The proportion of patient visits with a diagnosis of gout increased between 2007 and 2011, and this increase was significant. It is hypothesized that gout visits are on the rise due to increases in obesity, hypertension, and purine-rich diets [1, 2]. Obesity increases the production of serum urate (sUA) levels and also decreases urate excretion while weight reduction has been associated with uric acid level declination . Along with risk factors, there are many disease associations with gout including metabolic syndrome, hypertension, and cardiovascular disease . Metabolic syndrome has been strongly associated with gout; 60% of US population with gout also has metabolic syndrome, a prevalence three times higher in those with gout . Metabolic syndrome has likely increased over the study years, helping explain the rise in gout diagnoses .
The number of gout visits in this study was not as high as noted in a similar prior study,  which could be attributed to several different factors. Although not specified in their methods, the Krishnan and Chen study appears to have used aggregated estimates for the years and databases studied, rather than the average annual estimates used in this study. Additionally, Krishnan and Chen only utilized NAMCS and NHAMCS-OPD, whereas this study also utilized NHAMCS-ED. Despite approximately 95 million visits attributed to the NHAMCS-ED, visits for gout in the ED were less likely. This likely increased the total number of overall visits without adding a commensurate number of gout-specific visits to the numerator. Further, while only 31% of the study population was aged 65 or older, 61% was female and the prevalence of gout is known to both increase with age and be more prevalent in males .
Another prior study with higher gout estimates by Zhu, et al. was based on participant reported data from the National Health and Nutrition Examination Survey (NHANES), which lends itself to estimating true prevalence . This study is based on provider reported ambulatory, outpatient and emergency visits, therefore limiting the ability to estimate the true prevalence of gout. This database distinction helps explain this difference in gout estimates. It is worth noting that NHANES as well as the data sources used for this study are all population-based surveys.
The study results are consistent with several international epidemiology studies which examined the prevalence of gout [19,20,21,22,23]. The prevalence of gout has increased significantly in the United Kingdom (UK) over the years of 1997 through 2012 according to a study which utilized the Clinical Practice Datalink . Another study which looked at gout prevalence in the UK and Germany from 2000 to 2005 with the IMS Disease Analyzer found a prevalence of 1.4% . A study of the Canadian province of British Columbia from 2000 to 2012 using PopulationDataBC found a prevalence of 3.8% in 2012, and there was a noted increase over the study period . A Swedish study examined gout trends from 2002 to 2012 and found a prevalence of 1.8% in 2012 as well as an increase over the study period.  A study in Taiwan utilizing the National Health Insurance Research Database found a higher prevalence rate of 6.24% over the study period of 2005 to 2010 . With the exception of the Taiwan study , all studies were consistent with this study’s findings with regards to gout prevalence and increasing prevalence over the years.
This study demonstrated an association between age, sex, race group and gout visits, with an increased proportion among older age groups (≥45 years of age), males, African American and ‘Other’ race groups. These finding are consistent with previous studies [1, 3, 8, 10] showing that the risk of developing gout is age-related, [1, 8] and that estrogen is protective in premenopausal women due to its uricosuric effect . ‘Other’ race within the databases consists of Asian, Native Hawaiian or other Pacific Islander, American Indian or Alaska Native, or more than one race reported. A higher prevalence of gout is well known in Asians and Pacific Islanders, as well as African Americans with genetics playing a role due to hyperuricemia-associated DNA sequence variations [24, 25]. However, diet and the presence of co-morbidities cannot be ruled out.
Hispanic/Latino individuals were found to be less likely to have a visit with gout than Non-Hispanic/Latinos. One possible explanation is related to diet. A previous study showed that Non-Hispanic/Latinos consume more red meat and seafood when compared to Hispanic/Latinos.  Diets rich in red meat and seafood are widely known to be associated with the production of uric acid . Given that Hispanic/Latino diets are typically more heavily based on grains and beans along with fresh fruits and vegetables, Hispanic/ Latinos may produce less uric acid resulting in a lower incidence of gout .
Patient visits with Medicaid and ‘Other’ insurance were less likely to have a diagnosis of gout. Despite the lack of statistically significant interaction effects in the multivariable model, this could be attributed to the role of age with the risk of developing gout [1, 8]. ‘Other’ insurance consisted of worker’s compensation, self-pay, no charge/charity, and other, while Medicaid also included the Children’s Health Insurance Program. Patients with ‘Other’ insurance or Medicaid are less likely to be older, the age group at the highest risk for gout.
Individuals were significantly less likely to have a visit with a diagnosis of gout in a hospital emergency setting than they were in a physician’s office. Patients are more likely to visit a provider’s office for routine check-ups and for chronic conditions like gout. While individuals may visit a hospital for an initial or particularly severe attack of gout, they are presumably more likely to visit their provider when simply attempting to help keep their gout under control. Furthermore, patients with gout are much more likely to visit their provider if they are being prescribed gout prophylaxis medication.
A study by Garg, et al. looked at gout-related health care utilization in US emergency departments utilizing the National Emergency Department Sample (NEDS) from 2006 to 2008 . The Garg study found approximately 0.7% of ED visits to be gout-related, slightly higher than 0.4% found in this study . A similar study by Jinno, et al. also utilized NEDS and examined gout ED visits from 2006 to 2012 . This study found 0.19% of visits with a primary diagnosis of gout . Although not exactly comparable to this study, which includes non-ED databases in addition to the NHAMCS-ED, similar findings with both of these studies include gout-related ED visits being more likely with men, and increasing age; and less likely with different insurance types [28, 29].
Diuretic use was four times more likely to be associated with a gout visit. Previous research has shown that individuals who have high blood pressure and are also taking a diuretic have an increased risk for acquiring gout . The diuretics’ mechanism of action is thought to contribute to gout, increasing uric acid reabsorption .
The graph of gout medication class by year showed consistency in use among the drug classes over the years. Antigout and antihyperuricemic medication classes remained the two most commonly prescribed treatments, while NSAIDs and steroids were used less. It is worth noting that due to drug class coding within the databases some medications could have been coded in both the antigout and antihyperuricemic class (i.e., allopurinol and febuxostat) since drugs may be coded in as many as four different medication classes. This might explain why the antigout percentage is greater than the antihyperuricemics. However, the findings in this study are consistent with the prior NAMCS and NHAMCS-OPD study which looked at gout treatment trends up through 2009 . These treatment trends can also be explained by typical prescribing patterns for a gouty attack versus prophylaxis treatment to prevent gout flare. NSAIDs and steroids are typically only used for gouty attacks and patients are treated prophylactically after an initial gout attack to prevent future attacks [2, 31]. In addition, the risk of side effects with NSAIDs such as gastrointestinal bleeds, renal failure, and hypertension likely impacted their use in treatment, especially in the case when chronic treatment is warranted [32, 33].
As evident from the figure showing the percentage of visits by year for individual gout drugs, allopurinol continues to be the most prescribed treatment with colchicine second, a finding also consistent with Krishnan and Chen . Allopurinol dominated the market as the only medication to reduce uric acid synthesis until the introduction of febuxostat in 2009 [2, 4, 11]. As expected, the percentage of visits with febuxostat increased following its approval. Despite this, allopurinol and colchicine use changed little from 2009 through 2011, evidence that febuxostat introduction had minimal impact on the treatment trends for the study years. Probenecid use has declined over the years which can be explained by its potential for drug-drug interactions as well as less favorable side effect profile, including risk of urolithiasis [2, 11, 34].
The previously mentioned international studies showed similar treatment trends. Allopurinol was prescribed for most patients in UK and Germany at 89 and 93% respectively; while colchicine use was only around 15–16% for both . Probenecid use was minimal (< 1%), but NSAIDs were utilized 80–90% for prophylaxis. . Allopurinol was also most commonly prescribed in British Columbia, Canada, with less than 1% use of febuxostat and probenecid . Colchicine and steroid use increased in British Columbia over the study period, while NSAID use declined by 31% . A study in Australia in 2005 found allopurinol to comprise 98.4% of all urate lowering therapy with probenecid at < 1% . There was a common theme from these studies of the overall underutilization of urate-lowering treatment for gout [19,20,21,22,23, 35].
The study is not without limitations. The observational, cross-sectional nature of the study design limited the authors to statements of association between visits with gout diagnosis and the factors of interest. No claims of causality can be made. Furthermore, the cross-sectional nature of the data sources used did not allow for repeated measurements on patients over time. Several variables of interest, including alcoholism, Parkinson’s disease, depression, hypertension, weight status, tobacco use, and losartan use had to be excluded from all analyses due to missing data and/or reliability issues. This is particularly unfortunate for variables such as hypertension and weight status, both known to be significantly associated with gout. All of the databases utilized are limited to three diagnoses. The NAMCS and NHAMCS-OPD include a data field to collect other specific disease states (includes hypertension, diabetes, and depression), but NHAMCS-ED does not and only collects the diabetes variable of interest in their other specific disease field. This likely contributed to the missing data for such highly prevalent conditions like hypertension and diabetes. The NAMCS and NHAMCS databases do not include federal offices or hospitals, including Veterans Affairs facilities where gout can be prevalent. In addition, the databases do not provide a true prevalence of gout, but rather a surrogate via visits for gout based on diagnostic codes from the three recorded diagnoses and gout medications prescribed at the visits. It is not uncommon for epidemiological studies to rely on diagnostic codes for estimating prevalence. Those studies which have relied on such codes have shown good accuracy. In addition, although gout medications were also used to identify gout visits, there is a chance that medications like colchicine and probenecid were used for conditions other than gout. However, such alternative uses are rare. Study strengths include the use of nationally representative, population-based surveys which allow for generalizing findings to the portion of the US population that is commensurate with the study population. Further, the databases are provider reported data which allows for more reliability of results as compared to patient reported data. This is the first study known to the authors to investigate febuxostat in the treatment of gout since its approval in 2009 .