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Yi-Fen Lei,1,2 Hsiu-Chen Lin,3,4 Hsiu-Li Lin,5 Yow-Sheng Uang,2 Hui-Wen Cheng,2 Li-Hsuan Wang2,6 1Department of Pharmacy, Mackay Memorial Hospital, Taipei 10449, Taiwan; 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; 3Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; 4Department of Clinical Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan; 5Department of Neurology, General Cathay Hospital, New Taipei City 22174, Taiwan; 6Department of Pharmacy, Taipei Medical University Hospital, Taipei 11031, TaiwanCorrespondence: Li-Hsuan WangSchool of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, TaiwanEmail shiuan@tmu.edu.twObjective: The effect of statins and fibrates on the risk of chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the effects of statins and fibrates on the risk of COPD in patients with hyperlipidemia.Patients and Methods: This study involved a retrospective cohort with a follow-up period of 6 years. We identified patients who were diagnosed as having hyperlipidemia between 2000 and 2016 from Taiwan’s National Health Insurance Research Database. A Cox proportional hazard model was used to estimate the risk of COPD among different groups. The dose-related effects of statins and fibrates on the risk of COPD were evaluated according to the defined daily dose (DDD).Results: Patients with hyperlipidemia not using statins and fibrates (group II) had a significantly higher risk of COPD compared with their comparison group, with an adjusted hazard ratio (HR) of 1.091 [95% confidence interval (CI): 1.034– 1.152, p < 0.01]. Dose-dependent reduction in the risk of COPD was observed in patients with hyperlipidemia using statins or fibrates compared with patients not using them. Moreover, with an increase in cumulative exposure, a reduced risk of COPD was observed in patients using more than 361 DDDs, with an adjusted HR of 0.474 (95% CI: 0.401– 0.559, p < 0.001). Patients on fibrate monotherapy using more than 541 DDDs were observed to have an adjusted HR of 0.454 (95% CI: 0.226– 0.910, p < 0.05) and those on statin monotherapy with over 361 DDDs were noted to have an adjusted HR of 0.583 (95% CI: 0.459– 0.740, p < 0.001).Conclusion: This study demonstrated that an increase in the cumulative exposure of statins and fibrates significantly reduced the risk of COPD in patients with hyperlipidemia, and the risk reduction appeared to be significantly dose dependent.Keywords: hyperlipidemia, statin, fibrates, chronic obstructive pulmonary disease, cohort study

Background Hypokalemia is a common clinical problem. The association between urinary tract infection (UTI) and hypokalemia is not clear. Hypokalemia is common in patients with UTI in clinical observation. The aim of the study is to determine if UTI is associated with hypokalemia. Methods Patients hospitalized with UTI and the control group were retrieved from the Longitudinal Health Insurance Database 2005. The control group was patients hospitalized with other reasons and were matched for the confoundings of UTI and hypokalemia. We analyze the risk of hypokalemia using logistic regression and calculate the odds ratio (OR) and 95% confidence interval (CI) of OR. Results We analyzed 43,719 UTI patients and control patients. Hypokalemia was found in 4540 (10.4%) patients with UTI and 1842 (4.2%) control patients. The percentage of patients with hypokalemia was higher in UTI patients (chi-square, p p Conclusions Urinary tract infection is associated with hypokalemia among inpatients. The association is independent of patients’ comorbidities and medications. Recurrent UTI is associated with increased hypokalemia in UTI patients.

Silymarin is a bioflavonoid compound mostly used in patients with chronic hepatic diseases (CHDs). It has been shown to inhibit retinal angiogenesis in in vitro and in vivo animal studies. Age-related macular degeneration (AMD) is a leading cause of vision impairment worldwide, and no definite preventive measures for AMD exist at present. Through this study, we aimed to investigate whether the use of silymarin affects the risk of AMD in patients with CHDs. Cox proportional hazard models were used to assess the hazard ratio (HR) of AMD in this population-based retrospective cohort study. The CHDs was associated with a higher risk of AMD (adjusted hazard ratio (aHR): 1.33, 95% CI 1.22–1.46), and the use of silymarin reduced the risk of AMD among patients with CHDs (aHR: 0.76, 95% CI: 0.67–0.87). A higher accumulative dose (defined daily dose [DDD] < 631 mg) of silymarin was associated with a lower risk of AMD, but the difference was nonsignificant. In conclusion, CHDs were associated with a higher incidence of AMD, and the use of silymarin was associated with a reduced risk of AMD in patients with CHDs. However, a higher accumulative DDD of silymarin did not reduce the risk of AMD.

Background: Freezing of gait (FOG) in Parkinson's disease (PD) is a devastating clinical phenomenon that has a detrimental impact on patients. It tends to be triggered more often during turning (complex) than during forwarding straight (simple) walking. The neural mechanism underlying this phenomenon remains unclear and requires further elucidation.Objective: To investigate the differences in cerebral functional magnetic resonance imaging responses between PD patients with and without FOG during explicitly video-guided motor imagery (MI) of various complex (normal, freezing) and simple (normal, freezing) walking conditions.Methods: We recruited 34 PD patients, namely, 20 with FOG and 14 without FOG, and 15 normal controls. Participants underwent video-guided MI of turning and straight walking, with and without freezing, while their brain blood oxygen level-dependent (BOLD) activities were measured. Gait analysis was performed.Results: While comparing FOG turning with FOG straight walking, freezers showed higher activation of the superior occipital gyrus, left precentral gyrus, and right postcentral gyrus compared with non-freezers. Normal controls also manifest similar findings compared with non-freezers, except no difference was noted in occipital gyrus activity between the two groups. Freezers also displayed a higher effect size in the locomotor regions than non-freezers during imagery of normal turning.Conclusions: Our findings suggest that freezers require a higher drive of cortical and locomotion regions to overcome the overinhibition of the pathways in freezers than in non-freezers. Compared with simple walking, increased dorsal visual pathway and deep locomotion region activities might play pivotal roles in tackling FOG in freezers during complex walking.

WHAT IS KNOWN AND OBJECTIVE Proton-pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are two of the most widely used acid-suppressive drugs (ASDs). Some studies have reported that prenatal ASD exposure may increase the risk of asthma and other allergic diseases. This study investigated the effects of ASDs on the risk of atopic dermatitis in patients with upper gastrointestinal diseases. METHODS This population-based retrospective cohort study used data of 289,850 patients with at least two diagnoses of upper gastrointestinal diseases (UGIDs) between 1 January 2001 and 31 December 2005, from Taiwan's National Health Insurance Research Database. The AD risks among ASD users and nonusers were compared. Differences in sociodemographic characteristics and potential covariates were examined. AD hazard ratios were estimated, and groups were compared using Cox proportional hazards regression analysis after adjustment for age, sex and other covariates. RESULTS AND DISCUSSION In total, 109,980 patients were included. The adjusted hazard ratio (HR) of AD risk in ASD users relative to that in nonusers was 1.52 (95% confidence interval [CI]: 1.40-1.64, p

BackgroundThe supplemental screw technique was introduced for salvage of lateral hinge fracture in medial open-wedge high tibial osteotomy (owHTO). The efficacy of its use in protection of lateral hinge fracture and corresponding biomechanical behaviors remained unclear. The current study was aimed to clarify if a supplemental screw can provide better protection to lateral hinge in biomechanical perspective.MaterialsAn in vitro biomechanical test was conducted. Tibial sawbones, commercial owHTO plates and a cannulated screw were utilized for preparing the intact, owHTO, and owHTO with cannulated screw insertion specimens. A “staircase” dynamic load protocol was adopted for axial compressive test with increasing load levels to determine structural strength and durability by using a material testing system, while a motion capture system was applied for determining the dynamic changes in varus angle and posterior slope of the tibia plateau with various specimen preparation conditions.ResultsType II lateral hinge fracture were the major failure pattern in all specimens prepared with owHTO. The insertion of a supplemental cannulated screw in medial owHTO specimens reinforced structural stability and durability in dynamic cyclic loading tests: the compressive stiffness increased to 58.9–62.2% of an intact specimen, whereas the owHTO specimens provided only 23.7–29.2% of stiffness of an intact specimen. In view of tibial plateau alignment, the insertion of a supplemental screw improved the structural deficiency caused by owHTO, and reduced the posterior slope increase and excessive varus deformity by 81.8% and 83.2%, respectively.ConclusionThe current study revealed that supplemental screw insertion is a simple and effective technique to improve the structural stability and durability in medial owHTO.

Background The use of dihydropyridine calcium channel blockers (DCCBs) was proposed to reduce the risk of Parkinson's disease (PD). This study aimed to evaluate the association between DCCB and its dose effect and the risk of PD in patients with newly diagnosed hypertension. Methods This population-based retrospective cohort study enrolled 107,207 patients with newly diagnosed hypertension, between 2001 and 2013, from Taiwan's National Health Insurance Research Database. Patients who had PD before hypertension or were taking antipsychotics for more than 30 days in the 6 months prior to the end of the observation period were excluded. A Cox proportional hazard model was used to estimate the risk of PD in different groups. The dose-related effects of DCCB on the risk of PD were evaluated according to the cumulative defined daily dose (DDD). Results We observed 832 (1.2%) PD cases in patients treated with DCCB as compared to 950 (2.4%) PD cases in those not treated with DCCB, during a median follow-up duration of 8.3 years and 6.2 years, respectively. The risk of PD in the DCCB-treated group (hazard ratio [HR] = 0.50) was significantly lower than that in the group without DCCB treatment. DCCB reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.61 to 0.37 for DDDs of 90–180 to >720. Conclusions DCCB treatment was associated with a significantly reduced risk of PD in patients with newly diagnosed hypertension. Further clinical trials are needed to confirm the proposed neuroprotective effects of DCCB in PD.

Choroidal neovascularization (CNV) is a common pathological feature in neovascular age-related macular degeneration, which is the leading cause of vision loss among elderly populations in developed countries. This study evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin anti-angiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. CAD was expressed in Ad-CAD-infected cells and inhibited the angiogenic activity in human umbilical vein endothelial cells in vitro. CAD expression was also found in various ocular tissues after in vivo subconjunctival Ad-CAD injection. Via bioluminescence imaging it is shown that a single subconjunctival injection of Ad-luciferase induced the expression of the transgene in the injected eyes within 24 h, which lasted for at least 112 days. Forty-two days after subconjunctival injection of Ad-CAD, retinal structure and function were unaffected, as measured using optical coherence tomography and electroretinography, respectively. After laser injury, subconjunctival Ad-CAD gene delivery significantly inhibited CNV lesions as measured via choroid flat-mounts (51% reduction at 21 days; p

Background The effect of gout on the risk of developing coronary artery disease (CAD) is uncertain. Some studies have found that gout is a risk factor for acute myocardial infarction. This study examined the changes in risk of CAD in gout patients taking allopurinol and/or benzbromarone, and analyzed the dose-response relationship of both drugs with CAD incidence. Methods The medical records of one million subjects from 2000 to 2011 were provided by the Taiwan National Health Insurance Research Database. Cox proportional hazard ratio was used to compare the risk of CAD in gout patients taking allopurinol or/and benzbromarone with those taking neither drug. Hazard ratios (HR) were adjusted for possible confounding factors, including age, gender, hypertension, hyperlipidemia, diabetes mellitus, chronic kidney disease, and relevant medications. Results Of 8047 gout patients, 1422 were treated with allopurinol (Group A), 4141 with benzbromarone (Group B), and 2484 with both drugs (Group A/B) during the follow-up period. Our results showed the incidence of CAD after adjusting for covariates for Group A, Group B, and Group A/B did not significantly differ from the comparison group. However, after adjustment for covariates in dose-response analyses, treatment with over 270 defined daily doses (DDDs) of allopurinol, and over 360 DDDs of benzbromarone, was associated with a significantly reduced risk of CAD. Conclusion We found that the use of allopurinol and benzbromarone, whether alone or in combination, had a linear dose-response relationship between the numbers of defined daily doses and the risk of CAD, especially in higher DDDs.

Background Primary family caregivers (PFCs) of children with cerebral palsy have many worries and concerns when their children face orthopedic surgery. Levels of PFC stress about the upcoming surgery is related to the child's level of gross motor function as well as the support they receive from medical professionals. Purpose The purposes of the present study were to (1) explore the levels of concern about orthopedic surgery; and (2) explore the predictive factors associated with concerns about orthopedic surgery among PFCs of children with cerebral palsy during the preoperative period. Methods A cross-sectional, correlational study was conducted. Primary family caregivers were assessed preoperatively using the Single-event Multilevel Surgery Scale, Social Support Scale, Gross Motor Function Classification System-Expanded and Revised, and background information form. Primary family caregivers were recruited from the outpatient department of orthopedic surgery and pediatric rehabilitation of a medical center in northern Taiwan. Data were analyzed by descriptive analysis, Pearson product-moment correlation, and multiple regression analysis. Results A total of 63 eligible subjects were enrolled in this study. Primary family caregivers had moderate levels of concern and mild-to-moderate levels of social support. The higher severity of motor function impairment in children with cerebral palsy, prior caregiving by PFCs for another family member, and PFCs' lower level of social support from healthcare providers were associated with higher levels of PFC concern. Conclusions Concerns about orthopedic surgery is an overlooked issue that needs more attention from healthcare providers. This study determined that PFCs who perceived a lack of social support from their healthcare providers and those with children who had limited gross motor function were more concerned and anxious about their children's upcoming orthopedic surgery. Health professionals should provide adequate health education and counseling to help PFCs of children with cerebral palsy in the decision-making process prior to orthopedic surgery.

Background A blood urea nitrogen to creatinine ratio (BCR) of 20 or greater indicates various physiological conditions. Whether glomerular filtration rate (GFR) estimates obtained using the Modification of Diet in Renal Disease (MDRD) study equation and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equations are affected by a high BCR remains unknown. Methods Patients who underwent urine creatinine clearance (CrCl) and serum blood urea nitrogen (BUN) and creatinine assessments on the same day were enrolled in our study. Those with BCR of 20 or greater and less than 20 were categorized into high- and low-BCR groups. The concordance on diagnosing chronic kidney disease (CKD) stages by using urine CrCl level and serum GFR estimates was assessed. Results More disagreement in CKD stage diagnosis was observed in the high-BCR group (weighted κ = 0.600 and 0.541 for the MDRD and CKD-EPI study equations, respectively) than in the low-BCR group (weighted κ = 0.816 and 0.758, respectively). Conclusions A BCR of 20 or greater caused misestimation of the CKD stage. GFR estimates for patients with high BCR should be interpreted cautiously.

Background Prescriptions for gastric acid–suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). Methods We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan’s Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid–suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid–suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. Results The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid–suppressive agents compared with patients with UGID without gastric acid–suppressive agents was 1.470 (95% confidence interval [CI] 1.267–1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377–2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098–1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022–2.075], p < 0.05). Conclusions Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid–suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.

Objective To evaluate the effect of whole-body vibration training on working-age people on haemodialysis. Design Consecutive case series study. Subjects Seventeen working-age participants on maintenance haemodialysis were enrolled. Methods A 12-week whole-body vibration training programme, including different postures, was designed. The study evaluated and compared physical fitness, including a list of tests such as the 5-repetition sit-to-stand test, hand grip test, 2-min step test, and 8-foot up-and-go test; modified Berg balance scale; static and dynamic balance function; and quality of life, using a quality of life questionnaire before and after the training. Results All physical fitness parameters, except grip strength on the left side, improved after whole-body vibration training. For balance, the modified Berg balance scale demonstrated enhanced scores for equilibrium, with eyes closed on a stable surface and eyes open on an unstable surface, and movement velocity under the fast condition along the left and right directions (p=0.011). No significant improvements in quality of life were found. Conclusion Whole-body vibration exercise training enhanced physical fitness and static and dynamic balance control in working-age participants on haemodialysis. LAY ABSTRACT This study designed a series of exercises in different postures on a whole-body vibration machine for individuals on maintenance haemodialysis and evaluated the changes in their physical fitness, postural control and quality of life before and after a 12-week programme. Seventeen working-age participants on maintenance haemodialysis were enrolled and completed the whole-body vibration training programme. There were no significant changes in the scores on the quality of life questionnaire for multifactorial aspects. However, the physical fitness parameters, including a list of tests, such as the 5-repetition sit-to-stand test, hand grip test of right side, 2-min step test and 8-foot up-and-go test, improved after the whole-body vibration training. Their postural control also demonstrated improvements in the modified Berg balance scale, equilibrium scores with eyes closed on a stable surface and eyes open on an unstable surface, and movement velocity under the fast condition along the left and right directions.

This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997–1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded. The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758–6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not. This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.

Objective 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. Methods 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). Results 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. Conclusions 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.

Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD.

Summary Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the “Taiwan Longitudinal Health Insurance Database 2000.” The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period.

We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson's disease (PD) in patients with diabetes mellitus (DM).This study enrolled 38,521 patients with newly-diagnosed DM, between 2001 and 2013, and compared them to the matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione.We observed that 544 (1.4%) patients developed PD during the follow-up median duration of 6.2 years in patients with newly-diagnosed DM or had a higher risk for PD than patients without DM (HR = 1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR = 0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0-90 to720, respectively.Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases. Key messages Newly-diagnosed diabetes mellitus slightly increases the risk for Parkinson's disease. Thiazolidinedione is associated with a lower risk of Parkinson's disease in a dose-dependent manner in patients with newly-diagnosed diabetes mellitus.

There is accumulating experimental evidence that human platelet lysate (HPL) made from platelet concentrates can replace fetal bovine serum (FBS) as a xeno-free clinical-grade supplement of growth media to expand mesenchymal stromal cells (MSCs). However, uncertainties exist in regard to impacts that various manufacturing methods of HPL can exert on the expansion and differentiation capacity of MSCs. In particular, there is a need to evaluate the possibility of implementing virus-inactivation treatment during HPL production to ensure optimal safety of industrial HPL pools. Expired human platelet concentrates from four different donors were pooled and subjected to freeze-thaw cycles (-80/+37 °C), followed or not by serum-conversion by calcium chloride, heat-treatment at 56 °C for 30 min, or solvent-detergent (S/D) virus inactivation. The concentrations of total proteins, growth factors and fibrinogen, and the chemical compositions of the HPLs were characterized. The impact of HPL supplementation on the cell morphology, doubling time, immunophenotype and trilineage differentiation capacity of Wharton jelly MSCs (WJMSCs) were compared over five passages, using FBS as a control and normalizing the protein content. Data showed that WJMSCs expanded equally well, exhibited a typical fibroblast morphology, had short doubling times, maintained their immunophenotypes, and differentiated into chondrocyte, osteocyte, and adipocyte lineages in all HPL-supplemented media, all of which were more effective than FBS. In conclusion, we found minimal detectable impact of the HPL manufacturing process, including S/D virus inactivation, on the suitability of expanding WJMSCs in vitro.

Microparticles (MPs) released by blood or endothelial cells are present in plasma for transfusion. They originate from the collected donor blood or are triggered by the variable steps taking place during collection and production/storage processes of blood components. While MPs may contribute to hemostasis, their presence in transfused plasma may lead to uncontrolled thrombin generation when transfused to susceptible cancer or hypercoagulable patients. Understanding the biochemical and cellular triggers of MP-mediated thrombogenesis is therefore crucial. We isolated platelet MPs (PMPs) present in platelet concentrate supernatant plasma (N-PMPs) or prepared by activation of isolated platelets using 0.1 IU/mL thrombin (T-PMPs). N-PMPs and T-PMPs were characterized by dynamic light scattering and counted by tunable resistive pulse sensing to determine population size and number. T-MPMs, but not N-PMPs, induced immediate, long-lasting, strong aggregation of THP-1 monocytic cells in vitro. In addition, co-cultures of THP-1 cells with both N-PMPs and T-PMPs triggered the generation of pro-coagulant tissue factor (TF)-bearing MPs from THP-1 cells. Therefore, some PMPs may induce THP-1 monocytic cell aggregation in vitro and trigger immune cell-mediated thrombogenicity linked to the release of pro-coagulant tissue factor-bearing MPs. Controlling the impact of the presence of PMPs in transfused blood components in certain patient population or critically ill patients deserves in-depth consideration.

BackgroundChronic kidney disease (CKD) is a serious medical problem and public health issue in Taiwan. Gastrointestinal symptoms frequently occur in patients with CKD, and proton pump inhibitors (PPIs) have therapeutic indications for gastrointestinal disorders involving excessive acid production. However, PPIs may also increase the risk of developing pneumonia through acute and irreversible gastric acid suppression. This study aimed to characterize differences in the risk of pneumonia in patients with CKD who use PPIs.MethodsThis population-based case–control cohort study in Taiwan collected data from the Taiwan Health Insurance Research Database. Cases studied consisted of all patients in the database with an initial diagnosis of CKD during the 5-year period from 1997 to 2002. Each patient with CKD who used PPIs during this 5-year period was tracked to identify the occurrence of any type of pneumonia. We estimated the adjusted hazard ratios (HRs) and 95% confidence interval (95% CI) by using multiple logistic regression analysis.ResultsThe adjusted HR of the risk of pneumonia for patients with CKD using PPIs was 2.21 (95% CI = 1.59–3.07, p

Summary The association between diabetes and benign prostatic hyperplasia remains inconclusive. In this case–control study, we examined the association of diabetes with benign prostatic enlargement (BPE) using the Longitudinal Health Insurance Database 2000 in Taiwan. In total, 20 152 patients with BPE as cases and 20 152 age-matched patients without BPE were included as controls. Conditional logistic regression analyses were performed to calculate the odds ratio (OR) and corresponding 95% CI for having been previously diagnosed with diabetes between cases and controls. We found that of the 40 304 sampled patients, 9492 (23.6%) had a history of diabetes before the index date. This mean age for the sampled patients was 65.9 with a standard deviation of 12.0 years. A Chi-squared test revealed that there was a significant difference in the prevalence of prior diabetes between cases and controls (25.3% vs. 21.8%, p

Leukoreduction in blood units could prevent patients undergoing transfusions from transfusion-associated adverse reactions (TAARs) such as febrile nonhemolytic transfusion reactions (FNHTRs). However, the effect of prestorage and poststorage leukoreduction on TAARs and its underlying mechanisms in stored blood components remains to be determined. Therefore, we investigated the impact of prestorage leukocyte-reduced (pre-LR) and poststorage leukocyte-reduced (post-LR) blood products, including red blood cells (RBCs) and apheresis platelets (PHs), on the incidence of FNHTRs and other TAARs in patients who received transfusions from 2009 to 2014 in a tertiary care center. We also investigated the difference of leukocyte-related bioactive mediators between pre- and post-LR blood components. The results indicated that prevalence of TAARs was significantly reduced in the transfusions of pre-LR blood components. Particularly, the prevalence of FNHTRs was significantly reduced in the pre-LR RBC transfusions and the prevalence of allergy reactions was markedly reduced in the pre-LR PH transfusions. Furthermore, in vitro evaluation of cytokines in the pre- and post-LR blood components revealed that IL-1β, IL-8 and RANTES levels were significantly elevated in the post-LR RBCs during the storage. In contrast, IL-1β, IL-6 and IL-8 levels were significantly elevated in the post-LR PHs during the storage. These findings suggested that prestorage leukoreduction had a diminishing effect on the development of TAARs, which could be associated with less accumulation of cytokines in the stored blood components.

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: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. Materials and Methods: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. Results: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). Conclusions: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.

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.

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 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.

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.

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.