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BackgroundNew drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations.MethodsThe EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach.ResultsThree overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended.ConclusionsThese recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

Hand osteoarthritis (HOA) is a common disorder frequently causing pain and impaired function with subsequent reduction in health-related quality of life. HOA is a very heterogeneous disease comprising several subsets, such as nodal interphalangeal (IP) OA, thumb base OA and erosive OA (EHOA). Although HOA was traditionally considered a mild disease, recent studies demonstrate that in at least 50% of patients the disease shows a radiographic progression at mid-term and in at least a quarter symptoms may persist. However, no association was seen between radiographic features and symptoms. EHOA is considered to be the most severe subset of HOA, with relevant clinical burden and worse outcome, which may evolves in joint instability and ankylosis, and subsequent disability. In keeping, EHOA is probably the subset in which prognosis may be better predicted.Compared to other OA localisations, the management of HOA may be sometimes difficult, due to its great heterogeneity. Furthermore, the treatment may be influenced by many factors, including HOA subtypes, disease severity, disease duration, number of joints involved, affected site, age of patients, and occupational activities.According with the EULAR recommendations three treatment modalities can been proposed: non-pharmacological, pharmacological, and surgical. In many patients these modalities should be combined, tailored to individual needs and risk factors.Although non-pharmacological therapies are important in the management of HOA, high quality evidence is lacking. The exercise seems useful when combined with education and joint protection. Advice regarding the use of electrotherapy, thermotherapy, ultrasound, TENS or laser therapy is conflicting, mainly due to the lack of eligible studies. So, their inclusion in recommendations relies mainly on consensus methods and expert opinion.As regard as the pharmacological therapy, the most realistic aim is the pain relief, due to limited evidence of reliable efficacy in modifying disease activity by drugs.Among analgesics, paracetamol is considered as the first choice and, if successful, the preferred for long term, although evidence supporting its use in HOA are few. In mild to moderate pain and when not many joints are affected, topical treatments are a good option for many aspects, including the cost effectiveness. If paracetamol or topical NSAIDs are insufficient, then the addition of opioid analgesics should be considered, although the evidence supporting its use in HOA is poor.In patients who respond inadequately to paracetamol or topical treatments, oral NSAIDs or COX-2 inhibitor should be used in substitution or in addition, possibly at lowest effective dose for the shortest period of time and taking into account individual patient risk factors, including age and comedications.Intra-articular (IA) long-acting corticosteroid is effective for painful flares of OA, especially trapeziometacarpal joint (TMC) OA and so, it should be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with HOA. There are contrasting opinions on the usefulness of IA hyaluronan (HA) in all existing recommendations. However, in two recent trials it seems more favourable than IA steroids.Disease modifying drugs for OA (DMOADs) are currently not available. Most studies have been performed with off-label drugs.The EHOA is the HOA subset deserving main attention by new treatment strategies, due to its severity and poor outcome. So, anti-cytokines biologic agents have been tested in some pilot studies using s.c. anakinra, humira and IA infliximab, with sometimes good results.Surgery is uncommonly performed in HOA, and evidence for its effectiveness is lacking. However, for HOA at the base of the thumb, evidence does support effectiveness of surgical therapy when conventional therapies have failed. These surgical interventions include trapeziectomy, arthrodesis, osteotomy, ligament reconstruction, and joint replacement. Surgery for areas other than the thumb base is not yet widely available as a treatment option.Disclosure of InterestNone declared

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.

Objectives:To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA).Methods:The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale.Results:Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint.Conclusion:Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

The objective was to assess knowledge and therapeutic approaches to the management of gout among healthcare professionals and people with/without gout, in Italy. This was a cross-sectional internet-based survey targeting general practitioners (GPs), specialists, pharmacists, and people with/without gout. Between December 2017 and March 2018, participants completed questionnaires on epidemiology, cause/risk factors, therapy objectives and management/treatment strategies to improve outcomes. Overall, 3184 people completed the survey: 699 GPs, 426 specialists, 655 pharmacists and 1404 subjects from the general population: 126 (9.0%) with and 1278 (91.0%) without gout. Notably, less than half of GPs, specialists and people without gout confirmed the published 1% prevalence of gout in Italy. Lifestyle was acknowledged as the main risk factor for gout by nearly 50% of specialists and GPs, while only 13.8% and 12.4%, respectively, considered the role of genetic factors. Uric acid overproduction was deemed as the cause of gout by 60% of GPs and specialists, whereas insufficient excretion by only 30%. Fewer than half of patients were aware that gout permanently damages joints, and even fewer of the renal and cardiovascular implications (19.4% and 12%, respectively); moreover, most people without gout replied that their doctor had never talked with them about uric acid and its correlation with gout development. Finally, GPs were divided on uric acid target levels (48.3% said <6 mg/dL and 18.9% <7 mg/dL). Despite major advances in the knowledge of physiopathological mechanisms of gout, the results of our survey highlight the many treatment and knowledge gaps in its management. Cooperation between multidisciplinary teams is required to break down barriers and ensure optimal treatment with effective and innovative agents of this ever-increasing debilitating condition.

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

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.

Treat-to-target is a therapeutic strategy aimed at improving disease outcome through the achievement of shared treatment goals, which has dramatically ameliorated the prognosis of widespread disorders, such as hypertension or diabetes. Conversely, efforts to delineate treat-to-target in systemic lupus erythematosus (SLE) have failed in pinpointing common goals and treatment strategies, probably because of disease heterogeneity and lack of measurable biomarkers predicting disease course and ensuring a safe treatment tapering during quiescence. Given the detrimental effects of persistent disease activity and protracted corticosteroid therapy on patients’ outcome in lupus, disease remission should be pursued whenever possible. Fortunately, clinical remission is currently realistic for a greater number of patients than it was in the past, yet tight monitoring is required in order for patients to benefit from disease- and corticosteroid-free intervals, while minimizing the risk of disease flares. In everyday practice, patients should be brought to the lowest level of disease activity ensuring a significant benefit over a persistently active disease, being either clinical remission or low disease activity.

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Objectives: To develop evidence based recommendations for the management of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. Results: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. Conclusion: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.