Traditional Chinese medicine in the treatment of patients with hyperuricemia: A randomized placebo-controlled double-blinded clinical trial.

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.

Modelling and assessing one- and two-drug dose titrations.

In health-care, there is a need to quantify medical errors. Among these errors, we observe wrong dose prescriptions. Drug dose titration (DT) is the process by which dosage is progressively adjusted to the patient till a steady dose is reached. Depending on the clinical disease, drug, and patient condition, dose titration can follow different procedures. Once modeled, these procedures can serve for clinical homogenization, standardization, decision support and retrospective analysis. Here, we propose a language to model dose titration procedures. The language was used to formalize one- and two-drug titration of chronic and acute cases, and to perform retrospective analysis of the drug titration processes on 253 patients diagnosed of diabetes mellitus type 2 and treated with metformin, 321 patients treated of chonic heart failure with furosemide, 155 patients with hyperuricemia treated with allopurinol as initial drug and febuxostat as alternative drug, and 187 hyperuricemia patients with primary drug allopurinol and supplementary drug probenecid, in order to identify different types of drug titration deviations from standard DT methods.

Clinical profile of cutaneous adverse drug reactions: a retrospective study of 1883 hospitalized patients from 2007 to 2016 in Shanghai, China.

BACKGROUND: Cutaneous adverse drug reactions (CADRs) are drug-induced skin reactions with or without systemic involvement, ranging from mild maculopapular exanthema (MPE) to life-threatening severe CADRs (S-CADRs). Due to their unpredictability and severity, early recognition of suspected causative drugs is highly recommended. However, the profile of CADRs remains unknown in China. OBJECTIVES: To assess the clinical profile, predominant causative drugs, and cost associated with CADRs in Shanghai, China. MATERIALS AND METHODS: Clinical records of inpatients admitted with a diagnosis of CADRs to the dermatology ward of Huashan Hospital from January 2007 to December 2016 were retrospectively studied. RESULTS: A total of 1,883 patients (1,231 female and 652 male), admitted with a diagnosis of CADR, were investigated. S-CADRs made up 21.99% of all cases (n=414), and urticaria (27.19%) was the most frequent reaction. Of the patients, 53.43% suffered from multiple drug-induced drug eruptions and the rest (45.83%) from single drug-induced drug eruptions. Overall, antimicrobials (28.85%) was the main drug group involved, and for S-CADRs, this was antiepileptic drugs (36.15%). The total cost for CADRs was RMB23,718,788.83 ($3,588,319.04). Both age and sex were related to admission cost (p=0.005 and p=7.84E-8, respectively). Antimicrobials were the most common treatment causing CADRs. CONCLUSION: The management of CADRs requires considerable medical cost. CADRs are not only a health problem but also a significant financial burden for affected individuals.

Retrospective study of 213 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis from China.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial. METHODS: A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG). RESULTS: The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection. CONCLUSION: The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

Association of gout medications and risk of cataract: a population-based case-control study.

BACKGROUND: The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship. AIM: To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout. DESIGN: Population-based nested case-control study. METHODS: We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract. RESULTS: The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract. CONCLUSIONS: In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

Molecular mechanisms involved in drug-induced liver injury caused by urate-lowering Chinese herbs: A network pharmacology study and biology experiments.

As an important part of the comprehensive treatment methods, the urate-lowering Chinese herbs could provide favorable clinical effects on hyperuricemia in its ability to invigorate spleen and remove dampness. Owing to the long-term duration, it brought up the potential adverse reactions (ADRs) and concerns about the drug-induced liver injury from these herbs. To address this problem, the bioinformatics approaches which combined the network pharmacology, computer simulation and molecular biology experiments were undertaken to elucidate the underlying drug-induced liver injury molecular mechanisms of urate-lowering Chinese herbs. Several electronic databases were searched to identify the potential liver injury compounds in published research. Then, the putative target profile of liver injury was predicted, and the interaction network was constructed based on the links between the compounds, corresponding targets and core pathways. Accordingly, the molecular docking simulation was performed to recognize the representative compounds with hepatotoxicity. Finally, the cell experiments were conducted to investigate the biochemical indicators and expression of the crucial protein that were closely associated with liver injury. In conclusion, the current research revealed that the compounds with potential liver injury including diosgenin, baicalin, saikosaponin D, tetrandrine, rutaecarpine and evodiamine from urate-lowering Chinese herbs, could lead to decline the survival rate of L-02 cell, increase the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in cell-culture medium, enhance the expression of p-p38/p38, while the p38 inhibitor could achieve the trend of regulating and controlling liver injury. These research findings bring further support to the growing evidence that the mechanism of the liver injury induced by the compounds from urate-lowering Chinese herbs may be associated with the activation of p38α.

"Yellow-dragon Wonderful-seed Formula" for hyperuricemia in gout patients with dampness-heat pouring downward pattern: a pilot randomized controlled trial.

BACKGROUND: In Traditional Chinese Medicine (TCM) theories, the typical clinical manifestations of gout are attributed to the "dampness-heat pouring downward." Therefore, TCM practitioners always consider prescribing the formulae which are believed to clear heat and drain dampness for the management of gout. This clinical trial aims: (1) to determine the hypouricemic effect of "Yellow-dragon Wonderful-seed Formula" (YWF) decoction in gout patients with dampness-heat pouring downward pattern and (2) to determine if gypsum could provide additional significant benefits to YWF. METHODS: A total of 72 hyperuricemic individuals with gout and dampness-heat pouring downward pattern were included with 62 of them completing the trial. Participants were randomly assigned to the YWF group, the YWF + gypsum group, or the allopurinol group. YWF and YWF + gypsum decoctions were orally administered for four weeks. Allopurinol was also orally administered for four weeks as the active control. Serum uric acid (sUA) level was the primary outcome measure. Urine urate level, scores on the SF-36 scale, erythrocyte sedimentation rate (ESR), X ray film, and C reactive protein (CRP) level were the secondary outcome measures. RESULTS: Compared with the values at week 0, YWF and YWF + gypsum did not significantly decrease the sUA level at each weekend reading. YWF, YWF + gypsum, and allopurinol decreased the urine urate levels and there were significant differences between the YWF group and the YWF + gypsum group. All the changes in the eight structures of SF-36 during the intervention period were not significantly different among the three groups and there was no significant difference in the CRP level among the three groups at each weekend reading. CONCLUSIONS: YWM, which modified on the basis of Two Wonderful Herbs Powder (2WHP), does not show significant hypouricemic effect. There is a possibility that Gypsum Fibrosum may provide additional effects to YWF in decreasing the urine urate levels but cannot add benefits to YWF in other outcome measures. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12001933 . Registered on 10 February 2012.

Comparison of fixed versus traditional weight-based dosing of rasburicase in a pediatric population.

BACKGROUND: The American Society of Clinical Oncology guidelines recommend rasburicase for the treatment of pediatric patients with hyperuricemia at risk of tumor lysis syndrome (TLS) using a weight-based dose of 0.1-0.2 mg/kg once daily for 1-7 days. However, there has been a trend in practice due to recent data showing benefit using a fixed-dose approach. The purpose of this study was to evaluate the efficacy and safety between fixed and weight-based dosing of rasburicase in a pediatric population. PROCEDURE: This was a retrospective chart review of 48 patients from January 1, 2007 to August 31, 2016 at Children's National Health System. Patients less than 18 years old with a documented diagnosis of a malignancy and baseline uric acid level were included; patients less than 30 kg at the time of rasburicase administration were excluded. RESULTS: The primary endpoint of this study was the treatment success of normalization of uric acid level (<5 mg/dl) within 24 hr of rasburicase administration. Eighty-three percent of patients had success with normalization of uric acid post rasburicase dose. Eighty-five percent of patients had success in the weight-based group compared to eighty-one percent in the fixed-dose group (P = 0.715). Mean percent reduction of uric acid at 24 hr was relatively similar between both groups (94% vs. 89%). CONCLUSION: Our results suggest that a fixed-dose strategy of rasburicase is both safe and effective in reducing uric acid levels in the pediatric patient population. A fixed dose of rasburicase 6 mg is a cost-effective treatment option for TLS.

Education Preferences of People With Gout: Exploring Differences Between Indigenous and Nonindigenous Peoples from Rural and Urban Locations.

OBJECTIVE: Gout typically responds well to medications, but adherence might be improved by education that meets individuals' needs in a way that is inclusive of their ethnicity and rurality. The aim of this study was to compare education preferences of Maori and New Zealand European (NZEuropean) individuals with gout, and of those living in rural or urban areas. METHODS: People with gout managed in primary care were recruited from 2 rural regions and 1 city within Aotearoa/New Zealand. Focus groups were held with 26 Maori and 42 NZEuropean participants (44 rural, 24 urban). Participants discussed education preferences for diet, medication, and ways of communicating. The nominal group technique was employed, whereby the group compiled a list of ideas and then participants individually ranked the 3 most important ideas for each topic. RESULTS: The most frequently prioritized ideas for the 3 topics were knowing one's own food triggers, knowing side effects of medications, and communicating via a general practitioner (GP) or specialist. More Maori participants prioritized natural remedies, easy to understand information, and communicating via television. More NZEuropean participants prioritized knowing the kinds of alcohol that trigger gout, communicating via GP/specialist, and receiving written information. More urban participants prioritized knowing to stay hydrated and medication doses as important information. CONCLUSION: Maori and NZEuropean individuals with gout report different understandings and education preferences around personal triggers of gout, treatment options, and ways of receiving information about gout. Further research is required to develop ethnicity-specific gout education resources internationally.

Case Report: Severe Hematological, Muscle and Liver Toxicity Caused by Drugs and Artichoke Infusion Interaction in an Elderly Polymedicated Patient.

BACKGROUND: Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital. OBJECTIVE: Evaluation of the cause of complaints and laboratory abnormalities and the involvement of artichoke infusion. RESULTS: The prominence of the inflammatory parameters was ruled out because of exhaustive autoimmune, infectious or para-neoplastic syndrome (blood cultures, serology, diagnostic imaging, bone marrow and bone biopsy, muscle biopsy and nerve, abdominal angiography) were carried out showing normal results. The evaluation pointed out that the concomitant intake of artichoke infusion may have been involved in the framework developed, since the drugs which were being administered to/by the patient have a metabolism mainly mediated by CYP450 3A4 and 2C9 that could be compromised when these isoenzymes are inhibited by phenolic and flavonoid compounds from plants. Colchicine was one of the last drugs took that have as side effects most of the symptoms felt by patient including diarrhea and anemia. CONCLUSION: The spontaneous and complete recovery of the patient and the negativity of research looking for other causes, conduce to a strong possibility of the interaction between artichoke and the drugs in the clinical presentation of this case.

Hypouricemic and arthritis relapse-reducing effects of compound tufuling oral-liquid in intercritical and chronic gout: A double-blind, placebo-controlled, multicenter randomized trial.

TRIAL DESIGN: In the double-blind, randomized, controlled trial, we aimed to evaluate the effects of compound tufuling oral liquid (CoTOL) on serum uric acid (sUA) levels and recurrence of acute gouty arthritis in intercritical and chronic gout treatment. METHODS: A total of 210 patients with gout were screened from 8 hospitals to observe the sUA and acute gouty arthritis recurrence rate-reducing effects of CoTOL in intercritical and chronic gout during a 12-week treatment. We treated 139 and 71 patients with CoTOL and the placebo, respectively, and evaluated their sUA levels, acute gouty arthritis recurrence rate, and adverse events at week 0, 6, and 12. RESULTS: Twenty-five and 12 patients in the treatment and control groups, respectively, had interrupted treatments, whereas 114 and 59 cases, respectively, completed their treatments. At the end of the 12-week treatment, the average decrease in sUA was 74.26 (95% confidence interval [CI]: 56.74-91.77 µmol/L) and 28.81 µmol/L (95% CI: 4.91-52.71 µmol/L) in the treatment and control groups, respectively (P = 0.004). The average decrease rate of sUA was 12.76% (95% CI: 9.82%-15.70%) and 4.57% (95% CI: 0.42%-8.71%) in the treatment and control groups, respectively (P = 0.004), and the gouty arthritis recurrence rate of the treatment group was lower than that of the control group (from week 6 to 12, 21.93% and 50.88% in the treatment and control group, respectively, P < 0.001; from baseline to week 12, 38.5% and 63.16%, respectively, P = 0.003). Severe adverse events were not observed in either groups, and fewer leucopenia incidences were observed in the treatment group than those in the control group (3/139 vs. 7/71, respectively, P = 0.033). CONCLUSION: CoTOL reduced sUA levels and effectively prevented acute arthritis recurrence in intercritical and chronic gout without serious adverse events.

Rasburicase-Induced Methemoglobinemia in a Patient with Glucose-6- Phosphate Dehydrogenase Deficiency.

BACKGROUND: Rasburicase is commonly used in patients with hematologic malignancies for tumor lysis syndrome prophylaxis and management. Methemoglobinemia is a serious rare adverse effect of rasburicase, more common in patients with G6PD deficiency. Prompt diagnosis and appropriate management of this condition can make the difference between successful recovery and significant morbidity. Here we discuss the link of rasburicase with methemoglobinemia and the pathophysiology behind increased incidence of this side effect in G6PD deficient patients. METHODS: We report the case of a 73-year-old African American man who developed methemoglobinemia on rasburicase treatment, who was later confirmed to be G6PD deficient. We reviewed the literature using Pubmed and Google Scholar using the following key words: "methemoglobinemia", "rasburicase", "urate oxidase", tumor lysis syndrome", G6PD deficiency", "hemolytic anemia" and "hyperuricemia". RESULTS: Rasburicase-induced methemoglobinemia is more common in patients with G6PD deficiency, and rasburicase is therefore contraindicated in these patients. Clinical presentation includes cyanosis, pallor, methemoglobin levels of 8-12%, and oxygen saturation gap which is evident from ABG analysis, though pulse oximetry is normal. Treatment consists of oxygen supplementation, ascorbic acid and blood transfusion. Importantly, methylene blue is avoided as therapy in G6PD deficiency as it can worsen the methemoglobinemia. CONCLUSION: Rasburicase-induced methemoglobinemia is a serious concern, especially in African- American patients. It should be considered when clinical signs and symptoms are present. Knowledge of this side effect is important in early diagnosis and successful management of the condition.

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout.

OBJECTIVE: Arhalofenate (ARH), in development for gout, has uricosuric and anti-flare activities. ARH plus febuxostat (FBX) were evaluated in subjects with gout for serum uric acid (SUA) lowering, drug interaction, and safety. METHODS: Open phase II trial in gout volunteers (NCT02252835). Cohort 1 received ARH 600 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 80 mg followed by 40 mg. FBX 40 mg was continued alone for 2 weeks. Cohort 2 received ARH 800 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 40 mg followed by 80 mg. FBX 80 mg was continued alone for 2 weeks. SUA, its fractional excretion (FEUA), and plasma oxypurines were assessed. Pharmacokinetics of FBX and ARH were determined alone and in combination for cohort 2. RESULTS: Baseline mean SUA was 9.4 mg/dl for cohort 1 (n = 16) and 9.2 mg/dl for cohort 2 (n = 16). The largest SUA decrease (63%) was observed with ARH 800 mg + FBX 80 mg, with all subjects reaching SUA < 6 mg/dl and 93% < 5 mg/dl. The area under the curve (AUC)(0-t) of ARH acid + FBX/ARH acid was 108%. The AUC(0-t) of FBX + ARH acid/FBX was 87%. As expected, FBX increased oxypurines and increases were unaffected by ARH co-administration. Baseline FEUA were low (3.5%-4.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe. CONCLUSION: ARH and FBX lowered SUA by complementary mechanisms. The combination provided greater decreases than each drug alone. The combination was well tolerated and appeared safe. TRIAL REGISTRATION: NCT02252835.

Steven Johnson Syndrome and Toxic Epidermal Necrolysis in a burn unit: A 15-year experience.

INTRODUCTION: The diffuse epidermal exfoliation seen in Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is similar to skin loss in second degree burns, and many of these patients are referred for treatment at burn centers. Treatment can differ markedly from center to center, and mortality can range from 25% to 70%, including a considerable morbidity. However, our experience over a 15-year period from 2000 to 2015 with 40 patients found a mortality rate of only 10% (4/40). The purpose of this paper is to discuss our treatment algorithm as a model for other centers treating SJS/TENs patients. METHODS: Records were reviewed for all patients admitted to the LAC+USC burn unit between 2000 and 2015 and 40 patients were identified with biopsy-proven SJS or TENS. These cases were reviewed for age, gender, initial and greatest TBSA, causative drug, pre-existing medical conditions, and morbidity and mortality. All data were entered into the SPSS statistical software package and all statistical analyses were performed using this program. RESULTS: Our treatment algorithm focused on early referral to a specialty burn unit, immediate discontinuation of the offending drug, fluid resuscitation, nutritional supplementation, and meticulous wound care. Average time to transfer to a burn unit was 3.36 days. Silver-releasing antimicrobial dressings were applied to the affected skin surface and changed every 3 days. Mupirocin coated petroleum gauze was used for facial involvement. Steroids were tapered and discontinued if initiated at an outside facility (58% of patients), and starting after 2001, all patients received a course of IVIG. All patients received fluid resuscitation and the majority received supplemental tube feedings (69%). Average length of total stay was 17.1 days and length of ICU stay 15.9 days. While 44% were transferred to another facility for further rehabilitative care, 37% of patients discharge to home. In patients discharged home with complete resolution of skin lesions, time to healing was an average of 14 days. DISCUSSION: With our 10% mortality rate in 40 patients, our study represents a relatively large study population while maintaining a relatively low mortality rate. The demographic data from our study largely aligns with the existing literature, and we therefore feel that our low mortality rate is due to our treatment algorithm, rather than to a less severe pathology in our patient population. This claim is supported by a standard mortality ratio of 1.68. This ratio proves a significantly improved mortality than would be expected based on disease severity on admission.

Effects of a Novel Fixed Combination of Nutraceuticals on Serum Uric Acid Concentrations and the Lipid Profile in Asymptomatic Hyperuricemic Patients : Results from the PICONZ-UA Study.

INTRODUCTION: Asymptomatic hyperuricemia is not a current indication for therapy as the definite role of serum uric acid elevation as a cardiovascular risk factor is extremely likely but still controversial. AIM: We designed a double blind, placebo-controlled, randomized study to assess the effects of a combination of nutraceuticals (ZinutriK®, containing a fixed combination of kampferol, baicalin, caffeine, and rutin) on serum uric acid levels, lipid variables and the global cardiovascular risk profile. METHODS: Sixteen individuals (mean age 59.0 ± 11.9 years, 4 women) with asymptomatic hyperuricemia completed the study. RESULTS: ZinutriK® treatment (4 weeks) reduced serum uric acid concentrations (from 7.9 + 0.9 to 7.0 + 0.7 mg/dL) when compared to both baseline and placebo (p < 0.006 and p < 0.001, respectively). Compared to both placebo and baseline, the same fixed combination of nutraceuticals also reduced circulating LDL cholesterol and increased HDL cholesterol concentrations within 4 weeks (p < 0.001 or less), thereby improving the Framingham risk score (p < 0.001 or less). Neither minor nor major side effects were observed. CONCLUSIONS: This study represents the first demonstration that a short-term therapy with a fixed combination of different natural substances can significantly reduce serum uric acid concentrations in asymptomatic hyperuricemic patients, with no side effects and a significant improvement in the lipid pattern and then in the global cardiovascular risk profile.

Patient and clinical characteristics associated with gout flares in an integrated healthcare system.

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.

Chuanhu anti-gout mixture versus colchicine for acute gouty arthritis: a randomized, double-blind, double-dummy, non-inferiority trial.

BACKGROUND: The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. METHODS: In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. RESULTS: A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). CONCLUSIONS: The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function.

Systematic review and meta-analysis of the clinical efficacy and adverse effects of Chinese herbal decoction for the treatment of gout.

BACKGROUND: In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. OBJECTIVES: In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. METHODS: We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. RESULTS: Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: -0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: -0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). CONCLUSIONS: Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions.

Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis.

Gout is an inflammatory joint disorder characterized by hyperuricaemia and precipitation of monosodium urate crystals in the joints. In the present study, we aimed to investigate the anti-inflammatory effect of trikatu, a herbal compound in monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and histopathological examination of ankle joints were determined in control and monosodium urate crystal-induced rats. In addition, analgesic (acetic acid-induced writhing response), anti-pyretic (yeast-induced pyrexia) and gastric ulceration effects were tested. The levels of lysosomal enzymes, lipid peroxidation and paw volume were significantly increased, and anti-oxidant status was found to be reduced in monosodium urate crystal-induced rats, whereas the biochemical changes were reverted to near normal levels upon trikatu (1000 mg/kg b.wt) administration. The trikatu has also been found to exhibit significant analgesic and anti-pyretic effects with the absence of gastric damage. In conclusion, the present results clearly indicated that trikatu exert a potent anti-inflammatory effect against monosodium urate crystal-induced inflammation in rats in association with analgesic and anti-pyretic effects in the absence of gastrointestinal damage.

Understanding the dose-response relationship of allopurinol: predicting the optimal dosage.

AIMS: The aim of the study was to identify and quantify factors that control the plasma concentrations of urate during allopurinol treatment and to predict optimal doses of allopurinol. METHODS: Plasma concentrations of urate and creatinine (112 samples, 46 patients) before and during treatment with various doses of allopurinol (50-600 mg daily) were monitored. Non-linear and multiple linear regression equations were used to examine the relationships between allopurinol dose (D), creatinine clearance (CLcr) and plasma concentrations of urate before (UP) and during treatment with allopurinol (UT). RESULTS: Plasma concentrations of urate achieved during allopurinol therapy were dependent on the daily dose of allopurinol and the plasma concentration of urate pre-treatment. The non-linear equation: UT = (1 - D/(ID50 + D)) × (UP - UR) + UR , fitted the data well (r(2) = 0.74, P < 0.0001). The parameters and their best fit values were: daily dose of allopurinol reducing the inhibitable plasma urate by 50% (ID50 = 226 mg, 95% CI 167, 303 mg), apparent resistant plasma urate (UR = 0.20 mmol l(-1), 95 % CI 0.14, 0.25 mmol l(-1)). Incorporation of CLcr did not significantly improve the fit (P = 0.09). CONCLUSIONS: A high baseline plasma urate concentration requires a high dose of allopurinol to reduce plasma urate below recommended concentrations. This dose is dependent on only the pre-treatment plasma urate concentration and is not influenced by CLcr .