The FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial.

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were -23.58, -33.06, -35.00, and -38.13 in the fimasartan group vs. -8.74, -10.17, -14.91, and -19.71 in the losartan group, p < 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients: ASCEND-TD: A Phase 3 Randomized, Double-Blind, Noninferiority Trial.

BACKGROUND AND OBJECTIVES: Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis with a baseline hemoglobin of 8-11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28-52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability. RESULTS: Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%). CONCLUSIONS: Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033.

A population-based study on the association between rheumatoid arthritis and voice problems.

The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.

Excessive Sleep and Lack of Sleep Are Associated With Slips and Falls in the Adult Korean Population: A Population-Based Cross-Sectional Study.

Few studies have evaluated the impacts of excessive sleep duration on falls. This study investigated the associations between sleep duration and falls among Korean adults in a wide range of age groups while adjusting for numerous confounding factors. Data collected from study participants ranging in age from 19 to 109 years old were analyzed from the 2013 Korean Community Health Survey (KCHS). Sleep duration was divided into 5 groups: ≤5, 6, 7, 8, and ≥9  hours per day. The relations between sleep duration and falls (≥1 time or ≥2 times per year) were analyzed using simple and multiple logistic regression analyses with complex sampling. Age, sex, days of vigorous or moderate physical activity, income, education, alcohol use, smoking, stress, obesity, hypertension, diabetes mellitus, hyperlipidemia, stroke, angina or myocardial infarction, arthritis, and asthma were controlled for as confounding factors. Associations between sleep duration and falls were analyzed in 19 to 40, 41 to 60, and 61+ year age groups. Furthermore, the relations between sleep duration and indoor versus outdoor falls were analyzed. Both ≤6 and ≥8  hours of sleep per day were significantly associated with an increased incidence of falls (≥1 time and ≥2 times per year) in the overall adult population (P < 0.001 in both instances). In a subgroup analysis, sleep durations of ≤5 and ≥9  hours were significantly associated with an increased incidence of falls (≥1 time a year) in each age group. Six hours of sleep was not significantly associated with falls (≥2 times per year) in the 61+ year age group, and 8 and 9  hours of sleep were not significantly associated with falls (≥2 times a year) in the 19 to 40 year age group. This study demonstrated that long as well as short sleep durations are associated with an increased incidence of falls. However, these relations were not evident in elderly populations with short sleep durations or in young adults with long sleep durations.

Prevalence and Associated Factors of Subjective Halitosis in Korean Adolescents.

This study was conducted to estimate the prevalence and associated factors of subjective halitosis in adolescents. In total, 359,263 participants were selected from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) from 2009 through 2013. Demographic data including age, sex, obesity and residency; psychosocial factors such as subjective health, stress, and economic levels; and dietary factors such as alcohol consumption; smoking; and fruit, soda, fast food, instant noodle, confection, and vegetable consumption were analyzed for correlations with halitosis using simple and multiple logistic regression analyses with complex sampling. In total, 23.6% of the participants reported the presence of halitosis. The following subjectively assessed factors were related to halitosis: poor health status (adjusted odds ratio [AOR] = 2.56), overweight or obese (AOR = 1.37), stress (AOR = 2.56), and lower economic levels (AOR = 1.85). The high intake of fast food (AOR = 1.15), instant noodles (AOR = 1.17), and confections (AOR = 1.17) and the low intake of fruits (AOR = 1.22) and vegetables (AOR = 1.19) were also related to halitosis. The prevalence of subjective halitosis in the studied adolescents was 23.6%. Specific psychosocial factors and dietary intake were related to halitosis.

Sleep Deprivation Is Associated with Bicycle Accidents and Slip and Fall Injuries in Korean Adolescents.

OBJECTIVE: This study sought to evaluate associations between sleep time and bicycle accidents, falls under various circumstances, and dental injuries in adolescents. METHODS: A total of 61,696 participants ranging from 12 to 18 years of age who completed the Korea Youth Risk Behavior Web-based Survey (KYRBWS) in 2013 were enrolled in this study. Bicycle riding accidents were analyzed for 17,232 bicycle-riding participants. Data were collected regarding the weekday sleep duration for the most recent 7 days, which was categorized as < 5.5 h, 5.5-6.5 h, 6.5-7.5 h, or ≥ 7.5 h per day, and the incidence of bicycle accidents, slips and falls under various circumstances, and dental injuries in the most recent 12 months. Adjusted odds ratios (aORs) were calculated among sleep groups for bicycle accidents, slips and falls, and dental injuries using simple and multiple logistic regression analyses with complex sampling. RESULTS: Bicycle riding accidents and slips and falls in classrooms, corridors, the ground, toilets, stairs, and other unspecified situations showed positive correlations with sleep deprivation. Comparisons of groups with ≥ 7.5 h sleep, < 5.5 h, 5.5-6.5 h sleep, and 6.5-7.5 h sleep revealed increased associations with slips and falls under various circumstances. In particular, the aORs were higher in the groups with less sleep (aOR of the 5.5 h group > the 5.5-6.5 h group > the 6.5-7.5 h group). There was no significant relationship between sleep deprivation and dental injury. CONCLUSIONS: This study demonstrated that sleep deprivation among Korean adolescents was associated with bicycle accidents and falls at home and school. Thus, adequate sleep may be needed to prevent accidents and falls.

The prevention of contrast-induced nephropathy by simultaneous hemofiltration during coronary angiographic procedures: a comparison with periprocedural hemofiltration.

BACKGROUND: Periprocedural (6 h pre- and 24 h post-angiography) hemofiltration appears to effectively prevent contrast-induced nephropathy (CIN) in chronic kidney disease (CKD) patients undergoing coronary angiography. However, this procedure over-uses medical resources, and the cessation of hemofiltration during coronary angiography results in persistent renal injury. In comparison, simultaneous hemofiltration performed only during coronary angiography requires fewer medical resources and can provide instantaneous protection against CIN. METHODS: Sixty-eight CKD patients (serum creatinine, 2.51±1.15 mg/dL) undergoing coronary angiography were randomized in a 1:2 ratio to receive either periprocedural (n=23) or simultaneous (n=45) hemofiltration. The expected CIN rate was similar for the two groups (41.3% versus 40.0%, p=0.769). RESULTS: On day 3 after contrast exposure, four and seven patients in the periprocedural and simultaneous groups, respectively experienced CIN (17.4% versus 15.6%, p=0.846). On days 5-30, seven and three patients in the periprocedural and simultaneous groups, respectively experienced CIN (30.4% versus 6.7%, p=0.009). The serum creatinine levels of patients in the periprocedural group transiently decreased on day 1 and persistently increased during days 5-30 compared with the simultaneous group. This difference between the two groups in terms of creatinine levels over time was statistically significant (F statistic=6.830; p=0.001, by ANCOVA). The cost of hemofiltration was doubled in the periprocedural group ($1066±83 versus $504±40, p<0.001). CONCLUSIONS: Simultaneous hemofiltration provide equal early (day 3) and better late-stage (days 5-30) renal protection against CIN at a significantly lower cost compared with periprocedural hemofiltration.

Correction of anemia with continuous erythropoietin receptor activator in Korean patients on long-term hemodialysis.

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (≥ 18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb ≥ 11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481).

Rapid analysis of plasma paraquat using sodium dithionite as a predictor of outcome in acute paraquat poisoning.

BACKGROUND: Paraquat poisoning can be lethal, and aggressive treatments might have little or no effect on severely poisoned patients. Accordingly, a convenient prognostic test is necessary to guide therapy for acute paraquat poisoning. Sodium dithionite reduces paraquat to a blue radical form in alkaline plasma with a paraquat detection sensitivity of 2.0 mg/L, which is a 100% lethal concentration at 10 to 12 hours postingestion. The prognostic utility of this simple reaction was examined prospectively. METHODS: Of 233 paraquat-poisoned patients, who were taken to the hospital within 12 hours after ingestion, the plasma samples obtained on arrival were tested using the sodium dithionite reaction. Standard saline containing 2.0 mg/L paraquat was used as the positive control. The test result was interpreted as being positive when the plasma test yielded a blue color darker than that of the positive control. The effects of aggressive treatment, including cyclophosphamide pulse and continuous venovenous hemofiltration, were evaluated retrospectively. RESULTS: The discharge survival rate was 41.6% (97 of 233). Ninety-seven of 142 patients with negative or equivocal plasma dithionite test survived. However, all 91 patients with positive plasma dithionite test died of multiorgan failure. Cyclophosphamide and/or continuous venovenous hemofiltration could not improve survival. CONCLUSIONS: In this single-center study, a positive plasma dithionite test was associated with 100% mortality, despite aggressive treatment. In contrast, negative or equivocal tests were associated with a 68% survival rate. It is believed that after further verification, this test can be used to guide therapy and predict the outcomes of patients suffering acute paraquat poisoning.

Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers.

Waste incinerating workers are exposed to various pyrolysis products including polycyclic aromatic hydrocarbons (PAHs). We examined their PAH exposure by assessing urinary 1-hydroxypyrene glucuronide (1-OHPG), as a measure of internal dose, and aromatic DNA adducts in peripheral white blood cells (WBCs), as a measure of biological effect dose. The potential effect of genetic polymorphisms of three enzymes involved in PAH metabolisms (i.e., CYP1A1, GSTM1, and GSTT1) on these exposure markers was also investigated.Twenty-nine employees including workers incinerating industrial wastes and 21 non-exposed on-site controls were recruited from a company handling industrial wastes in South Korea. Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects working near incinerators. Urinary 1-OHPG was assayed by synchronous fluorescence spectroscopy (SFS) after immunoaffinity purification using monoclonal antibody 8E11. Aromatic DNA adducts in peripheral WBC were measured by the nuclease P1-enhanced post-labelling assay. Genotypes were assessed by PCR-based methods. Information on smoking habits and use of personal protective equipment were collected by self-administered questionnaire. Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (P=0.006, by Kruskal-Wallis test). A statistically significant dose-response increase in 1-OHPG levels was seen with the number of cigarettes consumed per day (r=0.686, P<0.001). Smoking and GSTM1 genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R(2)=0.565, P<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R(2)=0.249, P=0.201). Aromatic DNA adducts were significantly correlated with log-transformed urinary 1-OHPG level (r=0.31, P=0.04). However, the partial correlation coefficient adjusting for age, sex, and cigarette consumption was not significant (r=0.15, P=0.17). The significant association exists only in individuals with the GSTM1 null genotype (Pearson's correlation coefficient, r=0.52, P=0.01; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.36, P=0.04). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTM1 genotype. These results remain to be confirmed in future larger studies.