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1.  Patient and clinical characteristics associated with gout flares in an integrated healthcare system 
Rheumatology International  2015;35(11):1799-1807.
Gout flares have been challenging to identify in retrospective databases due to gout flares not being well documented by diagnosis codes, making it difficult to conduct accurate database studies. Previous studies have used different algorithms, and in this study, we used a computer-based method to identify gout flares. The objectives of this study were to identify gout flares in gout patients newly initiated on urate-lowering therapy and evaluate factors associated with a patient experiencing gout flares after starting drug treatment. This was a retrospective cohort study identifying gout patients newly initiated on a urate-lowering therapy (ULT) during the study time period of January 1, 2007–December 31, 2010. The index date was the first dispensed ULT prescription during the study time period. Patients had to be ≥18 years of age on index date, have no history of prior ULT prescription during 12 months before index date, and were required to have 12 months of continuous membership with drug benefit during pre-/post-index. Electronic chart notes were reviewed to identify gout flares; these reviews helped create a validated computer-based method to further identify patients with gout flares and were categorized into 0 gout flares, 1–2 gout flares, and ≥3 gout flares during the 12 months post-index period. Multivariable logistic regression was used to examine patient and clinical factors associated with gout flares during the 12-month follow-up period. There were 8905 patients identified as the final cohort and 68 % of these patients had one or more gout flares during the 12-month follow-up: 2797 patients (31 %) had 0 gout flares, 4836 (54 %) had 1–2 gout flares, and 1272 patients (14 %) had ≥3 gout flares. Using a multivariate regression analyses, factors independently associated with 1–2 gout flares and ≥3 gout flares versus no gout flares were similar, however, with slight differences, such as younger patients were more likely to have 1–2 gout flares and patients ≥65 years of age had ≥3 gout flares. Factors such as male gender, not attaining sUA goal, having ≥3 comorbidities, diuretics use, no changes in initial ULT dose, and not adhering to ULT all were associated with gout flares versus no gout flares. Using a new method to identify gout flares, we had the opportunity to compare our findings with the previous studies. Our study findings echo other previous studies where older patients, male, diuretics, having a greater number of comorbidities, and non-adherence are more likely to have more gout flares during the first year of newly initiating ULT. There is an unmet need for patients with gout to be educated and managed more closely, especially during the first year.
doi:10.1007/s00296-015-3284-3
PMCID: PMC4611012  PMID: 25991397
Gout; Gout flares; Urate-lowering therapy; Adherence; Serum uric acid goal
2.  Sex differences in gout epidemiology: evaluation and treatment 
Annals of the Rheumatic Diseases  2006;65(10):1368-1372.
Background
Little is known about the characteristics, evaluation and treatment of women with gout.
Objective
To examine the epidemiological differences and differences in treatment between men and women in a large patient population.
Methods
The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate‐lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate‐lowering treatment.
Results
A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease‐9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate‐lowering treatment had appropriate surveillance of serum urate levels post‐initiation of urate‐lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing.
Conclusions
Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.
doi:10.1136/ard.2006.051649
PMCID: PMC1798311  PMID: 16644784
3.  Patients and providers view gout differently: a qualitative study 
Chronic illness  2010;6(4):263-271.
Objective
We sought to examine patients’ and providers’ views on the treatment of gout to better understand why management is suboptimal.
Methods
In-depth telephone interviews were conducted with gout patients (n=26) who initiated treatment with a urate-lowering drug (ULD) in the prior 6 months and with providers who care for gout patients (n=15). The interviews were audiotaped and transcribed verbatim. Using qualitative methods, results were analyzed and themes were identified. Interviews focused on the acute management, chronic management, and prevention and improvement strategies.
Results
Providers viewed the majority of patients as having excellent relief with nonsteroidal anti-inflammatories, colchicine and glucocorticoids while some patients felt these medications were ineffective. Providers felt most patients had a good understanding of the rationale for ULD therapy and that patients responded well. Some patients felt ULDs triggered, worsened or had no impact on their disease. Most providers thought medication adherence was relatively good. Some patients reported discontinuing medications. Discontinuations were largely purposeful and due to clinical or financial concerns. Most providers thought their skills adequate to teach disease self-management behaviors. Patients requested more information and longer visit times.
Conclusions
Providers view gout as easily managed while patients report challenges and purposeful nonadherence.
doi:10.1177/1742395310378761
PMCID: PMC3134238  PMID: 20675361
medication use; gout treatment; medication adherence; qualitative
4.  A cross-sectional internet-based patient survey of the management strategies for gout 
Background
Almost half of the patients with gout are not prescribed urate-lowering therapy (ULT) by their health care provider and >50 % use complementary and alternative therapies. Diet modification is popular among gout patients due to known associations of certain foods with gout flares. The interplay of the use of dietary supplements, diet modification, and ULT adherence in gout patients is not known. Despite the recent interest in diet and supplements, there are limited data on their use. Our objective was to assess ULT use and adherence and patient preference for non-pharmacological interventions by patients with gout, using a cross-sectional survey.
Methods
People who self-reported physician-diagnosed gout during their visit to a gout website (http://gouteducation.org) were invited to participate in a brief anonymous cross-sectional Internet survey between 08/11/2014 to 04/14/2015 about the management of their gout. The survey queried ULT prescription, ULT adherence, the use of non-pharmacological interventions (cherry extract, diet modification) and the likelihood of making a lifelong diet modification for gout management.
Results
A total of 499 respondents with a mean age 56.3 years were included; 74 % were males and 74 % were White. Of these, 57 % (285/499) participants were prescribed a ULT for gout, of whom 88 % (251/285) were currently taking ULT. Of those using ULT, 78 % (97/251) reported ULT adherence >80 %. Gender, race, and age were not significantly associated with the likelihood of receiving a ULT prescription or ULT adherence >80 %. Fifty-six percent of patients with gout preferred ULT as a lifelong treatment for gout, 24 % preferred cherry extract and 16 % preferred diet modification (4 % preferred none). Men had significantly lower odds of preferring ULT as the lifelong treatment choice for gout vs. other choices (p = 0.03). We found that 38.3 % participants were highly motivated to make a lifelong dietary modification to improve their gout (score of 9–10 on a 0–10 likelihood scale). Older age was significantly associated with high level of willingness to modify diet (p = 0.02).
Conclusion
We found that only 57 % of gout patients reported being prescribed ULT. 40 % of gout patients preferred non- pharmacological interventions such as cherry extract and diet modification for gout management. The latter finding requires further investigation.
doi:10.1186/s12906-016-1067-3
PMCID: PMC4774197  PMID: 26931313
Gout; Cherry extract; Cherry juice; Complementary medicine; Allopurinol; Febuxostat; Internet study; Survey; Natural supplements; Diet modification
5.  A National Survey of Veterans Affairs Rheumatologists for Relevance of Quality of Care Indicators for Gout Management 
Arthritis care & research  2010;62(9):1306-1311.
Objective
To determine the relevance of current gout Quality indicators (QIs).
Methods
Members of the Veterans Affairs Rheumatology Consortium were invited to participate in an online survey and provide opinions (rank 0–10) regarding existing gout QIs. Opinions sought on each QI were 1) relevance to United States Veterans, 2) likelihood to improve gout care, and 3) ease of electronic capture. Participants were also asked to rank their top 3 gout QIs.
Results
Participating VA rheumatologists were mainly male, of mean age 51.3 years and experienced in the management of gout. All 10 gout QIs were considered relevant, with a score of 8.2 of higher. The initiation of urate lowering therapy, monitoring of urate levels after initiation of urate lowering therapy, and treatment of acute gout with anti-inflammatory agents scored the highest with regards to likely to improving gout care, with the first 2 QIs also felt to be most relevant. Adjustment of initial allopurinol dosing in patients with renal impairment and in those receiving concurrent azathioprine/6-mercaptopurine were perceived as the QIs most amenable to electronic capture. The top ranked QIs were initiation of urate-lowering therapy with frequent gout attacks, serum urate monitoring after initiation of urate lowering therapy and adjustment of initial allopurinol dose to renal function.
Conclusions
In a national survey of VA rheumatologists, most gout QIs were thought to be highly relevant. QIs related to initiation of urate lowering therapy, serum urate monitoring, and initial dosing of allopurinol were ranked the most important for veterans with gout.
doi:10.1002/acr.20192
PMCID: PMC2943024  PMID: 20235197
Quality Indicators; Gout; Veterans Affairs
6.  Concordance of the management of chronic gout in a UK primary‐care population with the EULAR gout recommendations 
Annals of the Rheumatic Diseases  2007;66(10):1311-1315.
Objectives
To assess concordance of the management of chronic gout in UK primary care with the European League Against Rheumatism (EULAR) gout recommendations.
Methods
A postal questionnaire was sent to all adults aged >30 years registered with two general practices. Patients with possible gout attended for clinical assessment, at which the diagnosis was verified clinically. Aspects of chronic gout management, including provision of lifestyle modification advice, use of urate‐lowering therapies (ULT) including dose titration to serum urate (SUA) level, prophylaxis against acute attacks, and diuretic cessation were assessed in accordance with the EULAR recommendations.
Results
Of 4249 (32%) completed questionnaires returned, 488 reported gout or acute attacks and were invited for clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout were identified. Advice regarding alcohol consumption was recalled by 59 (41%), weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower in allopurinol users than non‐users (318 vs 434 μmol/l) and was less often >360 μmol/l in allopurinol users (23% vs 75%). Eight patients had recently commenced allopurinol; two of these also were taking prophylactic colchicine or non‐steroidal anti‐inflammatory drugs. Of 25 patients with diuretic‐induced gout, 16 (64%) were still taking a diuretic.
Conclusion
Treatment of chronic gout is often suboptimal and poorly concordant with EULAR recommendations. Lifestyle advice is infrequently offered, and allopurinol is restricted to a minority. Persistent hyperuricaemia was often seen in allopurinol non‐users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary.
doi:10.1136/ard.2007.070755
PMCID: PMC1994300  PMID: 17504843
gout; primary health care; lifestyle risk reduction; allopurinol; EULAR recommendations
7.  The Dynamics of Chronic Gout Treatment: medication gaps and return to therapy 
Objective
To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy.
Methods
We identified persons from two integrated delivery systems 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of one prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy.
Results
There were 4,166 new users of urate-lowering drugs (97% received allopurinol) of whom 2,929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45 to 74 (<45 referent) and greater duration of urate-lowering drug use prior to the gap was associated with resuming treatment within one year. In contrast, receipt of NSAIDs or glucocorticoids in the year prior to the gap was associated with a reduced likelihood of resuming therapy.
Conclusions
The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions given the clinical consequences of nonadherence.
doi:10.1016/j.amjmed.2009.05.026
PMCID: PMC2813203  PMID: 20102992
persistence; adherence; compliance; gout; urate lowering drugs
8.  Quality of Care for Gout in the US Needs Improvement 
Arthritis and rheumatism  2007;57(5):822-829.
Objective
To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care.
Methods
Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics.
Results
Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of ≥1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers.
Conclusion
Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts.
doi:10.1002/art.22767
PMCID: PMC3619972  PMID: 17530682
Gout; Veterans; Quality of care; Quality indicators; Physician adherence
9.  Allopurinol and mortality in hyperuricaemic patients 
Rheumatology (Oxford, England)  2009;48(7):804-806.
Objectives. While studies have suggested that gout and hyperuricaemia are associated with the risk of premature death, none has investigated the role of urate-lowering therapy on this critical outcome. We examined the impact of allopurinol, the most commonly used urate-lowering drug, on the risk of mortality in hyperuricaemic patients.
Methods. From a population of hyperuricaemic veterans of [serum urate level >416 μmol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n = 2483) and non-users (n = 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models.
Results. Of the 9924 veterans (males, 98% and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95% CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95% CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was −111 μmol/l (−1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 μmol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95% CI −0.55, −0.81).
Conclusion. Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.
doi:10.1093/rheumatology/kep069
PMCID: PMC4481712  PMID: 19447769
Allopurinol; Mortality; Hyperuricaemia; Gout
10.  SLC2A9 Is a High-Capacity Urate Transporter in Humans 
PLoS Medicine  2008;5(10):e197.
Background
Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.
Methods and Findings
We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200–500 μM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 μM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case–control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size −0.12 mm Hg, 95% CI −0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size −0.03 mm Hg, 95% CI −0.39 to 0.31, p = 0.82).
Conclusions
This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.
Editors' Summary
Background.
Blood is continually pumped around the human body to deliver the chemicals needed to keep the body's cells alive and to take cellular waste products to the kidneys where they are filtered out of the blood and excreted in the urine. In healthy people, the levels of nutrients and waste products in serum (the liquid part of blood) fall within “normal” ranges but in ill people these levels can be very different. For example, serum uric acid (urate) levels are usually increased in people with gout. In this arthritic condition, uric acid crystallizes in the joints (often those in the big toe) and causes swelling and intense pain. Increased serum urate levels, which are also associated with high blood pressure, diabetes, and several other important conditions, can be caused by eating food that is rich in chemicals called purines (for example, liver, dried beans, and port). The body also converts its own purines into uric acid so genetic variations in the enzymes involved in purine breakdown can alter serum urate levels, as can variations in the rate of urate removal from the body by the kidneys. Urinary urate excretion is controlled by urate transporters, proteins that carry urate into and out of the kidney cells. Uricosuric drugs, which are used to treat gout, reduce serum urate levels by inhibiting a urate transporter that reabsorbs urate from urine.
Why Was This Study Done?
Several urate transporters have already been identified but recently, using an approach called genome-wide association scanning, scientists found that some genetic variants of a human gene called SLC2A9 are more common in people with high serum urate levels than in people with normal levels. SLC2A9 encodes a glucose transporter (a protein that helps to move the sugar glucose through cell membranes) and is highly expressed in the kidney's main urate handling site. Given these facts, could SLC2A9 (the protein made from SLC2A9) be a urate transporter as well as a glucose transporter? In this study, the researchers investigate this possibility and also ask whether genetic variations in SLC2A9 might be responsible for the association between serum urate levels and high blood pressure.
What Did the Researchers Do and Find?
The researchers first expressed SLC2A9 in frog eggs, a type of cell that does not have its own urate transporter. They found that urate rapidly moved into eggs expressing SLC2A9 but not into control eggs, that SLC2A9 transported urate about 50 times faster than glucose, and that glucose stimulated SLC2A9-mediated urate transport. Similarly, overexpression of SLC2A9 in human embryonic kidney cells more than doubled their urate uptake. Conversely, when the researchers used a technique called RNA interference to reduce the expression of mouse SLC2A9 in mouse cells that normally makes this protein, urate transport was reduced. Next, the researchers looked at two small parts of SLC2A9 that vary between individuals (so-called single polynucleotide polymorphisms) in nearly 900 men who had had their serum urate levels and urinary urate excretion rates measured. They found that certain genetic variations at these two sites were associated with increased serum urate levels and decreased urinary urate excretion. Finally, the researchers used a statistical technique called meta-analysis to look for an association between one of the SLC2A9 gene variants and blood pressure. In two separate meta-analyses that together involved more than 20, 000 participants in several studies, there was no association between this gene variant and blood pressure.
What Do These Findings Mean?
Overall, these findings indicate that SLCA9 is a high capacity urate transporter and suggest that this protein plays an important part in controlling serum urate levels. They provide confirmation that common genetic variants in SLC2A9 affect serum urate levels to a marked degree, although they do not show exactly which genetic variant is responsible for increasing serum urate levels. They also provide important new insights into how the kidneys normally handle urate and suggest ways in which this essential process may sometimes go wrong. Thus, these findings could eventually lead to new treatments for gout and possibly for other diseases that are associated with increased serum urate levels.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050197.
The UK National Health Service Direct health encyclopedia provides detailed information for patients about gout
MedlinePlus provides links to many sources of information about gout (in English and Spanish), including “What is gout?”, an easy-to-read guide from the US National Institutes of Arthritis and Musculoskeletal and Skin Diseases
Wikipedia also has pages on gout, uric acid, and SCL2A9 (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The Arthritis Research Campaign also has information on gout
Mark Caulfield and colleagues show that theSLC2A9 gene, which encodes a facilitative glucose transporter, is also a high-capacity urate transporter.
doi:10.1371/journal.pmed.0050197
PMCID: PMC2561076  PMID: 18842065
11.  Gout 
BMJ Clinical Evidence  2011;2011:1120.
Introduction
Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute gout? What are the effects of treatments to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: colchicine, corticosteroids, corticotropin (ACTH), non-steroidal anti-inflammatory drugs (NSAIDs), sulfinpyrazone, xanthine oxidase inhibitors, advice to lose weight, advice to reduce alcohol intake, and advice to reduce dietary intake of purines.
Key Points
Gout is characterised by deposition of urate crystals, causing acute monoarthritis and crystal deposits (tophi) in the skin. Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.Diagnosis is usually clinical, supported by presence of hyperuricaemia.Risk factors are those associated with hyperuricaemia, including: older age; non-white ethnicity; obesity; consumption of alcohol, meat, and fish; and use of diuretics.Hyperuricaemia may be associated with an increased risk of cardiovascular events; we don't know whether it is an independent risk factor.
We don't know whether NSAIDs reduce pain and tenderness in an acute attack of gout, although they are commonly used in clinical practice. They are associated with increased risks of gastrointestinal, and possible cardiovascular, adverse effects. Indometacin is widely used to treat acute gout despite the absence of RCT evidence of benefit. Etoricoxib is as effective as indometacin with reduced risks of gastrointestinal adverse effects.
Colchicine may be more effective than placebo at improving symptoms in acute gout. Its use is limited by the high incidence of adverse effects; although these may be reduced with low-dose colchicine regimens. Low-dose colchicine may be as effective at reducing pain in gout and may produce fewer adverse effects than high-dose colchicine.
We don't know whether intra-articular or parenteral corticosteroids, or corticotropin (ACTH), improve symptoms in acute gout. Oral corticosteroids seem as effective as NSAIDs and may have fewer short-term adverse events.
We don't know whether colchicine prevents attacks of gout in people with prior episodes, but it may reduce the risk of an attack in a person starting allopurinol treatment.
We don't know whether advice to lose weight or reduce alcohol or dietary purine intake prevents further attacks of gout.
We don't know whether sulfinpyrazone reduces the risk of recurrent attacks compared with placebo or other treatments.
We don't know whether xanthine oxidase inhibitors reduce the risk of recurrent attacks in the long term when compared with placebo or other treatments. Higher doses of febuxostat may increase the risks of gout attacks within the first 8 weeks of treatment compared with placebo, and compared with allopurinol.
PMCID: PMC3275296  PMID: 21575286
12.  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) 
Annals of the Rheumatic Diseases  2006;65(10):1312-1324.
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.
doi:10.1136/ard.2006.055269
PMCID: PMC1798308  PMID: 16707532
EULAR; gout; guidelines; treatment
13.  Gout  
BMJ Clinical Evidence  2008;2008:1120.
Introduction
Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute gout? What are the effects of treatments to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: colchicine, corticosteroids, corticotrophin (ACTH), non-steroidal anti-inflammatory drugs (NSAIDs), sulfinpyrazone, xanthine oxidase inhibitors, advice to lose weight, advice to reduce alcohol intake, advice to reduce dietary intake of purines.
Key Points
Gout is characterised by deposition of urate crystals, causing acute monoarthritis and crystal deposits (tophi) in the skin. Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.Diagnosis is usually clinical, supported by signs of hyperuricaemia.Risk factors are those associated with increased serum urate concentrations, including: older age; non-white ethnicity; obesity; consumption of alcohol, meat, and fish; and use of diuretics.Hyperuricaemia may be associated with an increased risk of cardiovascular events; we don't know whether it is an independent risk factor.
We don't know whether NSAIDs reduce pain and tenderness in an acute attack of gout, although they are commonly used in clinical practice. They are associated with increased risks of gastrointestinal, and possible cardiovascular, adverse effects. Indometacin is widely used to treat acute gout despite the absence of RCT evidence of benefit. Etoricoxib is as effective as indometacin with reduced risks of gastrointestinal adverse effects.
Although it has been widely used for many years, we don't know whether oral colchicine improves symptoms in acute gout. Its use is limited by the high incidence of adverse effects.
We don't know whether intra-articular, parenteral or oral corticosteroids, or corticotropin (ACTH), improve symptoms in acute gout.
We don't know whether colchicine prevents attacks of gout in people with prior episodes, but it may reduce the risk of an attack in a person starting allopurinol treatment. We don't know whether advice to lose weight or reduce alcohol or dietary purine intake prevents further attacks of gout.We don't know whether allopurinol or febuxostat, orsulfinpyrazone reduce the risk of recurrent attacks compared with placebo or other treatments.
PMCID: PMC2907998  PMID: 19445790
14.  Noise Reduction and Image Quality Improvement of Low Dose and Ultra Low Dose Brain Perfusion CT by HYPR-LR Processing 
PLoS ONE  2011;6(2):e17098.
Purpose
To evaluate image quality and signal characteristics of brain perfusion CT (BPCT) obtained by low-dose (LD) and ultra-low-dose (ULD) protocols with and without post-processing by highly constrained back-projection (HYPR)–local reconstruction (LR) technique.
Methods and Materials
Simultaneous BPCTs were acquired in 8 patients on a dual-source-CT by applying LD (80 kV,200 mAs,14×1.2 mm) on tube A and ULD (80 kV,30 mAs,14×1.2 mm) on tube B. Image data from both tubes was reconstructed with identical parameters and post-processed using the HYPR-LR. Correlation coefficients between mean and maximum (MAX) attenuation values within corresponding ROIs, area under attenuation curve (AUC), and signal to noise ratio (SNR) of brain parenchyma were assessed. Subjective image quality was assessed on a 5-point scale by two blinded observers (1:excellent, 5:non-diagnostic).
Results
Radiation dose of ULD was more than six times lower compared to LD. SNR was improved by HYPR: ULD vs. ULD+HYPR: 1.9±0.3 vs. 8.4±1.7, LD vs. LD+HYPR: 5.0±0.7 vs. 13.4±2.4 (both p<0.0001). There was a good correlation between the original datasets and the HYPR-LR post-processed datasets: r = 0.848 for ULD and ULD+HYPR and r = 0.933 for LD and LD+HYPR (p<0.0001 for both). The mean values of the HYPR-LR post-processed ULD dataset correlated better with the standard LD dataset (r = 0.672) than unprocessed ULD (r = 0.542), but both correlations were significant (p<0.0001). There was no significant difference in AUC or MAX. Image quality was rated excellent (1.3) in LD+HYPR and non-diagnostic (5.0) in ULD. LD and ULD+HYPR images had moderate image quality (3.3 and 2.7).
Conclusion
SNR and image quality of ULD-BPCT can be improved to a level similar to LD-BPCT when using HYPR-LR without distorting attenuation measurements. This can be used to substantially reduce radiation dose. Alternatively, LD images can be improved by HYPR-LR to higher diagnostic quality.
doi:10.1371/journal.pone.0017098
PMCID: PMC3037968  PMID: 21347259
15.  Allopurinol Therapy in Gout Patients Does Not Associate with Beneficial Cardiovascular Outcomes: A Population-Based Matched-Cohort Study 
PLoS ONE  2014;9(6):e99102.
Introduction
Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.
Methods
Patients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.
Results
With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08–1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10–1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73–0.95) for cardiovascular events compared with the allopurinol group.
Conclusions
The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.
doi:10.1371/journal.pone.0099102
PMCID: PMC4045898  PMID: 24897240
16.  The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age 
BMC Geriatrics  2012;12:11.
Background
The incidence of gout rises with increasing age. Management of elderly (≥65 years) gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT) in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial.
Methods
Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL) gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function) once daily. Flare prophylaxis was provided throughout the study duration.
Study endpoints were the percent of elderly subjects with sUA <6.0 mg/dL at the final visit, overall and by renal function status, percent change in sUA from baseline to final visit, flare rates, and rates of adverse events (AEs).
Results
Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0%) than febuxostat 40 mg (61.7%; p < 0.001) or allopurinol (47.3%; p < 0.001) for achieving the primary efficacy endpoint. Febuxostat 40 mg was also superior to allopurinol in this population (p = 0.029). In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028) and febuxostat 80 mg (82.5%; p < 0.001) compared to allopurinol 200/300 mg (46.9%). Compared to allopurinol 200/300 mg, the mean percent change in sUA from baseline was significantly greater for both febuxostat 80 mg (p < 0.001) and febuxostat 40 mg (p = 0.011) groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments.
Conclusions
These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg) in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated.
Trial registration
clinicaltrials.gov NCT#00430248
doi:10.1186/1471-2318-12-11
PMCID: PMC3368715  PMID: 22436129
17.  Prescription and dosing of urate-lowering therapy, rather than patient behaviours, are the key modifiable factors associated with targeting serum urate in gout 
Background
Long term serum urate (SU) lowering to a target of <0.36 mmol/l (6 mg/dl) is recommended for effective gout management. However, many studies have reported low achievement of SU targets. The aim of this cross-sectional study was to examine the clinical and psychological factors associated with SU targets in patients with gout.
Methods
Patients with gout for <10 years were recruited from primary and secondary care settings. SU target was defined as SU concentration <0.36 mmol/L at the time of the study visit. Both clinical and psychological factors associated with SU target were analysed. The relationship between SU target and measures of gout activity such as flare frequency, tophi, work absences, and Health Assessment Questionnaire-II was also analysed.
Results
Of the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36 mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose, patient confidence to keep SU under control, female sex, and ethnicity were independently associated with SU target. Other patient psychological measures and health-related behaviours, including adherence scores, were not independently associated with SU target in those taking ULT. Creatinine clearance, diuretic use, age, and body mass index were not associated with SU target. Patients at SU target reported lower gout flare frequency, compared with those not at target (p = 0.03).
Conclusions
ULT prescription and dosing are key modifiable factors associated with achieving SU target. These data support interventions focusing on improved use of ULT to optimise outcomes in patients with gout.
doi:10.1186/1471-2474-13-174
PMCID: PMC3493372  PMID: 22978848
Gout; Urate; Target; Allopurinol
18.  Impaired response or insufficient dosage? – examining the potential causes of ”inadequate response” to allopurinol in the treatment of gout 
Objectives
Gout is one of the most common forms of arthritis. It is well established that urate lowering therapy that aims for a serum urate less than at least 0.36mmol/l (6mg/dL) is required for successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor is the most commonly used urate lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol, these patients can be considered to have “inadequate response” to allopurinol. Herein we examine the potential mechanisms and implications of inadequate response to allopurinol.
Methods
The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.
Results
The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be “partially resistant” to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and or function such that oxypurinol is rendered less effective, and/or drug interactions.
Conclusions
It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician toward making a therapeutic choice that is more likely to result in achieving the serum urate target.
doi:10.1016/j.semarthrit.2014.05.007
PMCID: PMC4225179  PMID: 24925693
19.  Allopurinol initiation and all-cause mortality in the general population 
Annals of the rheumatic diseases  2014;74(7):1368-1372.
Background
Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population.
Methods
We conducted an incident user cohort study with propensity score matching using a UK general population database. The study population included individuals aged ≥40 years who had a record of hyperuricaemia (serum urate level >357 µmol/L for women and >416 µmol/L for men) between January 2000 and May 2010. To closely account for potential confounders of allopurinol use and risk of death, we constructed propensity score matched cohorts of allopurinol initiators and comparators (non-initiators) within 6-month cohort accrual blocks.
Results
Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92).
Conclusions
In this general population study, allopurinol initiation was associated with a modestly reduced risk of death in patients with hyperuricaemia and patients with gout. The overall benefit of allopurinol on survival may outweigh the impact of rare serious adverse effects.
doi:10.1136/annrheumdis-2014-205269
PMCID: PMC4222989  PMID: 24665118
20.  Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice 
BMC Family Practice  2013;14:170.
Background
Gout is estimated to affect 1.4% of adults in the UK. Appropriate and timely management is essential to reduce the risk of further flares, complications, and to reduce cardiovascular disease risk. The British Society for Rheumatology and British Health Professionals in Rheumatology (BSR/BHPR) and the European League Against Rheumatism (EULAR) have published guidance regarding the management of gout, thereby providing standards against which performance can be measured. This audit was designed to assess the extent to which patients diagnosed with gout in one primary care medical practice in North Staffordshire, UK, are managed in accordance with current best practice guidelines, and to identify strategies for improvement where appropriate.
Methods
Audit criteria were derived from the EULAR and BSR/BHPR guidelines; standards were set arbitrarily, but with consideration of patient comorbidity and other factors which may influence concordance. An electronic search of the practice records was performed to identify adults with a diagnosis of gout. Medical record review with a descriptive analysis was undertaken to assess the extent to which medical management adhered to the predefined standards.
Results
Of the total ≥18 year-old practice population (n = 8686), 305 (3%) patient records included a diagnosis of gout. Of these, 74% (n = 226) had an electronic record of serum uric acid (SUA), and 11% (n = 34) and 53% (n = 162) a measure of estimated glomerular filtration rate (eGFR) ever and serum glucose since diagnosis respectively. 34% (n = 105) of patients had ever taken urate-lowering therapy with 25% (n = 77) currently prescribed this at the time of data extraction. Dose adjustment and monitoring of treatment according to SUA was found to be inadequate. Provision of lifestyle advice and consideration of comorbidities was also lacking.
Conclusions
The primary care management of gout in this practice was not concordant with national and international guidance, a finding consistent with previous studies. This demonstrates that the provision of guidelines alone is not sufficient to improve the quality of gout management and we identify possible strategies to increase guideline adherence.
doi:10.1186/1471-2296-14-170
PMCID: PMC3830984  PMID: 24225170
Gout; Management; Audit; Primary care; Allopurinol; Serum uric acid
21.  African American patients with gout: efficacy and safety of febuxostat vs allopurinol 
Background
African Americans are twice as likely as Caucasians to develop gout, but they are less likely to be treated with urate-lowering therapy (ULT). Furthermore, African Americans typically present with more comorbidities associated with gout, such as hypertension, obesity, and renal impairment. We determined the efficacy and safety of ULT with febuxostat or allopurinol in African American subjects with gout and associated comorbidities and in comparison to Caucasian gout subjects.
Methods
This is a secondary analysis of the 6-month Phase 3 CONFIRMS trial. Eligible gouty subjects with baseline serum urate (sUA) ≥ 8.0 mg/dL were randomized 1:1:1 to receive febuxostat 40 mg, febuxostat 80 mg, or allopurinol (300 mg or 200 mg depending on renal function) daily. All subjects received gout flare prophylaxis. Primary efficacy endpoint was the proportion of subjects in each treatment group with sUA < 6.0 mg/dL at the final visit. Additional endpoints included the proportion of subjects with mild or with moderate renal impairment who achieved a target sUA < 6.0 mg/dL at final visit. Adverse events (AEs) were recorded throughout the study.
Results
Of the 2,269 subjects enrolled, 10.0% were African American and 82.1% were Caucasian. African American subjects were mostly male (89.5%), obese (BMI ≥ 30 kg/m2; 67.1%), with mean baseline sUA of 9.8 mg/dL and mean duration of gout of 10.4 years. The proportions of African American subjects with a baseline history of diabetes, renal impairment, or cardiovascular disease were significantly higher compared to Caucasians (p < 0.001). ULT with febuxostat 80 mg was superior to both febuxostat 40 mg (p < 0.001) and allopurinol (p = 0.004). Febuxostat 40 mg was comparable in efficacy to allopurinol. Significantly more African American subjects with mild or moderate renal impairment achieved sUA < 6.0 mg/dL in the febuxostat 80 group than in either the febuxostat 40 mg or allopurinol group (p < 0.05). Efficacy rates in all treatment groups regardless of renal function were comparable between African American and Caucasian subjects, as were AE rates.
Conclusions
In African American subjects with significant comorbidities, febuxostat 80 mg is significantly more efficacious than either febuxostat 40 mg or allopurinol 200/300 mg. Febuxostat was well tolerated in this African American population.
Please see related article: http://www.biomedcentral.com/1741-7015/10/15
doi:10.1186/1471-2474-13-15
PMCID: PMC3317813  PMID: 22316106
22.  Clinical and health care use characteristics of patients newly prescribed allopurinol, febuxostat and colchicine for gout 
Arthritis care & research  2013;65(12):2008-2014.
Background
Gout is a common inflammatory arthritis with the increasing prevalence in the developed countries. It is well-known that many patients with gout have significant comorbidities and high health care utilization.
Methods
Using US insurance claims data (2009–2011), a population-based cohort study was conducted to describe clinical characteristics and health care utilization patterns in patients with gout newly prescribed allopurinol, febuxostat or colchicine.
Results
There were 25,051 allopurinol, 4,288 febuxostat and 6,238 colchicine initiators. Mean age was 53 years and 83%–87% were male. More than half of patients had hypertension and hyperlipidemia, 20% had diabetes and 10% cardiovascular disease. The mean uric acid level (mg/dl) was similar at baseline ranging from 8.1 to 8.5 across the groups. Compared to allopurinol or colchicine initiators, febuxostat initiators had more comorbidities and greater health care uses including outpatient, inpatient or emergency room visits, both at baseline and during the follow-up. Use of gout related drugs, such as opioids, steroids and non-steroidal anti-inflammatory drugs, was most common in febuxostat and least common in colchicine initiators. The median daily dose at both start and end of treatment was 300mg for allopurinol, 40mg for febuxostat, and 1.2mg for colchicine. The dosage of allopurinol and febuxostat was rarely increased during the follow-up.
Conclusion
Patients who started allopurinol, febuxostat or colchicine for gout generally had hyperuricemia and multiple comorbidities. Febuxostat initiators had more comorbidities and greater use of health care resources and gout-related drugs than other groups. Overall, the dosages of allopurinol or febuxostat remained unchanged over time.
doi:10.1002/acr.22067
PMCID: PMC4096791  PMID: 23861232
gout; allopurinol; febuxostat; colchicine
23.  Allopurinol desensitization with A 2 weeks modified protocol in an elderly patients with multiple comorbidities: a case report 
Background
Allopurinol is an effective urate-lowering drug that is well tolerated by the majority of patients. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol.
Case presentation
75 year old male patient with gout, renal insufficiency, history of metastatic colorectal carcinoma status post-resection was referred to Allergy clinic for a maculopapular eruption that developed 1 week after initiating therapy with allopurinol. The rash resolved with discontinuation of allopurinol. However, his serum urate level rose to 19.9 mg/dl. We initially proposed a slow 4 week oral allopurinol desensitization. The treating nephrologist felt it was critical to lower urate more rapidly. As a result, we modified the dose and standard 4 week protocol down to 2 weeks. A suspension of allopurinol was prepared by the allergy nurse practitioner with a 300 mg allopurinol tablet. The sensitization protocol was modified as a starting dose of 0.3 mg escalating to a final dose of 300 mg/day in 2 weeks. There was no reaction during or after the desensitization. The patient’s urate level normalized (6.3 mg/dl) and has continued on 300 mg allopurinol daily without reaction.
Conclusion
A 2 week modified allopurinol desensitization protocol is a safe alternative for elderly patients with multiple comorbidities.
doi:10.1186/1710-1492-10-52
PMCID: PMC4326512  PMID: 25685161
Allopurinol hypersensitivty; Oral drug desensitization; Slow desensitization; Hyperuricemia; Gout; Maculopapular exanthema
24.  Racial and Gender Disparities in Patients with Gout 
Gout affects 8.3 million Americans according to NHANES 2007–2008, roughly 3.9% of the U.S. population. Gout has significant impact on physical function, productivity, health-related quality of life (HRQOL) and health care costs. Uncontrolled gout is also associated with significant utilization of emergent care services. Women are less likely to have gout than men, but in the postmenopausal years the gender difference in disease incidence decreases. Compared to Whites, racial/ethnic minorities, especially blacks, have higher prevalence of gout. On the other hand, blacks are less likely to receive quality gout care, leading to a disproportionate morbidity. Women are less likely than men to receive allopurinol, less likely to get joint aspirations for crystal analyses for establishing diagnosis, but those on urate-lowering therapy are as/more likely as men to get serum urate check within 6-months of initiation. While a few studies provide the knowledge related to gender and race/ethnicity disparities in gout, several knowledge gaps exist in gout epidemiology and outcomes differences by gender and race/ethnicity. These should be explored in future studies.
doi:10.1007/s11926-012-0307-x
PMCID: PMC3545402  PMID: 23315156
Gout; Hyperuricemia; Race; Ethnicity; Gender; Disparity; Epidemiology; Prevalence; Genetic risk factors; Adverse effects
25.  Health-related quality of life and treatment satisfaction in patients with gout: results from a cross-sectional study in a managed care setting 
Background
Patient satisfaction with treatment directly impacts adherence to medication.
Objective
The objective was to assess and compare treatment satisfaction with the Treatment Satisfaction Questionnaire for Medication (TSQM), gout-specific health-related quality of life (HRQoL) with the Gout Impact Scale (GIS), and generic HRQoL with the SF-12v2® Health Survey (SF-12) in patients with gout in a real-world practice setting.
Methods
This cross-sectional mail survey included gout patients enrolled in a large commercial health plan in the US. Patients were ≥18 years with self-reported gout diagnosis, who filled ≥1 prescription for febuxostat during April 26, 2012 to July 26, 2012 and were not taking any other urate-lowering therapies. The survey included the TSQM version II (TSQM vII, score 0–100, higher scores indicate better satisfaction), GIS (score 0–100, higher scores indicate worse condition), and SF-12 (physical component summary and mental component summary). Patients were stratified by self-report of currently experiencing a gout attack or not to assess the discriminant ability of the questionnaires.
Results
A total of 257 patients were included in the analysis (mean age, 54.9 years; 87% male). Patients with current gout attack (n=29, 11%) had worse scores than those without gout attack on most instrument scales. Mean differences between current attack and no current attack for the TSQM domains were: −20.6, effectiveness; −10.6, side effects; −12.1, global satisfaction (all P<0.05); and −6.1, convenience (NS). For the GIS, mean differences were: 30.5, gout overall concern; 14.6, gout medication side effects; 22.7, unmet gout treatment needs; 11.5, gout concern during attack (all P<0.05); and 7.9, well-being during attack (NS). Mean difference in SF-12 was −6.6 for physical component summary (P<0.05) and −2.9 for mental component summary (NS). Correlations between several TSQM and GIS scales were moderate.
Conclusion
The TSQM and GIS were complementary in evaluating the impact of gout flare on treatment satisfaction and HRQoL. Correlations between the two instruments supported the relationship between treatment satisfaction and HRQoL.
doi:10.2147/PPA.S83700
PMCID: PMC4501348  PMID: 26185426
febuxostat; gout; gouty arthritis; Treatment Satisfaction Questionnaire for Medicine; Gout Impact Scale; SF-12

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