Prevalence of tobacco dependence and associated factors among patients with schizophrenia attending their treatments at southwest Ethiopia; hospital-based cross-sectional study.

BACKGROUND: Tobacco smoking is the most typically employed in patients with mental disorders; among them, patients with schizophrenia are the very best users. The rate of smoking among patients with schizophrenia is between two and three times greater than the general population in western countries. However, there is a scarcity of studies on the magnitude and associated factors of tobacco dependence among patients with schizophrenia in Ethiopia. Therefore, we assessed the prevalence of tobacco dependence and associated factors among patients with schizophrenia at Mettu Karl referral, Bedelle, and Agaro hospitals, Southwest, Ethiopia.
METHOD: Hospital-based the multistage stratified cross-sectional study design was conducted among 524 patients with schizophrenia who are on treatment. Fagerstrom Test for Nicotine Dependence (FTND) was used to screen the prevalence of tobacco dependence. Analysis of data was done using SPSS version 24. RESULT: The prevalence of tobacco dependence among study participants was 22.3% (95% CI) (18.6, 26). Concerning the severity of tobacco dependence, 3.5%, 13.8%, and 5% of the respondents report moderate, high, and very high levels of tobacco dependence respectively. The proportions of tobacco dependence among male schizophrenic patients 88 (25.8%) were higher compared to their counterparts 27 (15.5%). After controlling the effects of cofounders in the final regression analysis, male gender (AOR 2.19, 95% CI = 1.25, 3.83), being on treatment for more than 5years (AOR 4.37, 95% CI = 2.11, 9.02), having a history of admission (AOR 4.01, 95% CI = 1.99, 8.11), and family history of mental illness (AOR 1.90, 95% CI = 1.04, 3.48) were shown to have a significant positive association with tobacco dependence. CONCLUSION AND RECOMMENDATION: A study show a significant proportion of tobacco dependence among people living with schizophrenia. Factors like, being male gender, being on treatment for more than 5 years, having a history of admission, and family history of mental illness was found to have a significant positive association with tobacco dependence. Hence, there is a need for coordinated and comprehensive management clinically to manage tobacco dependence along with identified risk factors in patients with schizophrenia. Also the finding call for the clinicians, managers, ministry of health and other stakeholders on the substance use prevention strategies that target personal and environmental control.

Introduction

Globally, cigarette smoking is among the highest 5 causes of risk mortality and is that the single largest preventable reason behind death; it promotes quite five million annual deaths, inflicting 11% of ischemic heart deaths and quite seventieth of respiratory organ, cartilaginous tube, and trachea cancer [1]. According to the report of WHO, cigarette smoking in the developed countries is the cause of 20% of preventable death [2]. The report shows that tobacco is estimated to kill about one billion people in the 21st century, particularly from low- and middle-income countries (LMICs) [3].

People living with mental illness are more likely to smoke and be at greater risk for smoking‐related health problems than the general population [4]. Mortality from smoking is higher among individuals living with mental illness supported by the report of the study comprised 600,000 respondents where tobacco-related conditions were contributed to 53% of total deaths in schizophrenia [5]. Smoking in schizophrenic patients contributes to a 20% decrease in their life expectancy compared to members of the general population [6].

The impact of smoking among patients with schizophrenia not only increases metabolism and vascular risks [7], also increases suicide risk [8]. It decreases the antipsychotic therapeutic effects as smoking induce the medication metabolism in the liver reducing up to 48% of the active metabolites in serum [9]. Schizophrenic-smokers show more hospitalization frequency (than schizophrenic non-smokers) and also require more depot medication, having fewer adherences to treatment [10].

A meta-analysis of 42 epidemiological studies across 20 different countries showed that people with schizophrenia have more than five times the odds of current smoking than the general population and smoking cessation rates are much lower in smokers with schizophrenia compared with the general population [11]. Another meta-analysis study was done in 8 countries based on 14 studies found that the average prevalence of current smokers among male schizophrenia patients were 72% [12].

According to one study from the United Kingdom (UK) done among 8 million patients, the prevalence of smoking among psychotic patients (schizophrenia, schizotypal and delusional disorders) was 44.6% [13].

A cross-sectional study was done in China among inpatient schizophrenic patients found that the prevalence rate of current smoking was 40.6%, which was 57.5% in males and 6.3% in females and the study described that factors such as being male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking [14].

A cross-sectional study was done in Singapore among male schizophrenic patients found that the lifetime prevalence of smoking cigarettes and current smokers are 54.1% and 42.4% respectively [15], in Iran as high as 71.6% [16], in Scotland 53.4% [17], and in Turkey 49% [18].

One a cross-sectional descriptive study was done in Southwest Nigeria among 367 patients with schizophrenia found that the lifetime prevalence and a current smoking rate of 20.4% and 25.9% were reported respectively [19]. Facility-based a cross-sectional study done in Jimma medical center in Ethiopia on tobacco dependence among people with mental illness found that the prevalence of current tobacco dependence among the study participants is 18.5% and specifically the prevalence of tobacco dependence among patients with schizophrenia was 29.1%; furthermore, the study described their level of tobacco dependence as 57.7% moderate, 29.5% higher and 12.8% very high [20].

Little information is available regarding nicotine dependence among patients with schizophrenia in Ethiopia. Thus, this study was aimed to assess the prevalence of tobacco dependence and associated factors among patients with schizophrenia attending their treatments at Mettu Karl, Bedelle, and Agaro hospitals, Southwest Ethiopia.

Materials and methods

Study setting and period

The study was conducted from 1st April to 30th June 2019 at the psychiatric clinic of three governmental health institutions (Hospitals) found in southwest Ethiopia, namely Mettu Karl referral, Bedelle and Agaro hospitals, which were 600 kilometer, 426 kilometer, and 397 kilometer far from Addis Ababa to the southwest, the capital city of Ethiopia, respectively.

Study design

Hospital-based a cross-sectional study was conducted.

Source population

All patients with schizophrenia attending follow-up treatments at Mettu Karl referral, Bedelle, and Agaro hospitals psychiatric clinic

Study population

Sample of patients with schizophrenia who attended the outpatient treatment at the psychiatric clinic of Mettu Karl referral, Bedelle, and Agaro hospitals during the data collection period

Inclusion and exclusion criteria

Adult patients (aged 18 and above) with schizophrenia who were already diagnosed previously as per the diagnostic criteria of the Diagnostic Statistical Manual of Mental Disorders, 4th and or 5th edition (DSM-IV or DSM-V) were included in the study and patients with schizophrenia whose illness was in the acute stage or in exacerbation of symptoms were excluded from the study.

Sample size determination

The minimum the sample size required for this study was determined by using the formula to estimate single population proportion, n = ((z ᾳ/2)2p(1-p))/d2 by using the following assumptions: the prevalence of tobacco dependence among patients with schizophrenia at the Jimma medical center was 29.1% [20], a 95% confidence interval (CI), 5% the margin of error and a non-response rate of 10%. We applied the single population proportion formula to give in = (1.96)2 * 0.291 (1–0.291) / (0.05)2 = 317.

Since multistage stratified sampling the technique was used to select study participants, using design effect the sample size was multiplied by 1.5, giving 476 considering that the questionnaire was self-administered and finally adding a 10% non-response rate, the final number of the study subject became 524.

Sampling technique

The multi-stage stratified sampling technique was used to select the study participants. Stratification was first done on the zone level, then by the hospitals found in the zones ().

The schematic presentation of the sampling procedure that was employed to select study participants from three zones, southwest, Ethiopia, 2019.

Where, n–is the average number of schizophrenic patients who were treated at the psychiatric clinic of each hospital per one month (data collection period) as reviewed from the patients’ registration book. P–is the number of schizophrenic patients who are allocated proportionally to the hospitals.

Data collection procedure and tools

An interviewer-administered a structured questionnaire was used to collect information. Questionnaires about demographic and other clinical factors were developed after an extensive review of the literature and similar study tools. We employed nine interviewers’ (data collectors) for 2 months data collection period for collecting data from the participants (patients with schizophrenia). The interviewers’ background or expertise was that they were all bachelors of degree and master of degree holders in psychiatric nursing. Hence, we (authors) believe that the interviewers’ background or expertise (being psychiatric professionals) can lead them to determine the capacity of patients to provide consent for the study. The study was done among patients with schizophrenia who were already diagnosed previously as per the diagnostic criteria of the Diagnostic Statistical Manual of Mental Disorders, 4th and or 5th edition (DSM-IV/DSM-V) and currently attending their treatments at health facilities (hospitals). The diagnosis of the patients was first confirmed by reviewing patients’ cards prior to starting data collection (interviewing the patients) and also interviewer’s perception of the patient capacity was determined based on the patient level of remission. Fagerstrom Test for Nicotine Dependence (FTND) has six items, with a total score ranging from 0 to 10 was used to measure nicotine dependence [21]. The FTND has been shown to have good test-retest reliability and validity in populations of smokers with mental health problems [22]. At a cut-off score ≥of 5, the FTND has good sensitivity and specificity (0.75 and 0.80, respectively) [23] and was considered to indicate tobacco dependence.

Alcohol use disorders (AUDs) were assessed using the four-item CAGE questionnaire (Cut down, Annoyed, Guilty, and Eye-opener). CAGE is short and easily applied in clinical practice. The sensitivity and specificity of CAGE at a cut-off score ≥ 2 was 0.71 and 0.90, respectively [11]. In this study, a total score ≥2 on CAGE was used to indicate an alcohol use disorder.

The severity of Dependence Scale (SDS) was used to assess Khat use disorder. It is a screening tool for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) ‐ defined Khat use disorder [24]. SDS is a brief and simple screening tool that was validated in Mizan, the Southwestern part of Ethiopia to identify individuals experiencing a Khat use disorder syndrome and experiencing high rates of adverse consequences in association with the use [25]. Each of the five items is scored on a 4-point scale (0–3). The total score is obtained through the addition of the 5-item ratings.

Data processing and analysis

Epi Data Version 3.1 was used for data entry following checks and coded for. Then, the data were exported to the Statistical Package for Social Science Version 24.0 for further analysis. Simple descriptive statistics (median, percentage, frequencies, and interquartile range) were used to compute demographic characteristics of participants. In addition, bivariable analysis was used to see the significance of the association. Variables that showed strong association (p-value <0.25) in bivariate analysis were entered into multivariable logistic regressions to identify independently associated variables. Multicollinearity was checked by the Variance Inflation Factor (VIF). Statistical significance was declared at a p-value less than 0.05. The significance of the association of the variables was described using Adjusted Odds Ratio (AOR) with a 95% confidence interval.

Data quality control

The questionnaire was prepared first in English and translated into Afaan Oromo/Amharic then back-translated to English by another person who was blinded for the English version to check the clarity of the questionnaire. To identify potential problems and to make important modifications, the questionnaire was pre-tested on 5% of the total study participants were randomly selected in the same population outside the study area in Jimma Medical center psychiatric clinic one week before the actual data collection date. The prepared questionnaire was checked thoroughly for its completeness, objective, and variable before it was distributed to respondents. Also, the collected data were checked for its completeness. The supervisor was three first-degree holder instructors. A pre-test was done after training is given to the supervisors on how to supervise data collection. The principal investigator checked for the completeness of filling questionnaires at the end of each data collection date. Any error, ambiguity, incompleteness, or another encountered problem was addressed immediately after the supervisor receives the filled questionnaire from each data collector.

Operational definition

Tobacco dependence = individuals who score FTND 5 and above.

A total FTND score of five indicates moderate nicotine dependence,

A a score of 6–7 indicates high nicotine dependence and

A a score of 8–10 indicates very high nicotine dependence

Schizophrenia: is a clinical diagnosis reached by a clinician based on DSM-IV/DSM-5 diagnostic criteria as reviewed from the patient card.

Physical illness: is any diagnosed medical problem like hypertension, diabetes Mellitus, heart failure made by the clinician during the follow-up period.

Substance use: ever use of any psychoactive substance in the past 12 months.

Ethical clearance

Ethical clearance was obtained from the Research, Ethical Review Board of Mettu University, college of health sciences, and the study was done according to the declaration of Helsinki. And also an approval letter was obtained from the head department of psychiatry. After the ethical review board has approved the consent procedure, selected participants were told about the nature, purposes, benefits, and adverse effects of the study and invited to participate. Participants were told the right to refuse or discontinue participation at any time they want. Confidentiality was ensured and all related questions, they raised were answered during data collection. Written informed consent was obtained from study participants.

Results

Socio-demographic characteristics of the study participants

A total of 524 participants was participating in the study, of which 515 responded, giving a response rate of 98.3%. The mean age (±SD) of the study, participants were 33.7 (±7.9) years of age. About 287 (55.7%) of the respondents were married. Among the respondents, 341 (66.2%) were male, 326 (63.3%) were Oromo, and 150 (29.1%) of the study participants had attended primarily (grade 1–8) education More than half of them had a family size of four or above and the median monthly incomes of the respondents were 700ETB, which ranges from 100-5000ETB. ()

Clinical and other substance-related characteristics of patients with schizophrenia

More than half of the participants were attending their treatment for less than 6years (56.7%). Of patients with a history of admission, about 17.1% were admitted 2times for their condition. Few of them had both family history of mental illness (15.7%) and substance use (17.1%). About one third (36.3%) of the study participants fulfilled alcohol use disorder using CAGE criteria. ()

Prevalence of tobacco dependence among patients with schizophrenia

The prevalence of tobacco dependence among patients with schizophrenia was 22.3% 95% CI (18.6, 26). Concerning the severity of tobacco dependence, about 3.5%, 13.8% and 5% of the respondents use moderate, high, and very excessive levels of tobacco dependence respectively. ()

More than half of the respondents, 308 (59.8), smoked less than 10 items of cigarettes on a daily basis. About one-fourth of schizophrenic patients with tobacco dependence smoke cigarettes within 5-30miutes soon after waking. The proportions of tobacco dependence among male schizophrenic patients 88 (25.8%) were higher compared to their counterparts 27 (15.5%).

Correlates of tobacco dependence among patients with schizophrenia

In the univariable logistic regression, different factors have been shown to have associated with tobacco dependence among patients with schizophrenia. Accordingly, male gender, unemployment, being on treatment for 5years, having a history of admission and frequent admission, presence of physical illness, family history of mental illness, being educated above secondary school

After controlling for cofounders, male gender (AOR 2.19, 95% CI = 1.25, 3.83), being on treatment for more than 5years (AOR 4.37, 95% CI = 2.11, 9.02), having a history of admission (AOR 4.01, 95% CI = 1.99, 8.11), and family history of mental illness (AOR 1.90, 95% CI = 1.04, 3.48) were shown to have a significant positive association with tobacco dependence in the final regression analysis. ()

Discussion

A cross-sectional study was conducted in three hospitals located in the southwestern part of Ethiopia revealed about one-quarter of patients with schizophrenia reported tobacco dependence. As the majority of the previously conducted studies targeted cigarette smoking among patients with schizophrenia, however, the current study aimed to determine the prevalence of tobacco dependence and its correlates among patients with schizophrenia. So, this could have additional benefits set direction or develop strategies to deal with the impacts of the problem.

The overall prevalence of tobacco dependence among schizophrenic patients was 25.9%. These results were higher compared to the prevalence of tobacco dependence among the general population in Ethiopia which is 7.9% [26]. This difference could be due to the chronic nature of the illness and is used as a form of self-medication, normalizing some central nervous system deficits involved in the disorder. The results were also higher compared to the finding of the study from Nigeria (20.4%) [19]. The possible difference might be explained due to differences in study instruments (FTND vs. PSE-10). However, the finding of the current study was lower than the result of a study from Turkey 49% [18], United Kingdom 44.6% [13], India 68.8% [27] and Ethiopia 29.1% [20]. The discrepancy might be attributable to the difference in study design, instruments, and study setting.

After controlling for confounders, the odds of developing tobacco dependence among patients who attended treatment for more than 5 years were 4.4 times higher than those who attended for less than 5years. This was in agreement with the findings of the study conducted in China [28] and the USA [29]. It is clear that, from the nature of Schizophrenia, at the time of treatment progress or illness become episodic, the intensity increase over time, exposing them to use tobacco in the form of self-medication [30]. Generally, the longer the duration of the treatment period, the higher the danger of developing tobacco dependence.

Individual patients having a family history of mental illness were 1.9times more likely to develop tobacco dependence compared to those without a family history of mental illness which was supported by the finding of previously conducted studies [31]. The notion was indicating the role of genetic factors in the etiology of smoking behaviour and the high comorbidity between nicotine dependence and schizophrenia [32].

Furthermore, gender was shown a significant association with tobacco dependence in patients living with schizophrenia was gender. Accordingly, in the current study, males were 2times more likely to develop tobacco dependence compared to their counterparts and this was in agreement with the finding of the previous study [14, 33]. The possible reason might be related to the fact that male schizophrenic patients were more likely to smoke tobacco as they experience a lesser intensity of negative symptoms compared to females [34].

Finally, the current study revealed patients with schizophrenia who was a history of admission were more likely to develop tobacco dependence compared to those attending their treatment on an out-patient basis. This was in line with the findings of the previously published studies [14]. The finding of the study supports an association of illness severity with admission history [35].

Limitations

One of the limitations of this study might be the cross-sectional study design, which does not allow causal inference. Again In the current study, patients who were living with schizophrenia and schizophrenia-like disorder attending inpatient care were excluded. Thus, the finding of the study may not be generalizable to all patients with schizophrenia or like disorder. Also, the lack of any scale measuring current psychopathology was another limitation of this study.

Conclusions

A study shows a significant the proportion of tobacco dependence among people living with schizophrenia. Factors like, being male gender, being on treatment for more than 5 years, having a history of admission, and family history of mental illness was found to have a significant positive association with tobacco dependence. Hence, there is a need for coordinated and comprehensive management clinically to manage tobacco dependence along with identified risk factors in patients with schizophrenia. Also the finding call for the clinicians, managers, ministry of health and other stakeholders on the substance use prevention strategies that target personal and environmental control.

15 Jan 2021

PONE-D-20-31418

Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia; Hospital-Based Cross-Sectional Study

PLOS ONE

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Reviewer #1: Abstract

In the first sentence the word ‘abused’ and ‘abuser’ is not right. There is no diagnostic criteria for tobacco abuse in DSM-5.

The introduction part can be shortened. There are a lot of research findings from all the over the world. It should be summarized to the most relevant researches and high quality evidence.

Materials and methods

Please include a statement on the type of the study design.

Please include some statements about the interviewer’s level of expertise. And the instrument that has been used to assess tobacco dependence (Fagerstrom Test for Nicotine Dependence (FTND)), was the instrument used in it’s original language or was it translated?

If it was translated, please specify the process of translation of this or other instruments.

Please put the reference paper which has validated the SDS instrument in Ethiopia.

Result

The 1st paragraph second sentence include the ‘mean age’. On the next sentences there are repetitions, please correct it. The last sentence the median (IQR) monthly income the IQR is not specified in a range of numbers.

2nd paragraph 3rd line include ‘family history’

Correlates of tobacco dependence among patients with schizophrenia

On the bivariate logistic regression,-- it is univariable logistic regression

There is inconsistency of the result from the table 3 and the above paragraph presented about the significant result on univariable and multivariable logistic regression.

Discussion

It needs further explanation on recommendation and the uniqueness of this study.

Reviewer #2: This study addressed the frequency of ND in patents with schizophrenia in Ethiopia. While similar study has already been published (Molla et al, 2017), the question is whether this study brings new data. This text needs major revision, and English language revision.

Introduction

Page 9-The impact of smoking among schizophrenic patients, not only increases metabolism and vascular risks-what is meant by „metabolism “?

It decreases the antipsychotic therapeutic effects as smoking induces the medication metabolism in the liver reducing up to 48% the active metabolites in serum (9). -please, be more specific-because smoking does not induce the metabolism of all antipsychotics

One hospital based cross sectional study done among 429 inpatients schizophrenic patients in China receive antipsychotic mono-therapy found that the prevalence rate of current smoking was 40.6%and 57.5% in males and 6.3% in females. -please, put the reference number in the parenthesis, and correct English grammar

A cross sectional study done in Singapore among male schizophrenic patients found that the lifetime prevalence and current smoker are 54.1%and 42.4%respectively (15). -life time prevalence of what?

Methods

How was schizophrenia confirmed? According to which classification system? It is unclear whether the patients were in-or out-patients or both.

Exclusion criteria-„patients who are seriously ill “-please define what this term refers to

Operational definitions: Chronic illness: past mental illness...how could past mental illnesses be defined, when participants already have schizophrenia?

The study lacks any measure of schizophrenia psychopathology (such as PANSS)

What about pharmacotherapy? Did patients receive antipsychotics?

Results

The mean (±SD) of the study participants were 33.7(±7.9) years-the term „age “is missing

66.2% were males-was mentioned twice

The section: „ Prevalence of tobacco dependence among patients with schizophrenia “is unclear and difficult to read. How many patients were current smokers? The data providing number (frequency) of smokers, and categories of FTND-defined nicotine dependence, need to be presented in a separate table

„Few of them had history of mental illness (15.7%)-it is unclear,

because all patients had schizophrenia

Discussion

Please, provide in the discussion the rates of nicotine dependence in Ethiopia general population, and then comment on the ND rate in schizophrenia patients, whether and how it differs compared to general population in the same country.

Limitations

The lack of any scale measuring current psychopathology is also a limitation.

The conclusion „a significant proportion of tobacco dependence...“ would be valid only if this ND frequency outnumbers smoking prevalence in Ethiopia general population.

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26 Jun 2021

Dear PLOS ONE,

Thank you for your comments, concerns and consideration of our manuscript. We tried to incorporate for comments and answer for comments written by yellow color

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming

Authors’ response: we did accept the comment and tried to address as our manuscript meets

2. Please describe in your methods section how capacity to provide consent was determined for the participants in this study. Please also state whether your ethics committee or IRB approved this consent procedure. If you did not assess capacity to consent please briefly outline why this was not necessary in this case.

Authors’ response: we have descried how capacity to provide consent and also stated as our ethical committee approved this consent procedure. Please see under ‘ethical clearance’ subtitle of materials ad methods section

3. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as:

a) the recruitment date range (month and year),

b) a description of how participants were recruited, and

c) descriptions of the specific locations where participants were recruited and where the research took place.

Authors’ response: we have provided sufficient additional information about the participant recruitment method and the demographic details of our participants. Please see under materials and methods section

4. Please include additional information regarding the interviewer-administered structured questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

Authors’ response: we have used the interviewer administered questionnaire to collect data in patients with schizophrenia since they don’t have similar level of educational background to clearly understand the queries and to reduce information bias.

5. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly.

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b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Authors’ response: All relevant data are included within the paper. The data would be guarded carefully by our research team for the only purpose of this scientific study and it is an ongoing project. Participants were not signed consent for data publicity. For all these reasons and following the indicators of the research review committee of college of health sciences, Mettu University, the authors must not upload the dataset to a stable, public repository. Interested, qualified researchers can access the data by requesting Dean College of health sciences of Mettu University, Desalegn Chilo (desalegchilo89@gmail.com) and the corresponding author, Defaru Desalegn (defdesalegn2007@gmail.com)

6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Authors’ response: we have deleted from any other section and we stated only in methods section

7. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works.

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

Authors’ response: we accept the comments and rephrased the documents for duplicated contents.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: No

Authors’ response: we accepted the comments and we have re-write our conclusion

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Authors’ response: Yes, we have used the appropriate statistical analysis …first after data were collected we checked, coded and entered into Epi data Version 3.1. Then, we exported to SPSS Version 24.0 for analysis. Assumptions were checked and bivariate and multivariate logistic analysis were done…

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Authors’ response: All relevant data are included within the paper. The data would be guarded carefully by our research team for the only purpose of this scientific study and it is an ongoing project. Participants were not signed consent for data publicity. For all these reasons and following the indicators of the research review committee of college of health sciences, Mettu University, the authors must not upload the dataset to a stable, public repository. Interested, qualified researchers can access the data by requesting Dean College of health sciences of Mettu University, Desalegn Chilo (desalegchilo89@gmail.com) and the corresponding author, Defaru Desalegn (defdesalegn2007@gmail.com)

4. Is the manuscript presented in an intelligible fashion and written in Standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Authors’ response: we accepted the comment and thoroughly edited the whole document for grammatical error or any other unclear contents.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Abstract

In the first sentence the word ‘abused’ and ‘abuser’ is not right. There is no diagnostic criteria for tobacco abuse in DSM-5.

Authors’ response: Accepted and replaced the word ‘abused’ and ‘abuser’ with the word ‘used’ and ‘user’ respectively.

The introduction part can be shortened. There are a lot of research findings from all the over the world. It should be summarized to the most relevant researches and high quality evidence.

Authors’ response: we accepted the comments and we have shortened the introduction.

Materials and methods

Please include a statement on the type of the study design.

Authors’ response: Study design was included in the manuscript

Please include some statements about the interviewer’s level of expertise.

Authors’ response: we have included the statements about the interviewer’s level of expertise under ‘data collection procedures and tools’ subtitle of methods section.

And the instrument that has been used to assess tobacco dependence (Fagerstrom Test for Nicotine Dependence (FTND)), was the instrument used in it’s original language or was it translated?

Authors’ response: we used the translated instrument

If it was translated, please specify the process of translation of this or other instruments.

Authors’ response: the process of translation was described under ‘data quality control’ subtitle of methods section

Please put the reference paper which has validated the SDS instrument in Ethiopia.

Authors’ response: Can be added, because it was validated at Mizan, Ethiopia

Result

The 1st paragraph second sentence include the ‘mean age’.

Authors’ response: we have included

On the next sentences there are repetitions, please correct it.

Authors’ response: we have omitted the repeated sentences

The last sentence the median (IQR) monthly income the IQR is not specified in a range of numbers.

Authors’ response: we accept the comment and corrected accordingly ‘‘the median monthly income of the respondents were 700ETB, which ranges from 100-5000ETB and the interquartile range is 1000.’’

2nd paragraph 3rd line include ‘family history’

Authors’ response: we have Included

Correlates of tobacco dependence among patients with schizophrenia

On the bivariate logistic regression,-- it is univariable logistic regression

There is inconsistency of the result from the table 3 and the above paragraph presented about the significant result on univariable and multivariable logistic regression.

Authors’ response: In our analysis part, for univariable analysis we have used a P –value of 0.25 or less as inclusion criteria for the final model so as not to miss important clinical variables. Accordingly male gender, unemployment, being on treatment for 5years, having a history of admission and frequent admission, presence of physical illness, family history of mental illness and being educated above secondary school. However, for the gender, we mistakenly stated and admit to edit to male.

Discussion

It needs further explanation on recommendation and the uniqueness of this study.

Authors’ response: we accept and addressed it

Reviewer #2: This study addressed the frequency of ND in patents with schizophrenia in Ethiopia. While similar study has already been published (Molla et al, 2017), the question is whether this study brings new data. This text needs major revision, and English language revision.

Authors’ response: our study addressed specifically the frequency of ND in patients with schizophrenia in Ethiopia. But, this (Molla et al, 2017) study, the previously done and published, was done among mental illness in general. Also our study assessed factors like Khat and alcohol by using independent instruments. In addition, we have revised the whole document for grammar and spelling error.

Introduction

Page 9-The impact of smoking among schizophrenic patients, not only increases metabolism and vascular risks-what is meant by „metabolism “?

Authors’ response: It mean that smoking increases the activity of cytochrome p450 isoenzyme 1A2 (CYP1A2) and UDP-glucuronosyltransefereses (UGT), which are responsible for drug metabolism (antipsychotics)

It decreases the antipsychotic therapeutic effects as smoking induces the medication metabolism in the liver reducing up to 48% the active metabolites in serum (9). -please, be more specific-because smoking does not induce the metabolism of all antipsychotics

Authors’ response: we have addressed above

One hospital based cross sectional study done among 429 inpatients schizophrenic patients in China receive antipsychotic mono-therapy found that the prevalence rate of current smoking was 40.6%and 57.5% in males and 6.3% in females. -please, put the reference number in the parenthesis, and correct English grammar

Authors’ response: we accepted the comment and corrected accordingly

A cross sectional study done in Singapore among male schizophrenic patients found that the lifetime prevalence and current smoker are 54.1%and 42.4%respectively (15). -life time prevalence of what?

Authors’ response: we have corrected as “life time prevalence of smoking cigarette …”

Methods

How was schizophrenia confirmed? According to which classification system? It is unclear whether the patients were in-or out-patients or both.

Authors’ response: as we described under operation definition schizophrenia is a clinical diagnosis reached by clinician based on DSM-IV or DSM-5 diagnostic criteria as reviewed from patient card and the study populations were sample of patients with schizophrenia who attended the out-patient treatment. Please under ‘study population’ subtitle of methods section

Exclusion criteria-„patients who are seriously ill “-please define what this term refers to

Authors’ response: we have defined it. Please see under ‘inclusion and exclusion criteria’ subtitle of methods section

Operational definitions: Chronic illness: past mental illness...how could past mental illnesses be defined, when participants already have schizophrenia?

Authors’ response: We accept the comments and corrected

The study lacks any measure of schizophrenia psychopathology (such as PANSS)

Authors’ response: yes, we didn’t assessed psychopathology and we accepted as the limitation of our study

What about pharmacotherapy? Did patients receive antipsychotics?

Authors’ response: Yes, but we didn’t assessed the type of antipsychotic they are taking

Results

The mean (±SD) of the study participants were 33.7(±7.9) years-the term „age “is missing

66.2% were males-was mentioned twice

Authors’ response: we accepted the comments and corrected

The section: „ Prevalence of tobacco dependence among patients with schizophrenia “is unclear and difficult to read. How many patients were current smokers? The data providing number (frequency) of smokers, and categories of FTND-defined nicotine dependence, need to be presented in a separate table

Authors’ response: we accept the comment and incorporated the points in result part in Table 3. for the rate of current , the tools will not assess in terms of current smokers rather on daily ,weekly and monthly basis as stated in Table 3.

„Few of them had history of mental illness (15.7%)-it is unclear,

because all patients had schizophrenia

Authors’ response: we appreciate your concern and corrected below. Indeed we mean to family history of mental illness rather than personal history including schizophrenia and other diagnosable mental illness. ‘‘Few of them had both family history of mental illness (15.7%) and substance use (17.1%)’’.

Discussion

Please, provide in the discussion the rates of nicotine dependence in Ethiopia general population, and then comment on the ND rate in schizophrenia patients, whether and how it differs compared to general population in the same country.

Authors’ response: we accepted the comments and we have provided the rates of nicotine dependence in Ethiopia general population in discussion and have compared with the current findings in schizophrenic patients.

Limitations

The lack of any scale measuring current psychopathology is also a limitation.

Authors’ response: we accepted the comments and added on the limitation part

The conclusion „a significant proportion of tobacco dependence...“ would be valid only if this ND frequency outnumbers smoking prevalence in Ethiopia general population.

________________________________________

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Reviewer #1: No

Reviewer #2: No

Authors’ response: No

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Additional comments

1. You state that "All relevant data are included within the paper". However, the rest of your response indicates that the relevant data are available upon request. Please confirm that your data is available upon request

Authors’ response: we admit our errors that we unintentionally responded as relevant data are available upon request and we all the authors agreed that all relevant data are included within the paper. The data would be guarded carefully by our research team for the only purpose of this scientific study and it is an ongoing project. Also, participants were not signed consent for data publicity. For all these reasons and following the indicators of the research review committee of college of health sciences, Mettu University, the authors must not upload the dataset to a stable, public repository. But, interested, qualified researchers can access the data by requesting Dean College of health sciences of Mettu University, Desalegn Chilo (desalegchilo89@gmail.com) and the corresponding author, Defaru Desalegn (defdesalegn2007@gmail.com)

2. You state that "the data would be guarded carefully by [y]our research team". Please confirm that your data will indeed be available upon request to researchers who submit data access requests and meet the criteria for access to confidential data.

Authors’ response: Interested, qualified researchers can access the data by requesting Dean College of health sciences of Mettu University, Desalegn Chilo (desalegchilo89@gmail.com) and the corresponding author, Defaru Desalegn (defdesalegn2007@gmail.com)

(2) Please describe in your methods section how capacity to provide consent was determined for the participants in this study.

Authors’ response: we have described how capacity to provide consent was determined for the participants in our study in our methods section specifically under ‘ethical clearance ‘

(3) We note that there is still some overlap within your Abstract and Introduction

Authors’ response: we appreciate your concerns and we have corrected accordingly. Please, see at our abstract and introduction.

Submitted filename: Response letter 2.docx

Click here for additional data file.

3 Aug 2021

PONE-D-20-31418R1

Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia ; Hospital-Based Cross-Sectional Study

PLOS ONE

Dear Dr. Desalegn,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

There are still serious problems with the English.  It is important that you have the manuscript edited by a native English speaker before you submit a revised manuscript in addition to carefully addressing the reviewers' technical comments.

Please submit your revised manuscript by Sep 17 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Stanton A. Glantz, PhD

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia ; Hospital-Based Cross-Sectional Study

Reviewer #1:

1. Abstract In the first sentence the word ‘abused’ and ‘abuser’ is not right. There is no criteria for tobacco abuse in DSM-5.

Authors’ response: Accepted and replaced the word ‘abused’ and ‘abuser’ with the word ‘used’ and ‘user’ respectively.

Re-reviewer response -Even though the word is changed the sentence is not written in a correct English grammar.

Result section of the abstract - Concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report high and very high level of tobacco dependence respectively [ this sentence is not correct, misses the word moderate].

2. The introduction part can be shortened. There are a lot of research findings from all the over the world. It should be summarized to the most relevant researches and high quality evidence.

Authors’ response: we accepted the comments and we have shortened the introduction.

Re-reviewer response – accepted

3. Materials and methods Please include a statement on the type of the study design.

Authors’ response: Study design was included in the manuscript

Re-reviewers response – accepted

4. Please include some statements about the interviewer’s level of expertise.

Authors’ response: we have included the statements about the interviewer’s level of expertise under ‘data collection procedures and tools’ subtitle of methods section.

Re-reviewers response – accepted

5. And the instrument that has been used to assess tobacco dependence (Fagerstrom Test for Nicotine Dependence (FTND)), was the instrument used in it’s original language or was it translated?

Authors’ response: we used the translated instrument

Re-reviewers response – accepted

6. If it was translated, please specify the process of translation of this or other instruments.

Authors’ response: the process of translation was described under ‘data quality control’ subtitle of methods section

Re-reviewers response – accepted

7. Please put the reference paper which has validated the SDS instrument in Ethiopia.

Authors’ response: Can be added, because it was validated at Mizan, Ethiopia.

Re-reviewers response – if the validation paper was not published in peer reviewed journal, you cannot say that it was validated

8. Result The 1st paragraph second sentence include the ‘mean age’.

Authors’ response: we have included

Re-reviewers response – accepted

9. On the next sentences there are repetitions, please correct it.

Authors’ response: we have omitted the repeated sentences

Re-reviewers response – accepted

10. The last sentence the median (IQR) monthly income the IQR is not specified in a range of numbers.

Authors’ response: we accept the comment and corrected accordingly ‘‘the median monthly income of the respondents were 700ETB, which ranges from 100-5000ETB and the interquartile range is 1000.’’

Re-reviewers response – this is still not correct. IQR should be in a range

11. On the bivariate logistic regression,-- it is univariable logistic regression. There is inconsistency of the result from the table 3 and the above paragraph presented about the significant result on univariable and multivariable logistic regression.

Authors’ response: In our analysis part, for univariable analysis we have used a P –value of 0.25 or less as inclusion criteria for the final model so as not to miss important clinical variables. Accordingly male gender, unemployment, being on treatment for 5years, having a history of admission and frequent admission, presence of physical illness, family history of mental illness and being educated above secondary school. However, for the gender, we mistakenly stated and admit to edit to male.

Re-reviewers response – on the paragraph it is still not edited. Table 4 is not written in a consistent manner. For example the ref. value is sometime on the first row and sometimes on the second row. The analysis you have done is not correlation therefore you should not use the words like “correlations”.

12. Discussion It needs further explanation on recommendation and the uniqueness of this study. Authors’ response: we accept and addressed it

Re-reviewers response – not addressed.

On the 4th paragraph 3rd line it says “The notion was indicating the role of genetic factors and nicotine dependence in the pathogenesis of schizophrenia” this needs further explanation. Are you saying that nicotine dependence is causing schizophrenia?

On the conclusion part it says female gender is associated with tobacco dependence and it should male gender.

In general the whole text needs English language revision. The whole manuscript is written in mundane fashion it should be written in attractive way to the readers.

Reviewer #2: The authors have addressed all comments, but there are still some issues in the text that must be improved

Abstract, Background: „Tobacco smoking is that the most typically employed in patients with mental disorders; among them, patients with schizophrenia area unit the very best users...“ This text is not clear, please, change

Abstract, results: Concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report high and very high level of tobacco dependence respectively-all three percentages need description., i.e., to which two of the three mentioned percentages do belong high and very high level of ND?

Results

The mean age (±SD) of the study participants were 33.7(±7.9) year age..-please, delete „age“ at the end of the sentence

Table 3. Please, explain what is „frequency“ and „percentage“. Does the „frequency“ actually refer to absolute numbers?

While male gender was associated with tobacco dependence in univariable logistic regression, female gender was associated with tobacco dependence in the final regression analysis. It is difficult to understand, so, please, explain this finding, and mention this also in the discussion.

Discussion

„The results were also higher compared to the finding of the study from Nigeria (20.4)“-percent?

References

References are not complete. Please, check and correct carefully all references.

For example, reference No 10 is lacking five additional authors, and the journal name. References 11 and 12 look very much alike, while the No 12 has no journal name

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

25 Sep 2021

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

2. Is the manuscript technically sounds, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

RESPONSE: We accepted the comments and tried to incorporate points that clearly stipulated the findings of the study.

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: I Don't Know

RESPONSE: In the current study, we used the Statistical Package for Social Science Version 24.0 for data analysis. Descriptive analysis (median, percentage, frequencies, and interquartile range) was used to compute demographic characteristics of participants. In addition, bivariable analysis was used to see the significance of the association. Variables that showed strong association (p-value <0.25) in bivariate analysis were entered into multivariable logistic regressions to identify independently associated variables. Multicollinearity was checked by the variance inflation factor (VIF). Statistical significance was declared at a p-value less than 0.05. The significance of association of the variables was described using AOR with a 95% confidence interval.

Unfortunately, there are some editorial errors that occurred during the write up of the result and discussion, such as the report of a female instead of a male in the discussion and exclusion parts. We admitted it and correctly accordingly. Other than this, we did our best and conducted detailed analysis as per the objectives of the study.

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

5. Is the manuscript presented in an intelligible fashion and written in Standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

RESPONSE: We have accepted and addressed all the English grammatical errors.

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia; Hospital-Based Cross-Sectional Study

Reviewer #1:

1. Abstract In the first sentence the word ‘abused’ and ‘abuser’ is not right. There is no criteria for tobacco abuse in DSM-5.

Authors’ response: Accepted and replaced the word ‘abused’ and ‘abuser’ with the word ‘used’ and ‘user’ respectively.

Re-reviewer response -Even though the word is changed the sentence is not written in a correct English grammar.

RESPONSE: Accepted and corrected as “Tobacco smoking is the most commonly used in patients with mental disorders; patients with schizophrenia are the most frequent users”.

Result section of the abstract - Concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report high and very high level of tobacco dependence respectively [ this sentence is not correct, misses the word moderate].

RESPONSE: Accepted and edited accordingly as “concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report moderate, high, and very high level of tobacco dependence respectively”.

2. The introduction part can be shortened. There are a lot of research findings from all the over the world. It should be summarized to the most relevant researches and high quality evidence.

Authors’ response: we accepted the comments and we have shortened the introduction.

Re-reviewer response – accepted

3. Materials and methods please include a statement on the type of the study design.

Authors’ response: Study design was included in the manuscript

Re-reviewers response – accepted

4. Please include some statements about the interviewer’s level of expertise.

Authors’ response: we have included the statements about the interviewer’s level of expertise under ‘data collection procedures and tools’ subtitle of methods section.

Re-reviewers response – accepted

5. And the instrument that has been used to assess tobacco dependence (Fagerstrom Test for Nicotine Dependence (FTND)), was the instrument used in it’s original language or was it translated?

Authors’ response: we used the translated instrument

Re-reviewers response – accepted

6. If it was translated, please specify the process of translation of this or other instruments.

Authors’ response: the process of translation was described under ‘data quality control’ subtitle of methods section

Re-reviewers response – accepted

7. Please put the reference paper which has validated the SDS instrument in Ethiopia.

Authors’ response: Can be added, because it was validated at Mizan, Ethiopia.

Re-reviewers response – if the validation paper was not published in peer reviewed journal, you cannot say that it was validated.

RESPONSE: The instrument was validated in Mizan, the Southwestern part of Ethiopia. This is the references and we have included also in “Manzar MD, Alamri M, Mohammed S, Khan MAY, Chattu VK, Pandi-Perumal SR, et al. Psychometric properties of the severity of the dependence scale for Khat (SDS-Khat) in polysubstance users. BMC Psychiatry. 2018;18(1):1–8.”

8. Result The 1st paragraph second sentence includes the ‘mean age’.

Authors’ response: we have included

Re-reviewers response – accepted

9. On the next sentences there are repetitions, please correct it.

Authors’ response: we have omitted the repeated sentences

Re-reviewers response – accepted

10. The last sentence the median (IQR) monthly income the IQR is not specified in a range of numbers.

Authors’ response: we accept the comment and corrected accordingly ‘‘the median monthly income of the respondents were 700ETB, which ranges from 100-5000ETB and the interquartile range is 1000.’’

Re-reviewers response – this is still not correct. IQR should be in a range

RESPONSE: IQR was thought to be midspread, the middle 50% of the measure of statistical dispersion, being equal to the difference between 75th and 25th percentiles, or between upper and lower quartiles, and we reported accordingly. Considering the comments we have reported in range.

11. On the bivariate logistic regression,-- it is univariable logistic regression. There is inconsistency of the result from the table 3 and the above paragraph presented about the significant result on univariable and multivariable logistic regression.

Authors’ response: In our analysis part, for univariable analysis we have used a P –value of 0.25 or less as inclusion criteria for the final model so as not to miss important clinical variables. Accordingly male gender, unemployment, being on treatment for 5years, having a history of admission and frequent admission, presence of physical illness, family history of mental illness and being educated above secondary school. However, for the gender, we mistakenly stated and admit to edit to male.

Re-reviewers response – on the paragraph it is still not edited. Table 4 is not written in a consistent manner. For example the ref. value is sometime on the first row and sometimes on the second row. The analysis you have done is not correlation therefore you should not use the words like “correlations”.

RESPOSE: Accepted ad edited accordingly

12. Discussion It needs further explanation on recommendation and the uniqueness of this study. Authors’ response: we accept and addressed it

Re-reviewers response – not addressed.

RESPONSE: we have included the statements supporting of the first of the discussion and conclusion.

On the 4th paragraph 3rd line it says “The notion was indicating the role of genetic factors and nicotine dependence in the pathogenesis of schizophrenia” this needs further explanation. Are you saying that nicotine dependence is causing schizophrenia?

RESPONSE: We accepted the comment and corrected the sentence as “the notion was indicating the role of genetic factors in the etiology of smoking behaviour and the high comorbidity between nicotine dependence and schizophrenia” and we are not saying that nicotine dependence is causing schizophrenia. That was an editorial error.

On the conclusion part it says female gender is associated with tobacco dependence and it should male gender.

RESPONSE: we accepted and edited accordingly. That was an editorial error.

In general the whole text needs English language revision. The whole manuscript is written in mundane fashion it should be written in attractive way to the readers.

RESPONSE: we have accepted and addressed all the English language grammar problems.

Reviewer #2: The authors have addressed all comments, but there are still some issues in the text that must be improved

RESPONSE: We have accepted and addressed all the issues in the text.

Abstract, Background: „Tobacco smoking is that the most typically employed in patients with mental disorders; among them, patients with schizophrenia area unit the very best users...“ This text is not clear, please, change

RESPONSE: we accepted and changed as “Tobacco smoking is the most commonly used in patients with mental disorders; patients with schizophrenia are the most frequent users”.

Abstract, results: Concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report high and very high level of tobacco dependence respectively-all three percentages need description., i.e., to which two of the three mentioned percentages do belong high and very high level of ND?

RESPONSE: Accepted and edited accordingly above as “concerning the severity of tobacco dependence, 3.5%, 13.8% and 5% of the respondents report moderate, high, and very high level of tobacco dependence respectively”.

Results

The mean age (±SD) of the study participants were 33.7(±7.9) year age..-please, delete „age“ at the end of the sentence

RESPONSE: Accepted and deleted the word “age” from the end of the sentence.

Table 3. Please, explain what is „frequency “ and percentage“. Does the „frequency“ actually refer to absolute numbers?

RESPONSE: Frequency refers to absolute numbers, while percentage refers to the relative frequency value divided by 100.

While male gender was associated with tobacco dependence in univariable logistic regression, female gender was associated with tobacco dependence in the final regression analysis. It is difficult to understand, so, please, explain this finding, and mention this also in the discussion.

RESPONSE: we accepted and edited accordingly. That was an editorial error.

Discussion

„The results were also higher compared to the finding of the study from Nigeria (20.4)“-percent?

RESPOSE: Accepted and corrected as 20.4%. That was an editorial error.

References

References are not complete. Please, check and correct carefully all references.

For example, reference No 10 is lacking five additional authors, and the journal name. References 11 and 12 look very much alike, while the No 12 has no journal name

RESPOSE: 10 corrected,

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No(1)

Submitted filename: Response to Reviwiers.docx

Click here for additional data file.

6 Nov 2021

PONE-D-20-31418R2Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia ; Hospital-Based Cross-Sectional StudyPLOS ONE

Dear Dr. Desalegn,

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Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

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Comments to the Author

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Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Authors have addressed the comments

However, there are some additional remarks:

In tables 1, 2 and 3, frequency should be replaced with numbers

References should all be edited in a uniform way, strictly according to the journal policy. For example, references no 5,6,8,9, 13,14,15,16,19, etc, have no journal name. Reference no 10 has full author first names, some references have name of the month, for example the ref no 20, which is missing journal volume and pages. Please, correct all references!

English grammar has to be checked and corrected

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

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17 Nov 2021

RESPONSE TO EDITOR AND REVIEWER’

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

RESPONSE: We have accepted and corrected all the references according to the journal policy.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Authors have addressed the comments

However, there are some additional remarks:

In tables 1, 2 and 3, frequency should be replaced with numbers

RESPOSE: Accepted and we have replaced frequency with numbers accordingly

References should all be edited in a uniform way, strictly according to the journal policy. For example, references no 5,6,8,9, 13,14,15,16,19, etc, have no journal name. Reference no 10 has full author first names, some references have name of the month, for example the ref no 20, which is missing journal volume and pages. Please, correct all references!

RESPONSE: We have accepted and corrected all the references according to the journal policy.

English grammar has to be checked and corrected

RESPONSE: we have accepted and addressed all the English language grammar problems.

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #2: No

Submitted filename: Response to Reviwiers.docx

Click here for additional data file.

29 Nov 2021

Prevalence of Tobacco Dependence and Associated Factors among Patients with Schizophrenia Attending Their Treatments at Southwest Ethiopia ; Hospital-Based Cross-Sectional Study

PONE-D-20-31418R3

Dear Dr. Desalegn,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Kenji Hashimoto, PhD

Section Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: References are again not presented in a uniform way. For example, some do mention the month, such as: Schizophrenia research. 2005 Jul 15;76(2-3):135-57., while others don't, for example: Neuropsychiatr Dis Treat. 2018;14:1535–43.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

6 Dec 2021

PONE-D-20-31418R3

Prevalence of tobacco dependence and associated factors among patients with schizophrenia attending their treatments at southwest Ethiopia; Hospital-based cross-sectional study

Dear Dr. Desalegn:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

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PLOS ONE

Table 1

Socio-demographic characteristic of patients with schizophrenias at southwest Ethiopia, 2019 (n = 515).

Variables	Category	Numbers (n)	Percentage (%)
Sex	Male	341	66.2
	Female	174	33.8
Age(in years)	18–24	59	11.5
	25–34	215	41.7
	35–44	178	34.6
	45–54	63	12.2
Religion	Muslim	332	64.5
	Orthodox	101	19.6
	Protestant	82	15.9
Ethnicity	Oromo	326	63.3
	Amhara	116	22.5
	SNNP	73	14.2
Marital status	Single	175	34.0
	Married	287	55.7
	Divorced/widowed	53	10.3
Educational status	No formal education	132	25.6
	Primarily school	150	29.1
	Secondary	116	22.5
	Above secondary	117	22.7
Residence	Urban	292	56.7
	Rural	223	43.3
Occupation	Government employed	103	20.0
	Self-employed	185	35.9
	Unemployed	227	44.1
Family size	<4	211	41.0
	≥4	304	59.0
Monthly Income	<700 ǁ ETB	264	51.3
	≥700 ETB	251	48.7

SNNP (South nations and nationalities and peoples)–stands for Kaffa, Dawuro, Yem, Walayta, Gurage and Silte, Median of monthly income, ETB–Ethiopian birr.

Table 2

Clinical and other substance-related characteristics of patients with schizophrenia, southwest Ethiopia, 2019 (n = 515).

Variables	Category	Numbers (n)	Percentage (%)
Admission history	No	308	59.8
	Yes	207	40.2
Frequency of admission	1	75	14.6
	2	88	17.1
	3	44	8.5
Physical illness	Yes	38	7.4
	No	477	92.6
Family history of mental illness	No	434	84.3
	Yes	81	15.7
Family history of substance use	No	427	82.9
	Yes	88	17.1
Alcohol use disorder	Yes	187	36.3
	No	328	63.7
Khat dependence	Yes	155	30.1
	No	360	69.9
Duration of illness	<6 years	292	56.7
	≥6 years	223	43.3
Treatment duration	<5 years	271	52.6
	≥5 year s	244	47.7

Table 3

Level of tobacco dependence and frequency of smoking amongst patients with schizophrenia attending their treatments at southwest Ethiopia, 2019 (n = 515).

Variables		Numbers (n)	Percentage (%)
Level of dependence	Moderate (5)	18	3.5
	High (6–7)	71	13.8
	Very high (8–10)	26	5
Frequency of smoking	Never	401	77.9
	Once or twice	34	6.6
	Daily or almost daily	37	7.2
	Weekly	21	4.1
	Monthly	22	4.3

Table 4

Factors associated with tobacco dependence among schizophrenic patients at Mettu Karl referral, Bedelle and Agaro hospitals, southwest Ethiopia, 2020 (N = 515).

Variable	Category	Tobacco use		COR, 95% (CI)	AOR, 95% (CI)
		Not dependent N (%)	Dependent N (%)
Sex	Female	147 (84.5)	27 (15.5)	Ref	Ref
	Male	253 (74.2)	88 (25.8)	1.89 (1.18,3.05)	2.19 (1.25,3.83)**
Occupational status	Government employed	79 (76.9)	24 (23.3)	Ref	Ref
	Self-employed	168 (90.8)	17 (9.2)	0.33 (0.17,0.66)	0.41 (0.17, 1.00)
	Unemployed	153 (67.4)	74 (32.6)	1.59 (0.93,2.72)	2.09 (0.98, 4.49)
Frequency of admission	None	146 (71.9)	57 (28.1)	Ref	Ref
	1	124 (80.0)	31 (20.0)	0.79 (0.43,1.45)	1.32 (0.66, 2.65)
	2	92 (81.4)	21 (18.6)	0.55 (0.29,1.03)	1.63 (0.66,4.01)
	3	38 (86.4)	6 (13.6)	0.46 (0.19,1.12)	0.67 (0.23,2.15)
Duration of treatment	<5years	220 (81.2)	51 (18.8)	Ref	Ref
	≥5years	180 (73.8)	64 (26.2)	1.53 (1.01,2.33)	4.37 (2.11,9.02)***
Educational status	No formal education	112 (84.8)	20 (15.2)	Ref	Ref
	Primarily school	117 (78.0)	33 (22.0)	1.58 (0.86, 2.92)	0.59 (0.25, 1.44)
	Secondary	88 (75.9)	28 (24.1)	1.78 (0.94,3.37)	0.91 (0.41,2.00)
	Above	83 (70.9)	34 (29.1)	2.29 (1.23,4.27)	0.73 (0.34,1.59)
Admission history	No	265 (86.0)	43 (14.0)	Ref	Ref
	Yes	135 (65.2)	72 (34.8)	3.29 (2.14,5.06)	4.01 (1.99, 8.11)**
Physical illness	Yes	25 (65.8)	13 (34.2)	1.91 (0.95,3.87)	1.79 (0.73,4.43)
	No	375 (78.6)	102 (21.4)	Ref	Ref
Alcohol use disorder	Dependent	151 (80.7)	36 (19.3)	1.33 (0.86,2.07)	1.12 (0.67,1.85)
	Non-dependent	249 (75.9)	79 (24.1)	Ref	Ref
Family history of mental illness	No	347 (80.0)	87 (20.0)	Ref	Ref
	Yes	53 (65.4)	28 (34.6)	2.11 (1.26,3.53)	1.90 (1.04,3.48)*

Abbreviations: OR, Odds Ratio; CI, Confidence Interval. Ref: Reference category NB.*Persisted significant at P-value <0.05, ** significant at P-value ≤0.001. *** Significant at P-value <0.0001.