Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease.

Whether the clinical trial treatment effect of urate-lowering therapy (ULT) in patient with chronic kidney disease (CKD) is generalizable to real-word settings is unclear. This study aimed to compare febuxostat with allopurinol for uric acid reduction and renal protection in patients with CKD. Adult CKD patients newly treated with ULT were identified using electronic health records from 2010 to 2015 from a large healthcare delivery system in Taiwan. Patients with renal replacement therapy or undergoing ULT for <3 months were excluded. Propensity score-matched cohort study design was conducted to compare outcomes between patients initiated with febuxostat or allopurinol therapy. Cox regression analyses were employed to compare the adjusted hazards ratio (aHR) of incident event of estimated glomerular filtration rate (eGFR) ≥ 30% decrease, and the difference in longitudinal changes in serum uric acid (SUA) and eGFR between groups was analyzed using linear mixed model. Overall, 1050 CKD patients who initiated febuxostat (n = 525) or allopurinol (n = 525) treatment were observed for 2.5 years. Compared with allopurinol, febuxostat use was associated with higher rate of patients maintaining SUA target <6 mg/dL in >80% of follow-up time with a reduction in mean SUA change. There were no significant differences in the mean eGFR changes over time between the febuxostat and allopurinol groups or in the risk of eGFR decline ≥30% of baseline. Febuxostat was associated with greater reduction in SUA level than allopurinol in patients with CKD. However, febuxostat and allopurinol showed no difference in renal function changes during study follow-up. These findings require further investigation with long-term follow up in CKD patients with hyperuricemia.

The impact of adoption of a new urate-lowering agent on trends in utilization and cost in practice.

OBJECTIVES: Changes in treatment choice of therapy and size of treated population that can lead to under- or overestimate of payer's budget are less likely to be reassured after reimbursement adoption of a new drug. The aim of this study was to evaluate the effects of febuxostat introduction and the modifications in its insurance coverage on the utilization and expenditure of urate-lowering therapy (ULT). METHODS: Electronic medical records for adults patients prescribed any ULT during 2010-2015 was derived from the largest medical organization in Taiwan. Aggregated estimates of ULT use and costs were assessed per 3-month and per patient per month (PPPM). Factors associated with total ULT expenditure were assessed using a time series design with factored Autoregressive Integrated Moving Average (ARIMA) models. RESULTS: ULT prevalent users increased 34.1% from 2010 to 2015 and a 123% increase in total ULT expenditure. Numbers on allopurinol and sulfinpyrazone both declined 31%, and on benzbromarone and febuxostat gradually increased to 38.21% and 22.89% of all users in 2015. Insurance payments PPPM ($4.44 to $9.22) and total monthly ULT cost ($32,946 to $ 85,732) growth more than doubled in 6 years, trend changes generated mostly by individuals switching to febuxostat. CONCLUSIONS: ULT use moved to favor benzbromarone and febuxostat; greater expensive uptake for febuxostat led to a rapid rise in ULT cost. Marginal values of increasing access to febuxostat for asymptomatic hyperuricemia should be focus on future studies to facilitate drug prices negotiation and ensure appropriate ULT use.

Increased ischemic stroke risk in patients with Behçet's disease: A nationwide population-based cohort study.

BACKGROUND: Behçet's disease (BD) is a recurrent, multisystemic, inflammatory disorder that mainly affects blood vessels. Because recurrent inflammation of blood vessels in the brain plays a crucial role in the development of ischemic stroke, we hypothesized that patients with BD might have an elevated risk of ischemic stroke. This potential association has been suggested in a few case reports, but not epidemiological studies. Hence, the present study aimed to examine the relation between BD and subsequent ischemic stroke in Taiwan using a nationwide, population-based database. METHODS: To establish a study cohort, the longitudinal data of 306 patients newly diagnosed with BD during 2000-2010 were extracted from the National Health Insurance Research Database, Taiwan. For comparison of ischemic stroke incidence, a control cohort of 1224 subjects without BD was established using a frequency-matched ratio of 1:4 for age, sex, and pre-existing comorbidities. RESULTS: During the 10-year follow-up, 13 (4.2%) patients with BD and 20 (1.6%) control subjects experienced ischemic stroke. Kaplan-Meier analysis revealed the higher prevalence of ischemic stroke in the BD group (log-rank test, p = 0.001). After adjusting for comorbidities and demographic characteristics, Cox regression analysis revealed that patients with BD had a 2.77-fold risk of ischemic stroke (95% confidence interval, 1.38-5.57) compared to control subjects. CONCLUSIONS: Patients with BD have an elevated risk of ischemic stroke. Hence, BD may affect the vascular system in the brain, resulting in a stroke event.

Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis.

BACKGROUND: Dengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections. METHODS: A nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF. RESULTS: Unexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118-0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV. CONCLUSIONS: Decreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.

Utility of human leukocyte antigen-B*58: 01 genotyping and patient outcomes.

AIM: Human leukocyte antigen (HLA-B*58:01) allele screening before allopurinol administration is recommended to prevent gene-mediated severe cutaneous adverse reactions (SCARs). The objective of the analysis was to examine the clinical utility and effects of HLA-B*58:01 genotyping on patient's outcomes in a practice setting. PATIENTS AND METHODS: The electronic medical records covering diagnosis, laboratory results, and prescription dispensing for patients who were newly treated with allopurinol or tested for HLA-B*58:01 were obtained from a large medical organization in Taiwan between 2010 and 2014. The uptake of HLA-B*58:01 testing, incidence of allopurinol-associated SCAR, and changes in urate-lowering agent utilization were assessed. RESULTS: A total of 17 532 allopurinol new users were identified from 2010 to 2014, and the HLA-B*58:01 test was ordered for 2844 (21.76%) of 13 069 new users when available between 2011 and 2014 in the study. The allopurinol-related SCAR events decreased from 0.21% (22/4460) to 0 (0/2167) after the introduction of HLA-B*58:01 testing, accompanied by a gradual increase from 8% (326/4207) to 31% (674/2167) in genotype testing rate. However, the HLA-B*58:01 testing performed before allopurinol prescription was 60.34%, and ~40% of patients were tested after already taking allopurinol. A shift from allopurinol to other urate-lowering agent regimens appeared among new allopurinol users. CONCLUSION: HLA-B*58:01 test was associated with the prevention of allopurinol-induced SCAR. The clinical utility of genotype testing may not be consistent with recommendations for testing, and treatment alternatives are a competitive intervention associated with effective implications in a real-world setting.

Quantitative comorbidity risk assessment of dementia in Taiwan: A population-based cohort study.

Dementia is one of the most burdensome illnesses in elderly populations worldwide. However, the literature about multiple risk factors for dementia is scant.To develop a simple, rapid, and appropriate predictive tool for the clinical quantitative assessment of multiple risk factors for dementia.A population-based cohort study.Based on the Taiwan National Health Insurance Research Database, participants first diagnosed with dementia from 2000 to 2009 and aged ≥65 years in 2000 were included.A logistic regression model with Bayesian supervised learning inference was implemented to evaluate the quantitative effects of 1- to 6-comorbidity risk factors for dementia in the elderly Taiwanese population: depression, vascular disease, severe head injury, hearing loss, diabetes mellitus (DM), and senile cataract, identified from a nationwide longitudinal population-based database.This study enrolled 4749 (9.5%) patients first diagnosed as having dementia. Aged, female, urban residence, and low income were found as independent sociodemographic risk factors for dementia. Among all odds ratios (ORs) of 2-comorbidity risk factors for dementia, comorbid depression and vascular disease had the highest adjusted OR of 6.726. The 5-comorbidity risk factors, namely depression, vascular disease, severe head injury, hearing loss, and DM, exhibited the highest OR of 8.767. Overall, the quantitative effects of 2 to 6 comorbidities and age difference on dementia gradually increased; hence, their ORs were less than additive. These results indicate that depression is a key comorbidity risk factor for dementia.The present findings suggest that physicians should pay more attention to the role of depression in dementia development. Depression is a key cormorbidity risk factor for dementia. It is the urgency of evaluating the nature of the link between depression and dementia; and further testing what extent controlling depression could effectively lead to the prevention of dementia.

Cost-effectiveness Analysis for Genotyping before Allopurinol Treatment to Prevent Severe Cutaneous Adverse Drug Reactions.

OBJECTIVE: Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA). METHODS: A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLA-B*58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening. A 1-year time frame and third-party payer perspective were modeled for both the entire cohort (base-case) and for the subgroup of patients with chronic kidney disease (CKD). RESULTS: The incremental cost-effectiveness ratio of genetic screening prior to ULA therapy was estimated as New Taiwan (NT) $234,610 (US$7508) per QALY gained in the base-case cohort. For patients with CKD, it was estimated as NT$230,925 (US$7390) per QALY. The study results were sensitive to the probability of benzbromarone/febuxostat-related hypersensitivity, and a negative predicted value of genotyping. CONCLUSION: HLA-B*58:01 screening gave good value for money in preventing allopurinol-induced SCAR in patients indicated for ULA therapy. In addition to the costs of genotyping, it is important to monitor ULA safety closely in adopting HLA-B*58:01 screening in practice.

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients.

A Bayesian Approach to Identifying New Risk Factors for Dementia: A Nationwide Population-Based Study.

Dementia is one of the most disabling and burdensome health conditions worldwide. In this study, we identified new potential risk factors for dementia from nationwide longitudinal population-based data by using Bayesian statistics.We first tested the consistency of the results obtained using Bayesian statistics with those obtained using classical frequentist probability for 4 recognized risk factors for dementia, namely severe head injury, depression, diabetes mellitus, and vascular diseases. Then, we used Bayesian statistics to verify 2 new potential risk factors for dementia, namely hearing loss and senile cataract, determined from the Taiwan's National Health Insurance Research Database.We included a total of 6546 (6.0%) patients diagnosed with dementia. We observed older age, female sex, and lower income as independent risk factors for dementia. Moreover, we verified the 4 recognized risk factors for dementia in the older Taiwanese population; their odds ratios (ORs) ranged from 3.469 to 1.207. Furthermore, we observed that hearing loss (OR = 1.577) and senile cataract (OR = 1.549) were associated with an increased risk of dementia.We found that the results obtained using Bayesian statistics for assessing risk factors for dementia, such as head injury, depression, DM, and vascular diseases, were consistent with those obtained using classical frequentist probability. Moreover, hearing loss and senile cataract were found to be potential risk factors for dementia in the older Taiwanese population. Bayesian statistics could help clinicians explore other potential risk factors for dementia and for developing appropriate treatment strategies for these patients.

Compliance with risk management plan recommendations on laboratory monitoring of antitumor necrosis factor-α therapy in clinical practice.

BACKGROUND/PURPOSE: A risk management plan (RMP) was introduced to monitor the association between initiation of antitumor necrosis factor-α (anti-TNF-α) therapy and tuberculosis (TB) and viral hepatitis infections. The aim of this study was to assess adherence and predictors of laboratory-testing rates among patients treated with anti-TNF-α therapy. METHODS: Data on patients receiving anti-TNF-α therapy between January 1, 2005, and November 31, 2013, were retrieved from a large medical organization in Taiwan. Newly-treated patients were categorized into pre- and post-RMP groups. Laboratory testing for TB and hepatitis B and C was ascertained and the proportion of new users receiving the test was compared between the pre- and post-RMP groups. Patient characteristics and concomitant medications used were investigated using multivariate logistic regression to determine the impact of each factor on laboratory testing. RESULTS: Among 1128 new users, the initial testing rate of chest X-ray (CXR) for latent TB infection increased from 60.26% before RMP to 76.38% after RMP implementation; hepatitis B surface antigen (HBsAg) increased from 31.13% to 51.42%; and hepatitis C virus antibody (HCVAb) increased from 32.2% to 54.10%. CXR was significantly associated with age >60 years, higher Quan-Charlson comorbidity index score, psoriasis, and use of prednisolone (≥7.5 mg/d). Patients aged 40-60 years and with prednisolone doses of ≥7.5 mg/d and history of cancer were more likely to receive HBsAg or HCVAb tests than their counterparts. CONCLUSION: The rate of laboratory test monitoring for anti-TNF-α therapy increased after RMP implementation. A strategy that integrates efforts from patient's education, health profession, and regulatory agencies is needed to improve safety screening and access to laboratory resources for the at-risk group of patients.

Analysis of ciprofloxacin by a simple high-performance liquid chromatography method.

A simple and sensitive high-performance liquid chromatographic method is described for the quantitative analysis of ciprofloxacin in pharmaceuticals and human plasma. The method employs reversed-phase chromatography using an RP-C18 column with an isocratic mobile phase of acetonitrile-2% acetic acid aqueous solution (16:84, v/v), umbelliferone as an internal standard, and a flow rate of 1.0 mL/min. The UV detector is set at 280 nm. The limit of detection is 0.25 microM (S/N = 3, injection volume = 10 microL). The regression equations are linear (r > 0.9999) over a range between 0.51 approximately 130 microM for the pharmaceutical analysis of ciprofloxacin and 0.51 approximately 64.8 microM for the biological analysis of ciprofloxacin in human plasma. The intra- and inter-day relative standard deviation and relative error are less than 3.39% and 5.71%, respectively. All the recoveries are greater than 93.8%. This method is successfully applied in a pharmacokinetic study of a volunteer who receives a 500 mg ciprofloxacin tablet.