Lung Function Impairment, Associating Hyperinflation with Impaired Diffusion Capacity and Transfer Coefficient, Is a Risk Factor for Hip Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Our objective is to determine if functional indices associated with emphysema on pulmonary function tests (DLCO-diffusion capacity of the lung for CO-; DLCO/AV-DLCO corrected for alveolar volume- and TLC-total lung capacity), considered alone or together, can identify COPD patients with osteoporosis. METHODS: 90 COPD patients underwent dual-energy X-ray absorptiometry (DEXA) and pulmonary function tests. RESULTS: 26% of the COPD patients were osteoporotic. In univariate analysis, each functional parameter associated with emphysema, analyzed separately, was not associated with osteoporosis. In contrast, patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient, defined by the association of the three functional indices (DLCO < 70%, DLCO/AV < 80% and CPT > 115%), had significantly more osteoporosis at the total hip (OR: 5.9, CI: 1.5-23.8, p = 0.013). In multivariate analysis, this phenotype was confirmed as an independent factor associated with hip osteoporosis. In contrast, COPD airway obstruction severity, based on FEV1 (%), was not associated with osteoporosis. A lower BMI, female gender and age were also identified as osteoporosis risk factors. CONCLUSIONS: COPD patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient are at higher risk for osteoporosis. Pulmonary function tests associated with emphysema detection can help to identify COPD patients with osteoporosis, in addition to the classical risk factors.

Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis.

OBJECTIVE: To synthesize evidence of the effect of contextual factors (CFs) on efficacy of urate-lowering therapy (ULT) on serum urate (SU) as outcome in gout patients. METHODS: Randomised controlled trials (RCTs) from (updated) Cochrane reviews were the starting point. RCTs were included if they explored the role of any CF on efficacy of ULT on SU in gout patients. For CFs with sufficient data (i.e. ≥3 trials), a mixed-effects meta-regression analysis was performed with trial and comparison as random effects, whereas specific CFs were modelled as fixed factors. RESULTS: Eight RCTs were included. Effect modification by CFs was explored for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous ULT use. Crude data stratified by renal function were available for four trials (36 randomised comparisons), and suitable for meta-analysis. Pooled estimates revealed that gout patients with a normal, mildly-, or moderately impaired renal function were consistently more likely to achieve SU target with ULT compared to control. Among RCTs comparing ULT to placebo (30 comparisons), effects of ULT on achieving SU target were not statistically different for those with normal (OR:66.87;[11.39-392.75]) compared to mildly (OR:28.54;[5.11-159.46]) and moderately (OR:21.45;[3.20-143.64]) impaired renal function, but seemed lower in those with severely impaired (OR:9.13;[0.96-86.97]) renal function. Data were insufficient to draw conclusions on effect modification by other CFs. CONCLUSION: Few RCTs report stratified analyses exploring the role of CFs. ULT seemed effective in reaching the SU target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage.

Development and usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy in gout.

BACKGROUND: The aim of this study is to develop and assess usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy (ULT) among gout patients in a clinical setting. METHODS: The content of the tool was based on the Integrated Change (I-Change) model. This model combines various socio-cognitive theories and assumes behavioral change is a result of becoming aware of the necessity of change by integrating pre-motivational, motivational, and post-motivational factors. An expert group (five gout experts, three health services researchers, and one health behavior expert) was assembled that decided in three meetings on the tool's specific content (assessments and personalized feedback) using information from preparatory qualitative studies and literature reviews. Usability was tested by a think aloud approach and validated usability questionnaires. RESULTS: The I-Change Gout tool contains three consecutive sessions comprising 80 questions, 66 tailored textual feedback messages, and 40 tailored animated videos. Navigation through the sessions was determined by the patients' intention to adapt suboptimal ULT adherence. After the sessions, patients receive an overview of the personalized advices and plans to support ULT adherence. Usability testing among 20 gout patients that (ever) used ULT and seven healthcare professionals revealed an overall score for the tool of 8.4 ± 0.9 and 7.7 ± 1.0 (scale 1-10). Furthermore, participants reported a high intention to use and/or recommend the tool to others. Participants identified some issues for further improvement (e.g. redundant questions, technical issues, and text readability). If relevant, these were subsequently implemented in the I-Change Gout tool, to allow further testing among the following participants. CONCLUSION: This study provides initial support for the usability by patients and healthcare professionals of the I-Change Gout tool to support ULT adherence behavior.

Development of a patient decision aid for the initiation of urate-lowering therapy in gout patients.

AIM: Shared decision-making improves patients' experiences with care, satisfaction with management decisions and possibly health outcomes. This study describes the development of a decision aid (DA) that supports patients with gout and their physicians in a face-to-face clinical setting to (a) decide whether or not to (re)start urate-lowering therapy (ULT) and (b) agree on the preferred ULT. METHODS: Recommendations of the International Patient Decision Aid Standards group guided the development. A steering group of experts in gout and health services research specified the scope. Nominal group technique meetings were organised in which patients ranked the importance of preidentified potential characteristics/attributes of ULT and discussed further needs regarding the DA. A literature search was conducted to collect evidence on gout outcomes with and without ULT. Subsequently, the DA prototype was designed and adjusted using feedback from the steering group and results of cognitive debriefing interviews among five gout patients. RESULTS: The final DA consists of six pages. First, the DA clarifies the decision at stake and describes gout including its risk factors, the role of lifestyle and treatment of flares. Next, risk of future flares with and without ULT in relation to serum uric acid levels is described and visualised. Relevant attributes of ULT are presented in an option grid distinguishing first-line and second-line ULT. Finally, patients' believes and preferences are explicitly addressed before making the shared decision. CONCLUSION: This study provides initial support for usability of a DA for gout patients eligible for starting ULT.

Outcomes of Care Among Patients With Gout in Europe: A Cross-sectional Survey.

OBJECTIVE: To assess health- and patient-centered outcomes in gout across Europe, and explore patient-, care-, and country-level characteristics associated with these outcomes. METHODS: Patients with self-reported physician-diagnosed gout from 14 European countries completed an online survey. Multivariable mixed-effect logistic and linear regressions were computed for health outcomes (gout flare recurrence) and patient-centered outcomes (patient satisfaction with current medication, and unaddressed goals), accounting for clustering within countries. The role of patient-, care-, and country-level factors was explored. RESULTS: Participants included 1029 patients, predominantly diagnosed by a general practitioner (GP). One or more gout flares were reported by 70% of patients and ≥ 3 flares by 32%. Gout patients reported 1.1 ± 1.2 unaddressed goals, and 80% were satisfied with current medication. Patients with ≥ 3 and ≥ 1 flares were less likely to be treated with urate-lowering therapy (ULT) (OR 0.52, 95% CI 0.39-0.70 and OR 0.38, 95% CI 0.28-0.53, respectively), but more likely to have regular physician visits (OR 2.40, 95% CI 1.79-3.22 and OR 1.77, 95% CI 1.30-2.41). Three or more gout flares were also associated with lower satisfaction (OR 0.39, 95% CI 0.28-0.56) and more unaddressed goals (ß 0.36, 95% CI 0.19-0.53). Notwithstanding, the predicted probability of being satisfied was still between 57% and 75% among patients with ≥ 3 flares but who were not receiving ULT. Finally, patients from wealthier and Northern European countries more frequently had ≥ 3 gout flares. CONCLUSION: Across Europe, many patients with gout remain untreated despite frequent reported flares. Remarkably, a substantial proportion of them were still satisfied with gout management. A better understanding of patients' satisfaction and its role in physicians' gout management decisions is warranted to improve quality of care and gout outcomes across Europe.

Non-steroidal anti-inflammatory drugs for acute gout.

BACKGROUND: Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals in and around joints. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat acute gout. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs)) for acute gout. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for studies to 28 August 2020. We applied no date or language restrictions. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and quasi-RCTs comparing NSAIDs with placebo or another therapy for acute gout. Major outcomes were pain, inflammation, function, participant-reported global assessment, quality of life, withdrawals due to adverse events, and total adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included in this update 28 trials (3406 participants), including 5 new trials. One trial (30 participants) compared NSAIDs to placebo, 6 (1244 participants) compared non-selective NSAIDs to selective cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs), 5 (712 participants) compared NSAIDs to glucocorticoids, 13 compared one NSAID to another NSAID (633 participants), and single trials compared NSAIDs to rilonacept (225 participants), acupuncture (163 participants), and colchicine (399 participants). Most trials were at risk of selection, performance, and detection biases. We report numerical data for the primary comparison NSAIDs versus placebo and brief results for the two comparisons - NSAIDs versus COX-2 inhibitors and NSAIDs versus glucocorticoids. Low-certainty evidence (downgraded for bias and imprecision) from 1 trial (30 participants) shows NSAIDs compared to placebo. More participants (11/15) may have a 50% reduction in pain at 24 hours with NSAIDs than with placebo (4/15) (risk ratio (RR) 2.7, 95% confidence interval (CI) 1.1 to 6.7), with absolute improvement of 47% (3.5% more to 152.5% more). NSAIDs may have little to no effect on inflammation (swelling) after four days (13/15 participants taking NSAIDs versus 12/15 participants taking placebo; RR 1.1, 95% CI 0.8 to 1.5), with absolute improvement of 6.4% (16.8% fewer to 39.2% more). There may be little to no difference in function (4-point scale; 1 = complete resolution) at 24 hours (4/15 participants taking NSAIDs versus 1/15 participants taking placebo; RR 4.0, 95% CI 0.5 to 31.7), with absolute improvement of 20% (3.3% fewer to 204.9% more). NSAIDs may result in little to no difference in withdrawals due to adverse events (0 events in both groups) or in total adverse events; two adverse events (nausea and polyuria) were reported in the placebo group (RR 0.2, 95% CI 0.0, 3.8), with absolute difference of 10.7% more (13.2% fewer to 38% more). Treatment success and health-related quality of life were not measured. Moderate-certainty evidence (downgraded for bias) from 6 trials (1244 participants) shows non-selective NSAIDs compared to selective COX-2 inhibitors (COXIBs). Non-selective NSAIDs probably result in little to no difference in pain (mean difference (MD) 0.03, 95% CI 0.07 lower to 0.14 higher), swelling (MD 0.08, 95% CI 0.07 lower to 0.22 higher), treatment success (MD 0.08, 95% CI 0.04 lower to 0.2 higher), or quality of life (MD -0.2, 95% CI -6.7 to 6.3) compared to COXIBs. Low-certainty evidence (downgraded for bias and imprecision) suggests no difference in function (MD 0.04, 95% CI -0.17 to 0.25) between groups. Non-selective NSAIDs probably increase withdrawals due to adverse events (RR 2.3, 95% CI 1.3 to 4.1) and total adverse events (mainly gastrointestinal) (RR 1.9, 95% CI 1.4 to 2.8). Moderate-certainty evidence (downgraded for bias) based on 5 trials (712 participants) shows NSAIDs compared to glucocorticoids. NSAIDs probably result in little to no difference in pain (MD 0.1, 95% CI -2.7 to 3.0), inflammation (MD 0.3, 95% CI 0.07 to 0.6), function (MD -0.2, 95% CI -2.2 to 1.8), or treatment success (RR 0.9, 95% CI 0.7 to 1.2). There was no difference in withdrawals due to adverse events with NSAIDs compared to glucocorticoids (RR 2.8, 95% CI 0.5 to 14.2). There was a decrease in total adverse events with glucocorticoids compared to NSAIDs (RR 1.6, 95% CI 1.0 to 2.5). AUTHORS' CONCLUSIONS: Low-certainty evidence from 1 placebo-controlled trial suggests that NSAIDs may improve pain at 24 hours and may have little to no effect on function, inflammation, or adverse events for treatment of acute gout. Moderate-certainty evidence shows that COXIBs and non-selective NSAIDs are probably equally beneficial with regards to improvement in pain, function, inflammation, and treatment success, although non-selective NSAIDs probably increase withdrawals due to adverse events and total adverse events. Moderate-certainty evidence shows that systemic glucocorticoids and NSAIDs probably are equally beneficial in terms of pain relief, improvement in function, and treatment success. Withdrawals due to adverse events were also similar between groups, but NSAIDs probably result in more total adverse events. Low-certainty evidence suggests no difference in inflammation between groups. Only low-certainty evidence was available for the comparisons NSAID versus rilonacept and NSAID versus acupuncture from single trials, or one NSAID versus another NSAID, which also included many NSAIDs that are no longer in clinical use. Although these data were insufficient to support firm conclusions, they do not conflict with clinical guideline recommendations based upon evidence from observational studies, findings for other inflammatory arthritis, and expert consensus, all of which support the use of NSAIDs for acute gout.

Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study.

OBJECTIVE: Research findings in gout result predominantly from studies about men and might not be generalizable to women. To improve insight into sex differences in gout, our study compared clinical characteristics and comorbidities of female and male patients with gout, and explored the influence of menopause on these differences. METHODS: Data from patients referred to 2 rheumatology clinics and diagnosed with gout were used. Clinical characteristics and comorbidities of each sex were compared univariately. Sex difference in comorbidities were further explored in multivariate logistic regression analyses adjusting for age, BMI, smoking, and alcohol consumption in both the total group and in those with gout onset ≥ 55 years (as a surrogate for menopausal state). RESULTS: There were 954 patients, including 793 (83%) men, included. Women were on average older (65 vs 62 yrs), were more often obese (54% vs 36%), had a higher serum uric acid (sUA) level (0.53 vs 0.49 mmol/L), used diuretics more often (60% vs 30%), and consumed alcohol less frequently (47% vs 72%). Additionally, women more frequently had reduced renal function (64% vs 31%), hypertension (78% vs 56%), heart failure (23% vs 12%), and type 2 diabetes (39% vs 17%; all P < 0.05). In those with gout onset ≥ 55 years, differences in comorbidities were less pronounced and disappeared after adjusting for lifestyle. CONCLUSION: Our study confirmed sex differences in clinical characteristics and comorbidities among newly diagnosed patients with gout, and revealed that sex differences in comorbidities among those with gout onset beyond the age of female menopause were strongly attenuated and fully explained by lifestyle.

Obstructive sleep apnea and the risk of gout: a population-based case-control study.

BACKGROUND: Patients with obstructive sleep apnea (OSA) might be at risk of gout because of pathophysiological mechanisms that can lead to hyperuricemia and eventually gout or because of shared risk factors between both diseases. The objective of the present study was to investigate the risk of gout in patients with OSA. METHODS: A population-based case-control study using the UK Clinical Practice Research Datalink GOLD including all patients aged 40 years and older with a first diagnosis of gout between 1987 and 2014. Gout cases were matched by year of birth, sex, and practice to non-gout controls. Conditional logistic regression estimated the risk of gout with an earlier diagnosis of OSA. Analyses were adjusted for lifestyle factors, comorbidities, and recent drug use. RESULTS: One hundred eleven thousand five hundred nine cases were matched with 210,241 controls. Patients with OSA were at increased risk of gout (OR 1.86; 95%CI (1.71-2.02). However, this association disappeared (OR 1.05; 95% CI 0.96-1.16) after adjustment for smoking status, body mass index (BMI), alcohol use, a history of heart failure, diabetes mellitus, renal function, and recent use of diuretics and other medications. Among females with OSA and patients with OSA associated with heart failure, renal impairment, or higher BMI, the risk of gout was however still increased when compared to the total control population. CONCLUSION: This study showed that the observed association between OSA and gout disappeared after adjustment.

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.

Anakinra for the treatment of acute gout flares: a randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial.

OBJECTIVES: To evaluate the efficacy and safety of anakinra in treating acute gout flares in a randomized, double-blind, placebo-controlled, active comparator, non-inferiority (NI) trial. METHODS: Patients with a crystal-proven acute gout flare were randomized (1: 1) to treatment with anakinra or treatment as usual (free choice: either colchicine, naproxen or prednisone). The primary end point was the change in pain between baseline and the averaged pain score on days 2-4 measured on a five-point rating scale. NI of anakinra would be established if the upper bound of the 95% CI of the numeric difference in changed pain scores between treatment groups did not exceed the NI limit of 0.4 in favour of treatment as usual, in the per-protocol (PP) and intention-to-treat (ITT) populations, assessed in an analysis of covariance model. Secondary outcomes included safety assessments, improvement in pain, swelling, tenderness and treatment response after 5 days, assessed using linear mixed models and binary logistic regression models. RESULTS: Forty-three patients received anakinra and 45 treatment as usual. Anakinra was non-inferior (mean difference; 95% CI) to treatment as usual in both the PP (-0.13; -0.44, 0.18) and ITT (-0.18; -0.44, 0.08) populations. No unexpected or uncommon (serious) adverse events were observed in either treatment arm. Analyses of secondary outcomes showed that patients in both groups reported similar significant reductions in their gout symptoms. CONCLUSION: Efficacy of anakinra was shown to be non-inferior to treatment as usual for the treatment of acute gout flares, suggesting that anakinra is an effective treatment alternative for acute gout flares. TRIAL REGISTRATION: Het Nederlands Trial Register, www.trialregister.nl, NTR5234.

Construct Validity of Radiographs of the Feet to Assess Joint Damage in Patients with Gout.

OBJECTIVE: To investigate construct validity of radiographic damage of the feet in gout. METHODS: Radiographs of the feet were scored using the Sharp/van der Heijde method. Factors associated with damage were investigated by a negative binomial model, and contribution of damage to health by linear regressions. RESULTS: Age, disease duration, serum uric acid, and tophi were associated with being erosive and erosion score. Tophi were associated with joint space narrowing. Erosions were associated (ß 0.47, 95% CI 0.09-0.84) with physical function, but damage was not associated with overall physical health. CONCLUSION: Our results support construct validity for radiographs of the feet when assessing joint damage in gout.

Individuals With Type 2 Diabetes Mellitus Are at an Increased Risk of Gout But This Is Not Due to Diabetes: A Population-Based Cohort Study.

The relationship between type 2 diabetes and gout is complex. The objective of this study was to understand the role of diabetes itself and its comorbidities within the association between type 2 diabetes and gout.We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD. Persons with type 2 diabetes were identified as persons on a noninsulin antidiabetic drug (NIAD) between 2004 and 2012, and were matched to 1 control based on age, sex, and general practice. We estimated gout risk in NIAD users using Cox regression analysis. All analyses were stratified for sex.In total, 221,117 NIAD users were identified. NIAD users had an increased risk of gout (hazard ratio (HR) 1.48; 95% CI 1.41-1.54). This association was stronger in women (HR 2.23; 95% CI 2.07-2.41) compared with men (HR 1.19; 95% CI 1.13-1.26). After adjustments for BMI, eGFR, hypertension, renal transplantation, diuretics, statins, low-dose aspirin, ciclosporin, and tacrolimus, the risk disappeared in women (HR 1.01; 95% CI 0.92-1.11) and reversed in men (HR 0.61; 95% CI 0.58-0.66) (P for interaction <0.001). When stratifying gout risk according to HbA1c in male and female NIAD users, we found an inverse association between raising HbA1c and incident gout in men only. Further adjustment gave similar results.Individuals with type 2 diabetes are at increased risk of gout. This is not due to diabetes itself, but to the comorbid conditions. Diabetes itself is apparently associated with a decreased risk of gout, especially in men.

Nonsteroidal anti-inflammatory drugs for treatment of acute gout.

CLINICAL QUESTION: Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? BOTTOM LINE: NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase inhibitors and glucocorticoids for treating acute gout. However, NSAIDs are associated with higher rates of adverse events and higher rates of withdrawal due to adverse events compared with cyclooxygenase inhibitors.

Content and construct validity of the Rheumatic Diseases Comorbidity Index in patients with gout.

OBJECTIVE: Gout has been associated with a large number of co-morbidities. As yet, no co-morbidity measure has been validated for use in clinical studies in gout. This study aims to evaluate the content and construct validity of the Rheumatic Diseases Comorbidity Index (RDCI) and a gout-specifically modified RDCI (mRDCI) in patients with gout. METHODS: In a cross-sectional sample of 122 patients with gout, data on co-morbidities were obtained during an interview, chart review and clinical examination. The data were used to compute the RDCI/mRDCI, a simple co-morbidity count, the Charlson Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). Content and construct validity was explored by assessing Spearman correlations between the two RDCI versions and between RDCI/mRDCI and the other co-morbidity indices, as well as demographic and clinical outcomes. In addition, we assessed the independent association between the RDCI/mRDCI and physical functioning (HAQ disability index), physical health (36-Item Short Form Health Survey) and direct health care and non-health care costs using multivariable regression analyses. RESULTS: The correlation between the RDCI and mRDCI was 0.86. Correlations between the RDCI/mRDCI and simple co-morbidity count, CCI or FCI varied between 0.72 and 0.88. Correlations with generic and gout-specific health outcomes were moderate and weak, respectively, with slightly better results for the mRDCI. Multivariable analyses showed that both the RDCI and mRDCI contributed to the variation in physical functioning, physical health and direct health care and non-health care costs. CONCLUSION: Both the RDCI and mRDCI have appropriate content and construct validity to evaluate the influence of co-morbidity on outcome in patients with gout.

Cost of illness and determinants of costs among patients with gout.

OBJECTIVE: To estimate costs of illness in a cross-sectional cohort of patients with gout attending an outpatient rheumatology clinic, and to evaluate which factors contribute to higher costs. METHODS: Altogether, 126 patients with gout were clinically assessed. They completed a series of questionnaires. Health resource use was collected using a self-report questionnaire that was cross-checked with the electronic patient file. Productivity loss was assessed by the Work Productivity and Activity Impairment Questionnaire, addressing absenteeism and presenteeism. Resource use and productivity loss were valued by real costs, and annual costs per patient were calculated. Factors contributing to incurring costs above the median were explored using logistic univariable and multivariable regression analysis. RESULTS: Mean (median) annual direct costs of gout were €5647 (€1148) per patient. Total costs increased to €6914 (€1279) or €10,894 (€1840) per patient per year when adding cost for absenteeism or both absenteeism and presenteeism, respectively. Factors independently associated with high direct and high indirect costs were a positive history of cardiovascular disease, functional limitations, and female sex. In addition, pain, gout concerns, and unmet gout treatment needs were associated with high direct costs. CONCLUSION: The direct and indirect costs-of-illness of gout are primarily associated with cardiovascular disease, functional limitations, and female sex.

Cardiovascular risk factors and comorbidities in patients with hyperuricemia and/or gout: a systematic review of the literature.

OBJECTIVE: To review the available literature on the likelihood of having cardiovascular (CV) risk factors and on developing CV comorbidities in patients with gout and/or asymptomatic hyperuricemia as an evidence base for generating multinational clinical practice recommendations in the 3e (Evidence, Expertise, Exchange) Initiative in Rheumatology. METHODS: A systematic literature search was carried out using MEDLINE, EMBASE, and The Cochrane Library, and abstracts presented at the 2010/2011 meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism, searching for CV risk factors and new CV comorbidities in patients with asymptomatic hyperuricemia and/or a diagnosis of gout. Trials that fulfilled predefined inclusion criteria were systematically reviewed. RESULTS: A total of 66 out of 8918 identified publications were included in this review. After assessment of the risk of bias, 32 articles with a high risk of bias were excluded. Data could not be pooled because of clinical and statistical heterogeneity. In general, both for asymptomatic hyperuricemia and for gout the hazard ratios for CV comorbidities were only modestly increased (1.5 to 2.0) as were the hazard ratios for CV risk factors, ranging from 1.4 to 2.0 for hypertension and from 1.0 to 2.4 for diabetes. CONCLUSION: Unlike the common opinion that patients with gout or hyperuricemia are at higher risk of developing CV disease, the actual risk to develop CV disease is either rather weak (for hyperuricemia) or poorly investigated (for gout).

The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including Cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors.

OBJECTIVE: To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to September 2011. Randomized controlled trials (RCT) or quasi-RCT in adults with acute gout that compared GC, colchicine, NSAID, IL-1 inhibitors, and paracetamol to no treatment, placebo, another intervention, or combination therapy were included. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events. Data were pooled where appropriate. RESULTS: Twenty-six trials evaluating GC (N = 5), NSAID (N = 21), colchicine (N = 2), and canakinumab (N = 1) were included. No RCT assessed paracetamol or intraarticular (IA) GC. No RCT compared systemic GC with placebo. Moderate quality evidence (3 trials) concluded that systemic GC were as effective as NSAID but safer. Low quality evidence (1 trial) showed that both high- and low-dose colchicine were more effective than placebo, and low-dose colchicine was no different to placebo with respect to safety but safer than high-dose colchicine. Low quality evidence (1 trial) showed no difference between NSAID and placebo with regard to pain or inflammation. No NSAID was superior to another. Moderate quality evidence (1 trial) found that 150 mg canakinumab was more effective than a single dose of intramuscular GC (40 mg triamcinolone) and equally safe. CONCLUSION: GC, NSAID, low-dose colchicine, and canakinumab all effectively treat acute gout. There was insufficient evidence to rank them. Systemic GC appeared safer than NSAID and lower-dose colchicine was safer than higher-dose colchicine.

Treatment of gout patients with impairment of renal function: a systematic literature review.

OBJECTIVE: To assess the efficacy and safety of gout-specific medications in gout patients with a comorbidity and/or comedication. METHODS: A systematic literature search for gout, its medication, and the most common comorbidities and comedications, using serum uric acid (SUA) levels as the primary, and adverse events as the secondary outcomes. RESULTS: Eight trials met inclusion criteria. Trials covered treatment with allopurinol, benzbromarone, rasburicase, or febuxostat in a gout population with mild or moderate renal insufficiency. High risk of bias (5/8 trials) and heterogeneity precluded formal metaanalysis. The trials showed the following hierarchy in efficacy (lowering the SUA below 6.0 mg/dl): febuxostat 80 mg (44%-71%) > febuxostat 40 mg (43%-52%) > allopurinol 100 mg or 200 mg (0-46%) after 6 months of therapy; rasburicase (46%) > allopurinol 300 mg (16%) after 7 days of therapy; benzbromarone 100-200 mg (93%) > allopurinol 100-200 mg (63%) after 9-24 months of therapy. The combination of allopurinol and benzbromarone seemed to be effective, with a significant reduction in the SUA from 7.8 to 5.7 mg/dl (p < 0.05) after 1 month. One study showed that 89% achieved the target SUA using higher doses of allopurinol than usually recommended for patients with renal impairment without an apparent increase in adverse events. In addition, allopurinol and benzbromarone significantly improved renal function. CONCLUSION: In gout patients with renal insufficiency febuxostat, rasburicase, benzbromarone, and allopurinol + benzbromarone seemed to be effective and safe; allopurinol may be cautiously titrated until the target uric acid level has been reached, and may improve renal function.