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BACKGROUND: Vascular access failure is a major cause of morbidity and hospitalization in hemodialysis populations worldwide. Erythropoietin (EPO) potentially can contribute to vascular access stenosis and occlusion by promoting intimal hyperplasia and thrombosis. Intravenous administration of EPO results in a severe, but transient, increase in drug concentration within the vascular access, whereas subcutaneous administration leads to a mild, but sustained, increase in the systemic circulation. The effect of route of administration of EPO on vascular access outcomes is uncertain. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 78 Korean hemodialysis patients were randomly assigned to receive either intravenous (n = 40) or subcutaneous (n = 38) EPO. INTERVENTIONS: EPO was administered during dialysis, and the dose was titrated to maintain hemoglobin levels between 9 to 12 g/dL. All patients received EPO 2 or 3 times/wk. Study duration was 4 to 77 months. OUTCOMES & MEASUREMENTS: The primary end point was time to vascular access failure. Analysis was performed using Cox regression analysis. RESULTS: The incidence of access failure was 4.7%/patient-year in the intravenous-therapy group and 12.0%/patient-year in the subcutaneous-therapy group, with an unadjusted hazard ratio of 3.24 (95% confidence interval, 1.31 to 8.00; P = 0.01). After adjustment for dialysis access type, vascular access age, previous intervention, serum phosphorus level, and diabetes mellitus, subcutaneous EPO administration was independently associated with increased vascular access failure (hazard ratio, 3.56; 95% confidence interval, 1.20 to 10.58; P = 0.02). There were no significant differences in either hemoglobin concentration or EPO dosage between the 2 groups during the study period. LIMITATIONS: Relatively small sample size and lack of complete symmetry between the 2 groups with respect to some baseline characteristics. CONCLUSIONS: This study suggests that the risk of vascular access failure may be greater with subcutaneous compared with intravenous administration of EPO in hemodialysis patients. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Handgrip strength (HGS) is suggested as an indirect assessment of nutritional status in chronic kidney disease (CKD) patients, but evidence is limited for non-dialysis-dependent CKD (NDD-CKD) patients. This cross-sectional study included 404 patients from the Phase II KoreaN Cohort Study for Outcome in Patients With CKD. HGS, measured twice in each hand, was the exposure, and malnutrition status was defined by a malnutrition-inflammation score (MIS) of 6 or higher. A logistic regression analysis adjusted for age, sex, diabetes mellitus (DM), hypertension, CKD stages, smoking, overhydration, education, and income status was used to assess malnutrition risk. The predictability of HGS for malnutrition was evaluated using the area under the curve (AUC). Patients with lower HGS were older, had a higher prevalence of DM, and lower estimated glomerular filtration rate. Higher HGS was significantly associated with lower malnutrition risk after adjustment (per 1 standard deviation increase, adjusted odds ratio, 0.47 [0.30-0.75]). Subgroup analyses showed no significant interaction between HGS and malnutrition risk across age, sex, DM, and CKD stage. HGS showed fair predictability for malnutrition in men (AUC 0.64 [0.46-0.83]) and women (AUC 0.71 [0.55-0.86]). In conclusion, HGS is a useful diagnostic indicator of malnutrition in NDD-CKD patients.

Background: Transmission intensity for mosquito-borne diseases are highly heterogenous and multi-factorial. Understanding risk factors associated to disease transmission allow the optimization of vector control. This study sets out to understand and compare the combined anthropogenic and environmental risk factors of four major mosquito-borne diseases, dengue, malaria, chikungunya and Japanese encephalitis in Thailand., Methods: An integrated analysis of mosquito-borne diseases, meteorological and ambient air pollutants of 76 provinces of Thailand was conducted over 2003-2021. We explored the use of generalized linear models and generalized additive models to consider both linear and non-linear associations between meteorological factors, ambient air pollutants and mosquito-borne disease incidence. Different assumptions on spatio-temporal dependence and nonlinearity were considered through province-specific and panel models, as well as different spline functions. Disease-specific model evidence was assessed to select best-fit models for epidemiological inference downstream., Results: Analyses indicated several findings which can be generally applied to all diseases explored: (1) higher AH above mean values was positively associated with disease case counts (2) higher total precipitation above mean values was positively associated with disease case counts (3) extremely high temperatures were negatively associated with disease case counts (4) higher SO2 and PM2.5 surface concentrations were negatively associated with disease case counts. However, the relationships between disease and RH, non-extreme temperatures and CO surface concentration were more mixed, with directions of associations changing across the different diseases considered., Conclusions: This study found protective and enhancing effects of meteorological and ambient air pollutant factors on mosquito-borne diseases burdens in Thailand. Further studies should employ these factors to understand and predict risk factors associated with mosquito-borne disease transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tewari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of this study was to evaluate whether the geriatric nutritional risk index (GNRI) is associated with chronic kidney disease (CKD) progression in patients with type 2 diabetes mellitus (DM). In total, 1100 patients with type 2 DM with a follow-up duration > 1 year were included in this longitudinal study. The risk of CKD progression was assessed according to GNRI quartiles. Patients in the lowest GNRI quartile exhibited a significantly lower estimated glomerular filtration rate (eGFR), compared with those in quartile four. Moreover, these patients had poorer glycemic control and lower hemoglobin levels, body mass index, and albumin levels. Additionally, they exhibited a greater annual decline in eGFR. Multivariate logistic regression analysis showed that old age (>60 years), baseline eGFR, the presence of proteinuria, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and low GNRI were significantly associated with CKD progression. GNRI may serve as a valuable predictive tool for identifying the risk of adverse renal outcomes in patients with type 2 DM. It may potentially serve as a more feasible measure for assessing the nutritional status of these patients, as well as for predicting their clinical outcomes.

Containment measures in high-risk closed settings, like migrant worker (MW) dormitories, are critical for mitigating emerging infectious disease outbreaks and protecting potentially vulnerable populations in outbreaks such as coronavirus disease 2019 (COVID-19). The direct impact of social distancing measures can be assessed through wearable contact tracing devices. Here, we developed an individual-based model using data collected through a Bluetooth wearable device that collected 33.6M and 52.8M contact events in two dormitories in Singapore, one apartment style and the other a barrack style, to assess the impact of measures to reduce the social contact of cases and their contacts. The simulation of highly detailed contact networks accounts for different infrastructural levels, including room, floor, block, and dormitory, and intensity in terms of being regular or transient. Via a branching process model, we then simulated outbreaks that matched the prevalence during the COVID-19 outbreak in the two dormitories and explored alternative scenarios for control. We found that strict isolation of all cases and quarantine of all contacts would lead to very low prevalence but that quarantining only regular contacts would lead to only marginally higher prevalence but substantially fewer total man-hours lost in quarantine. Reducing the density of contacts by 30% through the construction of additional dormitories was modelled to reduce the prevalence by 14 and 9% under smaller and larger outbreaks, respectively. Wearable contact tracing devices may be used not just for contact tracing efforts but also to inform alternative containment measures in high-risk closed settings., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: A pertinent risk factor of upper respiratory tract infections (URTIs) and pneumonia is the exposure to major ambient air pollutants, with short term exposures to different air pollutants being shown to exacerbate several respiratory conditions., Methods: Here, using disease surveillance data comprising of reported disease case counts at the province level, high frequency ambient air pollutant and climate data in Thailand, we delineated the association between ambient air pollution and URTI/Pneumonia burden in Thailand from 2000 - 2022. We developed mixed-data sampling methods and estimation strategies to account for the high frequency nature of ambient air pollutant concentration data. This was used to evaluate the effects past concentrations of fine particulate matter (PM 2.5 ), sulphur dioxide (SO 2 ), and carbon monoxide (CO) and the number of disease case count, after controlling for the confounding meteorological and disease factors., Results: Across provinces, we found that past increases in CO, SO 2, and PM 2.5 concentration were associated to changes in URTI and pneumonia case counts, but the direction of their association mixed. The contributive burden of past ambient air pollutants on contemporaneous disease burden was also found to be larger than meteorological factors, and comparable to that of disease related factors., Conclusions: By developing a novel statistical methodology, we prevented subjective variable selection and discretization bias to detect associations, and provided a robust estimate on the effect of ambient air pollutants on URTI and pneumonia burden over a large spatial scale., (© 2023. The Author(s).)

Introduction: Singapore lacks robust data on the sizes of the key populations that are most at risk for HIV. Using the network scale-up method for hidden or hard-to-reach populations, we estimate the sizes of five key populations-male clients of female sex workers (MCFSW), men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID) and transgender people-and profile the ages and ethnicities of respondents with the high-risk contacts they report knowing., Methods: We conducted a cross-sectional online survey between March and May 2019 (n = 2802) using a network scale-up instrument previously developed for Singapore. Participants were recruited using an existing panel and online advertising, and the sample reweighted by age, sex, ethnicity and education attained to represent the general adult population. We built a Bayesian hierarchical model to estimate the sizes of the five key populations for HIV in Singapore., Results: After adjustment, the sizes of the at-risk populations are estimated to be: 76,800 (95% credible interval [CI]: 64,200-91,800) MCFSW; 139,000 (95% CI: 120,000-160,000) MSM; 8030 (95% CI: 3980-16,200) FSW; 3470 (95% CI: 1540-7830) PWID and 18,000 (95% CI: 14,000-23,200) transgender people. Generally, men reported knowing more people in all the high-risk groups; older people reported knowing more MCFSW, FSW and transgender people; and younger people reported knowing more MSM. There was a bimodal effect of age on those who reported knowing more PWIDs: people in their 20s and 60s reported more contacts., Conclusions: This study demonstrates that a size estimation study of hidden populations is quickly and efficiently scalable through using online surveys in a socially conservative society, like Singapore, where key populations are stigmatized or criminalized. The approach may be suitable in other countries where stigma is prevalent and where barriers to surveillance and data collection are numerous., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Dengue is a major vector-borne disease worldwide. Here, we examined the spatial distribution of extreme weekly dengue outbreak risk in Singapore from 2007 to 2020. We divided Singapore into equal-sized hexagons with a circumradius of 165 m and obtained the weekly number of dengue cases and the surface characteristics of each hexagon. We accounted for spatial heterogeneity using max-stable processes. The 5-, 10-, 20-, and 30-year return levels, or the weekly dengue case counts expected to be exceeded once every 5, 10, 20, and 30 years, respectively, were determined for each hexagon conditional on their surface characteristics remaining constant over time. The return levels were higher in the country's east, with the maximum weekly dengue cases per hexagon expected to exceed 51 at least once in 30 years in many areas. The surface characteristics with the largest impact on outbreak risk were the age of public apartments and the percentage of impervious surfaces, where a 3-year and 10% increase in each characteristic resulted in a 3.8% and 3.3% increase in risk, respectively. Vector control efforts should be prioritized in older residential estates and places with large contiguous masses of built-up environments. Our findings indicate the likely scale of outbreaks in the long term.

Background: Little is known about the changes in hemodynamic parameters during arteriovenous (AV) access maturation using duplex ultrasound according to radiocephalic fistula (RCF), brachiocephalic fistula (BCF), and AV graft (AVG) in incident hemodialysis (HD) patient. The objective of this study was to evaluate changes and differences in brachial artery flow rate (BAFR) and related parameters affecting maturation by duplex ultrasound in incident HD patients according to access type., Methods: This study was an observational study conducted from March 2019 to October 2020. During the study period, 109 incident patients underwent new AV access creation, of which 100 were included in the study. The duplex ultrasound was performed on the day prior to access creation, further, day 1, 2 weeks, and 4 weeks later after access creation in incident HD patients., Results: Among all the patients, 38 (38%) received BCF, while 26 (26%) underwent RCF. Of the patients with AVG, 18 (50%) had a forearm loop AVG. The overall mean age was 62.2 ± 13.8 years (range, 32-89). The BAFR increased about 6.9 times in the RCF, 17.4 times in the BCF, and 19.5 times in the AVG at day 1. The median BAFR measured on day 1 was 580.4 mL/min for RC, 1029.0 mL/min for BC, and 1133.0 mL/min for AVG. Relative to the values measured in week 4, the BAFR on day 1 was 69.5% in RCF, 90.6% in BCF, and 93.9% in AVG. The acceleration decreased most significantly on day 1( p  < 0.05). The acceleration time increased significantly on day 1 ( p  < 0.05) and beyond during maturation in the RCF and BCF. The BAFR of the RCF had a significantly negative correlation with the pulsatility index. The BAFR of the BCF showed a significantly positive correlation with the systolic and diastolic blood pressure but negatively correlated with pulse rate. The BAFR of the AVG showed a significant positive correlation with the diameter of the outflow vein., Conclusions: There were differences in the clinical and duplex parameters during maturation according to access type. The most dramatic changes of duplex parameters were on the day after AV access creation regardless of AV access types. Though RCF had a lower BAFR rate compared to BCF and AVG, it already had a sufficient BAFR required for adequate HD treatment the day after creation. The BAFR of BCF was not different from that of AVG.

The Incompatible Insect Technique (IIT) strategy involves the release of male mosquitoes infected with the bacterium Wolbachia . Regular releases of male Wolbachia -infected mosquitoes can lead to the suppression of mosquito populations, thereby reducing the risk of transmission of vector-borne diseases such as dengue. However, due to imperfect sex-sorting under IIT, fertile Wolbachia -infected female mosquitoes may potentially be unintentionally released into the environment, which may result in replacement and failure to suppress the mosquito populations. As such, mitigating Wolbachia establishment requires a combination of IIT with other strategies. We introduced a simple compartmental model to simulate ex-ante mosquito population dynamics subjected to a Wolbachia -IIT programme. In silico, we explored the risk of replacement, and strategies that could mitigate the establishment of the released Wolbachia strain in the mosquito population. Our results suggest that mitigation may be achieved through the application of a sterile insect technique. Our simulations indicate that these interventions do not override the intended wild type suppression of the IIT approach. These findings will inform policy makers of possible ways to mitigate the potential establishment of Wolbachia using the IIT population control strategy.

As countries transition from pandemic mitigation to endemic COVID-19, mass testing may blunt the impact on the healthcare system of the liminal wave. We used GeoDEMOS-R, an agent-based model of Singapore's population with demographic distributions and vaccination status. A 250-day COVID-19 Delta variant model was run at varying maximal rapid antigen test sensitivities and frequencies. Without testing, the number of infections reached 1,021,000 (899,400-1,147,000) at 250 days. When conducting fortnightly and weekly mass routine rapid antigen testing 30 days into the outbreak at a maximal test sensitivity of 0.6, this was reduced by 12.8% (11.3-14.5%) and 25.2% (22.5-28.5%). An increase in maximal test sensitivity of 0.2 results a corresponding reduction of 17.5% (15.5-20.2%) and 34.4% (30.5-39.1%). Within the maximal test sensitivity range of 0.6-0.8, test frequency has a greater impact than maximal test sensitivity with an average reduction of 2.2% in infections for each day removed between tests in comparison to a 0.43% average reduction per 1% increase in test frequency. Our findings highlight that mass testing using rapid diagnostic tests can be used as an effective intervention for countries transitioning from pandemic mitigation to endemic COVID-19.

Background: Hyponatremia overcorrection can result in irreversible neurologic impairment such as osmotic demyelination syndrome. Few prospective studies have identified patients undergoing hypertonic saline treatment with a high risk of hyponatremia overcorrection., Methods: We conducted a post hoc analysis of a multicenter, prospective randomized controlled study, the SALSA trial, in 178 patients aged above 18 years with symptomatic hyponatremia (mean age, 73.1 years; mean serum sodium level, 118.2 mEq/L). Overcorrection was defined as an increase in serum sodium levels by >12 or 18 mEq/L within 24 or 48 hours, respectively., Results: Among the 178 patients, 37 experienced hyponatremia overcorrection (20.8%), which was independently associated with initial serum sodium level (≤110, 110-115, 115-120, and 120-125 mEq/L with 7, 4, 2, and 0 points, respectively), chronic alcoholism (7 points), severe symptoms of hyponatremia (3 points), and initial potassium level (<3.0 mEq/L, 3 points). The NASK (hypoNatremia, Alcoholism, Severe symptoms, and hypoKalemia) score was derived from four risk factors for hyponatremia overcorrection and was significantly associated with overcorrection (odds ratio, 1.41; 95% confidence interval, 1.24-1.61; p < 0.01) with good discrimination (area under the receiver-operating characteristic [AUROC] curve, 0.76; 95% CI, 0.66-0.85; p < 0.01). The AUROC curve of the NASK score was statistically better compared with those of each risk factor., Conclusion: In treating patients with symptomatic hyponatremia, individuals with high hyponatremia overcorrection risks were predictable using a novel risk score summarizing baseline information.

The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010-2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved satisfactory model performance (R2EpiEstim = 0.95, R2EpiFilter = 0.97), but disparities in performance were large at finer spatial scales when case counts are low (MASE EpiEstim = 1.23, MASEEpiFilter = 0.59). Impervious surfaces and vegetation with structure dominated by human management (without tree canopy) were positively associated with increased transmission intensity. Vegetation with structure dominated by human management (with tree canopy), on the other hand, was associated with lower dengue transmission intensity. We showed that dengue outbreaks were preceded by sustained periods of high transmissibility, demonstrating the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response., Competing Interests: The authors have declared that no competing interests exist.

Introduction: COVID-19 transmission within overcrowded migrant worker dormitories is an ongoing global issue. Many countries have implemented extensive control measures to prevent the entire migrant worker population from becoming infected. Here, we explore case count outcomes when utilizing lockdown and testing under different testing measures and transmissibility settings., Methods: We built a mathematical model which estimates transmission across 10 different blocks with 1000 individuals per block under different parameter combinations and testing conditions over the period of 1 month. We vary parameters including differences in block connectivity, underlying recovered proportions at the time of intervention, case importation rates and testing protocols using either PCR or rapid antigen testing., Results: We estimate that a relatively transmissible environment with fortnightly PCR testing at a relatively low initial recovered proportion of 40%, low connectivity where 10% of contacts occurred outside of the infected individuals' block and a high importation rate of 1 100 000 per day, results in an average of 39 (95%Interval: 9-121) new COVID-19 cases after one month of observation. Similar results were observed for weekly rapid antigen testing at 33 (9-95) cases., Interpretation: Our findings support the need for either fortnightly PCR testing or weekly rapid antigen testing in high population density environments such as migrant worker dormitories. Repeated mass testing is highly effective, preventing localized site outbreaks and reducing the need for site wide lockdowns or other extensive social distancing measures within and outside of dormitories., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Introduction: Despite of the routine use of erythropoietin in hemodialysis patients to correct anemia, its administration route's effects on hemoglobin variability and cardiovascular events remain elusive. Herein, we determined different erythropoietin administration routes' effects on hemoglobin variability in hemodialysis patients and the associated factors of hemoglobin variability and cardiovascular events., Methods: This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of <25%., Results: In this analysis, 37 patients (51.1%) were male, and the mean age was 50.6 ± 12.5 years. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high group was a significant independent risk factor for cardiovascular events (p = 0.03)., Conclusion: The risk out of the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.

The release of Wolbachia-infected mosquitoes is a promising disease intervention strategy that aims to control dengue and other arboviral infections. While early field trials and modelling studies suggest promising epidemiological and entomological outcomes, the overall cost effectiveness of the technology is not well studied in a resource rich setting nor under the suppression approach that aims to suppress the wild-type mosquito population through the release of Wolbachia-infected males. We used economical and epidemiological data from 2010 to 2020 to first ascertain the economic and health costs of dengue in Singapore, a high income nation where dengue is hyper-endemic. The hypothetical cost effectiveness of a national Wolbachia suppression program was then evaluated historically from 2010 to 2020. We estimated that the average economic impact of dengue in Singapore from 2010 to 2020 in constant 2010US$ ranged from $1.014 to $2.265 Billion. Using empirically derived disability weights, we estimated a disease burden of 7,645-21,262 DALYs from 2010-2020. Under an assumed steady-state running cost of a national Wolbachia suppression program in Singapore, we conservatively estimate that Wolbachia would cost an estimated $50,453-$100,907 per DALYs averted and would lead to an estimated $329.40 Million saved in economic costs over 2010 to 2020 under 40% intervention efficacy. Wolbachia releases in Singapore are expected to be highly cost-effective and its rollout must be prioritised to reduce the onward spread of dengue., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2021 Soh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic has resulted in the closure or partial closure of international borders in almost all countries. Here, we investigate the efficacy of imported case detection considering quarantine length and different testing measures for travellers on arrival., Methods: We examine eight broad border control strategies from utilizing quarantine alone, pre-testing, entry and exit testing, and testing during quarantine. In comparing the efficacy of these strategies, we calculate the probability of detecting travellers who have been infected up to 2 weeks pre-departure according to their estimated incubation and infectious period. We estimate the number of undetected infected travellers permitted entry for these strategies across a prevalence range of 0.1-2% per million travellers., Results: At 14-day quarantine, on average 2.2% (range: 0.5-8.2%) of imported infections are missed across the strategies, leading to 22 (5-82) imported cases at 0.1% prevalence per million travellers, increasing up to 430 (106-1641) at 2%. The strategy utilizing exit testing results in 3.9% (3.1-4.9%) of imported cases being missed at 7-day quarantine, down to 0.4% (0.3-0.7%) at 21-day quarantine, and the introduction of daily testing, as the most risk averse strategy, reduces the proportion further to 2.5-4.2% at day 7 and 0.1-0.2% at day 21 dependent on the tests used. Rapid antigen testing every 3 days in quarantine leads to 3% being missed at 7 days and 0.7% at 14 days, which is comparable to PCR testing with a 24-hour turnaround., Conclusions: Mandatory testing, at a minimal of pre-testing and on arrival, is strongly recommended where the length of quarantining should then be determined by the destination country's level of risk averseness, pandemic preparedness and origin of travellers. Repeated testing during quarantining should also be utilized to mitigate case importation risk and reduce the quarantining duration required., (© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients., Methods: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed., Results: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02)., Conclusion: There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Over 105 million dengue infections are estimated to occur annually. Understanding the disease dynamics of dengue is often difficult due to multiple strains circulating within a population. Interactions between dengue serotype dynamics may result in complex cross-immunity dynamics at the population level and create difficulties in terms of formulating intervention strategies for the disease. In this study, a nationally representative 16-year time series with over 43 000 serotyped dengue infections was used to infer the long-run effects of between and within strain interactions and their impacts on past outbreaks. We used a novel identification strategy incorporating sign-identified Bayesian vector autoregressions, using structural impulse responses, historical decompositions and counterfactual analysis to conduct inference on dengue dynamics post-estimation. We found that on the population level: (i) across-serotype interactions on the population level were highly persistent, with a one time increase in any other serotype associated with long run decreases in the serotype of interest (range: 0.5-2.5 years) and (ii) over 38.7% of dengue cases of any serotype were associated with across-serotype interactions. The findings in this paper will substantially impact public health policy interventions with respect to dengue.

Mass gathering events have been identified as high-risk environments for community transmission of coronavirus disease 2019 (COVID-19). Empirical estimates of their direct and spill-over effects however remain challenging to identify. In this study, we propose the use of a novel synthetic control framework to obtain causal estimates for direct and spill-over impacts of these events. The Sabah state elections in Malaysia were used as an example for our proposed methodology and we investigate the event's spatial and temporal impacts on COVID-19 transmission. Results indicate an estimated (i) 70.0% of COVID-19 case counts within Sabah post-state election were attributable to the election's direct effect; (ii) 64.4% of COVID-19 cases in the rest of Malaysia post-state election were attributable to the election's spill-over effects. Sensitivity analysis was further conducted by examining epidemiological pre-trends, surveillance efforts, varying synthetic control matching characteristics and spill-over specifications. We demonstrate that our estimates are not due to pre-existing epidemiological trends, surveillance efforts, and/or preventive policies. These estimates highlight the potential of mass gatherings in one region to spill-over into an outbreak of national scale. Relaxations of mass gathering restrictions must therefore be carefully considered, even in the context of low community transmission and enforcement of safe distancing guidelines., Competing Interests: The authors have declared that no competing interests exist.

Chronic disease burdens continue to rise in highly dense urban environments where clustering of type II diabetes mellitus, acute myocardial infarction, stroke, or any combination of these three conditions is occurring. Many individuals suffering from these conditions will require longer-term care and access to clinics which specialize in managing their illness. With Singapore as a case study, we utilized census data in an agent-modeling approach at an individual level to estimate prevalence in 2020 and found high-risk clusters with >14,000 type II diabetes mellitus cases and 2000-2500 estimated stroke cases. For comorbidities, 10% of those with type II diabetes mellitus had a past acute myocardial infarction episode, while 6% had a past stroke. The western region of Singapore had the highest number of high-risk individuals at 173,000 with at least one chronic condition, followed by the east at 169,000 and the north with the least at 137,000. Such estimates can assist in healthcare resource planning, which requires these spatial distributions for evidence-based policymaking and to investigate why such heterogeneities exist. The methodologies presented can be utilized within any urban setting where census data exists.

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.

Background: With more countries exiting lockdown, public health safety requires screening measures at international travel entry points that can prevent the reintroduction or importation of the severe acute respiratory syndrome-related coronavirus-2. Here, we estimate the number of cases captured, quarantining days averted and secondary cases expected to occur with screening interventions., Methods: To estimate active case exportation risk from 153 countries with recorded coronavirus disease-2019 cases and deaths, we created a simple data-driven framework to calculate the number of infectious and upcoming infectious individuals out of 100 000 000 potential travellers from each country, and assessed six importation risk reduction strategies; Strategy 1 (S1) has no screening on entry, S2 tests all travellers and isolates test-positives where those who test negative at 7 days are permitted entry, S3 the equivalent but for a 14 day period, S4 quarantines all travellers for 7 days where all are subsequently permitted entry, S5 the equivalent for 14 days and S6 the testing of all travellers and prevention of entry for those who test positive., Results: The average reduction in case importation across countries relative to S1 is 90.2% for S2, 91.7% for S3, 55.4% for S4, 91.2% for S5 and 77.2% for S6. An average of 79.6% of infected travellers are infectious upon arrival. For the top 100 exporting countries, an 88.2% average reduction in secondary cases is expected through S2 with the 7-day isolation of test-positives, increasing to 92.1% for S3 for 14-day isolation. A substantially smaller reduction of 30.0% is expected for 7-day all traveller quarantining, increasing to 84.3% for 14-day all traveller quarantining., Conclusions: The testing and isolation of test-positives should be implemented provided good testing practices are in place. If testing is not feasible, quarantining for a minimum of 14 days is recommended with strict adherence measures in place., (© International Society of Travel Medicine 2020.)

An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100-242) and 2008 cases in the country as a whole (95% CI: 1170-2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies., Competing Interests: The authors have declared that no competing interests exist.

Background: With at least 94 countries undergoing or exiting lockdowns for contact suppression to control the COVID-19 outbreak, sustainable and public health-driven exit strategies are required. Here we explore the impact of lockdown and exit strategies in Singapore for immediate planning., Methods: We use an agent-based model to examine the impacts of epidemic control over 480 days. A limited control baseline of case isolation and household member quarantining is used. We measure the impact of lockdown duration and start date on final infection attack sizes. We then apply a 3-month gradual exit strategy, immediately re-opening schools and easing workplace distancing measures, and compare this to long-term social distancing measures., Findings: At baseline, we estimated 815 400 total infections (21.6% of the population). Early lockdown at 5 weeks with no exit strategy averted 18 500 (2.27% of baseline averted), 21 300 (2.61%) and 22 400 (2.75%) infections for 6, 8 and 9-week lockdown durations. Using the exit strategy averted a corresponding 114 700, 121 700 and 126 000 total cases, representing 12.07-13.06% of the total epidemic size under baseline. This diminishes to 9 900-11 300 for a late 8-week start time. Long-term social distancing at 6 and 8-week durations are viable but less effective., Interpretation: Gradual release exit strategies are critical to maintain epidemic suppression under a new normal. We present final infection attack sizes assuming the ongoing importation of cases, which require preparation for a potential second epidemic wave due to ongoing epidemics elsewhere., Funding: Singapore Ministry of Health, Singapore Population Health Improvement Centre., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s). Published by Elsevier Ltd.)

Background: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful., Methods: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R 0 ] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R 0 value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures., Findings: For the baseline scenario, when R 0 was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000-320 000), corresponding to 7·4% (IQR 6·5-8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000-776 000) when R 0 was 2·0, corresponding to 19·3% (17·8-20·6) of the Singaporean population, and 1 207 000 cases (1 164 000-1 249 000) when R 0 was 2·5, corresponding to 32% (30·9-33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6-99·9) when R 0 was 1·5, by 93·0% (81·5-99·7) when R 0 was 2·0, and by 78·2% (59·0 -94·4) when R 0 was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R 0 of 1·5., Interpretation: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines., Funding: Singapore Ministry of Health, Singapore Population Health Improvement Centre., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aims: Maintaining the patency of vascular access (VA) in hemodialysis (HD) patients is important and can be life-saving. We investigated the effects of aspirin resistance and mean platelet volume (MPV) on VA failure in HD patients., Methods: We enrolled 163 patients on maintenance HD. VA failure was defined as thrombosis or a decrease of > 50% of the normal vessel diameter, as revealed by angiography., Results: Aspirin resistance was observed in 17 of 109 patients in whom this parameter was measured, and was not significantly associated with VA failure (p = 0.051). The mean MPV was 9.15 ± 0.05 fL. The 163 patients were grouped by the median MPV value (9.08 fL) at baseline; patients with higher MPVs (n = 82) had lower platelet counts (p = 0.002) and albumin levels (p = 0.009). During 34 months of follow-up, 65 VA failures (39.9%) occurred. The Kaplan-Meier curve revealed significant differences between the two groups in terms of cumulative VA failure (54.1% vs. 35.3%, p = 0.018). On multivariate analysis, the MPV (hazard ratio [HR], 1.794; 95% confidence interval [CI], 1.066 to 3.020; p = 0.028), platelet count (HR, 1.003; 95% CI, 1.001 to 1.006; p = 0.01), and smoking status (HR, 1.894; 95% CI, 1.019 to 3.519; p = 0.043) independently predicted VA failure., Conclusion: A high MPV was associated with an increased risk of VA failure, whereas aspirin resistance showed only a weak association. The MPV may predict VA survival in HD patients.

Background/aims: Hepatitis A virus (HAV) is a self-limiting infectious disease, but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains unknown. The purpose of this study was to describe and compare the seropositive rate of anti-HAV antibody among hemodialysis subjects in two hospitals according to age group., Methods: A total of 170 hemodialysis subjects were evaluated for the seropositive rate of the anti-HAV IgG antibody and its titer., Results: Of the 170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon 78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the subjects were over 40 years old. The median vintage of hemodialysis was 29.0 months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n = 73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while the seropositive rate increased with age for subjects aged 40 or older (p for trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon 11.7). Only age influenced seropositivity. The only factor that influenced the antibody level was the location of hospital (p < 0.001)., Conclusion: The seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%, which is similar to findings in the general population. Active immunization against hepatitis A is strongly recommended for hemodialysis subjects under 40 years of age after anti-HAV testing.

Background: Elevated serum alkaline phosphatase (AP) and γ-glutamyl transferase (γ-GT) are commonly observed in patients with acute pyelonephritis. The goal of this study was to examine the clinical significance of elevated serum AP and γ-GT levels and to explore the mechanisms underlying these changes., Methods: We examined serum AP and γ-GT levels in 438 patients with acute pyelonephritis. Urine AP/creatinine (Cr), urine γ-GT/Cr, fractional excretion of AP, and fractional excretion of γ-GT (FE γ-GT ) were evaluated in patients with elevated and normal serum levels. AP isoenzymes were also examined., Results: We identified 77 patients (17.6%) with elevated serum AP and 134 patients (30.6%) with elevated serum γ-GT. Among them, both enzymes were elevated in 64 patients (14.6%). Older age, longer hospital stay, elevated baseline serum Cr, and complicated pyelonephritis were associated with increases in serum AP and γ-GT. Multivariate analysis showed that high serum AP levels were significantly correlated with renal impairment (odds ratio, 2.13; 95% confidence interval, 1.08-4.19; P = 0.029). FE γ-GT was significantly lower in patients with elevated serum enzyme levels. The liver fraction for AP isoenzyme profile did not increase in patients with elevated serum AP., Conclusion: Our results demonstrated that elevated serum AP and γ-GT levels are associated with complicated pyelonephritis and renal impairment. Lower FE γ-GT levels in patients with elevated serum enzymes may be the result of decreased urinary excretion of these enzymes.

Background and Aims: Malnutrition and inflammation are closely linked to vascular calcification (VC), the severity of which correlate with adverse outcome. However, there were few studies on the interplay between malnutrition, inflammation and VC progression, rather than VC presence per se. We aimed to determine the relationship of malnutrition, inflammation, abdominal aortic calcification (AAC) progression with survival in hemodialysis (HD) patients., Methods: Malnutrition and inflammation were defined as low serum albumin (< 40 g/L) and high hs-CRP (≥ 28.57 nmol/L), respectively. We defined AAC progression as an increase in AAC score using lateral lumbar radiography at both baseline and one year later. Patients were followed up to investigate the impact of AAC progression on all-cause and cardiovascular mortality., Results: AAC progressed in 54.6% of 97 patients (mean age 58.2±11.7 years, 41.2% men) at 1-year follow-up. Hypoalbuminemia (Odds ratio 3.296; 95% confidence interval 1.178-9.222), hs-CRP (1.561; 1.038-2.348), low LDL-cholesterol (0.976; 0.955-0.996), and the presence of baseline AAC (10.136; 3.173-32.386) were significant risk factors for AAC progression. During the mean follow-up period of 5.9 years, 38(39.2%) patients died and 27(71.0%) of them died of cardiovascular disease. Multivariate Cox regression analysis adjusted for old age, diabetes, cardiovascular history, and hypoalbuminemia determined that AAC progression was an independent predictor of all-cause mortality (2.294; 1.054-4.994)., Conclusions: Malnutrition and inflammation were significantly associated with AAC progression. AAC progression is more informative than AAC presence at a given time-point as a predictor of all-cause mortality in patients on maintenance HD., Competing Interests: The authors have declared that no competing interests exist.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hypo-osmotic hyponatremia. There are several etiologies of SIADH including neuroendocrine tumor, pulmonary disease, infection, trauma, and medications. Here, we report a case of SIADH associated with a schwannoma involving the mediastinum in a 75-year-old woman who presented with nausea, vomiting, and general weakness. Laboratory testing showed hypo-osmolar hyponatremia, with a serum sodium level of 102mmol/L, serum osmolality of 221mOsm/kg, urine osmolality of 382mOsm/kg, urine sodium of 55 mmol/L, and plasma antidiuretic hormone (ADH) of 4.40 pg/mL. Chest computed tomography identified a 1.5-cm-sized solid enhancing nodule in the right lower paratracheal area. A biopsy specimen was obtained by video-assisted thoracoscopic surgery, which was diagnosed on pathology as a schwannoma. The hyponatremia was completely resolved after schwannoma resection and plasma ADH level decreased from 4.40 pg/mL to 0.86 pg/mL. This case highlights the importance of suspecting and identifying the underlying cause of SIADH when faced with refractory or recurrent hyponatremia, and that on possibility is mediastinal schwannoma., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare.

Background: In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex., Methods: Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively., Results: The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01-1.25) and 1.09 (1.01-1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio., Conclusions: Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD., Competing Interests: The authors have declared that no competing interests exist.

Background: End-stage renal disease is a common predisposing condition for the development of hypoglycaemia., Aim: To determine the effect of hypoglycaemia on the mortality of patients undergoing maintenance dialysis., Methods: Retrospective and descriptive analyses were performed in five dialysis centres in the Republic of Korea between June 2002 and August 2008. We enrolled 1685 patients who had undergone dialysis for at least 1 month., Results: We identified 453 episodes of hypoglycaemia in 256 of 1685 patients (15.2%); 189 patients (73.8%) had diabetes, whereas the other patients did not. The occurrence of hypoglycaemia in patients receiving dialysis appeared to be a life-threatening complication because 27.0% of patients died within two days of the onset of a hypoglycaemic episode. Older age, low serum albumin levels and infections were independent risk factors for total mortality in these patients. Furthermore, the absence of diabetes, age and serum glucose levels were independent factors associated with early mortality within two days of the development of hypoglycaemia., Conclusion: Although several factors were associated with mortality, the degree of hypoglycaemia, absence of diabetes and old age were associated with early mortality. Elderly hypoglycaemic patients, especially those without diabetes, should be closely monitored., (© 2016 Royal Australasian College of Physicians.)

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population., Competing Interests: The authors have no potential conflicts of interest to disclose.

Diabetic bladder dysfunction (DBD) is a common complication of type 2 diabetes mellitus (T2DM). The association between DBD and progression of diabetic nephropathy has not been clarified. In this study, we investigated the relationship between post-voiding residual urine (PVR) with decline in renal function in patients with type 2 diabetes. This retrospective study included 164 patients at a single center. We collected medical histories and laboratory findings of patients undergoing uroflowmetry from January 1, 2008 to October 30, 2013. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study equation. We evaluated whether greater PVR was a risk factor for faster decline of GFR during a 1-year follow-up. The subjects' mean age was 65±12 years, duration of diabetes 12.8±8.8 years, baseline serum creatinine level 106.1±53.0 μmol/L, and eGFR was 64.6±25.2 mL/min/1.73 m(2). Mean PVR was 69.8±96.3 mL and in 17.7% of subjects, PVR>100 mL. In linear regression analysis, PVR was independently associated with GFR decrease (standardized β coefficient=0.2, P=0.009). Multiple logistic analysis showed that subjects with PVR>100 mL had a 2.8-fold higher risk of an eGFR change during 1 year higher than the median value of all subjects (95% confidence interval, 1.1-6.8; P=0.03). Increased PVR was independently associated with a more rapid decline in renal function in patients with type 2 diabetes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In this paper, we demonstrated thin film semitransparent anode electrode using Ni/Ag/Ni (3/6/3 nm) on green and red phosphorescent OLEDs, which have basically high efficiency and good optical characteristics. Moreover, we applied this semitransparent anode on flexible green and red phosphorescent OLEDs, which were then optimized for possible applications on flexible substrates. First, we studied optimization using various conditions of Ni/Ag/Ni electrodes via transmittance and sheet resistance. We then fabricated the devices on a glass substrate with ITO or Ni/Ag/Ni electrodes as well as on a flexible substrate with a Ni/Ag/Ni electrode for green and red phosphorescent OLEDs. Consequently, we could be proposed that the potential of our semitransparent anode electrode is demonstrated. Green phosphorescent OLEDs characteristics using ITO or Ni/Ag/Ni anode electrodes were coincided and those of the red phosphorescent OLEDs were improved by semitransparent electrodes at 10,000 cd/m2 criterion. Therefore, this research suggests for additional studies to be conducted on flexible and high-performance phosphorescent OLED displays and light applications for ITO-free processes.

We investigated a light emission mechanism of blue phosphorescent organic light emitting diodes (PHOLEDs), using a stepwise doping profile of 2, 8, and 14 wt.% within the emitting layer (EML). We fabricated several blue PHOLEDs with phosphorescent blue emitter iridium(III) bis[(4,6-difluorophenyl)-pyridinato-N,C2]picolinate doped in N,N'-dicarbazolyl-3,5-benzene as a p-type host material. A blue PHOLED with the highest doping concentration as part of the EML close to an electron transporting layer showed a maximum luminous efficiency of 20.74 cd/A, and a maximum external quantum efficiency of 10.52%. This can be explained by effective electron injection through a highly doped EML side. Additionally, a white OLED based on the doping profile was fabricated with two thin red EMLs within a blue EML maintaining a thickness of 30 nm for the entire EML. Keywords: Blue Phosphorescent Organic Light Emitting Diodes, Stepwise Doping Structure, Charge Trapping Effect.

Background/aims: Diabetic cystopathy is a frequent complication of diabetes mellitus. This study assessed the association between the post-voiding residual (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding symptoms., Methods: This study investigated 42 patients with type 2 diabetes who were followed regularly at our outpatient clinic between July 1, 2008 and June 30, 2009. No patient had voiding problems or International Prostate Symptom Scores (IPSSs) ≥ 12. An urologist performed the urological evaluations and the PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was considered abnormal, which was the primary study outcome., Results: The mean patient age was 60 ± 10 years; the IPSS score was 3.7 ± 3.3; and the diabetes duration was 11.9 ± 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50 mL. The presence of overt proteinuria or microalbuminuria was associated with an increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a significantly lower estimated glomerular filtration rate (eGFR) compared with those with a PVR ≤ 50 mL (59.2 ± 27.1 mL/min/1.73 m(2) vs. 28.7 ± 23.3 mL/min/1.73 m(2); p < 0.001). Multivariate logistic analysis revealed that a lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04) was a significant risk factor for a PVR > 50 mL., Conclusions: Patients with diabetic nephropathy had a significantly higher PVR and a lower eGFR was associated with an abnormal PVR.

Green phosphorescent organic light emitting diodes (PHOLEDs) were developed using a mixed layer system. They were fabricated with 4,4'-N,N'-dicarbazolyl-biphenyl (CBP) and typical charge transporting materials, which are 4,4'-bis[N-(naphthyl)-N-phenylamino]biphenyl (NPB) as a hole transporting material and 1,3,5-tris(N-phenylbenzimidazole-2-yl)benzene (TPBi) as an electron transporting material, mixed at each interface in a stacked organic layer to reduce the hole injection barrier and extend the recombination zone. We introduced a mixed layer for the hole transporting layer side, the electron transporting layer side, and on both sides to make a bulk heterojunction. This reduced the driving voltage, and the luminous efficiency (LE) was increased to 500 cd/m2. The optimized device showed a maximum LE of 59.87 cd/A and a maximum external quantum efficiency of 17.52%.

We suggested that Ni/Ag/Ni semitransparent electrodes for the exchange of indium-tin-oxide (ITO) electrode, which is the most commonly used as a transparent electrode in spite of the structural defects, limited supply of indium, and toxic, could be apply on flexible Organic Light-Emitting Diodes (OLEDs). Red phosphorescent OLEDs (PHOLEDs) using different types of electrodes as ITO and various conditions of Ni/Ag/Ni electrode were fabricated and analyzed. The electrical and optical properties of device using Ni/Ag/Ni electrode were improved than that of devices on ITO glass substrate at the 10,000 cd/m2 criterion due to the micro-cavity effect even though their transmittance has lower than ITO glass. In addition, we also fabricated red PHOLEDs of same structure on Ni/Ag/Ni flexible substrate of various conditions. As a result, flexible red PHOLED showed competitive characteristics compared to the device on a glass substrate. Therefore, this study could be suggested to additional research on flexible OLEDs display and light applications for ITO-free fabrication.

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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The authors describe the fabrication of white organic light-emitting diodes (WOLEDs) with dual electron transporting layers (D-ETL) using 2,9-dimethyl-4,7-diphenyl-1,10-phenanhroline/ 4,7-diphenyl-1,10-phenanthroline (BPhen) and bis-(2-methyl-8-quinolinolate)-4-(phenylphenolato) aluminum/BPhen. Stepwise D-ETL easily transports electrons easily to the emitting layer and reduces the leakage of electrons. Therefore, WOLEDs with D-ETL show higher external quantum efficiency (EQE) when compared to a control WOLED with a single ETL device. The optimized WOLEDs showed a peak EQE of 13.0%, luminous efficiency of 27.4 cd/A, and Commission Internationale de L'Eclairage coordinates of (0.40, 0.39) at 1000 cd/m2.

We report an improvement of efficiency in red phosphorescent organic light-emitting diodes (PHOLEDs) based on a combination of heterojunction (HJ) structure and mixed host (MH) system using a phosphorescent red emitter: bis(2-phenylquinolinato)-acetylacetonate iridium III [Ir(pq)2(acac)] doped in 4,4,N,N'-dicarbazolebiphenyl (CBP) of hole transport type host material and 1,3,5-tris(N-phenylbenzimidazole-2-yl)benzene (TPBi) of electron transport type host material. This combination device resulted in an effective electron and hole balance and distribution of the recombination zone. Therefore, highly efficient red PHOLEDs with maximum luminous efficiency and external quantum efficiency of 21.93 cd/A and 14.09% were achieved. Moreover, the combination device showed a power efficiency of 9.51 lm/W, which is higher than 7.61 lm/W in the control device at a luminance of 1000 cd/m2.

We investigated blue fluorescent organic light-emitting diode (OLED) with a charge control layer (CCL) to produce high efficiency and improve the half-decay lifetime. Three types of devices (device A, B, and C) were fabricated following the number of CCLs within the emitting layer (EML), maintaining the thickness of whole EML. The CCL and host material, 2-methyl-9,10-di(2-naphthyl)anthracene, which has a bipolar property, was able to control the carrier movement with ease inside the EML. Device B demonstrated a maximum luminous efficiency (LE) and external quantum efficiency (EQE) of 9.19 cd/A and 5.78%, respectively. It also showed that the enhancement of the half-decay lifetime, measured at an initial luminance of 1,000 cd/m2, was 1.5 times longer than that of the conventional structure. A hybrid white OLED (WOLED) was also fabricated using a phosphorescent red emitter, bis(2-phenylquinoline)-acetylacetonate iridium III doped in 4,4'-N,N'-dicarbazolyl-biphenyl. The property of the hybrid WOLED with CCL showed a maximum LE and an EQE of 13.46 cd/A and 8.32%, respectively. It also showed white emission with Commission International de L'Éclairage coordinates of (x = 0.41, y = 0.33) at 10 V.

Compared with other materials, zinc oxide (ZnO) exhibits stability in air, high-electron mobility, transparency and low light sensitivity. We investigated these properties in ZnO thin-film transistors (TFTs) containing a cross-linked poly(vinyl alcohol) (C-PVA) (1:3) buffer layer stacked between the semiconductor and gate dielectric. We measured the impact of this C-PVA layer on gate bias stress. We measured the transfer characteristics of the saturation region to determine the threshold voltage and the field-effect mobility of the transistors. We recorded a threshold voltage of 11.53 V in the ZnO TFTs with the C-PVA buffer layer, the field-effect mobility was 0.2 cm2/Vs. There was a positive shift in the threshold voltage of deltaV(TH) approximately 10 V in response to the application of a gate bias stress of 20 V. The positive shift in the threshold voltage was lower than that in pristine ZnO TFTs. This finding suggests that the shift in threshold voltage was due to reduced charge trapping at the semiconductor-gate dielectric interface. Our report indicates that the organic buffer layer enhanced the stability of ZnO TFTs.

Systematic studies on carrier injection and transport are very important for achieving high efficiency in OLEDs. We demonstrate excellent green phosphorescent organic light-emitting diodes (OLED) with lithium quinolate (Liq) doped in 1,3,5-tris(N-phenylbenzimidazole-2-yl) benzene (TPBi) as the electron transport layer (ETL). The doping concentration of Liq was varied from 0% to 10%. The optimized green phosphorescent OLED with 5% Liq in the ETL showed the best efficiencies, which were maximum luminous efficiency, power efficiency, and quantum efficiency of 65.76 cd/A, 57.39 Im/W, and 20.03%, respectively. Moreover, high triplet energy states of TCTA and TPBi as a triplet exciton-blocking layer (TEBL) played a role in efficient exciton confinement.