Managing hypertension in frail oldest-old—The role of guideline use by general practitioners from 29 countries

Céline Roulet; Zsofia Rozsnyai; Katharina Tabea Jungo; Milly A. van der Ploeg; Carmen Floriani; Donata Kurpas; Shlomo Vinker; Sanda Kreitmayer Pestic; Ferdinando Petrazzuoli; Kathryn Hoffmann; Rita P. A. Viegas; Christian Mallen; Athina Tatsioni; Hubert Maisonneuve; Claire Collins; Heidrun Lingner; Rosy Tsopra; Yolanda Mueller; Rosalinde K. E. Poortvliet; Jacobijn Gussekloo; Sven Streit

doi:10.1371/journal.pone.0236064

Peer Review History

Original SubmissionApril 7, 2020
5 May 2020 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-20-09925 Managing hypertension in frail oldest-old – the role of guideline use by general practitioners from 29 countries PLOS ONE Dear Prof. Dr. Streit, 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. Two experts raised several points to revise. Oldest-old without fraility control might be difficult to recruit and it is the limitation of this study. We would appreciate receiving your revised manuscript by Jun 19 2020 11:59PM. When you are 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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Please do not edit.] 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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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: In this study, the authors analyzed the data of the worldwide survey from GPs, and investigated whether guideline use influence the treatment choice for hypertensive oldest-old with frailty defined by Fried criteria. They found that GPs who used guidelines are less experienced and more female, but there was no specific tendency with respect to guideline use to treat frail oldest-old. Major points The authors speculate that guideline use had no effect on treatment decisions in frail oldest-old, because of the absence of specific and clear recommendations in most current guidelines for this population group. However, this speculation could suffer from the absence of positive control group in which guideline use significantly affects the treatment. Given that their questionnaires were limited to the treatment of the oldest-old, it might be helpful to assess the treatment of oldest-old with non-frailty and compare the results in those with frailty. The hypothesis can be strengthened, if there is any difference in treatment tendency between the guideline users and non-users in non-frailty patients. The reviewer recommends to show the table to summarize the recommendation of treatment in oldest-old with or without frailty among clinical guidelines. If there is no specific recommendation to these populations in guidelines, the recommendation to treatment in older patients can be alternatively shown. Reviewer #2: Dear Authors, Thank you for submitting the research. The topic is important and the results are relevant. Though the manuscript is written in a sufficient way, please find some minor suggestions for improvement: - Abstract section Design/Section could be supplemented with some setting description; - Abstract Methods section lists the countries that participated in the study: Europe, Brasil, Israel and New Zealand. But the first is continent and the others are countries. I suggest writing "European countries". By the way, I'd see it rational to mention the countries participating in the research. - I suggest adding some explanation about the guidelines in the Introduction section. Are they national, international, similar in some countries, etc. Are they available in all countries? - In the Setting section you mention EGPRN as an example. I suggest to include some other as well or not mention organization at all. - Please describe how the GPs were selected to involve as the participants. Was the criterion(s) similar for all the countries or local coordinators decided? How their contacts for sending the questionnaire link were gathered? - I suggest adding some statistics on GPs distribution among the countries. Maybe adding (if it's available) urban/rural distribution. I believe it would be valuable to present some more correlations between demographics and using the guidelines. Of course, if it's available. ****** 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: 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0236064.r001
Revision 1
18 Jun 2020 Author Response 1st Reviewer comments: 1. In this study, the authors analyzed the data of the worldwide survey from GPs and investigated whether guideline use influence the treatment choice for hypertensive oldest-old with frailty defined by Fried criteria. They found that GPs who used guidelines are less experienced and more female, but there was no specific tendency with respect to guideline use to treat frail oldest-old. Major points The authors speculate that guideline use had no effect on treatment decisions in frail oldest-old, because of the absence of specific and clear recommendations in most current guidelines for this population group. However, this speculation could suffer from the absence of positive control group in which guideline use significantly affects the treatment. Given that their questionnaires were limited to the treatment of the oldest-old, it might be helpful to assess the treatment of oldest-old with non-frailty and compare the results in those with frailty. The hypothesis can be strengthened, if there is any difference in treatment tendency between the guideline users and non-users in non-frailty patients. Response: We thank the reviewer for pointing out this important aspect. We agree that the absence of positive control group with oldest old patients without frailty is a limitation of our study. We therefore clarified this point in the section “Limitations and strengths” on page 12. We consciously chose to focus on frail oldest-old because of two main reasons. First, recommendations for this specific population are missing from most hypertension guidelines. This fact is described in the literature [references 1 and 2 below] as well as in guidelines. For example, these two citations from the hypertension guideline of the European Society of cardiology (ESC) state that “all of the above recommendations relate to relatively fit and independent older patients, because physically and mentally frail and institutionalized patients have been excluded in most RCTs of patients with hypertension” and “In some patients, best achievable BP may be higher than the recommended target” [3]. Secondly, this population group is especially at risk for negative consequences of too aggressive blood pressure treatment while oldest-old without frailty may have a greater tolerance [4]. 2.The reviewer recommends to show the table to summarize the recommendation of treatment in oldest-old with or without frailty among clinical guidelines. If there is no specific recommendation to these populations in guidelines, the recommendation to treatment in older patients can be alternatively shown. Response: We appreciate this suggestion and we added a new table to summarize the main recommendations in the appendix S3. We chose to present the recommendations for frail oldest-old of the three most mentioned guidelines, which were effective at the time of our study in 2016. We hope this table will help to get an overview of the contents of the guidelines. We also provided the information on guidelines changes since then (refer to the Discussion Section on page 11). 2nd Reviewers comments: 1. Dear Authors, Thank you for submitting the research. The topic is important and the results are relevant. Though the manuscript is written in a sufficient way, please find some minor suggestions for improvement: - Abstract section Design/Section could be supplemented with some setting description; Response: We completed this section with the following sentence: “Cross-sectional study among currently active GPs from 29 countries using a case-vignettes survey.” 2. Abstract Methods section lists the countries that participated in the study: Europe, Brazil, Israel and New Zealand. But the first is continent and the others are countries. I suggest writing "European countries". By the way, I'd see it rational to mention the countries participating in the research Response: We thank the reviewer for this comment and adapted in the abstract as follows: “GPs from 26 European countries and from Brazil, Israel and New Zealand were invited”. We listed all the countries under “Results” on page 8. 3. I suggest adding some explanation about the guidelines in the Introduction section. Are they national, international, similar in some countries, etc. Are they available in all countries? Response: This comment is relevant and we agree that some more explanations about the different guidelines would help the reader. We chose to integrate a short description of the guidelines in the “Introduction” on page 5. 4. In the Setting section you mention EGPRN as an example. I suggest to include some other as well or not mention organization at all. Response: We agree with this remark and removed the name of this organization. 5. Please describe how the GPs were selected to involve as the participants. Was the criterion(s) similar for all the countries or local coordinators decided? How their contacts for sending the questionnaire link were gathered? Response: We are happy to clarify this point. The GPs were contacted by a national coordinator, which we collaborate with through national and European organizations, as explained in the section “Methods” from page 5 to 7. To clarify the inclusion criteria, we adapted the subsection “Participants” on page 6 as follow: “The only inclusion criteria to participate in the ATTENTIVE study, was to be currently active as a GP”. National coordinators sent the link of the survey per e-Mail, except in Ukraine where a paper version was distributed as detailed on page 6 and 7. More explanations on the data collection can be found in the original publications of the ATTENTIVE study [5,6]. 6. I suggest adding some statistics on GPs distribution among the countries. Maybe adding (if it's available) urban/rural distribution. I believe it would be valuable to present some more correlations between demographics and using the guidelines. Of course, if it's available. We thank the reviewer for this relevant comment. Data about the location of GP’s practices were collected in the ATTENTIVE study. We therefore completed our sections “Methods” and “Results” as well as Table 1. We found no association between GPs’ geographical location and guideline use. References 1) Messerli FH, Sulicka J, Gryglewska B. Treatment of hypertension in the elderly. N Engl J Med. 2008;359(9): 972–3. author reply 973-974. 2) Roberts RG, Wynn-Jones J. Research and rural; EGPRN and EURIPA-finding common ground. October 2013, Malta. Eur J Gen Pract. 2015;21(1): 77-81 3) Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021‐3104. 4) Streit S, Poortvliet RKE, Gussekloo J. Lower blood pressure during antihypertensive treatment is associated with higher all-cause mortality and accelerated cognitive decline in the oldest-old – data from the Leiden 85-plus Study. Age and Ageing. 2018;47(4): 545-550. 5) Streit S, Verschoor M, Rodondi N, Bonfim D, Burman RA, Collins C, et al. Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries. BMC Geriatr. 2017;17(1): 93. 6) Streit S, Gussekloo J, Burman RA, Collins C, Kitanovska BG, Gintere S, et al. Burden of cardiovascular disease across 29 countries and GPs' decision to treat hypertension in oldest-old. Scand J Prim Health Care. 2018(1): 89-98. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0236064.r002
29 Jun 2020 Decision Letter - Tatsuo Shimosawa, Editor Managing hypertension in frail oldest-old – the role of guideline use by general practitioners from 29 countries PONE-D-20-09925R1 Dear Dr. Streit, 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, Tatsuo Shimosawa, M.D., Ph.D. 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 #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: (No Response) ****** 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 https://doi.org/10.1371/journal.pone.0236064.r003
Formally Accepted
30 Jun 2020 Acceptance Letter - Tatsuo Shimosawa, Editor PONE-D-20-09925R1 Managing hypertension in frail oldest-old – the role of guideline use by general practitioners from 29 countries Dear Dr. Streit: 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 Prof. Tatsuo Shimosawa Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0236064.r004

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