Symptom Exacerbations of Patients Attending a Community Mental Health Center During the COVID-19 Pandemic. / Bir Toplum Ruh Sagligi Merkezi'nde Takip Edilen Hastalarda COVID-19 Salgini Sürecinde Belirtilerde Alevlenmeler.

OBJECTIVE: The aim of this study was to examine the effect of the COVID-19 pandemic on the clinical conditions of the patients with bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) in a community mental health center (CMHC). METHOD: Symptom exacerbations, emergency service admissions, drug dose increases, additional medication prescriptions, and psychiatric hospitalizations of patients with BD and SSD in the CMHC were evaluated retrospectively. The data from the 1-year prior, 6-months prior, 6-months after the onset and 1-year after the onset of the pandemic were compared. Hospital and CMHC medical records were used for outcomes. Personal and Social Performance (PSP) Scale was used to assess the level of functioning. RESULTS: 107 patients with the diagnosis of BD and 121 patients with the diagnosis of SSD were recruited. In the BD group, there was increase in the frequency of symptom exacerbations (p=0.001) and additional medication prescriptions or increased dose (p=0.007), with decrease in emergency service admissions (p=0.039) during the pandemic. In the patients with SSD, the number of patients with exacerbation of symptoms (p=0.001) and with increased dose or additional medication prescriptions (p=0.004) were higher during the pandemic. There was no increase in the rate of hospitalized patients in the period of first 6 months and first one year. Symptom exacerbations were more frequent in the SSD group with Covid (+) in family (p=0.016). CONCLUSION: The fact that the hospitalization rates remained the same despite an increase in the acute exacerbations provides info on the role of CMHCs and how mental health system functioned during the pandemic.

Safety profile of recombinant adjuvanted anti-herpes zoster vaccine (RZV) in high-risk groups: Data from active surveillance program. Puglia (Italy), 2021-23.

BACKGROUND: Since 2021 a recombinant adjuvanted anti-Herpes Zoster vaccine(Recombinant Zoster Vaccine, RZV) is offered in Italy to high-risk patients. Few real-life data about RZV safety are available in target populations. OBJECTIVES: This study investigates Adverse Events Following Immunization(AEFIs), baseline disease flare-ups, and Herpes Zoster (HZ) episodes occurring after RZV administration in a heterogeneous population of fragile patients to design its safety profile. METHODS: This is a retrospective population-based study. RZV-vaccinated patients at Bari Policlinico General Hospital vaccination clinic from October 1st, 2021, to March 31st, 2023, were enrolled. Subjects were screened for reason of RZV eligibility and baseline chronic pathologies. AEFIs occurred in the first 7-days post-vaccination period were collected, and baseline disease flare-ups and post-vaccination HZ episodes were assessed via a 3-month follow-up. RESULTS: Five-hundred-thirty-eight patients were included and total of 1,031 doses were administered. Most patients were vaccinated due to ongoing immunosuppressive therapy(54.65 %); onco-hematological and cardiovascular conditions were the most common chronic baseline pathologies. Out of 1,031 follow-ups, 441 AEFI cases were reported(42.7/100). The most common symptoms were injection site pain/itching(35.60/100), asthenia/malaise(11.44/100), and fever (10.09/100). Four serious AEFIs occurred(0.38/100). Older age, male sex, and history of cardiovascular diseases(OR:0.71; 95CI:0.52-0.98; p-value <0.05) were found to decrease AEFIs risk, while endocrine-metabolic illnesses(OR:1.61; 95CI:1.15-2.26; p-value <0.05) increased it. Twelve patients(2.23 %) reported a flare-up/worsening of their baseline chronic condition within the first three months after vaccination(mean interval 31.75 days, range 0-68 days). Patients with rheumatological illnesses had a higher risk of relapse(OR:16.56; 95CI:3.58-76.56; p-value <0.001), while male sex behaved as a protective factor. Twelve patients who completed the vaccination cycle(2.43%) had at least one HZ episode by the long-term follow-up. CONCLUSIONS: The study demonstrates RZV safety in a significant number of high-risk patients. Hence, RZV should be actively offered as part of tailored vaccination programs to decrease the burden of HZ in fragile populations.

Patient-reported experience with Fabry disease and its management in the real-world setting: results from a double-blind, cross-sectional survey of 280 respondents.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a heterogeneous clinical presentation. Patients with FD may exhibit early signs/symptoms including neuropathic pain, gastrointestinal complaints, and dermatologic manifestations. FD may ultimately progress to renal, neurologic, and cardiac dysfunction. Current treatments for FD have significantly improved the management and outcomes for patients with FD, but important clinical and convenience limitations still exist. METHODS: To illuminate the impact of FD on daily life from the patient's perspective, we asked adult patients (≥ 18 years old) with FD in the United States and Canada to complete a 33-question online survey to assess patient-reported disease severity, management, and treatment outcomes. RESULTS: A total of 280 respondents with FD completed the survey; they had a mean age of 47 years, and 68% (191/280) were women. Most were currently receiving FD treatment (84%, 234/280) with enzyme replacement therapy (ERT) (89%, 208/234) or chaperone therapy (11%, 26/234). Common symptoms included low energy/fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands/feet (60%, 168/280), ringing in ears/hearing loss (54%, 151/280), general body pains/pain crises (51%, 143/280), and abdominal/stomach pain (50%, 140/280). More than half (51%, 144/280) of respondents reported their symptoms as bothersome (38%, 106/280) or difficult to control (14%, 38/280). Temporary symptom worsening between infusions was reported by about half of respondents: 51% (108/211) currently receiving ERT and 48% (14/29) previously receiving ERT. Only 48% (59/122) of respondents reported their symptom worsening to their physician. Of those who reported it, 41% (24/59) said that their physician prescribed medication to manage their symptoms or changed their treatment regimen. CONCLUSIONS: Our analysis highlights the gap between current standard-of-care in disease monitoring and patient perception of disease progression among patients with FD. This information may be helpful for healthcare providers and drug developers seeking to improve the care of patients with FD by addressing unmet needs of high relevance.

Long-term Impact of Tropical Cyclones on Disease Exacerbation Among Children with Asthma in the Eastern United States, 2000-2018.

BACKGROUND: Tropical cyclones are associated with acute increases in mortality and morbidity, but few studies have examined their longer-term health consequences. We assessed whether tropical cyclones are associated with a higher frequency of symptom exacerbation among children with asthma in the following 12 months in eastern United States counties, 2000-2018. METHODS: We defined exposure to tropical cyclones as a maximum sustained windspeed >21 meters/second at the county center and used coarsened exact matching to match each exposed county to one or more unexposed counties. We used longitudinal, de-identified administrative claims data to estimate the county-level, monthly risk of experiencing at least one asthma exacerbation requiring medical attention among commercially insured children aged 5-17 with prior diagnosis of asthma. We used a difference-in-differences approach implemented via a Poisson fixed effects model to compare the risk of asthma exacerbation in the 12 months before versus after each storm in exposed versus unexposed counties. RESULTS: Across 43 tropical cyclones impacting the eastern United States, we did not observe evidence of an increase in the risk of symptom exacerbation in the 12 months following the storm (random-effects meta-analytic summary estimate: risk ratio = 1.03 [95% confidence interval = 0.96, 1.10], I2 = 17%). However, certain storms, such as Hurricane Sandy, were associated with a higher risk of symptom exacerbation. CONCLUSIONS: These findings are consistent with the hypothesis that some tropical cyclones are detrimental to children's respiratory health. However, tropical cyclones were not associated in aggregate with long-term exacerbation of clinically apparent asthma symptoms among a population of children with commercial health insurance.

How common are side effects of treatment to prevent gout flares when starting allopurinol?

The studyRoddy E, Bajpai R, Forrester H, et al. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink. Ann Rheum Dis 2023;82:1618-25.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

The clinical benefits of sodium-glucose cotransporter type 2 inhibitors in people with gout.

Gout is the most common form of inflammatory arthritis worldwide and is characterized by painful recurrent flares of inflammatory arthritis that are associated with a transiently increased risk of adverse cardiovascular events. Furthermore, gout is associated with multiple cardiometabolic-renal comorbidities such as type 2 diabetes, chronic kidney disease and cardiovascular disease. These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of serum urate concentrations and traditional cardiovascular risk factors. Although better implementation of standard gout care could improve gout outcomes, deliberate efforts to address the cardiovascular risk in patients with gout are likely to be required to reduce mortality. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are approved for multiple indications owing to their ability to lower the risk of all-cause and cardiovascular death, hospitalizations for heart failure and chronic kidney disease progression, making them an attractive treatment option for gout. These medications have also been shown to lower serum urate concentrations, the causal culprit in gout risk, and are associated with a reduced risk of incident and recurrent gout, potentially owing to their purported anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both the symptoms of gout and its comorbidities.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Epstein-Barr virus reactivation and disease flare of systemic lupus erythematosus.

SLE affects females rather than males with a ratio of about 9:1. Owing to the high morbidity with multiple organ involvement, SLE flare-up remains a challenge for women's health. In an accumulation of the past 70 years of studies globally, EBV has been found to be strongly associated with SLE. In the past two decades, EBV reactivation has been proven as prevalent in SLE patients as well as being strongly associated with higher SLE activity and higher prevalence of SLE flare. Hence, strategies to control EBV reactivation in SLE including pharmacological (such as Tenofovir prodrugs TDF and TAF) and non-pharmacological approaches are being developed. The heterogeneity of SLE constitutes clinical challenges, suggesting a stratification of SLE into subgroups based on EBV reactivation or non-reactivation is reasonable. Future-wise, adding anti-EBV reactivation medication to current immunosuppressants for the subgroup of SLE patients with EBV reactivation could be beneficial to achieve long-term remission of SLE.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

Predicting Response to In-Hospital Pulmonary Rehabilitation in Individuals Recovering From Exacerbations of Chronic Obstructive Pulmonary Disease / Predicción de la respuesta a la rehabilitación pulmonar hospitalaria en personas que se recuperan de exacerbaciones de la enfermedad pulmonar obstructiva crónica

Background: Predicting the response to pulmonary rehabilitation (PR) could be valuable in defining admission priorities. We aimed to investigate whether the response of individuals recovering from a COPD exacerbation (ECOPD) could be forecasted using machine learning approaches. Method: This multicenter, retrospective study recorded data on anthropometrics, demographics, physiological characteristics, post-PR changes in six-minute walking distance test (6MWT), Medical Research Council scale for dyspnea (MRC), Barthel Index dyspnea (BId), COPD assessment test (CAT) and proportion of participants reaching the minimal clinically important difference (MCID). The ability of multivariate approaches (linear regression, quantile regression, regression trees, and conditional inference trees) in predicting changes in each outcome measure has been assessed. Results: Individuals with lower baseline 6MWT, as well as those with less severe airway obstruction or admitted from acute care hospitals, exhibited greater improvements in 6MWT, whereas older as well as more dyspnoeic individuals had a lower forecasted improvement. Individuals with more severe CAT and dyspnea, and lower 6MWT had a greater potential improvement in CAT. More dyspnoeic individuals were also more likely to show improvement in BId and MRC. The Mean Absolute Error estimates of change prediction were 44.70m, 3.22 points, 5.35 points, and 0.32 points for 6MWT, CAT, BId, and MRC respectively. Sensitivity and specificity in discriminating individuals reaching the MCID of outcomes ranged from 61.78% to 98.99% and from 14.00% to 71.20%, respectively. Conclusion: While the assessed models were not entirely satisfactory, predictive equations derived from clinical practice data might help in forecasting the response to PR in individuals recovering from an ECOPD. Future larger studies will be essential to confirm the methodology, variables, and utility.(AU)

Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series.

Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ±â€…11.3 mL/min/1.73 m2; SU: 8.6 ±â€…2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ±â€…19.0 mL/min/1.73 m2; SU: 9.5 ±â€…1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ±â€…9.9 vs 52.3 ±â€…14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ±â€…8.1 [CKD] vs 14.1 ±â€…7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ±â€…5.8 vs 19.3 ±â€…4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ±â€…20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ±â€…15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.

Serum Urate and Recurrent Gout.

Importance: Approximately 12 million adults in the US have a history of gout, but whether serum urate levels can help predict recurrence is unclear. Objective: To assess associations of a single serum urate measurement with subsequent risk of acute gout flares and subsequent risk of hospitalizations for gout among patients in the UK with a history of gout. Design, Setting, and Participants: This retrospective study included patients with a history of gout identified from the UK between 2006 and 2010 who were followed up through Primary Care Linked Data medical record linkage until 2017 and through the Hospital Episode Statistics database until 2020. Exposures: Serum urate levels at enrollment. Main Outcome and Measure: Rate of recurrent acute gout, ascertained by hospitalization, outpatient, and prescription/procedure records, and adjusted rate ratios using negative binomial regressions. Results: Among 3613 patients with gout (mean age, 60 years; 3104 [86%] men), 1773 gout flares occurred over a mean follow-up of 8.3 years. Of these, 1679 acute gout flares (95%) occurred in people with baseline serum urate greater than or equal to 6 mg/dL and 1731 (98%) occurred in people with baseline serum urate greater than or equal to 5 mg/dL. Rates of acute gout flares per 1000 person-years were 10.6 for participants with baseline urate levels less than 6 mg/dL, 40.1 for levels of 6.0 to 6.9 mg/dL, 82.0 for levels of 7.0 to 7.9 mg/dL, 101.3 for levels of 8.0 to 8.9 mg/dL, 125.3 for urate levels of 9.0 to 9.9 mg/dL, and 132.8 for levels greater than or equal to 10 mg/dL. Rate ratio of flares were 1.0, 3.37, 6.93, 8.67, 10.81, and 11.42, respectively, over 10 years (1.61 [1.54-1.68] per mg/dL). Rates of hospitalization per 1000 person-years during follow-up were 0.18 for those with baseline serum urate less than 6 mg/dL, 0.97 for serum urate of 6.0 to 6.9 mg/dL, 1.8 for serum urate of 7.0 to 7.9 mg/dL, 2.2 for serum urate of 8.0 to 8.9 mg/dL, 6.7 for serum urate of 9.0 to 9.9 mg/dL, and 9.7 for serum urate greater than or equal to 10 mg/dL. Rate ratios of hospitalization for gout, adjusting for age, sex, and race were 1.0, 4.70, 8.94, 10.37, 33.92, and 45.29, respectively (1.87 [1.57-2.23] per mg/dL). Conclusions and Relevance: In this retrospective study of patients with a history of gout, serum urate levels at baseline were associated with the risk of subsequent gout flares and rates of hospitalization for recurrent gout. These findings support using a baseline serum urate level to assess risk of recurrent gout over nearly 10 years of follow-up.

Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus.

OBJECTIVES: We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS). METHODS: Patients aged 12-18 years diagnosed with SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5 mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4 weeks apart, followed by a booster (third) dose at 4-6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored. RESULTS: A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4 weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups (p = .498). AdoSLE on High-IS had lower anti-RBD IgG (p < .001), Wuhan NT (p < .001), and IFN-γ-ELISpot (p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose (p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12 weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups. CONCLUSION: AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.

Risk of gout flare after medication: prescription symmetry sequence analysis.

OBJECTIVES: The research aimed to study the following questions: (1) five well-known gout-related medications were selected to test the validity of the prescription symmetry sequence analysis in Taiwan; (2) four exploratory medications were selected to test their relation to gout flares. METHODS: We utilized the 2003-2017 dataset of the Taiwan National Health Insurance Program containing all claims data with 2 million beneficiaries as a data source. In order to explore the temporal association, we designed a scenario of medication-induced gout flares. Nine medications were selected as the index agent, including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, pyrazinamide, metformin, pioglitazone, fenofibrate, and losartan. The gout flare was defined as subjects with use of the marker agent for treatment of gout flares. The observation-window period between initiation of the index agent and initiation of the marker agent was 1 year. Subjects who used an index agent and a marker agent on the same day were excluded. The prescription symmetry sequence analysis was carried out to compare the observed number of persons who took an index agent prior to starting a marker agent with the observed number of persons who took a marker agent before starting an index agent. The adjusted sequence ratio (adjusted SR) with 95% confidence interval was applied to estimate the relation between an index agent and the marker agent. RESULTS: Among five medications including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, and pyrazinamide, the adjusted sequence ratio ranged from 1.15 to 3.35 and all reached statistical significance. Fenofibrate use and losartan use were associated with a lower probability of gout flares, with reaching statistical significance (adjusted SR = 0.60 for fenofibrate and adjusted SR = 0.92 for losartan). Metformin use was associated with a greater probability of gout flares, with reaching statistical significance (adjusted SR = 1.14). Pioglitazone use did not reach statistical significance. CONCLUSION: Based on the confirmatory analysis including five well-known gout-related medications, this study supports that the prescription symmetry sequence analysis can be used to detect an adverse drug event associated with one potential offending agent. The exposure to fenofibrate or losartan might be a protective factor against gout flares. Metformin use could be associated with a greater probability of gout flares, but this finding should be validated by other studies. KEY POINTS: • What is already known about this subject? 1. The prescription symmetry sequence analysis is a useful method for detecting an adverse drug reaction associated with one potential offending drug. 2. Numerous medications are found to induce gout flares. • What does this study add? 1. The prescription symmetry sequence analysis supports the evidence that aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol and pyrazinamide are associated with a greater probability of gout flares. 2. The exposure to fenofibrate or losartan might be a protective factor against gout flares. 3. Metformin use could be associated with a greater probability of gout flares. • How might this impact on clinical practice or future developments? 1. Clinicians should always consider the possibility of medication-induced gout flares. If gout flares develop, discontinuation of risky medications is the first step. Then prescribing cascades can be eliminated.