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ObjectiveUnilateral sensorineural hearing loss is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood unilateral sensorineural hearing loss and analyze the associated audiological features.Study DesignRetrospective analysis of a prospectively recruited cohort Setting: Tertiary referral center Methods: We enrolled 38 children with unilateral sensorineural hearing loss and performed physical, audiological, imaging, and congenital cytomegalovirus examinations as well as genetic testing using next-generation sequencing targeting 30 deafness genes. The audiological results were compared across different etiologies.ResultsCausative genetic variants were identified in eight (21.1%) patients, including five withGJB2variants, two withPAX3variants, and one withEDNRBvariant.GJB2variants were associated with mild-to-moderate unilateral sensorineural hearing loss in various audiogram configurations, whereasPAX3andEDNRBvariants were associated with profound unilateral sensorineural hearing loss in flat audiogram configurations. In addition, whole genome sequencing and extended next-generation sequencing targeting 213 deafness genes were performed in two multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and congenital cytomegalovirus infection were observed in nine and two patients without definite genetic diagnoses.ConclusionGenetic underpinnings can contribute to approximately 20% of childhood unilateral sensorineural hearing loss, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of unilateral sensorineural hearing loss in children.

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.

Spasticity is a common complication for patients with stroke, but only few studies investigate the relation between spasticity and voluntary movement. This study proposed a novel automatic system for assessing the severity of spasticity (SS) of four upper-limb joints, including the elbow, wrist, thumb, and fingers, through voluntary movements. A wearable system which combined 19 inertial measurement units and a pressure ball was proposed to collect the kinematic and force information when the participants perform four tasks, namely cone stacking (CS), fast flexion and extension (FFE), slow ball squeezing (SBS), and fast ball squeezing (FBS). Several time and frequency domain features were extracted from the collected data, and two feature selection approaches based on recursive feature elimination were adopted to select the most influential features. The selected features were input into five machine learning techniques for assessing the SS for each joint. The results indicated that using CS task to assess the SS of elbow and fingers and using FBS task to assess the SS of thumb and wrist can reach the highest weighted-average F1-score. Furthermore, the study also concluded that FBS is the optimal task for assessing all the four upper-limb joints. The overall result shown that the proposed automatic system can assess four upper-limb joints through voluntary movements accurately, which is a breakthrough of finding the relation between spasticity and voluntary movement.

Cynanchum paniculatum (Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(−) PR(−)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(−)) in a 24 h scratch assay. Our data suggested that ER(−) PR(−) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(−) cells, and this correlated with MMP-2 regulation. The migration of ER(−) PR(−) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.

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.

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis.

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.

Aim 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. Methods 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. Results 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. Conclusion 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.

In this paper, the flow stresses, the constitutive equation, processing map and the critical conditions of dynamic recrystallization (DRX) of the hot forged QCr0.8 alloy are studied by hot compressive test in the 750-900°C temperature and 0.01-10s-1 strain rate ranges using Gleeble-1500D thermo-mechanical simulator. The compression reduction of thermal compression deformation is 50%. The results show that the thermal deformation temperatures and strain rates have a significant effect on the high temperature deformation behavior of the alloy. The higher the temperature, the smaller the strain rate and the easier the DRX of the alloy is found.The peak stresses of the alloy decreases with the increase of temperature and increases with the increase of the strain rates.The flow stresses during hot deformation can be described by a hyperbolic sine function. The activation energy Q of the thermal compression deformation is determined to be 370.8KJ/mol. The constitutive equation and processing map of the alloy are established. Critical strains of DRX εc are studied by the inflection point characteristic of the lnθ-ε curve of the alloy and the corresponding minimum value of the ∂θ (∂θ)/∂ε-ε curve.

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.

Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The participants were 1,478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items and the second for confirmatory factor analysis. The factor analysis identified three factors: F1 (sialorrhea, akathisia, dystonia, and dyskinesia), F2 (gait and bradykinesia), and F3 (muscle rigidity and tremor). The present results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: central dopaminergic mechanisms with the pathophysiology other than acute parkinsonism (F1), acute parkinsonism observed during action (F2), and acute parkinsonism observed at rest (F3).

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.

Cynanchum paniculatum (Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(−) PR(−)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(−)) in a 24 h scratch assay. Our data suggested that ER(−) PR(−) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(−) cells, and this correlated with MMP-2 regulation. The migration of ER(−) PR(−) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.

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.

Background: PIM-Taiwan criteria were first established in 2010 for potentially inappropriate medications (PIMs). Currently, updating of PIM criteria is mandatory because of newly established evidence and newly developed medications. This study aims to evaluate the prevalence of PIM based on country-specific PIM criteria and factors associated with PIM use by applying 2010 version and newly updating PIM-Taiwan criteria in a cohort with polypharmacy. Methods: The baseline data of Medication Safety Review Clinic Taiwan (MSRC–Taiwan) study were used to investigate the prevalence of PIMs. Older patients (aged ⩾65 years) who were either having polypharmacy or visited ⩾3 different physicians were enrolled between August and October 2007. Bivariate analysis and multivariate logistic regressions were used to evaluate the factors associated with PIM use. Results: The prevalence of having at least one PIM was 46.1% for 2010 version and increased to 74.6% for 2018 version. The average number of PIMs generally to be avoided per patient also increased for 2018 version (0.2 versus 1.2, p < 0.0001). In contrast, the average number of PIMs considering chronic conditions per patient decreased (0.6 versus 0.3, p < 0.001). The associated chronic conditions of PIM users were distinct between 2010 and 2018 version. The major leading PIMs were benzodiazepines (BZDs) in both versions of criteria. Conclusions: As there were significant differences in medication lists between PIM-Taiwan version 2010 and 2018, the prevalence of PIM and factors associated with PIM users varied accordingly. Physicians should pay special attention before prescribing BZDs which keep being the major leading PIM.

BACKGROUND 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. METHODS 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. RESULTS Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P

AIM 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. METHODS 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. RESULTS 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%. CONCLUSION 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.

Aim 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. Methods 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. Results 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. Conclusion 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.

Objective: Little is known about the prescription pattern of psychotropic drugs for patients with schizophrenia in Pakistan. The purpose of this study was to evaluate the characteristic features of psychotropic drug prescriptions for patients with schizophrenia in Pakistan. Methods: Three centers in Pakistan participated in a large scale collaborative study known as Research on Asian Prescription Pattern (REAP). The 2016 REAP survey included centers from 15 countries in Asia and used a unified research protocol. The design of the study was quantitative and of descriptive epidemiology. Analysis was made on the data collected from three centers i.e., Lahore, Karachi and Islamabad. The data collected in Pakistan were compared with those from other Asian countries. The details of REAP were presented on the homepage of REAP (http://www.REAP.Asia). Results: From Pakistan, 298 patients were included. Patients with schizophrenia in Pakistan received higher rate of antipsychotic polypharmacy and a higher rate of co-prescription of mood stabilizers and anxiolytics when compared with participants from other South Asian countries (India and Bangladesh). Conclusion: The main findings of the study were that a majority of the patients were prescribed antipsychotic polypharmacy drugs in Pakistan. Insufficient training on the use of psychotropic drugs and a lack of treatment guideline are considered to be the major contributing factors. Further education and training on the proper use of psychotropic drugs are recommended to psychiatrists in Pakistan. The guidelines on pharmacotherapy for patients with schizophrenia should also be developed and promoted in Pakistan.

Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis. Conversely, AR knockdown suppressed lactate formation and inflammation. Using cultured liver cancer cells, we also demonstrated that AKT1 was essential for AR-induced dysregulation of AKT/mTOR signaling, metabolic reprogramming, antioxidant defense, and inflammatory responses. These findings suggest that aberrantly overexpressed/over-activated hepatic AR promotes HCC development at least in part by interacting with oncogenic AKT1 to augment AKT/mTOR signaling. Inhibition of AR and/or AKT1 might serve as an effective strategy for the prevention and therapy of liver cancer.

Air Engines (AE) are commonly designed to work in combination with internal combustion engines (ICE) due to low energy density. The emission of heat from ICE boosts the efficiency of Air Engines, whereas the high-pressure gas from AE serves as a form of turbo charging for ICE, increasing its efficiency. Unlike batteries, the air tank that AE requires is not limited by certain restrictions in order to prolong its lifetime, therefore, the Air Hybrid System is believed to have great potential. There has already been quite some research on power management strategy of electric hybrid systems, however, little is done on Air hybrid systems. A numerical models of Air Hybrid Systems is established using MATLAB in this study, the characteristics of the model, such as the efficiency map and driving cycles are further analyzed to obtain the optimal energy management strategy for Air Hybrid Systems. These findings are expected to help the realization of physical models and the establishment of controller design. Through genetic algorithms, the optimal system structures, operation modes and power management strategies are found to ensure that both engines are operating within the most efficient range. Simulation results suggest that the efficiency of the Air Hybrid System is 26.13% higher comparing to a lone Air Engine.

Aim 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. Methods 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. Results 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. Conclusion Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

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.

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.

Capturing hand motions for hand function evaluations is essential in the medical field. Various data gloves have been developed for rehabilitation and manual dexterity assessments. This study proposed a modular data glove with 9-axis inertial measurement units (IMUs) to obtain static and dynamic parameters during hand function evaluation. A sensor fusion algorithm is used to calculate the range of motion of joints. The data glove is designed to have low cost, easy wearability, and high reliability. Owing to the modular design, the IMU board is independent and extensible and can be used with various microcontrollers to realize more medical applications. This design greatly enhances the stability and maintainability of the glove.

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

Aims Little is known about electroconvulsive therapy (ECT) use in Asian inpatients with schizophrenia. This study examined trends of ECT use for schizophrenia patients in Asia between 2001 and 2009 and its independent demographic and clinical correlates. Methods Data on 6761 hospitalized schizophrenia patients (2001 = 2399, 2004 = 2136, and 2009 = 2226) in nine Asian countries and territories were collected by either chart review or interviews during a 1-month period. Patients’ sociodemographic and clinical characteristics, prescriptions of psychotropic drugs and ECT use were recorded using a standardized protocol and data-collection procedure. Results The frequency of ECT was 3.3% in the whole sample; rising from 1.8% in 2001 to 3.3% in 2004 and 4.9% in 2009 (P

Introduction Research in prescription pattern of antidepressants in Asia is lacking. This study aims to compare the antidepressants prescription pattern in Asia in 2003–2004 and 2013. Methods The Research in East Asia Psychotropic Prescription Pattern on Antidepressants (REAP-AD) had worked collaboratively in 2003–2004 (REAP-AD 2003/2004) and 2013 (REAP-AD 2013) to study the prescription pattern of antidepressants in Asia. The REAP-AD 2013 study was conducted in China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand using a unified research protocol and questionnaire. Results Forty psychiatric centers participated in REAP-AD 2013 and a total of 2,319 patients receive antidepressants were analyzed. In 2013, 39.6% of the antidepressant prescriptions were for diagnoses other thandepressive disorder compared with 38.4% in REAP-AD 2003/2004. Out of all the antidepressants listed in the Anatomical Therapeutic Chemical Classification index by the World Health Organization Collaborating Center for Drug Statistics Methodology (Oslo), only 38% antidepressants were prescribed in participating centers in 2013 compared with 46% in REAP-AD 2003/2004. The selective serotonin reuptake inhibitors were the most common antidepressant prescribed in the participating centers, which was similar to the 2003–2004 survey. Prescription of newer generation antidepressants had increased in 2013 survey; on the contrary, prescription of tricyclic antidepressants had reduced. Discussion This study has contributed significantly in relation to the changing patterns of antidepressant use in all the participating Asian centers in the last 10 years. The findings are important in shaping optimal antidepressant prescription and future policy making.

Objective Little is known about the pattern of QT interval (QTc) prolongation in Asian patients with schizophrenia. This study examined trends of QTc prolongation in schizophrenia inpatients in six Asian countries and territories between 2004 and 2008/2009 and its independent demographic and clinical correlates. Method Data on 3482 hospitalized schizophrenia patients (2004 = 1826 and 2008/2009 = 1656) in six Asian countries and territories were collected by either chart review or interviews during a 1-month period. Patients' sociodemographic and clinical characteristics, prescriptions of psychotropic drugs, and QTc interval were recorded using a standardized protocol and data collection procedure. Results The frequency of QTc prolongation (>456 ms) was 2.4% in the whole sample, decreasing from 3.1% in 2004 to 1.6% in 2008/2009 (p = 0.004) with wide intercountry variations. However, this decreased trend was driven by decreased QTc prolongation detected in China and Hong Kong (both p-values

Introduction This study was to assess differences in the symptom profile of depressive illness across various countries/territories in Asia. The study was a part of the Research on Asia Psychotropic Prescription project. The participating countries/territories include China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand. Methods The pattern of depressive symptoms in 1,400 subjects with depressive disorder from 42 psychiatric centers in 10 Asian countries/territories was assessed. We collected information on socio-demographic and clinical characteristics with a standardized protocol and data collection procedure. Results The most common presentations of depressive symptoms were persistent sadness, loss of interest, and insomnia. Similar findings were found regardless of the region, country, or its income level. Patients with depressive disorder from high-income countries presented significantly more with vegetative symptom cluster (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.

Insulin is associated with the progression of numerous different types of cancer. However, the association between insulin and non-small cell lung carcinoma (NSCLC) remains unknown. The aim of the present study was to evaluate the role of insulin in the proliferation, migration and drug resistance of NSCLC cells, and to determine whether the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway was involved. NSCLC cells were treated with insulin in the absence or presence of LY294002, an inhibitor of the PI3K/Akt pathway. Following co-incubation with insulin, cell proliferation and drug resistance were measured by MTT; cell migration was examined by wound healing and Transwell assays; and the expression of cyclin A, proliferating cell nuclear antigen (PCNA), p27, matrix metalloproteinase 3 (MMP3), P-gp and proteins involved in the PI3K/Akt pathway were assessed via western blotting. The results of the current study demonstrated that insulin enhanced the proliferation, migration and drug resistance of NSCLC cells. Correspondingly, insulin upregulated the expression of cyclin A, PCNA, MMP3, P-gp and downregulated p27 expression in NSCLC cells. Following treatment with insulin, it was demonstrated that phospho-Akt expression increased in a dose-dependent manner. However, the effects of insulin on NSCLC cells was inhibited by the PI3K/Akt pathway inhibitor LY294002. Therefore, the results of the current study indicate that insulin is associated with the development of NSCLC by activating the PI3K/Akt pathway. This may improve understanding of the mechanism of action of insulin in NSCLC in the future.

The aberrant expression of retinoic acid receptor-α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells. The expression of RARα was significantly elevated in LSCC tissues compared with adjacent noncancerous tissues (78.1 vs. 6.3%, P