A proposed approach to confirm heroin administration - Regional differences in heroin purity is a major factor.

In forensic toxicology, a marker of street heroin use is urgent especially in the absence of urinary 6-monoacetylmorphine. ATM4G, the Glucuronide of Acetylated product of Thebaine compound 4 Metabolite (ATM4), arising from byproducts of street heroin synthesis has been considered as a useful marker in some European studies. However, whether ATM4G is a universal marker particularly in Southeast Asia due to 'street' heroin with high purity, it's still unclear. To investigate putative markers for different regions, ATM4G and other metabolites including the Acetylated product of Thebaine compound 3 Metabolite (ATM3) and thebaol, also originated from thebaine were detected in 552 urine samples from heroin users in Taiwan. Results were compared with that from samples collected in the UK and Germany. Only a sulfo-conjugate of ATM4, ATM4S, was detected in 28 Taiwanese users using a sensitive MS3 method whilst out of 351 samples from the UK and Germany, ATM4G was present in 91. Thebaol-glucuronide was first time detected in 118. No markers were detected in urine following herbal medicine use or poppy seed ingestion. The presence of ATM4S/ATM4G might be affected by ethnicities and heroin supplied in regions. Thebaol-glucuronide is another putative marker with ATM4G and ATM4S for street heroin use.

Macrocytosis among patients with heroin use disorder.

PURPOSE: Few empirical studies have investigated hematological parameters among people with a heroin use disorder. This study explores the prevalence of macrocytosis and associated factors among patients with heroin use disorder who were entering methadone maintenance treatment (MMT) in Taiwan. PATIENTS AND METHODS: In this cross-sectional study, hematological parameters were measured and the prevalence of macrocytosis was assessed in a sample of 958 patients with a heroin use disorder entering the MMT program at Tsaotun Psychiatric Center in Taiwan. The demographic characteristics, heroin-related issues, other substance use history, and other clinical variables were analyzed. Univariate analysis was used to assess the association of all variables. Multivariable logistic regression was used to identify the relationship between the significant factors and macrocytosis. RESULTS: The study found that nearly one-fifth (19.5%) of the participants had macrocytosis. Older age, longer duration of heroin use, and more days of alcohol use within the previous month were associated with macrocytosis. CONCLUSION: We found that concurrent use of alcohol was an important factor related to macrocytosis among people with a heroin use disorder. The prevalence of macrocytosis indicated that alcohol use is common among this population. It is suggested that policies and practices regarding alcohol use should be addressed within methadone maintenance programs.

Allergic rhinitis increases the risk of incident panic disorder among young individuals: A nationwide population-based cohort study in Taiwan.

BACKGROUND: Studies have reported an association between allergy and panic disorder. However, few studies have explored the relationship between allergic rhinitis and panic disorder. Previous studies were limited by cross-sectional study designs, self-reported symptoms, absence of matched controls, and lack of consideration of the influence of steroid and comorbidities. This study aimed to explore the longitudinal association between allergic rhinitis and panic disorder in a large population-based cohort of young people. METHODS: In this study, 79,917 new cases of allergic rhinitis between 1998 and 2012 in individuals younger than 20 years were identified from Taiwan's National Health Insurance Research Database. One control (nonallergic rhinitis) per case (allergic rhinitis) was randomly selected from the remaining sample, matching for age, sex, residence, and insurance premium. Both groups were followed until the end of 2013 for incidence of panic disorder. Cox regression analysis was performed, adjusting for sex, age, residence, insurance premium, systemic steroids, asthma, atopic dermatitis, allergic conjunctivitis, attention deficit hyperactivity disorder, depression, and Charlson index. RESULTS: Allergic rhinitis was associated with a 2-fold increase in risk for panic disorder after adjustment for other variables. Additional independent risk factor of panic disorders were female sex, older age group, and depression. LIMITATIONS: Lifestyle, substance use, smoking by the patient or family members, and psychosocial stressors were not evaluated. CONCLUSIONS: Allergic rhinitis was associated with increased risk of panic disorder. Assessment and intervention of allergy rhinitis among young people with panic disorder are critical.

Leptin/Adiponectin ratio as a potential biomarker for metabolic syndrome in patients with schizophrenia.

OBJECTIVE: Leptin and adiponectin are adipokines which have opposing roles in the development of insulin resistance and metabolic syndrome (MetS). Leptin/adiponectin ratio (L/A ratio) has been proposed as a good biomarker for MetS in general population. This study aimed to compare the strength of association between MetS and leptin, adiponectin and L/A ratio, as well as to assess their performance to diagnose MetS in patients with schizophrenia. METHODS: Patients diagnosed with DSM-IV schizophrenia and under clozapine or olanzapine monotherapy for at least six months were recruited. We used the modified ATP III criteria for Asians to evaluate subjects for a diagnosis of MetS. RESULTS: We recruited 262 study subjects with schizophrenia, and classified them into those with MetS (n = 87) and those without MetS (n = 175). Leptin level was positively correlated with BMI, waist circumference, and insulin level. Adiponectin level was negatively correlated with most metabolic parameters, except glucose level. L/A ratio was positively correlated with most metabolic parameters, except levels of glucose and HDL-C. Significant gender differences existed in leptin levels, adiponectin levels, and L/A ratio. Without and with adjustment of age and gender, binary logistic regression analysis showed that leptin level, adiponectin level, and L/A ratio were significantly associated with MetS. The area under curve (AUC) of L/A ratio and leptin level for MetS was 0.744 (95% CI = 0.685-0.802) and 0.666 (95% CI = 0.601-0.731). The AUC of adiponectin level for the absence of MetS was 0.717 (95% CI = 0.655-0.780). The discriminative strength of L/A ratio for MetS was better in men than in women. CONCLUSIONS: The present study results suggest that L/A ratio may be a preferential marker of metabolic syndrome in patients with schizophrenia compared to leptin or adiponectin alone.

Sleep disturbance and its associations with severity of dependence, depression and quality of life among heroin-dependent patients: a cross-sectional descriptive study.

BACKGROUND: Sleep disturbance is common and may adversely affect treatment outcome, mental health, and quality of life in heroin-dependent patients. Previous studies have focused upon patients receiving treatment. We conducted a cross-sectional descriptive study to explore the 1-month prevalence of sleep disturbance and its associations with socio-demographic, substance-related characteristics, severity of dependence, severity of depression, and quality of life among heroin-dependent patients before entering treatment program. METHODS: The sample (n = 514) comprised individuals with heroin dependence attending the methadone maintenance treatment program and the therapeutic community at a psychiatric center in Nantou, Taiwan between 2008 and 2014. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) with a global score greater than 5 indicating sleep disturbance. Centre for Epidemiologic Studies Depression Scale, Severity of Dependence Scale, and World Health Organization Quality of Life-BREF were also approached. T-test, chi-square tests, and multivariate logistic regression were performed to measure associations between variables and sleep disturbance. RESULTS: The 1-month prevalence of sleep disturbance (PSQI > 5) was 76.3% among 514 subjects with heroin dependence. Heroin users with sleep disturbance had significantly more life events in the previous year, higher rate of unemployment, greater cigarette consumption, more substance related criminal convictions, longer length of heroin use, higher rate of injectors, greater severity of dependence, greater severity of depression, and lower quality of life compared to those without sleep disturbance. Severity of dependence, severity of depression, and physical health domain of quality of life remained significantly associated with sleep disturbance after adjusting for other variables. CONCLUSION: Heroin-dependent patients had a high 1-month prevalence of sleep disturbance, and this was associated with greater severity of dependence, greater severity of depression, and poorer physical health-related quality of life. Early assessments and interventions for sleep disturbance among patients with heroin dependence are recommended.

Effects of selective serotonin reuptake inhibitors on glaucoma: A nationwide population-based study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants. Glaucoma is the second leading cause of blindness globally and iatrogenic glaucoma has been implicated across disparate medication classes. Available studies that have sought to determine the association between SSRI exposure and glaucoma have provided mixed results. The aim of the study herein was to investigate whether an association exists between SSRI exposure and glaucoma incidence. METHODS: Glaucoma cases were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of glaucoma between 1997 and 2009. The date wherein the cases were diagnosed with glaucoma was operationalized as the index date. The control group was comprised of individuals within the database who were not diagnosed with glaucoma. 15,865 glaucoma cases were compared to 77,014 sex-, age-, residence- and insurance premium-matched controls on measures of prescribed duration and dosage of SSRIs up to 365 days before index date to proxy SSRIs exposure. RESULTS: Individuals receiving SSRIs were at greater risk of glaucoma incidence (OR = 1.39; 95% CI = 1.29-1.50); the foregoing increased likelihood was reduced after adjusting for confounding variables (aOR = 1.09; 95% CI = 1.00,1.18). SSRI treatment of longer duration (i.e. >365 days) and higher doses (≥1 defined daily dose) were associated with greater risk of glaucoma incidence (aOR = 1.36; 95% CI = 1.08-1.71). Subgroup analysis showed that the effect of SSRIs on glaucoma was limited to individuals younger than 65 years of age (aOR = 1.37; 95% CI = 1.25-1.50), without diabetes (aOR = 1.39; 95% CI = 1.27-1.52), without hypertension (aOR = 1.46; 95% CI = 1.31-1.63) or hypercholesterolemia (aOR = 1.35; 95% CI = 1.23-1.48). CONCLUSION: Treatment with SSRIs was associated with greater risk of having a diagnosis of glaucoma, particularly in individuals with longer duration and/or higher average dose of SSRI. Our findings suggest that individuals receiving SSRIs treatment for extended periods of time and/or at relatively higher therapeutic doses should be monitored for symptoms associated with glaucoma.

Depression and severity of substance dependence among heroin dependent patients with ADHD symptoms.

BACKGROUND AND OBJECTIVES: Comorbid attention deficit hyperactivity disorder (ADHD) symptoms are highly prevalent among heroin-dependent patients. We aim to investigate differences in dependence severity, depression, and quality of life between heroin-dependent patients with and without ADHD-screened positive. METHODS: Heroin-dependent participants (n = 447) entering methadone maintenance treatment were divided into ADHD-screened positive (ADHD-P) and ADHD-screened negative (ADHD-N) groups according to scores of Adult ADHD Self-Report Scale (ASRS). Mini-International Neuropsychiatric Interview was used to identify current and lifetime depressive episodes and suicidality. Substance use disorder, depression, family support, and quality of life in two groups were also assessed. RESULTS: About 7.8% (n = 35) scored 24 or higher of ASRS indicating highly likely Adult ADHD. More heroin-dependent patients of ADHD-P had a current depressive episode (p = .02). They had higher Center for Epidemiological Studies Depression (CESD) scores (p = .003), and more severe heroin dependence (p = .006). Poorer family support and quality of life in physical, and psychological domains were found in patients of ADHD-P compared to ADHD-N. DISCUSSION AND CONCLUSIONS: Heroin-dependent patients of ADHD-P represent a vulnerable minority. They were comorbid with regard to depression, greater substance dependence severity, and poorer quality of life. SCIENTIFIC SIGNIFICANCE: Assessment for ADHD symptoms in heroin-dependent patients may be indicated for the effective management of the complex problems of these patients. (Am J Addict 2017;26:26-33).

Comparison of socio-demographic characteristics, substance, and depression among male heroin users attending therapeutic community and methadone maintenance treatment program in Nantou, Taiwan.

BACKGROUND: Little is known about differences between the characteristics and psychopathological symptoms of heroin users attending TC or MMT in Asia. This study aimed to compare characteristics and prevalence of depressive disorders among male heroin users in TC and MMT program in Nantou, Taiwan. METHODS: The study sample (n = 705) comprised male heroin users with heroin dependence recruited from the MMT program and TC program at a psychiatric center in Nantou, Taiwan between 2006 and 2014. Socio-demographic and heroin-related characteristics were obtained from self-report questionnaires. DSM-IV diagnoses of heroin dependence, major depressive disorder, and dysthymic disorder were evaluated by trained interviewers. T-test and chi-square test and multivariate logistic regression were performed to measure the differences on variables between samples of TC and MMT. RESULTS: Compared to MMT, TC participants had poorer family support, higher rate of unmarried, higher rate of unemployment, earlier onset of heroin use, longer length of heroin use, and lower daily dosage of heron. MMT heroin users had higher 1-month prevalence of major depressive disorder than TC participants. We found the distribution of current major depression disorder differed between heroin users choosing different treatment models even controlling for other demographic factors, substance related factors and psychosocial factors. The underlying explanations require further investigation. CONCLUSIONS: This study found differences in the characteristics and prevalence of psychopathology. Further study to explore the effect of these differences on the outcome between MMT and TC is warranted.

Differential effects of olanzapine and clozapine on plasma levels of adipocytokines and total ghrelin.

Second-generation antipsychotics (SGAs) have been associated with an increased liability for weight gain and metabolic side effects. Among SGAs, clozapine and olanzapine had great liability to induce weight gain and metabolic adverse reactions. Leptin, adiponectin, and total ghrelin play important roles in energy homeostasis and are suggested to be biomarkers of metabolic disturbances. The purpose of the present study was to investigate the differential effects of antipsychotics (olanzapine and clozapine) on the levels of adipocytokines (leptin and adiponectin) and total ghrelin. Three hundred and thirty-three patients with schizophrenia under clozapine or olanzapine monotherapy were recruited. Control participants were recruited from a healthy community population based on a health investigation (N=119). Fasting blood samples for glucose, cholesterol, triglycerides, leptin, adiponectin, and total ghrelin were analyzed. There were significant differences in the levels of cholesterol, triglycerides, and glucose between these three groups. Post hoc comparisons showed that the olanzapine group had the highest levels of cholesterol and triglycerides. The levels of leptin, adiponectin, and total ghrelin were also significantly different between the three groups after controlling age and body mass index (BMI). Post hoc comparisons showed that the olanzapine group had the lowest levels of adiponectin and total ghrelin. The present study found that the uses of olanzapine and clozapine were associated with changes in adipocytokines and total ghrelin, even after adjusting potential confounding factors. Olanzapine had greater influences on adiponectin and total ghrelin than clozapine. The changes in adipocytokines and total ghrelin were a direct effect of antipsychotics on hormonal pathways of energy homeostasis, rather than the result of weight gain.

Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan: a prospective cohort study.

INTRODUCTION AND AIMS: Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines. DESIGN AND METHODS: This prospective cohort study with six-month follow up assesses the effect of methadone on QTc interval among a sample (n = 170) of heroin users in a methadone maintenance treatment program in Taiwan. Demographic data, substance use history, medical history and laboratory studies were collected at study enrollment. Twelve-lead electrocardiograms were performed for all participants both at study enrollment and six months later. RESULTS: The median daily methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P < 0.001) was found at six-month follow up. QTc interval prolongation in the sample at baseline was 2.9%, and at six months was 12.4%. A positive correlation was found between comorbid amphetamine use frequency in the past month and QTc interval change. Methadone dose was not associated with QTc change. DISCUSSION AND CONCLUSIONS: An increase of mean QTc interval was found among methadone maintenance patients at six-month follow up. Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment.

Prevalence, correlates, and risk perception of HIV infection among heroin users in Central Taiwan.

We investigated the prevalence and correlated factors of human immunodeficiency virus (HIV) among heroin users attending methadone maintenance treatment (MMT) programs in Central Taiwan, and explored the degree of risk perception of HIV infection among the participants. Our study participants were 781 heroin users seeking treatment at the MMT program at Tsaotun Psychiatric Center in Taiwan. The presence of HIV antibodies was identified by microparticle enzyme immunoassay and confirmed by western blot. Multivariate logistic regression was used to identify the independent correlates of HIV infection. The mean age of the sample was 36.1 years [standard deviation (SD) = 7.6]; of the patients, 710 (90.9%) were men. The prevalence of HIV infection among our study population was 20.7%. Multivariate logistic regression analysis revealed that HIV infection was independently associated with the age of the patients of initial heroin use, heroin injection use, nondrug-related criminal convictions, needle-sharing behaviors, and sharing injection paraphernalia. A strong agreement existed between self-reported HIV serostatus and the results of laboratory analyses, with 88.8% of patients reporting their condition correctly. We found a high rate of HIV infection among patients in the MMT program. Factors associated with HIV infection were mostly related to drug-use behaviors. These findings stress the importance of education regarding drug-risk behaviors.

High prevalence but low awareness of hepatitis C virus infection among heroin users who received methadone maintenance therapy in Taiwan.

BACKGROUND: This study investigates the prevalence and correlates of hepatitis C virus (HCV) infections among heroin dependent individuals who received methadone maintenance therapy in Taiwan. Also, we investigate users' awareness of HCV. METHODS: Participants were 773 heroin users entering the methadone maintenance treatment (MMT) program at Tsaotun Psychiatric Center in Taiwan. The presence of HCV antibodies was detected. Multivariate logistic regression was used to identify the relationship between HCV infection and correlates. RESULTS: The prevalence of HCV infection was 90.8%. All participants who were HIV-positive were also infected with HCV. Multivariate logistic regression analysis showed that the route of heroin administration (injection), HIV-infection, and criminal records were significantly related to HCV infection. Few (34.8%) HCV positive heroin users were aware of their infection. CONCLUSION: An extremely high prevalence of HCV infection but low awareness of their infection status was found among MMT patients in Taiwan. These findings highlight the importance of education regarding risky behaviors and the necessity for HCV treatment for this population in Taiwan.

Essentiality of HIV testing and education for effective HIV control in the national pilot harm reduction program: the Taiwan experience.

In 2005, a national pilot harm reduction program (PHRP), which mainly included a methadone maintenance treatment program (MMTP) and a needle/syringe exchange program (NSP), was implemented in Taiwan. We conducted this study to evaluate the effectiveness of harm reduction measures on HIV control among injecting drug users (IDUs) between PHRP and nonPHRP. The data on HIV, collected from incumbent Taiwanese authorities, were analyzed for their associations, risk and protective factors with PHRP measures. While the monthly HIV incidences did not show significant differences before and after PHRP in the four areas with PHRP (Taipei City, Taipei County, Taoyuan County and Tainan County), a significant increase in the HIV incidence was found in the 21 areas without PHRP. Hence, the implementation of the PHRP did result in a significant difference in the monthly HIV incidence between areas with and without the PHRP. Mandatory HIV testing was significantly associated with the HIV incidence according to the generalized estimation equations (GEE) model. With adjustments of time period and area with PHRP, and urban area, protective factors associated with HIV incidence were: educational materials, condoms, dilution water, and alcohol sponges/swabs. MMTP contributed to a higher HIV incidence, probably due to the concurrent HIV testing upon admission. Since HIV testing was not required in the NSP, the HIV testing-dependent MMTP may explain the association of the PHRP intervention and an increased HIV incidence. In summary, HIV testing and education were essential for effective HIV control upon implementing the PHRP.

A prospective study of glucose homeostasis in quetiapine-treated schizophrenic patients by using the intravenous glucose tolerance test.

Increasing attention has been paid recently to the potential diabetogenic effect of second-generation antipsychotics (SGAs). The objective of this prospective study was to evaluate the effects of quetiapine treatment on pancreatic beta-cell function in SGA-naïve schizophrenic patients. Seventeen schizophrenic subjects completed an eight-week trial. The metabolic parameters were assessed at weeks 0, 2, 4, and 8. We measured glucose homeostasis with the intravenous glucose tolerance test. After the eight-week treatment, body weight and body mass index showed to be significantly increased compared to those at baseline. No significant changes were found in serum levels of fasting glucose, insulin, total cholesterol, and high-density lipoprotein. Insulin resistance and insulin secretion were significantly increased. Incidences of clinically significant weight gain and treatment-emergent metabolic syndrome were 11.8% and 11.8%, respectively. This study result confirms the association of quetiapine treatment and impairment of glucose homeostasis in schizophrenic patients.

Suicide attempts prior to starting methadone maintenance treatment in Taiwan.

This study investigates recent (one-month) and lifetime prevalence of suicide attempts, and factors associated with one-month suicide attempts among heroin users (n=488) seeking treatment at a methadone maintenance programme in Taiwan. Data were collected by structured interview on demographics, use of heroin and other substances, criminal convictions, depression, social networks, and history of suicide attempt (lifetime suicide attempt, and suicide attempt and suicide ideation in the previous month). Prevalence of recent (one-month) suicide attempt was 10.9% and lifetime prevalence was 17.8%. The finding that so many heroin users had made a suicide attempt in the very recent past is both disturbing and little researched. Recent suicidal attempts were associated with severity of heroin dependence, needle sharing, higher educational level, increased levels of depression, and number of stressful life events. It is suggested that methadone maintenance programmes should routinely screen at intake for previous suicidal behaviour and especially for recent suicidal attempts.

Severity of heroin dependence in Taiwan: reliability and validity of the Chinese version of the Severity of Dependence Scale (SDS[Ch]).

The development of instruments to assess substance use that are easy to use, valid and reliable across cultures is an important task. The present study investigates the reliability and validity of the Chinese language version of the SDS (SDS([Ch])) when used to measure severity of dependence among heroin users in Taiwan (n=522). Data were collected on demographic data, heroin use behaviours, and criminal convictions. Taiwanese heroin users recorded high SDS([Ch]) scores and the results support the validity and reliability of the Chinese version of the SDS. A positive correlation was found between SDS([Ch]) scores and DSM-IV criteria for heroin dependence. SDS([Ch]) scores were positively related to heroin injection, frequency of heroin injection, spending on heroin, earlier age of onset of heroin use and more drug-related criminal convictions. The findings support the suggestion that the concept of dependence as assessed by the SDS has cross-cultural validity.