PONE-D-22-00300Association between recent overdose and chronic pain among individuals in treatment for opioid use disorderPLOS ONE

Dear Dr. Hartz,

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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: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

Reviewer #2: Yes

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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: Yes

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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: This study addressed the relations between chronic pain and opioid overdose. The author used a survey database (Survey of Key Informants Patients; SKIP) of 3577 opioid use disorder individuals under treatment during 2017-2018. The database has 3738 complete the substance use survey, it excluded 161 who did not response to opioid overdose and chronic pain items. The author has also tested the representative of the SKIP database through comparison with another database of Treatment Episode Data Set (TEDS) at 2017. They used Chi-square tests for this comparison and showed consistency between these two data sets. Active chronic pain is defined as answer “yes” in the last 7 days or “yes” in the last 30 days from the “Have you suffered from chronic pain?” item. The author found that the active chronic pain of opioid use disorder (OUD) were more likely to have opioid overdose in the past month than no history chronic pain (OR=1.55). They suggest that chronic pain treatment may reduce opioid overdose.

This is an interesting study. It points out that the chronic pain in the last one month is a factor relating to opioid overdose in OUD patients. Chronic pain management should be considered in the reduction of opioid overdose. The writing has some minor revisions which need to be corrected for more clearance.

Minor comments:

1.In abstract, line 21-22, it said “Chronic pain increases risk for opioid overdose in the general population and among individuals with opioid use disorder”. This “general population” raised up the doubt if opioid could be assessible easily in drug store or over-the-counter.

2.In introduction, line 38-39, it said “…deaths due to opioid overdose surpassed motor vehicle accidents….”. The reference did not show this record. The current citation is pointing toward opioid-related mortality across the US by opioid type. This should be corrected.

3.In material and method, line 82, “The response rate in this group…”. This is not clear of which response rate. Following this correction, could the SKIP questionnaire add-up as a supplement so that the reader may understand the composition of the SKIP database. If the questionnaire has a web-page, it could be added also.

Reviewer #2: English language and style: English language and style are fine/minor spell check required

1.General comments: It is confused to identify the term “active chronic pain”, and the authors used chronic pain and active chronic pain in the manuscript, the definition of active chronic pain should be given in the introduction to help the reader understand the different forms of pain. Also, OUD (opioid use disorder) was select as the population, but it is vague why OUD patients were selected in this article since these patients need opioid treatment.

2.Title: The title reflects the content and problem studied.

3.Abstract: The background mention general population and OUD individuals, however, this study only recruited OUD individuals. The statistical analysis was not addressed clearly in method. The main results, conclusions, and implications of the investigation are addressed.

4.Key Words: The keywords are representative of the subject studied and exposed.

5.Introduction: The contexts of introduction section did not arranged logically. For example, Line 47-49 contained two contrast sentences; and no special point of view was proposed. Line 50-52 ”higher average pain levels in the year before treatment for substance use disorder are associated with increased risk of overdose in the year following treatment” could be re-write to make the meaning more clearly. The prevalence rate of opioid overdose from the reference should be presented. The objective of the study is mentioned, but the justification and the importance of this study should be reinforced.

6.Materials and Methods: In 2.1 Data section, authors collected the data from SKIP, in the abstract only mentioned 2017 Treatment Episode Data Set to evaluate the generalizability of the sample. SKIP seems to be more appropriate addressed in abstract. In the variable definition, it is suggested to address the rationale to allocate yes in the last 7 days and yes in the last 30 days with chronic pain into active chronic pain category from previous references. Section 2.5 (comparison to representative sample) is more suitable moved prior to section 2.3 (statistical association). There is a detailed description of the statistical tests used and how the authors addressed missing data.

7.Results: The 3.1 section could be moved to the beginning of the result. Although the representativeness of SKIP sample section was descripted in details, the importance of addressing this issue was not seen in the manuscript. In table 2, IV drug in past month and current inpatient treatment were not mentioned in method section as variables.

8.Discussion: Line 250-251 could be re-allocated in introduction section to explain the possible mechanism. The suggestion of applying other pain management strategies in OUD patients for further benefit in discussion is reasoned. However, the results were not compared with previous research findings and the key points from research results of table 1, 2 and 3 were not disclosure and emphasized.

9.Conclusion: The authors show in a very precise way of the main results of this study. The practical application of this research is explained.

10.References: The bibliography used is extensive. The writing of the bibliography is correct.

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Reviewer #1: No

Reviewer #2: No

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Association between recent overdose and chronic pain among individuals in treatment for opioid use disorder

PONE-D-22-00300R1

Dear Dr. Hartz,

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,

Wen-Lung Ma, PhD

Academic 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

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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

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

Reviewer #2: Yes

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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

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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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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: (No Response)

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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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