Diagnostic accuracy of computed tomography in adults with suspected acute appendicitis at the emergency department in a private tertiary hospital in Tanzania

Masawa K. Nyamuryekung’e; Miten R. Patel; Ahmed Jusabani; Ali A. Zehri; Athar Ali

doi:10.1371/journal.pone.0276720

Peer Review History

Original SubmissionApril 30, 2021
18 May 2021 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-21-13993 DIAGNOSTIC ACCURACY OF COMPUTED TOMOGRAPHY IN ADULTS WITH SUSPECTED ACUTE APPENDICITIS AT THE EMERGENCY DEPARTMENT IN PRIVATE TERTIARY HOSPITAL IN TANZANIA PLOS ONE Dear Dr. Nyamuryekung'e, 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 issues and revise accordingly. Please submit your revised manuscript by Jun 28 2021 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. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Robert Jeenchen Chen, MD, MPH Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. [Note: HTML markup is below. 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: No Reviewer #2: No ****** 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: No ****** 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: No ****** 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: The authors aimed to study the diagnostic accuracy of acute appendicitis (AA) by computed tomography (CT) in Tanzania. They recruited 180 patients suspected AA with CT retrospectively in a single hospital. The reference standards were histological examination of the removed appendix as well as clinical follow‐up for 14 days of participants who did not have surgery. After excluded 7 patients with negative CT and loss of follow-up, 173 participants were included in analysis of which 45 had and 128 did not have AA. The CT's diagnostic accuracy for AA was 97.5%, sensitivity and specificity were 91.6% and 100% respectively. The authors concluded the diagnostic accuracy was comparable to the studies conducted outside of Africa. Comments: 1. The accuracy of CT to diagnose AA has been well documented. The authors hypothesized the equipment or experience in interpretation of CT in Tanzania, Africa might be different from the outside of Africa. The images of the study were generated by Philips, Ingenuity model, 128 slices with 64 detector rows. All 4 radiologists interpreting the images had at least trained as Master of Medicine in medical radiology. The equipment and experience in interpretation of CT in this hospital (Aga Khan Hospital) of Tanzania were at the same level as previous studies conducted outside of Africa. The results of this study are expected. 2. This is a retrospective study without clear inclusion criteria. The authors recruited the patients with right lower abdominal pain with suspected AA by physicians (no criteria about how to suspect AA) and underwent CT scans. The inaccurate diagnostic criteria before CT resulted in a high portion of patients without AA in the study. There were 45 case (26%) of AA and 68 cases (39%) of urolithiasis in the study population. The sample size estimation on page 12 used the prevalence of 0.43, which is much higher than 26% in the study population. Therefore, the sample size estimation was invalid. 3. The Fig. 1 illustrated the study population. At top of the Fig. 1, it displayed 7 cases of missing data were excluded. The rest of the Fig. 1 demonstrated the outcomes of the 180 cases. However, there were 7 cases with negative CT and loss of follow-up should be excluded from this study cohort. This exclusion was not demonstrated in the Fig. 1. Reviewer #2: This is a retrospective diagnostic accuracy study conducted at a private tertiary hospital in Tanzania. The authors aimed to assess the diagnostic accuracy of a computed tomography scan for acute appendicitis in patients with suspected acute appendicitis at the emergency department. They found that the high diagnostic accuracy (97.5%) was comparable to that demonstrated in meta-analysis from studies conducted outside of Africa. This reviewer is an applied statistician and methodologist. I have several concerns. The entire manuscript needs to be closely edited by someone more proficient with the nuances of the English language as there are multiple sites in which the grammar could be improved. 1. Methodology- The period of this study conducted in the “Methodology” section was different from that recorded in “Abstract”. Which one was correct? Please revise. 2. Methodology- The authors wrote that “Adult patients above ten years of age were included in the study….”. This is different from definition of adult (>14 years of age) in the SRMA conducted by Rud B, et al. (2019). Please explain more. 3. Methodology- Presenting results for diagnostic test assessment include sensitivity, specificity, diagnostic odds ratio, and AUC. The authors should consider adding. 4. Methodology-The authors wrote that “The image interpreters were four consultant medical radiologists rotating through an on-call schedule”. Please give the Kappa value between these four radiologists. 5. Methodology- The authors wrote that “Sample size estimation based on Buderer formula of diagnostic accuracy for unknown disease prevalence”. But this is a retrospective study, why do this calculate? Please explain more. 6. Results-Please give a more detailed demographic table about these 180 included participants. 7. Results- The authors wrote that “the mean participants’ age was 35 years with a range (10 to 71)…”. Formally, for continuous variable like age, it must report as mean with standard deviation or 95% confidence interval. Please revise. 8. Results- Please revise the form for reporting the proportion. As example, line 81 states that “the first assessor was a medical officer in 40 %, but line 83 states that “six percent of the …..”. It must be consistent. 9. Results- Line 96-97 states that “A total of 35 participants determined to have normal appendices, without alternative diagnoses (27) and equivocal CT results (8) ….”. I think that the notations (27) and (8) stood for the numbers of participants but they were same as notations for cite references. Please revise. 10. Results- Please unify the number part, don’t use English and Arabic numerals interchangeably. 11. Results- In Line 108-111, Please give the 95% confidence intervals for sensitivity, specificity, diagnostic accuracy, positive and negative predictive value. 12. Results- The authors wrote that “No significant differences were observed…”. Does any statistical method was used? Which value of p-value was considered to be statistically significant? 13. Can’t find the list of abbreviations. ****** 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:** Cheng-Chung Fang 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.0276720.r001
Revision 1
2 Nov 2021 Author Response RESPONSE TO REVIEWERS [Note: HTML markup is below. 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: No Reviewer #2: No ________________________________________ 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: No ________________________________________ 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: No ________________________________________ 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: The authors aimed to study the diagnostic accuracy of acute appendicitis (AA) by computed tomography (CT) in Tanzania. They recruited 180 patients suspected AA with CT retrospectively in a single hospital. The reference standards were histological examination of the removed appendix as well as clinical follow‐up for 14 days of participants who did not have surgery. After excluded 7 patients with negative CT and loss of follow-up, 173 participants were included in analysis of which 45 had and 128 did not have AA. The CT's diagnostic accuracy for AA was 97.5%, sensitivity and specificity were 91.6% and 100% respectively. The authors concluded the diagnostic accuracy was comparable to the studies conducted outside of Africa. Comments: 1. The accuracy of CT to diagnose AA has been well documented. The authors hypothesized the equipment or experience in interpretation of CT in Tanzania, Africa might be different from the outside of Africa. The images of the study were generated by Philips, Ingenuity model, 128 slices with 64 detector rows. All 4 radiologists interpreting the images had at least trained as Master of Medicine in medical radiology. The equipment and experience in interpretation of CT in this hospital (Aga Khan Hospital) of Tanzania were at the same level as previous studies conducted outside of Africa. The results of this study are expected. There were no prior published studies examining the diagnostic accuracy of CT for acute appendicitis in the sub-Sahara Africa. Given the justification of this study that the assumption of similar performance might not necessarily be true, this question was explored. 2. This is a retrospective study without clear inclusion criteria. The authors recruited the patients with right lower abdominal pain with suspected AA by physicians (no criteria about how to suspect AA) and underwent CT scans. The inaccurate diagnostic criteria before CT resulted in a high portion of patients without AA in the study. There were 45 case (26%) of AA and 68 cases (39%) of urolithiasis in the study population. The sample size estimation on page 12 used the prevalence of 0.43, which is much higher than 26% in the study population. Therefore, the sample size estimation was invalid. Criteria for suspecting acute appendicitis, right iliac fossa colicky abdominal pain of less than 10 days duration. This has been clarified in the manuscript. As a result of the lower prevalence of acute appendicitis in this study, the corresponding precision is lowered to 0.067 as opposed to our sample size estimation of 0.05. This information has been added in the manuscript as a limitation of the study. 3. The Fig. 1 illustrated the study population. At top of the Fig. 1, it displayed 7 cases of missing data were excluded. The rest of the Fig. 1 demonstrated the outcomes of the 180 cases. However, there were 7 cases with negative CT and loss of follow-up should be excluded from this study cohort. This exclusion was not demonstrated in the Fig. 1. Revised. Reviewer #2: This is a retrospective diagnostic accuracy study conducted at a private tertiary hospital in Tanzania. The authors aimed to assess the diagnostic accuracy of a computed tomography scan for acute appendicitis in patients with suspected acute appendicitis at the emergency department. They found that the high diagnostic accuracy (97.5%) was comparable to that demonstrated in meta-analysis from studies conducted outside of Africa. This reviewer is an applied statistician and methodologist. I have several concerns. The entire manuscript needs to be closely edited by someone more proficient with the nuances of the English language as there are multiple sites in which the grammar could be improved. 1. Methodology- The period of this study conducted in the “Methodology” section was different from that recorded in “Abstract”. Which one was correct? Please revise. Revised. 2. Methodology- The authors wrote that “Adult patients above ten years of age were included in the study….”. This is different from definition of adult (>14 years of age) in the SRMA conducted by Rud B, et al. (2019). Please explain more. In the setting in which the study was conducted, patients above the age of 10 years were managed with adult surgeons. On further review, there were a total of 4 participants below the age of 14, making this 2.2% of the sample size. This information has been added in the manuscript. 3. Methodology- Presenting results for diagnostic test assessment include sensitivity, specificity, diagnostic odds ratio, and AUC. The authors should consider adding. Considerations given; ROC analysis not deemed necessary as the index test results and gold standard were either positive or negative (dichotomous) and not a scale. 4. Methodology-The authors wrote that “The image interpreters were four consultant medical radiologists rotating through an on-call schedule”. Please give the Kappa value between these four radiologists. Each radiologist interpreted the results independently, depending on when he/she was on call. This has been clarified in the manuscript. 5. Methodology- The authors wrote that “Sample size estimation based on Buderer formula of diagnostic accuracy for unknown disease prevalence”. But this is a retrospective study, why do this calculate? Please explain more. Sample size calculation was done to ascertain the confidence of the results and to know the sample size required to reach this confidence. 6. Results-Please give a more detailed demographic table about these 180 included participants. Additional information provided. 7. Results- The authors wrote that “the mean participants’ age was 35 years with a range (10 to 71)…”. Formally, for continuous variable like age, it must report as mean with standard deviation or 95% confidence interval. Please revise. Revised. 8. Results- Please revise the form for reporting the proportion. As example, line 81 states that “the first assessor was a medical officer in 40 %, but line 83 states that “six percent of the …..”. It must be consistent. Revised. 9. Results- Line 96-97 states that “A total of 35 participants determined to have normal appendices, without alternative diagnoses (27) and equivocal CT results (8) ….”. I think that the notations (27) and (8) stood for the numbers of participants but they were same as notations for cite references. Please revise. Revised. 10. Results- Please unify the number part, don’t use English and Arabic numerals interchangeably. Revised. 11. Results- In Line 108-111, Please give the 95% confidence intervals for sensitivity, specificity, diagnostic accuracy, positive and negative predictive value. Revised. 12. Results- The authors wrote that “No significant differences were observed…”. Does any statistical method was used? Which value of p-value was considered to be statistically significant? This subgroup analysis has been omitted due to limited samples 13. Can’t find the list of abbreviations. List of Abbreviations Added. ________________________________________ 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: Cheng-Chung Fang 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. ________________________________________ In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Remove my information/details). Please contact the publication office if you have any questions. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0276720.r002
16 Nov 2021 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-21-13993R1DIAGNOSTIC ACCURACY OF COMPUTED TOMOGRAPHY IN ADULTS WITH SUSPECTED ACUTE APPENDICITIS AT THE EMERGENCY DEPARTMENT IN A PRIVATE TERTIARY HOSPITAL IN TANZANIAPLOS ONE Dear Dr. Nyamuryekung'e, 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 revise. Please submit your revised manuscript by Dec 31 2021 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Robert Jeenchen Chen, MD, MPH 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: (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: No Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: No ****** 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 Reviewer #2: No ****** 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: No Reviewer #2: No ****** 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: The authors submitted a revised manuscript and responded to the questions. However, my concerns are still unresolved. 1. As the authors’ reply, the inclusion criteria of the study were: patients with right iliac fossa colicky abdominal pain of fewer than 10 days duration. There were no other physical examinations or laboratory tests to justify the impression of acute appendicitis (such as Alvarado score). The loose criteria made the high percentage (39%) of urolithiasis in the study population. The conclusion: “The commonest alternative diagnosis was urolithiasis and should be considered during the evaluation of adult patients with suspected acute appendicitis.” is inappropriate. Emergency physicians usually perform more studies for patients with right lower abdominal colic pain before CT. If we adopt the authors’ criteria, we would perform CT for every patient with right lower abdominal colic pain. 2. The rationale for performing this study is lacking. The reason: “There were no prior published studies examining the diagnostic accuracy of CT for acute appendicitis in the sub-Sahara Africa.” is not acceptable. Reviewer #2: This is my second review of this manuscript. The authors have replied and made many revisions regarding previous reviewers’ major concerns. Yet there remained some issues. 1. First, the entire manuscript still needs to be closely edited by someone more proficient with the nuances of the English language as there are multiple sites in which the grammar could be improved. 2. Methodology- The authors wrote that “Adult patients above ten years of age were included in the study….”. This is different from the definition of adult (>14 years of age) in the SRMA conducted by Rud B, et al. (2019). Please explain more. Authors' response: In the setting in which the study was conducted, patients above the age of 10 years were managed with adult surgeons. On further review, there were a total of 4 participants below the age of 14, making this 2.2% of the sample size. This information has been added to the manuscript. Reviewer response: But I still have concerns about why the author doesn’t include the adult patients above 14 years as same as in the SRMA conducted by Rud, B, et al. (2019). 3. Methodology- Presenting results for diagnostic test assessment include sensitivity, specificity, diagnostic odds ratio, and AUC. The authors should consider adding. Authors response: Considerations given; ROC analysis not deemed necessary as the index test results and the gold standard were either positive or negative (dichotomous) and not a scale. Reviewer response: Whether the index test results and the gold standard were either positive or negative (dichotomous), it still can calculate the AUROC. 4. Methodology-The authors wrote that “The image interpreters were four consultant medical radiologists rotating through an on-call schedule”. Please give the Kappa value between these four radiologists. Authors' response: Each radiologist interpreted the results independently, depending on when he/she was on call. This has been clarified in the manuscript. Reviewer response: My concern is that whether the image interpreters were done by two independent radiologists? 5. Methodology- The authors wrote that “Sample size estimation based on Buderer formula of diagnostic accuracy for unknown disease prevalence”. But this is a retrospective study, why does this calculate? Please explain more. Authors' response: Sample size calculation was done to ascertain the confidence of the results and to know the sample size required to reach this confidence. Reviewer response: To my knowledge, more data is better. Additionally, when the authors do sample size estimation based on the Buderer formula, the disease prevalence that the authors utilized according to the SRMA is 0.43 as described in Line 70-73, but the prevalence of this study is 0.25. Would it cause underestimation or upper estimation of the power? 6. Results-Please give a more detailed demographic table about these 180 included participants. Authors response: Additional information provided. Reviewer response: I still can’t find the additional information in one Table. As the authors describe the summary results through Line 81 to 97 in the Result section. 7. Results- The authors wrote that “No significant differences were observed…”. Does any statistical method was used? Which value of p-value was considered to be statistically significant? Authors response: This subgroup analysis has been omitted due to limited samples Reviewer response: Tests for Two Independent Sensitivities (netdna-ssl.com) 8. In Abstract, the Confidence Interval of 91.96 to 100%), 96.7% (95% Confidence Interval of 91.82 to 99.100%), and 97.6% (95% Confidence Interval of 93.88 to 99.31%), respectively. What is 99.100%? Please revised. Additionally, please change (95% Confidence Interval of 91.82 to 99.100%) to (95% C.I.: 91.82-99) through all manuscript. 9. In Result, the authors wrote that “Participants above 14 years of age contributed to 97.8% of 84 the sample; there were 2 participants of age 12 years and 1 participant each of age 11 and 10 years”. I really can’t understand and what it means? 10. In Line 110-112, the authors wrote that “A total of 35 participants, of which 27 had determined to have normal appendices without 111 alternative diagnoses and 8 with equivocal features of AA on CT”. but the total included participants is 178, why 35? ****** 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:** Cheng-Chung Fang 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.0276720.r003
Revision 2
31 Dec 2021 Author Response Response to Reviewer #1: 1. Details of evaluations performed by emergency medicine physicians including additional tests have been included in the manuscript. 2. The rationale has been refined further. Responses to Reviewer #2: 1. Grammatical and typographical errors reviewed and rectified. 2. To conform with the SMRA study, patients below the age of 14 have been excluded from the analysis of this study. 3. AUROC added and additional subgroup analyses. 4. The images were interpreted by one of four radiologists who was on call. This information has been clarified in the manuscript. 5. More data is certainly better. However, this also means more use of resources for data collection procedures, and sometimes this has ethical implications, hence calculating what would be needed allows one to know how much data collection is adequate. The lower prevalence of acute appendicitis in our study affected the precision of the results. This has been discussed in the discussion section. 6. Table one has been reviewed to contain more demographic details. 7. The reporting of results has been revised. 9. This section has been revised. 10. This section has been revised. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0276720.r004
12 Jan 2022 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-21-13993R2DIAGNOSTIC ACCURACY OF COMPUTED TOMOGRAPHY IN ADULTS WITH SUSPECTED ACUTE APPENDICITIS AT THE EMERGENCY DEPARTMENT IN A PRIVATE TERTIARY HOSPITAL IN TANZANIAPLOS ONE Dear Dr. Nyamuryekung'e, 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 revise. Please submit your revised manuscript by Feb 26 2022 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Robert Jeenchen Chen, MD, MPH 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: (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: No Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: (No Response) ****** 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: (No Response) ****** 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: No Reviewer #2: (No Response) ****** 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: The authors submitted a revised manuscript and responded to the questions. The authors stated that “The Alvarado score (AS) was not documented. However, based on symptoms assessed and the results of the CBC, the AS was computed for each patient. The mean AS was 4.64 (95% CI 4.32-4.97), those with AS of 1 to 4 were 50.6%”. As the authors’ replied, the inclusion criteria of the study were too loose. The AS of the patients less than 4 were 50.6% of the study patients, who should not receive abdominal CT for suspect acute appendicitis. The loose criteria made the high percentage (39%) of urolithiasis in the study population. The conclusion: “The commonest alternative diagnosis was urolithiasis and should be considered during the evaluation of adult patients with suspected acute appendicitis.” is inappropriate. Emergency physicians usually perform more examinations, such as urinalysis and abdominal ultrasonography for patients with right lower abdominal colic pain before CT. The diagnosis of urolithiasis is easy to identify by these examinations. If we adopt the authors’ criteria, we would perform CT for every patient with right lower abdominal colic pain. Reviewer #2: This is my second review of this manuscript. The authors have replied and made revisions regarding previous reviewers’ major concerns. Yet there remained more issues. 1. In my first comment, the authors stated that “The image interpreters were four consultant medical radiologists rotating through an on-call schedule. Please give the Kappa value between these four radiologists”. And the authors replied as “Each radiologist interpreted the results independently, depending on when he/she was on call. This has been clarified in the manuscript”. For this comment, my question was “whether the same image was interpreted by two or more radiologists or just one? If two or more radiologists have interpreted the same image, I would like to know how the degree of the consistent outcome through giving the kappa values? But if just one radiologist interpreted for one image, this may be lead to an inconsistent outcome and must have been addressed. 2. In my first comment, I have stated that “Please give the 95% confidence intervals for sensitivity, specificity, diagnostic accuracy, positive and negative predictive value”, but I suggest the authors revise the terms of confidence intervals into more formula terms. For example, (95% Confidence Interval of 0.79 to 0.96) to (95% C.I.: 0.79-0.96). the same terms through this manuscript like this term also please address accordingly. Additionally, do not use the percentage and decimal point interchangeably, please unify. ****** 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 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.0276720.r005
Revision 3
19 Mar 2022 Author Response Comments to the Author Reviewer #1: The authors submitted a revised manuscript and responded to the questions. The authors stated that “The Alvarado score (AS) was not documented. However, based on symptoms assessed and the results of the CBC, the AS was computed for each patient. The mean AS was 4.64 (95% CI 4.32-4.97), those with AS of 1 to 4 were 50.6%”. As the authors’ replied, the inclusion criteria of the study were too loose. The AS of the patients less than 4 were 50.6% of the study patients, who should not receive abdominal CT for suspect acute appendicitis. The loose criteria made the high percentage (39%) of urolithiasis in the study population. The conclusion: “The commonest alternative diagnosis was urolithiasis and should be considered during the evaluation of adult patients with suspected acute appendicitis.” is inappropriate. Emergency physicians usually perform more examinations, such as urinalysis and abdominal ultrasonography for patients with right lower abdominal colic pain before CT. The diagnosis of urolithiasis is easy to identify by these examinations. If we adopt the authors’ criteria, we would perform CT for every patient with right lower abdominal colic pain. Response: Thank you for your comments. For uniformity, the inclusion criteria were adopted from a meta-analysis and systematic on the same subject by Bo Rud et al, 2019. The use of USS prior to CT introduces a confounding effect on the assessment of CT’s diagnostic performance, and this is an exclusion criterion, in this study and the systematic review quoted above. The concerns on the use of AS have been analyzed and discussed, using the AS threshold of 4 would have resulted in 50% less CT scans, and missed 4 AA. Recommendations for the use of AS in assessing patients with suspected acute appendicitis have been emphasized. The recommendation by the authors referred to above had been rectified in an earlier revised version and is not present in the current revised version. Results of urinalysis done have been described and analyzed. Reviewer #2: This is my second review of this manuscript. The authors have replied and made revisions regarding previous reviewers’ major concerns. Yet there remained more issues. 1. In my first comment, the authors stated that “The image interpreters were four consultant medical radiologists rotating through an on-call schedule. Please give the Kappa value between these four radiologists”. And the authors replied as “Each radiologist interpreted the results independently, depending on when he/she was on call. This has been clarified in the manuscript”. For this comment, my question was “whether the same image was interpreted by two or more radiologists or just one? If two or more radiologists have interpreted the same image, I would like to know how the degree of the consistent outcome through giving the kappa values? But if just one radiologist interpreted for one image, this may be lead to an inconsistent outcome and must have been addressed. 2. In my first comment, I have stated that “Please give the 95% confidence intervals for sensitivity, specificity, diagnostic accuracy, positive and negative predictive value”, but I suggest the authors revise the terms of confidence intervals into more formula terms. For example, (95% Confidence Interval of 0.79 to 0.96) to (95% C.I.: 0.79-0.96). the same terms through this manuscript like this term also please address accordingly. Additionally, do not use the percentage and decimal point interchangeably, please unify. Response to comment 1. The concern for four independent radiologists evaluating the CT introduces inter-observer variability. This is has been discussed as a limitation of this study. Response to comment 2. This has been rectified. Thank you for your comments. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0276720.r006
12 May 2022 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-21-13993R3DIAGNOSTIC ACCURACY OF COMPUTED TOMOGRAPHY IN ADULTS WITH SUSPECTED ACUTE APPENDICITIS AT THE EMERGENCY DEPARTMENT IN A PRIVATE TERTIARY HOSPITAL IN TANZANIAPLOS ONE Dear Dr. Nyamuryekung'e, 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 revise. Please submit your revised manuscript by Jun 26 2022 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Robert Jeenchen Chen, MD, MPH Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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 Reviewer #3: All comments have been addressed Reviewer #4: (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: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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: No Reviewer #3: Yes Reviewer #4: No ****** 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: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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: The authors submitted the third revision of their manuscript. Same as the previous revisions, the authors did not directly respond to my questions, and they did not make point-to-point responses. The study population did not change after these revisions. Therefore, my questions were not resolved after the revisions. This study is a retrospective chart review study and has many inclusion biases when calculating the diagnostic accuracy of CT in acute appendicitis. I do not wish to make comments anymore, as my previous comments are still unresolved. Reviewer #2: This is my third review of this manuscript. The authors have replied and made many revisions regarding previous reviewers’ major concerns. I have no more comments. Thanks. Reviewer #3: Page 12, line 128: In the discussion section, the statement of "10239 hours" is incorrect, and should be "10239 minutes". Reviewer #4: Dear authors, Please see my comments in the attached pdf-file. You revised the manuscript several times before so I have focused on only important questions. I wish you the very best. Good Luck! ****** 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 Reviewer #2: No Reviewer #3: Yes:** JyhWen Chai Reviewer #4: 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. Attachments Attachment Submitted filename: PONE-D-21-13993_R3_reviewer.pdf https://doi.org/10.1371/journal.pone.0276720.r007
Revision 4
29 Sep 2022 Author Response Response to Reviewers Reviewer #1: The authors submitted the third revision of their manuscript. Same as the previous revisions, the authors did not directly respond to my questions, and they did not make point-to-point responses. The study population did not change after these revisions. Therefore, my questions were not resolved after the revisions. This study is a retrospective chart review study and has many inclusion biases when calculating the diagnostic accuracy of CT in acute appendicitis. I do not wish to make comments anymore, as my previous comments are still unresolved. Response to reviewer 1: Thank you for your review. The risk of inclusion bias due to the retrospective nature of the study has been added as a limitation. Below are the comments that were made on the previous review, and I have tried to break them down so that I may be able to provide appropriate responses Reviewer #1: The authors submitted a revised manuscript and responded to the questions. The authors stated that “The Alvarado score (AS) was not documented. However, based on symptoms assessed and the results of the CBC, the AS was computed for each patient. 1. The mean AS was 4.64 (95% CI 4.32-4.97), those with AS of 1 to 4 were 50.6%”. As the authors’ replied, the inclusion criteria of the study were too loose. The AS of the patients less than 4 were 50.6% of the study patients, who should not receive abdominal CT for suspect acute appendicitis. The loose criteria made the high percentage (39%) of urolithiasis in the study population. 2. The conclusion: “The commonest alternative diagnosis was urolithiasis and should be considered during the evaluation of adult patients with suspected acute appendicitis.” is inappropriate. 3. Emergency physicians usually perform more examinations, such as urinalysis and abdominal ultrasonography for patients with right lower abdominal colic pain before CT. The diagnosis of urolithiasis is easy to identify by these examinations. 4. If we adopt the authors’ criteria, we would perform CT for every patient with right lower abdominal colic pain. Response to Reviewer 1: 1. For uniformity, the inclusion criteria were adopted from a meta-analysis and systematic on the same subject by Bo Rud et al, 2019, whereby the Alvarado Score was not used for participant selection. However, as noted Alvarado Score was not performed in routine clinical practice to evaluate patients with suspected Acute Appendicitis; it was calculated in this study based on the workup performed. Had the AS been conducted in routine clinical practice and an AS of < 4 chosen to determine the need to perform CT, 50% fewer CT scans would have been conducted and missed 4 Acute Appendicitis. In the discussion, based on these results, we emphasise and advocate the routine use of AS to guide further management of patients with suspected AA. 2. This conclusion was removed in an earlier version and is not present in the current version. 3. Patients who underwent USS before CT were excluded from this study as this would introduce a confounding effect on CT’s diagnostic performance. Urinalysis was done in 134 patients and was normal in 79.1%, 19.4% showing microscopic hematuria, and pyuria with leucocytes in 1.5%. Urinalysis was not associated with a diagnosis of AA on binomial logistic regression (Positive for Acute Appendicitis or negative for Acute Appendicitis). This information is included in the revised manuscript 4. In the discussion section, we have emphasised and advocated the need to conduct an AS for patients with suspected AA before further management, as the results of this study also show that it would have decreased unnecessary CT scans. Reviewer #2: This is my third review of this manuscript. The authors have replied and made many revisions regarding previous reviewers’ major concerns. I have no more comments. Thanks. Response to reviewer 2: Thank you for your review. Reviewer #3: Page 12, line 128: In the discussion section, the statement of "10239 hours" is incorrect, and should be "10239 minutes". Response to reviewer 3: Thank you for the review. The change has been made Reviewer #4: Dear authors, please see my comments in the attached pdf-file. You revised the manuscript several times before so I have focused on only important questions. I wish you the very best. Good Luck! Response to reviewer 4: Thank you for the comments. 1. It is not unusual for patients to present late in this setting present due to various health-seeking behaviours, and we wanted to ensure we do not exclude them from the study due to health-seeking behaviour. However, by day 5, the cumulative percentage of patients who had presented to the EMD was 93%. 2. A medical officer is a registered medical doctor with a Doctor of Medicine degree qualification only. This definition has been added to the revised manuscript 3. A general surgery specialist was the first assessor in 23% of the cases. This has been included in the revised manuscript 4. We have rectified the noted errors in the placement of less than and greater than symbols. 5. Duration of illness was defined as the number of days from onset of abdominal pain to emergency medicine department orientation. The definition has been included in the revision. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0276720.r008
13 Oct 2022 Decision Letter - Robert Jeenchen Chen, Editor DIAGNOSTIC ACCURACY OF COMPUTED TOMOGRAPHY IN ADULTS WITH SUSPECTED ACUTE APPENDICITIS AT THE EMERGENCY DEPARTMENT IN A PRIVATE TERTIARY HOSPITAL IN TANZANIA PONE-D-21-13993R4 Dear Dr. Nyamuryekung'e, 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, Robert Jeenchen Chen, MD, MPH 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 Reviewer #4: 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 Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #4: 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: No Reviewer #4: 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 Reviewer #4: 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: This is my fourth review of this manuscript. The authors have replied and made many revisions regarding previous reviewers’ major concerns. I have no more comments. Thanks. Reviewer #4: Dear authors, thank you for your reply. I am very happy with the revision. You have answered all my comments. ****** 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 Reviewer #4: No ******** https://doi.org/10.1371/journal.pone.0276720.r009
Formally Accepted
19 Oct 2022 Acceptance Letter - Robert Jeenchen Chen, Editor PONE-D-21-13993R4 Diagnostic accuracy of computed tomography in adults with suspected acute appendicitis at the emergency department in a private tertiary hospital in Tanzania Dear Dr. Nyamuryekung'e: 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. Robert Jeenchen Chen Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0276720.r010

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