First-year estimated glomerular filtration rate variability after pre-end-stage renal disease program enrollment and adverse outcomes of chronic kidney disease.

BACKGROUND: Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease (ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD). METHODS: We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC). RESULTS: A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 [95% confidence interval (CI) 1.02-1.04], 1.04 (1.03-1.04), 1.16 (1.14-1.18), 1.16 (1.14-1.17) and 1.04 (1.03-1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11-3.38), 8.34 (6.33-10.98), 19.08 (11.89-30.62), 13.08 (8.32-20.55) and 6.35 (4.96-8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes. CONCLUSIONS: The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.

Longitudinal progression trajectory of random urine creatinine as a novel predictor of ESRD among patients with CKD.

BACKGROUND: The clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. METHODS: We modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. RESULTS: By group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1-12%) and 9% (95% CI: 2-17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with "medium" and "high-declining" urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a "stable-low" trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00-2.12) after considering the competing risk of death. CONCLUSIONS: Random urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

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

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

Uric acid predicts adverse outcomes in chronic kidney disease: a novel insight from trajectory analyses.

Background: Very little is known about longitudinal trajectories of serum uric acid (SUA) over the course of chronic kidney disease (CKD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of end-stage renal disease (ESRD) and all-cause mortality among CKD patients. Methods: We conducted a prospective cohort study from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 5090 CKD patients aged 20-90 years between 2003 and 2015. An individual's SUA trajectory was defined by group-based trajectory modeling in four distinct patterns: high, moderate-high, moderate and low. Time to ESRD and death was analyzed by multiple Cox regression. Results: A total of 948 ESRD events and 472 deaths occurred with incidence rates of 57.9 and 28.7 per 1000 person-years, respectively. Compared with those with a low SUA trajectory, the adjusted hazard ratio of patients for incident ESRD was in a dose-response manner as follows: moderate, 1.89 [95% confidence interval (CI), 1.37-2.60]; moderate-high, 2.49 (1.75-3.55); and high, 2.84 (1.81-4.47); after considering the competing risk of death. For all-cause mortality, the corresponding risk estimate of the same SUA trajectory was 1.38 (95% CI, 0.89-2.12), 1.95 (1.22-3.10) and 4.52 (2.48-8.26), respectively. The unfavorable effect of elevated SUA trajectories on progression to ESRD was differentially higher among CKD patients without using urate-lowering agents at baseline (P for interaction = 0.018). Conclusions: Elevated SUA trajectories are associated with accelerated kidney failure and all-cause mortality in CKD patients. Adequate experimental evidence is urgently needed to inform when and how to optimize SUA in this population.

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

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

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

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

Trends in the growth of literature of telemedicine: A bibliometric analysis.

Over the past two decades, the use of telemedicine as a way to provide medical services has grown as communication technologies advance and patients seek more convenient ways to receive care. Because developments within this field are still rapidly evolving, identifying trends within telemedicine literature is an important task to help delineate future directions of telemedicine research. In this study, we analyzed 7960 telemedicine-related publication records found in the Science Citations Index - Expanded database between 1993 and 2012. Bibliometric analyses revealed that while the total growth in telemedicine literature has been significant in the last twenty years, the publication activity per country and over time has been variable. While the United States led the world in the cumulative number of telemedicine publications, Norway ranked highest when we ordered countries by publications per capita. We also saw that the growth in the number of publications per year has been inconsistent over the past two decades. Our results identified that neuroscience neurology and nursing as two fields of research in telemedicine that have seen considerable growth in interest in this field, and are poised to be the focus of research activity in the near future.

Functional limitations and somatic diseases are independent predictors for incident depressive disorders in seniors: Findings from a nationwide longitudinal study.

PURPOSE: Few nationwide comprehensive studies analyzed the factors leading to the onset of depression in correlation with medical disease and other related factors concerning geriatric depression. This study examined medical diseases with other factors which lead to depression among the elderly. METHODS: This Taiwan-based longitudinal study examined a collection of 1467 seniors aged over 65. Subjects who fit this criteria were initially interviewed in 2003, and then four years later. Independent variables included baseline demographics, chronic medical illnesses, and the change of subjects' self-perceived health status, functional limitations including ADL, IADL and mobility limitation factors. The dependent variable was the symptoms of incident depression, as ascertained by the ten-item questionnaire during the later session. The logistic regression analyses were used to examine some of the predictors related to depressive disorders. RESULTS: The findings showed that heart conditions (adjusted OR=1.55, 95% CI: 1.12-2.15, p=0.008) and joint disorders (adjusted OR=1.51, 95% CI: 1.09-2.09, p=0.013), as well as functional limitations, particularly IADL (adjusted OR=1.81, 95% CI: 1.24-2.65, p=0.002) and ADL (adjusted OR=1.77, 95% CI: 1.27-2.47, p=0.001) were independently associated with the onset of depression among the elderly population. CONCLUSION: These findings indicated that when classifying symptoms of depression in geriatric patients with several underlying medical diseases, keen attention should be directed to the type of medical disorders and the functional deterioration in terms of daily activities and autonomic capabilities.

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

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

Factors associated with infection by 2009 pandemic H1N1 influenza virus during different phases of the epidemic.

OBJECTIVE: The focus of this study was to ascertain the factors associated with 2009 pandemic influenza H1N1 (pH1N1) infection during different phases of the epidemic. METHODS: In central Taiwan, 306 persons from households with schoolchildren were followed sequentially and serum samples were taken at three sampling time-points starting in the fall of 2008, shortly after influenza vaccination. Participants who seroconverted between two consecutive blood samplings were considered as having serological evidence of infection. A generalized estimation equation (GEE) with a logistic link to account for household correlations was applied to identify factors associated with pH1N1 infections during the pre-epidemic (April-June) and epidemic (September-October) periods. RESULTS: The results showed that receiving an inactivated seasonal influenza vaccine (ISIV) and having a hemagglutination inhibition assay (HI) titer of 40 or higher resulted in a significantly lower likelihood of pH1N1 infection during the pre-epidemic period only, for both children and adults (adjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.12-0.9). Having a previous infection by pH1N1 with a baseline titer of 20 or higher resulted in a significantly lower likelihood of infection by pH1N1 during the epidemic period (adjusted OR 0.06, 95% CI 0.02-0.16). CONCLUSIONS: Our results provide the first serological evidence to suggest a protection effect from receiving an ISIV against pH1N1 infection only when the HI titer reaches 40 or higher during the pre-epidemic period. This study gives an important insight into the control and intervention measures required for preventing infections during future influenza epidemics.

Serological evidence of subclinical transmission of the 2009 pandemic H1N1 influenza virus outside of Mexico.

BACKGROUND: Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April-June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics. METHODOLOGY/PRINCIPAL FINDINGS: Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1:40 or more during two periods: April-June and September-October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26-May 3. The incidence rates during the pre-epidemic phase (April-June) and the first wave (July-October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R(0), was 1.16 (95% confidence interval (CI): 0.98-1.34). CONCLUSIONS: Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April-June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network.

Serological response and persistence in schoolchildren with high baseline seropositive rate after receiving 2009 pandemic influenza A(H1N1) vaccine.

The serological response of the current 2009 H1N1 pandemic influenza monovalent vaccine in children exhibiting high baseline seropositive rate was evaluated though a community-based household study. Seroprotection rate of >90% and seroconversion rate of >50% were observed in children one month after receiving the pandemic vaccine. Among children with low baseline antibody titer, a significant lower seroconversion rate (55%) was observed in children who received seasonal trivalent inactivated vaccine (TIV) prior to pandemic vaccine, when compared with those receiving the pandemic vaccine only (86%). Persistence of antibody against the pandemic influenza virus was observed 6 months after vaccination in >80% of children presenting seroprotective antibody levels.

Sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students susceptible to psychosis.

BACKGROUND: Early interventions can improve treatment outcomes for individuals with major psychiatric disorders and with nonspecific symptoms but increasingly impaired cognitive perception, emotions, and behaviour. One way used to identify people susceptible to psychosis is through the schizotypal personality trait. Persons with schizotypal characteristics have been identified with the widely used Schizotypal Personality Questionnaire-Brief. However, no suitable instruments are available to screen individuals in the Taiwanese population for evidence of early psychotic symptoms. OBJECTIVES: The purpose of this study was to test the sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students' susceptibility to psychosis. DESIGN: Two-stage, cross-sectional survey design. SETTING AND PARTICIPANTS: The self-administered scale was tested in a convenience sample of 618 undergraduate students at a medical university in Taiwan. Among these students, 54 completed the scale 2 weeks apart for test-retest reliability, and 80 were tested to identify their susceptibility to psychosis. DATA COLLECTION AND ANALYSIS: In Stage I, participants with scores in the top 6.5% were classified as the high-score group (n=40). The control group (n=40) was randomly selected from the remaining participants with scores <15 and matched by gender. These 80 students were asked to participate in psychiatric interviews in Stage II. The instrument was tested for reliability using intraclass correlation coefficients and the Kuder-Richardson formula 20. The instrument was analysed for optimal sensitivity and specificity using odds-ratio analysis and receiver operating characteristic curves. RESULTS: The 22-item Chinese version of the Schizotypal Personality Questionnaire-Brief had a 2-week test-retest reliability of 0.82 and internal consistency of 0.76. The optimal cut-off score was 17, with odds ratios of 24.4 and an area under the receiver operating characteristic curves of 0.83. The instrument had a sensitivity of 80.0% and specificity of 85.9% in identifying undergraduate students' susceptibility to psychosis. CONCLUSIONS: The Chinese version Schizotypal Personality Questionnaire-Brief is a reliable instrument, but should not be used as a screening tool until its psychometric properties have been evaluated in more detail. Other screening tools need to be used in future studies with the CSPQ-B to improve the accuracy of identifying susceptibility to psychosis among young adults.

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

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

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

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