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Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs.We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in the Research on Asian Psychotropic Prescription Patterns Consortium. Mood stabilizer doses were converted to lithium carbonate equivalents (Li-eq milligrams per day). We compared relatively high (900 Li-eq mg/day) versus lower MS doses by bivariate comparisons, followed by multivariable linear regression to identify factors associated with higher MS doses.Among 1647 participants, MS dose averaged 584 (confidence interval, 565-603 Li-eq mg/d). Preliminarily, the 13.1% of the subjects given greater than 900 mg/d versus those given lower doses were younger, male, currently hospitalized, not currently depressed, and reported lifetime suicidal ideation; they also received relatively high doses of antipsychotics, received electroconvulsive treatment within the previous 12 months, and had greater ratings of tremors and sedation. By linear regression modeling, the mean proportion given high doses of MS was associated significantly and independently with higher doses of antipsychotics, younger age, male sex, hospitalized, more years of illness, country, higher body mass index, recent electroconvulsive treatment, and being in illness remission.Relatively high doses of MSs for BD are prevalent, but vary markedly among Asian countries, and are particularly likely among young males, ill for many years, and given high doses of antipsychotics or ECT. These characteristics allow better identification of patient profiles that can guide treatment of BD patients.

OBJECTIVE Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology.Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia.Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability.An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism.Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia.Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed.A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P 0.01).Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.

Objective Regular surveys are important to monitor the use of psychotropic medications in clinical practice. This study examined the psychotropic prescription patterns in adult Asian schizophrenia patients based on the data of the Research on Asian Psychotropic Prescription (REAP) 2016 survey. Methods : This cross-sectional survey across 15 Asian countries/territories collected socio-demographic and clinical data with standardized procedures between March and May 2016. The socio-demographic and clinical characteristics of the patients were recorded with a standardized questionnaire. Results Altogether 3,537 adult patients with schizophrenia were consecutively screened and enrolled in the survey. The mean age was 38.66 ± 11.55 years and 59.7% of the sample were male. The mean dose of antipsychotics in chlorpromazine equivalents (CPZeq) was 424 ± 376 mg/day; 31.3% and 80.8% received first- and second- generation antipsychotics, respectively and 42.6% had antipsychotic polypharmacy, 11.7% had antidepressants, 13.7% had mood stabilizers, 27.8% had benzodiazepines, and 45.6% had anticholinergics. Conclusions Psychotropic prescription patterns in Asian adult patients with schizophrenia varied across countries. Regular surveys on psychotropic medications for schizophrenia are important to monitor pharmacotherapy practice in Asia.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.

Work-related musculoskeletal disorders (WMSD) refer to musculoskeletal injuries caused by the occupation. Physical therapists (PTs) suffer from a high risk of WMSD despite their extensive knowledge in ergometrics and injury prevention. This study aims to discover the incidence and prevalence of WMSD among PTs using Taiwan's nationwide claims database. The trend of annual patients seeking rehabilitation and the prevalence of WMSD among PTs were presented. The age- and gender-specific incidence of WMSD were also calculated. The prevalence of WMSD in PTs varied from 6.1% to 75.2%, and the incidence ranged from 6.1 to 29.1 per 100 person-years during 1997 and 2012. For those aged ≤30 years, the incidence was higher in females than males (incidence rate ratio = 1.08, 95% confidence interval [CI]: 1.02-1.14, P = .011), whereas for those aged from 31 to40 years, females had lower incidence of WMSD than males (incidence rate ratio = 0.88, 95% CI: 0.80-0.96, P = .007). The patients/PTs ratio was higher (270.56-337.74) in 1998 and 2004 to 2007 and became stable (245.93-252.82) in 2008 to 2012, correlating with a rise in the WMSD prevalence in 1999 to 2007 and a steady prevalence after 2008 (63.5%-66.3%) in PTs. In conclusion, the risk of WMSD among PTs was positively correlated to the frequency of patients seeking rehabilitation service. In addition, age and gender were important risk factors for developing WMSD among PTs.

Kaempferitrin is extracted in significantly high quantities from the leaves of Cinnamomum osmophloeum, which belongs to a group of plant species that comes under the genus Cinnamomum, well-known for its established anti-diabetic property in Chinese medicine. Oral administration of kaempferitrin and Cinnamomum osmophloeum extract reduced blood sugar in alloxan-induced diabetic rats and improved the lipid profile in hamsters respectively. In this paper we studied the differential protein expression profile using mass spectrometry approach in the kaempferitrin-treated conditioned medium of liver cancer cell line HepG2. We discovered that 33 genes were up/down-regulated consistently between two biological samples. A slightly different version of the analysis software selected 28 genes, and the final 18 genes that appeared in both lists were selected. Interestingly, 5 proteins out of 18 were either exosomal markers or reported in high frequency of occurrence in exosome/secreted vesicles. We also examined the extracellular particles with atomic force microscopy (AFM), which showed that the conditioned medium of kaempferitrin treated had larger vesicles and fewer small vesicles. Expression of some lipid-regulating genes were also altered. Our data suggested that extracellular vesicle secretions may be regulated by kaempferitrin, and regulation of lipid profile by kampeferitrin involves multiple mechanisms.

Background Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. Subjects and methods Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight pre-obese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. Results In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. Conclusion Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

Background: Recent years have witnessed wide applications of exergames to balance training among the older adults. However, research concerning balance training with the use of Kinect for Xbox has remained scarce. While previous studies have shown the positive effects of exergames on improving balance and preventing falling among the older adults, there has been a paucity of empirical evidence supporting the superiority of Kinect exercise to conventional exercise over balance training among the older adults. Therefore, this study aimed to compare the feasibility, safety, and effectiveness of Kinect exercise against conventional exercise over balance training among the community older adults. Method: A total of 20 participants were randomly assigned to the Kinect Exercise Group (N = 10) or the Conventional Exercise Group (N = 10) for a 5-week balance training (45 minutes a time, 2 times a week). Assessor blinding was employed to assess the participants’ performance before and after the treatment, including 30-Second Chair Stand Test (30-sec CST), Timed Up and Go (TUG), Functional Reach Test (FRT), and One-Leg Stance Test (OLST) respectively with eyes open and closed. Subjective feeling of the intensity of pain and side effects were recorded throughout the investigation period. Nonparametric statistics was used for data analysis. Results: Within-group comparison between the pre-test and post-test indicated that significant differences existed in all of the 5 tests (30-sec CST, TUG, FRT, OLST with eyes open, and OLST with eyes closed) in the Kinect exercise group. To the Conventional exercise group, however, significant differences were only observed in 30-sec CST, FRT and OLST with eyes open. With regard to between-group comparison, significant differences were only found in FRT. Conclusion: Such results indicated that both treatments were helpful in improving the participants’ balance performance, that Kinect exercise was more effective in terms of overall balance ability, and that Kinect exercise was particularly beneficial to functional reach enhancement in comparison with traditional exercise. Kinect exercise could be a feasible, safe, and effective alternative for dynamic balance training among older adults.

Introduction Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. Methods Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. Results Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. Discussion These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

Potentially inappropriate medication (PIM) was associated with adverse clinical outcomes and higher healthcare resource utilization among older patients. In order to investigate the prevalence of PIM use based on three different sets of criteria and their associated factors among older patients in the emergency department (ED) in Taiwan. The National Health Insurance Research Database was used for this cross-sectional study. Older patients who visited the ED at least once in 2009 were enrolled. PIMs were identified based on the Beers Criteria, PIM-Taiwan criteria, and PRISCUS criteria. Average patient age was 76.7 ± 7.4 years and patients visited the ED 1.8 ± 2.1 times in 2009. The prevalence and frequency of being prescribed at least one PIM at each visit were high according to all three sets of criteria. Performance of the PIM-Taiwan criteria was only inferior to that of the Beers Criteria. The most important factor associated with PIM was the number of medications prescribed in the ED, and PIM use was associated with higher annual health resource utilization in the ED. PIM use was a significant issue and was associated with higher annual emergency care resource utilization in the ED.

Background Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. Methods Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression. Loss- and gain-of function assays were performed to investigate the role of Chibby in NPC cells. Western blot, cell proliferation, Glucose uptake, Lactate release, ATP level, and O2 consumption assays were used to determine the mechanism of Chibby regulation of underlying targets. Finally, immunohistochemistry assay of fresh NPC and nasopharyngeal normal tissue sample were used to detect the expression of Chibby, β-Catenin, and PDK1 by immunostaining. Results We observed that Chibby, a β-catenin-associated antagonist, is down-regulated in nasopharyngeal carcinoma cell lines and inhibits Wnt/β-Catenin signaling induced Warburg effect. Mechanism study revealed that Chibby regulates aerobic glycolysis in NPC cells through pyruvate dehydrogenase kinase 1(PDK1), an important enzyme involved in glucose metabolism. Moreover, Chibby suppresses aerobic glycolysis of NPC via Wnt/β-Catenin-Lin28/let7-PDK1 cascade. Chibby and PDK1 are critical for Wnt/β-Catenin signaling induced NPC cell proliferation both in vitro and in vivo. Finally, immunostaining assay of tissue samples provides an important clinical relevance among Chibby, Wnt/β-Catenin signaling and PDK1. Conclusions Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/β-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0769-4) contains supplementary material, which is available to authorized users.

As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries.This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling.Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalizationoutpatient care, psychiatricgeneral-medical programs, and young age (all P0.001), but not with country, sex, or AD dose.The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

Aim We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. Methods Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. Results Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. Conclusion Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

Auditory neuropathy is an important entity in childhood sensorineural hearing loss. Due to diverse etiologies and clinical features, the management is often challenging. This study used an integrative patient-history, audiologic, genetic, and imaging-based approach to investigate the etiologies and audiologic features of 101 children with auditory neuropathy. Etiologically, 48 (47.5%), 16 (15.8%), 11 (10.9%), and 26 (25.7%) children were categorized as having acquired, genetic, cochlear nerve deficiency-related, and indefinite auditory neuropathy, respectively. The most common causes of acquired and genetic auditory neuropathy were prematurity and OTOF mutations, respectively. Patients with acquired auditory neuropathy presented hearing loss earlier (odds ratio, 10.2; 95% confidence interval, 2.2–47.4), whereas patients with genetic auditory neuropathy had higher presence rate of distortion product otoacoustic emissions (odds ratio, 10.7; 95% confidence interval, 1.3–85.4). In patients with different etiologies or pathological sites, moderate to strong correlations (Pearson’s r = 0.51–0.83) were observed between behavioral thresholds and auditory steady-state response thresholds. In conclusion, comprehensive assessments can provide etiological clues in ~75% of the children with auditory neuropathy. Different etiologies are associated with different audiologic features, and auditory steady-state responses might serve as an objective measure for estimating behavioral thresholds.

Background and Objective: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. Methods: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. Results: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses ( P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness ( P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics ( P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics ( P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics ( P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. Conclusion: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.

The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia.Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug.Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015).Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.

// Jie Jiang 1 , Guojun Geng 1 , Xiuyi Yu 1 , Hongming Liu 1 , Jing Gao 1 , Hanxiang An 2 , Chengfu Cai 1 , Ning Li 1 , Dongyan Shen 3 , Xiaoqiang Wu 3 , Lisheng Zheng 4 , Yanjun Mi 1, 2 , Shuyu Yang 5 1 Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 3 Biobank, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 5 Xiamen Diabetes Institution, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Correspondence to: Shuyu Yang, email: yangshuyu2016@126.com Yanjun Mi, email: Myjgj_77@163.com Keywords: dihydroartemisinin, non-small-cell lung cancer, Warburg effect, metastasis, NF-κB Received: April 06, 2016 Accepted: November 02, 2016 Published: November 24, 2016 ABSTRACT Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-κB signaling to inhibit the GLUT1 translocation. Blocking the NF-κB signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-κB signaling pathway and DHA may deserve further investigation in NSCLC treatment.

OBJECTIVE Long-term follow-up data regarding the association between methamphetamine use and cardiovascular and cerebrovascular complications are scarce. We investigated the risk of complications in methamphetamine users over a decade. METHODS A total of 1,315 inpatients treated for methamphetamine use were recruited from the Psychiatric Inpatient Medical Claims database in Taiwan between January 1, 1997, and December 31, 2000, and matched with a population proxy comparison group at a ratio of 1:4 through propensity score matching. All patients were monitored for any incident complication until December 31, 2010. Cox proportional hazards model was used to estimate the risk of ICD-9-CM cardiovascular diseases and stroke events. RESULTS The patients were mostly male, and approximately half were younger than 30 years. The methamphetamine cohort had higher incidences of cardiovascular diseases and stroke events than the comparison cohort (87.5/10,000 vs 55.3/10,000 person-years, P < .001) and was significantly associated with an increased risk of the complications (hazard ratio [HR] = 1.55, P < .001), particularly arrhythmia (HR = 1.92, P = .014) and hemorrhagic stroke (HR = 2.09, P = .001). The risk of cardiovascular sequelae was more significant in younger patients (< 30 y) (HR = 2.22, P = .001), whereas the risk of stroke events was higher among the older patients (≥ 30 y) (HR = 1.86, P = .001). CONCLUSIONS Methamphetamine use is significantly associated with a risk of subsequent cardiovascular and cerebrovascular complications. Age appears to be an effect modifier for the risk estimation.

Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P

PURPOSE Little is known regarding the trend of polypharmacy in Asia. We used data from 5 Asian countries to examine the patterns of antidepressant (AD) prescription and trends of psychotropic polypharmacy over time. METHODS We used the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to examine the patterns of AD prescriptions in clinical settings in China, Japan, Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie, concomitant use of ≥2 classes of psychotropic) among individuals receiving AD prescriptions in 2004 and 2013 using multivariable logistic regression models in different diagnostic categories. RESULTS The proportion of patients with psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35-0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD prescriptions, concomitant use of anxiolytics (including sedative-hypnotics) decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15-1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004). CONCLUSIONS This is the first study examining trends in psychotropic polypharmacy in East Asia. We found a generally decreasing trend of psychotropic polypharmacy in contrast to the increasing trend reported from Western countries. These findings could offer significant implications for health system reform or policy making.

Depressive disorders are common in old age. Antipsychotics (APs) are often used as an adjunctive treatment with antidepressants (ADs) in this population but its patterns of use in Asia are not known. This study explored the rate of combination of APs and ADs in older adult psychiatric patients in Asia.This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses.A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs.Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.

Aim Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy. Methods Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk-set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity-scoring method in sensitivity analyses to validate any associations. Results Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose-dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044). Conclusion This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

To investigate the relationship between benzodiazepine and risk of developing pneumonia in patients with schizophrenia, whose benzodiazepine dosage and usage frequency was higher than that of the general population. We conducted a nested case–control study to assess the association between benzodiazepine use and pneumonia among patients with schizophrenia. By using the Taiwan National Health Insurance Research Database, we identified a schizophrenia cohort comprising 34,929 patients during 2000–2010. Within the schizophrenia cohort, 2501 cases of pneumonia and 9961 matched control patients (1:4 ratio) were identified. Benzodiazepine exposure was categorized by drug, treatment duration, and daily dose. Conditional logistic regression models were used to examine the association between benzodiazepine exposure and the risk of pneumonia. The current use (within 30 days) of midazolam led to the highest pneumonia risk (adjusted risk ratio = 6.56, P

Study design A retrospective cohort. Introduction The benefits of early rehabilitation after hand tendon repair have not been analyzed using population-based datasets. Purpose of the study to analyze whether early rehabilitation reduces the resurgery risk and the use of rehabilitation resources. Methods Patients (n = 1219) who underwent hand tendon repairs followed by rehabilitation were identified from a nationwide claims database and divided into 3 groups: early ( 6 wk) rehabilitation. The resurgery rate and the use of rehabilitation resources after tendon repair were calculated. Cox proportional hazards models were used to evaluate the relevant predictors of resurgery. Results The early rehabilitation group exhibited the lowest resurgery rate and used the fewest rehabilitation resources. Compared with late rehabilitation, early or intermediate rehabilitation conferred protective effects against resurgery in patients without a concomitant upper-limb fracture. Conclusion Our findings suggest the benefit of early rehabilitation after hand tendon repair. Level of evidence 4

Background:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.Methods:The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.Results:The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (Conclusions:Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Aim The aim of the present study was to survey the prevalence of antipsychotic polypharmacy and combined medication use across 15 Asian countries and areas in 2016. Methods By using the results from the fourth survey of Research on Asian Prescription Patterns on antipsychotics, the rates of polypharmacy and combined medication use in each country were analyzed. Daily medications prescribed for the treatment of inpatients or outpatients with schizophrenia, including antipsychotics, mood stabilizers, anxiolytics, hypnotics, and antiparkinson agents, were collected. Fifteen countries from Asia participated in this study. Results A total of 3744 patients' prescription forms were examined. The prescription patterns differed across these Asian countries, with the highest rate of polypharmacy noted in Vietnam (59.1%) and the lowest in Myanmar (22.0%). Furthermore, the combined use of other medications, expressed as highest and lowest rate, respectively, was as follows: mood stabilizers, China (35.0%) and Bangladesh (1.0%); antidepressants, South Korea (36.6%) and Bangladesh (0%); anxiolytics, Pakistan (55.7%) and Myanmar (8.5%); hypnotics, Japan (61.1%) and, equally, Myanmar (0%) and Sri Lanka (0%); and antiparkinson agents, Bangladesh (87.9%) and Vietnam (10.9%). The average psychotropic drug loading of all patients was 2.01 ± 1.64, with the highest and lowest loadings noted in Japan (4.13 ± 3.13) and Indonesia (1.16 ± 0.68), respectively. Conclusion Differences in psychiatrist training as well as the civil culture and health insurance system of each country may have contributed to the differences in these rates. The concept of drug loading can be applied to other medical fields.

The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia.Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data.Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P 0.001), higher number of depressive symptoms (OR = 1.09, P = 0.016), being treated in psychiatric hospital (OR = 0.5, P = 0.002), living in high income countries/territories (OR = 2.4, P = 0.002), use of benzodiazepines (OR = 1.4, P = 0.013) and diagnosis of 'other psychiatric disorders' (except mood, anxiety disorders and schizophrenia) (OR = 2.7, P 0.001) were significantly associated with physical comorbidities.Physical comorbidities in older patients prescribed with antidepressants were common in Asia. Integrating physical care into the treatment of older psychiatric patients should be urgently considered.

Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD.In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs.The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence.We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

This paper proposes a data glove system integrated with six-axis inertial measurement unit sensors for evaluating the hand function of patients who have suffered a stroke. The modular design of this data glove facilitates its use for stroke patients. The proposed system can use the hand’s accelerations, angular velocities, and joint angles as calculated by a quaternion algorithm, to help physicians gain new insights into rehabilitation treatments. A clinical experiment was performed on 15 healthy subjects and 15 stroke patients whose Brunnstrom stages (BSs) ranged from 4 to 6. In this experiment, the participants were subjected to a grip task, thumb task, and card turning task to produce raw data and three features, namely, the average rotation speed, variation of movement completion time, and quality of movement; these features were extracted from the recorded data to form 2-D and 3-D scatter plots. These scatter plots can provide reference information and guidance to physicians who must determine the BSs of stroke patients. The proposed system demonstrated a hit rate of 70.22% on average. Therefore, this system can effectively reduce physicians’ load and provide them with detailed information about hand function to help them adjust rehabilitation strategies for stroke patients.

Our study aimed to assess the psychometric validity of the conceptual disorganization item and other items of the Brief Psychiatric Rating Scale (BPRS) for detecting disorganized speech in patients with schizophrenia. We included 357 schizophrenia patients with disorganized speech and 1082 without disorganized speech from the survey centers in India, Indonesia, Japan, Malaysia, and Taiwan, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. After adjusting the effects of confounding variables, a binary logistic regression model was fitted to identify BPRS items independently associated with disorganized speech. Receiver operating characteristic (ROC) curves were used to identify optimum cut-off scores and their sensitivities and specificities for detecting disorganized speech. After adjusting the effects of confounding variables, the fitted binary logistic regression model indicated that conceptual disorganization (P < 0.0001), uncooperativeness (P = 0.010) and excitement (P = 0.001) were independently associated with disorganized speech. The ROC curve revealed that the conceptual disorganization item could accurately detect disorganized speech in patients with schizophrenia both separately and in combination with uncooperativeness and excitement. The subscale for conceptual disorganization, uncooperativeness and excitement items in the BPRS is a promising psychometric tool for detecting disorganized speech.

The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long-term prognoses. In this study, we used a nationwide population-based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders.In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed.In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7-year follow-up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%.Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future.

Objective The aim of this paper was to analyze medical utilization patterns of female patients with anorexia nervosa before their first inpatient care visit for anorexia nervosa using the National Health Insurance Research Database (NHIRD) of Taiwan. Method We selected female anorexia nervosa patients (n = 239) and control participants hospitalized for peptic ulcers (n = 478) or appendectomy (n = 478) who were matched by age and incident year from two subsets of the NHIRD. The number of visits, specialists, diagnosis distribution, and selected procedures used in ambulatory services during the 2-year period before the index admission were identified and compared. Healthcare service expenditures were also analyzed. Results Compared to the control groups, the female anorexia nervosa patients used more outpatient services (anorexia nervosa, 58.6 ± 45.0 visits; peptic ulcers, 45.3 ± 37.3 visits; appendectomy, 32.5 ± 26.0 visits), mainly due to psychiatric visits. Anorexia nervosa patients were more likely to have received a diagnosis of digestive, endocrine/metabolic, and mental disorders than patients in the control groups. Although nearly equal percentages of patients in the three groups had obtained a diagnosis of a digestive disease, anorexia nervosa patients received digestive disease diagnoses with greater frequency. Conclusions We posit that the various physical symptoms of anorexia nervosa patients and physicians' low level of suspicion of anorexia nervosa led to delayed diagnoses and greater medical utilization than that of the controls groups. Education to raise awareness of anorexia nervosa and other eating disorders among physicians is warranted.

OBJECTIVE Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice. METHOD In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association. RESULTS Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001). CONCLUSIONS Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

Aims.For nearly a century, the incidence of cancer in people with schizophrenia was lower than in the general population. In the recent decade, the relationship between cancer and schizophrenia has become obscured. Thus, we investigated the cancer risk among young and middle-aged patients with schizophrenia.Methods.Records of newly admitted patients with schizophrenia (n = 32 731) from January 2000 through December 2008 were retrieved from the Psychiatric Inpatient Medical Claims database in Taiwan, and the first psychiatric admission of each patient during the same period was defined as the baseline. We obtained 514 incident cancer cases that were monitored until December 2010. Standardised incidence ratios (SIRs) were calculated to compare the risk of cancer between those with schizophrenia and the general population. Stratified analyses of cancer incidences were performed by gender, site of cancers and duration since baseline (first psychiatric admission).Results.The incidence of cancer for all sites was slightly higher than that of the general population for the period (SIR = 1.15 [95% CI 1.06–1.26], p = 0.001). Men had a significantly higher incidence of colorectal cancer (SIR = 1.48 [95% CI 1.06–2.06], p = 0.019). Women had a higher incidence of breast cancer (SIR = 1.47 [95% CI 1.22–1.78], p < 0.001). Intriguingly, the risk for colorectal cancer was more pronounced 5 years after the first psychiatric admission rather than earlier (SIR = 1.94 [1.36–2.75], p < 0.001) and so was the risk for breast cancer (SIR = 1.85 [1.38–2.48], p < 0.001). The cancer incidence was higher in patients with schizophrenia contradicting the belief that schizophrenia was protective of cancers.Conclusions.Our analyses suggest that men and women with schizophrenia were more vulnerable to certain types of cancers, which indicates the need for gender-specific cancer screening programs. The fact that risk of colorectal cancer was more pronounced 5 years after the first psychiatric admission could imply the impact of unhealthy lifestyles or the possibility of delayed diagnoses.

This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals.In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure.Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals.Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

A hand injury can greatly affect a person's daily life. Physicians must evaluate the state of recovery of a patient's injured hand. However, current manual evaluations of hand functions are imprecise and inconvenient. In this paper, a data glove embedded with 9-axis inertial sensors and force sensitive resistors is proposed. The proposed data glove system enables hand movement to be tracked in real-time. In addition, the system can be used to obtain useful parameters for physicians, is an efficient tool for evaluating the hand function of patients, and can improve the quality of hand rehabilitation.

Objective The aim of this study was to survey the use of antipsychotic polypharmacy (APP) in older Asian patients with schizophrenia and examine its demographic and clinical correlates. Methods Information on hospitalized patients with schizophrenia aged 55 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns study. Data on 1439 patients in 6 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, and Taiwan were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. Results The frequency of APP prescription was 51.6% in the pooled sample with wide intercountry variations. Multiple logistic regression analysis of the whole sample showed that patients on APP had higher antipsychotic doses and also were more likely to receive first-generation antipsychotics. Conclusions Use of APP was common in older Asian patients with schizophrenia. Given the limited evidence supporting its efficacy, the potentially severe side effects and high costs, APP should be used with caution in this population. The reasons for and outcomes of the use of APP in this patient population merit further exploration.

Objective: This study examined the prescribing patterns of several first- (FGAs) and second-generation antipsychotic (SGAs) medications administered to older Asian patients with schizophrenia during the period between 2001 and 2009. Method: Information on hospitalized patients with schizophrenia aged 65 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001–2009). There were no older patients in Thailand, therefore data on 467 patients in eight Asian countries and territories including China, Hong Kong SAR, India, Japan, Korea, Malaysia, Singapore, and Taiwan were analysed. Cross-sectional socio-demographic data, clinical characteristics and antipsychotic prescriptions were assessed using a standardized protocol and data collection procedure. Results: Of the 467 patients, 192 patients (41.1%) received FGAs only, 166 (35.5%) received SGAs only and 109 (23.3%) received a combination of FGAs and SGAs. Of the FGAs, haloperidol was the most commonly used (31.3%; mean 9.4 ± 6.7 mg/day), followed by chlorpromazine (15.4%; mean 126.4 ± 156.4 mg/day) and sulpiride (6.6%; mean 375.0 ± 287.0 mg/day). Of the SGAs, risperidone was the most commonly used (31.5%; mean 4.5 ± 2.7 mg/day), followed by olanzapine (13.1%; mean 13.6 ± 6.5 mg/day), quetiapine (7.3%; mean 325.0 ± 237.3 mg/day) and aripiprazole (1.9%; mean 17.6 ± 7.7 mg/day). Conclusions: FGAs and higher doses of certain SGAs (risperidone, olanzapine and quetiapine) were still commonly dispensed to older Asian patients with schizophrenia. Considering older patients’ reduced tolerability of potentially severe side effects associated with FGAs and higher doses of certain SGAs, continuing education and training addressing the rational use of antipsychotics in this population is clearly needed.

This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.

Objective The aim of the study was to survey the frequency of tardive dyskinesia (TD) in patients with schizophrenia and its demographic and clinical correlates in selected Asian countries. Method A total of 6,761 hospitalized schizophrenia patients in nine Asian countries and territories were examined from 2001 to 2009. TD was evaluated as "present" or "absent" according to the clinical judgment of experienced psychiatrists. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Results The frequency of TD in the whole sample was 5.0% with wide variations between countries (0 - 14.9%). Multiple logistic regression analysis showed that the following variables were independently associated with TD: study time, study site, older age, male gender, more severe negative and extrapyramidal symptoms and less anticholinergic drugs. Conclusions A generally low frequency of TD in Asian schizophrenia patients with inter-ethnic variations was recorded. It is unclear whether the low prevalence of TD compared with Western data is real or the result of it being insufficiently recognized.

Recent studies indicate relatively high international rates of adjunctive psychotropic medication, includ- ing mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001-2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions : China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4 % (n=1377/6761) of hospitalized schizo- phrenia patients, with increased usage over time. Mood-stabilizer use was significantly and indepen- dently associated in multivariate logistic modeling with : aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabil- izers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.

Objective The aim of this study was to survey the use of anticholinergic medication (ACM) in Asia between 2001 and 2009 and examine its demographic and clinical correlates. Method A total of 6 761 hospitalized schizophrenia patients in 9 Asian countries and territories were examined between 2001 and 2009. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Results The frequency of ACM prescription decreased from 66.3% in 2001, to 52.8% in 2004 and 54.6% in 2009, with wide inter-country variations at each time period. Multiple logistic regression analysis of the whole sample showed that patients taking ACM presented with more severe positive, negative, and extrapyramidal symptoms. They were also more likely to receive first-generation and depot antipsychotics and antipsychotic polypharmacy, and less likely to receive second-generation ones. Conclusions The wide variation in ACM prescription across Asia suggests that a combination of clinical, social, economic and cultural factors play a role in determining the use of these drugs. Regular reviews of ACM use are desirable to reveal the discrepancy between treatment guidelines and clinical practice.

Benzodiazepines are commonly prescribed to patients with schizophrenia in many countries, but as little is known about such treatment in Asia, we evaluated their adjunctive use for 6761 in-patients diagnosed with schizophrenia in nine Asian countries using a cross-sectional study design in 2001, 2004 and 2008. Multivariate logistic regression and multivariate linear regression analyses were performed to assess predictors of benzodiazepine use and dose, respectively. Overall, 54% of the patients received adjunctive benzodiazepines at an average daily dose equivalent to 30.3 mg diazepam, with minor changes over the years sampled. Benzodiazepine use was highest in Taiwan and Japan, lowest in Thailand and China, and was associated with fewer years ill, presence of delusions (OR 1.24), hallucinations (OR 1.22), disorganized speech (OR 1.17), social or occupational dysfunction (OR 1.16), and use of mood stabilizers (OR 3.15), antiparkinsonian (OR 1.79) or antidepressant drugs (OR 1.33), and lower doses of antipsychotics (all p=0.016 to

In this study, a novel DNA electrochemical probe (locked nucleic acid, LNA) was designed and involved in constructing an electrochemical DNA biosensor for detection of promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα) fusion gene in acute promyelocytic leukemia for the first time. This biosensor was based on a 'sandwich' sensing mode, which involved a pair of LNA probes (capture probe immobilized at electrode surface and biotinyl reporter probe as an affinity tag for streptavidin-horseradish peroxidase (streptavidin-HRP). Since biotin can be connected with streptavidin-HRP, this biosensor offered an enzymatically amplified electrochemical current signal for the detection of target DNA. In the simple hybridization system, DNA fragment with its complementary DNA fragment was evidenced by amperometric detection, with a detection limit of 74 fM and a linear response range of 0.1-10 pM for synthetic PML/RARα fusion gene in acute promyelocytic leukemia (APL). Otherwise, the biosensor showed an excellent specificity to distinguish the complementary sequence and different mismatch sequences. The new pattern also exhibited high sensitivity and selectivity in mixed hybridization system.

The pathophysiology of stress urinary incontinence (SUI) is multifactorial. The aim of this study was to explore the factor determining the symptom severity of SUI. One hundred twenty-four women with SUI were retrospectively investigated. Clinical data for analyses included demographics, pelvic organ prolapse quantification, SUI severity using a 4-point Likert scale, ultrasound, 1-h pad tests, and urodynamic studies. Data were analyzed using the Spearman's rho test and Kruskal–Wallis test. The symptom severity was not correlated with risk factors of SUI or the morphologic manifestations representing urethral support defect, but was significantly correlated with urine loss on 1-h pad test, Valsalva leak point pressure (VLPP) grading, and maximum urethral closure pressure (MUCP). Women with higher SUI severity had greater urine loss on 1-h pad tests, worse VLPP grading, and lower MUCP. Urethral sphincter function appears to be an important determinant for the symptom severity of SUI.

We determined the reliability of real-time ultrasound for detecting involuntary or reflex pelvic floor muscle contraction.A total of 118 women with the symptomatic and urodynamic evidence of stress urinary incontinence were recruited in a 3-year period from tertiary referral urogynecology clinics. Under the oral instruction of strong coughing involuntary pelvic floor muscle contraction was detected using introital ultrasound in real-time and cine loop modes. Two dynamic imaging features were considered involuntary pelvic floor muscle contraction, including an inward clitoral motion and a superior-anterior anorectal lift before or during coughing.Real-time ultrasound had good reliability to detect involuntary pelvic floor muscle contraction. For interobserver and intra-observer reliability Cohen's kappa was 0.645 to 0.679. Of the 118 women real-time ultrasound before or during coughing showed an inward clitoral motion in 100 (93%) and an anorectal lift in 108 (92%). Neither type of contraction during coughing was identified in 2 women. Although the 2 contraction patterns were synchronized in 88% of women, for this synchronization kappa was only 0.159, indicating poor coordination between these 2 involuntary activities.Real-time ultrasound is a reliable tool for detecting involuntary pelvic floor muscle contraction.

Objective To determine the reliability and validity of new ultrasound parameters, measured in the polar coordinate system, for quantifying pelvic floor muscle action. Methods This was a prospective study, from January 2005 to December 2007, in 209 women with urodynamic stress incontinence, to validate new ultrasound parameters for quantifying pelvic floor muscle contraction. The examination of each patient included intravaginal digital palpation of voluntary pelvic floor muscle contractility and an ultrasound assessment of the positions of the bladder neck and anorectal junction at rest and during pelvic floor muscle contraction. The position of the bladder neck was expressed by bladder neck angle and bladder neck distance from the lower border of the pubic symphysis, and the position of the anorectal junction was expressed by the levator hiatal angle and sagittal hiatal diameter. The vector lengths of the motion of the bladder neck and anorectal junction during pelvic floor muscle contraction were calculated from the positions at rest and during pelvic floor muscle contraction by mathematical formulae. Results There was good inter- and intraobserver reliability of measurement of ultrasound parameters on stored volumes. During pelvic floor muscle contraction, elevated bladder neck distance and shortened sagittal hiatal diameter were valid parameters representing stronger pelvic floor muscle contractility, with shortened sagittal hiatal diameter having the best correlation (r = − 0.348, P < 0.001). Conclusion The methods used in this study appear to be reliable for quantifying pelvic floor muscle action. The bladder neck distance with respect to the lower border of the pubic symphysis and the sagittal hiatal diameter were both valid parameters reflecting PFM contractility. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.