Rates and trends in healthcare-detected incidence of anorexia nervosa and bulimia nervosa: A national health insurance claim data study in Taiwan, 2002-2013.

OBJECTIVE: This study aimed to examine the incidence rates of diagnosed anorexia nervosa (AN) and bulimia nervosa (BN) and their variations over time in Taiwan. METHOD: The data of individuals with AN and BN, as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification's (ICD-9-CM), were extracted from merged databases by means of unique identification numbers. To fulfill the criteria of incident cases, individuals must not have had an AN or BN diagnosis in the preceding 2 years. The time trends were analyzed using Joinpoint regression analysis. RESULTS: The overall AN and BN incidence rates were 1.1 and 6.1 per 100,000, respectively. There was no significant change in the overall incidence rate for AN or both sexes across the study period. A significant increase in AN incidence occurred in the age groups of 10-14 and 30-39 years. The overall incidence rate of BN increased significantly in the few years before 2009 and then decreased. A similar trend occurred among the females and groups aged above 20 years. There was no significant change in the overall BN incidence rate over the whole period. DISCUSSION: Compared with Western countries, the AN incidence in Taiwan is very low, whereas the BN incidence is in the lower end of the range. The findings that the age of the first-time detected AN and BN is older in Taiwan and that the significant increases in age-specific incidence are mainly among adults suggest that more effort is needed to detect individuals with AN and BN at a younger age in Taiwan.

Irradiation Enhances Abscopal Anti-tumor Effects of Antigen-Specific Immunotherapy through Regulating Tumor Microenvironment.

Ionizing radiation therapy is a well-established method of eradicating locally advanced tumors. Here, we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size. The combination of local RT and CTGF/E7 vaccination also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation induced the expression of high-mobility group box 1 protein (HMGB-1) in apoptotic tumor cells and stimulated dendritic cell (DC) maturation, consequently inducing antigen-specific immune responses. Additionally, local irradiation eventually increased the effector-to-suppressor cell ratio in the tumor microenvironment. Overall, local irradiation enhanced the antigen-specific immunity and anti-tumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. These findings suggest that the combination of irradiation with antigen-specific immunotherapy is a promising new clinical strategy for cancer therapy.

Mapping the biological oxidative damage of engineered nanomaterials.

Novel engineered nanomaterials (ENMs) are being introduced into the market rapidly with little understanding of their potential toxicity. Each ENM is a complex combination of diverse sizes, surface chemistries, crystallinity, and metal impurities. Variability in physicochemical properties is poorly understood but is critically important in revealing adverse effects of ENMs. A need also exists for discovering broad relationships between variations in these physicochemical parameters and toxicological endpoints of interest. Biological oxidative damage (BOD) has been recognized as a key mechanism of nanotoxicity. An assortment of 138 ENMs representing major classes are evaluated for BOD elicited (net decrease in the antioxidant capacity of ENM-exposed human blood serum, as compare to unexposed serum) using the 'Ferric Reducing Ability of Serum' (FRAS) assay. This robust and high-throughput approach has the ability to determine the co-effects which multiple physicochemical characteristics impart on oxidative potential, and subsequently to identify and quantify the influence of individual factors. FRAS BOD approach demonstrated the potential for preliminary evaluation of potential toxicity of ENMs, mapping the within- and between-class variability of ENMs, ranking the potential toxicity by material class, and prioritizing the ENMs for further toxicity evaluation and risk assessment.

Characteristics, Treatment Patterns, and Clinical Outcomes of Chronic Hepatitis B Across 3 Continents: Retrospective Database Study.

INTRODUCTION: The prevalence of chronic hepatitis B virus (HBV) infection is high in many countries; however, robust, real-world epidemiological data are lacking. This study describes the prevalence, characteristics, treatment patterns, and long-term clinical outcomes of patients with chronic HBV infection in the US, Germany, and Taiwan. METHODS: This was a retrospective cohort analysis of three healthcare/insurance claims databases. Individuals were identified as patients with chronic HBV infection if their records contained HBV diagnostic codes from 1 January 2010 to 31 December 2012 (Germany and Taiwan) or 1 January 2013 (USA). Included patients were indexed on 1 January 2013. Patients' demographics, clinical characteristics, and healthcare utilisation were described. Treatment patterns and long-term clinical outcomes over follow-up (to 31 December 2016 or loss to follow-up) were estimated. RESULTS: The prevalence of chronic HBV infection was 0.10%, 0.17%, and 2.39% in the US, Germany, and Taiwan respectively. Prevalence was very low in children, increased rapidly in adulthood, and peaked in 50- < 65 year olds before declining in the elderly. More US (16.6%) and German (15.4%) patients were HIV ± HCV coinfected than in Taiwan (4.1%). Baseline clinical characteristics and healthcare utilisation were broadly similar between countries. In total, 19.2%, 11.1%, and 5.9% of non-coinfected adult patients received treatment at index in the US, Germany, and Taiwan, respectively; most frequently with nucleos(t)ide analogue monotherapy (94.4%, 97.2%, 99.8% of treated patients, respectively) and rarely with interferons (0.27%, 1.63%, and 0.06%, respectively). Untreated Taiwanese patients were more likely to remain untreated than elsewhere, and treated Taiwanese patients were less likely to persist with therapy. Generally, the cumulative incidence of long-term clinical outcomes was lowest in Germany. CONCLUSION: This study provides a contemporary, real-world, intercontinental snapshot of chronic HBV infection. Long-term sequelae occurred in all populations, and treatment levels were low, suggesting an unmet need for (or access to) effective treatments.

Changes in Pramipexole Utilization after Introduction of the Extended-Release Formulation: A Nationwide Study in Taiwan.

BACKGROUND: Real-world impact of extended-release formulations of oral drugs should ideally be evaluated in population-based health data. OBJECTIVE: To evaluate changes in utilization of the dopamine agonist pramipexole for Parkinson's disease after the introduction of extended-release (ER) pramipexole in Taiwan. PATIENTS AND METHODS: Source data were derived from National Health Insurance claims. Patients with a diagnosis of Parkinson's disease and pramipexole prescriptions were identified. Drug use patterns from 2009 through 2011 (only the immediate-release [IR] formulation was available) and from 2012 through 2017 (both the IR and ER formulations were available) were assessed. Outcomes of interest were levodopa equivalent dose per day (LEDD) and 1-year adherence, as measured by the medication possession ratio (MPR). RESULTS: LEDDs associated with pramipexole ER prescriptions were more than twice as large as that associated with pramipexole IR, both in pramipexole used in monotherapy and that used in combination therapy. One-year MPRs for pramipexole ER initiators were all larger than 73% from 2012 through 2016 and 1-year MPRs for pramipexole IR initiators were less than 65% in 2010 and 2011. CONCLUSION: Introduction of pramipexole ER to Taiwan resulted in higher LEDD in prescriptions with pramipexole. Patients with Parkinson's disease who were initiated on pramipexole ER had better adherence to the medication than those who were prescribed pramipexole IR.

Prognostic Factors of Early Stage Epithelial Ovarian Carcinoma.

We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21⁻0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47⁻14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02⁻5.07, p = 0.004) and who received 3⁻5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47⁻7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21⁻0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13⁻0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens.

OBJECTIVE: Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. METHODS: Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3-6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. RESULTS: A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3-5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). CONCLUSION: Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.

The effect of magnolol on Ca2+ homeostasis and its related physiology in human oral cancer cells.

OBJECTIVE: Magnolol, a polyphenol compound from herbal medicines, was shown to alter physiology in various cell models. However, the effect of magnolol on Ca2+ homeostasis and its related physiology in oral cancer cells is unclear. This study examined whether magnolol altered Ca2+ signaling and cell viability in OC2 human oral cancer cells. METHODS: Cytosolic Ca2+ concentrations ([Ca2+]i) in suspended cells were measured by using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay. RESULTS: Magnolol at concentrations of 20-100 µM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 50%. Magnolol (100 µM) induced Mn2+ influx suggesting of Ca2+ entry. Magnolol-induced Ca2+ entry was partially suppressed by protein kinase C (PKC) regulators, and inhibitors of store-operated Ca2+ channels. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished magnolol-evoked [Ca2+]i rises. Conversely, treatment with magnolol abolished BHQ-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 partially inhibited magnolol-induced [Ca2+]i rises. Magnolol at 20-100 µM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). CONCLUSIONS: Together, in OC2 cells, magnolol induced [Ca2+]i rises by evoking partially PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Magnolol also caused Ca2+-independent cell death. Therefore, magnolol-induced cytotoxicity may not be involved in activation mechanisms associated with intracellular Ca2+ mobilization in oral cancer cells.

Screening frequency and histologic type influence the efficacy of cervical cancer screening: A nationwide cohort study.

OBJECTIVE: To evaluate the influence of age, screening interval, and histologic type on the effect of Pap smears in cervical cancer screening. MATERIALS AND METHODS: Data were retrieved from the Taiwan National Cancer Registry and Cervical Cancer Screening Registration System for the period from 2002 to 2010. Age, Pap smear interval, FIGO stage, and histology were further analyzed. RESULTS: A total of 12,294 women with cervical cancer were enrolled, including 10,040 with squamous cell carcinoma (SCC), 1720 with adenocarcinoma (ADC), 401 with adenosquamous carcinoma (ASC), and 133 with small cell neuroendocrine carcinoma (SMC). Women who had a Pap smear at an interval of <3 years had a significantly higher proportion of stage I disease than women who had never undergone cervical cancer screening (p < 0.0001). Greater than 40% of women with SCCs in each age group had never had a Pap smear; however, women with ADCs were predominantly in the younger age and greater than 40% of women with ADCs had Pap smear at intervals < 3 years. CONCLUSIONS: Pap smear is more effective in screening for cervical SCCs compared to cervical ADCs. Improving adherence to screening recommendations is important for the prevention of cervical SCC, especially in elderly women.

Tongue color changes within a menstrual cycle in eumenorrheic women.

Tongue color ( shé sè) has been used to diagnose abnormal body conditions for thousands of years in traditional Chinese Medicine ( zhong yi). However, it is not clear whether tongue color alters with physiological changes within a normal menstrual cycle ( yuè jing zhou qi). This study investigated difference in tongue color between the follicular phase and luteal phase in eumenorrheic women. Tongue surface photographs were taken in the follicular phase and the luteal phase of thirty-two volunteers with biphasic basal body temperature. Color values on five areas of the tongue surface were examined and comparisons of color values were made between the two phases according to the red-green-blue (RGB), hue-saturation-brightness (HSB), luminance-a-b (Lab), and cyan-magenta-yellow-black (CMYK) models. Based on the RGB model, the values of green and blue in the tip area were larger in the follicular phase than both in the luteal phase. The values of magenta and yellow based in the CMYK model were smaller in the tip area in the follicular phase than that in the luteal phase. The saturation in the tip area was smaller in the follicular phase than that in the luteal phase. Based on the Lab model, b value in the middle area was smaller in the follicular phase than that in the luteal phase. The data revealed that tongue color varied within a eumenorrheic menstrual cycle, suggesting that tongue color differences between the follicular and luteal phases need to be considered while practicing tongue diagnosis ( shé zhen) or performing clinical studies among childbearing women.

IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients.

Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk-scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend <0.001 for DFS and OS). Therefore, acombination of clinical and immunological parameters can provide a practical scoring system to predict the survival of patients with ovarian carcinoma. IL17a and IL21 can potentially be used as prognostic and therapeutic biomarkers.

Overexpression of CHI3L1 is associated with chemoresistance and poor outcome of epithelial ovarian carcinoma.

We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001)and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001)and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.

Biological oxidative damage by carbon nanotubes: fingerprint or footprint?

Carbon nanotubes (CNTs) have received much attention for performance and toxicity, but vary substantially in terms of impurity type and content, morphology, and surface activity. This study determined the decrease of antioxidant capacity, defined as biological oxidative damage (BOD), of CNTs-exposed serum. The variability in several physicochemical properties of CNTs and their links to BOD elicited in human serum were explored. Tremendous variation in transition metal type and content (104-fold), specific surface area (SSA, nine-fold), and BOD were observed. Mass specific BOD (mBOD) varied from 0.006-0.187 µmol TEU mg(-1), whereas surface area specific BOD (sBOD) varied from 0.068-0.42 µmol TEU m(-2). The sBOD increased in a stepwise fashion from ∼0.1-0.32 µmol TEU m(-2) for tubes with outer diameter less than 10 nm. The mBOD and sBOD may be useful denominators of surface activity and impurity content and assist in designing safer CNTs.

Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden).

OBJECTIVE: Identify time-points when the elevated postpartum maternal breast cancer risk peaks. METHODS: A case-control study nested within the Swedish Fertility Register included 34,018 breast cancer cases from the Swedish Cancer Register between 1961 and 1995. From the Fertility Register, 170,001 eligible subjects matched to the cases by age were selected as controls. Analysis contrasted risk between uniparous (7084 cases and 31,703 controls) and nulliparous (5411 cases and 22,580 controls) women and between biparous (13,239 cases and 65,858 controls) and uniparous women. Logistic regression analysis included indicator variables representing each year of age, ages at delivery, and time since delivery. RESULTS: Comparing uniparous with nulliparous women the transient increase in maternal breast cancer risk peaked 5 years following delivery (odds ratio= 1.49, 95% confidence interval 1.01-2.20) and leveled off 15 years postpartum. Biparous women had a transient increase in risk that was lower at its peak than that of uniparous women, occurring about 3 years following second delivery. CONCLUSIONS: A time window of 5 years postpartum when maternal breast cancer risk is highest was observed. Establishing timing of peak transient increase in postpartum breast cancer risk may define the latent period required for pregnancy hormones in promoting progression of breast cells that have undergone early stages of malignant transformation.