An updated systematic review and meta-analysis of randomised controlled trials on the effects of urate-lowering therapy initiation during a gout flare.

BACKGROUND: There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare. METHODS: This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680. RESULTS: A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment. CONCLUSION: There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.

Incidence and factors associated with chronic chikungunya arthritis following chikungunya virus infection.

OBJECTIVES: Chikungunya virus infection is a mosquito-borne illness. First-phase symptoms include fever, malaise, rash, and arthritis (self-limiting). Some patients can have chronic-phase symptoms, including chronic tenosynovitis, bursitis, and arthritis. This study aimed to determine the incidence and risk factors of chronic arthritis in patients with chikungunya infection. METHODS: This retrospective cohort study analysed all adults diagnosed with chikungunya infection between 2015 and 2020 at our centre. Baseline and follow-up symptoms were evaluated in serologically confirmed cases. Chronic chikungunya arthritis was persistent arthritis >3 months after the onset. Patients who had preexisting chronic inflammatory arthritis and were lost to follow-up before 3 months from diagnosis were excluded. RESULTS: This study enrolled 120 patients. The median age was 51 (IQR 14) years, and 78% were female. The median number of joints with arthritis was 4 (IQR 8). The initial visual analog scale (VAS) score was 50 mm (IQR 40). Small joints of the hands, wrist, and knee (44.2%, 43.3%, and 42.3%, respectively) were the most affected. The incidence of chronic chikungunya arthritis was 40.4%. From the multivariable logistic regression, the initial number of joints with arthritis, initial VAS scores, and female sex were independently associated with chronic chikungunya arthritis with odds ratios of 1.09 (95% confidence interval [CI] 1.01-1.18), 1.03 (95% CI 1.01-1.06), and 4.17 (95% CI, 1.05-16.67), respectively. CONCLUSIONS: Chronic chikungunya arthritis is common in patients with chikungunya virus infection. Its predictive factors include the initial number of joints with arthritis, initial VAS scores, and female sex.

Medium Cut-Off versus Low-Flux Dialyzers in Hemodialysis Patients with COVID-19: Clinical Outcomes and Reduction in Interleukin-6.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive morbidity and mortality worldwide. Hemodialysis (HD) patients are both vulnerable to COVID-19 infection and tend to suffer greater disease severity and mortality. This retrospective study aimed to compare medium cut-off (MCO) and low-flux (LF) membrane dialyzers in terms of interleukin-6 (IL-6) reduction, change in inflammatory state, intradialytic complications, and mortality in chronic HD patients with COVID-19. METHOD: HD patients with a confirmed COVID-19 infection were admitted to the hospital for 10-14 days and underwent HD at the COVID-HD unit. Choice of dialyzer membrane used (MCO vs. LF) depended on the primary nephrologist(s). We collected data on demographics, baseline characteristics, laboratory results, diagnosis, treatments, HD prescription, hemodynamic status during HD, and mortality at 14 and 28 days after. RESULTS: IL-6 reduction ratio (RR) in the MCO group was 9.7 (interquartile range, 71.1) percent, which was significantly higher than that of the LF group (RR, -45.7 [interquartile range, 70.2] percent). The incidence rate of intradialytic hypotension in the MCO group was 3.846 events per 100 dialysis hours (95% confidence interval [CI], 1.954-6.856), which was significantly lower than that of the LF group (9.057; 95% CI, 5.592-13.170). Overall, mortality was not significantly different between the two groups. CONCLUSION: The MCO membrane was more effective in removing IL-6 and was better tolerated than the LF membrane. Large, randomized controlled trials are required to confirm the relative benefits of the MCO membrane, especially mortality. However, due to the COVID-19 pandemic, our results suggest that the MCO membrane may be beneficial in chronic HD patients with COVID-19.

Prevalence, Risk Factors, and Outcomes of Gout Flare in Patients Hospitalized for PCR-Confirmed COVID-19: A Multicenter Retrospective Cohort Study.

OBJECTIVE: The study aimed to describe the prevalence and outcomes of gout flare in patients with comorbid gout hospitalized for coronavirus disease 2019 (COVID-19). Factors associated with gout flare and hospital length of stay were explored. METHODS: This retrospective cohort study included adults with comorbid gout who were hospitalized for PCR-confirmed COVID-19 between March 2020 and December 2021 in 3 hospitals in Thailand. Prevalence, characteristics, and outcomes of gout flare were described. Factors associated with gout flare were explored using least absolute shrinkage and selection operator selection and multivariate logistic regression. The association between gout flare and hospital length of stay was explored using multivariate linear regression. RESULTS: Among 8697 patients hospitalized for COVID-19, 146 patients with comorbid gout were identified and gout flare occurred in 26 (18%). Compared to those without flare, patients with gout flare had higher baseline serum urate and lower prevalence of use of urate-lowering therapy (ULT) and gout flare prophylaxis medications. One-third of gout flare episodes were treated with ≥ 2 antiinflammatory medications. Logistic regression identified GOUT-36 rule ≥ 2, a predictive index for inpatient gout flare, as the only factor associated with gout flare (odds ratio 5.46, 95% CI 1.18-25.37). Gout flare was found to be independently associated with hospital length of stay and added 3 days to hospital course. CONCLUSION: Gout flare occurred in 18% of patients with comorbid gout hospitalized for COVID-19 and added up to 3 days to hospital length of stay. Patients with suboptimal ULT appeared to be at high risk for gout flare during COVID-19 hospitalization.

Early versus Late Allopurinol Initiation in Acute Gout Flare (ELAG): a randomized controlled trial.

OBJECTIVE: Currently available guidelines on urate-lowering therapy (ULT) initiation in acute gout flare are conflicting. We compared the time to complete resolution of acute gout flare between early and late allopurinol initiation. METHODS: This 28-day, randomized controlled, open-label trial included patients with crystal-proven gout who were presented with acute gout flare within 72 h of arthritis onset. Exclusion criteria were advanced renal failure, ongoing ULT, and presence of the HLA-B*5801 allele. Allopurinol was used on days 1 and 14 in early and late groups, respectively. Primary outcome was time to complete arthritis resolution, and secondary outcomes were time to clinical resolution; arthritis relapse; laboratory parameters; and adverse events. RESULTS: One hundred seventeen patients were randomized to early and late allopurinol groups (n = 59 and 58, respectively). One patient in each group was lost to follow-up; therefore, 115 patients were included in the modified intention-to-treat analysis. Baseline characteristics were comparable between the groups. The median time to complete resolution was not significantly different between the early and late allopurinol groups (6 [5-14] and 6 [5-7] days, respectively; p = 0.14). The median time to clinical resolution was 4 [3-6] days in both groups (p = 0.12). Other secondary outcomes were not significantly different. Serious adverse events did not occur in either group. CONCLUSIONS: Early allopurinol initiation during an acute gout flare did not lead to significant changes in time to resolution, flare recurrence, and inflammatory markers. Key Points • Allopurinol Initiation in Gout.

Therapeutic plasma exchange with standard hemodialysis machine as an alternative to dedicated apheresis device: A 5-year experience.

Patients suffering from various diseases have been shown to benefit from therapeutic plasma exchange (TPE). However, in developing countries, there are many obstacles hindering the establishment and initiation of TPE programs. These include inadequate funding and lack of government healthcare coverage. Our center in Thailand practices a unique membrane plasma separator technique using a hemodialysis machine incorporated with a plasma separator. Over a 5 year period, there were 130 such sessions conducted in 24 patients. The indications for TPE treatment included neurological, hematological, and nephrological diseases. Overall, response to TPE was good. Some TPE-related adverse events did occur, but none were life-threatening. Unfortunately, infection remained a problem and was sometimes a cause of death. Future challenges include minimization of infection rates and making TPE treatment readily accessible to patients.

Risk factors for venous thromboembolism (VTE) recurrences in Thai patients without cancer.

INTRODUCTION: Studies in Western countries show that VTE recurrent rates are lower in the presence of a transient provoking factor, older age, female sex and/or hormonal use, while thrombophilia (factor V Leiden or prothrombin mutation) has no predictive role. This study aimed to determine the incidence and risk factors of recurrent VTE in Asian patients. METHOD: This is a retrospective cohort study in adult VTE patients who were diagnosed during 2004-2014, had no active cancer and followed-up for at least 1 year. RESULTS: There were 198 patients. The mean age was 58.2 ± 17.6 years and 68.2% were female. The diagnoses were deep vein thrombosis (56%), pulmonary embolism (32%) or both (12%). They were provoked by major surgery in 21.7%. Thrombophilia (antiphospholipid syndrome or protein C or protein S deficiency) was found in 11.6%. The recurrent rate during the median follow-up time of 52 months was 2.2 (95% confidence interval [CI] 1.46-3.31) per 100 patient-years. Presence of thrombophilia was independently associated with recurrences with the adjusted hazard ratio (aHR) of 3.52 (95% CI 1.32-9.42, p = 0.01). There were 144 patients who discontinued anticoagulants. During the median time of 55 months after stopping anticoagulants, the recurrent rate was 4.3 per 100 patient-years. Thrombophilia was associated with recurrences with aHR of 4.00 (95% CI 1.42-11.31, p = 0.01), while male sex, younger age, provoking conditions and hormone use showed no significant association. CONCLUSION: VTE recurrent rate in Asians is comparable to Caucasians, but thrombophilia is the strongest risk factor.