Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Visit-to-visit glycemic variability is a strong predictor of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus: Competing risk analysis using a national cohort from the Taiwan diabetes study.

BACKGROUND: This study aims to examine the association between visit-to-visit glucose variability, which was measured by coefficient of variation (CV) of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), and risk of chronic obstructive pulmonary disease (COPD) in a large number of patients with type 2 diabetes with an average follow-up of 7.58 years. METHODS: We conducted a retrospective cohort study on 27,257 patients with type 2 diabetes who participated in the National Diabetes Case Management Program in Taiwan. Visit-to-visit variability in HbA1c and FPG at baseline and the incidence of COPD were analyzed using a modified Cox proportional hazards model considering competing risks. RESULTS: A total of 2,346 incident cases of COPD. Patients were grouped into tertiles of FPG-CV and HbA1c-CV. The incidence rates in the first, second, and third tertiles were 9.87, 11.06, and 13.19, respectively, for FPG-CV and 10.2, 11.81, and 12.07, for HbA1c-CV per 1000 person-years. After adjusting for age, gender, diabetes duration, treatment type, smoking, hypertension, hyperlipidemia, baseline FPG and HbA1c levels, and complications, both FPG-CV and HbA1c-CV were independently associated with COPD. The hazard ratios of COPD for the third terile compared with the first tertile of FPG-CV were 1.26 (95% confidence interval [CI]: 1.13-1.40). Moreover, the hazard ratios of COPD for the third and second tertiles compared with the first tertile of HbA1c-CV were 1.13 (1.02-1.25) and 1.13 (1.02-1.26), respectively. CONCLUSIONS: Patients with FPG-CV higher than 34.6% or HbA1c-CV higher than 8.4% exhibited an increased risk of COPD. This finding confirmed the linear relationship of FPG-CV and HbA1c-CV to COPD. Visit-to-visit variability in FPG and HbA1c levels are strong predictors of COPD in patients with type 2 diabetes. Future studies should focus on lung dysfunction in diabetes, and adequate glucose control strategy in regular clinical practices must be established for COPD prevention.

Highly Diverse Efficacy of Salvage Treatment Regimens for Relapsed or Refractory Peripheral T-Cell Lymphoma: A Systematic Review.

BACKGROUND: The goal of this study was to perform a systematic review to examine the efficacy and safety of various salvage therapy regimens on patients with relapsed/refractory PTCL. METHOD: The electronic searches were performed using PubMed, Cochrane Library, EMBASE, and Web of Science from inception through June 2015, with search terms related to relapsed/refractory PTCL, salvage chemotherapy regimens, and clinical trials. An eligible study met the following inclusion criteria: (1) Patients had refractory or relapsed PTCL; (2) drug regimens were used for salvage therapy; (3) the study was a clinical trial; (4) the study reported on a series of at least 10 patients of PTCL. RESULTS: Of 35 records identified, a total of 14 studies were eligible for systematic reviews, and 12 different salvage regimens were investigated. A total of 618 relapsed/refractory PTCL patients were identified. The ORRs ranged from 22% for those treated with lenalidomide to 86% for those with brentuximab vedotin. By the three most frequent subtypes, the ORRs ranged from 14.2% to 71.5% for patients with the PTCL-NOS subtype, 8% to 54% for AITL subtypes, and 24% to 86% for the ALCL subtype. The medians of DOR, PFS, and OS ranged from 2.5 to 16.6 months, 2.6 to 13.3 months, and 3.6 to 14.5 months, respectively. The most frequently reported grade 3 or 4 adverse events (AEs) were hematological AEs, such as neutropenia and thrombocytopenia. CONCLUSION: The efficacy of salvage therapy regimens is highly diverse for patients with relapsed/refractory PTCL; this heterogeneity in therapeutic effects might be due to the diversity in mechanisms, PTCL subtype distribution, and/or numbers/profiles of prior therapy. Comparative studies with matched pair analysis are warranted for more evidence of the salvage treatment effect on relapsed or heavily pretreated patients with PTCL.

The relationship between accessibility of healthcare facilities and medical care utilization among the middle-aged and elderly population in Taiwan.

OBJECTIVE: The purpose of this study was to explore the relationship between accessibility of healthcare facilities and medical care utilization among the middle-aged and elderly population in Taiwan. DESIGN: Cross-sectional study from 2007 Taiwan Longitudinal Study on Ageing (TLSA) survey. SETTING: Community-based study. PARTICIPANTS: A total of 4249 middle-aged and elderly subjects were recruited. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Outpatient visits within 1 month, and hospitalization, emergency visits as well as to shop in pharmacy stores within 1 year, respectively. RESULTS: Adjusting for important confounding variables, the middle-aged and elderly with National Health Insurance (NHI) and commercial insurance compared with those with NHI alone tended to have outpatient visits. The middle-aged and elderly with longer time to access healthcare facilities were less likely to shop in pharmacy stores compared with those with <30 min. The middle-aged and elderly who perceived inconvenient to access health care tended to shop in pharmacy stores compared with those with perceived convenience. CONCLUSIONS: Our study of Taiwan's experience could provide a valuable lesson for countries that are planning to launch universal health insurance system, locate budgets in health care and transportation. The middle-aged and elderly who were facing more challenges in accessing health care, no matter in perceived accessibility or real time to access health care, had less outpatient visits and more drug stores shopping. Strategic policies are needed to improve accessibility in increasing patients' perception on access and escalating convenience of transportation system for improving accessibility.

The relationship between self-reported tobacco exposure and cotinines in urine and blood for pregnant women.

To explore the relationship of self-reported exposure to tobacco smoke and the cotinine levels in the urine and blood over the follow-up period for pregnant women. Three hundred ninety-eight pregnant women undergoing prenatal care were interviewed in different trimesters at three hospitals in central Taiwan using a structured questionnaire. Based on their self-reported smoking experience, the participants were classified into three groups (25 smokers, 191 passive smokers, and 182 non-smokers) and were tracked in this study up to the time of delivery. Cotinine levels were tested for the maternal blood and urine at the end of each trimester and for the umbilical cord-blood of the newborns. All specimens were measured using a sensitive high-performance liquid chromatographic (HPLC) technique. In general, urinary cotinine levels were higher in subjects who smoked (including current- and ex-smokers) than those who never smoked. The pattern of distribution of cotinine levels among smoking/ETS exposure group in the urine sample was similar to that in the blood sample. The umbilical cord-blood cotinine levels was found to be highest in the active smoking group, followed by the ETS group exposed to ETS both at home and in the workplace. Over the course of the pregnancies, there was an increase in cotinine levels in urine and maternal blood for each of 3 exposure groups. Exposure to smoking by self-reported information in pregnant women has been found to be directly related to the levels of cotinine in the umbilical cord-blood of the fetus. Cotinine is a sensitive measure of ETS exposure, but if biochemical analysis is not available or convenient for a pregnant woman, then self-reported exposure to ETS can provide a good estimate if the information is gathered by a well-trained interviewer in a structured way.

Prenatal smoking exposure and neonatal DNA damage in relation to birth outcomes.

This study investigated whether mothers with prenatal environmental tobacco smoke (ETS) exposure increased the newborn genetic damage and adverse birth outcomes. Study participants were women receiving prenatal care at three hospitals in Central Taiwan and their newborns. Participants were divided into two groups (nonsmokers and ETS-exposed non-smokers) based on maternal ETS-exposed status. Comet assay were performed for cord blood samples. Infants born to mothers with prenatal ETS exposure had the highest mean cord blood DNA damage score (69.7 +/- 42.3) and poorer birth outcomes. No negative fetal growth effects appeared among newborns with low DNA damage levels. Among newborns with high DNA damage levels (comet scores >50), those born to prenatal ETS exposure had an average reduction of 252.7 g in birth weight, 1.10 cm shorter in length and a 0.92-cm decrease in head circumference, compared to newborns with no smoking exposure. This study shows that the DNA damage scores can be used as an effect-modifier on the relationships between ETS exposure and adverse birth outcome. The association appears more apparent for the ETS exposure in relation with more severe DNA damage.