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PONE-D-21-03064

A comparison of comorbidity measures for predicting mortality after elective hip and knee arthroplasty: A cohort study of data from the National Joint Registry in England and Wales

PLOS ONE

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PLOS ONE

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[I have read the journal's policy and the authors of this manuscript have the following

competing interests: MW (Stryker, Heraeus, DePuy), AB (Stryker) and JMW (Amgen)

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Deringer) for companies outside the submitted work. MRW (Hip International) and

JMW (Bone and Joint Research, Journal of Orthopaedic Research) declare journal

editorial positions. JMW is a board member for the British Orthopaedic Research

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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: The article concludes that standard comorbidity measures are not needed to predict mortality after elective arthroplasty surgery of the hip and knee. The result is coherent with previously published result but provides additional certainty due to the large sample size with high quality data. The result is important since there is a common misconception that comorbidity (as captured from administrative data) should always be used in prediction models of mortality after such surgery. It is showed in the paper that a simpler model with age, sex and ASA class is good enough, and would therefore be preferred due to simplicity.

I have some comments:

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1. It might be interesting to compare the models with a base model only. Hence, a model with age and sex only. I suspect that such model would not perform much worse than model 1?

2. I am a little skeptical to the use of the Brier score. It is a common measure of discriminatory ability, but it is actually quite insensitive for rare events data, as seen from the tables where this metric is almost constant. I would consider omitting this metric. A near-by-alternative might be the Index of Prediction Accuracy (IPA) instead. It is still based on the Brier score but with a better scale.

3. I agree that external validation seems to be outside the scope of the article. The data set is quite big, however, so I am just wondering whether it wouldn’t be possible to save a small portion from the original data for later assessment?

4. You should probably discuss if there was any (and if so, how much) censoring, especially for the one-year time frame. If relevant, you might discuss why you did not consider a time-dependent ROC-curve.

5. I would suggest a sensitivity analysis without stratification for the bootstrap replicates used for the confidence intervals. I think you should have a reasonably good chance to succeed without it (which would be a strength).

Smaller issues

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1. The use of logistic regression might be a little problematic. Nevertheless, I would use it myself (I am not saying I know a better method!), but it might be discussed as a limitation that this method is actually not recommended for very rare outcomes (which is what we have here).

2. I am lacking some details of how you treated patients with surgeries performed on multiple joints. They can only die once I think.

3. Is it reasonable that patients with ASA class V get elective surgery?

4. You refer to the comorbidity indices as being “continuous”. I guess this might be a quite reasonable approximation for the Elixhauser score (which is on a discrete scale from 0 to 30). I am less convinced for CCI, however, since it is a weighted sum with only a limited set of possible values.

5. There has been some (relatively recent and perhaps valid) criticism concerning the weights used in CCI. Might be worth considering? See https://www.jclinepi.com/article/S0895-4356(16)30676-X/pdf

6. It might be noted that Elixhauser herself did not recommend using her tool as a combined measure. Therefore, it might be relevant to point out that what is not working, is to use her tool as is commonly done in practice, although usage according to her original suggestion might still work (which is usually not possible, however, due to limited data and the need of too many variables).

7. I would prefer to have some data on ASA class (and perhaps diagnosis) already in table 1 and 2 (it is now in the supplement).

8. It might be beneficial to instead include some additional data concerning individual comorbidities (according to CCI/Elixhauser) in the supplement. It might be slightly outside the scope of the article, but I do think it would be interesting to be able to compare conditions from the UK to similar data from other countries (as from other papers).

Tiny issues

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9. Abstract: I propose to describe the data as “linked” rather than “combined”.

10. Abstract: “Mortality _after_ 90 days”. Shouldn’t this be “Mortality _within_ 90 days”?

11. I am not a native English speaker (and I know you are) but for me “sex” would sound more accurate than “gender”, since you use administrative register data. Or were the patients surveyed for gender identity? (You do actually have “sex” in fig 5.)

12. I thought ASA was a “class” (not a “grade”)? (I am not sure of the difference myself but this is what I have been told).

13. Background: Isn’t Guernsey part of the register (NJR) name (it is mentioned later).

14. Background: “the main focus within joint replacement surgery has been on the Charlson Comorbidity (CCI) and Elixhauser indices”. I think the RxRisk score has been used quite a bit as well (at least in Australia). Could perhaps be mentioned?

15. You state that the “original” Elixhauser includes 30 conditions. This is true but since it originally included 31, it might be a little confusing what is actually meant by “original” (one condition was dropped in an update made in 2004).

16. Methods: Was “HES” used for Wales as well?

17. Methods: I think that what you refer to as “predictors” might be considered “potential predictors” or similar?

18. You might spell out the meaning of “ICD-10” the first time you use this acronym.

19. Predictors section: What is meant by “All available episodes up to the primary”. I suppose that the start of HES indicates a lower limit. When was that?

20. There is a mention of a Brier score of “0.0.0034” (two decimal marks).

21. You mention as a strength that you do not need to rely on data that is older than 10 years (and I agree!). But you do in fact include data from early 2011 (which strictly speaking was more than ten years ago).

22. You mention that HES data from private hospitals were not included and that those patients might be healthier than other patients. I agree, but I also suppose that in some other countries, private hospitals might also have other incitements to report additional comorbidities due to reimbursement? But I suppose you do not have that issue in the UK?

23. Figure 1 and 2: I would prefer dates as “2011-01-01” (month before day since I think this is more common in other countries.

24. Table 1 and 2 have some superscripts which are not explained.

25. For figures S5 etc I think you should clarify that age and sex were included in the models (otherwise the ROC curves should be less smooth).

26. I think you have too many digits in your confidence intervals for AUC. If you have “only” 2000 bootstrap replicates you should only include one significant digit. If you need two digits, you are recommended to have 10000 replicates (according to the documentation for the pROC R package).

27. I would recommend including pagination and line numbers for the sake of the reviewers :-)

Reviewer #2: - I think it would be better and more consistent to use arthroplasty instead of replacement consistently throughout the whole article and consequently using the abbreviations THA and TKA rather than using both terms at different sections of the article.

- I would suggest pointing out the most commonly encountered specific comorbidities which might have been correlating / predicting mortality after THA or TKA ...It would have ideal to include them in the analysis in addition to the use of the whole scores parameters.

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Reviewer #1: Yes: Erik Bülow

Reviewer #2: Yes: Mahmoud Abdel Karim

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A comparison of comorbidity measures for predicting mortality after elective hip and knee replacement: A cohort study of data from the National Joint Registry in England and Wales

PONE-D-21-03064R1

Dear Dr. Penfold,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Osama Farouk

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #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: I am thankful for the opportunity to review this nice paper once more. The authors have provided thorough and well-motivated answers to all my questions. I feel more than satisfied! I am looking forward to reading this article in print!

P.S. As a small side note (no action requested), I would just like to expand on my comment no. 15, regarding the number of Elixhauser comorbidities. The authors are right that Elixhauser et al. (1998) refers to 30 comorbidities (my mistake!). Those are listed in table 1 from 1998. The second comorbidity is “Cardiac arrhythmias” and the 6:th is “Hypertension (combined)”. Some later papers (for example Quan et al 2005; https://doi.org/10.1097/01.mlr.0000182534.19832.83) have split hypertensions to either “uncomplicated” or ”complicated”. Hence, with a total of 31, while still refereeing to the original paper.

In addition to the published papers, The Elixhauser comorbidity software is provided by the AHRQ (https://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp#archives). It was described in a tech note from 2004 that “[Cardiac arrhythmias] was removed for FY2004, Version 2.0.” (p 6; https://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/Table1-FY2004-V2_1.pdf). Thus, leaving 29 comorbidities for later versions of the software.

A rhetorical question (no need for explicit response): How many Elixhauser comorbidities are there in table 1 and 2 of the now revised manuscript?

Reviewer #2: Thank you so much for replying to the comments and suggestions raised. I think you have managed to address all of them.

Thank you for your efforts and interesting article.

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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: Erik Bülow

Reviewer #2: Yes: Mahmoud Abdel Karim