Tele-monitoring flares using a smartphone app in patients with gout or suspected gout: a feasibility study

Objectives Gout flares are painful and disabling. We developed a smartphone app for patients to tele-monitor gout flares surveyed by clinicians. This study aimed to assess patient acceptability, technical and clinical feasibility. Methods Adult patients with either established gout or high suspicion thereof were recruited if they possessed a smartphone and reported a recent arthritis attack. A smartphone application was used to identify gout flares by asking during 90 consecutive days: 1) what is your pain score (0–10), 2) are your joints warm, 3) are your joints swollen and 4) are you currently experiencing a gout flare. The clinician was alerted via email if a flare occurred. Patient acceptability was assessed using the Technology Acceptance Model. Technical feasibility consisted of reported technical issues and clinical feasibility of actions taken by the clinician regarding gout flare alerts. Results 29 included patients completed the study. Participants mean age was 57 years and all but one were male. Adherence rate was 96% (110 out of 2,910 queries were missed). Patients had a positive attitude towards app use, found the app very easy to use (mean usability score 81 out of 100) and were neutral to positive on its usefulness. There were four minor technical issues. A total of 100 gout flare alerts were generated that led to 18 proactive contacts with patients. Conclusion A smartphone app to monitor gout flares was developed and tested, showing high adherence, good acceptability and clinical feasibility for established gout patients. Trial registration Netherlands Trial Register, https://www.trialregister.nl, NL6435

Purinergic Signaling in the Regulation of Gout Flare and Resolution

Gout flares require monosodium urate (MSU) to activate the NLRP3 inflammasome and secrete sufficient IL-1β. However, MSU alone is not sufficient to cause a flare. This is supported by the evidence that most patients with hyperuricemia do not develop gout throughout their lives. Recent studies have shown that, besides MSU, various purine metabolites, including adenosine triphosphate, adenosine diphosphate, and adenosine bind to different purine receptors for regulating IL-1β secretion implicated in the pathogenesis of gout flares. Purine metabolites such as adenosine triphosphate mainly activate the NLRP3 inflammasome through P2X ion channel receptors, which stimulates IL-1β secretion and induces gout flares, while some purine metabolites such as adenosine diphosphate and adenosine mainly act on the G protein-coupled receptors exerting pro-inflammatory or anti-inflammatory effects to regulate the onset and resolution of a gout flare. Given that the purine signaling pathway exerts different regulatory effects on inflammation and that, during the inflammatory process of a gout flare, an altered expression of purine metabolites and their receptors was observed in response to the changes in the internal environment. Thus, the purine signaling pathway is involved in regulating gout flare and resolution. This study was conducted to review and elucidate the role of various purine metabolites and purinergic receptors during the process.

SToRytelling to Improve Disease outcomes in Gout (STRIDE-GO): a multicenter, randomized controlled trial in African American veterans with gout

Background Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs). Methods In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence. Results The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p > 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p = 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p = 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p = 0.003), and 6 months, 29.5 vs. 34.5 (p = 0.03), respectively. Conclusions A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout. Trial registration Registered at ClinicalTrials.gov NCT02741700

Which attributes are the most and least important to patients when considering gout flare burden over time? A best-worst scaling choice study

Objective Several factors contribute to the patient experience of gout flares, including pain intensity, duration, frequency, and disability. It is unknown which of these factors are most important to patients when considering flare burden over time, including those related to the cumulative experience of all flares, or the experience of a single worst flare. This study aimed to determine which flare attributes are the most and least important to the patient experience of flare burden over time. Methods Participants with gout completed an anonymous online survey. Questions were aimed at identifying which attributes of gout flares, representing both individual and cumulative flare burden, were the most and least important over a hypothetical six-month period. A best-worst scaling method was used to determine the importance hierarchy of the included attributes. Results Fifty participants were included. Difficulty doing usual activities during the worst flare and pain of the worst flare were ranked as the most important, while average pain of all flares was considered the least important. Overall, attributes related to the single worst gout flare were considered more important than attributes related to the cumulative impact of all flares. Conclusion When thinking about the burden of gout flares over time, patients rank activity limitation and pain experienced during their worst gout flare as the most important contributing factors, while factors related to the cumulative impact of all flares over time are relatively less important.

Mechanosensitive TRPV4 is required for crystal-induced inflammation

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1β which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.

The role of dual energy computed tomography in the differentiation of acute gout flares and acute calcium pyrophosphate crystal arthritis

Objectives To analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD). Methods Thirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition. Results Sensitivity of DECT for gout was 63% (95% CI 0.41–0.81) with a specificity of 92% (0.41–0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23–0.83) and 92% (0.74–0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73–0.99) and a specificity of 83% (0.52–0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59–1.00) and 92% (0.74–0.99), respectively. Conclusion DECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis. Key Points• DECT offers a lower sensitivity for acute gout flares than previously described.• DECT sensitivity for acute CPP crystal arthritis is less than the already validated ultrasound.

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.

Treatment of Acute Gout Flares in the Emergency Department: Prescribing Patterns and Revisit Rates

Background The incidence and health care costs of gout flares have increased in the United States. The increased costs may be a result of a lack of adherence to treatment guidelines and medication knowledge. Identifying causes for this trend is vital to mitigate inappropriate resource use. Objectives The aim was to identify pharmacotherapy use related to gout treatment before, during hospital visit or stay, and on discharge in patients presenting to the emergency department (ED) with gout flares. Secondary end points included opioid use, revisit rates, and associated risk factors. Methods We performed a retrospective cohort study at a community teaching hospital ED. All consecutive patients visiting the ED from January 2016 to July 2019 with a primary diagnosis of gout flare were included. Data were extracted from the electronic medical records. Results The analysis included 214 patients. Anti-inflammatory medication was not prescribed in 33.6% during the hospital visit and 29.6% of patients on discharge. History of opioid use (odds ratio [OR] = 3.3; 95% CI = 1.3-8.6; P = 0.014) and gastroesophageal reflux disease (OR = 3.5; 95% CI = 1.09-10.9; P = 0.035) were associated with opioid prescription on discharge. ED revisits within 90 days for any gout-related or non–gout-related cause were recorded in 16.8% of patients. Conclusion and Relevance Roughly 30% of patients did not receive an anti-inflammatory on discharge, and opioids were frequently overused in gout management in the ED. There is an opportunity for further education of health care providers regarding gout treatment.