The effect of end-of-life decision-making tools on patient and family-related outcomes of care among ethnocultural minorities: A systematic review

Ayah Nayfeh; Lesley Gotlib Conn; Craig Dale; Sarah Kratina; Brigette Hales; Tracey Das Gupta; Anita Chakraborty; Ru Taggar; Robert Fowler

doi:10.1371/journal.pone.0272436

Peer Review History

Original SubmissionOctober 12, 2021
4 Apr 2022 Decision Letter - Lucy E. Selman, Editor PONE-D-21-32778The effect of end-of-life decision-making tools on patient and family-related outcomes of care among ethnocultural minorities: a systematic reviewPLOS ONE Dear Dr. Nayfeh, 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. ============================== Please address the reviewers' comments and in particular ensure that the limitations are acknowledged. Please also review the paper for length and reduce the word count by being more concise. ============================== Please submit your revised manuscript by May 19 2022 11:59PM. 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Thank you for stating the following financial disclosure: “This study was funded by the Sunnybrook AFP Association through the Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario; the Department of Critical Care Medicine at Sunnybrook Health Sciences Centre; the Division of Palliative Medicine, Department of Medicine, University of Toronto; the Dalla Lana School of Public Health, University of Toronto; and the Global Institute of Psychosocial, Palliative and End-of-Life Care. Ayah Nayfeh is supported, in part, by funding from the Social Sciences and Humanities Research Council.” Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. 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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 ****** 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 ****** 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: Thank you very much for the opportunity to review this well written manuscript on the important topic of the effect of end-of-life decision-making tools on outcomes of care among ethno cultural minorities. The authors have reviewed studies on a variety of end-of-life decision-making tools from a broad perspective: tools for patients, family and healthcare workers, focused on proactive (e.g. ACP) and actual decisions about life prolonging treatments. This broad perspective is relevant, and at the same time results in a diversity of outcomes. Though the manuscript is interesting, there are some aspects that would benefit from further explanation: 1. Abstract: conclusion could be more informative (see conclusion in the main text) 2. Introduction: the sentence “Prior research has shown a strong association between patient race/ethnicity and use of life-prolonging treatments, hospital stays, and death in intensive care units” needs additional information or rephrasing: more or less use of LPT? Length of hospital stays? As for mortality, do you mean higher mortality or location of dying? 3. Methods, study selection: did both authors screen all titles? Or only the first 50 together and the rest ‘split up’? Does the Kappa statistic reflect the screening of 50 titles or all titles? 4. Methods, data collection: it is not clear to me why data was inductively coded, nor how the coding was done and the codes were subsequently used 5. Methods, quality assessment: the MMAT can be used in reviews that include various designs, both quantitative and qualitative. The authors have chosen to apply MMAT only for qualitative and mixed methods studies, not for the RCTs and other quantitative designs. Furthermore, the quality of studies varied, with 19 studies rated of high quality and 6 of low quality. The authors do not make any distinction in quality in the results. Suggestion to do this, or otherwise discuss the quality in the Discussion section: what is the influence on the interpretation of the results? 6. The results section is rather extensive, due to the summing of outcomes and tools. Please provide less detail, this is already provided in the tables. Focus on the synthesis, whether positive/negative or no effects were found. Now focus often seems on positive results, e.g. on page 10: eleven studies evaluated ACP, of which (only?) 4 had a positive result. From the results section, I have no idea whether these were high quality studies in large groups of patients. You could consider discussing the tools and the effect on outcomes (instead of the other way round), in line with your conclusion. 7. Discussion: can you elaborate on the effectiveness of tools for minorities as compared to other populations (e.g. review Stacey, review Thodé)? And whether tools for minorities seem effective due to adapted communication or a cultural adaptation? Can people with impaired health literacy in general also benefit from the tools found in your review? 8. Discussion: it struck me that all studies were in the USA, and one in Australia. Can you elaborate on that? Minor comments a. End of life or end-of-life? Please be consistent b. Maybe out of scope, but suggestion to acknowledge the health sciences librarian Reviewer #2: The authors present a systematic review, looking for articles assessing interventions to encourage end of life discussions and decisions. They search from the perspective of wanting to identify studies adapted for patients cultural backgrounds. The methods (apart from the issues raised below) seem sound, and the conduct of the research appears to be rigorous. This review will add to the literature and be of interest to readers from many areas of medicine. Major issues include: # The search strategy seems to omit most of the terms associated with treatment limitations. Therefore many studies could have been missed, particularly region specific papers, where a specific limitation phrase is used. Examples of terms related to treatment limitations that could have been included are: Treatment ceiling, POLST, Not for CPR, DNR, goals-of-care etc # Each theme you have identified should have a statement regarding the strength/reliability of the findings after your synthesis of the data presented the papers. This is in addition to assessing each individual paper for quality/bias etc. Minor issues include: # Not registering this study prospectively - eg in PROSPERO # Your title and abstract should reflect that this study was about adults, not children # Data are pleural, this should be corrected throughout ****** 6. 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: Yes:** Irene Jongerden 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. https://doi.org/10.1371/journal.pone.0272436.r001
Revision 1
16 May 2022 Author Response Thank you for the opportunity to revise and re-submit our manuscript “The effect of end-of-life decision-making tools on patient and family-related outcomes of care among ethnocultural minorities: a systematic review” (PONE-D-21-32778) for PLOS ONE. Below we have addressed each of the points provided by the Editor and two reviewers. Editor’s comments: 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: Thank you for raising inconsistencies with PLOS ONE’s style requirements. We have revised the title page, main body of the manuscript (i.e., line numbers, heading size, figures/tables) and supporting information to be in accordance with PLOS ONE style guidelines. 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Response: Thank you for noting this discrepancy. The funding information section has been updated in the PLOS ONE system. Grant numbers for awards received have been included, where applicable. 3. Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Response: We would like to add the following to our financial disclosure statement: “This study was funded by the Sunnybrook AFP Association through the Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario; the Department of Critical Care Medicine at Sunnybrook Health Sciences Centre; the Division of Palliative Medicine, Department of Medicine, University of Toronto; the Dalla Lana School of Public Health, University of Toronto; and the Global Institute of Psychosocial, Palliative and End-of-Life Care. Ayah Nayfeh is supported, in part, by funding from the Social Sciences and Humanities Research Council (752-2020-1352). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Response: Data related to this manuscript is provided as part of the submitted article and supporting information. We have adjusted our Data Availability statement in the PLOS ONE system. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. Response: The ORCID iD for the corresponding author has been updated in the PLOS ONE system. Reviewer #1: 1. Abstract: conclusion could be more informative (see conclusion in the main text) Response: Thank you for this feedback. The following sentence has been added to the conclusion statement in the abstract to provide more information on the findings (page 2, line 49): Advance care planning programs, healthcare provider-led interventions and decision aides increased documentation of end-of-life care plans and do-not-resuscitate orders, and educational tools reduced preferences for life-prolonging care. To stay in line with the 300-word count maximum for the abstract, we have subsequently removed other text from the abstract. 2. Introduction: the sentence “Prior research has shown a strong association between patient race/ethnicity and use of life-prolonging treatments, hospital stays, and death in intensive care units” needs additional information or rephrasing: more or less use of LPT? Length of hospital stays? As for mortality, do you mean higher mortality or location of dying? Response: Thank you for this comment – we agree that this sentence could use further clarification. We have revised the sentence to read (page 3, line 107): Prior research has shown a strong association between patient race/ethnicity and increased use of life-prolonging treatments, longer hospital stays, and intensive care units (ICU) as a location of death. 3. Methods, study selection: did both authors screen all titles? Or only the first 50 together and the rest ‘split up’? Does the Kappa statistic reflect the screening of 50 titles or all titles? Response: We have added more information in the manuscript to clarify the process that was followed for study screening/selection (page 6, lines 177). Specifically, the two reviewers independently screened the first 50 articles to calibrate and reconcile any disagreements with the screening process. The remaining titles and abstracts were split for screening for potential eligibility between the two reviewers. After all titles and abstracts were screened for potential eligibility, the full text of potentially eligible articles were assessed independently by both reviewers to confirm that inclusion criteria were met. The Cohen’s Kappa statistic represents interrater reliability for the full-text screening phase of potentially eligible articles. 4. Methods, data collection: it is not clear to me why data was inductively coded, nor how the coding was done and the codes were subsequently used. Response: We have adjusted the language to better describe the process that was followed for data analysis and how codes were used to analyze the data (page 6, line 190): Each outcome measure was used as a label to code and extract data from eligible studies. Extracted data were categorized and synthesized by outcome measure for each type of tool. An overall narrative description of study findings (including point estimates of association and statistical significance) were described to show the range of effects across the different studies. The heterogeneity of eligible studies did not allow for pooling of data to synthesize results. 5. Methods, quality assessment: the MMAT can be used in reviews that include various designs, both quantitative and qualitative. The authors have chosen to apply MMAT only for qualitative and mixed methods studies, not for the RCTs and other quantitative designs. Furthermore, the quality of studies varied, with 19 studies rated of high quality and 6 of low quality. The authors do not make any distinction in quality in the results. Suggestion to do this, or otherwise discuss the quality in the Discussion section: what is the influence on the interpretation of the results? Response: Thank you for this comment. We selected quality assessment tools based on the recommendations of Zeng et al. (2015) for different research methodologies. Based on their assessment, the authors recommended using MMAT for qualitative and mixed method research designs; quantitative research designs (such as case-control, observational cohort, and non-randomized intervention studies) were given other recommendations. We highlighted the recommended quality assessments tools on page 7, line 212 of the manuscript. Thank you also for the suggestion to reflect on the quality of study findings in the discussion section. We have incorporated statements around the overall quality of evidence to support interpretation of results in the discussion section (page 18, line 483; page 19, line 515). Reference: Zeng X, Zhang Y, Kwong JSW, Zhang C, Li S, Sun F, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med. 2015;8(1):2–10. 6. The results section is rather extensive, due to the summing of outcomes and tools. Please provide less detail, this is already provided in the tables. Focus on the synthesis, whether positive/negative or no effects were found. Now focus often seems on positive results, e.g. on page 10: eleven studies evaluated ACP, of which (only?) 4 had a positive result. From the results section, I have no idea whether these were high quality studies in large groups of patients. You could consider discussing the tools and the effect on outcomes (instead of the other way round), in line with your conclusion. Response: Thank you for this important comment. We agree that the results section could be presented in a more concise manner. As suggested, we re-organized the results section such that the findings are organized by tools rather than by outcomes. This is more in line with our conclusion statement. This approach also allows readers to more easily comprehend the influence of different tools on patient and family-related outcomes of care. We have also revised the results section to be more concise by focusing primarily on the synthesis of findings and overall strength/reliability of evidence. In doing so, the results section was cut down by almost four pages. Additional details that support interpretation of the findings can be found in the supporting tables. 7. Discussion: can you elaborate on the effectiveness of tools for minorities as compared to other populations (e.g. review Stacey, review Thodé)? And whether tools for minorities seem effective due to adapted communication or a cultural adaptation? Can people with impaired health literacy in general also benefit from the tools found in your review? Response: Thank you for this suggestion to enhance the discussion section of this manuscript. We have reflected on our findings in the context of prior reviews and discussed potential application and generalizability to other populations as well. Specifically, we have included the following paragraph on page 18, line 486: Our review found that culturally-tailored [23] and faith-based ACP programs [22,29] do not have a strong influence on advance directive completion rates among racial/ethnic minorities. Non-tailored end-of-life decision-making tools appear to have a similar effect on outcomes of care among ethnocultural minority groups as compared to other populations. Prior reviews have shown increased documentation of care plans at the end of life after using structured communication tools; reduced patient anxiety after participating in multifaceted ACP programs; and feasibility/acceptability among participants using decision aides [2,58]. However, we were not able to determine whether the tools identified in our review reduce healthcare utilization and hospitalization for minority patients at a similar rate to Caucasian counterparts. 8. Discussion: it struck me that all studies were in the USA, and one in Australia. Can you elaborate on that? Response: Although our search strategy retrieved articles around end-of-life decision-making beyond the USA (including from the UK, Canada, France, Australia, Saudi Arabia, Iran, China), the majority of these studies did not meet our criteria for inclusion in the review. The main reason for exclusion was that the study did not evaluate or test the effect of the tool or intervention, or the study did not focus on a racial/ethnic, cultural or religious minority group. We anticipated that most studies would be based in the US healthcare system considering growing recognition and conversations around racial/ethnic disparities in health. It is possible that there were region-specific terms that were missed in our search. We attempted to address this limitation by including text word and keyword searchers in our strategy to capture studies that describe key concepts around end-of-life decision-making. For example, we searched for articles that included the following terms within 3 or 4 words of each other: (life adj3 (prolong* or sustain* or support)).tw,kf. (care adj3 (terminal or palliative or intensive or critical or hospice)).tw,kf. ((ill or illness) adj3 (terminal* or serious* or critical)).tw,kf. ((withdraw or withhold* or refus* or discontinu* or remov* or terminat) adj3 (treatment or care or therap* or intervention* or medical)).tw,kf. ((plan or decision) adj4 (care or medical or treatment)).tw,kf. Despite casting a wide net in our search, however, there may have been region-specific terms that were missed in our search. This is an important limitation that we have addressed in the manuscript (page 22, line 598). 9. End of life or end-of-life? Please be consistent Response: Thank you for raising this comment. We are aware that some journals prefer to use the terms “end of life” and “end-of-life care” differently. We have attempted to adhere to the language rule that specifies hyphens when the term is being used as a descriptor for a process, event, etc. and no hyphens when it is used by its own. For example(s): We wish to improve end-of-life care. We wish to improve care at the end of life. 10. Maybe out of scope, but suggestion to acknowledge the health sciences librarian Response: This is a wonderful suggestion – we have included an acknowledgement of the health sciences librarian in the manuscript. Reviewer #2: 10. The search strategy seems to omit most of the terms associated with treatment limitations. Therefore many studies could have been missed, particularly region specific papers, where a specific limitation phrase is used. Examples of terms related to treatment limitations that could have been included are: Treatment ceiling, POLST, Not for CPR, DNR, goals-of-care etc. Response: Thank you for this important comment. We are fairly confident that the text word and keyword function in our search strategy captured studies related to goals of care, POLST, CPR and DNR. For example, our search included: (goal adj3 care).tw,kf [this would have captured any article where the words ‘goal’ and ‘care’ were within 3 words of each other]. resuscitation/ or cardiopulmonary resuscitation/ or respiration, artificial/ or resuscitation orders/ [this would have captured any article with terms related to do-not-resuscitate (DNR) and CPR] (life adj3 (prolong* or sustain* or support)).tw,kf [this would have captured any article related to Physician Orders for Life Sustaining Treatment (POLST)] Certainly, there may be other region-specific terms that were missed in our search. This is an important limitation that we have addressed in the manuscript (page 22, line 598). 11. Each theme you have identified should have a statement regarding the strength/reliability of the findings after your synthesis of the data presented the papers. This is in addition to assessing each individual paper for quality/bias etc. Response: Thank you for this comment – we have adjusted the results section such that the focus is on the synthesis of findings and overall quality of evidence. A statement around the overall strength and reliability of findings has been included for every outcome measure under each tool (in addition to each individual quality/risk of bias assessment). 12. Not registering this study prospectively - eg in PROSPERO Response: We acknowledge our unintended oversight with not registering this review in PROSPERO. As this systematic review is complete, we were not able to register the review retrospectively. We acknowledge this oversight in the manuscript that the work progressed beyond the point of being able to register it by the time we attempted to register. This has been addressed in the limitations section of the manuscript (page 22, line 604). 13. Your title and abstract should reflect that this study was about adults, not children Data are pleural, this should be corrected throughout. Response: Thank you for this suggestion. We have added information in the abstract to indicate to readers that this review focuses on the adult patient population. Grammar corrections have also been made throughout the manuscript. Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0272436.r002
20 Jul 2022 Decision Letter - Lucy E. Selman, Editor The effect of end-of-life decision-making tools on patient and family-related outcomes of care among ethnocultural minorities: a systematic review PONE-D-21-32778R1 Dear Dr. Nayfeh, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Lucy E. Selman, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Thank you for your revision, which we are pleased to accept. The reviewer highlighted the spelling of 'aid' - please amend to 'aid' throughout. 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: 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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 #1: 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: 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 #1: Compliments on the revised version! It has improved significantly. Just one minor comment: as far as I know, it is 'decision aids' rather than 'decision aides'. ****** 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: Yes: Irene Jongerden ******** https://doi.org/10.1371/journal.pone.0272436.r003
Formally Accepted
27 Jul 2022 Acceptance Letter - Lucy E. Selman, Editor PONE-D-21-32778R1 The effect of end-of-life decision-making tools on patient and family-related outcomes of care among ethnocultural minorities: a systematic review Dear Dr. Nayfeh: 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. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr Lucy E. Selman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0272436.r004

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