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Objectives: Few studies on tumour necrosis factor (TNF) inhibitor-associated tuberculosis (TB) and hepatic events have been performed in regions where these risks are elevated. This study aimed to provide a direct comparison between adalimumab and etanercept in a high-risk population and to address the implications for physicians working with patients in such an environment.Method: Data collected from the National Health Insurance Research Database (NHIRD) in Taiwan between 2007 and 2011 were analysed retrospectively for incidences of eight adverse events associated with TNF-α inhibitors. Hazard ratios (HRs) of adalimumab vs. etanercept were calculated using a Cox proportional hazards model.Results: During this 5-year period, 86 events of TB were reported after 5317 person-years of exposure to adalimumab (1.62 events per 100 person-years), compared to 44 events after 7690 person-years of exposure to etanercept (0.57 events per 100 person-years). For serious hepatic events that led to hospitalization, 0.75 events were reported per 100 person-years of exposure to adalimumab compared to 0.39 events per 100 person-years of exposure to etanercept. Adjusted HRs for TB [aHR 3.06, 95% confidence interval (CI) 2.09-4.49, p < 0.0001], hospitalization due to a hepatic event (aHR 2.05, 95% CI 1.27-3.30, p = 0.0035), and serious infection (aHR 1.48, 95% CI 1.19-1.84, p = 0.0005) attained significance.Conclusions: TNF-α-targeting therapies with the monoclonal antibody adalimumab confers significant added risk of TB and serious hepatic events compared to therapies with the soluble fusion protein etanercept. Tailored strategies to attenuate these risks are warranted in high-risk regions such as Taiwan. [ABSTRACT FROM AUTHOR]

The Hsinchu Branch of TLRI and Dairy Association Taiwan R.O.C. implemented the national DHI program. In 2014, the DHI daity farmers were encouraged to improve cattle breeding performance and cow fertility with lower caving ease and higher rate of pregnancy. Of the 28,399 cows from DHI farms in 2018, there were 51 farms to raise 250 head of high-prolific ten-tons cows. In the summer of 2019 (June-September), the daily milk yield decreased by 2.9- 6.5% compared with the amount of daily milk in April-May (25.28 kg). In 2019, there were 158 high-prolific ten-tons cows, which were raised in 35 households. Their daily milk yield in April and May was 33.51 and 31.34 kg, respectively, and daily milk yield from June to September were 31.26, 29.93, 29.49 to 30.36 kg. It shows that summer heat stress can cause a 12% reduction in milk production. In 2019, the ratio of primiparous cows was 35.0% (5,045/14,404) and the average age of primipara was 26.2 months. [ABSTRACT FROM AUTHOR]

Objectives We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children. Methods Between January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively. Results Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm 3 ) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm 3 ), thrombocytopenia (platelet count <150 000/mm 3 ), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001). Conclusion Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes. [ABSTRACT FROM AUTHOR]

Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were Escherichia coli (31%), Staphylococcus aureus (13.6%), and Klebsiella pneumoniae (12.7%) overall. However, there was a steady increase in the proportions of E. coli and Enterococcus faecium isolated from bacteremia cases (both P < 0.001), while the proportions of Acinetobacter spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among E. coli and K. pneumoniae , while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in E. coli . Of concern is the alarming increase in vancomycin resistance among E. faecium , rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant S. aureus has remained stable at 51.2% overall. In conclusion, E. coli , with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of E. faecium in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade., Importance: AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of E. faecium causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions., Competing Interests: The authors declare no conflict of interest.

BACKGROUND: Disseminated Mycobacterium avium complex infection (DMAC) has symptoms and microscopic findings similar to those of TB in HIV patients. To inform a clinical algorithm-based differential diagnosis, we aimed to characterise the clinical features of DMAC. METHODS: This was a retrospective cohort study of 192 HIV-positive patients with culture-confirmed mycobacterial infections hospitalised during 1996-2016 at a major HIV/AIDS treatment centre in Taiwan. RESULTS: HIV patients with DMAC ( n = 58) had a three times higher 1-year mortality than those with TB ( n = 98) (48.3% vs. 16.3%, P < 0.001). DMAC and TB were not distinguishable by the WHO TB screening criteria (fever, cough, night sweats or weight loss). Nevertheless, DMAC was characterised by a lower median CD4 count (5.0 cells/µL vs. 38.5 cells/µL, P < 0.001), lower median body mass index (BMI) (17.7 kg/m² vs. 19.7 kg/m², P = 0.002) and the absence of chest radiographic findings ( P < 0.001). Simultaneous presence of CD4 <20 cells/µl, BMI <18.5 kg/m² and negative chest radiographic finding had a 98% specificity for diagnosing DMAC against TB or other types of mycobacterial infections. CONCLUSION: DMAC is an important differential diagnosis of TB in HIV patients. A simple rule based on CD4, BMI and chest radiography may inform the decision to start anti-DMAC treatment in patients with mycobacterial infection.

Objective: To investigate the association between acute myocardial infarction (AMI) and recent exposure to antipsychotic agents in people with serious mental illness (SMI), and modifying influences., Method: A case-crossover design was applied using the Taiwan National Health Insurance Research Database (NHIRD) to compare the exposure frequency of antipsychotic agents within individuals of schizophrenia or bipolar disorder between 60-day case and control periods prior to their first AMI episode during 1996-2007., Results: A sample of 834 patients with incident AMI was analysed. AMI was significantly associated with more recent antipsychotic exposure in schizophrenia after adjustment (OR 1.87, 95% confidence interval 1.15-3.03) bipolar disorder (OR 1.06, 0.51-2.21). This association in schizophrenia was significantly stronger in men and in patients without previous diagnoses of cardiovascular risk factors., Conclusion: These findings are consistent with a short-term risk effect of antipsychotic exposure on risk of AMI and identify potentially vulnerable groups. Further research is required to clarify underlying biological mechanisms., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %, comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection.

Taiwan CDC investigated four cases of recurrent imported vivax malaria during 2003-2010. Molecular genotyping results and the lack of inter-episodes travel history indicated that two of the patients, who acquired vivax malaria in Indonesia and the Solomon Islands, respectively, suffered relapses after an interval of 3-4 months, despite completing standard-dose primaquine therapy (30 mg/day for 14 days) for the first episode. Treatment with a higher dose of primaquine (60 mg/day for 14 days) prevented further relapse in both patients. This finding calls for further monitoring of the therapeutic efficacy of primaquine in treating Plasmodium vivax acquired in southeast Asia and Oceania., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Setting: A prison in northern Taiwan., Objective: To compare safety and the completion rate of the 4-month daily rifampicin regimen (4R) vs. the standard 6-month daily isoniazid regimen (6H) for latent tuberculosis infection (LTBI) in prison inmates., Design: This was an open-label randomised trial among human immunodeficiency virus negative male inmates. Inmates without active tuberculosis (TB) who tested positive for both the tuberculin skin test and QuantiFERON®-TB Gold In-Tube were eligible, but those with baseline glutamic pyruvic transaminase (GPT) levels ≥ 120 U/l, bilirubin levels ≥ 2.4 U/l or a platelet count < 150 k/mm(3) were excluded. The primary endpoint was any adverse event that resulted in discontinuation of LTBI treatment., Results: Participants (n = 373; 14% hepatitis B surface antigen positive, 21% anti-hepatitis C virus [HCV] positive) were randomised (stratified by hepatitis B virus, HCV status and 2-year prison term) to receive either 4R or 6H under directly observed treatment. The 4R group (n = 190) was less likely to experience an adverse event leading to discontinuation of treatment (2% vs. 12%, P < 0.001 for all adverse events; 0% vs. 8%, P < 0.001 for hepatotoxicity), and more likely to complete LTBI treatment (86% vs. 78%, P = 0.041), compared with the 6H group (n = 183)., Conclusions: 4R is safer and has a higher completion rate than 6H as treatment for LTBI among male prison inmates.

Background: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART)., Aim: To provide such an estimate using a semi-parametric projection., Design: Statistical analysis., Methods: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population., Results: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group., Discussion: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.

We studied the reliability and validity of the World Health Organization quality of life (WHOQOL) assessment instrument in patients with human immunodeficiency virus (HIV) infection. WHOQOL-BREF was used to assess 136 HIV-infected outpatients. The results were analyzed and compared with data from 213 healthy persons. The Cronbach's alpha for internal consistency ranged from 0.74 to 0.85 across domains in HIV-infected patients. The test-retest reliability ranged from 0.64 to 0.79 across domains at average 4-week retest interval. Factor analysis identified four major factors: social, psychological, environment, and physical, consistent with the four domains of the instrument. The scores of all four domains correlated positively with self-evaluated health status and happiness (r range: 0.52-0.60 and 0.55-0.73 across domains, respectively), and correlated negatively with the number and severity of symptoms (r range: -0.40 to -0.47 and -0.41 to -0.52, respectively). The scores of physical, psychological and social domains, but not the environment domain, discriminated between healthy persons and HIV-infected patients (all p < 0.01). We conclude that the WHOQOL-BREF can be a useful quality-of-life instrument in patients with HIV infection.

Background: Limited data are available on the clinical significance of cryptococcaemia, which occurs in 10-30% of patients with cryptococcal diseases., Aim: To describe the clinical features of cryptococcaemia and identify its prognostic factors., Study Design: Retrospective cohort study., Methods: All adult patients with Cryptococcus neoformans isolated from blood culture at the National Taiwan University Hospital, Taipei, 1981-2001, were included. Demographic and clinical information was obtained from medical records., Results: Fifty-two patients were diagnosed and treated for cryptococcaemia. Acquired immunodeficiency syndrome (24/52, 46%), immunosuppressive therapy (12/52, 23%) and decompensated liver cirrhosis (11/52, 21%) were the three major predisposing conditions. Forty-two patients (81%, n=52) had sepsis, including four patients with septic shock, when blood cultures were obtained. Of the 38 patients in whom lumbar puncture was done, cerebrospinal fluid culture showed meningeal involvement in 32 (84%). The 30-day fatality rate was 37%. Liver cirrhosis, septic shock at presentation, an initial APACHE II score >/=20, age >/=60 years and female gender were associated with mortality under univariate analysis. Starting antifungal therapy within 48 h after blood culture was associated with improved survival. Under multivariate analysis, liver cirrhosis remained a strong independent predictor of mortality at 30 days after blood culture (HR 16.3, 95%CI 2.6-101.7, p=0.003)., Discussion: Patients with cryptococcaemia have a high risk of mortality within 30 days. Sepsis and meningeal involvement are common. Those with liver cirrhosis have a particularly poor prognosis.

The prevalence of antibiotic-resistant bacteria in Taiwan is due to the heavy use of antimicrobial agents in both animal husbandry and clinical practice over the past decades. Minimum inhibitory concentrations (MICs) of linezolid were established for 371 clinical isolates of staphylococci, pneumococci, enterococci and group A streptococci from Taiwan. All isolates tested including those resistant to beta-lactams, erythromycin, vancomycin and quinupristin-dalfopristin were uniformly susceptible to linezolid, with MICs ranging from 0.125 to 2 mg/l. Our data support the observation that there is no cross-resistance between linezolid and other classes of antimicrobial substances.

Klebsiella pneumoniae has been the leading cause of pyogenic liver abscess in Taiwan during the period from 1985 to 1999, which is different from other countries. The present study investigated the in vitro antimicrobial susceptibilities of 51 K. pneumoniae isolates collected from blood cultures of patients with liver abscess in Taiwan during the period from 1993-1997, and typed by pulsed-field gel electrophoresis (PFGE). All 51 isolates were resistant to ampicillin, but susceptible to other antimicrobial agents. The minimum inhibitory concentrations (MICs) were less than 1 microg/ml for the third- and fourth-generation cephalosporins, monobactam, carbapenems, and ciprofloxacin. In comparison, 62 isolates of K. pneumoniae from community-acquired bacteremic patients without liver abscess had similar antimicrobial susceptibilities, while 142 isolates from patients with hospital-acquired bacteremia without liver abscess were much less susceptible to all of the tested antimicrobial agents. PFGE molecular epidemiologic analysis found 20 out of 51 isolates belonged to eight clusters of genetically related strains, with two or three isolates in each clusters. The other 31 isolates were genetically distinct strains. This study demonstrated that K. pneumoniae isolates which cause liver abscess in Taiwan remained susceptible to a wide range of antimicrobial agents and that they were not genetically related.

Objectives: To describe the incidence and presentations of invasive amoebiasis (IA) in patients with HIV infection in an area endemic for amoebic infection and to assess the role of the indirect haemagglutination (IHA) assay in the diagnosis of IA in HIV-infected patients., Design: Retrospective study of 18 cases of IA and HIV infection., Setting: A university hospital, the largest centre for management of HIV-associated complications in Taiwan., Methods: Medical, microbiological and histopathological records of 296 HIV-infected patients and serological data of IHA assay of 126 HIV-infected patients were reviewed to identify cases of IA from 23 June 1994 to 31 March 1999. An IHA titre > or = 1 : 128 was considered positive. Clinical characteristics of HIV-infected patients with IA and without IA were compared., Results: Eighteen of the 296 patients (6.1%) with HIV infection were diagnosed with IA: 12 patients were diagnosed with definite IA and six with probable IA. The clinical manifestations included amoebic colitis (13 patients), amoebic liver abscess (nine), both colitis and abscess (four), and pleural effusion (two). IA was the initial presentation of HIV infection in nine patients. Co-infection with other enteric pathogens was diagnosed in six patients with IA. Compared with the 161 patients without IA who were newly diagnosed with HIV infection, the nine patients with IA had a higher median CD4+ lymphocyte count (202 x 10(6)/l versus 33 x 10(6)/l; P = 0.0017), were less likely to be diagnosed with AIDS (55.6% versus 85.4%; P = 0.039), and had fewer concurrent AIDS-defining illnesses (median number 0 versus 2; P = 0.003). Estimated mean survival duration was not significantly different between the two groups (597 days versus 611 days). Fourteen out of 126 patients (11.1%) had an IHA titre > or = 1 : 128. Of the 18 patients diagnosed with IA, 13 had a titre > or = 1 : 128. The sensitivity of IHA assay in the diagnosis of IA was 72.2% (13 out of 18) and the specificity was 99.1% (107 out of 108). The positive predictive value of IHA test for IA of this patient population was 92.9% (13 out of 14) whereas the negative predictive value was 95.5% (107 out of 112)., Conclusion: IA is an increasingly important parasitic disease among patients with HIV infection in Taiwan. IHA assay has a good specificity and high negative predictive value in diagnosis of IA.

An open label, randomized comparative study was conducted to evaluate the safety and efficacy of cefepime, in comparison with ceftazidime, in the treatment of adult hospitalized Chinese patients with severe bacterial infections. Forty patients with severe infections including septicemia, urinary tract infection and bacterial pneumonia were randomly assigned to receive treatment with cefepime (2 g intravenously every 12 h) or ceftazidime (2 g intravenously every 8 h). The cefepime group (20 evaluable patients) and ceftazidime group (16 evaluable patients) were comparable with respect to age, sex, underlying diseases and distribution of infection type. In both groups urinary tract infection was the most common type of infection and Escherichia coli was the most common etiologic microorganism. The rates of satisfactory clinical response were similar in the cefepime and ceftazidime groups (95 versus 93.7%; 95% confidence interval: -0.14 - 0.17, P = 0.87). The bacteriological response rates of the cefepime and ceftazidime groups did not differ significantly (88.9 versus 85.7%; 95% confidence interval: -0.30 - 0.36, P = 0.85). Both cefepime and ceftazidime were well tolerated, with similar incidence of side effects. The results of this study suggest that cefepime is as safe and effective as ceftazidime for the treatment of serious infections in adult hospitalized Chinese patients.

Mutations of the p53 gene were investigated in 80 surgical specimens of primary gastric cancer by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations were detected in 18 tumors (22.5%) and localized to exons 5, 7 and 8. Mutations did not follow a random distribution among different subtypes, but instead clustered in the group of papillary adenocarcinomas, in which 7/12 (58.3%) cases were mutated. Positivity for p53 mutation was significantly higher in intestinal-type (37.5%) than in diffuse-type carcinomas (12.5%). These results suggest that gene alterations of p53 are not rare and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach. Twenty of 21 p53 mutations were represented by single nucleotide changes, mostly missense mutations (19 events) and one nonsense mutation. Transversional mutations constitute the majority of p53 mutations (65%) and only 20% of mutations show G:C to A:T transitions. It is possible that the etiologies of gastric cancer in different geographical areas are different.

The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.