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Few studies have comprehensively and systematically analyzed nationwide samples. This study purposed to explore temporal trends and predictors of medical resource utilization and medical outcomes in these patients to obtain data that can be used to improve healthcare policies and to support clinical and administrative decision-making. This study used nationwide population data contained in the Longitudinal Health Insurance Database of Taiwan. The 14,970 inguinal hernia repair patients were enrolled in this study (age range, 18–100 years) from 1997 to 2013 in Taiwan. After temporal trends analysis of demographic characteristics, clinical characteristics, and institutional characteristics, predictors of postoperative medical resource utilization and medical outcomes were evaluated through multiple linear regression analysis and Cox regression analysis. The prevalence of inguinal hernia repair per 100,000 population significantly decreased from 195.38 in 1997 to 39.66 in 2013 (p

This retrospective study included COPD patients who attended our medical center between January and October 2018, and analyzed the outcomes of their influenza vaccination, including medical visits, hospitalization, medical expenses, and the incidence of respiratory failure. Airflow limitation was stratified according to GOLD guidelines. Overall, 543 COPD patients were enrolled, including 197, 113, 126, and 107 mild, moderate, severe, and very severe patients, respectively. Of all the participants, 238 received an influenza vaccination (43.8%), which significantly reduced hospital utilization for moderate (odds ratio [OR] 0.22, 95%CI 0.09–0.51), severe (OR 0.19, 95%CI 0.08–0.44), and very severe patients (OR 0.15, 95%CI 0.05–0.5) compared to mild patients (OR 0.51, 95%CI 0.2–1.26), reduced emergency department utilization for moderate (OR 0.33, 95%CI 0.14–0.77), severe (OR 0.22, 95%CI 0.10–0.52), and very severe patients (OR 0.30, 95%CI 0.10–0.88) compared to mild patients (OR 0.64, 95%CI 0.30–1.37), and reduced the occurrence of respiratory failure for moderate (OR 0.20, 95%CI 0.06–0.68), severe (OR 0.40, 95%CI 0.16–0.98), and very severe patients (OR 0.36, 95%CI 0.15–0.82) compared to mild patients (OR 0% CI 0.14–3.20). Influenza vaccination is more effective in COPD patients with moderate, severe, and very severe airflow obstruction than in those with mild obstruction with respect to hospital utilization, emergency department utilization, and respiratory failure.

Protobothrops mucrosquamatus (Trimeresurus mucrosquamatus) is a medically important species of pit viper with a wide geographic distribution in Southeast Asia. Bites by P. mucrosquamatus mostly involve the extremities. Little is known about the toxic effects of P. mucrosquamatus envenoming to the head because of the infrequency of such occurrence. To better delineate the clinical manifestations of envenoming to the head, we report three patients who suffered from P. mucrosquamatus bites to the head and were treated successfully. All three patients developed progressive soft tissue swelling extending from head to neck, with two patients expanding further onto the anterior chest wall. Mild thrombocytopenia was noted in two patients. One patient had transient acute renal impairment and airway obstruction, necessitating emergent intubation. All three patients received high doses of species-specific antivenom with recovery within 1 week. No adverse reactions to antivenom were observed.

Background Little is known about the emergency department (ED) visits from drug-related injury among older adults in Taiwan. This study seeks to identify risk factors associated with adverse drug events (ADEs) leading to ED visits. Methods We prospectively conducted a case–control study of patients 65 years and older presenting to the ED. ED visits between March 1, 2009 and Feb 28, 2010 identified by investigators for suspected ADEs were further assessed by using the Naranjo Adverse Drug Reaction probability scale. For each patient with an ADE, a control was selected and time-matched from the ED population of the study hospital. The association between the risk of adverse drug events and triage, age, gender, serum alanine transaminase (ALT), serum creatinine, number of medications, and Charlson Comorbidity Index scores were analyzed using logistic regression. Results Of 20,628 visits, 295 ADEs were physician-documented in older adults. Independent risk factors for ADEs included number of medications (adjusted odds ratio [OR] = 4.1; 95% confidence interval [CI] 2.4–6.9 for 3–7 drugs; adjusted OR = 6.4; 95% CI 3.7–11.0 for 8 or more drugs) and increased concentration of serum creatinine (adjusted OR = 1.5; 95% CI 1.1–2.2). Diuretics, analgesics, cardiovascular agents, anti-diabetic agents and anticoagulants were the medications most commonly associated with an ADE leading to ED visits. Conclusions This study suggests that prevention efforts should be focused on older patients with renal insufficiency and polypharmacy who are using high risk medications such as anticoagulants, diuretics, cardiovascular agents, analgesics, and anti-diabetic agents.

Background The cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in electrolyte and fluid transport in epithelial cells, and women with cystic fibrosis (CF), caused by CFTR gene mutations, have a higher incidence of infertility. Methods In the present study, we investigated the expression of CFTR in porcine oviduct and its functional role in oviductal HCO(3)(-) secretion and embryo development with RT-PCR, western blot, patch-clamp, short-circuit current (I(sc)), pH measurement and embryo culture. Results RT-PCR and western blot analysis showed the expression of CFTR mRNA and protein in the oviduct with its localization demonstrated by immunohistochemistry. The whole-cell patch-clamp recording revealed a forskolin (FSK)-activated current with electrophysiological and pharmacological characteristics of CFTR. The I(sc) measurement showed that FSK-stimulated an increase in the I(sc), which could be significantly reduced by CFTR inhibitor or removal of both CO(2) and HCO(3)(-). pH measurement showed a FSK stimulated alkalization at the apical surface, which could be inhibited by CFTR inhibitor, indicating CFTR-mediated HCO(3)(-) secretion. Mouse embryo development from 2-cell to morula or blastocyst stage was significantly inhibited in the absence of HCO(3)(-) or when co-cultured with HCO(3)(-) secretion-deficient CFTR mutant cells as compared with the wild-type. RT-PCR, western blot and immunostaining showed the expression of soluble adenylate cyclase (sAC), the known HCO(3)(-) sensor, in embryos. Treatment with its inhibitors, 2-hydroxyestradiol and KH7, prevented the HCO(3)(-) dependent embryo development. Conclusion The present results suggest that CFTR-mediated oviductal HCO(3)(-) secretion may be vital for sAC-dependent early embryo development, a defect of which may contribute to the reduced fertility seen in women with CF.

Well-designed and performed pivotal trials are critical in providing the efficacy and safety of a new drug for regulatory approval. The success of clinical drug development relies on the ability of clinical trial leaders to design and conduct international clinical studies. Physicians can do good clinical practice quality trials by following the protocols accurately but may not be able to design a complicated trial or lead an international clinical trial team. Clinical trial leaders are rarely born but have to be trained and learn through clinical research experience. Academic centers and drug industries have identified this need and proactively designed programs to nurture the clinical trial leaders of tomorrow via multidisciplinary programs. Using Taiwan as an example, the government has set up a Center of Excellence for Clinical Trials and Research (CECTR) in four medical centers. These national CECTRs complete a nationwide clinical trial network; strengthen clinical trial and clinical research infrastructure; set up national clinical trial and translational research centers; provide education and training for clinical researchers, doctors, nurses, and pharmacists; and improve quality, capacity, capability, and results of clinical trials. They are among the best in the world. Major pharmaceutical companies sponsored 200 international clinical trials for New Drug Applications in Taiwan in 2007. Our clinical investigators showed their clinical trial leadership by chairing many international clinical trials in Asia and worldwide. A Clinical Trial Academy for the training of clinical research leaders in Asia-Pacific is held regularly at the National CECTR at National Taiwan University Hospital. In collaboration with distinguished speakers from the industry, academia, and the local regulatory agency, promising young physicians from Asia-Pacific are trained in practical small-group workshops. Topics selected included how to perform international investigator meetings, how to write principal investigator (PI)-initiated clinical trial protocols, the concept of new drug development from the perspective of industry, experience in the institutional review board review of investigational new drug protocols, and so on. These investments in human resources have been well reflected in the number of clinical trials performed in Taiwan. Other than Australia, Taiwan has the highest number of PI-initiated clinical trials in Asia. We believe a good clinical research environment can attract young physicians to develop careers in clinical research and become clinical trial leaders of tomorrow.

Envenoming by Protobothrops mucrosquamatus and Viridovipera stejnegeri accounts for the majority of venomous snakebites in Taiwan. We conducted a retrospective study to systematically examine the clinical manifestations and responses to antivenom therapy after P. mucrosquamatus and V. stejnegeri envenoming. Information on demographic characteristics, treatments, and systemic/local complications were abstracted from medical charts between 1991 and 2006. One hundred forty-nine patients with P. mucrosquamatus envenoming and 51 with V. stejnegeri envenoming were eligible for the final analysis, and they differed in terms of patient age, bite site, local bruising, proportion of patients needing >/= 3 vials of antivenom, and mean hospital stay. Univariate analysis revealed that P. mucrosquamatus envenoming had a higher risk of developing rhabdomyolysis, cellulitis, necrosis, and skin graft. Our findings suggested that P. mucrosquamatus envenoming was associated with a greater risk of severe clinical events, and monitoring for major clinical complications would be recommended.

The present study investigated the effects of dopamine on chloride transport across cultured rat caudal epididymal epithelium. The results showed that dopamine induced a biphasic short-circuit current (Isc) in a concentration-dependent manner. The dopamine-induced response consisted of an initial rapid spike followed by a sustained phase. The alpha and beta adrenoreceptor inhibitors, phentolamine and propranolol, inhibited the initial spike and the sustained phase, respectively, suggesting a contribution of adrenergic receptors. The response was almost abolished by removing the extracellular Cl-, suggesting that the dopamine-induced short-circuit current is primarily a Cl- current. The response was inhibited by the apical Cl- channel blocker, diphenylamine-dicarboxylic acid, and the Ca2+-activated Cl- channel blocker, disulfonic acid stilbene, indicating that Cl- may pass through two types of Cl- channels on the apical side. Preloading monolayers with the intracellular Ca2+ chelator BAPTA/AM abolished the initial spike and greatly reduced the second phase in the Isc response to dopamine. Pretreating the monolayers with an adenylate cyclase inhibitor, MDL12330A, inhibited all of the second Isc response and part of the initial spike. Also, characteristics of the Cl- currents induced by dopamine were observed in whole-cell patch-clamp recording. The increases of intracellular cAMP and Ca2+ induced by dopamine were also measured. The results suggest that extracellular dopamine activates Ca2+-dependent and cAMP-dependent regulatory pathways, leading to activation of both Ca2+-dependent and cAMP-dependent Cl- conductances in epididymal epithelial cells.

The aim of this study was to investigate the functional expression of cystic fibrosis transmembrane conductance regulator (CFTR) with electrophysiological and molecular technique in rat oviduct epithelium. In whole-cell patch clamp, oviduct epithelial cells responded to 100 µM 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) with a rise in inward current in Gap-free mode, which was inhibited successively by 5 µM CFTR(inh)-172, a CFTR specific inhibitor, and 1 mM diphenylamine-2-carboxylate (DPC), the Cl − channel blocker. The cAMP-activated current exhibited a linear current-voltage (I-V) relationship and time- and voltage-independent characteristics. The reversal potentials of the cAMP-activated currents in symmetrical Cl − solutions were close to the Cl − equilibrium, 0.5±0.2 mV (n=4). When Cl − concentration in the bath solution was changed from 140 mM to 70 mM and a pipette solution containing 140 mM Cl − was used, the reversal potential shifted to a value close to the new equilibrium for Cl − , 20±0.6 mV (n=4), as compared with the theoretic value of 18.7 mV. In addition, mRNA expression of CFTR was also detected in rat oviduct epithelium. Western blot analysis showed that CFTR protein is found in the oviduct throughout the cycle with maximal expression at estrus, and immunofluorescence and immunohistochemistry analysis revealed that CFTR is located at the apical membrane of the epithelial cells. These results showed that the cAMP-activated Cl − current in the oviduct epithelium was characteristic of

Ethnopharmacological relevance Ophiopogonis Radix (Maidong in Chinese), the root of Ophiopogon japonicus , is widely used in local medicines of China, Japan and some south-eastern Asian countries. According to the traditional Chinese medicine (TCM) principle, Ophiopogonis Radix nourishes the yin , promotes body fluid production, moistens the lung, eases the mind and clears away heart fire. This review summarizes the achievements of the investigations in botany, phytochemistry, quality control, traditional uses, pharmacological activities and clinical studies on O. japonicus ; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. Materials and methods O. japonicus -related information was collected from various resources, including books on Chinese herbs and the Internet databases, such as Google Scholar, SciFinder, Web of Science, Elsevier, ACS, PubMed and China Knowledge Resource Integrated (CNKI). Results O. japonicus is widely distributed in East Asia, especially in China. Numerous compounds were identified from this plant. The main components of O. japonicus include steroidal saponins, homoisoflavonoids and polysaccharides, which exhibited various pharmacological activities, such as cardiovascular protection, anti-inflammation, anticancer, anti-oxidation, immunomodulation, cough relief, antimicrobial, and anti-diabetes. Conclusions O. japonicus is a common traditional Chinese herbal drug used as the main ingredient in many prescriptions. Modern researches verified that O. japonicus can be used either as a healthy food or a therapeutic agent for disease prevention and treatment. The molecular mechanisms and chemical principles of this herbal medicine should be further explored.

Neurotransmitter-controlled Cl- secretions play an important role in maintenance of the epididymal microenvironment for sperm maturation. This study was carried out to investigate the effect of carbachol (CCH) on the cultured rat epididymal epithelium and the signal transduction mechanisms of this response. In normal K-H solution, CCH added basolaterally elicited a biphasic Isc response consisting of a transient spike followed by a second sustained response. Ca2+ activated Cl- channel blocker disulfonic acid stilbene (DIDS, 300 microM) only inhibited part of the CCH-induced Isc response, while nonselective Cl- channel blocker diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced all, indicating the involvement of different conductance pathways. Both peaks of the CCH-induced Isc response could be significantly inhibited by pretreatment with an adenylate cyclase inhibitor, MDL12330A (50 microM). An increase in intracellular cAMP content upon stimulation of CCH was measured. All of the initial peak and part of the second peak could be inhibited by pretreatment with Ca2+-chelating agent BAPTA/AM (50 microM) and an endoplasmic reticulum Ca2+ pump inhibitor, Thapsigagin (Tg, 1 microM). In a whole-cell patch clamp experiment, CCH induced an inward current in the single cell. Two different profiles of currents were found; the first component current exhibited an outward rectifying I-V relationship in a time and voltage-dependent manner, and the current followed showed a linear I-V relationship. The carbachol-induced current was found to be partially blockable by DIDS and could be completely blocked by DPC. The above results indicate that the CCH-induced Cl- secretion could be mediated by Ca2+ and cAMP-dependent regulatory pathways.

Snake envenoming in pregnancy may cause fetal death and maternal mortality or morbidity. However little is known about the toxic effects and optimal management of snake envenoming because of the rarity of cases. We report three cases in Taiwan in the past 15 years of pregnant women who were treated successfully after being bitten by Trimeresurus stejnegeri with local envenoming. Two of the three patients received treatment with equine-derived hemotoxic bivalent F(ab)/2 antivenom without development of any adverse effects. All three women recovered uneventfully and subsequently had normal deliveries. Telephone follow-up of the three children 6-10 years later showed no developmental delay of the children. (authors)

A 74-year-old woman presented to the emergency department with acute onset of pallor, pain and numbness over her left hand. She had a history of right hemicolectomy for colon cancer. There was no history of trauma or recent fever. On examination, paleness, coldness and weak pulses were noted along the ulnar side of her left forearm and hand (Figure 1A). Radial artery pulses at the wrist were normal. The neurologic …

Rhabdophis tigrinus is a common colubrid snake that can be found in an extensive geographical region in East Asia. It consists of two subspecies: R.t. tigrinus (yamakagashi) and R.t. formosanus (Taiwan tiger keelback). R. tigrinus possesses two different sets of poisonous glands: the Duvernoy's glands in the maxilla, and the nuchal glands in the dorsal skin of the neck. We report the first case in current English literature of toxin ophthalmia caused by the nuchal gland secretion of R.t. formosanus. The patient was a 40-year-old man whose right eye was sprayed by the nuchal gland fluid of R.t. formosanus. He presented with symptoms of foreign body sensation, progressive burning pain, and blurred vision. Ophthalmologic examination revealed diffuse superficial punctate keratitis, corneal stromal edema with Descemet folds, and conjunctival congestion. The patient responded well to topical treatment with a corticosteroid, antihistamine, and antibiotic, and had a favorable clinical course and outcome.

Summary Objective To retrospectively investigate the 10-year experience of prenatal diagnosis of fetal chromosome aberrations by second-trimester amniocentesis. Methods Data were collected at Taichung Veterans General Hospital between 1995 and 2004 from cytogenetic analyses of cultured amniocytes from second-trimester amniocentesis. The main indications for amniocentesis included advanced maternal age, abnormal maternal serum screening results, and abnormal ultrasound findings. Chromosome aberrations included autosomal aneuploidies, sex chromosome aneuploidies, polyploidies, and rearrangements. Variant chromosomes were considered to be normal and excluded. Results A total of 7,028 amniocenteses were performed and analyzed for chromosome aberrations. Among these, 4,026 (57.29%) were for advanced maternal age, 1,500 (21.34%) for abnormal maternal serum screening results, 553 (7.87%) for abnormal ultrasound findings, and 949 (13.50%) for other reasons. The highest detection rate of chromosome aberrations was in cases undergoing amniocentesis for abnormal ultrasound findings (8.86%), followed by other reasons (2.74%), abnormal maternal serum screening results (2.60%), and advanced maternal age (2.31%). Chromosome aberrations were detected in 207 cases (2.90%), including fetuses of 93 older mothers, 39 mothers with abnormal serum screening results, 49 mothers with abnormal ultrasound findings, and 26 mothers with other reasons for amniocentesis. Of fetuses with chromosome aberrations, 144 (69.56%) had trisomy 13, trisomy 18, trisomy 21, or sex chromosome disorder. The other 63 cases (30.44%) included balanced translocation, unbalanced abnormality, inversion, and marker chromosome. Conclusion For daily practice, our data could offer a database for proper genetic counseling, such as termination issues and future pregnancies.

The aim of our present study was to investigate the short-circuit current response to carbachol in cultured rat cauda epididymal epithelia and the signal transduction mechanisms involved. Carbachol added basolaterally induced a concentration-dependent increase in short-circuit current (Isc) across the epididymal epithelium consisting of a rapidly rising phase and a long term sustained response. The response was almost abolished by removing Cl(-) from the extracellular medium and blockable by pretreating the tissues with DPC, indicating a substantial contribution of Cl(-) secretion to the carbachol-induced response. The muscarinic acetylcholine receptor antagonist atropine inhibited the response, but the nicotinic acetylcholine receptors antagonist curarine had no effect, suggesting that only the muscarinic acetylcholine receptors mediated the secretory response of the basolateral side of rat cauda epididymal epithelium to carbachol. Addition of carbachol to the apical side of the tissue was found not to elicit an Isc response. These results suggested that muscarinic receptors are present in the basolateral side of rat cauda epididymal epithelium. Activation of these receptors by acetylcholine released from the nerve endings regulates epididymal transepithelial Cl(-) secretion. Cholinergic stimulation therefore contributes to the formation of luminal fluid microenvironment.

Hybrid Swiss virgin mice (Kuan-min strain) were challenged intravaginally with uv-inactivated herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) twice a week for 16 times and subsequently with croton oil or control medium twice a week for 27 times. After a period of 180 days the exposure to HSV-2 plus control medium induced premalignant and malignant lesions of the cervix and vagina in 50.0% of the mice. The exposure to HSV-2 plus croton oil induced similar lesions in 78.2% of the mice. The exposure to HSV-1 combined with either control medium or croton oil induced lesions in 37.2 and 58.3% of the mice, respectively. No malignant lesions were found in the control mice. These results reveal that (1) HSV-1 and HSV-2 have a similar oncogenic potential, and (2) croton oil can promote the induction of cervical and vaginal cancers with HSV-1 and HSV-2. Additionally, these results suggest that the virus-induced carcinogenesis of cervix and vagina might be similar to the classical two-stage carcinogenesis model. This animal model seems to be more suitable for studying the prevention and treatment of cervical and vaginal cancers because the period of this experiment is significantly shorter than that of experiments reported by other investigators and the frequency of the malignant lesion is significantly higher than or similar to that of the same lesion reported in other experiments.

Crotaline snakebites (Protobothrops mucrosquamatus and Trimeresurus stejnegeri) are a common medical emergency in Taiwan that can be effectively treated by a bivalent F(ab’)2 antivenom. We investigated the differences in the clinical outcomes of patients who received different therapeutic regimens of antivenom in a medical center where clinical toxicologists followed the poison control center (PCC) guidelines (medical group) and surgeons did not (surgical group). The medical records of inpatients with crotaline snakebites between 1991 and 2005 were reviewed and information on demographics, treatments, adverse effects of antivenom, and complications was abstracted and analyzed. A total of 179 patients (90 medical, 89 surgical) were eligible for study. There was no significant intergroup difference in baseline characteristics except that the dose of antivenom and the probability of antibiotic use were both higher in the surgical group (5.9 ± 4.2 vials vs. 2.7 ± 1.6 vials; 93% vs. 60%). Multiple logistic regression adjusting for age, gender, calendar year of envenomation, severity of envenomation, and antibiotic use did not disclose evidence of any difference in various clinical outcomes between medical and surgical patients. The lower dose of antivenom recommended by the PCC may be as effective and safe as the higher dose used in the surgical group for the treatment of crotaline snakebites. [J Formos Med Assoc 2007;106(12):1057–1062]

Background To evaluate the clinical association of extrastructurally abnormal chromosomes (ESACs) with pregnancy outcome based on the cytogenetic characteristics of the ESACs. Methods We retrospectively reviewed 12 ESAC cases identified from 12,991 cases who received genetic amniocentesis between January 1983 and March 2008. Prenatal ultrasound findings, characteristics of ESACs (karyotypes, special features, origin, inheritance) and pregnancy outcomes were recorded. Results The prenatal prevalence of ESACs was 0.092% (12/12,991). Of the 12 ESAC cases, all were de novo . Seven (58.3%) originated from nonacrocentric chromosomes and the other 5 (41.7%) were from acrocentric chromosomes, with 3 originating from chromosome 15. Six of the 12 cases (50%) were large ESACs; however, the other 6 (50%) were medium to small ESACs. All acrocentric ESACs contained dicentric and bisatellite characteristics. Using FISH and SKY techniques, the origins of 2 cases (patients 10 and 12) were clearly identified to be from chromosomes 15 and 10, respectively. Five of the 12 ESAC cases (41.7%) had congenital anomalies found by prenatal ultrasound. All were nonacrocentric in origin that were medium (1/5) to large (4/5) in size. After prenatal genetic counseling, 8 of the 12 (66.7%) couples opted to terminate the pregnancy. The other 4 (33.3%) continued the pregnancy and their babies were delivered at term normally and were followed-up, with normal development ranging from 2 to 17 years. Conclusion With sophisticated cytogenetic characterization and ultrasound examination, it is possible to precisely categorize most fetuses with ESACs as being either at high risk of abnormality or at a relatively low risk.