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  • The study protocol was approved by the Ethic Committees of Wuhan Mental Health Center and Shenzhen Kangning Hospital. Before respondents were interviewed, written consent was obtained from all of the subjects and their guardians, and declarations of anonymity and confidentiality had been made. Verbal consent also obtained from each included inpatient's responsible physician. For the compensation of time spent in participating in this study, each respondent had been given a gift prior to the interview. This cross-sectional, two-site, hospital-based survey was conducted between January 2011 and June 2013. Subjects were recruited by consecutively screening patients with schizophrenia who attended the psychosis inpatient wards of Wuhan Mental Health Center and Shenzhen Kangning Hospital in Wuhan and Shenzhen, two of the largest cities in China. These two cities, one located in south-central area and the other located in southeastern coastal area of China, are typical examples of the metropolitan regions of mainland China, in terms of their financial conditions and levels of health care service. Both hospitals are the largest specialty psychiatric hospitals of local areas, with 610 and 450 hospital beds, respectively. They are responsible for mental health services of the residents of Wuhan and Shenzhen, and thus have a catchments area of approximately 10,020,000 and 10,547,400, respectively. Patients who satisfied the following inclusion criteria were invited to participate in the study: 1) age 18–60 years; 2) men and women with a DSM-IV diagnosis of schizophrenia; 3) inpatients of psychosis wards; 4) had been treated with a stable dose of oral antipsychotic mono-therapy for at least four weeks before entry into the study, irrespective of the presence or absence of combination use of other non-antipsychotic drugs. Subjects with severe medical conditions, obvious intellectual disorders, active non-nicotine substance dependence, and organic psychosis, and who were prescribed two or more classes of antipsychotic agents, were excluded from this study. Although our subjects were inpatients, they were allowed to smoke regularly every day, except the time for sleep and taking drugs. Patients could easily buy cigarettes of most cigarette brands at reasonable prices in their psychiatric wards. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of antipsychotic drugs were recorded using a standardized protocol and data collection procedure. Data on patients' socio-demographic variables and clinical characteristics were collected through a questionnaire designed for this study. AAO refers to age at the first psychotic symptom reported by the patients themselves or informants [41]. Alcohol user was defined as a person who drank at least one alcoholic beverage per month in the past year [42]. Case records of included subjects were additionally reviewed for the following clinical variables: number of hospitalizations, length of illness, family history of psychiatric disorders, and types and doses of current antipsychotic drugs. Unclear or inaccurate answers were confirmed again with patients themselves and/or their guardians. Discrepancies were solved by consensus between patients and their guardians or responsible psychiatrists. Because of different types of neuroleptics used, daily doses were converted into chlorpromazine equivalents (CPZ-eqs) for statistical analysis [43], [44]. We also administered a standardized cigarette smoking questionnaire to record smoking habit of each subject, including the average number of cigarettes smoked per day. Items of smoking questionnaire were adapted from the instruments of 2008 US National Health Interview Survey (hereafter refer to “NHIS definition” of smoking) [45]. It comprised of two questions. The first question, asked of all respondents, is “have you smoked at least 100 cigarettes in your entire life?” Respondents answering “yes” are classified as ever smokers, and those who answer “no” are classified as never smokers and excluded from subsequent cigarette use questions. Ever smokers are then asked a second question: “do you now smoke cigarettes every day, some days or not at all?” Respondents who answer “every day” or “some days” are classified as current smokers and those who answer “not at all” are categorized into former smokers. Heavy smokers were defined as those smoking at least 20 cigarettes daily [46]. Psychopathology of schizophrenia in the 4-week period preceding the interview was measured using the Chinese version of Positive and Negative Symptom Scale (PANSS) with subscales for positive symptoms (PANSS-P), negative symptoms (PANSS-N), and general psychopathological symptoms (PANSS-G) [47]. Drug-related extrapyramidal side effects (EPS) were assessed using Simpson Angus Scale (SAS) [48], Barnes Akathisia Rating Scale (BARS) [49], and Abnormal Involuntary Movement Scale (AIMS) [50]. The diagnostic threshold scores for the presence of pseudoparkinsonism and akathisia were ≥7 in SAS [51] and ≥2 in BARS global clinical assessment item [49], respectively. A score of 3 or more on any of the first 7 AIMS items, or a score of 2 or more on any two of the first 7 AIMS items, was taken to be indicative of dyskinesia [52]. The Chinese versions of these assessment instruments have been shown to be reliable and valid for measuring the psychotic symptoms and drug-related EPS of Chinese schizophrenia patients [53]–[56], the internal consistency of all the rating instruments (three subscales of PANSS, SAS, BARS, and AIMS) was good in this study (Cronbach α coefficients ranged between 0.74 and 0.93). Two raters, an experienced psychiatrist and a clinical psychologist, were responsible for all of the assessments. Prior to the study, both raters underwent a training course on the use of PANSS, SAS, BARS, and AIMS. Before the beginning of this study, an inter-rater correlation coefficients ranging from 0.81 to 0.93 was obtained in 11 voluntary schizophrenia patients between the two raters for all assessment scales. Once participants agreed to participate in this study, they were told that the main goal of this study was to help clinicians understand the relationship between schizophrenia and smoking, and the results might be helpful for the management and rehabilitation of schizophrenia. Hence, supplying real information about the smoking behaviors was of vitally importance for this study. Our raters were also required to be patient to help respondents recall their smoking details during the course of interview. The completeness of all interview and physical examination records was checked daily by the survey team leader. Errors, omissions and other flaws were solved during the fieldwork period of this survey. For the analysis, we used the SPSS software for Windows, version 15.0 (SPSS Ltd.). According to the smoking status diagnosed by NHIS definition, prevalence rates for ever, current and former cigarette smoking were calculated. Because the number of former smoker in our sample was very small (N = 3), the following univariate and multivariate analyses only focused on current and never smokers. In univariate analysis, the comparison between current smokers and never smokers with respect to socio-demographic and clinical characteristics was performed by independent sample t-test, Mann-Whitney U test, and chi-square test as appropriate. Multivariate logistic regression was used to identify factors associated with current smoking. Associations between current smoking and all potential predictors were assessed in univariate analyses, followed by multivariate analyses of the selected subsets. A variable was selected if it was statistically significant at the nominal two-sided 0.05 level in univariate analysis. We quantified associations of predictors and current smoking by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for each variable. To clarify whether schizophrenia inpatients have higher current smoking rate than Chinese general population, we introduced the latest smoking data from the 2010 Global Adult Tobacco Survey in China (2010 GATS China) [57]–[59] as the comparison reference. The 2010 GATS China was a nationally representative household survey of non-institutional men and women aged 15 and older, and was conducted between December 2009 and March 2010. The survey was completed with high response rate (96.0%) and high qualities by strict quality control measures, and successfully collected 13,354 Chinese adults' tobacco use data. Since our study sample and the external standard population, 2010 GATS China sample, were not comparable in terms of age and gender structures, we compared the smoking rates between schizophrenia and the general population by calculating the Indirectly Standardized Prevalence Ratios (ISPRs) [60], [61]. Specifically, this indirect standardization approach applied the stratum specific smoking rates (i.e., age and gender specific rates) of 2010 GATS China population to the number of individuals in the corresponding stratum in our sample. An expected number of smokers was generated for each stratum, and the total expected was used in the denominator. The numerator was the total number of observed smokers in our schizophrenia sample. ISPR was the ratio of the observed number of smokers in our study sample over the expected number of smokers in the general population. Its 95%CI was estimated through formulas proposed by Rothman and Boice [62].
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