The effect of the COVID-19 pandemic on delirium incidence in Ontario long-term care homes: A retrospective cohort study

Lydia Kennedy; John P. Hirdes; George Heckman; Samuel D. Searle; Caitlin McArthur

doi:10.1371/journal.pone.0311098

Peer Review History

Original SubmissionMay 6, 2024
10 Jul 2024 Decision Letter - Kathleen Bennett, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-24-17753The effect of the COVID-19 pandemic on delirium incidence in Ontario long-term care homes: A retrospective cohort studyPLOS ONE Dear Dr. McArthur, 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. In particular, reviewers identified that the risk of bias in the results was very high. Please submit your revised manuscript by Aug 24 2024 11:59PM. 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Thank you for stating the following financial disclosure: The study is supported in part by funding from the Government of Canada's New Frontiers in Research Fund (NFRF; NFRFG-2020-00500) for collaboration in the EU Horizon 2020 research and innovation project Individualized CARE for Older Persons with Complex Chronic Conditions in Home Care and Nursing Homes (I-CARE4OLD, Grant Agreement No 965341). In addition, it received funding through the Canadian Institutes of Health Research (CIHR Reference # GA6-177780 )." Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript is well written and informative. The data presented are relevant for clinical practice and policy makers, but there are some major issues needing attention from the authors. First, delirium underdetection was extremely probable in the context of pandemic waves, because clinical resources were engaged into the care of COVID-19 cases and prevention of infection spread. The circumstance that the incidence of delirium was reduced during pandemic waves and raised in the inter-wave period supports this assumption. Therefore, the riskof bias in the results of this manuscript is very high. Furthermore, were any of the participating nursing homes involved in COVID-19 outbreaks? Considering the characteristics of SARS-CoV-2 infection during the first and the second wave, this occurrence is extremely probable. How were these outbreaks managed? Did they affect the delirium incidence? In older patients, delirium is one of the possible clinical presentations of COVID-19, so an increase in the delirium occurrence during pandemic waves should have been expected. But surprisingly, the incidence of delirium was higher during the inter-peak period. It is also unclear if some patients who had a long nursing home stay were included in both the pre-pandemic and the pandemic groups. How were these cases, that stayed in nursing homes from 2019 to 2021, managed? Frailty index calculation was also based on clinical data collected not always during the periods of observation, but in some cases at the moment of admission into nursing homes, which may have substantially preceeded the actual period of observation. Therefore, since frailty is a dynamic process, the present analysis may have been based on inactual measurements of frailty. Reviewer #2: The article is well written, with clear tables and figures. Furthermore it provides great insights in delirium incidence in Ontario, Canada. It gives very interesting insights and results, that are thoroughly discussed. Figure 1 is difficult to read and should be uploaded in better quality. ****** 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: Yes: Kelly Sabbe ******** [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. 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Revision 1
19 Aug 2024 Author Response Reviewer #1 Review Comments to the Author The manuscript is well written and informative. The data presented are relevant for clinical practice and policy makers, but there are some major issues needing attention from the authors. Thank you for your suggested revisions to our manuscript. We have addressed these below, as well as in the attached revised manuscript. 1. First, delirium under detection was extremely probable in the context of pandemic waves, because clinical resources were engaged into the care of COVID-19 cases and prevention of infection spread. The circumstance that the incidence of delirium was reduced during pandemic waves and raised in the inter-wave period supports this assumption. Therefore, the risk of bias in the results of this manuscript is very high. We have revised the discussion to further address this risk of bias in regard to the comments above with the following lines. “For the purposes of this study, we did not have access to any data regarding whether a LTC home experienced a COVID-19 outbreak, nor how they managed it. Therefore, the scope of this study did not extend to further investigate this variable. Those that experienced COVID-19 outbreaks may very well have had additional resource shortages that posted a barrier to clinically identifying the signs of delirium in their residents when attention was focused on controlling spread of disease. Assessing these characteristics would be extremely informative in future studies to obtain a clearer picture.” (Lines 347-353) 2. Furthermore, were any of the participating nursing homes involved in COVID-19 outbreaks? Considering the characteristics of SARS-CoV-2 infection during the first and the second wave, this occurrence is extremely probable. How were these outbreaks managed? Did they affect the delirium incidence? In older patients, delirium is one of the possible clinical presentations of COVID-19, so an increase in the delirium occurrence during pandemic waves should have been expected. But surprisingly, the incidence of delirium was higher during the inter-peak period. We have revised the discussion to address the topic of assessing LTC homes with COVID-19 outbreaks. Identifying and analyzing these homes was beyond the scope of this study but has now been explicitly stated within the discussion and suggested for a future point of study. The following lines have been included: “Further research would be pertinent to examine delirium rates in a LTC population of residents known to be infected with COVID-19 compared with those who were not. For the purposes of this study, we did not have access to any data regarding whether a LTC home experienced a COVID-19 outbreak, nor how they managed it.” (Lines 345-348) “In addition, infection with COVID-19 led to a great number of resident deaths. This was not accounted for by our study, and therefore our results may reflect a lower incidence as it does not consider delirium developed directly prior to resident deaths. That said, in the first wave of COVID-19 when most LTC deaths occurred, the median infection rate was 4.6% of residents per home. 15% of homes had severe outbreaks where 20% or more residents died, and just 5% of LTC homes accounted for over 54% of resident deaths [43]. In that light, it may be the case that a multi-level analysis adjusting for LTC home level covariates may be useful for future research.” (Lines 355-361) 3. It is also unclear if some patients who had a long nursing home stay were included in both the pre-pandemic and the pandemic groups. How were these cases, that stayed in nursing homes from 2019 to 2021, managed? It is certainly possible that LTC residents who had a long nursing home stay are included within both the pre-pandemic and pandemic groups. The main objective of our study was to characterize delirium incidence and see how this was affected by the emergence of the COVID-19 pandemic. Our interest was directed on the effect of time, versus the effect of clinical characteristics. Each group had patients with delirium at the baseline assessment deleted so that we could investigate development of new delirium. Therefore, if there was overlap in the residents between both groups, it was determined to not have a significant impact on the delirium incidence obtained. To specify this within the manuscript, the following lines were edited and added. “As the aim of this study was to investigate the development of new delirium from baseline to follow-up, residents with indicators of delirium on their baseline assessment were excluded. Residents who remained in LTC throughout the period of study between February 1, 2019, and March 31, 2021, may have been included in both the comparison and pandemic samples. However, as residents with baseline delirium were deleted in both samples, it was determined that this would not have a large effect on the final incidences obtained.” (Lines 148-154) 4. Frailty index calculation was also based on clinical data collected not always during the periods of observation, but in some cases at the moment of admission into nursing homes, which may have substantially preceded the actual period of observation. Therefore, since frailty is a dynamic process, the present analysis may have been based on unactual measurements of frailty. As noted within the “Sample construction” section, quarterly assessments do not capture all of the variables used within the calculation for frailty index. This is because the quarterly assessments are used to track the status of a resident in between comprehensive assessments and focuses on items that are not expected to change acutely. In the case of our study, this clinical data only needed to be collected from prior assessments when the baseline assessment was a quarterly. Therefore, only a subset of each sample needed these variables brought forward. The variables brought forward also only represented a subset of the variables used for frailty index calculation. Finally, in order to bring those variables forward, the most recent comprehensive (annual or admission) assessment that had been completed in the preceding 12 months was used. The following lines have been edited and added in order to better clarify this. “Admission and annual assessments are comprehensive and include all of the variables required for our study. However, quarterly assessments are shorter to complete and do not include certain items that are not expected to change acutely. Therefore, for a subset of each sample where a quarterly assessment was used as a resident’s baseline, certain independent variables of interest were not carried forward. These were therefore obtained from the most recent admission or annual assessment completed in the preceding year. As noted, variables carried forward included those expected to remain fairly constant, for example, marital status, hearing/vision impairment, Alzheimer’s status, and a subset of variables used within the Frailty Index.” (Lines 129-136) Reviewer #2 Review Comments to the Author The article is well written, with clear tables and figures. Furthermore, it provides great insights in delirium incidence in Ontario, Canada. It gives very interesting insights and results, that are thoroughly discussed. Thank you for your suggested revisions on our manuscript. We have addressed these below and in the revised manuscript. 1. Figure 1 is difficult to read and should be uploaded in better quality. Figure 1 has been reuploaded and reviewed using the PACE software to achieve a high quality figure for publication. https://doi.org/10.1371/journal.pone.0311098.r002
13 Sep 2024 Decision Letter - Kathleen Bennett, Editor The effect of the COVID-19 pandemic on delirium incidence in Ontario long-term care homes: A retrospective cohort study PONE-D-24-17753R1 Dear Dr. McArthur, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Kathleen Bennett Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0311098.r003
Formally Accepted
5 Nov 2024 Acceptance Letter - Kathleen Bennett, Editor PONE-D-24-17753R1 PLOS ONE Dear Dr. McArthur, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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 Professor Kathleen Bennett Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0311098.r004

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