PONE-D-20-04896

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear MR SHAH,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

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a) Please include additional information regarding the survey or 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. Please also include the exact number of individuals involved in the pilot testing of the questionnaire.

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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: Partly

Reviewer #2: Partly

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

Reviewer #1: No

Reviewer #2: Yes

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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: No

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: Reviewer’s comments

1. What is the aim of the study? There more than one version

a. This study aims to evaluate the current thromboprophylaxis practice and management of patients with risks of developing DVT in different clinics, to determine the adherence to thromboprophylaxis guidelines and to assess healthcare providers’ (HCPs) knowledge, practice and attitudes towards deep vein thrombosis risks and prophylaxis with the goal of optimizing care and ensuring rational practices.

b. An observational study was conducted in which patients from multiple clinics were enrolled to investigate the rational use of DVT prophylaxis using the Caprini risk assessment tool

c. This study aims to investigate current thromboprophylaxis practice at two university hospitals in North Cyprus by evaluating the management of patients with a low, medium, and high risk of developing DVT who are treated in different clinics to determine the adherence to thromboprophylaxis guidelines and to assess healthcare providers’ knowledge, practices and attitudes towards deep vein thrombosis risks and prophylaxis

Please harmonize the statements in different sections

2. Where was the study done?

a. An observational study was conducted in which patients from multiple clinics were enrolled to investigate the rational use……..

b. The study was conducted in the general wards of two leading tertiary university hospitals, namely, Near East University Hospital (NEUH) and Dr. Suat Günsel Kyrenia University Hospital (SGKUH) in

c. Study settings are not described

3. The inclusion criteria were acute and chronically ill medical patients…. But table 1 shows patients from diverse wards – including orthopaedic and surgery? This needs to be described.

4. Although the authors reported having followed up participants to asses for possible complications, the development of post-discharge complications (deep venous thrombosis signs and symptoms, pulmonary embolism or adverse effects of medications) was not obvious in the manuscript.

5. The statement “The average length of hospitalization was 12.48 days (median of 11 days)” is unclear. Did the authors report the mean (average – 12.48) and median (11) at the same time? Why were the two measures reported together?

6. Table 2 describes "major" risk factors. Why are these risk factors called major? I am not sure if the term major is used in the Caprin score.

7. In some areas, absolute numbers and percentages are given without reference to what is the denominator. A reader would struggle to identify the denominator. One of these sentences includes "Four of these patients (30.76%) developed 6 minor complications. Anticoagulation therapy was stopped in 2 patients (50%)”

8. The importance of table 3 is unclear. What does table 3 answer? It looks redundant if there is nothing exclusive that it adds to the study.

9. There are several areas where authors used the word "female" to refer to "females."

Reviewer #2: Reviewer Comments

Manuscript Title: The rational use of thromboprophylaxis in hospitalized patients and the perspectives of health care providers in Northern Cyprus

General Impression: The paper describes an important area of thromboprophylaxis. However, some clarifications to the manuscript are required.

1. Materials and Methods:

a) Study Setting and Subjects: “All inpatients admitted between 01 April 2018 and 01 July 2018 who met the inclusion criteria were included in the analysis”. The authors need to clarify and edit the exclusion criteria stated. (lines 87 to 89) as the language is unclear

b) Did the authors have a predetermined minimum required sample size for their analysis plan?

c) The authors also need to clarify at what point data was initially collected-did this happen while patient was still on the ward or after they had been discharged. Also, it’s not clear what data was collected from the patient’s chart/record

d) Ethical consideration: The authors clearly state that they received IRB ethics approval. However, it is also essential to state whether study participants provided written or verbal informed consent prior to participation and if not, state justification for waiver of this requirement

2. Observational Results:

a) Patient demographics and characteristics:

The authors need to mention the number of patients admitted during the 3-month study period from which they selected participants as stated in the methods section.

Table 1: Table shows that the patients included some from the Orthopedics and Surgery clinics- The authors need to clarify their patient sample description in the Methods Section (line 85)-Are these ‘medical’ patients?

To improve readability, authors should consider making the percentage proportions reported consistent by using uniform number of decimal values throughout the manuscript.

3. Discussion:

a) The authors have made many comparisons of their findings to those from similar studies elsewhere. However, I expected the authors to also expound the implications of their findings on the knowledge gaps in relation to those on rationality of thromboprophylaxis in this study

b) Limitations: Was the sampling method ideal and was the sample size for the different phases adequate to draw conclusions? This needs to be considered.

Both study sites are university (teaching) hospitals. Could this have affected the findings on knowledge levels of physicians/nurses?

Also, whilst the authors assessed nurse and physicians’ knowledge on DVT, it is not clear if the HCWs are aware of the Caprini’s RAM and if this is actually standard of practice. Is it possible that the low utilization/rationalization of thromboprophylaxis could have been due to lack of awareness?

Finally,the authors need to check the language and revise text where necessary throughout the manuscript to improve readability.Ensure the references are correctly written

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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.

PONE-D-20-04896R1

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear Dr. SHAH,

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 submit your revised manuscript by Jul 05 2020 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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

We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, 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: No

Reviewer #2: Yes

**********

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

Reviewer #1: No

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 #1: No

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: Yes

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 #1: 1.The sample size calculation is stil not clear. Authors reported using 50% response distribution as one of the parameters in the sample size calculation. What was this response referring to? Is this a justifiable way of sample size calculation?

2.Mean and median still appear in table 3. Is there a need for continous variables to be described/ summarised in both ways?

3. In table 3: How were the comparisons made? were mean or median used for the comparisons of continous variables?

4. The Mann-Whitney U test and the Kruskal-Wallis tests were reported as the methods used to compare diffrences accross groups. One would then assume that the data were deemd as being assymetrical . Yet, mean(and SD) were compared as seen in the texts (line 264, 267, 270, 272. etc)

Reviewer #2: The authors have addressed all my previous comments satisfactorily.

The authors should have a second look at the wording and punctuation and correct any typos in the manuscript

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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: Julius Mwita

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.

PONE-D-20-04896R2

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear Dr. SHAH,

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 submit your revised manuscript by Jul 27 2020 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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

We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Please kindly address the few additional comments from the reviewers.

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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

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 #1: Yes

Reviewer #2: Partly

**********

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

Reviewer #1: Yes

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 #1: No

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: Yes

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 #1: All the comments have been addressed. No more comments from my side. The manuscript can be accepted for publication

Reviewer #2: Abstract: Ensure you use a uniform tense throughout the abstract.The 'Aims' section is stated in present tense.

Ensure that the proportions mentioned here match those in the results and discussion sections

Discussion:

Line 313

"Indeed, after assessing 180 patients using the Caprini risk assessment tool, finding of the current study show that thromboprophylaxis regimens were appropriately provided to only approximately 52.2% of patients, consistent with the studies by White RH et al..."

The percentage proportion stated here does not add up with that stated in the abstract (47.7%).The authors should consider correcting this statement to reduce its ambiguity .

Conclusion:

There is some repetition in the authors conclusion.It needs to be made more succinct and focused on their study

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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: Julius Mwita

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.

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PONE-D-20-04896R3

Dear Dr. SHAH,

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,

Joel Msafiri Francis, MD, MS, 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

**********

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: The authors have addressed all the comments in the 'Response to reviewer comments' and just need to double check that these changes are included in the main text.For example the proportion of rationally managed patients is 52.3% according to figure 1 but is stated as 52.2% in the abstract and discussion sections.

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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