also estimated, within the exposed group for patients receiving/not receiving methotrexate. RESULTS: Twenty-four thousand two hundred nineteen patients with psoriasis and 94,820 controls were identified. The absolute rate of fracture in psoriasis patients was 58 per 10,000 person-years (95% CI 55, 61) and 53 per 10,000 person-years in the matched controls (CI 52, 54). Psoriasis patients had a 10% increased risk of fracture compared to their matched controls (HR = 1.10; 95% CI 1.04, 1.16). Methotrexate use was not associated with increased risk (HR = 0.91; 95% CI 0.72, 1.15). CONCLUSIONS: Identifying additional clinical factors associated with increased fracture risk is important in improving fracture risk stratification. Further work is needed to determine the relationship between age of onset of psoriasis and fracture risk, explore causative explanations, and identify if existing fracture risk stratification tools underestimate fracture risk in patients with psoriasis.

Does a modified STarT Back Tool predict outcome with a broader group of musculoskeletal patients than back pain? A secondary analysis of cohort data.

OBJECTIVES: The STarT Back Tool has good predictive performance for non-specific low back pain in primary care. We therefore aimed to investigate whether a modified STarT Back Tool predicted outcome with a broader group of musculoskeletal patients, and assessed the consequences of using existing risk-group cut-points across different pain regions. SETTING: Secondary analysis of prospective data from 2 cohorts: (1) outpatient musculoskeletal physiotherapy services (PhysioDirect trial n=1887) and (2) musculoskeletal primary-secondary care interface services (SAMBA study n=1082). PARTICIPANTS: Patients with back, neck, upper limb, lower limb or multisite pain with a completed modified STarT Back Tool (baseline) and 6-month physical health outcome (Short Form 36 (SF-36)). OUTCOMES: Area under the receiving operator curve (AUCs) tested discriminative abilities of the tool's baseline score for identifying poor 6-month outcome (SF-36 lower tertile Physical Component Score). Risk-group cut-points were tested using sensitivity and specificity for identifying poor outcome using (1) Youden's J statistic and (2) a clinically determined rule that specificity should not fall below 0.7 (false-positive rate <30%). RESULTS: In PhysioDirect and SAMBA, poor 6-month physical health was 18.5% and 28.2%, respectively. Modified STarT Back Tool score AUCs for predicting outcome in back pain were 0.72 and 0.79, neck 0.82 and 0.88, upper limb 0.79 and 0.86, lower limb 0.77 and 0.83, and multisite pain 0.83 and 0.82 in PhysioDirect and SAMBA, respectively. Differences between pain region AUCs were non-significant. Optimal cut-points to discriminate low-risk and medium-risk/high-risk groups depended on pain region and clinical services. CONCLUSIONS: A modified STarT Back Tool similarly predicts 6-month physical health outcome across 5 musculoskeletal pain regions. However, the use of consistent risk-group cut-points was not possible and resulted in poor sensitivity (too many with long-term disability being missed) or specificity (too many with good outcome inaccurately classified as 'at risk') for some pain regions. The draft tool is now being refined and validated within a new programme of research for a broader musculoskeletal population. TRIAL REGISTRATION NUMBER: ISRCTN55666618; Post results.

Clinical diagnosis of symptomatic midfoot osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

OBJECTIVE: To derive a multivariable diagnostic model for symptomatic midfoot osteoarthritis (OA). METHODS: Information on potential risk factors and clinical manifestations of symptomatic midfoot OA was collected using a health survey and standardised clinical examination of a population-based sample of 274 adults aged ≥50 years with midfoot pain. Following univariable analysis, random intercept multi-level logistic regression modelling that accounted for clustered data was used to identify the presence of midfoot OA independently scored on plain radiographs (dorso-plantar and lateral views), and defined as a score of ≥2 for osteophytes or joint space narrowing in at least one of four joints (first and second cuneometatarsal, navicular-first cuneiform and talonavicular joints). Model performance was summarised using the calibration slope and area under the curve (AUC). Internal validation and sensitivity analyses explored model over-fitting and certain assumptions. RESULTS: Compared to persons with midfoot pain only, symptomatic midfoot OA was associated with measures of static foot posture and range-of-motion at subtalar and ankle joints. Arch Index was the only retained clinical variable in a model containing age, gender and body mass index. The final model was poorly calibrated (calibration slope, 0.64, 95% CI: 0.39, 0.89) and discrimination was fair-to-poor (AUC, 0.64, 95% CI: 0.58, 0.70). Final model sensitivity and specificity were 29.9% (95% CI: 22.7, 38.0) and 87.5% (95% CI: 82.9, 91.3), respectively. Bootstrapping revealed the model to be over-optimistic and performance was not improved using continuous predictors. CONCLUSIONS: Brief clinical assessments provided only marginal information for identifying the presence of radiographic midfoot OA among community-dwelling persons with midfoot pain.

Post-operative enteral immunonutrition for gynecologic oncology patients undergoing laparotomy decreases wound complications.

OBJECTIVES: The aim of this study is to determine if peri-operative immune modulating dietary supplements decrease wound complications in gynecologic oncology patients undergoing laparotomy. METHODS: In July 2013 we instituted a practice change and recommended pre- and post-operative oral immune modulating diets (IMDs) to patients undergoing laparotomy. We retrospectively compared patients who received IMDs to those who did not for the study period July 2012 to June 2014. Our outcome of interest was the frequency of Centers for Disease Control surgical site infections (CDC SSIs). RESULTS: Of the 338 patients who underwent laparotomy during the study period, 112 (33%) received IMDs post-operatively. There were 89 (26%) wound complications, including 69 (78%) CDC SSI class 1, 7(8%) class 2 and 13(15%) class 3. Patients receiving IMDs had fewer wound complications than those who did not (19.6% vs. 33%, p=0.049). After controlling for variables significantly associated with the development of a wound complication (ASA classification, body mass index (BMI), history of diabetes mellitus or pelvic radiation, length of surgery and blood loss) consumption of IMDs remained protective against wound complications (OR 0.45, CI 0.25-0.84, p=0.013) and was associated with a 78% reduction in the incidence of CDC SSI class 2 and 3 infections (OR=0.22, CI 0.05-0.95, p=0.044). CONCLUSIONS: Post-operative IMDs are associated with fewer wound complications in patients undergoing laparotomy for gynecologic malignancy and may reduce the incidence of CDC SSI class 2 and 3 infections.

Demographic and clinical factors associated with radiographic severity of first metatarsophalangeal joint osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

OBJECTIVE: To explore demographic and clinical factors associated with radiographic severity of first metatarsophalangeal joint osteoarthritis (OA) (First MTPJ OA). DESIGN: Adults aged ≥50 years registered with four general practices were mailed a Health Survey. Responders reporting foot pain within the last 12 months were invited to undergo a clinical assessment and weight-bearing dorso-plantar and lateral radiographs of both feet. Radiographic first MTPJ OA in the most severely affected foot was graded into four categories using a validated atlas. Differences in selected demographic and clinical factors were explored across the four radiographic severity subgroups using analysis of variance (ANOVA) and ordinal regression. RESULTS: Clinical and radiographic data were available from 517 participants, categorised as having no (n = 105), mild (n = 228), moderate (n = 122) or severe (n = 62) first MTPJ OA. Increased radiographic severity was associated with older age and lower educational attainment. After adjusting for age, increased radiographic first MTPJ OA severity was significantly associated with an increased prevalence of dorsal hallux and first MTPJ pain, hallux valgus, first interphalangeal joint (IPJ) hyperextension, keratotic lesions on the dorsal aspect of the hallux and first MTPJ, decreased first MTPJ dorsiflexion, ankle/subtalar joint eversion and ankle joint dorsiflexion range of motion, and a trend towards a more pronated foot posture. CONCLUSIONS: This cross-sectional study has identified several dose-response associations between radiographic severity of first MTPJ OA and a range of demographic and clinical factors. These findings highlight the progressive nature of first MTPJ OA and provide insights into the spectrum of presentation of the condition in clinical practice.

Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis.

BACKGROUND: Hyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout. DESIGN: Systematic review and meta-analysis. METHODS: Electronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors. RESULTS: Six papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17-1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25-1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14-1.44) and CHD mortality (HR 1.42, 95% CI 1.22-1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction. CONCLUSIONS: Gout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors.

A systematic review of radiographic definitions of foot osteoarthritis in population-based studies.

OBJECTIVE: To identify the methods used in population-based epidemiological studies to diagnose radiographic foot osteoarthritis (OA) and to estimate the population prevalence of radiographic foot OA. METHOD: Electronic databases searched included Medline, Embase, CINAHL and Ageline (inception to May 2009). The search strategy combined search terms for radiography, OA, foot, and specific foot joints. Predetermined selection criteria were applied. Data extracted from each paper included: sample population, radiographic views taken, foot joints examined, scoring system used, definition of OA applied, reliability of radiographic scoring and prevalence of radiographic OA in the foot. RESULTS: Titles and abstracts of 1035 papers were reviewed and full-texts of 21 papers were obtained. Fifteen papers met inclusion criteria and a further 12 papers were included after screening references. Radiographic views were frequently not specified (NS) but a combination of antero-posterior (AP) and lateral (Lat) views was most commonly reported. The first metatarsophalangeal (MTP) joint was the most commonly examined joint (n=20, 74%). Nineteen studies (70%) used the Kellgren and Lawrence (K&L) grading system, 95% of which defined OA as K&L grade> or =2. Estimates of the prevalence of radiographic first MTP joint OA (defined as K&L> or =2) in middle-aged to older adults ranged from 6.3 to 39%. Significant statistical heterogeneity prevented pooling of prevalence estimates. CONCLUSION: There are comparatively few studies examining radiographic foot OA. Existing studies mainly focus on the first MTP joint and use the K&L grading system. Future studies are needed to quantify the prevalence of radiographic OA at the different joint complexes within the foot.

Are hallux valgus and big toe pain associated with impaired quality of life? A cross-sectional study.

Hallux valgus (HV) is common with a standardised prevalence of 28.4% in adults older than 40 years. It has been shown to associate with impaired quality of life (QOL) in small hospital based studies. Previous studies of association between HV, function and disability are based on the presence or absence of regional foot pain which may be due to other foot pathology and is not specific to HV. The objective of this study is to examine the association between self reported HV, big toe pain and impaired QOL in a primary care population. We hypothesise that presence of self-reported HV alone, big toe pain alone and both together will associate with progressively impaired QOL. This hypothesis is based on the known association of concurrent HV and foot pain with impaired physical function and the fact that foot pain and not foot deformity impairs functional status. Our study shows that concurrent HV and big toe pain but not isolated HV associates with impaired overall satisfaction with health and low score on the physical, psychological and social domains of World Health Organization Quality of Life-BREF (WHOQOL-BREF).

Is gout associated with reduced quality of life? A case-control study.

OBJECTIVES: To compare quality of life (QOL) between gout cases and controls in a primary care population and to investigate whether impaired QOL in gout is secondary to co-morbid factors or to intrinsic factors related to gout itself. METHODS: A postal questionnaire was sent to all adults aged over 30 yrs registered with two general practices. The questionnaire assessed a history of gout (doctor diagnosed, or episodes suggestive of acute crystal synovitis) and medical and musculoskeletal co-morbidities. QOL was assessed using the WHOQoL-Bref instrument. Possible cases of gout attended for clinical assessment where the diagnosis was verified on clinical grounds. Overall QOL, satisfaction with health and QOL across four domains were compared between gout cases and controls and then entered into a linear regression model adjusting for gout, age, gender, body mass index and medical and musculoskeletal co-morbidities. RESULTS: Of 13 684 questionnaires mailed, 3082 completed questionnaires were returned (23%). From 289 suggested cases of gout, 137 cases were confirmed by clinical assessment. Compared with controls, cases had impaired overall QOL (15.67 vs 16.41, P = 0.003), satisfaction with health (13.16 vs 14.45, P < 0.001) and physical health-related QOL (14.08 vs 15.95, P < 0.001). On multi-variate analysis, gout remained associated with impaired physical health-related QOL (beta = -0.059, P = 0.001) but not overall QOL (beta = -0.024, P = 0.198) or satisfaction with health (beta = -0.028, P = 0.142). CONCLUSIONS: Gout associates with poor overall QOL mainly resulting from associated co-morbidity. Physical health-related QOL, however, remains impaired after adjustment for co-morbidities.

Validation of a self-report instrument for assessment of hallux valgus.

OBJECTIVES: To validate an instrument for self-reported hallux valgus (HV). METHODS: The self-report instrument consists of five line drawings for each foot depicting a sequential increase in HV angle of 15 degrees developed from a photograph of a normal foot. Participants were asked to select the picture which best represented their left and right feet in turn. Four hundred and fifty-nine subjects completed the self-report instrument: 100 attending a hospital rheumatology clinic and 359 who participated in a community questionnaire study. Three hundred and eighty-four completed it on two occasions (1-2 months apart in 71 subjects and 3-6 months apart in 313) and were assessed once by a blinded observer. Twenty-five subjects were assessed by the blinded observer on two occasions. Validity of the instrument was assessed by the weighted kappa statistic for subject-observer agreement and reliability by the weighted kappa statistics for subject repeatability and observer repeatability. These analyses were repeated for HV dichotomised as present or absent. RESULTS: For the five-grade HV scale, weighted kappa scores (left and right feet combined) were 0.45 for subject-observer agreement, 0.53 at 1-2 months and 0.51 at 3-6 months for subject repeatability, and 0.82 for observer repeatability. For the dichotomised scale (left and right feet combined), sensitivity was 75% and specificity was 82%: kappa scores were 0.55 for subject-observer agreement, 0.63 at 1-2 months and 0.61 at 3-6 months for subject repeatability and 0.83 for observer repeatability. CONCLUSIONS: The HV self-report instrument provides a valid and reliable assessment of the presence and severity of HV and appears suitable for use in epidemiological studies.

EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 12 key propositions were generated after three Delphi rounds. Propositions included both non-pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. CONCLUSIONS: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert, representing 13 European countries. Ten key propositions regarding diagnosis were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Wherever possible the sensitivity, specificity, likelihood ratio (LR), and incremental cost-effectiveness ratio were calculated for diagnostic tests. Relative risk and odds ratios were estimated for risk factors and co-morbidities associated with gout. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key propositions were generated though three Delphi rounds including diagnostic topics in clinical manifestations, urate crystal identification, biochemical tests, radiographs, and risk factors/co-morbidities. Urate crystal identification varies according to symptoms and observer skill but is very likely to be positive in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)). Classic podagra and presence of tophi have the highest clinical diagnostic value for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79), respectively). Hyperuricaemia is a major risk factor for gout and may be a useful diagnostic marker when defined by the normal range of the local population (LR = 9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric acid concentrations at the time of investigation. Radiographs have little role in diagnosis, though in late or severe gout radiographic changes of asymmetrical swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR = 6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods, alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension, diabetes, obesity, and chronic renal failure) are associated with gout. SOR for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed using a combination of research based evidence and expert consensus. The evidence for diagnostic tests, risk factors, and co-morbidities was evaluated and the strength of recommendation was provided.