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Chronic kidney disease (CKD) poses significant challenges to public health and healthcare systems, demanding a comprehensive understanding of its progressive nature. Prior methods have often fallen short in capturing the dynamic and individual variability of renal function. This study aims to address this gap by introducing a novel approach for the individualized assessment of CKD progression. A cohort of 1042 patients, comprising 700 with stage 3a and 342 with stage 3b to stage 5 CKD, treated at a veteran general hospital in Taiwan from 2006 to 2019, was included in the study. A comprehensive dataset spanning 12 years, consisting of clinical measurements, was collected and analyzed using joint models to predict the progression to hemodialysis treatment. The study reveals that the estimated glomerular filtration rate (eGFR) can be considered an endogenous factor influenced by innate biochemical markers. Serum creatinine, blood pressure, and urinary protein excretion emerged as valuable factors for predicting CKD progression. The joint model, combining longitudinal and survival analyses, demonstrated predictive versatility across various CKD severities. This innovative approach enhances conventional models by concurrently incorporating both longitudinal and survival analyses and provides a nuanced understanding of the variables influencing renal function in CKD patients. This personalized model enables a more precise assessment of renal failure risk, tailored to each patient's unique clinical profile. The findings contribute to improving the management of CKD patients and provide a foundation for personalized healthcare interventions in the context of renal diseases. [ABSTRACT FROM AUTHOR]

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3–5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan–Meier estimation method, based on patients' true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about the gender and age differences associated with the effects of economic fluctuations on hospitalization for cardiovascular diseases. This paper investigates the impact of economic fluctuations on hospitalization for ischemic heart disease (IHD), stroke, and hypertension by age and gender between January 1996 and December 2012 in Taiwan. Methods: We adopted a multiple-input time series analysis to examine the strength of the immediate and latent effects of the 17-year quarterly unemployment rates (UR), air pollution exposure (APE), gross domestic product (GDP), per capita consumption expenditure in cigarette and alcohol (ECA), and per capita healthcare expenditure (HE) on the adjusted quarterly incidence rate of hospitalization. The data used in this paper were retrieved from the National Health Insurance Research Database and the website of the Directorate-General of Budget, Accounting and Statistics (DGBAS), Executive Yuan. Results: Our findings indicate that higher UR increased IHD hospitalization in young men and women and middle-aged women but reduced stroke hospitalization in young men. Higher APE increased IHD hospitalization in young men but reduced it for young women, increased stroke hospitalization in old men and middle-aged women but reduced it for young men, and increased hypertension hospitalization in middle-aged men and young women. Higher ECA reduced IHD hospitalization in middle-aged men, increased stoke hospitalization in middle-aged and old men and middle-aged women. Higher HE reduced IHD hospitalization in old men, young and old women, reduced stroke hospitalization in old women, and reduced hypertension hospitalization in young and middle-aged women. Conclusions: Overall, we found that the economic fluctuations caused increased harmful effects in certain population subgroups but also brought some soothing effects to some groups. [ABSTRACT FROM AUTHOR]

Background: In the third quarter of 2008, a major financial crisis hit many developed countries. Taiwan suffered its own share: a rise in unemployment and a severe decline in gross domestic product. This study is to address the health consequences of this crisis on different socioeconomic populations in Taiwan.Methods: A sample of 6,225,766 men and 5,417,651 women, was obtained and their admissions data over 2007-2012 were retrieved. Stratified into three income levels, the sample was examined on the 147,921 episodes of hospitalization due to depressive illnesses (DIs) over that period by an interrupted time series analysis for monthly incidence rates of DI hospitalizations RESULTS: The adjusted incidence rates of hospitalization (AIRH) for DIs among the low income were 10 times that of the high income group. The AIRHs were generally higher in all of three female income groups than they were in the three male income groups. The low income men and women showed increases (of 18.0% and 14.2%, respectively) beginning in April 2008 that sustained for two years. The high income women exhibited a 5.0% monthly rise in the rate of DI hospitalizations.Limitations: Our time series models can control some confounding factors, but the ecological fallacy remained.Conclusions: This study provides evidence that the economic recession resulted in increased rates of DI hospitalization in Taiwan, especially among the low income population. Women of higher incomes may have suffered a more enduring impact. [ABSTRACT FROM AUTHOR]

Aims: To assess the relationships between alcohol-related mortality and socio-demography in Taiwan. Methods: Using 2002-2006 data from the national death-diagnosis registration system, we calculated the alcohol-attributed disease mortality of those aged 15 and older in 348 townships in Taiwan. This study provides spatial clustering of alcohol-attributed disease mortality rates and area socio-demographic conditions across townships, examining the relationship between the two using a spatial autoregressive model. Results: The relative risk of death due to alcohol-attributed diseases was estimated to increase by 2.1 and 0.9% as a result of a 1% increase in the percentage of men and aboriginal residents, respectively. The risk of death was estimated to decrease by 25% for every 1 year increase in education level. Industrialization and labor participation were also found to be predictors of the outcome measure in areas with differing levels of urbanization. Conclusions: This study provides significant evidence that township-level relationships between alcohol-related mortality and socioeconomic variables exist in Taiwan. Public health policymakers should better prioritize the specific areas in which comprehensive intervention should be undertaken accordingly. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients has significantly prolonged. An increasing number of HIV-infected patients are aging and concurrent use of medications are not uncommon for management of metabolic complications and cardiovascular diseases related to aging and prolonged exposure to cART. Methods: We reviewed medical records of all HIV-infected patients aged 40 years or older who had been followed at a university hospital for HIV care in Taiwan between January and December 2013. A standardized case record form was used to collect information on demographics and clinical characteristics, comorbidity, cART, and concurrent medications. Results: During the study period, 610 patients aged 40 to 49 years (mean, 44.1) and 310 aged 50 years or older (mean, 58.8) sought HIV care at this hospital. Compared with patients aged 40 to 49 years, those aged 50 years or older were significantly more likely to be female (15.9% vs 3.8%); to have received cART (97.7% vs 94.8%) and a lower plasma HIV RNA load (1.6 vs 1.7 log10 copies/ml); and to have diabetes mellitus (18.4% vs 4.6%), hypertension (31.0% vs 10.8%), hyperlipidemia (29.4% vs 11.6%), coronary artery disease (6.8% vs 0.5%), and an estimated glomerular filtration rate <60 ml/min/1.73 m2 (11.5% vs 2.7%); and were significantly less likely to have syphilis. Other than HIV infection, patients aged 50 years or older were more likely to have been receiving two or more concurrent medications than those aged 40 to 49 years (22.9% vs 6.4%). Conclusions: Our findings show a significant proportion of the HIV-infected patients aged 50 years or older have multiple comorbidities that may increase the risk for cardiovascular and renal complications. Issues of poly-pharmacy among the HIV-infected patients who are aging should be addressed to ensure adherence and minimize drug-drug interactions. [ABSTRACT FROM AUTHOR]

Background The effects of alcohol taxes and prices on drinking and mortality are well established, but the effects of alcohol taxes on measures of alcohol-related morbidity from noninjury health outcomes have not been fully elucidated. We assess the 2 opposing effects of alcohol tax policy interventions (tax rate increase in 2002 and decrease in 2009) on alcohol-attributed diseases ( AADs) in Taiwan. Methods Admissions data from 1996 to 2010 were retrieved from the National Health Insurance Research Database ( NHIRD) claims file and analyzed in this study. Data on 430,388 men and 34,874 women aged 15 or above who had an admission due to an AAD were collected. An interrupted time series analysis examining the effects of the implementation of alcohol tax policy on quarterly age- and sex-specific incidence rates of hospitalization for AADs was employed. The same method was also used to analyze hospitalizations for alcoholic liver disease. Results The teen/adult groups all showed significant ( p < 0.05) changes in the adjusted incidence rate of hospitalization ( AIRH) for AADs and alcoholic liver disease in 2002. Men aged 15 to 64 years showed an abrupt decline in the rate of AADs (9.1%) and in the rate of alcoholic liver disease (10.3%). A 16% reduction in the AAD rate was found in teen/adult women after the alcohol tax increase. In contrast, a 17.4% increase in the same rate was seen in the first quarter of 2010 for this group. A similar pattern was presented for the AIRH for alcoholic liver disease among women. The effect of tax intervention was not significant among the elderly. Conclusions This study provides evidence that alcohol taxation in response to international trade liberalization has resulted in an immediate reduction of AADs in Taiwan. The policy of increasing alcohol tax rates may have favorable influences on the time trend for the rate of AADs, most notably among young and middle-aged men and women. [ABSTRACT FROM AUTHOR]

Objectives To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated. Methods Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case–control study was conducted to assess the impact of TDR on treatment outcomes. Results The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003–06 to 5.1% in 2007–10. In the matched case–control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS >2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P < 0.001). In patients receiving regimens with GSS ≤2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06–1.12, P = 0.07). Conclusions In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤2.5 was associated with poorer treatment responses than regimens with GSS >2.5. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to examine the association between psychoactive drug use and motor vehicle crash (MVC) injuries requiring hospitalization in southern Taiwan. A case-control study was conducted in southern Taiwan from January 2009 to December 2009. The cases included car or van drivers who were involved in MVCs and required hospitalization. Demographic and trauma-related data were collected from questionnaires and hospital and ambulance records. Urine and/or blood samples were collected on admission. The controls consisted of drivers who were randomly recruited while driving on public roads. Study subjects were interviewed and asked to provide urine samples. All blood and urine samples were tested for alcohol and a number of other legal and illegal drugs. Only those subjects who provided urine and/or blood specimens were included in the study. During the study period, 254 case patients and 254 control drivers were enrolled. The analysis showed an odds ratio (OR) of 3.41 (95% confidence intervals (95% CI), 1.76-6.70; p < 0.001) for persons taking benzodiazepines, and an OR of 3.50 (95% CI, 1.81-6.85; p < 0.001) for those taking alcohol (blood alcohol concentrations (BAC) ≥ 0.8 g/l) with regard to hospitalizations due to MVCs. For persons taking combinations of benzodiazepines and alcohol, the OR increased to 5.12 (95% CI: 1.77-15.91, p < 0.001). This study concluded that drug use among motor vehicle drivers increases the risk of MVCs that require hospitalization. From a public health perspective, the high risk ratios are concerning, and preventive measures are warranted. [ABSTRACT FROM AUTHOR]

It is known that taxation on alcohol products may effectively reduce the alcohol consumption. However, whether alcohol taxation may lead to a decrease in alcohol attributed disease mortality (ADM) has been inclusively. We conducted this time-series analysis to assess the effect of alcohol tax policy intervention in 2002 on rate of ADM in Taiwan. Mortality data were retrieved from Taiwan's Death Registry. We employed the autoregression integrated moving average technique to examine secular patterns of quarterly rate of ADM in residents aged 15 or above between 1991 and 2007, and to determine whether alcohol tax policy intervention, imposed in January 2002, had affected the time trend in rate of ADM in subsequent years. We observed a statistically significant reduction in the rate of ADM following the implementation of alcohol tax policy for all sex- and age-specific segments of population. Further analyses revealed that the effect was most obvious in men aged 15-64 years, who showed an abrupt decline in AMD rate (10.9%) in the first quarter of 2002. For elderly men and women, the tax intervention was followed by a gradually declining trend of ADM, with a magnitude ranging from 0.53% per season (elderly women) to 0.63% per season (elderly men). This study demonstrated that alcohol taxation policy may pose favorite influences on the time trend of ADM rate in Taiwan, and such influence was most noteworthy in young and middle aged men. [ABSTRACT FROM AUTHOR]

Background/purpose: Despite provision of free-of-charge human immunodeficiency virus (HIV) care and antiretroviral therapy in Taiwan, a substantial proportion of patients experience late HIV diagnosis. We investigated the risk factors for late HIV diagnosis in Taiwan.Methods: Structured interviews were conducted among newly diagnosed HIV-infected patients to collect data on demographics, socio-behavioral variables and clinical profiles within 1 year preceding HIV diagnosis from August 2006 to July 2008. Multivariate analysis was performed to identify factors associated with missed opportunities for HIV testing and late HIV diagnosis (< 200 CD4 cells/μL).Results: Among 227 newly diagnosed HIV-infected patients, 107 (47%) had late HIV diagnosis. Patients who had first positive tests for HIV at voluntary testing sites [odds ratio (OR): 0.22; 95% confidence interval (CI): 0.10-0.50], regular sexual partners at HIV diagnosis (OR: 0.30; 95% CI: 0.14-0.68), and unprotected sex in the preceding 3 months (OR: 0.16; 95% CI: 0.07-0.34) were less likely to have late HIV diagnosis. Missed opportunities for HIV testing after seeking medical attention occurred in 47 patients (20.7%) and were more common in patients with late HIV diagnosis than in those who received an earlier diagnosis (23.0% vs. 15.8%, p = 0.03). Patients with late HIV diagnosis were more likely than their counterparts to have received a diagnosis of seborrheic dermatitis (7.4% vs. 0.8%, p = 0.02) and community-acquired pneumonia (5% vs. 0%, p = 0.02), for which HIV testing was not offered by the health care providers.Conclusion: Late HIV diagnosis is not uncommon in Taiwan. Regular risk assessment and provision of routine HIV testing in medical encounters and increase of accessibility to voluntary HIV testing could facilitate earlier diagnosis of HIV infection. [ABSTRACT FROM AUTHOR]

Background: Parvovirus B19 is associated with erythema infectiosum in children or arthralgia and arthritis in adults. The virus is relatively conserved and nucleotide identity is expected in viruses that are epidemiologically related. Here, we describe the first cluster of parvovirus infection among hospital staff documented in Taiwan.Methods: Active surveillance was conducted in coronary care units (CCUs) at a 2200-bed teaching hospital for 1 month in 2007. A case defined clinically as occurring in a patient or staff in CCUs with new onset of fever or rash. Serum was tested for parvovirus B19 IgM and IgG by immunoblotting and DNA by nested polymerase chain reaction. When viremia was detected, nucleotide sequences were analyzed and compared with those of two clinical isolates. The attack rate was defined as the cumulative incidence of acute infection in CCU staff and patients during the study period.Results: Among 57 staff and 15 patients, five nurses met the clinical case definition. Three had acute infection as demonstrated by viral DNA and IgM. The attack rate was 5.3% for the staff and zero for patients. Seroprevalence rate was lower in staff than in patients (26.3%vs. 53.3%). The isolates collected from three cases were highly similar to a community isolate, and they varied with each other by 2-6 nucleotides. The isolate collected from a nurse was identical to that from her friend 3 weeks apart and was concordant with mutual transmission. A sequence with 45 nucleotide variations was identified from a staff member with chronic infection who was negative for IgM and had only weak IgG anti-VP1 reaction with immunoblotting. We did not find any patient as the source of infection.Conclusion: We identified a cluster of parvovirus infection that was caused by three circulating strains which did not support the hypothesis of transmission of a single strain in CCUs. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the combined effect of temperature and air pollutant levels on daily non-accidental deaths and cardiovascular causes of mortality. In this study, associations were assessed by means of time-series analyses over the period 1995-1999 for Kaohsiung, Taiwan's largest industrial city, which has a subtropical climate. Ambient exposures to various air pollutants, including carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), nitrogen dioxide (NO2), and particulate matter (PM10), were estimated from the arithmetic means of all daily measurements taken by an air quality monitoring station nearest to the residential district. Generalized additive models with non-parametric spline were used to identify associations between daily mortality and air pollutants as well as the air pollutant-temperature interaction correlation. Our findings indicate that CO is associated with increased risks of non-accidental and cardiovascular mortality. For a 0.2 ppm increase in CO, the increased relative daily risk of non-accidental death is at least 4% on the same day, when the mean temperature is above 24.8°C, while the increased relative risk of mortality due to cardiovascular diseases is 7% two days later at 19.7°C. The study also suggests a statistically significant interaction between CO concentration and daily mean temperature, with non-accidental mortality increasing with a warm outdoor temperature and the effect of CO on cardiovascular mortality being modified by a cold climate. Further reduction of CO pollution is thus deemed crucial for the benefit of public health. [ABSTRACT FROM AUTHOR]

Background/purpose: Human immunodeficiency virus (HIV)-infected patients are more susceptible to tuberculosis (TB), which might be the initial presentation of HIV infection. This study assessed the frequency and results of HIV testing among patients diagnosed with TB at a university hospital from 2000 to 2006.Methods: Surveillance data for all reported TB cases from 2000 to 2006 were reviewed to identify patients with unknown HIV serostatus who received HIV testing when TB was diagnosed. Trends in HIV testing among TB patients were examined, and factors associated with HIV infection were analyzed.Results: From 2000 to 2006, 3643 patients were diagnosed with TB, and 49 with HIV infection prior to TB diagnosis were excluded. Of the 3594 patients with unknown HIV status before TB diagnosis, 1035 (28.8%) were offered HIV testing. There was an increasing trend of providing HIV testing to TB patients that ranged from 16.1% to 43.7% (p < 0.001), and the overall prevalence of HIV infection among TB patients was 5.6% (95% CI, 4.3-7.1%) of those tested. Compared with TB patients without HIV infection, those with HIV infection were more likely to be aged < 50 years [adjusted odds ratio (aOR), 8.0; 95% CI, 4.4-14.6), male (aOR, 7.1; 95% CI, 3.0-16.9), and present with extrapulmonary TB (aOR, 2.8; 95% CI, 1.7-4.6).Conclusion: The frequency of HIV testing among TB patients remained low at the university hospital providing TB and HIV care in Taiwan from 2000 to 2006. Among those tested for HIV infection, age < 50 years, male gender and presentation of extrapulmonary TB were associated with HIV infection. [ABSTRACT FROM AUTHOR]

Background/purpose: Since the late 1980s, the Taiwanese government has provided all HIV-infected citizens with free access to antiretroviral therapy. Recently, there is controversy as to whether or not free access to expensive highly active antiretroviral therapy (HAART) should be continued for HIV-infected patients. This study aimed to evaluate the cost-effectiveness of HAART therapy.Methods: HAART-associated improvement in survival was obtained by analyzing the follow-up data of all HIV-positive patients identified during April 1984 to March 1997 (pre-HAART era) and May 1997 to April 2003 (HAART era) in Taiwan. Data on quality of life in HIV-positive patients was obtained from a cross-sectional survey of 224 patients using standard gamble method and World Health Organization Quality of Life-BREF instrument. Information regarding the cost of HAART was obtained from the National Health Insurance (NHI).Results: In 2000, the average annual NHI expenditure on HAART per HIV-positive patient receiving HAART was NT$210,018 (US$6177, at an exchange rate of 34.0 NT$/US$). In the AIDS group, the cost was NT$176,441 (US$5189) per life year gained and NT$241,700 (US$7109) per quality-adjusted life year gained. For non-AIDS patients, the corresponding costs were NT$226,156 (US$6652) and NT$332,582 (US$9782), respectively. These estimates have not yet included the additional cost savings from HAART-associated reduction in hospitalization and use of antimicrobial agents for opportunistic infections, and the additional life years gained from the reduction in HIV transmission under the universal availability of HAART.Conclusion: HAART for HIV infection is cost-effective, especially when the societal and epidemiologic factors are considered. We recommend that the policy of providing free HAART to all HIV-infected citizens be continued. [ABSTRACT FROM AUTHOR]

Architects design according to a combination of client needs and their own ideas. This work examines how architects in Taiwan frequently choose to obtain design information from the client or from their own professional field. The statistical structural equation modeling and LISREL techniques are applied to demonstrate how architects select information using memory accessibility and message diagnosis during the early stages of design. Architects were first found to seek architectural information and then to stress the special needs of the client over the standard information available to the architect. This finding helps designers consider how a client's design thinking and how an architect's normal approach to working with a client are used to integrate information into a design. [ABSTRACT FROM AUTHOR]

Describes the spectrum of opportunistic infections (OI) related to AIDS and the changes of morbidity and mortality associated with HIV infection in Taiwan over a five-year period. Diagnostic procedures for etiologic diagnosis; Prophylaxis regimens against OI; Follow-up and care of patients; Spectrum of OI and malignancies associated with HIV infection; Changes of clinical characteristics, morbidity and mortality over the study period.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3–5 kidney disease who were treated at a public veteran's hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3–5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b–5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b–5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented. [ABSTRACT FROM AUTHOR]

In studying the epidemiology of parvovirus 4 (PARV4) in Taiwan, we detected DNA in plasma of 3 mothers and their newborns with hydrops. In 1 additional case, only the mother had PARV4 DNA. Our findings demonstrate that PARV4 can be transmitted through the placenta. [ABSTRACT FROM AUTHOR]

Abstract: Background: The transmission routes of PARV4 are not completely understood. The first PARV4 serological study suggested that PARV4 is transmitted predominantly through parenteral route. Objectives: To set up an immunoblot system for studying the epidemiology of PARV4 infection in HIV-1 infected patients in Taiwan. Study design: Recombinant fusion proteins SUMOVP2 (a.a. 272–630 of PARV4 open reading frame 2) and SUMOVP3 (a.a. 604–914) were made and used as antigens in immunoblot. Plasma samples were from HIV-1 infected intravenous drug users IDU (69), homosexuals (66) and heterosexuals (68). Results: PARV4 IgG seropositive rate was 73.9%, 71.2% and 58.8%; IgM seropositive rate was 40.5%, 16.7% and 17.6% in IDUs, homosexuals and heterosexuals, respectively. Longitudinal samples were available from two homosexuals positive for IgM anti-PARV4, persistent IgM response was found over a period of 9 and 21 months, respectively. Conclusions: PARV4 is a common viral infection in HIV-1 infected homosexuals and heterosexuals in Taiwan. The detection of IgM anti-PARV4 does not always suggest recent PARV4 infection. [Copyright &y& Elsevier]

Summary: Objectives: To retrospectively determine the prevalence of anti-hepatitis A virus (HAV) antibody in HIV-positive persons with different routes of HIV exposure and to describe its characteristics in order to guide vaccination policy. Methods: The prevalence of anti-HAV antibody was compared between 1580 HIV-positive persons seeking medical attention and 2581 HIV-negative controls seeking health check-ups, who had undergone anti-HAV tests between 2004 and 2007. Comparisons were also made among groups of the HIV-positive patients who had acquired HIV via different routes of transmission. A multivariate logistic regression model was built to identify independent variables associated with anti-HAV seropositivity. Results: The overall prevalence of anti-HAV antibody was 60.9% in the HIV-positive and 48.0% in the controls (p <0.001). The overall adjusted odds ratio (AOR) for positive anti-HAV antibody was 2.604 (95% confidence interval (CI) 2.106–3.219) in HIV-positive persons compared with HIV-negative persons. In addition, HIV-positive men who have sex with men (MSM), heterosexuals, and injecting drug users (IDU) all had significantly higher AOR for positive anti-HAV antibody than HIV-negative persons. In HIV-positive persons, older age (AOR 1.284, 95% CI 1.246–1.322) and IDU (AOR 5.137, 95% CI 3.499–7.542) were independently associated with an increased prevalence of anti-HAV antibody. Nearly 90% of the IDU had become seropositive for HAV after age 36–40 years, compared with heterosexuals and MSM after age 46–50 years, and controls after age 51–55 years. Conclusion: Our findings suggest that age groups to be targeted for HAV vaccination vary with the different routes of HIV exposure. [Copyright &y& Elsevier]

BACKGROUND Hepatic hydatid cyst disease, caused by the parasite Echinococcus granulosus, is endemic in certain rural areas of the world, but not in most of East Asia outside Mainland China. In Taiwan, only one autochthonous case has been reported over the past 40 years. We present the case of an urban 91-year-old female patient without international travel history for more than 40 years. CASE REPORT The 91-year-old woman who used a wheelchair came to the Emergency Department reporting melena for 2 days and 1 episode of coffee-grounds vomitus. Epigastric tenderness was present. An incidental finding of elevated liver enzymes along with the clinical picture prompted further survey. Computed tomography revealed a 14×10×12 cm homogeneous cystic lesion in the right hepatic lobe with a partially calcified wall. On sonograms, a similar lesion was found, and the pathognomic "water-lily" sign was visualized along with the isoechoic-to-hypoechoic internal septa, fulfilling the diagnosis despite the patient's refusal to undergo magnetic resonance imaging studies and invasive definite diagnostic procedures. Although anthelmintic chemotherapy and invasive therapeutic measures were also refused, her symptoms improved and was not recurrent under supportive measures. However, the cyst was still present 12 months after discharge. CONCLUSIONS The case highlights that in areas with few cases of hepatic hydatid disease, the accurate diagnosis could be missed in patients without a significant epidemiological history. However, once imaging findings, especially those that are pathognomic, are appropriately interpreted on at least 2 imaging modalities, such cases could be diagnosed without further definitive studies.

Background/purpose: Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations., Methods: We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group., Results: Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05-1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99-7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86-5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05-0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09-0.80)., Conclusions: While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO., (Copyright © 2019. Published by Elsevier B.V.)

Background: Cardiovascular disease (CVD) is an emerging cause of morbidity and mortality among HIV-positive patients receiving successful combination antiretroviral therapy, but their CVD risk has been rarely investigated in Asia-Pacific region. We aimed to assess the CVD risk of HIV-positive Taiwanese outpatients., Methods: We did cross-sectional questionnaire interviews to collect information of HIV-positive Taiwanese patients aged 40-79 at the HIV clinics of a medical center from 1 March to 31 August, 2017. The Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) risk score and Data-Collection on Adverse effects of Anti-HIV Drugs (D:A:D) risk score were used to estimate their CVD risk., Results: Of the screened 1251 patients, 1006 (80.4%) with complete data to assess their CVD risk were included for analyses. The prevalence of patients aged 40-75 and with a high CVD risk was 30.6% by FRS, 3.7% by D:A:D (R) risk score, and 22.2% by ASCVD risk score. In multiple logistic regression, older age, current smoking, higher systolic blood pressure, and higher triglyceride and fasting glucose levels were independently associated with the ASCVD risk score ≥7.5%. If current smokers aged 55-59 had stopped smoking, the proportions of them with a 10-year CVD risk of ≥10% by FRS and ≥7.5% by ASCVD risk score would have decreased by 35.3% and 20.0%, respectively., Conclusions: Higher CVD risk estimates among HIV-positive Taiwanese aged 40-75 were associated with an older age, current smoking, higher systolic blood pressure, hypertriglyceridemia, and hyperglycemia. Smoking cessation could potentially lead to significant decreases of CVD risk., (Copyright © 2019. Published by Elsevier B.V.)

The objective of the study was to explore the dynamic effects of socioeconomic status (SES) and lifestyle behaviors on the risks of metabolic syndrome (MS) or cardiovascular disease (CVD) in life course. The data of 12,825 subjects (6616 males and 6209 females) who underwent repeated examinations and answered repeated questionnaires from 2006 to 2014 at the Major Health Screening Center in Taiwan, was collected and analyzed. The trajectory of trends in the subjects' SES and lifestyle mobility over time was observed, and the effects of factors with potential impacts on health were tested and analyzed using multiple logistic regression and a generalized estimated equation model. A 10% increase in MS prevalence was observed over the nine-year period. The average Framingham CVD score for people with MS was estimated to be about 1.4% (SD = 1.5%). Except for middle-aged women, marriage was found to raise the risk of CVD, whereas increasing education and work promotions independently reduced CVD risk for the majority of subjects. However, the risk of CVD was raised by half for young men who had a job or lost a job in comparison to continuously unemployed young men. Physical activity was only found to be advantageous for disease prevention in those aged less than 40 years; increased exercise levels were useless for reducing CVD risk among older men. Alcohol drinking and betel chewing caused increased CVD risk in the old and young subjects, respectively, whereas vegetarian diets and vitamin C/E intake were helpful in preventing CVD, even if those habits were ceased in later life. For middle-aged women, getting sufficient sleep reduced CVD risk. We concluded that SES and lifestyle behaviors may have different effects on health over time, among various populations. Accordingly, suggestions can be provided to healthcare workers in designing health promotion courses for people at different life stages.

Aims: To assess the relationships between alcohol-related mortality and socio-demography in Taiwan., Methods: Using 2002-2006 data from the national death-diagnosis registration system, we calculated the alcohol-attributed disease mortality of those aged 15 and older in 348 townships in Taiwan. This study provides spatial clustering of alcohol-attributed disease mortality rates and area socio-demographic conditions across townships, examining the relationship between the two using a spatial autoregressive model., Results: The relative risk of death due to alcohol-attributed diseases was estimated to increase by 2.1 and 0.9% as a result of a 1% increase in the percentage of men and aboriginal residents, respectively. The risk of death was estimated to decrease by 25% for every 1 year increase in education level. Industrialization and labor participation were also found to be predictors of the outcome measure in areas with differing levels of urbanization., Conclusions: This study provides significant evidence that township-level relationships between alcohol-related mortality and socioeconomic variables exist in Taiwan. Public health policymakers should better prioritize the specific areas in which comprehensive intervention should be undertaken accordingly., (© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Autoimmune diseases-related arthritis has been rarely reported in HIV-1-infected patients. We aimed to investigate the incidence and clinical manifestations of autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in Taiwan., Methods: We retrospectively reviewed medical records of all HIV-infected patients who had a diagnosis of autoimmune arthritis between 1993 and 2013. Demographic characteristics, clinical manifestations, serial CD4 and CD8 lymphocyte counts and plasma HIV viral loads, HLA-B27 status, and treatment response to HIV and rheumatic diseases were recorded., Results: During the 20-year study period, totally 26 HIV-infected patients with autoimmune arthritis (0.7%) were diagnosed among 3623 HIV-infected patients. There were 18 patients with ankylosing spondylitis (AS), six with rheumatoid arthritis (RA), one with psoriatic arthritis, and one with Sjögren's syndrome. HLA-B27 antigens were all detected positive of AS patients. Fifteen patients (57.7%) developed autoimmune arthritis after HAART was initiated. The median age and CD4(+) T lymphocyte counts at the diagnosis of autoimmune arthritis were 35 (20-62 years) and 406 (3-695 cells/μL), respectively. Three patients had typical presentations of Reiter's syndrome. Both AS and RA patients achieved a good virological response with undetectable plasma HIV RNA load 12 months after receiving HAART(85.71% vs. 80%, respectively, p = 0.999). The treatment response to antirheumatic medications were similar between AS patients and RA patients (77.8% vs. 50%, p = 0.3068), but seems to be better than that reported for the general population (30-40%)., Conclusion: A low prevalence of autoimmune arthritis among HIV-infected patients in the era of HAART was similar to that of the general Taiwanese population. Clinical manifestations of HIV-infected patients were similar to those described in HIV-uninfected patients. However, the treatment response to antirheumatic agents was better in HIV-infected patients in our study., (Copyright © 2013. Published by Elsevier B.V.)

Objectives: The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs)., Methods: We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators., Results: During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62)., Conclusions: Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens., (Copyright © 2014. Published by Elsevier Ltd.)

The effects of drug resistance on HIV-1 replication capacity have been studied, but data from clinical isolates are few. We accessed the patients with HIV-1 infection at the National Taiwan University Hospital who experienced virological failure. Genotypic susceptibility and replication capacity of clinical HIV-1 isolates were measured. There were 80 patients enrolled between September 2007 and August 2010. The HIV-1 replication capacity declined significantly with the increasing number of major resistance-associated mutations (RAMs) to protease inhibitors (PIs) (p<0.001); however, it did not decline significantly with the increasing RAMs to first-line nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) (p=0.098). Regarding the effects of resistance to antiretroviral drugs in salvage therapy, decreased replication capacity was noted with the increasing RAMs to darunavir/ritonavir (p<0.001) and specific RAMs (L100I, K101P, and Y181C/I/V) to etravirine (p<0.001). Although NNRTI-related RAMs have less remarkable effects, both PI- and NNRTI-related RAMs reduced replication capacity, especially RAMs to darunavir/ritonavir and etravirine, which are commonly used in salvage therapy for treatment of patients infected with highly resistant HIV. Thus, decreased viral fitness during the emergence of RAMs suggests the importance of continued optimal antiretroviral treatment even when virological failure was noted.

Objective: To assess the incidence of acute pancreatitis in human immunodeficiency virus-positive patients with triglyceride (TG) greater than 500 mg/dL after highly active antiretroviral therapy., Methods: Sequential TG levels during follow-up and episodes of acute pancreatitis were retrospectively reviewed in 347, 417, and 571 patients enrolled in periods 1 (2000-2002), 2 (2003-2005), and 3 (2006-2008), respectively. The incidence of acute pancreatitis, defined as consistent clinical symptoms and elevated amylase and/or lipase levels, was estimated., Results: A total of 5356 TG measurements were performed during the follow-up for 698.22, 884.14, and 1215.69 person-years in periods 1, 2, and 3, respectively. Overall, 9.89% of patients had at least one TG greater than 500 mg/dL. Five patients with TG less than 500 mg/dL developed acute pancreatitis. The crude incidences of acute pancreatitis were 0.6%, 0.5%, and 0.2%, and the incidence rates were 2.86, 2.26, and 0.82/1000 person-years in periods 1, 2 and 3, respectively (all, P > 0.05). The incidence rates of acute pancreatitis when TG levels were less than 500, less than 1000, and less than 1500 mg/dL ranged from 1.2 to 4.9/1000 person-years, whereas it was 0/1000 person-years when TG levels were greater than 500, greater than 1000, and greater than 1500 mg/dL, respectively., Conclusion: The risk of acute pancreatitis was low among human immunodeficiency virus-positive patients who developed hypertriglyceridemia after receiving highly active antiretroviral therapy.

Introduction: Although access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era., Methods: Medical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed., Results: During the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis., Conclusions: Respiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.

An outbreak of human immunodeficiency virus (HIV) infection occurred among injecting drug users (IDU) in Taiwan between 2003 and 2006, when an extremely high prevalence of hepatitis C virus (HCV) infection was also detected. To determine whether clusters of hepatitis D virus (HDV) infection occurred in this outbreak, 4 groups of subjects were studied: group 1, HIV-infected IDU (n = 904); group 2, HIV-infected non-IDU (n = 880); group 3, HIV-uninfected IDU (n = 211); and group 4, HIV-uninfected non-IDU (n = 1,928). The seroprevalence of hepatitis B virus (HBV) was 19.8%, 18.4%, 17.1%, and 6.7%, and HDV seroprevalence among HBV carriers was 75.4%, 9.3%, 66.7%, and 2.3%, for groups 1, 2, 3, and 4, respectively. Ninety-nine of 151 (65.6%) HDV-seropositive IDU had HDV viremia: 5 were infected with HDV genotype I, 41 with genotype II, 51 with genotype IV, and 2 with genotypes II and IV. In the phylogenetic analysis, only one cluster of 4 strains within the HDV genotype II was identified. Among patients with HCV viremia, a unique cluster within genotype 1a was observed; yet, patients within this cluster did not overlap with those observed in the HDV phylogenetic analysis. In summary, although IDU had a significantly higher HDV seroprevalence, molecular epidemiologic investigations did not support that HDV was introduced at the same time as HCV among IDU.

The present study investigated the chemical composition of Isochrysis galbana Parke, a marine microalga which is widely used as a feedstock in aquaculture. From gas chromatography/mass spectrometric analysis the mono-sugar compositions of I. galbana were 2.1% fucose, 2.5% rhamnose, 2.7% arabinose, 8.5% xylose, 15.7% mannose, 32.7% galactose and 35.8% glucose. The polysaccharides of I. galbana were able to induce prointerleukin-1beta (pro-IL-1beta) protein expression within murine macrophages. Furthermore, five kinds of chlorophyll and one sterol were separated from the ethanolic extracts, including pheophorbide-a, ethyl pheophorbide-a, 10S-10-hydroxypheophytin-a, 10R-10-hydroxypheophytin-a, (132-R)-pheophytin-a, and brassicasterol. In addition, the major soluble components of the ethanol/n-hexane extract were 9-octadecenoic acid (E) (38.4%), hexadecanoic acid (23.3%), tetradecanoic acid (15.7%), and octadecanoic acid (7.2%), but only a few polyunsaturated fatty acids were found, such as 9,12,15-octadecatrienoic acid (1.9%), 9,12-octadecadienoic acid (Z,Z) (3.4%), and docosahexaenoic acid (0.2%). This is the first occasion that polysaccharides from I. galbana have been demonstrated to exert immunomodulatory properties by the induction of IL-1 within macrophages.

Background/purpose: Non-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care., Methods: The medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates., Results: During the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome., Conclusion: The incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival., (Copyright (c) 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

Background: Risk of pneumocystosis after discontinuation of primary or secondary prophylaxis among HIV-infected patients before CD4 counts increase to >==200 cells/microL (early discontinuation) after receiving highly active antiretroviral therapy (HAART) is rarely investigated., Methods: Medical records of 660 HIV-infected patients with baseline CD4 counts <200 cells/microL who sought HIV care and received HAART at a university hospital in Taiwan between 1 April, 1997 and 30 September, 2007 were reviewed to assess the incidence rate of pneumocystosis after discontinuation of prophylaxis for pneumocystosis., Results: The incidence rate of pneumocystosis after HAART was 2.81 per 100 person-years among 521 patients who did not initiate prophylaxis or had early discontinuation of prophylaxis, which was significantly higher than the incidence rate of 0.45 per 100 person-years among 139 patients who continued prophylaxis until CD4 counts increased to >==200 cells/microL (adjusted risk ratio, 5.32; 95% confidence interval, 1.18, 23.94). Among the 215 patients who had early discontinuation of prophylaxis after achievement of undetectable plasma HIV RNA load, the incidence rate of pneumocystosis was reduced to 0.31 per 100 person-years, which was similar to that of the patients who continued prophylaxis until CD4 counts increased to >==200 cells/microL (adjusted risk ratio, 0.63; 95% confidence interval, 0.03, 14.89)., Conclusions: Compared with the risk of pneumocystosis among patients who continued prophylaxis until CD4 counts increased to >==200 cells/microL after HAART, the risk was significantly higher among patients who discontinued prophylaxis when CD4 counts remained <200 cells/microL, while the risk could be reduced among patients who achieved undetectable plasma HIV RNA load after HAART.

Background and Purpose: Kaposi's sarcoma (KS) continues to occur in patients with human immunodeficiency virus (HIV) infection in the era of highly active antiretroviral therapy (HAART), and remains the most common HIV-associated malignancy. This retrospective study was conducted to describe the change in incidence and characteristics of HIV-associated KS in Taiwan., Methods: The medical records of patients with HIV infection who received a diagnosis of KS at the National Taiwan University Hospital between June 1994 and March 2008 were reviewed., Results: During the 14-year study period, 62 HIV-infected patients were diagnosed with KS, which included 40 definite diagnoses (64.5%) by pathology and 22 probable diagnoses (35.5%) ascertained by characteristic lesions, compatible clinical manifestations, and response to treatment. Most of the patients were men who have sex with men (MSM; n = 53; 85.5%). At the time of diagnosis of KS, the median CD4 count was 20 cells/microL (range, 1-371 cells/microL). A considerable decline in the incidence of KS in HIV-infected patients since the introduction of HAART was demonstrated; in the pre-HAART era, 18 of 175 patients (10.3%; 95% confidence interval [CI], 6.53- 15.75) developed KS, compared with 44 of 1615 patients in the HAART era (2.7%; 95% CI, 2.03-3.65) [p < 0.0001]. The prognosis of HIV-infected patients with KS has improved since the introduction of HAART, as the mortality rate has declined from 77.8% in the pre-HAART era to 34.1% in the HAART era (p = 0.002)., Conclusions: The incidence of KS in HIV-infected patients and the mortality rate of these patients significantly declined in the HAART era, although KS continued to occur in patients with advanced HIV infection.

Background: The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population., Methods: Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis., Results: In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype-transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed., Conclusions: The result supports that the NRG3 gene is a susceptibility gene for schizophrenia.

Background and Purpose: Clinical manifestations and outcome of toxoplasmic encephalitis (TE) in patients at late stage of human immunodeficiency virus (HIV) infection have not been previously reported in Taiwan. The aim of this study was to describe the clinical and radioimaging characteristics and treatment response in HIV-infected patients with TE in Taiwan., Methods: Medical records of all HIV-infected patients who were diagnosed as having TE between June 1994 and December 2006 at the National Taiwan University Hospital, Taipei, Taiwan, were reviewed by use of a standardized case record form. Diagnosis of TE was based on clinical manifestations, serology, and radioimaging findings plus clinical and radiographic response to anti-toxoplasmosis therapy., Results: During the 12-year study period, 18 patients (1.2%) with 19 episodes of TE were identified. The median CD4+ lymphocyte count was 15 cells/microL and plasma HIV RNA load was 179,000 copies/mL at the diagnosis of TE. TE was the initial presentation of HIV infection in around two-thirds of the patients. Fever, focal neurological deficit, cognitive dysfunction, and altered mental status were the most common presenting symptoms. The typical radioimaging findings, multiple enhanced lesions with mass effect, were most common in the cerebral cortex, followed by the basal ganglia, cerebellum and brain stem. Compared with those who survived TE, the 3 patients who died of TE were older (52 vs 37 years, p=0.016) and had a higher incidence of cognitive impairment (100.0% vs 37.5%, p=0.063) and altered mental status (100.0% vs 18.8%, p=0.025)., Conclusions: TE was a rare HIV-related infectious complication in our cohort. Advanced age and altered mental status were associated with an increased mortality in HIV-infected patients with TE.

Background and Purpose: The seroprevalence of viral hepatitis and spectrum of infectious complications among human immunodeficiency virus (HIV)-infected injection drug users (IDUs) remains unclear in Taiwan, although there has been a significant increase in the prevalence of HIV infection among IDUs in the last 2 to 3 years., Methods: The medical records of HIV-infected IDUs who sought medical care at a referral hospital for HIV care from June 1994 to December 2006 were retrospectively reviewed. A standardized case record form was used to collect demographic, clinical, laboratory and microbiologic data., Results: During the 12-year study period, a total of 102 HIV-infected IDUs with a median age of 39.5 years (range, 19 to 73 years) sought HIV care at the referral hospital. The male-to-female case ratio was 6 and males were significantly older than females (39.5 vs 28 years, p<0.001). The overall median CD4+ cell count and plasma HIV RNA load by reverse transcriptase-polymerase chain reaction at enrollment were 374 cells/microL and 4.45 log(10) copies/mL, respectively. The CD4+ cell count of HIV-infected IDUs enrolled after year 2003 was significantly higher than those enrolled before 2003 (438 vs 23 cells/microL, p<0.001). The seroprevalence of hepatitis C virus (86.6% overall) increased over time, while that of hepatitis B virus decreased in the patients born after 1984, when nationwide hepatitis B vaccination was started in Taiwan. Gram-positive bacteria were causative for 69.7% of the 33 bacteremic episodes, and Staphylococcus aureus was the leading pathogen (16 episodes), with methicillin-sensitive S. aureus accounting for 11 bacteremic episodes (33.3%). The most common bacterial infection was infective endocarditis. Tuberculosis occurred more frequently in men, and extrapulmonary tuberculosis was more common than pulmonary tuberculosis and was associated with a lower CD4+ count., Conclusions: Bacteremia, infective endocarditis and tuberculosis were the three most common patterns of infection among HIV-infected IDUs who sought medical care at a referral hospital; and methicillin-sensitive S. aureus was the most common etiology of bacteremia. The high seroprevalence of hepatitis B and C and subsequent hepatic complications may present a future challenge to the health care system.

Purpose: To determine the characteristics of cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU) in the era of highly active antiretroviral therapy (HAART)., Methods: We reviewed data from 47 of 79 consecutive patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis., Results: The incidence of CMV retinitis in AIDS patients has markedly decreased over the recent 10 years. The characteristics of CMV retinitis have changed. Development of IRU occurred in 24.4%., Conclusions: Symptomatic IRU develops in a significant number of patients with inactive CMV retinitis following successful HAART. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

Purpose: Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated., Results: Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/muL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis., Conclusion: While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.

Objectives: To determine the prevalence and trends of antiretroviral drug resistance among HIV-1-infected Taiwanese patients who have been provided with free-of-charge antiretroviral therapy (ART) since 1990., Methods: Blood samples collected from 786 HIV-1-infected patients from 1999 to 2006 were subjected to genotypic resistance assay. Antiretroviral resistance mutations were identified in accordance with the antiretroviral resistance mutation list of the International AIDS Society-USA Consensus Guidelines. Trends of resistance were studied in patients enrolled in two periods: before (period 1, January 1999 to December 2003) and after (period 2, January 2004 to December 2006) the CRF07&#95;BC outbreak among injection drug users (IDUs)., Results: The frequency of HIV-1 isolates harbouring one or more primary mutations associated with antiretroviral resistance to reverse transcriptase inhibitors or protease inhibitors increased significantly from 6.6% in period 1 to 12.7% in period 2 (P = 0.003). A significant increase in prevalence of antiretroviral drug resistance was observed among men who have sex with men and patients infected with HIV subtype B. In multivariate analysis, hepatitis C virus (HCV) exposure, which exhibited collinearity with injection drug use and infection with CRF07&#95;BC, represented a lower risk for infection with resistant viruses., Conclusions: Our findings suggest that the prevalence of antiretroviral resistance has increased in Taiwan over the past 8 years after the introduction of combination ART. IDUs who were HCV-seropositive and infected with CRF07&#95;BC were at lower risk for infection with antiretroviral-resistant viruses.

Osteonecrosis, a disabling complication associated with antiretroviral therapy (ART) and human immunodeficiency virus (HIV) infection, has rarely been reported in an Asian population. After an observation of 3,250 person-years (PY), 11 of 967 (1.1%) HIV-infected patients at a median age of 34 years developed osteonecrosis involving the hip joints (incidence, 3.4 per 1,000 PY). Their median CD4+ lymphocyte count had increased from 35 cells/microL at the diagnosis of HIV infection to 297 cells/microL at the diagnosis of osteonecrosis. The crude rate of osteonecrosis increased from 0% in patients without exposure to ART to 2.6 and 1.7% in patients with exposure to nucleoside reverse transcriptase inhibitors (NRTIs) and who had undergone highly active antiretroviral therapy (HAART) for 5 years or longer, respectively (P=0.18 and 0.09, respectively). Among the patients receiving HAART, the estimated incidence of osteonecrosis was 4.2 per 1,000 PY. Patients with osteonecrosis had a longer duration of exposure to NRTIs (1,641 versus 1,264 days, P=0.26) and to HAART (1,603 versus 1,251 days, P=0.42), a higher serum triglyceride (median, 1,130 versus 351 mg/dL; P=0.09), and a higher proportion of lipodystrophy (81.8 versus 15.0%, P<0.0001). Our report suggests that osteonecrosis is a rare complication in HIV-infected patients with prolonged exposure to ART with resultant metabolic complications.

Background: Risk of recurrent nontyphoid Salmonella (NTS) bacteremia and trends of antimicrobial resistance of NTS remain unknown in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART)., Methods: Ninety-three patients who received a diagnosis of NTS bacteremia from June 1994 through June 2006 were prospectively followed up. Incidence of recurrent NTS bacteremia was compared between the pre-HAART era (June 1994-March 1997) and the HAART era (April 1997-June 2006). Prevalence of antimicrobial resistance was compared among the NTS isolates obtained in the pre-HAART era, the early HAART era (April 1997-June 2002), and the late HAART era (July 2002-June 2006)., Results: Compared with patients enrolled in the pre-HAART era, patients who received HAART had an incidence of recurrent NTS bacteremia that was significantly reduced by 96%; the incidence of recurrent NTS bacteremia was 2.56 cases per 100 person-years in the HAART era, compared with 70.56 cases per 100 person-years in the pre-HAART era (rate ratio, 0.036; 95% confidence interval, 0.012-0.114; P<.001). In the HAART era, the incidence of recurrent NTS bacteremia did not increase among patients receiving fluoroquinolone prophylaxis for 30 days (3.95 cases per 100 person-years), with a rate ratio of 0.43 (95% confidence interval, 0.07-2.58). Although resistance to ampicillin, cotrimoxazole, and chloramphenicol decreased, the proportion of NTS isolates resistant to fluoroquinolones increased from 0% in the pre-HAART era to 6.2% in the early HAART era and 34.2% in the late HAART era (P=.002)., Conclusions: The risk of recurrent NTS bacteremia decreased significantly in the HAART era, although NTS isolates obtained from HIV-infected patients were increasingly resistant to fluoroquinolones.

We compared changes in the relative frequencies of opportunistic illnesses (OIs) among 1,044 Taiwanese persons with HIV infection who were enrolled in three study periods from June 1994 to June 2004: before the introduction of highly active antiretroviral therapy (HAART); early HAART; and late HAART. Nearly two-thirds of those newly diagnosed with HIV infection had CD4 counts below 200/mm(3). Among a total of 1,182 OIs, candidiasis, Pneumocystis carinii pneumonia, and tuberculosis were the most common in all three study periods within 3 months after enrollment. Within 3 to 12 months after enrollment, the number of OIs declined significantly. Only 81 cases of OIs were diagnosed, the most common of which were cytomegalovirus disease, tuberculosis, candidiasis, and Mycobacterium avium complex infection. Except for the decreasing frequency of Kaposi's sarcoma, there was no significant change in the relative frequency of each individual OI within 3 months and within 3-12 months after enrollment across the three study periods. We concluded that despite the significant decrease in the number of AIDS-related OIs, the relative frequencies of common OIs did not change significantly after the introduction of HAART.

We assessed the survival of 1,044 HIV-infected persons enrolled in three periods: period 1, 1994 to 1997 (before the introduction of highly active antiretroviral therapy [HAART]); period 2, 1997 to 2000 (early-HAART); and period 3, 2000 to 2004 (late-HAART). As of 30 June 2005, 259 (24.8%) persons had died after a median observation duration of 985 days (range, 2 - 4,025 days). The mortality rate declined from 33.75 per 100 person-years in the pre-HAART era to 6.51 per 100 person-years in the late-HAART era (P < 0.0001). The adjusted hazard ratios for death in persons with a baseline CD4 count of <200 cells/mul in periods 2 and 3 were 0.605 (P = 0.007) and 0.371 (P < 0.0001), respectively, when compared with persons enrolled in period 1; the adjusted hazard ratio for death was 0.611 for persons enrolled in period 3 when compared to period 2 (P = 0.01). Our study suggested that the survival of persons in the late stage of HIV infection in Taiwan continued to improve in the late HAART era.

Background: Whether risk of invasive amebiasis due to Entamoeba histolytica is higher among human immunodeficiency virus (HIV)-infected persons than uninfected persons remains unclear, although intestinal colonization by Entamoeba dispar is common among men who have sex with men. Our objective was to determine the prevalence of invasive amebiasis and intestinal colonization by E histolytica and E dispar in HIV-infected persons and uninfected controls., Methods: We assessed the prevalence of invasive amebiasis by case review of 951 HIV-infected persons and by serologic studies of 634 of the 951 HIV-infected persons, 429 uninfected controls with gastrointestinal symptoms, and 178 uninfected healthy controls using indirect hemagglutination antibody assay. We assessed the rate of intestinal colonization by E histolytica and E dispar by fecal antigen and polymerase chain reaction tests in 332 asymptomatic HIV-infected persons and 144 of the 178 uninfected healthy controls., Results: Forty-nine (5.2%) of 951 HIV-infected persons had 51 episodes of invasive amebiasis. A high indirect hemagglutination antibody titer was detected in 39 (6.2%) of 634 HIV-infected persons compared with 10 (2.3%) of 429 uninfected controls with gastrointestinal symptoms and 0 of 178 uninfected healthy controls (P<.001). Stool specimens from 40 (12.1%) of 332 HIV-infected persons and 2 (1.4%) of 144 uninfected healthy controls were positive for E histolytica or E dispar antigen (P<.001). Ten (25.0%) of the 40 antigen-positive stool specimens from HIV-infected persons contained E histolytica., Conclusion: Persons infected with HIV in Taiwan are at increased risk for invasive amebiasis and exhibit a relatively high frequency of elevated antibody titers and intestinal colonization with E histolytica.

The purpose of the study was to evaluate the reliability and validity of the two generic instruments, the WHOQOL and the SF-36, for assessing health-related quality of life in 224 patients with HIV infection. The internal consistency ranged from 0.75 to 0.86 across the WHOQOL-BREF domains and from 0.72 to 0.93 across the SF-36 scales. The scores of all WHOQOL-BREF domains and SF-36 scales correlated positively with the measure of happiness, Sat-HRQOL and self-perceived health status, and correlated negatively with the number and intensity of symptoms. Patients with higher CD4 cell counts scored significantly higher on G4 (general health), three WHOQOL-BREF domains, seven SF-36 scales, and PCS (physical component summary). Patients with fewer symptoms and with less intensity of symptoms had significantly higher scores on all four domains of WHOQOL-BREF, eight scales, PCS, and MCS (mental component summary) of the SF-36 scale. The correlations between the physical, psychological, and social domains of the WHOQOL-BREF and PF (physical functioning), MH (mental health), and SF (social functioning) of the SF-36 were 0.51, 0.75, and 0.54, respectively. There is also good correlation between PCS of the SF-36 and the physical domain of the WHOQOL-BREF (r = 0.48), and between MCS and all four domains of the WHOQOL-BREF (r range = 0.60-0.75). The WHOQOL-BREF domains showed fewer floor or ceiling effect than the SF-36 scales. We concluded that both the WHOQOL-BREF and the SF-36 are reliable and valid health related quality-of-life instruments in patients with HIV infection.

Background and Purpose: Nosocomial bloodstream infection (NBSI) is common in patients with human immunodeficiency virus (HIV) infection. This study evaluated the incidence, causative pathogens, and outcome of NBSIs in hospitalized HIV-infected patients at a university hospital in Taiwan., Methods: The medical records of all HIV-infected patients who developed NBSIs from June 1994 to June 2003 were retrospectively reviewed. A standardized case record form was used to collect demographic, clinical, laboratory, and microbiologic data., Results: During the study period, 57 episodes of NBSIs occurred in 51 HIV-infected patients whose median age was 37 years (range, 23 to 60 years). All of the patients were at HIV infection stage C. The incidence of NBSIs was 2.3 per 1000 person-days of hospitalization (41.4 per 1000 discharges). More than three-fourths of the 57 episodes (77.2%) were classified as primary NBSIs. Other infection foci included respiratory tract (6 episodes), urinary tract (3), surgical site (2), and skin (2). Staphylococcus species were the leading pathogens (42.1%). The crude and attributable mortality rates in patients with NBSIs during the study period were 38.6% and 26.1%, respectively. Multivariate analysis using a logistic regression model revealed that shock and hypoalbuminemia at the onset of NBSIs were the 2 factors predictive of mortality., Conclusions: NBSIs in hospitalized patients in the late stage of HIV infection were associated with a high attributable mortality rate. Staphylococcus species were the leading pathogen responsible for NBSIs. Presentations of shock and hypoalbuminemia were predictive of mortality.

Two novel bacteria, with an optimum growth temperature of approximately 60 degrees C, were isolated from Lu-shan hot springs in the central region of Taiwan. These isolates were aerobic, thermophilic, halotolerant, pink-pigmented, heterotrophic and resistant to gamma-radiation. Both pleomorphic, short, rod-shaped cells and coccoid cells were observed. Strains LS-286 (= ATCC BAA-452 = BCRC 17198) and LS-293T (= ATCC BAA-406T = BCRC 17173T) represented a novel species of the genus Rubrobacter, according to a phylogenetic analysis of the 16S rRNA gene, DNA-DNA hybridization, biochemical features and fatty acid composition. The name Rubrobacter taiwanensis sp. nov. is proposed for this novel species, with LS-293T as the type strain.