Effect of smoking cessation interventions on abstinence and tuberculosis treatment outcomes among newly diagnosed patients: a randomized controlled trial

ABSTRACT The study evaluates the effectiveness of smoking cessation interventions [Behavioral Change Communication (BCC) and Behavioral Change Communication plus bupropion (BCC+)] compared to conventional Directly Observed Therapy Short Course (DOT) treatment in improving pulmonary tuberculosis treatment outcomes and abstinence among newly diagnosed pulmonary tuberculosis (PTB) patients, highlighting the scarcity of robust experimental studies. The current randomized controlled trial, conducted at Ojha Institute of Chest Diseases between October 2017 and June 2019, randomized 292 patients who were current smokers with newly diagnosed pulmonary tuberculosis into three arms: control (n = 97), BCC (n = 97), and BCC+ (n = 98) arms. The outcomes of the interventions were compared in terms of favorable treatment outcomes and abstinence achieved at the end of 6 months. Baseline characteristics were compared between groups. Cox regression quantified the effect size of interventions for both outcome variables and reported as (crude and adjusted) hazard ratios with 95% confidence intervals (CI). No statistically significant difference was observed in baseline characteristics in each arm. Both BCC+ and BCC showed a statistically significant effect in achieving favorable PTB outcomes at 6 months (aHR 2.37, 95% CI 1.52–3.70 and aHR 2.34, 95% CI 1.51–3.60), as well as for abstinence from smoking at 6 months (BCC+: aHR 4.03, 95% CI 2.18–7.44 and BCC: aHR 3.87, 95% CI 2.12–7.05) compared to the control arm. Both BCC and BCC+ aided by pharmacologic agents such as bupropion when incorporated with conventional DOTs were found to be significantly effective in attaining favorable tuberculosis treatment outcomes as well as in attaining smoking abstinence at the end of the 6-month treatment. 
IMPORTANCE
 This study shows that adding smoking cessation programs (with or without extra drugs like bupropion) to standard Directly Observed Treatment Short Course (DOTs) treatment for people who have recently been diagnosed with pulmonary tuberculosis has a great positive impact on how well the overall antituberculosis treatment works. Our trial shows very promising results for such a combined therapy (DOTs and smoking cessation) in a country where the burden of both tuberculosis and smoking is very high.


Revision Guidelines
To submit your modified manuscript, log into the submission site at https://spectrum.msubmit.net/cgi-bin/main.plex.Go to Author Tasks and click the appropriate manuscript title to begin.The information you entered when you first submitted the paper will be displayed; update this as necessary.Note the following requirements: • Upload point-by-point responses to the issues raised by the reviewers in a file named "Response to Reviewers," NOT IN YOUR COVER LETTER • Upload a compare copy of the manuscript (without figures) as a "Marked-Up Manuscript" file • Upload a clean .DOC/.DOCX version of the revised manuscript and remove the previous version • Each figure must be uploaded as a separate, editable, high-resolution file (TIFF or EPS preferred), and any multipanel figures must be assembled into one file • Any supplemental material intended for posting by ASM should be uploaded separate from the main manuscript; you can combine all supplemental material into one file (preferred) or split it into a maximum of 10 files, with all associated legends included For complete guidelines on revision requirements, see our Submission and Review Process webpage.Submission of a paper that does not conform to guidelines may delay acceptance of your manuscript.
Data availability: ASM policy requires that data be available to the public upon online posting of the article, so please verify all links to sequence records, if present, and make sure that each number retrieves the full record of the data.If a new accession number is not linked or a link is broken, provide Spectrum production staff with the correct URL for the record.If the accession numbers for new data are not publicly accessible before the expected online posting of the article, publication may be delayed; please contact production staff (Spectrum@asmusa.org)immediately with the expected release date.
Publication Fees: For information on publication fees and which article types are subject to charges, visit our website.If your manuscript is accepted for publication and any fees apply, you will be contacted separately about payment during the production process; please follow the instructions in that e-mail.Arrangements for payment must be made before your article is published.
ASM Membership: Corresponding authors may join or renew ASM membership to obtain discounts on publication fees.Need to upgrade your membership level?Please contact Customer Service at Service@asmusa.org.
The ASM Journals program strives for constant improvement in our submission and publication process.Please tell us how we can improve your experience by taking this quick Author Survey.
Thank you for submitting your paper to Spectrum.

Sincerely, Sadjia Bekal
Editor Microbiology Spectrum Reviewer #1 (Comments for the Author): The authors did a meticulously thorough job, highly commendable.Research protocols are clearly observed and carefully implemented.The research findings are clearly reported without ambiguity.However there seem to be a minor error on line 309 -310 "...Similar insignificant effect of another SCI, nicotine replacement therapy (NRT), was reported by However Aryanpur et al, ( 14) reported that 'counseling plus bupropion' was more effective in attaining.)Kindly revisit this segment of the report for better understanding.Thank you for the privilege of reviewing your work.Below you will find my comments, instructions from the Spectrum editorial office, and the reviewer comments.
Please return the manuscript within 60 days; if you cannot complete the modification within this time period, please contact me.If you do not wish to modify the manuscript and prefer to submit it to another journal, notify me immediately so that the manuscript may be formally withdrawn from consideration by Spectrum.

Revision Guidelines
To submit your modified manuscript, log into the submission site at https://spectrum.msubmit.net/cgi-bin/main.plex.Go to Author Tasks and click the appropriate manuscript title to begin.The information you entered when you first submitted the paper will be displayed; update this as necessary.Note the following requirements: • Upload point-by-point responses to the issues raised by the reviewers in a file named "Response to Reviewers," NOT IN YOUR COVER LETTER • Upload a compare copy of the manuscript (without figures) as a "Marked-Up Manuscript" file • Upload a clean .DOC/.DOCX version of the revised manuscript and remove the previous version • Each figure must be uploaded as a separate, editable, high-resolution file (TIFF or EPS preferred), and any multipanel figures must be assembled into one file • Any supplemental material intended for posting by ASM should be uploaded separate from the main manuscript; you can combine all supplemental material into one file (preferred) or split it into a maximum of 10 files, with all associated legends included For complete guidelines on revision requirements, see our Submission and Review Process webpage.Submission of a paper that does not conform to guidelines may delay acceptance of your manuscript.
Data availability: ASM policy requires that data be available to the public upon online posting of the article, so please verify all links to sequence records, if present, and make sure that each number retrieves the full record of the data.If a new accession number is not linked or a link is broken, provide Spectrum production staff with the correct URL for the record.If the accession numbers for new data are not publicly accessible before the expected online posting of the article, publication may be delayed; please contact production staff (Spectrum@asmusa.org)immediately with the expected release date.
Publication Fees: For information on publication fees and which article types are subject to charges, visit our website.If your manuscript is accepted for publication and any fees apply, you will be contacted separately about payment during the production process; please follow the instructions in that e-mail.Arrangements for payment must be made before your article is published.

ASM Membership:
Corresponding authors may join or renew ASM membership to obtain discounts on publication fees.Need to upgrade your membership level?Please contact Customer Service at Service@asmusa.org.
The ASM Journals program strives for constant improvement in our submission and publication process.Please tell us how we can improve your experience by taking this quick Author Survey.
Thank you for submitting your paper to Spectrum.

Sincerely, Sadjia Bekal Editor Microbiology Spectrum
Reviewer #1 (Comments for the Author): I confirmed that the authors adequately addressed the concerns I raised during the initial review process RE -REVIEW REPORT BY ABRAHAM TERNA LAN 22 nd January, 2024.
Effects of smolking cessation intervention on abstinence and tuberculosis treatment outcomes among newly diagnosed patients: A randomized controlled trial by Muhammed Tahir Khan et al., based on my previous comments and concerns raised I wish to confirmed that the authors satisfactorily attended to the issues I raised as shown below indicated in alphabetical order "A" and "B" to represent the review concerns and the corrections thereof respectively.
A. However, there seem to be a minor error on line 309 -310 "...Similar insignificant effect of another SCI, nicotine replacement therapy (NRT), was reported by However Aryanpur et al, ( 14) reported that 'counseling plus bupropion' was more effective in attaining…, B. has been modified to (line 305-311) "similar positive effects of the SCIs on abstinence from smoking among tuberculosis patients (1,12,14,23,35)   The authors did a meticulously thorough job, highly commendable.Research protocols are clearly observed and carefully implemented.The research findings are clearly reported without ambiguity.However there seem to be a minor error on line 309 -310 "...Similar insignificant effect of another SCI, nicotine replacement therapy (NRT), was reported by However Aryanpur et al, (14) reported that 'counseling plus bupropion' was more effective in attaining.)Kindly revisit this segment of the report for better understanding.

RESPONSE:
The part has been rewritten for clarity.
-23R1 (Effect of smoking cessation interventions on abstinence and tuberculosis treatment outcomes among newly diagnosed patients: A randomized controlled trial) Dear Dr. Muhammad Tahir Khan: give attention to references and their format according to journal policy.For example, references 25 and 35 are incomplete and not found by readers in their current format.A link will be helpful.RESPONSE: The references are removed.Other references are also put according to the journal's referencing style (ASM Journals).Reviewer's Comment: Reviewer #1 (Comments for the Author):