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Short-term calorie reduction (SCR) requires individuals to reduce their calorie intake to less than 50% of normal requirements and has shown good tolerance and potential benefits in prior studies addressing gynecological cancer patients. More studies are needed to further confirm its safety, feasibility, and effects in patients with different cancers, including hematological malignancies. This pilot cohort study with a matched-pair comparison group was registered at ClinicalTrails.gov [201810112RIND]. Adult patients diagnosed with advanced-stage diffuse large-B cell lymphoma were recruited (SCR group) and matched with one comparison patient (comparison group), each in a manner blinded to their outcomes. The SCR group undertook at least two cycles of 48 h water fast along with their chemotherapy R-CHOP. Descriptive analysis and generalized estimating equations were used to analyze the data. Six participants completed multiple cycles of SCR and were compared to their six counterparts in the comparison group. The results showed that SCR is safe and feasible in terms of a high compliance rate and stable nutritional status. The SCR was associated with benefits in post-chemotherapy hematological parameters (i.e., erythrocyte [p &lt, 0.001] and lymphocyte counts [p &lt, 0.001]). More randomized controlled trials are needed to validate the effects of SCR on different types of cancer populations.

Background Sliding-scale insulin has been widely used in treating inpatient hyperglycemia. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and possible adverse effects of sliding-scale insulin in hospitalized patients. Methods PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov registry were searched for studies published up to May 2015. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size using random effects models. Results Eleven RCTs containing a total of 1322 patients were identified. Among eight studies in which the RISS was compared with other regimens, no significant difference was observed in the percentage of patients who achieved the mean blood glucose level between the two groups, which was determined according to the numbers of blood samples (RR: 2.84; 95% CI: 0.94 to 8.59) and patients (RR: 1.75; 95% CI: 0.86 to 3.55). The mean blood glucose level (weighted mean difference = 27.33, 95% CI: 14.74 to 39.92) and incidence of hyperglycemic events were significantly higher in the RISS group than in the non-sliding-scale group. No significant difference in the incidence of severe hypoglycemia and length of hospitalization between the groups was identified. Conclusions The overall results of the meta-analysis indicated that applying the RISS alone or in combination with other antidiabetic medications did not provide any benefits in blood glucose control, but was accompanied by an increased incidence of hyperglycemic events. Therefore, we suggest that the use of sliding-scale insulin be discontinued in hospitals.

Children are more susceptible to medication errors because of differences in pharmacokinetics and pharmacodynamics compared to adults. Weight changes are common with growth in children and computer systems frequently are not updated with current information, which result in inaccurate weight-based dosing and thus harm children. This study evaluated the impact of a Computerized Physician Order Entry system with standardized pediatric dosing decision support (PDDS) function on reducing pediatric dosing errors. Outpatient prescriptions were analyzed from January to March during 2010 and 2011. The total number of pediatric prescriptions was 72,431 and 80,532 prior to and after system implementation, respectively. Out of 72,431 prescriptions, 1617 (2.23%) dosing errors were retrospectively detected by the system, whereas 15 dosing errors (0.02%) were detected by pharmacists prior to system implementation. Incorporating the system into practice resulted in a total of 210 successfully blocked dosing near misses, including 14 potentially fatal and 11 serious near misses. The final dosing error rate was significantly reduced from 2.23% to 0.66% (p

Asthma is one of the commonest causes of morbidity and mortality in childhood. The goals of the present study were to design a valid medication assessment tool for evaluating the quality of medication use according to recommendations of updated asthma guidelines for children aged from 5 to 12 years, and to quantify adherence to guideline recommendations.Two primary care settings in Scotland, UK.Recommendations related to the long-term management of asthmatic children in the British Thoracic Society/Scottish Intercollegiate Guidelines Network and Global Initiative for Asthma guidelines were identified and corresponding criteria were created. These criteria were incorporated to generate an assessment tool named MAT ASTHMA-PAED. Two phases of field-testing were undertaken and the tool was also subject to examination by a focus group of specialist practitioners. Thereafter, MAT ASTHMA-PAED was modified accordingly.Applicability and adherence to each criterion and overall adherence to the MAT ASTHMA-PAED.The MAT ASTHMA-PAED field-testing was undertaken in two primary care practices in Scotland, United Kingdom and 77 asthmatic children were recruited. Results of the pilot study field-testing showed a high overall adherence of 70.0 % (95 % CI: 58.7-81.3 %) to the guidelines. Low adherence (50 %) was seen for 4 criteria, whereas 8 criteria were considered high-adherence criteria (70 %). The final MAT ASTHMA-PAED comprised of 25 criteria was produced based on the results of field testing and the opinions from the focus group.Although high utility of MAT ASTHMA-PAED criteria was found, there were gaps in the implementation of certain recommendations, particularly in relation to demonstrated satisfactory technique of inhaler. Moreover, further studies assessing the use of oral steroids and exercise-induced asthma, and wider implementation of MAT ASTHMA-PAED are required.

Background: Taiwan has separated drug prescribing and drug dispensing services since 1997. Because of this, patients with chronic illness as well as those with diseases that have a relatively stable status may have their prescriptions refilled in nearby clinic pharmacies without having to go to hospitals. Methods: Shuang-Ho Hospital in Taipei, Taiwan, implemented a drive-through pharmacy service as a more convenient refilling system to provide patients in need with a more effective way to refill their prescriptions. To assess the efficacy of this new refilling system, changes in patient drug prescription behavior were compared 6 months before and 6 months after the system was deployed. Results: We found an increase in the overall refilling prescription rate, with an increased use of online reservations (7.9% vs. 4.9%, p

SummaryObjectiveThe aim of this study was to evaluate the reversible factors that could possibly affect outcomes of anti-tuberculosis (anti-TB) treatment.MethodsA retrospective observational nested case–control study was performed to evaluate the association of patient and clinical factors with anti-TB therapy outcomes as defined by the World Health Organization (WHO).ResultsTo examine the impact of a variety of factors on the outcomes of anti-TB treatment, a total of 302 TB patients were included in the study. Univariate analysis revealed that age, gender, concurrent hypertension, asthma/chronic obstructive pulmonary disease, or liver disease, worsened baseline blood urea nitrogen or creatinine, ethambutol 20 cigarettes per day) was significantly associated with a decreased odds of cure or treatment completion (odds ratio 0.23, 95% confidence interval 0.05–0.98, p=0.047).ConclusionsAs smoking significantly inhibits the effectiveness of TB treatment, the integration of smoking cessation into TB treatment programs is strongly advocated to reduce the dual global burden of smoking and TB.

Breakthrough pain (BTP) has been defined as a transient exacerbation of pain that occurs to patients with otherwise stable baseline persistent pain. It is one of the most prevalent and formidable symptoms cancer patients have to face which can be classified into 4 types: predictable incident pain, unpredictable incident pain, idiopathic pain, and end-of-dose pain. Because of the characteristics of BTP, its management should be based on a consistent definition and thorough assessment including the determination of intensity, quality, duration, and other factors related to current treatment and so on. Medical treatment aims at reducing the frequency and intensity of BTP. Medication effectiveness should be sufficient for patients’ daily living activities, and devoid of side effects, dependence or drug–drug interactions. BTP should be clearly distinguished from chronic pain. Clinicians should be capable of using assessment tools for further identification and individual management. It is worth probing into these issues further in Taiwan from the aspects of different races, cancer types, and disease stages to evaluate the quality of patients’ pain control during and after cancer therapy and to develop appropriate local management and guidelines.

Background/Purpose The aim of this study was to assess the long-term effect of pharmacy interventions on patients and health care providers, and switching from prescribing extemporaneous powder dosage forms to liquid dosage forms. Methods An education program for parents was conducted. An attitude, knowledge and behavior questionnaire was employed to measure the efficacy of the education program. Medication management policies were then executed by providing an in-service to pediatricians, establishing dosage-switching guidelines and adding liquid dosage forms of necessary medications into the hospital formulary. Dosage-switching guidelines of pediatric medications were established by surveying the most prescribed extemporaneous powder dosage forms at the Taipei Medical University–Wan Fang Hospital. These guidelines were introduced to every pediatrician, nurse and pharmacist. The prescribing rate of extemporaneous powder prescriptions was monitored to measure the outcomes of the interventions. Results The mean scores of attitude, knowledge and practice significantly improved towards a positive use of commercially available liquid medications after the patient education program for the parents. Prescriptions for extemporaneous powder dosage forms significantly decreased from 1600 (2.54%) to 13 (0.022%) monthly in the 4 th year and were reduced to zero in the 6 th year. Conclusion This study demonstrated that the pharmacists' interventions were able to change the parents' knowledge, attitude and practice towards pediatric drug dosage forms and the prescribing pattern. Effective assurance in children's medication safety can be achieved through collaboration between medical professionals and parents.

Purpose The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects. Materials and Methods Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into ≤ 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay. Results IGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women ≤ 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 ± 0.039404) than men of same age group (0.228326 ± 0.050979, p < 0.01) and women ≤ 50 years (0.247667 ± 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women. Conclusions The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.

To study the efficacy of vagus nerve stimulation (VNS) therapy as an adjunctive treatment for intractable epilepsy in patients under 12 years of age, we analyzed 2-year postimplant data of 35 consecutive patients. Of the 35 patients, 18 (51.4%) at 6 months, 18 (51.4%) at 12 months, and 21 (60.1%) at 24 months showed ≥50% reduction in seizure frequency (responders). Although incremental seizure freedom was noted, no patient remained seizure-free throughout the 3 study periods. Partial response (≥50% seizure reduction in 2 or less study periods) was seen in 8 (22.9%) patients. Twelve patients (34.3%) were nonresponders. Out of 29 patients with primary generalized epilepsy, 20 (68.9%) and, out of 6 patients with focal epilepsy, 3 (50%) had ≥50% seizure control in at least one study period. No major complications or side effects requiring discontinuation of VNS therapy were encountered. We conclude that (1) patients with intractable primary generalized epilepsy respond better to VNS therapy, (2) cumulative effect of neuromodulation with improving responder rate to seizure freedom with continuation of VNS therapy is noted, and (3) VNS therapy is safe and is well tolerated in children receiving implant under 12 years of age.

SummaryBackground Recombinant human thyrotropin (rhTSH) can be used to enhance radioiodine therapy for shrinking multinodular goitre. The aim of this meta-analysis was to compare the effectiveness of rhTSH pretreatment and radioiodine therapy with that of radioiodine alone for treating benign nodular goitre. Methods The PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov databases were searched to identify studies published before September 2014. A meta-analysis was performed to calculate the pooled effect size using random-effects models. The primary outcome was the reduction in thyroid volume. Secondary outcomes included thyroid function, extent of tracheal compression, radioactive iodine uptake, incidence of hypothyroidism and other complications. Results Nine RCTs including 416 patients were selected. The reductions in thyroid volume were significantly greater in the rhTSH pretreatment groups than those in the radioiodine alone groups at 12 months (weighted mean difference: 14·42%; 95% CI: 4·51–24·34% in high-dose rhTSH vs radioiodine alone; weighted mean difference: 19·66%; 95% CI: 3·67–35·65% in low-dose rhTSH vs radioiodine alone). The incidence of hypothyroidism in the high-dose rhTSH groups was significantly higher than that in the radioiodine alone groups. No significant difference in the incidence of hypothyroidism occurred between the low-dose rhTSH groups and the radioiodine alone groups. Conclusions The overall results indicated that using rhTSH before radioiodine therapy resulted in a greater thyroid volume reduction than radioiodine therapy alone. An increased incidence of hypothyroidism was observed in patients receiving high-dose rhTSH. Low-dose rhTSH before radioiodine therapy is more efficacious than radioiodine therapy alone for treating nontoxic benign thyroid nodules.

Objectives Although zolpidem is listed as a controlled drug in Taiwan, patients' behavior has not been restricted and has led to the problem of doctor shopping behavior (DSB), leading to overutilization of medical resources and excess spending. The National Health Insurance Administration in Taiwan has instituted a new policy to regulate physicians' prescribing behavior and decrease DSB. This retrospective study aimed to analyze the DSB for zolpidem by insomnia patients and assess related factors. Design and participants Data were extracted from the Longitudinal Health Insurance Database in Taiwan. Individuals with a diagnosis of insomnia who received more than one prescription of zolpidem in 2008 were followed for 24 mo. Doctor shopping was defined as ≥ 2 prescriptions by different doctors within ≥ 1 day overlapping in the duration of therapy. The percentage of zolpidem obtained through doctor shopping was used as an indicator of the DSB of each patient. Results Among the 6,947 insomnia patients who were prescribed zolpidem, 1,652 exhibited DSB (23.78%). The average dose of zolpidem dispensed for each patient during 24 mo was 244.21 daily defined doses. The doctor shopping indicator (DSI) was 0.20 (standard deviation, 0.23) among patients with DSB. Younger age, chronic diseases, high number of diseases, higher premium status, high socioeconomic status, and fewer people served per practicing physicians were all factors significantly related to doctor shopping behavior. Conclusion Doctor shopping for zolpidem appears to be an important issue in Taiwan. Implementing a proper referral system with efficient data exchange by physician or pharmacist-led medication reconciliation process might reduce DSB.

An efficient and scalable method is reported for the isolation of costatolide (2), a naturally-occurring and HIV-1-specific non-nucleoside reverse transcriptase inhibitor, from the latex of Calophyllum teysmannii Miq. var. inophylloide (King.) P. F. Stevens (Clusiaceae). An overall yield of 10.6% of costatolide (2), with a purity of 96%, was obtained by repetitive recrystallization of the latex from a single organic solvent, subsequent to the pre-treatment of latex with hexane and dichloromethane to remove undesirable oily material. A second major component of the latex, soulattrolide (3), another HIV-1 non-nucleoside reverse transcriptase inhibitor, was also isolated. Both compounds were characterized by spectroscopic and chromatographic analyses and their in vitro anti-HIV activities were also confirmed. The results suggest that sufficient quantities of costatolide for preclinical and clinical development can be obtained in a relatively low-cost manner from the natural source.

Robustaflavone, a naturally occurring biflavanoid isolated from Rhus succedanea , was found to be a potent inhibitor of hepatitis B virus (HBV) replication in 2.2.15 cells, with an effective concentration (EC 50 ) of 0.25 μ M, and a selectivity index (SI, IC 50 /EC 90 ) of 153. Robustaflavone hexaacetate inhibited HBV replication with an EC 50 of 0.73 μ M, but exhibited no cytotoxicity at concentrations up to 1000 μ M. Combinations of robustaflavone with penciclovir and lamivudine displayed synergistic anti-HBV activity, having the most pronounced effects when the combination ratios were similar to the ratio of EC 50 potencies. Thus, a 1:1 combination of robustaflavone and penciclovir exhibited an EC 50 of 0.11 μ M and an SI of 684, while a 10:1 combination of robustaflavone and lamivudine exhibited an EC 50 of 0.054 μ M and an SI of 894. Statistical analyses of the combination data using the Combostat® program confirmed that robustaflavone exhibited synergism with both penciclovir and lamivudine.

To establish efficacy of vagus nerve stimulation (VNS) therapy in the treatment of intractable epilepsy, we compared outcome data from the baseline period to the maintenance period (7 to 24 months post-implant) by calculating the mean seizure frequency at 6-month intervals (7 to 12 months - first study period, 13 to 18 months - second study period, and 19 to 24 months - third study period), in 39 consecutive patients on unchanged antiepilepsy drug (AED) regimen for 24 months following the VNS implant. Of the 39 patients24 (61.5%) at first study period, 25 (64.1 %) at second study period and 25 (64.1 %) at third study period were responders (≥50% reduction in seizures). Twenty one (53.9 %) patients were responders in all three study periods. Incremental seizure control was seen in 15 of these 21 patients. Although 3 (7.7%), 4 (10.3 %) and 8 (20.5%) patients had a total (100%) seizure control at first, second and third study periods respectively, no patient remained seizure-free through all 3 study periods. Seven (17.9%) patients were partial responders (≥ 50% seizure reduction in two or less study periods). Eleven patients (28.2%) were non-responders (< 50% seizure reduction in all 3 study periods). Twenty three patients (59%) had partial epilepsy with and without secondarily generalization and 16 patients (41%) had primary generalized epilepsy. Eleven (47.8%) of the 23 patients with partial epilepsy and 10 (62.5%) of the 16 patients with generalized epilepsy were responders in all three study periods. We conclude that: 1) More than 60 % of patients on unchanged AED regimen continued to be responders at 24 months following the VNS implant. 2) A trend towards increasing responder rate with increasing duration of VNS therapy was observed.3) No major complications or side effects requiring discontinuation of VNS therapy were noted.

Robustaflavone, a naturally occurring biflavanoid isolated from the seed kernel extract of Rhus succedanea, was found to be a potent in vitro inhibitor of hepatitis B, with an effective concentration (EC50) of 0.25 μM and an in vitro selectivity index ( IC 50 EC 90 ) of 153. Further studies suggested that inhibition of HBV DNA polymerase is the mechanism of action.

According to Taiwan Department of Health and World Health Organization statistics, hepatic tumors are the second leading cause of death from malignant disease in Taiwan, with 600,000 deaths from HBV (hepatitis B virus ) infected complication annually. Hepatitis B virus infection is thus an important issue in public health policy.The aims of this study were to investigate hepatitis B knowledge and screening behavior and then identify significant prediction factors of hepatitis B screening behavior.A cross-sectional survey and convenience sampling were used to investigate 282 outpatients at the one target hospital. Descriptive statistics, independent t test, one-way ANOVA, Spearman relation, and multiple regression were used to analyze impact factors.Slightly over half (55.7%) of the participants had received HBV screening. The average hepatitis B knowledge score was 9.38, with an average correct rate of 72.2%."Whether friends and relatives suffer from hepatitis B", "knowledge of hepatitis B", "perceived barriers to action", and "cue for action" explained 12.3% of total variance. Of these, "perceived barriers of action" was the most important predictor of hepatitis B screening behavior.Although participant knowledge of hepatitis B was relatively good, the screening rate was less than ideal. Results point to "perceived barriers of action" as a key factor affecting screening behavior. We suggest establishing an independent outpatient service to offer screening for hepatitis B in order to reduce waiting time and provide greater convenience. We also suggest the implementation of a policy to unify charges to raise public motivation to undergo screening.探討某醫療機構之門診民眾對B型肝炎的認知及其篩檢行為的影響因素2011年衛生署資料顯示，肝癌位居國人癌症死因第二位，世界衛生組織也指出每年約有60萬人死於B肝病毒感染的相關合併症，由國內外現況可知B肝病毒感染是不容忽視的公共衛生議題。了解民眾對B型肝炎的認知程度與執行篩檢之現況、並探討影響民眾執行B型肝炎篩檢行為的相關因素。以方便取樣方式、選取282位門診民眾為對象，以描述性統計、獨立t檢定、單因子變異數分析、Spearman相關及複迴歸分析等方法分析。55.7%民眾曾接受過篩檢且B型肝炎認知之平均得分為9.38、總平均答對率72.2%；而「親友是否罹患肝炎」、「B型肝炎認知」、「障礙性認知」及「行動線索」等變項對於篩檢行為的解釋力為12.3%，其中「障礙性認知」為最重要的預測因子。民眾B型肝炎認知有中上程度，但篩檢率不盡理想，結果發現「障礙性認知」是影響篩檢行為的關鍵因素，故建議未來可設立獨立門診進行有關B型肝炎篩檢的服務，減少民眾候診時間、增加便利性，也建議政策單位將篩檢費用列入考量，以提升民眾篩檢行為的動力。

Background Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are common allergic diseases. Environmental factors were indicated to influence the development of allergic diseases. Objective To evaluate the correlation between the month of birth and the prevalence of allergic diseases in Taiwan. Methods Data from 104,455 children were collected from the National Insurance Research Database of Taiwan. Subjects were identified by at least two service claims for ambulatory care or one claim for inpatient care. All of the enrolled patients were aged 7∼15 years in 2010. In a bio-clinical data analysis, total immunoglobulin E (IgE) and ImmunoCAP™ allergen data (CAP) from mothers and infants were collected in a medical center in Taiwan. Correlations between children's allergic factors and the season of birth were assessed. Results A significant difference in the prevalence of BA according to the month of birth (Χ2 = 18.2, p

Summary Background The use of a vancomycin dosing nomogram is an alternative and more cost-effective method to conventional dosing; it reliably allows the achievement of trough vancomycin serum concentrations of 5–15mg/l, with a successful clinical response. Recent guidelines have further recommended that the trough concentration be maintained at 15–20mg/l for complicated infections. However, to date no published nomogram has been constructed to achieve the optimal trough of 15–20mg/l in an Asian population. This study aimed to develop two vancomycin nomograms for the achievement of trough concentrations of 5–15mg/l and 15–20mg/l in the Taiwanese population, and to ensure the clinical efficacy and safety of such nomograms. Methods The estimated concentrations and the real concentrations in our patient population were compared between six pharmacokinetic models to see which was the most precise. As the Ambrose method was the best at predicting the trough, this was used to create two nomograms, one for a target trough at 5–15mg/l and the other for a target trough at 15–20mg/l. We then evaluated the nomograms by analyzing the number of patients with the target vancomycin trough concentration, clinical and microbiological outcomes, and safety. Results More patients who had dosing according to the nomogram had a vancomycin trough concentration within the desired target range than patients who had conventional dosing (65.1% vs. 32.1%, p = 0.001). These patients also had a higher rate of ‘cure' as the clinical response (35.7% vs. 27.1%) and ‘eradication' as the microbiological response (46.4% vs. 29.2%), and a lower rate of nephrotoxicity (14.3% vs. 22.9%). For the patients with a complicated infection, more had a trough between 15 and 20mg/l when vancomycin was dosed with the nomogram than when dosed conventionally (41.2% vs. 12.1%, p = 0.019). Conclusions We found that when dosing vancomycin with these nomograms, patients tended to have vancomycin trough concentrations within the target range and also to have a better outcome with regard to clinical efficacy and the safety profile.

Objective A pharmacist-managed antibiotic intravenous to oral (i.v.-top. o.) conversion program has been incorporated to minimize unnecessary i.v. antibiotic usage. This study evaluated the clinical and economical impacts of a pharmacist-directed i.v.-to-p.o. conversion program for levofloxacin in Taiwan. Methods Data was retrospectively collected by chart review during the pre-intervention period (PIP). During the intervention proactive conversion period (PCP), pharmacists reviewed and intervened on all levofloxacin orders. The detailed reimbursements for medications and inpatient expenses from the Bureau of National Health Insurance (NHI), Taiwan were calculated. The clinical impacts during the PIP and PCP were compared with the duration of the i.v. levofloxacin therapy, total used i.v./p.o. ratio levofloxacin, and total length of hospital stay. The financial impact was compared with medication costs and total inpatient expenditures. Results The mean length of hospital stay was significantly decreased from 27.2 days to 16.1 days (p = 0.001) after the conversion program was implemented. The i.v. over p.o. ratio for DDD was 3.0 ± 0.6 vs. 2.1 ± 0.6 for PIP vs. PCP group (p = 0.032). The cost of the levofloxacin was significantly decreased ($ 568.9 ± 262.9 vs. $ 449.0 ± 266.4, PIP vs. PCP, p = 0.044). The total inpatient expenditures were also significantly reduced ($ 6,096 ± 5,164.0 vs. $ 3,649.6 ± 3, 740.4, PIP vs. PCP, p = 0.017). Conclusions The pharmacist-managed i.v.-to-p.o. conversion service not only decreased the length of hospital stays, but also produced significant cost savings, both on medication costs and the total inpatient expenditures. This represents strong evidence for implementing the i.v.-to-p.o. conversion service in Taiwan.

You-Meei Lin1, Jui-Yu Wu2, Ying-Chen Chen3, Yu-Der Su3, Wen-Tin Ke3, Hsiu-O Ho31Department of Pharmacy, Shuang Ho Hospital, 2Department of Biochemistry, School of Medicine, 3School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROCObjectives: In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized.Methods: SMEDDS formulated with Myritol® and surfactant mixture (Smix) of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween® 20 (A, C, E, G, M, S, N, T, O) or Tween® 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G-V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study.Results: FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor® was enhanced by about 1.14-1.22-fold.Conclusion: SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.Keywords: SMEDDS, fenofibrate, microemulsion, dissolution, TPGS

A series of naturally occurring and synthetic biflavonoids was evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv (Mtb). Compounds 6, 24, and 25 demonstrated 96, 95, and 87% inhibition, respectively, at a screening concentration of 12.5 μg/mL. The type of linkage and the presence of methoxy- and nitro-substituents in biflavonoids may contribute to the observed inhibitory activity. The results of this study represent the discovery of biflavonoids as a potential new class of antituberculosis agent.

Color reversion in soybean oil can be prevented by reducting the enzyme activity of soybeans before cracking and flaking. Soybean oil extracted from steamed, intact soybeans (18% moisture) had lower Rm (max. red) values in RBD oil, higher amounts of γ-tocopherol, plus its isomers, in both crude and RBD oil, and also higher amounts of hydratable phosphatides in crude oil than those in the oils from the same beans without steam treatment. For soybean pretreatments, a toasting process is less effective than the steaming process for the inhibition of color reversion of soybean oil. To prevent the occurrence of color reversion in RBD soybean oil, the amount of γ-tocopherol and γ-TED (5-[tocopheryloxy]-γ-tocopherol) should be above 550 ppm in crude oil.

Nanoliposomes are useful carriers in drug delivery. Radiolabeled nanoliposomes have potential applications in radiotherapy and diagnostic imaging. In this study, the biodistribution and pharmacokinetics of 188Re-BMEDA-labelled pegylated liposomes (RBLPL) and unencapsulated 188Re-BMEDA administered by the i.v. route in murine C26-colon tumour-bearing mice were investigated. MicroSPECT/CT images were performed to evaluate the distribution and tumor targeting of RBLPL in mice. For the biodistribution study, the highest uptake of liposome in tumors was 3.62% +/- 0.73% at 24 h after RBLPL administration, and the tumor to muscle ratio of RBLPL was 7.1-fold higher than that of 188Re-BMEDA. With image analysis, the highest SUV in tumor was 2.81 +/- 0.26 at 24 h after injection of RBLPL. The Pearson correlation analysis showed a positive correlation of tumor targeting or uptake of RBLPL between biodistribution and microSPECT semi-quantification imaging analysis (r = 0.633). The results of the pharmacokinetics revealed that the area under the tissue concentration-time curve (AUC) of RBLPL was 4.7-fold higher than that of unencapsulated 188Re-BMEDA. These results suggested the potential benefit and advantage of 188Re-labeled nanoliposomes for imaging and treatment of malignant diseases.

Neonatal screening for hyperphenylalaninemia (HPA) has been performed in Taiwan for more than 20 years. In this paper, we studied 21 cases of HPA caused by phenylalanine hydroxylase (PAH) deficiency. These patients were detected by a single newborn screening center over ten-years, and the incidence was one in 63,690. According to the initial plasma phenylalanine levels, four of the 21 patients belonged to classical phenylketonuria (PKU), seven were mild PKU, and ten were mild HPA. They commenced diet control at the age of 47 +/- 22 (17-106) days. Fourteen patients completed IQ tests, three of the 14 patients having classical PKU, five having mild PKU, and six having mild HPA. Their average IQ scores were within normal ranges (full-scale IQ 98 +/- 14, verbal IQ 92 +/- 8, and performance IQ 104 +/- 19), but patients with classical PKU tended to have lower IQ scores than other patients. Since classical PKU is rare in Taiwan, further studies including detailed neuropsychological tests will be required to evaluate the effect of treatment in this group of patients.

Naturally occurring anti-HIV-1 agent (+)-calanolide A was found to be active against all of the strains of Mycobacterium tuberculosis tested, including those resistant to the standard antitubercular drugs. Efficacy evaluations in macrophages revealed that (+)-calanolide A significantly inhibited intracellular replication of M. tuberculosis H37Rv at concentrations below the MIC observed in vitro. Preliminary mechanistic studies indicated that (+)-calanolide A rapidly inhibits RNA and DNA synthesis followed by an inhibition of protein synthesis. Compared with known inhibitors, this scenario is more similar to effects observed with rifampin, an inhibitor of RNA synthesis. Since (+)-calanolide A was active against a rifampin-resistant strain, it is believed that these two agents may involve different targets. (+)-Calanolide A and its related pyranocoumarins are the first class of compounds identified to possess antimycobacterial and antiretroviral activities, representing a new pharmacophore for anti-TB activity.

Ornithine transcarbamylase (OTC) deficiency is the most common inherited urea cycle disorder. It is an X-linked semidominant disease with variable severity affecting both males and females. The characteristics and course have not been assessed in Taiwanese. This study analyzed the phenotype and genotype of OTC deficiency in Taiwanese.During the period from January 1993 to December 2001 inclusive, 8 patients had the diagnosis of OTC deficiency by the criteria of hyperammonemia, hypocitrullinemia, and orotic aciduria. All 10 exons of the OTC gene were analyzed for mutations.Among the 8 cases, 3 belonged to the early-onset group (initial symptoms before or equal to age 28 days) and 5 belonged to the late-onset group (median onset age, 18 months; range, 8 months to 52 years). One case in the former group, and 4 cases in the latter group survived (mean survival, 8.2 years; range, 3 to 16 years). The average time between initial symptoms and diagnosis was 60 months in the late-onset group. Analysis of the OTC genes detected 5 different mutations in 5 patients, including 3 novel mutations: 42delT, 652GA, and 791CA. IQ tests, conducted in 3 patients, revealed low scores (mean, 53; range, 40 to 72).Both early-onset and late-onset cases of OTC deficiency were identified in Taiwanese. The diagnosis was delayed in these patients, and their outcomes were poor. All mutations detected were different and most of them have not been reported in other populations, which may explain the variability of phenotypes in Taiwanese patients.

Fibril formation is the basis of amyloid production in a number of disease states, such as Alzheimer's disease, diabetes and immunocytic dyscrasias. Compounds that inhibit fibril formation could be directly relevant to the treatment of amyloid diseases, and may also provide a foundation for the development of interventions in other molecular condensation diseases ranging from sickle cell anemia to atherosclerosis. We developed an economical and convenient high-throughput method for screening compounds against fibril formation in microwell plates. Chalcones, flavonoids and biflavonoids were screened against fibril formation by a recombinant antibody variable domain (V1). Chalcones 6 and 14 were found to demonstrate inhibition at 0.1 microM in 79 microM of protein solution in both test tube and microwell plate assays. The concentration of protein in the microwell plate assay could be as low as 5 microM using ThT as a monitoring agent. Molecular modeling studies indicated that both compounds could be individually docked into a binding site at the monomer-monomer interface of the V(L) protein dimer. These studies suggested that these compounds could potentially stabilize the VL dimer and therefore reduce its tendency to form fibrils. These findings may provide the basis for a new therapeutic approach to prevent or treat amyloid diseases.

A series of naturally occurring and synthetic biflavonoids was evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv (Mtb). Compounds 6, 24, and 25 demonstrated 96, 95, and 87% inhibition, respectively, at a screening concentration of 12.5 microg/mL. The type of linkage and the presence of methoxy- and nitro-substituents in biflavonoids may contribute to the observed inhibitory activity. The results of this study represent the discovery of biflavonoids as a potential new class of antituberculosis agent.

Seizure disorder and sleep apnea are common chronic disorders in children, but the relationship between sleep apnea and seizure control has not been studied in the pediatric population. This retrospective review included nine children with neurodevelopmental disorders who had well-documented sleep apneic episodes and seizure disorders. Seizure frequency was reduced in five patients (56%) in the first 12 months after sleep apnea treatment without changes in their antiepileptic medications. Sleep apnea can be one of the seizure precipitants in children with epilepsy. This study indicates the importance of identifying sleep apnea when treating children with intractable epilepsy, particularly in those who are at high risk.

Eleven biflavonoids, including amentoflavone (1), agathisflavone (2), robustaflavone (3), hinokiflavone (4), volkensiflavone (5), morelloflavone (7), rhusflavanone (9), succedaneaflavanone (10), GB-1a (11), GB-1a 7"-O-beta-glucoside (13), and GB-2a (14) isolated from Rhus succedanea and Garcinia multiflora, as well as their methyl ethers, volkensiflavone hexamethyl ether (6), morelloflavone heptamethyl ether (8), and GB-1a hexamethyl ether (12), were evaluated for their anti-HIV-1 RT activity. The results indicated that compounds 3 and 4 demonstrated similar activity against HIV-1 reverse transcriptase (RT), with IC50 values of 65 microM. Compounds 1, 2, 7, 11, and 14 were moderately active against HIV-1 RT, with IC50 values of 119 microM, 100 microM, 116 microM, 236 microM, and 170 microM, respectively. Morelloflavone (7) also demonstrated significant antiviral activity against HIV-1 (strain LAV-1) in phytohemagglutinin-stimulated primary human peripheral blood mononuclear cells at an EC50 value of 6.9 microM and a selectivity index value of approximately 10. The other biflavonoids were either weakly active, inactive, or not selective against HIV-1 in human lymphocytes.

A three-solvent system was used to determine the Hildebrand solubility parameters of organic nonelectrolytes. The experimental Hildebrand solubility parameter represents a weighted average of the mole fraction solubilities of the solute in these three individual solvents (ethyl acetate, 1-propanol, and 1,2-propanediol). The solvent system estimated the Hildebrand solubility parameters of solutes within a range from 8.9 to 14.8 (cal/cm 3 ) 2 1 . Deviations ranged from 0.8 to 12.9%, with the highest value at the extreme and well within 10% at the median. Estimation of the Hildebrand solubility parameters of solutes within a wider range and with somewhat better accuracy was made with a five-solvent system (hexane, ethyl acetate, 1-propanol, 1,2-propanediol, and water).

We have characterized the basic amino acid methylation of three members of the 70,000-Da heat shock protein superfamily, hsp68, hsc70, and BiP, in Balb/c 3T3 cells. It appears that a lysyl residue is the only methylation site in BiP and that both lysyl and arginyl residues are methylated in hsp68 and hsc70. In all cases, ϵ- N -trimethyllysine is the predominant methyllysine species. Both N G -monomethylarginine and N G , N G -dimethylarginine are identified as the methylarginine species. The stoichiometry of the methylation is indirectly determined by using the amount of actin methylation as a reference. Three, four, and four methyl groups are incorporated into lysyl residues of hsp68, hsc70, and BiP, respectively. The level of lysyl methylation in hsc70 remains unchanged under different growth conditions. On the other hand, the arginyl methylation in hsc70 varies considerably. In confluent Balb/c 3T3 cells, there are 1.8 and 1.3 methyl groups in dimethylarginine and monomethylarginine, respectively. In nonconfluent cells, the amount of monomethylarginine is similar to that in confluent cells, but dimethylarginine is not detectable. Furthermore, in both confluent and nonconfluent cells, the level of monomethylarginine is reduced 5- to 10-fold after arsenite treatment. However, in 3T3 cells transformed by Rous sarcoma virus (SR-RSV 3T3 cells), the level of arginine methylation is constitutively lower and cannot be reduced further by arsenite.

Two Zn-finger proteins, TFIIIA (a constituent of 7S RNP particles) and p43 (a constituent of 42S RNP particles), were detected in ovary extracts of juvenile Xenopus laevis females by in vitro binding of radiolabeled divalent metals. Proteins fractionated by SDS-PAGE (sodium dodecylsulfate-polyacrylamide gel electrophoresis) were transferred by Western blotting onto nitrocellulose membranes, probed with 65Zn2+, 63Ni2+, or 109Cd2+, and visualized by autoradiography. Detection limits for TFIIIA were approx 0.07 micrograms/well by 109Cd(2+)-probing, 0.13 micrograms/well by 65Zn(2+)-probing, and 0.26 mu/well by 63Ni(2+)-probing. Protein p43 was more clearly visualized by probing with 63Ni2+ than with 65Zn2+ or 109Cd2+. After purified TFIIIA was cleaved with cyanogen bromide, 65Zn2+, 109Cd2+, and 63Ni2+ distinctly labeled the 22 kDa middle fragment; 65Zn2+ and 109Cd2+ also labeled the 11 kDa N-terminal fragment, but did not label the 13 kDa C-terminal fragment. These results are consistent with the notion that the radioligands were bound to finger-loop domains of TFIIIA, which occur in the middle and N-terminal fragments. Based on the abilities of nonradioactive metal ions to compete with 65Zn2+ for binding to TFIIIA on Western blots, the relative affinities of the metals for TFIIIA were ranked as follows: Zn2+ = Cu2+ greater than or equal to Hg2+ greater than Cd2+ greater than Co2+ greater than or equal to Ni2+. Even at a 1000-fold molar excess, Mn2+ did not compete with 65Zn2+ for binding to TFIIIA. Probing Western blots with the radiolabeled metal ions greatly facilitates the detection, isolation, and quantitation of TFIIIA and p43.

The extract of the roots of Euphorbia kansui, which has been widely used in Chinese folk medicine for the treatment of cancer, demonstrated antileukemic activity against the P-388 lymphocytic leukemia in mice. Bioassay-directed fractionation of the active extract led to the isolation and characterization of two novel antileukemic diterpene esters, kansuiphorin A [1] [13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate- 20- hexadecanoate] and kansuiphorin B [2] [6,7-epoxy-13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-do decanoate-20- hexadecanoate], whose structures were established from spectral evidence and chemical transformation. Kansuiphorins A and B demonstrated potent antileukemic activity with T/C greater than or equal to 176 and 177% at 0.1 and 0.5 mg/kg, respectively. The selectivity of kansuiphorin A, which inhibits the growth of particular cell types within the disease-oriented human cancer cell line panels, is discussed.