Clinical outcomes, medical costs, and medication usage patterns of different somatic symptom disorders and functional somatic syndromes: a population-based study in Taiwan.

BACKGROUND: Somatic symptom disorders (SSD) and functional somatic syndromes (FSS) are often regarded as similar diagnostic constructs; however, whether they exhibit similar clinical outcomes, medical costs, and medication usage patterns has not been examined in nationwide data. Therefore, this study focused on analyzing SSD and four types of FSS (fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional dyspepsia). METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance (NHI) claims database to investigate the impact of SSD/FSS. The study included 2 615 477 newly diagnosed patients with SSD/FSS and matched comparisons from the NHI beneficiary registry. Healthcare utilization, mortality, medical expenditure, and medication usage were assessed as outcome measures. Statistical analysis involved Cox regression models for hazard ratios, generalized linear models for comparing differences, and adjustment for covariates. RESULTS: All SSD/FSS showed significantly higher adjusted hazard ratios for psychiatric hospitalization and all-cause hospitalization compared to the control group. All SSD/FSS exhibited significantly higher adjusted hazard ratios for suicide, and SSD was particularly high. All-cause mortality was significantly higher in all SSD/FSS. Medical costs were significantly higher for all SSD/FSS compared to controls. The usage duration of all psychiatric medications and analgesics was significantly higher in SSD/FSS compared to the control group. CONCLUSION: All SSD/FSS shared similar clinical outcomes and medical costs. The high hazard ratio for suicide in SSD deserves clinical attention.

Inter- and Intrarater Reliability of the Gap-Kalamazoo Communication Skills Assessment Form Among Occupational Therapy Interns.

IMPORTANCE: Effective communication skills (CS) are essential for occupational therapists. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool for assessing the CS of medical residents. However, the interrater reliability for the nine CS domain scores ranges from poor to good. The intrarater reliability remains unclear. OBJECTIVE: To examine the inter- and intrarater reliability of the GKCSAF's nine domain scores and total score among occupational therapy interns. DESIGN: Repeated assessments with the GKCSAF. SETTING: Medical center psychiatry department. PARTICIPANTS: Twenty-five interns and 49 clients with mental illness, recruited from August 2020 to December 2021. OUTCOMES AND MEASURES: The transcripts of 50 evaluation interviews between clients and interns were used. Three independent raters assessed each transcript twice, at least 3 mo apart. RESULTS: The GKCSAF demonstrated poor interrater reliability for the nine domain scores (weighted κ = .08-.30) and the total score (intraclass correlation coefficient [ICC] = .22, 95% confidence interval [CI] [.10, .35]). The GKCSAF showed poor to intermediate intrarater reliability for the nine domain scores (weighted κ = .27-.73) and fair reliability for the total score (ICC = .69, 95% CI [.60, .77]). CONCLUSIONS AND RELEVANCE: The GKCSAF demonstrates poor interrater reliability and poor to intermediate intrarater reliability for the nine domain scores. However, it demonstrates fair intrarater reliability in assessing the overall CS performance of occupational therapy interns. Significant variations were observed when different raters assessed the same interns' CS, indicating inconsistencies in ratings. Consequently, it is advisable to conservatively interpret the CS ratings obtained with the GKCSAF. Plain-Language Summary: It is essential for occupational therapists to effectively communicate with clients. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool that is used to assess the communication skills of medical residents. The study authors used the GKCSAF with occupational therapy interns in a medical center psychiatry department to assess how effectively they interviewed clients with mental illness. This study aids occupational therapy personnel in the interpretation of GKCSAF results. The study findings also highlight the importance of developing reliable and standardized measures to assess communications skills in the field of occupational therapy.

Better resolving of anti-CD38 antibody interference with blood compatibility testing by using manual polybrene method compared with dithiothreitol-pretreatment indirect antiglobulin test.

BACKGROUND: It is advised to pretreat the reagent erythrocytes with Dithiothreitol (DTT) to denature the surface CD38 to prevent anti-CD38 monoclonal antibodies (MoAb) from interfering with the blood compatibility test. Anti-CD38 has little impact on the Polybrene test, but it is still unknown how sensitive it is to detect irregular antibodies and how effective it is when compared to the standard DTT-based method. METHODS: Twenty-one patients receiving daratumumab (N = 13) and isatuximab (N = 8) had their serum collected. Standard anti-sera (anti-c, D, E, Fyb , Jka , M, Mia ) with serial dilution were added to patients' serum. Antibody screening tests were performed simultaneously using the manual polybrene method (MP) and DTT-pretreated, automatic indirect antiglobulin test (DTT-IAT) to compare the detection sensitivity. These two methods' operating times and costs were also analyzed. RESULTS: Both MP and DTT-IAT can overcome the interference caused by anti-CD38 MoAb. However, MP is more sensitive in detecting anti-M and anti-Mia and is comparable to DTT-IAT in detecting other antibodies. In terms of cost and operating time, MP is also far superior to DTT-IAT. CONCLUSION: MP is a cost-effective alternative to DTT-IAT in resolving anti-CD38 interference and is especially suitable for populations with a high prevalence of anti-M and anti-Mia . However, both methods have a well-known drawback of low detection sensitivity for anti-K, and K-units should be provided to patients to prevent hemolytic transfusion reactions.

Effects of nonlinear internal gravity waves on normal-incident reflection measurements of seafloor sediments.

Sonar data acquired by sub-bottom profilers and echosounder systems are widely used to estimate geoacoustic properties of marine sediments. However, the uncertainty of the seabed property estimates caused by water-column variability may limit the application. In this paper, the acoustic focusing and defocusing effects of nonlinear internal gravity waves on normal-incident acoustic reflection measurements are studied. The experiment data were collected in the South China Sea from two transceiver moorings located at two different sites, one of which contained strong nonlinear internal waves (NIWs), while another site did not. The observed reflection intensity variation at the internal wave site varied up to 10 dB. On the other hand, the bottom reflections at the other site without internal waves were stable, and a seafloor sediment sample collected there was analyzed to validate the sediment type inferred from bottom loss. Numerical simulations using ray-tracing and parabolic equation models confirmed the cause of this intensity fluctuation by the acoustic focusing and defocusing of NIWs. This study eventually showed that NIWs may induce a significant bias for geoacoustic property estimates from seabed reflection coefficients.

The Influence of Diabetes Mellitus on the Risks of End-Stage Kidney Disease and Mortality After Liver Transplantation.

This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78-3.99) and 2.61 (95% CI, 1.63-4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72-1.55) and 1.28 (95% CI, 1.04-1.59) for PLTDM group and pre-existing DM group compared to those without DM group, respectively. The sensitivity analysis for the risk of ESKD and death also revealed the consistent result. Pre-existing DM has significant increase the risk of post-LT ESKD and mortality. The role of PLTDM should be explored to explain postoperative morbidity and mortality.

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study.

BACKGROUND: Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge. METHODS: Data were retrieved from Taiwan's National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities. RESULTS: For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89-1.02] in the propensity score study design and 1.06 (95% CI 1.01-1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34). CONCLUSIONS: The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.

Specific personality traits and associated psychosocial distresses among individuals with heroin or methamphetamine use disorder in Taiwan.

BACKGROUND/PURPOSE: Previous studies showed the association between substance use disorders (SUDs) and borderline and antisocial personality disorders. Substance abusers may have emotional, somatic and interpersonal distresses. This study aimed to investigate the associations between substance, personality and psychosocial distresses. METHODS: This cross-sectional, questionnaire-based study recruited 39 individuals with heroin use disorder (HUD), 111 with methamphetamine use disorder (MUD) and 101 as the control group in a rural area of Taiwan. The Tridimensional Personality Questionnaire (TPQ) and Opiate Treatment Index were used to assess the association between personality and psychosocial conditions. Deviations of the three personality dimensions of TPQ (novelty seeking, harm avoidance, and reward dependence) could reflect eight personality patterns. RESULTS: We found SUD was associated with high novelty seeking and harm avoidance traits and explosive (borderline) personality pattern, whereas HUD was also linked with sensitive (narcissistic) pattern. Subjects with HUD tended to have more deviant personality traits than subjects with MUD. For subjects with SUDs, all three personality dimensions and sensitive (narcissistic) personality patterns were associated with emotional and somatic distresses, and those with explosive (borderline) and sensitive (narcissistic) patterns had poor social functioning. CONCLUSION: Our results indicate substance abusers with high novelty seeking and harm avoidance, corresponding to explosive (borderline) or sensitive (narcissistic) patterns, to have a higher tendency to suffer from somatic and psychosocial distresses.

Risk of Infective Endocarditis After Invasive Dental Treatments: Case-Only Study.

BACKGROUND: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE. METHODS: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT. RESULTS: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94-1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02-1.26) for 1 to 4 weeks after IDTs. CONCLUSIONS: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.

Measures of Heart Rate Variability in Individuals With Somatic Symptom Disorder.

OBJECTIVE: Little is known about autonomic nervous system activity in individuals with somatic symptom disorder (SSD) as defined by DSM-V criteria. The aims of this study were to investigate whether individuals with SSD differ from healthy controls in heart rate variability (HRV) measures of autonomic nervous system activity and whether sex has a moderating effect on this association. METHODS: We recruited 168 individuals with SSD (35.1% men) and 106 healthy controls (27.4% men). Demographics, HRV, and psychological factors were measured using the Patient Health Questionnaire-15, Health Anxiety Questionnaire, Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory. Multiple regression analysis was used to examine the association of SSD with HRV, adjusting for demographic and psychological measures. RESULTS: Individuals with SSD had lower levels of total-power HRV and low-frequency HRV, but no differences in high-frequency (HF)-HRV were found. HRV differences between SSD and controls varied by sex and age (triple interaction TP-HRV ß = -0.222, p < .001; low-frequency HRV ß = -0.332, p < .001; and HF-HRV ß = -0.167, p = .006). Whole-sample multiple regression analyses revealed significant sex differences in the magnitudes of the association between BDI-II with HF-HRV (ß of sex*BDI-II: 0.761, p = .005) and analyses stratified by sex indicated that HF-HRV was significantly correlated with depression in men with SSD (r = -0.491, p < .001) but not in women with SSD (r = 0.057, p = .558). CONCLUSIONS: These results suggest that patients with SSD demonstrate different patterns of HRV and the patterns of association between HRV indices and psychological factors vary between men and women.

Prevalence and clinical correlates of flunitrazepam-related complex sleep behaviors.

AIM: Complex sleep behaviors (CSB) are often associated with the use of hypnotic drugs. This study investigated the prevalence and correlates of CSB among psychiatric patients who were given flunitrazepam. METHODS: From June 2011 to May 2012, a total of 268 psychiatric outpatients who had received flunitrazepam for at least 3 months were enrolled. Data on occurrence of CSB, demographic characteristics, flunitrazepam dosage and duration of use, psychiatric diagnoses, physical illnesses, and alcohol use were collected. Logistic regression analysis was used to examine the clinical correlates of CSB. RESULTS: Sixty-six participants (24.6%) reported experiencing CSB. Logistic regression analysis showed that a high dosage (>2 mg/day) of flunitrazepam (odds ratio [OR] = 1.941, 95% confidence interval [CI] = 1.090-3.455, P = 0.024) and alcohol use (OR = 1.948, 95%CI = 1.023-3.709, P = 0.042) were significantly associated with the occurrence of CSB. Sex, age, duration of flunitrazepam use, psychiatric diagnoses, and physical illnesses were not significantly associated with the occurrence of CSB. CONCLUSION: CSB among flunitrazepam users should be monitored routinely, especially among those receiving a high dosage who also consume alcohol.

Application of the Chinese Version of the Whiteley Index-7 for Detecting DSM-5 Somatic Symptom and Related Disorders.

BACKGROUND: The Whiteley Index-7 (WI-7) is frequently used for evaluating patients with suspected hypochondriasis. However, information about its use on somatic symptom and related disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is still lacking. This study investigated the psychometric properties of the Mandarin Chinese version of the WI-7 and its application to evaluation of somatic symptom and related disorders. METHODS: Participants completed the WI-7 and received diagnostic interview based on both Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and DSM-5 criteria. Exploratory factor analysis was performed, and the test-retest reliability and the internal consistency of the WI-7 were assessed. Receiver Operating Characteristic curves were established, and the area under the curve was calculated to determine the cutoff point to distinguish DSM-IV somatoform disorders and DSM-5 somatic symptom and related disorders, respectively. RESULTS: A total of 471 subjects were recruited for this study. The exploratory factor analysis of the WI-7 identified a single factor. The internal consistency and test-retest reliability of the WI-7 were 0.829 and 0.836, respectively. The area under Receiver Operating Characteristic curve using WI-7 to distinguish DSM-5 somatic symptom and related disorders is 0.660, higher than that when applying to distinguish DSM-IV somatoform disorders. The sensitivity and specificity at an optimal cutoff point of 0/1 are 0.645 and 0.675, respectively. CONCLUSION: The Mandarin Chinese version of the WI-7 is a potentially useful tool to detect individuals with DSM-5 somatic symptom and related disorders.

The relation between the patient health questionnaire-15 and DSM somatic diagnoses.

BACKGROUND: Our purpose was to examine the reliability and validity of the Chinese version of the Patient Health Questionnaire-15 (PHQ-15) in Taiwan, and to explore its relation to somatoform disorders (DSM-IV) and to somatic symptom and related disorders (DSM-5). METHODS: We recruited 471 individuals, 151 with somatoform disorders and 200 with somatic symptom and related disorders. Subjects completed the Chinese version of the PHQ-15, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and received a DSM-IV- and DSM-5-based diagnostic interview. We performed exploratory factor analysis and assessed test-retest reliability, internal consistency, and correlation with BDI-II/BAI to confirm reliability and validity, and carried out ROC curve analysis to determine suitability for evaluation or screening purposes. PHQ-15 scores were compared between patients with various DSM-IV psychiatric diagnoses (such as DSM-IV somatoform disorders, panic disorder, other anxiety/depressive disorders) or no DSM-IV diagnosis and patients with DSM-5 somatic symptom and related disorders or no DSM-5 diagnosis. RESULTS: The Chinese version identified cardiopulmonary, pain-fatigue, and gastrointestinal as major factors and had good reliability (0.803-0.930), internal consistency (0.637-0.861), and correlation coefficients with BDI-II/BAI (0.407-0.619, 0.536-0.721, respectively). The PHQ-15 scores were similar in patients with somatoform disorders and patients with panic disorder; higher in patients with somatoform disorders and panic disorder than in patients with other anxiety/depressive disorders; and significantly higher in patients with somatic symptom and related disorders than in patients without this diagnosis. The AUC of the PHQ-15 was 0.678 (cutoff 6/7) for screening somatoform disorders (DSM-IV) and 0.725 (cutoff 4/5) for screening somatic symptom and related disorders (DSM-5). CONCLUSIONS: The Chinese version of the PHQ-15 is suitable for evaluating somatic symptom and related disorders. The preponderance of somatic symptom disorder in our sample, lack of evaluation of functional disorders, and recruitment solely from psychiatric clinics are possible limitations.

Differences in Clinical Features of Methamphetamine Users with Persistent Psychosis and Patients with Schizophrenia.

BACKGROUND: Methamphetamine exerts neurotoxic effects and elicits psychotic symptoms. This study attempted to compare clinical differences between methamphetamine users with persistent psychosis (MAP) and patients with schizophrenia. In addition, we examined the discrimination validity by using symptom clusters to differentiate between MAP and schizophrenia. METHODS: We enrolled 53 MAP patients and 53 patients with schizophrenia. The psychopathology of participants was assessed using the Chinese version of the Diagnostic Interview for Genetic Studies and the 18-item Brief Psychiatric Rating Scale. Logistic regression was used to examine the predicted probability scores of different symptom combinations on discriminating between MAP and schizophrenia. The receiver operating characteristic (ROC) analyses and area under the curve (AUC) were further applied to examine the discrimination validity of the predicted probability scores on differentiating between MAP and schizophrenia. RESULTS: We found that MAP and schizophrenia demonstrated similar patterns of delusions. Compared to patients with schizophrenia, MAP experienced significantly higher proportions of visual hallucinations and of somatic or tactile hallucinations. However, MAP exhibited significantly lower severity in conceptual disorganization, mannerism/posturing, blunted affect, emotional withdrawal, and motor retardation compared to patients with schizophrenia. The ROC analysis showed that a predicted probability score combining the aforementioned 7 items of symptoms could significantly differentiate between MAP and schizophrenia (AUC = 0.77). CONCLUSION: Findings in the current study suggest that nuanced differences might exist in the clinical presentation of secondary psychosis (MAP) and primary psychosis (schizophrenia). Combining the symptoms as a whole may help with differential diagnosis for MAP and schizophrenia.

[18F]-Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value as a Predictor of Adjuvant Chemotherapy Benefits in Patients With Nasopharyngeal Carcinoma.

BACKGROUND: The role of adjuvant chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is controversial, and the identification of adequate predictive factors is warranted. Therefore, we aimed to investigate whether the mean standardized uptake value (SUV) measured on [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict the survival benefits for NPC patients that receive adjuvant chemotherapy. MATERIALS AND METHODS: The data for 174 NPC patients who underwent PET/computed tomography before chemoradiation between January 2004 and January 2012 were reviewed. The SUV75% was recorded for primary tumors. All patients received intensity-modulated radiotherapy and cisplatin-based chemotherapy. Adjuvant chemotherapy consisted of 3 cycles of 75 mg/m(2) cisplatin and 1,000 mg/m(2) fluorouracil for 4 days. RESULTS: The optimal cutoff value was 8.35 for SUV75%, with 112 (64.4%) patients having lower SUV75% and 62 (35.6%) having higher SUV75%. Patients with lower SUV75% had significantly better 5-year overall survival (OS) and distant metastasis-free survival. Multivariate analysis revealed that tumor stage, SUV75%, and adjuvant chemotherapy were significant prognostic factors for OS. Patients with higher SUV75% had significantly higher 5-year OS rates with adjuvant chemotherapy than without adjuvant chemotherapy (84.3% vs. 32.4%, respectively; p < .001). However, in the lower SUV75% group, no differences in 5-year OS were observed between patients who received and those who did not receive adjuvant chemotherapy (92.4% vs. 93.3%, respectively; p = .682). CONCLUSION: The SUV75% on FDG PET for primary tumors could successfully identify NPC patients who may benefit from adjuvant chemotherapy.

A tool to predict risk for gastric cancer in patients with peptic ulcer disease on the basis of a nationwide cohort.

BACKGROUND & AIMS: Patients with gastric ulcers have significantly higher risk of gastric cancer, especially within 2 years after diagnosis. We used data from a national database to develop a personalized risk prediction model for patients with peptic ulcer diseases. METHODS: We collected data from Taiwan's National Health Insurance Research Database on 278,898 patients admitted for the first time with a primary diagnosis of peptic ulcer disease. We used the data to develop a nomogram, which we validated by discrimination and calibration, and in a test cohort. Cumulative incidences of study subjects predicted by the nomogram were examined. RESULTS: In total, 1269 subjects developed gastric cancer. Age, sex, peptic ulcer sites, peptic ulcer complications, Helicobacter pylori eradication, nonsteroidal anti-inflammatory drug use, and surveillance endoscopy were independent factors associated with risk of gastric cancer (all P < .001). The concordance index for the nomogram developed on the basis of these factors was 0.78. Study subjects were divided into quartiles of predicted risk scores; from lowest score quartile to highest, cumulative incidences at 1 year were 7.4/10,000 people, 14.2/10,000 people, 25.5/10,000 people, and 86.6/10,000 people. The cumulative incidences at 2 years were 9.3/10,000 people, 20.9/10,000 people, 38.0/10,000 people, and 135.7/10,000 people for the same quartiles of risk scores. The nomogram was validated in an independent cohort, and similar incidence values were determined. CONCLUSIONS: We developed and validated a nomogram to predict risk for gastric cancer 1 and 2 years after diagnosis of peptic ulcer disease. The nomogram provides a prognostic tool that can be easily used for individuals and can help physicians explain risk levels to patients.

Clozapine induces autophagic cell death in non-small cell lung cancer cells.

BACKGROUND/AIMS: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. METHODS: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. RESULTS: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. CONCLUSIONS: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth.

The deregulation of epigenetics was involved in early and subsequent carcinogenic events. Reversing cancer epigenetics to restore a normal epigenetic condition could be a rational approach for cancer treatment and specialized prevention. In the present study, we found that the expression levels of two epigenetic markers, histone H3K27 trimethylation (H3K27me3), was low but histone H3S10 phosphorylation (pH3Ser10) was high in human bladder cancer tissues, which showed opposite expression patterns in their normal counterparts. Thus, we investigated whether a natural product, emodin, has the ability to reverse these two epigenetic modifications and inhibit bladder cancer cell growth. Emodin significantly inhibited the cell growth of four bladder cancer cell lines in a dose- and time-dependent manner. Emodin treatment did not induce specific cell cycle arrest, but it altered epigenetic modifications. Emodin treatment resulted in the suppression of pH3Ser10 and increased H3K27me3, contributing to gene silencing in bladder cancer cells. Microarray analysis demonstrated that oncogenic genes including fatty acid binding protein 4 (FABP4) and fibroblast growth factor binding protein 1 (HBP17), RGS4, tissue inhibitor of metalloproteinase 3 (TIMP3), WNT5b, URB, and collagen, type VIII, alpha 1 (COL8A1) responsible for proliferation, survival, inflammation, and carcinogenesis were significantly repressed by emodin. The ChIP assays also showed that emodin increased H3K27me3 but decreased pH3Ser10 modifications on the promoters of repressed genes, which indicate that emodin reverses the cancer epigenetics towards normal epigenetic situations. In conclusion, our work demonstrates the significant anti-neoplastic activity of emodin on bladder cancer cells and elucidates the novel mechanisms of emodin-mediated epigenetic modulation of target genes. Our study warrants further investigation of emodin as an effective therapeutic or preventive agent for bladder cancer.

Readiness to quit as a predictor for outcomes of smoking-reduction programme with transdermal nicotine patch or bupropion in a sample of 308 patients with schizophrenia.

Readiness to quit has been found to predict smoking-cessation outcomes in a general population. However, little is known about the relationship between the readiness to quit and smoking-reduction outcomes in patients with schizophrenia treated with pharmacological adjuvants. The aim of this study was to examine the association between readiness to quit and smoking-reduction outcomes in patients with schizophrenia. A total of 308 subjects using nicotine replacement therapy (NRT) (N = 242) or bupropion (N = 66) participated in an 8-week smoking-reduction programme. Participants were categorised into precontemplators (N = 127), contemplators (N = 76) and preparators (N = 105) to quit smoking based on the transtheoretical model. There was a significant difference in change in number of cigarettes (NOC) (p = 0.007) and Fagerstrom test for nicotine dependence (FTND) score (nicotine dependence level) (p = 0.029) across the stages of change. A linear regression model revealed trend of increasing reduction in NOC and FTND scores in different stages of change (NOC: B = -1.22, t = -2.81, p = 0.005; FTND: B = -0.43, t = -2.57, p = 0.011). However, the 7-day point prevalence of abstinence was 5.5% (18/308), but there was no significant association between stage of change and smoking cessation (p = 0.26), possibly due to a very small sample size of successful quitters. In summary, among a cohort of institutionalised chronic schizophrenia patients receiving 8-week NRT or bupropion, stage of change can predict smoking reduction and may serve as a useful indicator for patients' preparedness before a trial of smoking reduction.