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Objective Proteoglycans and glycosoaminoglycans play many roles in connective tissue formation, their accumulation in myxomatous tissues may influence the associated mechanical behaviour of the mitral valve, as well as the extracellular matrix of the eye. Open-angle glaucoma (OAG) and mitral valve prolapse (MVP) may share similar phathophysiology. We hypothesised that MVP increased the risk of developing glaucoma. Methods The research was a retrospective cohort study using a longitudinal health insurance database from the National Health Insurance programme. The database was a randomly sampled population of 1 073 891 followed for 13 years from 1996 to 2008. There were 21 677 subjects with MVP, and 86 708 subjects without MVP were propensity score matched and served as a comparison group. Cox proportional hazards analysis was performed and adjusted for several comorbidities to evaluate the adjusted HR for OAG in the MVP group. Results The incidence rate of OAG in patients in the non-MVP and MVP groups were 10.17 and 16.05 per 10 000 person-years, respectively. The adjusted HR for OAG in the MVP group was 1.88 (95% CI 1.58 to 2.23). A significantly elevated risk of OAG in patients with MVP was also identified in the four stratified age groups. The cumulative incidence of OAG was assessed by Kaplan–Meier analysis. The analysis revealed that the MVP group had a higher incidence of OAG than the comparison group during the follow-up period (p Conclusions This population-based study demonstrated that pre-existing MVP is a significant predictor for the development of OAG, after adjusting for possible confounding factors.

The goal of the present study was to compare the arsenic methylation capacities in elementary school and junior high school students in an area of Taiwan with low arsenic exposure, and explore the influence of both arsenic methylation capacity and obesity on insulin resistance in these children and adolescents using the HOMA-IR index. We recruited 303 elementary school students and 319 junior high school students in Taipei City from September 2007 to November 2011. Concentrations of inorganic arsenic (arsenite + arsenate), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Insulin resistance was determined by HOMA-IR. Elementary school students had significantly lower inorganic arsenic percentage and a higher DMA(V) percentage than junior high school students. It seems that the former had better arsenic methylation capability than the latter. The HOMA-IR value was significantly and positively related to the sum of the urinary inorganic and methylated arsenic (TotalAs) concentrations and also the BMI Z score, with the regression coefficients (β) being 0.058 (p 0.001) and 0.001 (p = 0.027), respectively. The higher BMI values and higher TotalAs concentration were associated with higher HOMA-IR values in children and adolescents in Taiwan.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

The rates of Cesarean delivery (C-section) have risen to >30 % in numerous countries. Increased risk of autism has been shown in neonates delivered by C-section. This study examined the incidence of autism in neonates delivered vaginally, by C-section with regional anesthesia (RA), and by C-section with general anesthesia (GA) to evaluate the risk of autism associated with C-section and obstetric anesthesia. During a mean follow-up of 4.3 years, the incidence of autism was higher in neonates delivered by C-section with GA than in neonates delivered vaginally, with an adjusted risk of 1.52 (95 % confidence interval 1.18–1.94). However, the adjusted risk of autism in neonates delivered by C-section with RA and in neonates delivered vaginally was nonsignificantly different.

Long-term memory requires activity-dependent synthesis of plasticity-related proteins (PRPs) to strengthen synaptic efficacy and consequently consolidate memory. Cytoplasmic polyadenylation element binding protein (CPEB)3 is a sequence-specific RNA-binding protein that regulates translation of several PRP RNAs in neurons. To understand whether CPEB3 plays a part in learning and memory, we generated CPEB3 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent, short-term fear memory in the contextual fear conditioning test and long-term spatial memory in the Morris water maze. The basal synaptic transmission of Schaffer collateral-CA1 neurons was normal but long-term depression evoked by paired-pulse low-frequency stimulation was modestly facilitated in the juvenile KO mice. Molecular and cellular characterizations revealed several molecules in regulating plasticity of glutamatergic synapses are translationally elevated in the CPEB3 KO neurons, including the scaffolding protein PSD95 and the NMDA receptors along with the known CPEB3 target, GluA1. Together, CPEB3 functions as a negative regulator to confine the strength of glutamatergic synapses by downregulating the expression of multiple PRPs and plays a role underlying certain forms of hippocampus-dependent memories.

We have previously described a microarray platform combining live basophils with protein arrays suitable for high-throughput detection of sensitisation against allergens. During optimisation of this technique, we observed severe losses of adhering cells during the washing steps, particularly after activation. In order to preserve cell binding, we tested the cell adhesion characteristics of different extracellular matrix proteins: human collagen I, fibronectin (FN) from bovine plasma and laminin (LN). FN was more effective than LN and collagen. Cell detachment after activation was in part due to reduced surface expression of VLA-4, the main ligand for FN, which was significantly decreased within 15 min of stimulation with 1 μg/mL calcium ionophore A23187, reaching a minimum after 2 h then slowly recovering. These optimised conditions were used for testing of well-characterised sera from allergic patients using two newly developed rat basophil leukaemia stable reporter cell lines (RBL NF-AT/GFP and RBL NF-AT/DsRed), which both express the human high-affinity IgE receptor alpha chain (FcεRIα). Both cell lines were able to detect sensitisation to specific allergens showing the expected bell-shaped dose–response curve, and correlated (R 2 = 0.75) with the standard beta-hexosaminidase assay, which is not suitable for an array format.

tudy Objective To explore the effects of metformin dose on cancer risk reduction in patients with type 2 diabetes. Design Population-based cohort study. Data Source National Health Insurance program Longitudinal Health Insurance Database. Patients A total of 65,754 age- and gender-matched patients without diabetes and no previous cancer diagnosis were extracted from the database. Measurements and Main Results We compared cancer risk among the subjects who had no diabetes, had type 2 diabetes but were not on diabetes drugs, used metformin only, used antidiabetic drugs other than metformin, or used metformin in combination with other antidiabetic drugs. Our results revealed dose-dependent effects of metformin on cancer risk and cancer onset times. A significant decrease in cancer risk was found in the monotherapy group who received more than 360 defined daily doses (DDDs) of metformin (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.24–0.66). The greatest decrease in cancer risk was observed in patients who took more than 1080 DDDs (HR 0.27, 95% CI 0.09–0.84). Significantly greater dose-dependent effects were seen in patients who used metformin in combination with other antidiabetic drugs. Conclusion The magnitude of cancer risk reduction and prolonged cancer onset times produced by metformin in patients with type 2 diabetes depended on the dose of metformin, regardless of whether metformin was used alone or combined with other antidiabetic drugs.

Even though a growing number of studies have found that patients with ankylosing spondylitis (AS) suffer from sexual problems, only very few studies have specifically addressed the relationship between AS and ED. Using a population-based data set, this case-control study aimed to examine the association of ED with a prior diagnosis of AS in Taiwan. We selected 2213 ED patients ≥40 years old and 17,704 matched controls. We considered the date of the first diagnosis of ED as the index date for cases. Multivariate logistic regression was performed to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between previously diagnosed AS and ED. A total of 224 out of the 19,917 sampled subjects (1.1%) had been diagnosed with AS before the index date. Prior AS was found in 42 (1.9%) cases and 182 (1.0%) controls. After adjusting for geographic location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, depressive disorder and alcohol abuse/alcohol-dependence syndrome, multivariate logistic regression revealed that cases were more likely to have been previously diagnosed with AS than controls (OR=1.58, 95% CI=1.09-2.19, P=0.019). There was an association between ED and AS. We suggest that physicians should be attentive to sexual complaints from AS patients in order to refer them to other specialists for multidisciplinary management.

Background: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. Methods: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. Results: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. Conclusions: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.

Background and purpose The pathogenesis of multiple sclerosis (MS) is still not fully understood, but multiple infections are known to be crucial in the development of the disease. Periodontitis caused by periodontopathic polymicrobial infections is among the most common chronic infectious disorders. This case–control study aimed to investigate the association between chronic periodontitis (CP) and MS using a population-based dataset in Taiwan. Methods This study included 316 cases who had a diagnosis of MS and 1580 randomly selected controls. We performed conditional logistic regressions to investigate the association between MS and having been previously diagnosed with CP. Results The results reveal that the prevalence of earlier CP was 25.6% and 15.4% for cases and controls, respectively (P

Background The most documented complication of scabies has been reported to be infection by group A streptococci, which has in turn been suggested to contribute to the development of glomerulonephritis. Objective This study aimed to investigate the risk of chronic kidney disease (CKD) subsequent to scabies utilizing a population-based dataset in Taiwan. Methods This retrospective matched-cohort study included 5071 subjects with scabies and 25 355 randomly selected comparison subjects. We individually tracked each subject for a 5-year period to identify those who subsequently received a diagnosis of CKD during the follow-up period. Stratified Cox proportional hazards regressions were performed to compute the hazard ratio (HR) of CKD during the 5-year follow-up period. Results The incidence rate of CKD during the 5-year follow-up period was 9.66 (8.51–10.93) per 1,000 person-years and 6.24 (5.82–6.69) per 1000 person-years for subjects with and without scabies respectively. The HR for CKD during the 5-year follow-up period for subjects with scabies was 1.34 (95% CI = 1.15–1.56) that of comparison subjects after adjusting for monthly income, hypertension, diabetes, obesity, stroke, coronary heart disease, chronic obstructive pulmonary disease, tobacco use disorder, hyperlipidemia and alcohol abuse during the 5-year follow-up period. Male subjects with scabies were 1.40 (95% CI = 1.14–1.71) times more likely than comparison subjects to suffer from subsequent CKD, and female study subjects were 1.27 (95% CI = 1.05–1.61) times more likely. Conclusions We concluded that there was an increased risk for CKD among patients suffering from scabies.

To make good profits, pricing is a competitive weapon of service firms. This paper is concerned with pricing strategies for services with substantial facility maintenance costs. To address the problem, a mathematical framework that incorporates service demand and facility deterioration is proposed. The facility and customers constitute a service system driven by Poisson arrivals and exponential service times. The most common log-linear customer demand and Weibull-distributed facility lifetime are also adopted. By examining the linkage between customer demand and facility deterioration in profit model, pricing policies of the service are investigated. Then analytical conditions of customer demand and facility lifetime are derived to achieve a unique optimal pricing policy. Finally, numerical examples are presented to illustrate the effects of parameter variations on the optimal pricing policy.

Neonatal hypoglycemia may cause severe neurological damages; therefore, tight glycemic control is crucial to identify neonate at risk. Previous blood glucose monitoring system (BGMS) failed to perform well in neonates; there are calls for the tightening of accuracy requirements. It remains a need for accurate BGMS for effective bedside diabetes management in neonatal care within a hospital population. A total of 300 neonates were recruited from local hospitals. Accuracy performance of a commercially available BGMS was evaluated against reference instrument in screening for neonatal hypoglycemia, and assessment was made based on the ISO15197:2013 and a tighter standard. At blood glucose level < 47 mg/dl, BGMS assessed met the minimal accuracy requirement of ISO 15197:2013 and tighter standard at 100% and 97.2%, respectively.

Objectives: The aim of this study was to investigate the effects of proton pump inhibitors (PPIs) on the risk of diabetes mellitus (DM) among patients with upper gastrointestinal disease (UGID). Methods: This was a retrospective cohort study with a follow-up period of 5 years. We identified 388,098 patients who were diagnosed with UGID between 2000 and 2006 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance program. We used Cox proportional hazard ratio (HR) to compare the risk of DM between UGID patients received PPIs and those did not receive PPIs. HRs were adjusted for possible confounders, including age, sex, hypertension, gout and/or hyperuricemia, coronary artery disease, stroke, pancreatitis, hyperlipidemia, obesity, H2-blocker use, and clozapine or olanzapine use. The dose-related effects of PPIs on the risk of DM were evaluated according to the defined daily dose (DDD). Results: The adjusted HR was 0.80 (95% CI, 0.73–0.88) for the study group (UGID patients with PPIs) compared with comparison group I (UGID patients without PPIs). Among patients who used PPIs, those older than 60 years of age had a lower risk of DM (HR, 0.73; 95% CI, 0.63–0.83) than those younger than 40 years. Additionally, the effect of PPIs was significantly dose-dependent (P for trend 540 DDDs of PPIs exhibited the greatest reduction in the risk of DM. Conclusions: Our results demonstrated a decreased risk of DM in UGID patients who used PPIs; the risk appeared to be significantly dose-dependent.

Our purpose was to evaluate the effects of a health education and telephone counseling program on knowledge and attitudes about colorectal cancer and screening and the psychological impact of positive screening results.A randomized controlled trial was conducted with 2 groups using a pretest and posttest measures design. Patients with positive colorectal cancer screening results were selected and randomly assigned to an experimental (n = 51) or control (n = 51) group. Subjects in the experimental group received a health education and telephone counseling program, while the control group received routine care only. Patients were assessed pretest before intervention (first visit to the outpatient) and posttest at 4 weeks after intervention (4 weeks after first visit to the outpatient).Patients in the experimental group had a significantly better level of knowledge about colorectal cancer and the psychological impact of a positive screening result than did the control group. Analysis of covariance revealed that the health education and telephone counseling program had a significant main effect on colorectal cancer knowledge.A health education and telephone counseling program can improve knowledge about colorectal cancer and about the psychological impact in patients with positive colorectal cancer screening results. The health education and telephone counseling program is an easy, simple, and convenient method of improving knowledge, improving attitudes, and alleviating psychological distress in patients with positive colorectal cancer screening results, and this program can be expanded to other types of cancer screening.

Background:This study aimed to evaluate the association of chronic rhinosinusitis with sudden sensorineural hearing loss using a population-based database.Methods:Sampled subject data were obtained from the Taiwan Longitudinal Health Insurance Database 2000. A total of 3325 patients with sudden sensorineural hearing loss were identified and 9975 controls were randomly selected. A conditional logistic regression was used to calculate the odds ratio for having been previously diagnosed with chronic rhinosinusitis, for cases and controls.Results and conclusion:The adjusted odds ratio of having prior chronic rhinosinusitis among cases compared to controls was 1.36 (95 per cent confidence interval = 1.16–1.60). The significant relationship between sudden sensorineural hearing loss and chronic rhinosinusitis was most pronounced among those patients aged 44 years or less (compared to controls) (odds ratio = 2.18; 95 per cent confidence interval = 1.63–2.92). However, the significant relationship between sudden sensorineural hearing loss and prior chronic rhinosinusitis was not sustained for patients older than 60 years compared to controls.

Aim Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is associated with a high mortality rate and increased medical care costs. Elderly patients might receive mechanical ventilation with respiratory treatment for the long term in respiratory care wards (RCW). This retrospective case–control study sought to determine the risk factors for geriatric patients who acquire a urinary tract infection with ESBL-producing Escherichia coli or Klebsiella pneumoniae in this type of hospital. Methods Two RCW participated in this study from September 2006 to March 2007. Patients suspected of having a UTI were enrolled in this study. Urine samples were collected for culture. The medical records and demographic data of patients, including days of hospitalization, comorbidities and duration of invasive instruments, were recorded. UTI was diagnosed by physicians. ESBL-producing isolates were detected using the phenotypic confirmatory tests according to the Clinical and Laboratory Standard Institute standards. Results There were 109 patients having 240 sets of clinical data and laboratory specimens. The prevalence of ESBL-producing isolates of E. coli. and K. pneumoniae were 39.5% and 69.7%, respectively. Patients with multiple underlying comorbidities (OR = 2.88, P

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC 90 s) from 2006-2007 (0.06 μg/ml) to 2008–2010 (0.12 μg/ml). The MIC 90 s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ( n = 602), ESBL-producing Klebsiella pneumoniae ( n = 736), and Acinetobacter baumannii ( n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC 90 values of tigecycline against MRSA, VRE, ESBL-producing E. coli , ESBL-producing K. pneumoniae , and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii . Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were E. coli . For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Background No previous study has investigated the incidence or risk of acute myocardial infarction (AMI) developing after the diagnosis of psoriasis in Asian populations. Objective We sought to evaluate the association between psoriasis and subsequent AMI during a 5-year follow-up period, using a nationwide Taiwanese population-based claims database, and taking clinical and demographic characteristics into consideration. Methods Our study cohort consisted of all patients with a first recorded diagnosis of psoriasis (N = 4752) between 1999 and 2001 and of patients without a diagnosis of psoriasis (N = 23,760) who were matched by age and sex (1:5) to the patients with psoriasis. Each patient was tracked using hospitalization data from 2001 until the end of 2006. Stratified Cox proportional hazard regressions (stratified by age and sex) were performed as a means of computing the 5-year AMI-free survivals after adjusting for possible confounding factors. Results Of the total sample, 70 patients (0.2%) had AMIs during the 5-year follow-up period: 22 (0.5% of the patients with psoriasis) from the study cohort and 48 (0.2%) from the comparison cohort. After adjusting for other factors, the hazard of AMI during the 5-year follow-up period was 2.10 times greater (95% confidence interval 1.27-3.43, P = .004) for patients with psoriasis than for comparison patients. Limitations We could not take into account some known risk factors for AMI, such as smoking and body mass index. Conclusions Psoriasis may confer an independent risk of AMI in Asian populations. We suggest that patients with psoriasis be made aware of the increased risk of AMI.

Choroidal neovascularization (CNV) is a key pathological feature of several leading causes of vision loss including neovascular age-related macular degeneration. Here, we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation, migration of endothelial cells, and vascular sprouting from rat aortic ring explants. In a rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10 &mu, g and 20 &mu, g of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10 &mu, g/mL and 20 &mu, g/mL of CAD27 instilled, respectively). Retinal function was unaffected, as measured using electroretinography in both groups receiving interareal injection or topical applications of CAD27 for at least fourteen days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in diseases such as neovascular age-related macular degeneration.

The purpose of this study is to investigate the alterations of kinetic characteristics in the step up/over test in patients with acute and chronic anterior cruciate ligament (ACL) deficiency. Twenty acute, twenty chronic ACL-deficient (ACLD) patients, and forty healthy controls participated in this study. The step up/over test was performed on a clinical force platform system to obtain the following variables: movement time, lift-up index and impact index. The percentages of the indexes from the stepping leg and time of step-up and swing- over were further calculated. These variables were examined statistically by using mixed repeated measure analysis of variance to reveal the differences between groups and between limbs. Smaller lift-up forces and longer swing-over time in both ACLD groups than those in the control group were found. One exception was the lift-up index in the affected side condition of the acute ACLD group, which was not significantly different from the controls. A reduced contribution to the impact index from the affected stepping leg was also found in the acute ACLD group. The acute ACLD group showed no significant change in their step-up strategy at the affected limbs, but they may have a poorer eccentric control of the affected knees on the step and thus put a larger portion of loading onto the unaffected landing leg. Our results indicated the lift-up index, swing-over time and load- distributing strategy at impact may be important parameters in monitoring functional recovery in patients with ACL deficiency. The detected alterations in these parameters could be used as a reference to design proper rehabilitation exercises for these patients. Key pointsThe lift-up index and the time of swing-over could be important parameters for indentifying functional impairments in patients with ACL deficiency.The differences between limbs were found only in the acute ACLD group with a larger lift-up index and smaller load-distribution at impact on the affected limb.The step up/over test on the clinical force platform system could be helpful in providing a reference to design proper rehabilitation exercise and to monitor the recovery of the functional ability in patients with ACL deficiency.

Rationale, aims and objectives This study aims to explore the relationship between doctor characteristics and prescribing behaviour for patients with urinary tract infections (UTIs) using a 2-year population-based data set in Taiwan. Methods This study used data from the Taiwan National Health Insurance Research Database. Our study sample consists of first-time ambulatory care visits for treatment of UTIs among female patients between 2005 and 2006 (n = 45 934). The primary outcome studied was ‘whether a broad-spectrum antibiotic was prescribed’, and the key independent variables were ‘doctor characteristics’. Doctor characteristics included gender, age ( 50), specialty, type (hospital-based vs. office-based) and practice location. Multivariate logistic regression analysis using generalized estimated equations was performed to assess the adjusted odds ratio of the doctors using broad-spectrum antibiotics. Results Among the sampled patients, 13.5% were prescribed broad-spectrum antibiotics at their first visit for treatment of UTIs. The adjusted odds of prescribing second-line antibiotics for doctors aged between 41–50 years and >50 years were 0.80 (P

This nationwide population-based study was carried out in Taiwan with the aim of comparing the risk of adverse pregnancy outcomes in women who received zolpidem treatment for insomnia during pregnancy with that in women who did not. The adverse outcomes identified and assessed were delivery of low-birth-weight (LBW) infants, preterm deliveries, delivery of small-for-gestational-age (SGA) infants, delivery of infants with congenital anomalies, and cesarean delivery. The incidences of these were compared between the groups after adjusting for other characteristics of the mothers and infants. The study used the Taiwan National Health Insurance Research Dataset (NHIRD) and birth-certificate registry. In total, the data from 2,497 mothers who received zolpidem treatment during pregnancy and those from 12,485 randomly selected mothers who did not receive the drug were included in the analysis. The results show that the adjusted odds ratios (ORs) for adverse pregnancy outcomes--LBW infants, preterm deliveries, SGA infants, and cesarean delivery--were all higher in mothers who received zolpidem treatment during pregnancy, relative to the randomly selected controls (1.39 (95% confidence interval (CI) = 1.17-1.64), 1.49 (95% CI = 1.28-1.74), 1.34 (95% CI = 1.20-1.49), and 1.74 (95% CI = 1.59-1.90), respectively). In conclusion, the risk of adverse pregnancy outcomes was higher in women who received zolpidem during pregnancy than in those who did not.

Background Epidural or spinal anesthesia involves several mechanisms hypothesized to reduce risk of surgical site infections (SSIs) during this decisive period. This study aims to compare the risk of SSI within 30 days of surgery for patients receiving total hip or knee replacement under general anesthesia versus those under epidural or spinal anesthesia. Methods We used the Longitudinal Health Insurance Database of Taiwan. A total of 3,081 patients who underwent primary total hip or knee replacement from 2002 to 2006 were included in the study. Multivariate logistic regression and propensity score analyses were carried out to explore the relationship between method of surgical anesthesia and SSI occurring within 30 days of surgery. Results Of the 3,081 sampled patients, 56 patients (1.8%) had 30-day SSIs; 33 (2.8% of all under general anesthesia) of them had general anesthesia, and 23 (1.2% of all under epidural or spinal anesthesia) had epidural or spinal anesthesia (P = 0.002). The odds of SSI for patients receiving total hip or knee replacement under general anesthesia were 2.21 (95% CI = 1.25-3.90, P = 0.007) times higher than those who had the same procedure under epidural or spinal anesthesia, after adjusting for the patient's age, sex, the year of surgery, comorbidities, surgeon's age, and hospital teaching status. Conclusions Total hip or knee replacement under general anesthesia is associated with higher risk of SSI compared with epidural or spinal anesthesia. Our results support the evolving concept of long-term consequences of anesthesia and emphasize the anesthesiologist's role in preventing SSIs.

Background and Purpose— Case reports or case series have reported the association between hyperthyroidism and cerebrovascular disease. However, hyperthyroidism has never been considered as a potential risk factor for stroke in young people. The aim of the present study is to estimate the risk for ischemic stroke among hyperthyroidism patients aged 18 to 44 years during a 5-year period after the diagnosis of hyperthyroidism as compared to a cohort of patients without hyperthyroidism during the same period. Methods— A total of 3176 patients with hyperthyroidism were included as the study cohort and 25 408 patients without hyperthyroidism were included as comparison cohort. Each patient was individually tracked for 5 years from their index ambulatory visit to identify those in whom ischemic stroke developed. Cox proportional hazard regressions were performed to compute the 5-year stroke-free survival rate between these 2 cohorts. Results— Of the total sample of 28 584 patients, 198 patients (0.7%) had ischemic strokes during the 5-year follow-up period (31 [1.0% of the hyperthyroidism patients] from the study cohort and 167 [0.6% of comparison patients] from the comparison cohort). After adjusting for the patient’s age, gender, income, level of urbanization, hypertension, diabetes, atrial fibrillation, hyperlipidemia, coronary heart disease, and whether they were using antiarrhythmics, the hazard of having ischemic stroke during the 5-year follow-up period was 1.44-times greater (95% CI, 1.02–2.12; P =0.038) for patients with hyperthyroidism than for patients in the comparison cohort. Conclusions— We conclude that hyperthyroidism is associated with an increased risk for ischemic stroke among young adults.

Despite the recent attention to patient safety and quality of care, no prior studies have addressed outcomes of hospitalization for pneumonia among patients with schizophrenia. This study investigated the extent to which clinical outcomes of pneumonia were different among patients with schizophrenia. This study used data from the Taiwan National Health Insurance Research Database. Of the total of 81 599 patients admitted with a principal diagnosis of pneumonia from 2002 to 2004, 949 had previously been admitted with a principal or secondary diagnosis of schizophrenia within the 2 years of their index pneumonia admission. We randomly selected 2847 pneumonia patients matched with the study group in terms of gender, age, year of admission, length of stay, and Charlson Comorbidity Index score as the comparison cohort. Conditional logistic regression models were used for analysis. Findings indicated a higher prevalence of adverse outcomes among patients with schizophrenia. Patients with schizophrenia were independently associated with a 1.81 times greater risk of intensive care unit admission (95% confidence interval [CI] = 1.37–2.40), a 1.37 times greater risk of acute respiratory failure (95% CI = 1.08–1.88), and a 1.34-fold greater risk of mechanical ventilation (95% CI = 1.04–1.92) after adjusting for characteristics of patients, physicians, hospitals, and potential clustering effects. Adjusted odds ratios were further evident among those treated in private hospitals and in regional/district hospitals. Significant barriers to prompt and appropriate medical care for pneumonia persist for patients with schizophrenia. Careful monitoring of physical health and proper integration between psychiatrists and physicians should be stressed to reduce poor clinical outcomes in this vulnerable population.

The purpose of the study was to investigate the risk of colorectal cancer among patients with biliary tract inflammation (BTI) compared to non-BTI patients during a 5-year follow-up period. The study group comprised 1,613 patients with BTI, among which 32 cases (1.98%) developed colorectal cancer. The comparison group included 8,065 randomly selected subjects (5 for every patient with BTI), 74 of whom contracted colorectal cancer (0.92%). Stratified Cox proportional hazard regressions were calculated to estimate the adjusted hazard of colorectal cancer between the study group and comparison group. The adjusted hazard ratio for colorectal cancer for patients with BTI was 6.54 times (95% CI = 3.07-13.92) as high as for those without BTI within a 1-year follow-up period, 3.20 times (95% CI = 1.93-5.30) as high within a 3-year follow-up period, and 2.21 times (95% CI = 1.45-3.37) as high within a 5-year follow-up period. We also found that the adjusted hazard ratio for colorectal cancer for those with bile duct inflammation was 3.30 times (95% CI = 1.87-5.84) as high as for those without BTI within the 5-year follow-up period. However, no increased hazard of colorectal cancer was observed for patients with gallbladder inflammation. We concluded that patients with BTI had a significantly higher risk of colorectal cancer compared to patients without BTI.

Background: Data regarding the wide spectrum of comorbidity amongst patients with multiple sclerosis (MS) are still scanty, especially in Asian populations. Our goal was to analyze comorbidity prevalences and risks amongst Chinese patients with MS, compared to matched controls. Methods: In total, 898 patients with MS and 4490 randomly matched individuals without MS were extracted from the National Health Insurance Research Dataset in Taiwan. We selected 30 comorbid medical conditions for analysis. Conditional logistic regression analyses were used to examine the risks of comorbidity between the two groups. Results: The regression analyses showed that patients with MS were more likely to have systemic lupus erythematosus (OR = 26.9, 95% CI = 10.3–70.3), depression (OR = 6.9, 95% CI = 5.3–8.9), peripheral vascular disorders (OR = 6.6, 95% CI = 4.0–11.0), deficiency anemias (OR = 4.9, 95% CI = 2.8–8.7), rheumatoid arthritis (OR = 4.8, 95% CI = 2.9–8.1) and fluid and electrolyte disorders (OR = 4.8, 95% CI = 2.8–8.3) than the matched controls. Conclusions: Patients with MS had higher risk of multiple medical comorbidities compared to a matched control group in an ethnic Chinese population.

The aim of the study was to examine seasonal variability in monthly admissions for community-acquired pneumonia (CAP) in Taiwan. Our study sample comprised 477,541 pneumonia patients in Taiwan between 1998 and 2005, inclusive. Results showed a fairly consistent seasonal pattern of pneumonia admissions, regardless of sex and age, and for the groups combined. Seasonal trends showed a peak in hospitalizations from January through April, followed by a sharp decrease in May and a trough from August through October. The auto-regressive integrated moving average (ARIMA) test found significant seasonality for all age and sex groups and for the whole sample (all p0.001). After adjusting for seasonality, month, and trends, the ARIMA regression models revealed that the monthly pneumonia admissions rate was significantly associated with ambient temperature, for the total sample, for female groups, and for the 65-74 andor =75 age groups (all p0.01). A 1 degrees C decrease in ambient temperature was associated with roughly a 0.03 increase in monthly pneumonia admissions rate (per 10,000 people) for the entire sample. We conclude the monthly pneumonia admissions rate was significantly associated with seasonality, and was higher in periods with low ambient temperatures.

In higher eukaryotes, the pre-replication complex (pre-RC) component Cdt1 is the major regulator in licensing control for DNA replication. The Cul4-DDB1-based ubiquitin ligase mediates Cdt1 ubiquitylation for subsequent proteolysis. During the initiation of chorion gene amplification, Double-parked (Dup), the Drosophila ortholog of Cdt1, is restricted to chorion gene foci. We found that Dup accumulated in nuclei in Cul4 mutant follicle cells, and the accumulation was less prominent in DDB1 mutant cells. Loss of Cul4 or DDB1 activity in follicle cells also compromised chorion gene amplification and induced ectopic genomic DNA replication. The focal localization of Orc2, a subunit of the origin recognition complex, is frequently absent in Cul4 mutant follicle cells. Therefore, Cul4 and DDB1 have differential functions during chorion gene amplification.

Objective.The purpose of this study was to investigate whether physicians with larger sepsis caseloads provide better outcomes, defined as lower in-hospital mortality rates, for patients with sepsis.Design.Retrospective cross-sectional study.Method.This study used pooled data from the 2002-2004 Taiwan National Health Insurance Research Database. A total of 48,336 patients hospitalized with a principal diagnosis of septicemia were selected and assigned to 1 of 4 caseload groups on the basis of their treating physician's sepsis caseload during the 3 years reflected in the pooled data (low caseload, less than 39 cases; medium caseload, 39–88 cases; high caseload, 89–176 cases; and very high caseload, more than 176 cases). Generalized estimating equation models were used for analysis.Results.Receipt of treatment from physicians in the very high, high, and medium caseload groups decreased patients' odds of inhospital mortality by 49% (95% confidence interval [CI], 0.41-0.67; P < .001 ), 40% (95% CI, 0.53-0.68; P < .001 ), and 18% (95% CI, 0.73-0.92; P < .001), respectively, compared with the odds for patients treated by low-caseload physicians. These findings persisted after partitioning out systematic physician-specific and hospital-specific variation and isolating the effects of most hospital, physician, and patient confounders.Conclusion.Patients treated by physicians who had a larger sepsis caseload had a substantially lower in-hospital mortality rate than did patients treated by physicians in the other caseload groups, and the difference was statistically significant. This result supports the “practice makes perfect” hypothesis.

A total of 393 isolates of A. baumannii were collected from patients treated at 19 teaching hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibitory zone diameters for tigecycline were determined by the broth microdilution method and the disk diffusion method, respectively. The MIC results were interpreted using the US FDA tigecycline susceptibility breakpoints for Enterobacteriaceae (susceptible [S]or=2 microg/mL; intermediate [I] 4 microg/mL; resistant [R]or=8 microg/mL). The disk diffusion results were interpreted by criteria recommended by Jones et al. (Sor=16 mm; I 13-15 mm; Ror=12 mm) and also by those recommended by the US FDA for Enterobacteriaceae (Sor=19 mm; I 15-18 mm; Ror=14 mm). The percentages of susceptible, intermediate and resistant isolates determined by the broth microdilution method were 80.9%, 12.2%, and 6.9%, respectively. The rates of susceptible, intermediate and resistant isolates by the disk diffusion method using the criteria of Jones et al. were 88.3%, 9.9% and 1.8% and using the US FDA criteria were 44.0%, 51.7% and 4.3%. Using the criteria recommended by Jones et al., the total error rate of the disk diffusion method in comparison with the broth microdilution method was 14.2% (56/393). For routine susceptibility testing of tigecycline against A. baumannii the broth microdilution method, not the disk diffusion method, should be used due to the poor correlation of results between these two methods interpreted either by the Jones et al. or US FDA criteria.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria in Taiwan. This study, part of TIST-2006 study, aimed to compare the in-vitro activity of tigecycline against clinical isolates of Gram-positive bacteria. A total of 805 isolates of Gram-positive bacteria were collected from patients treated at 20 teaching hospitals. Minimum inhibitory concentrations (MICs) of tigecycline for these isolates were determined by the broth microdilution method according to the guidelines of the Clinical and Laboratory Standards Institute, and by the Etest as per the manufacturer's instructions. Susceptibility results were interpreted by the MIC criteria recommended by the US FDA. Agreement between the two methods was low: 80.7% for methicillin-resistant Staphylococcus aureus (MRSA), 27.2% for Streptococcus pneumoniae, 22.8% for other Streptococcus spp., and 30.8% for vancomycin-resistant E. faecium (VRE). There were no very major or major errors noted. Tigecycline exhibited excellent in-vitro activity against Gram-positive cocci, including MRSA, VRE, S. pneumoniae and other Streptococcus spp. isolates in Taiwan. Correlation between MIC values determined using the broth microdilution and Etest methods for these organisms was poor.

We employed 1,1-diphenyl-2-picrylhydrazyl hydrate (DPPH)- and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-electron spin resonance (ESR) to study the effects of suppression of reactive oxygen species (ROS) by eight selected coumarin derivatives under oxidative conditions. Esculetin was the most potent radical scavenger among the eight tested compounds. Our results suggest that the number of hydroxyl groups on the ring structure of coumarins is correlated with the effects of ROS suppression. We also investigated the effect of the derivatives on the inhibition of xanthine oxidase (XO) activity, and the structure-activity relationships (SARs) of these derivatives against XO activity were further examined using computer-aided molecular modeling. All determined derivatives competitively inhibited XO. The results of the structure-based molecular modeling exhibited interactions between coumarins and the molybdopterin region of XO. The carbonyl pointed toward the Arg880, and the ester O atom formed hydrogen bonds with Thr1010. Esculetin, which bears two hydroxyl moieties on its benzene rings, had the highest affinity toward the binding site of XO, and this was mainly due to the interaction of 6-hydroxyl with the E802 residue of XO. The hypoxanthine/XO reaction in the DMPO-ESR technique was used to assess the combined effect on enzyme inhibition and ROS suppression by these coumarins, and the results showed that esculetin was the most potent agent among the tested compounds. We further evaluated the effects of the test compounds on living cells, and esculetin was still the most potent agent at protecting cells against ROS-mediated Abeta-damage among the tested coumarins.

A sustained increase in the cytosolic Ca2+concentration ([Ca2+]i) can cause cell death. In this study, we found that, in cultured porcine aortic smooth muscle cells, endoplasmic reticulum (ER) stress, triggered by depletion of Ca2+stores by thapsigargin (TG), induced an increase in the [Ca2+]iand cell death. However, the TG-induced death was not related to the [Ca2+]iincrease but was mediated by targeting of activated Bax to mitochondria and the opening of mitochondrial permeability transition pores (PTPs). Once the mitochondrial PTPs had opened, several events, including collapse of the mitochondrial membrane potential, cytochrome c release, and caspase-3 activation, occurred and the cells died. TG-induced cell death was completely inhibited by the pan-caspase inhibitor Z-VAD-fmk and was enhanced by the Ca2+chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid (BAPTA), suggesting the existence of a Ca2+-dependent anti-apoptotic mechanism. After TG treatment, Ca2+-sensitive mitogen-activated protein kinase (MAPK) activation was induced and acted as a downstream effector of phosphatidylinositol 3-kinase (PI 3-kinase). The protective effect of Z-VAD-fmk on TG-induced cell death was reversed by BAPTA, PD-098059 (an MAPK kinase inhibitor), or LY-294002 (a PI 3-kinase inhibitor). Taken together, our data indicate that ER stress simultaneously activate two pathways, the mitochondrial caspase-dependent death cascade and the Ca2+-dependent PI 3-kinase/MAPK anti-apoptotic machinery. The Bax activation and translocation, but not the [Ca2+]iincrease, may activate mitochondrial PTPs, which, in turn, causes activation of caspases and cell death, whereas Ca2+-dependent MAPK activation counteracts death signaling; removal of Ca2+activated a second caspase-independent death pathway.

Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of healthcare-associated infections in intensive care units (ICUs). Prior studies have shown that decolonization of MRSA carriers is an effective method to reduce MRSA infections in ICU patients. However, there is currently a lack of data on its effect on mortality and medical cost. Methods Using a quasi-experimental, interrupted time-series design with re-introduction of intervention, we evaluated the impact of active screening and decolonization on MRSA infections, mortality and medical costs in the surgical ICU of a university hospital in Taiwan. Regression models were used to adjust for effects of confounding variables. Results MRSA infection rate decreased from 3.58 (baseline) to 0.42‰ (intervention period) (P P P = 0.038). After adjusting for effects of confounding variables, the active screening and decolonization program was independently associated with a decrease in in-hospital MRSA infections (adjusted odds ratio: 0.3; 95% CI: 0.1 to 0.8) and 90-day mortality (adjusted hazard ratio: 0.8; 95% CI: 0.7 to 0.99). Cost analysis showed that $22 medical costs can be saved for every $1 spent on the intervention. Conclusions Active screening for MRSA and decolonization in ICU settings is associated with a decrease in MRSA infections, mortality and medical cost.

Dementia and cancer are 2 common diseases in the elderly. This retrospective cohort study used a population-based insurance claim dataset, merged with a cancer registry, to test whether risk reduction of cancers occurs at various primary sites after diagnosis of dementia. The study included a cohort of 3282 patients who were first diagnosed with dementia between 2001 and 2002. A control cohort consisted of 13,128 subjects matched for age, sex, and year of enrollment. The site of cancer and duration between the diagnosis of dementia and cancer were analyzed. Among the dementia cases, 169 patients (5.2%) were diagnosed with cancer during a median observation period of 40 months. In the control group, 976 subjects (7.4%) were diagnosed with cancer, during a median observation period of 46 months. During a 7-year follow-up period, the adjusted hazard ratio for cancer among dementia patients was 0.77 (95% confidence interval, 0.65-0.91), and significantly lower for colon (0.54, 0.29-0.99) and prostate cancers (0.44, 0.20-0.98). This study showed an inverse association between cancer and dementia. Further studies focusing on colon and prostate cancers may help elucidate the underlying mechanism and expand the therapeutic strategies.

Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that downregulates translation of multiple plasticity-related proteins (PRPs) at the glutamatergic synapses. Activity-induced synthesis of PRPs maintains long-lasting synaptic changes that are critical for memory consolidation and chronic pain manifestation. CPEB3-knockout (KO) mice show aberrant hippocampus-related plasticity and memory, so we investigated whether CPEB3 might have a role in nociception-associated plasticity. CPEB3 is widely expressed in the brain and peripheral afferent sensory neurons. CPEB3-KO mice with normal mechanosensation showed hypersensitivity to noxious heat. In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, CPEB3-KO animals showed normal thermal hyperalgesia and transiently enhanced mechanical hyperalgesia. Translation of transient receptor potential vanilloid 1 (TRPV1) RNA was suppressed by CPEB3 in dorsal root ganglia (DRG), whereas CFA-induced inflammation reversed this inhibition. Moreover, CPEB3/TRPV1 double-KO mice behaved like TRPV1-KO mice, with severely impaired thermosensation and thermal hyperalgesia. An enhanced thermal response was recapitulated in non-inflamed but not inflamed conditional-KO mice, with cpeb3 gene ablated mostly but not completely, in small-diameter nociceptive DRG neurons. CPEB3-regulated translation of TRPV1 RNA may play a role in fine-tuning thermal sensitivity of nociceptors.

The relationship between androgen deprivation therapy (ADT) and coronary heart disease (CHD) remains controversial. Furthermore, the majority of such studies focused on Caucasian populations, and there is still a paucity of studies among Asian populations. This population-based study aimed to investigate the relationship between ADT and CHD in an ethnic Chinese (i.e., Taiwanese) population. We used data sourced from the Taiwan 'Longitudinal Health Insurance Database'. This study included 1278 patients with prostate cancer in the study group and 1278 subjects without prostate cancer in the comparison group. Each patient was individually tracked for a 3-year period to identify those who had subsequently received a diagnosis of CHD. The results showed that the incidence rate of CHD during the 3-year follow-up period was 4.69 (95% CI: 2.99-5.48) per 100 person-years and 2.67 (95% CI: 2.15-3.27) per 100 person-years for the study and comparison cohort, respectively. The Cox proportional hazard regression showed that the hazard ratio for CHD during the 3-year follow-up period for prostate cancer patients was 1.65 (95% confidence interval (CI) = 1.25-2.16) compared with comparison subjects after adjusting for patients' geographic location, monthly income, urbanization level, hypertension, diabetes, hyperlipidemia, and stroke. However, we failed to find a significant difference in the adjusted hazard of CHD during the 3-year follow-up period between prostate cancer patients who did and those who did not receive ADT (hazard ratio = 1.12, 95% CI = 0.79-1.59). We concluded that prostate cancer but not ADT was significantly associated with CHD. In addition, a common cause of prostate cancer and coronary heart disease could exist.

The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non- RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI [confidence interval] 1.43–1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73–0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis.

The purpose of this study was to evaluate the efficacy of gene delivery of angiogenesis inhibitor, vasostatin (VS), in suppressing experimental model of choroidal neovascularization (CNV). A mammalian expression vector carrying VS, pCMV3-VS, was constructed and evaluated for its ability to produce VS in transfected cells using western blot analysis and a cell viability assay. CNV was induced in Brown Norway rats by fundus argon laser photocoagulation and evaluated by fundus fluorescein angiography (FAG). Ten days post-laser treatment, gene delivery was achieved by intramuscular (IM) injection of poly-(N-vinyl pyrrolidone) (PVP) polymer conjugated with pCMV3-VS (PVP-VS) or a control vector (PVP-vector). Systemic VS expression was analysed by western blot analysis and enzyme linked immunosorbent assay (ELISA), and the extent of CNV was monitored by FAG analysis at different time intervals post-PVP treatment. Transfection of pCMV3-VS into muscle cells resulted in increased production and release of exogenous VS, which specifically inhibited the proliferation of endothelial cells. Besides, IM injection of PVP-VS, but not PVP-vector, led to elevated VS level in plasma for 30 days. After laser photocoagulation, rats injected with PVP-VS exhibited significantly lower incidence of CNV comparing with animals of control groups (P0.01) for at least 42 days. Moreover, rats treated with PVP-VS also showed a significant reduction in the CNV lesions compared with control groups (P0.001) for at least 42 days. Above all, no overt adverse effects were observed in rats received PVP-VS. These results demonstrate the potential of IM VS gene delivery for CNV treatment.

In the present study, the roles of protein kinase C (PKC) in BSA-derived advanced glycosylation end products (BSA-AGEs)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were investigated. Treatment of RAW 264.7 cells with BSA-AGEs caused dose- and time-dependent increases in NO release and iNOS expression in RAW 264.7 cells, whereas BSA alone had no effect on iNOS induction. The tyrosine kinase inhibitor (genistein), the phosphatidylinositol-specific phospholipase C inhibitor (U-73122), the phosphatidylcholine-specific phospholipase C inhibitor (D-609), and the PKC inhibitors (staurosporine, Ro 31-8220, and Go 6976) all inhibited BSA-AGE-induced NO release and iNOS expression in RAW 264.7 cells. Stimulation of RAW 264.7 cells with BSA-AGEs resulted in the formation of inositol monophosphate; the response was attenuated by U-73122 and genistein. BSA-AGEs stimulated PKC-alpha, -betaI, -delta, and -eta but not -zeta translocation from the cytosol to the membrane. However, incubation of RAW 264.7 cells with BSA-AGEs increased phosphorylation of PKC-zeta at threonine-410, which reflects activation of PKC-zeta, indicating the possible involvement of these PKC isoforms in AGE-mediated effects. Pretreatment of RAW 264.7 cells with U-73122, D-609, and genistein reduced the AGE-stimulated translocation of PKC-alpha, -betaI, -delta, and -eta and activation of PKC-zeta. Taken together, these data suggest that BSA-AGEs might activate PKC and subsequently induce iNOS expression and NO release.

Background The burden of cancer is likely to increase among the human immunodeficiency virus (HIV)-positive population as it ages due to successful antiretroviral therapy (ART). The purpose of this study was to determine the risk of cancer in HIV-infected patients. Methods This study was a matched nested case–control study. It was performed using the National Health Insurance Research Database of Taiwan. The control group included non–HIV-infected patients matched by sex, age, and year of enrollment. Logistic regression analyses were performed and simultaneously adjusted for potential confounders (income, urbanization, and Charslon index of comorbidity to evaluate HIV infection as an independent risk of cancer. We calculated the overall and sex-specific standardized incidence ratios (SIR) to investigate the pattern of cancer risk and overall cancer risk in the patients with HIV infection. Results Of the 1,115 HIV-infected patients, 104 (9.33%) developed cancer during the 11-year follow-up period. The risk of cancer for patients with HIV infection was significant (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 2.92–5.19) after adjustment for potential confounders. There was a significantly increased risk of developing non-Hodgkin lymphoma (SIR = 25.73, 95% CI = 6.83-90.85), cervical cancer (SIR = 4.01, 95% CI = 1.0-16.06), lymphoma (SIR = 20.26, 95% CI = 5.86-70.10), and respiratory and intrathoracic cancer (SIR = 20.09, 95% CI = 2.34-172.09) compared with the control group. In addition, HIV-infected patients were at significant risk for renal, oral, breast, liver, skin, and colorectal cancer. Conclusions Patients with HIV infection are at increased risk for several specific cancers. Our results support the implementation of an active and accelerated cancer screening schedule for patients with HIV infection to increase their life span.

Background Altered immune function after appendicectomy has been associated with autoimmune disease, even though the mechanisms are not clearly elucidated. This study aimed to investigate whether the frequency of new-onset type II diabetes was increased after appendicectomy in a case–control study. Methods This was a retrospective cohort study from the Taiwan Longitudinal Health Insurance Database 2000. The relative risk was compared with that in the general population using population-based data. Each patient was tracked for a 3-year interval to identify those who developed type II diabetes. Cox proportional hazard regression analysis was used to assess the risk of type II diabetes during follow-up. Results A total of 31 512 patients were included in the study, of whom 5252 had an appendicectomy (study cohort) and 26 260 were matched for comparison. Some 714 patients (2·3 per cent) developed type II diabetes during the 3-year follow-up, 161 in the study cohort (3·1 per cent) and 553 in the comparison cohort (2·1 per cent). The adjusted hazard ratio (HR) for type II diabetes in the study cohort was 1·45 (95 per cent c.i. 1·22 to 1·74). This increased risk was most pronounced in men (adjusted HR 1·47, 1·16 to 1·88) and in those with a perforated appendix (adjusted HR 2·28, 1·71 to 3·03), and applied only to patients younger than 65 years of age. Conclusion An increased risk of new-onset type II diabetes within 3 years after appendicectomy was found in patients aged less than 65 years. The risk was highest in men and in those with complicated appendicitis.

Purpose Topiramate is an effective anti-epileptic drug and can be associated with increased risk for urolithiasis because of its effects on acid–base profile. Evidences that supported an association of topiramate and urolithiasis were limited to case reports or series. We investigated the association of topiramate and urolithiasis in a nationwide population-based cohort study. Methods We analyzed 1377 patients receiving topiramate and 1377 age- and gender-matched control patients (not receiving topiramate) between 1997 and 2008. The risk of urolithiasis was analyzed using Kaplan–Meier analysis, followed by Cox proportional hazard regression. Results Of the 2754 patients, 79 (2.9%) patients developed urolithiasis in two (interquartile range: 1.2–4.2) years. The proportion of patients who developed urolithiasis in the patients receiving topiramate was not different from that of the control patients ( p =0.138, χ 2 test). The urolithiasis free survival was not different between the patients receiving topiramate and the control patients ( p =0.168) in Cox proportional hazard regression. The duration and total dosage of topiramate were not associated with risk of urolithiasis in patients receiving topiramate ( p =0.482 and p =0.751). Conclusion Topiramate may not increase the risk of urolithiasis. The duration and the total dosage of topiramate were not associated with urolithiasis risks.

Objective The recurrence rate after acute cystitis treatment failure with inappropriate antimicrobials remains unclear. The goal of this study was to explore the relationship between cystitis recurrence and nonadherence of antimicrobial prescriptions to national guidelines using a nationwide population-based data set. Methods This was a retrospective longitudinal observational cohort study that was conducted using the clinical records of the National Health Insurance Research Database in Taiwan from 2006-2007. After excluding patients younger than 18 years of age, with concurrent infections, urinary tract anomaly, and no antimicrobial treatment, the remaining study population included 36,395 patients with acute cystitis. We evaluated the hazard ratio (HR) of cystitis recurrence within 28 days between the adherence and nonadherence groups using Cox proportional hazard regression analysis. Results Adherence to antimicrobial prescription guidelines was the factor that most strongly influenced acute cystitis recurrence, with a HR of 0.91 (95% confidence interval 0.87-0.95) after adjusting for all variables. The incidence rate of acute cystitis in patients receiving antimicrobials adherent to national guidelines was 59.78 per 10,000 person-days. The results of the likelihood ratio test indicated that age, sex, and guideline nonadherence were significant risk factors for recurrent cystitis. The percentage of first-generation cephalosporin prescription was 31.61%, making it the most frequently prescribed guideline-recommended drug. Conclusion Acute cystitis patients with or without multiple chronic comorbidities should be treated with antimicrobials that adhere to recommended guidelines to attain a better therapeutic outcome.

Background: The Venturi-principle atomizer is a commonly used device in otolaryngology practices. The purpose of this study is to evaluate the possible route of bacterial contamination from the nasal vestibule to the atomizer tip through the jet airflow created during the use of the Venturi atomizer. Methods: Thirty nostrils from 15 enrolled volunteers were tested. The aerosols generated by spraying sterilized saline into the nostrils were collected using a specially made aerosol-collecting nozzle cap. The collected samples were sent for bacterial culture, and nasal vestibular swab cultures were performed for comparison. Results: In the aerosol-exposed group, 18 out of 30 samples (60%) were positive for bacterial growth, confirming the bacterial contamination from the nasal vestibule to the atomizer tip through the reverse jet airflow. The bacteria species in 8 of the 18 positive samples were identical to those from the nasal swab culture results from the same nostril. Conclusion: In ordinary otolaryngology practices, there are significant risks for bacterial contamination from the nasal vestibule to the tip of the Venturi atomizer even without direct contact. Clinicians must be more aware of this pattern of contamination, which has not been reported in the existing literature.