Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis

Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014). Selection criteria: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. Primary outcomes: rate of adverse events and death. The quality was assessed with the Jadad’s scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40–240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6–85) and febuxostat (range 41.8–80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.     

Treatment of acute gout: A systematic review

Objective

Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis.

Methods

A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements.

Results

Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra.

Conclusion

NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.     

Recent diuretic use and the risk of recurrent gout attacks: the online case-crossover gout study

OBJECTIVE: To assess several putative risk factors, including thiazide and loop diuretics use, thought to trigger recurrent gout attacks. METHODS: We conducted an internet-based case-crossover study involving subjects who had a gout attack within the past year. Patients were recruited online and asked to provide access to medical records. Data were obtained on specific diuretic use on each day over the 2-day period prior to an acute gout attack (hazard period) and on each day of 2 days during the intercritical period (control period). We examined the relation of all diuretic use and use of specific diuretics, i.e., thiazide and loop, to the risk of recurrent gout attacks using a conditional logistic regression model adjusting for alcohol consumption and purine intake. RESULTS: One hundred ninety-seven subjects completed both control and hazard period questionnaires. Participants were predominantly male (80%) and over half had a college education. The median time between onset of gout attack and logging on to the website was 2 days. Adjusting for alcohol consumption and purine intake, the odds ratio (OR) for recurrent gout attacks from all diuretic use over the last 48 h was 3.6 (95% confidence interval 1.4-9.7). OR of recurrent gout attacks were 3.2 and 3.8 for use of thiazide and loop, respectively. CONCLUSION: Recent use of diuretics is associated with a significantly increased risk for recurrent gouty arthritis. The increased risk of gout attacks from either thiazide or possibly loop diuretic therapies represents an important modifiable risk factor in patients with gout.     

Combination urate-lowering therapy in the treatment of gout: What is the evidence?

Background

Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach.

The clinical efficacy of urate-lowering therapy in acute gout: a meta-analysis of randomized controlled trials

Clinical Rheumatology - Gout is a common chronic disease with a high recurrence rate. To date, the debate continues about the best time for using urate lowering therapy (ULT) during an acute gout...     

Intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature

STUDY OBJECTIVES: There is some evidence that magnesium, when infused into asthmatic patients, can produce bronchodilation in addition to that obtained from standard treatments. This systematic review examined the effect of intravenous magnesium sulfate used for patients with acute asthma managed in the emergency department. METHODS: Only randomized controlled trials were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with intravenous magnesium sulfate versus placebo. Trials were identified from the Cochrane Airways Review Group register, which consists of a combined search of EMBASE, MEDLINE, and CINAHL databases and hand-searching of 20 key respiratory journals. Bibliographies from included studies and known reviews were searched. Primary authors and content experts were contacted. Data were extracted and methodologic quality was assessed independently by 2 reviewers. Missing data were obtained from authors. RESULTS: Seven trials (5 adult, 2 pediatric) involving a total of 668 patients were included. Overall, admission to hospital was not statistically reduced using magnesium sulfate (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.09 to 1.02). In the severe subgroup, admissions were reduced in those receiving magnesium sulfate (OR 0.10, 95% CI 0.04 to 0.27). Overall, patients receiving magnesium sulfate demonstrated nonsignificant improvements in peak expiratory flow rates (PEFR) when all studies were pooled (weighted mean difference [WMD] 29 L/min, 95% CI -3 to 62). In studies of patients with severe acute asthma, PEFR WMD improved by 52 L/min (95% CI 27 to 78) favoring magnesium sulfate treatment. The absolute FEV(1) also improved by 10% predicted (95% CI 4 to 16) in patients with severe acute asthma. No clinically important changes in vital signs or side effects were reported. CONCLUSION: Current evidence does not clearly support routine use of intravenous magnesium sulfate in all patients with acute asthma presenting to the ED. However, magnesium sulfate appears to be safe and beneficial for patients who present with severe acute asthma. Practice guidelines need to be changed to reflect these results.     

Systemic steroid therapy for acute gout: A clinical trial and review of the literature

Nonsteroidal antiinflammatory drugs are frequently used as initial therapy in acute gout. In select cases, however, colchicine has been recommended as an alternative therapy. A review of the literature raises significant concerns regarding the cost to benefit ratio of using colchicine in this setting. A survey of alternative forms of therapies showed few studies investigating the efficacy and side effects of a short course of oral steroids, and little support for this modality in standard textbooks. Our preliminary study suggests that a short course of oral corticosteroid therapy can be used effectively for acute gout when NSAIDs are contraindicated. The use of prednisone 30 to 50 mg or its equivalent initially, and gradually tapered over 10 days, results in clinical resolution without rebound arthropathy or steroid complications in most patients. As a result, we rarely use colchicine in the management of acute gout in our practice.     

Effectiveness of interventions for the treatment of acute and prevention of recurrent gout--a systematic review

OBJECTIVE: To determine the evidence for the effectiveness of treatments for acute gout and the prevention of recurrent gout. METHOD: Seven electronic databases were searched for randomized controlled trials of treatments for gout from their inception to the end of 2004. No language restrictions were applied. All randomized controlled trials of treatments routinely available for the treatment of gout were included. Trials of the prevention of recurrence were included only if patients who had had gout and had at least 6 months of follow-up were studied. RESULTS: We found 13 randomized controlled trials of treatment for acute gout, two of which were placebo controlled. Colchicine was found to be effective in one study; however, the entire colchicine group developed toxicity. The only robust conclusion from studies of non-steroidal anti-inflammatory drugs is that pain relief from indometacin and etoricoxib are equivalent. We found one randomized controlled trial, reported only as a conference abstract, of recurrent gout prevention. CONCLUSION: The shortage of robust data to inform the management of a common problem such as gout is surprising. All of the drugs used to treat gout can have serious side effects. The incidence of gout is highest in the elderly population. It is in this group, who are at a high risk of serious adverse events, that we are using drugs of known toxicity. The balance of risks and benefits for the drug treatment of gout needs to be reassessed.     

内镜治疗急性胆源性胰腺炎的系统评价

目的:评价内镜治疗急性胆源性胰腺炎的临床疗效和安全性.方法:通过计算机检索全面收集全世界关于内镜治疗急性胆源性胰腺炎的随机对照试验/或半随机对照试验,并辅手工检索和其他检索.按照纳入排除标准纳入文献,由两名研究者独立筛选并提取资料,采用Handbook5.0推荐的质量评价标准评价纳入研究的方法学质量,采用RevMan5.0软件进行统计学处理.结果:最终纳入4个研究,包括317例患者.Meta分析结果显示内镜组治疗组与传统治疗组相比,在腹痛缓解时间(OR=-2.98,95%CI:-4.98,0.97)、白细胞复常时间(OR=-4.63,95%CI:-5.29,-3.97)、血淀粉酶复常时间(OR=-3.85,95%CI:-4.49,-3.21)、并发症发生率(OR=0.34,95%CI:0.18,0.66)和住院时间(OR=-7.51,95%CI:-9.89,-5.13)方面存在统计学差异.结论:当前研究显示,与传统治疗组相比,内镜治疗组能显著减少急性胆源性胰腺炎的腹痛缓解时间、白细胞及血淀粉酶复常时间,降低并发症的发生,缩短住院时间.     

Treatment of acute Charcot foot with bisphosphonates: a systematic review of the literature

Aim/hypothesis  

We undertook a systematic review of the literature concerning the efficacy and safety of bisphosphonates in acute Charcot neuropathic osteoarthropathy.     

Magnesium sulfate for acute asthma in adults: a systematic literature review

Magnesium sulfate (MgSO(4)) has been considered as an adjunct therapy for severe and life-threatening asthma exacerbation. The literature search was performed using MEDLINE, EMBASE, Cochrane Library and Google Scholar to summarize the current state of knowledge regarding magnesium therapy in acute exacerbation of adult asthma. A total of 16 trials and 4 meta-analyses were identified. As results, intravenous MgSO(4) was beneficial in severe exacerbation, but evidence for nebulized magnesium was insufficient. However, larger trials are required to draw confirmative conclusions on the efficacy. Regarding the safety concern, the risk of major toxicity appears to be very low at usual doses described in the literature. Additionally, results from 4 surveys were examined on the gaps between knowledge and practice, and on the barrier to the use of MgSO(4) at emergency departments. This literature review summarized the up-to-date evidence on the issues regarding the use of MgSO(4) for acute asthma. We expect more studies to be conducted for evidence making in the Asian-Pacific regions.