Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer.

BACKGROUND: Patients with chronic diseases are at higher risk of requiring domiciliary and nursing home care, but how different chronic diseases compare in terms of risk is not known. We examined initiation of domiciliary care and nursing home admission among patients with heart failure (HF), stroke, COPD and cancer.
METHODS: Patients with a first-time hospitalization for HF, stroke, COPD or cancer from 2008-2016 were identified. Patients were matched on age and sex and followed for five years.
RESULTS: 111,144 patients, 27,786 with each disease, were identified. The median age was 69 years and two thirds of the patients were men. The 5-year risk of receiving domiciliary care was; HF 20.9%, stroke 25.2%, COPD 24.6% and cancer 19.3%. The corresponding adjusted hazard ratios (HRs), with HF patients used as reference, were: stroke 1.35[1.30-1.40]; COPD 1.29[1.25-1.34]; and cancer 1.19[1.14-1.23]. The five-year incidence of nursing home admission was 6.6% for stroke, and substantially lower in patients with HF(2.6%), COPD(2.6%) and cancer (1.5%). The adjusted HRs were (HF reference): stroke, 2.44 [2.23-2.68]; COPD 1.01 [0.91-1.13] and cancer 0.76 [0.67-0.86]. Living alone, older age, diabetes, chronic kidney disease, depression and dementia predicted a higher likelihood of both types of care.
CONCLUSIONS: In patients with HF, stroke, COPD or cancer 5-year risk of domiciliary care and nursing home admission, ranged from 19-25% and 1-7%, respectively. Patients with stroke had the highest rate of domiciliary care and were more than twice as likely to be admitted to a nursing home, compared to patients with the other conditions.

Introduction

Patients with chronic diseases such as heart failure (HF), stroke, chronic obstructive pulmonary disease (COPD) and cancer are at a considerable risk of hospital admission and death but little is known about the consequence of these conditions on the ability of patients to live, unaided, in the community [1-5]. As a result of improvement in treatment, most patients with chronic diseases are living longer and getting older, underscoring the importance of looking beyond mortality and hospitalizations when assessing the impact of each of these conditions on patients and society. One approach would be to assess quality of life and functional status, as defined by capability to perform activities of daily living. However, it is difficult to measure quality of life in large-scale patient cohorts, and little is known how well these patients are living with their disease. Similarly, functional capacity is hard to measure in community studies, although these conditions may cause fatigue and impaired functional status, possibly preventing patients from carrying out normal activities of daily living and managing independently at home [6-9]. Domiciliary support such as help with shopping, meal preparation, personal care and cleaning and, in extreme cases, institutional care, for example nursing home admission, may be needed and can be used as objective measures of patients’ autonomy and ability to live unaided. Also, domiciliary care and nursing home admission reflect an important measure of the personal, family and societal burden of chronic conditions. Loss of autonomy and possible separation from a spouse or family can lead to loss of self-esteem, indolence and depression. We know that patients with chronic conditions are at higher risk of needing these types of support than those without [10, 11]. But how the risk of domiciliary care and nursing home admissions compare between different types of chronic conditions is not known. To further evaluate these consequences of chronic diseases, we conducted a nationwide study in Denmark using cross-linkage of health and administrative registries.

Methods

Data sources

A unique personal identification number is assigned to all residents in Denmark which makes linkage of nationwide registries at an individual level possible [12]. Danish nationwide registries hold information on sociodemographic characteristics, all hospital admissions and claimed drug prescriptions [13, 14]. Data on domiciliary care in the community have been available since 2008 and data on nursing home admission since 1994 [15]. The study was approved by the Danish Data Protection Agency and data are available from Statistics Denmark upon application for researchers located in Denmark. Register-based studies in which individuals cannot be identified do not require ethical approval in Denmark.

Study population and baseline variables

We designed a retrospective cohort study of all Danish residents with a first ever hospitalization for HF, stroke, COPD or cancer between January 1, 2008 and December 31, 2016 and followed these patients for up to five years. Patients were required to be alive at discharge and were excluded if they had received domiciliary care, were living in a nursing home, or had any of the other conditions of interest prior to study inclusion. Each patient entered the study on their date of discharge and was individually matched with patients from the other groups of diseases based on age, sex and calendar year. All matched patients were followed until an outcome of interest occurred, death, for a maximum of 5 years or until end of study (December 31, 2017). Comorbidities were identified by hospital discharge ICD-10 codes in a 10-year period prior to qualifying hospitalization; S1 Appendix. Diabetes mellitus, dementia and depression were additionally identified by at least one filled prescription for a disease-specific drug in the preceding 6 months. Ongoing use of medication was defined by at least one filled prescription of the drug in the preceding 6 months or 7 days after discharge but was not included in the adjusted Cox regression analyses; S2 Appendix.

Outcome measures

The primary outcomes were initiation of domiciliary care and admission to a nursing home. Domiciliary care was defined as help given if there are tasks in the home that the citizen can no longer carry out themselves. In Denmark domiciliary care covers three main areas: 1) Personal care, including bathing, dressing and eating, 2) Practical help such as shopping, cleaning and doing laundry, and 3) Food service [16]. Nursing home is defined as an institution where citizens live if they can no longer take care of themselves.

Statistics

Baseline characteristics for HF, stroke, COPD and cancer patients were described by use of proportions for categorical variables and medians/quartiles for continuous variables. Cumulative incidence curves for initiation of domiciliary care and nursing home admission, with death as a competing risk, were estimated using the Aalen-Johansen method and differences between the diseases were compared using Gray’s test [17, 18]. We also used cause-specific Cox regression to compare the risk of initiation of domiciliary care and nursing home admission between patient groups. The Cox regression analyses were adjusted for age, sex, marital status, calendar year, and comorbidities (ischemic heart disease, atrial fibrillation, chronic kidney disease and diabetes) and stratified by who each patient was matched with. Adjusted variables were chosen before any analysis was done and were based on clinical relevance and known prognostic importance. The variables sex, age, calendar year and marital status were tested for interactions with the diseases in relation to both outcomes. Log (-log(survival)) curves were used to evaluate the proportional hazard assumption. The assumption of linearity of age was tested by including a variable of age squared.

The SAS statistical software package, version 9.4 (SAS Institute, Cary, North Carolina; USA) and and R, version 3.5.1 (R development Core Team) were used for all analyses.

Results

Baseline characteristics

Following matching on age, sex and calendar year we identified 111,144 patients, 27,786 with each disease. Baseline characteristics of patients in the four disease groups are shown in Table 1. The median age was 69 and two thirds of the patients were men. Patients with HF were more likely to have ischemic heart disease, atrial fibrillation, diabetes and chronic kidney disease that the others. Patients with stroke had the highest proportion with dementia and depression and patients with COPD were more likely to be living alone.

Table 1

Baseline characteristics a first hospitalization for HF, stroke, COPD or cancer.

	Heart failure	Stroke	COPD	Cancer
No. Patients	27786	27786	27786	27786
Age, median (Q1-Q3)	69 (60–76)	69 (60–76)	69 (60–76)	69 (60–76)
Male	18502 (67)	18502 (67)	18502 (67)	18502 (67)
Civil status (%)
Living alone	8902 (32)	8636 (31)	10155 (37)	7412 (27)
Comorbidities (%)
IHD	16339 (59)	5593 (20)	7059 (25)	3956 (14)
Atrial fibrillation	12663 (46)	5570 (20)	5372 (19)	3091 (11)
Diabetes	6967 (25)	4598 (17)	4514 (16)	3387 (12)
CKD	4464 (16)	1559 (6)	2173 (8)	1428 (5)
Dementia	195 (0.7)	309 (1.1)	216 (0.8)	135 (0.5)
Depression	3247 (12)	4198 (15)	4531 (16)	2490 (9)
Pharmacotherapy* (%)
Antiplatelets, any	15209 (55)	18806 (68)	7830 (28)	5237 (19)
Lipid-lowering drugs	14594 (52)	17423 (63)	8161 (29)	6721 (24)
Thiazides	4298 (15)	4463 (16)	4114 (15)	3319 (12)
Loop diuretics	16381 (59)	1848 (7)	5004 (18)	1988 (7)
Beta blockers	19668 (71)	6320 (23)	6110 (22)	4350 (16)
ACE-I/ARB	20761 (75)	11461 (41)	9149 (33)	8098 (29)

COPD—chronic obstructive pulmonary disease; IHD—ischemic heart disease;

ACE-I—angiotensin-converting enzyme inhibitors, ARB—angiotensin-II receptor blockers;

*Filled in prescriptions 180 days prior to admission or 7 days after discharge.

Initiation of domiciliary care

Over five years of follow-up (median time: 1395 days; quartile 1- quartile 3: 670–1825 days) the need for domiciliary care was 20.9% [20.4%–21.4%] in HF patients, 25.2% [24.7%–25.7%] in stroke patients, 24.6% [24.1%–25.1%] in patients with COPD and 19.3% [18.8%–19.7%] in patients with cancer; P< 0.0001; Fig 1A. The competing risk of death was 16.2% [15.7%–16.6%], 10.0% [9.6%–10.3%], 17.3% [16.9%–17.8%] and 25.4% [24.9%–26.0%]; P<0.0001, among HF-, stroke-, COPD- and cancer patients respectively; Fig 1B. In adjusted analyses with HF patients as reference group, the likelihood of initiating domiciliary care was significantly higher for both stroke—(HR 1.35 [1.30–1.40]), COPD—(HR 1.29 [1.25–1.34]) and cancer patients (HR 1.19 [1.14–1.23]); Fig 2. Other factors associated with initiation of domiciliary support included older age (HR 1.06 [1.06–1.06] per 1-year increase in age), female gender (HR 1.14 [1.11–1.17]) and living alone (HR 1.92 [1.88–1.98]); Fig 2. Living alone was associated with a greater need for domiciliary care in both men than women; however, the association was significantly stronger in men (men: HR 2.22 [2.14–2.29] vs women: HR 1.60 [1.53–1.63]; P for interaction<0.0001). Most comorbidities were also associated with higher likelihood of domiciliary care especially dementia (HR 1.58 [1.44–1.75]), depression (HR 1.56 [1.51–1.62]) and chronic kidney disease (HR 1.53 [1.47–1.59]) but also diabetes (HR 1.26 [1.22–1.30]) and atrial fibrillation (HR 1.13 [1.10–1.18]).

Fig 1

Cumulative incidence of domiciliary care initiation (A) with death as a competing risk (B) in patients with HF, stroke, COPD or cancer.

Fig 2

Multivariable Cox regression model of factors associated with initiation of domiciliary care in patients with HF, stroke, COPD or cancer.

Nursing home admission

The overall incidence of nursing home admission was low, but large differences were observed between groups; patients with stroke had an incidence of 6.6% [6.4%–6.9%] compared to patients with HF 2.6% [2.4%–2.8%], COPD 2.6% [2.5%–2.8%] and cancer 1.5% [1.4%–1.7%]; P<0.0001; Fig 3A. The competing risk of death was highest in patients with cancer (37.8% [37.2%–38.4%]), similar in patients with COPD 27.6% [27.1%–28.2%] and HF 24.4% [23.9%–24.9%], and lowest among patients with stroke 14.2% [13.8%–14.6%]; P<0.0001; Fig 3B. In adjusted analyses, with HF patients as reference, the likelihood of nursing home admission was more than twice as high for patients with stroke (HR 2.44 [2.23–2.68]), the same for patients with COPD (HR 1.01 [0.91–1.13]), and significantly lower for patients with cancer HR = 0.76 [0.67–0.86]; Fig 4. As for domiciliary care, age (HR 1.06 [1.06–1.06] per 1-year increase in age) and living alone (HR 1.92 [1.88–1.98]) were strongly associated with nursing home admission. The association of living alone and nursing home admission was seen in both men (HR 2.74 [2.52–2.98]) and women (HR 1.58 [1.42–1.77]); but was significantly stronger in men (P for interaction <0.001). In contrast to the findings regarding domiciliary care, male gender (HR 1.08 [1.01–1.16]) was associated with a higher likelihood of nursing home admission. As for comorbidities, dementia (HR 4.00 [3.47–4.61]) and depression (HR 2.14 [1.98–2.31]) were particularly associated with admission to a nursing home, as were chronic kidney disease (HR 1.21 [1.10–1.34]) and diabetes (HR 1.31 [1.20–1.41]) (Fig 4).

Fig 3

Cumulative incidence of nursing home admission (A) with death as a competing risk (B) in patients with HF, stroke, COPD or cancer.

Fig 4

Multivariable Cox regression model of factors associated with nursing home admission in patients with HF, stroke, COPD or cancer.

Discussion

Domiciliary care was initiated in around 20–25% of patients within 5 years of discharge, following a first hospitalization for either HF, stroke, COPD or cancer. Patients with HF had a significant lower likelihood of needing this assistance than patients with stroke (who had the highest likelihood), COPD or cancer. Nursing home admission occurred in 2–7% of patients within 5 years, with the incidence more than twice as high in patients with stroke compared to the other diseases. Factors associated with both initiation of domiciliary care and nursing home admission included older age, living alone and non-cardiac comorbidities.

The conditions we examined, and other chronic diseases, are characterised by symptoms such as fatigue breathlessness and associated with reduced physical ability, all of which tend to worsen over time and may lead to loss of independence and the need for support in the community or residential care. Between 1 in 4 and 1 in 5 of patients in our study had domiciliary care initiated within 5 years of discharge, and most needed within 1 year. This highlights a different but important aspect of disease trajectory not necessary is reflected by hospitalizations or mortality and likely reflecting progressive worsening of symptoms and functional status. Furthermore, it reflects an important impact of these chronic conditions at both the level of the individual patient and for society more generally. Thus, domiciliary and nursing home care reflect the broader societal burden of these chronic conditions and may be valuable additional metrics of the effect of treatment on chronic diseases, their economic consequences and, potentially, quality of care.

The need for domiciliary care and, especially, the incidence of nursing home admission, was highest among stroke patients. This may reflect the particular effect of stroke on vision, speech, swallowing, use of limbs, and bladder control all of which may make affected individuals dependent on the help of others [19]. HF, COPD and cancer don’t usually cause this same range of disabilities and this may explain the higher need for community and residential care associated with stroke, compared with these other conditions. Although patients with stroke had a markedly higher risk of nursing home admission, it is important to point out that the absolute risk of nursing home admission was low. Furthermore, death was a major competing risk for the other conditions, especially in cancer, which might have led to an underestimation of the real differences in utilization of these support services.

It was somewhat surprising that both COPD and cancer patients were significantly more likely than patients with HF to have domiciliary care initiated after hospital discharge. For COPD this might be related to the condition being associated with lower social status and a higher proportion of patients with COPD living alone; this may mean that such patients had less personal support to allow them to live without help [20]. With respect to cancer, this condition may still be perceived as a more deadly than HF, making access to benefits such as domiciliary care easier [21]. However, this is hypothesis is speculative and need further investigation and verification.

Other factors such as the impact of comorbidities, mental health, cognitive function and social support beyond severity of the chronic disease might be important in the evaluation of the need to initiate domiciliary care, or to admit a patient to a nursing home. Indeed, we saw a significant association between comorbidities such as diabetes and chronic kidney disease with both domiciliary care and nursing home admission. Of note, comorbidities which are linked to mental health problems and cognitive dysfunction, i.e. depression and dementia showed a particularly strong association with each outcome, indicating that mental health and cognitive function might be as important as physical limitations in determining whether independent living can be maintained. The importance of spousal support was evident from the significant association of living alone and likelihood of both domiciliary care and nursing home admission. Notably we found a significant interaction of sex and living alone on both outcomes, i.e. to be living alone had a higher impact on men than on women, presumably reflecting that women in general are better to take care of themselves.

Strengths and limitations

The main strengths of our study are that we have a nationwide unselected cohort of patients with a first ever hospitalization for either HF, stroke, COPD or cancer followed in a real life setting with complete follow-up on all patients, except those who emigrated from Denmark during the study period. The main limitations are absence of certain clinical variables, such as HF severity; cancer type, stage and treatment; performance status, stroke score and pulmonary function tests which could help us identify the severity of the conditions of interest. Together with possible other unmeasured confounders these factors could have influenced our results in ways we have not been able to account for in our analyses. Thus, as is always the case with observational studies, the associations we found are not necessarily causal. Data on hours and type of domiciliary care are not adequately collected and therefore domiciliary care may cover a wide spectrum of services. We did not have access to data on self-care autonomy such as activities of daily living. Finally, our findings were based on the Danish healthcare and social systems and therefore may not be applicable to other countries.

Conclusions

One out of five patients have domiciliary care initiated within 5 years of first hospitalization for HF, stroke, COPD or cancer. Patients with stroke were most likely to receive domiciliary care and were more than twice as likely to be admitted to a nursing home as patients with any of the other conditions examined. Comorbidities, living alone and older age were associated with higher likelihood of receiving each type of care. Domiciliary care and nursing home admission may be valuable additional metrics of the impact of chronic diseases on both patients and on society, the effect of treatment on these conditions and of the quality of care.

ICD-10 codes.

(DOCX)

Click here for additional data file.

ATC classification codes.

(DOCX)

Click here for additional data file.

7 Apr 2021

PONE-D-21-02090

Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer

PLOS ONE

Dear Dr. Rørth,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 10 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,

Antonio Cannatà

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

and

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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

Reviewer #1: No

Reviewer #2: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Overall Comments:

Thank you for the opportunity to review this manuscript. This is an interesting retrospective cohort study using Danish nationwide registries to compare risk of needing domiciliary care or nursing home care between patients with HF, stroke, COPD, and cancer. The statistical methods that the authors employ appear to be appropriate, though I am not a statistician myself. I have a few comments/questions outlined below:

Methods

- In terms of clarity, I suggest the authors start with describing the overall approach to this study. It appears to be a retrospective cohort study.

- page 11 “ Comorbidities were identified by hospital discharge codes in a 10-year period prior to qualifying hospitalization”

o Please provide more details about this---do you mean ICD10 codes that are coded/associated with that particular admission?

- page 11 “Diabetes mellitus, dementia and depression were additionally identified by at least one filled prescription for a disease-specific drug in the preceding 6 months.”

o Please provide an Appendix where details on which disease-specific drugs you used to define these co-morbidities.

- page 11, “Ongoing use of medication was defined by at least one filled prescription of the drug in the preceding 6 months or 7 days after discharge but was not included in the adjusted Cox regression analyses.”

o Do you mean the variable reflecting filled prescription was not included in the model?

Results

- Would be interesting to know how many patients in each cohort (HF/stroke/COPD/cancer) developed one of the other conditions of interest over the follow up period, and if development of additional conditions of interest affected risk of receiving domiciliary care or admission to nursing home. Patients at particularly high risk for needing receiving domiciliary care or admission to nursing home likely also have multimorbidity of these illnesses.

- The rate of nursing home admission in this study is surprisingly very low. In the US it is much more common (https://www.hcup-us.ahrq.gov/reports/statbriefs/sb205-Hospital-Discharge-Postacute-Care.jsp ). This may be because the differences in how domiciliary care and nursing home care is funded between the two countries. In the US, it is cheaper for insurance companies to pay for nursing home care rather than a home health aid 24/7. This doesn’t necessarily reflect patient or family preferences. It could also potentially provide an example of what utilization of these services might be if our healthcare/society in the US was different. I know you briefly mention that your findings may not be applicable to other countries, but might be interesting to discuss what might be learned from the differences.

Reviewer #2: This is an interesting paper that describes the clinical management out of the hospital of patients affected by chronic diseases such as heart failure (HF), stroke, chronic obstructive pulmonary disease (COPD) and cancer.

I have some comments:

- It would be very interesting to evaluate the same outcomes in these two subgroups of patients: one of ‘’living alone’’ and other one ‘’supported by relatives’’. The family’s support could modify the necessity of domiciliary care initiation and nursing home admission.

- It would be very interesting a clinical evaluation of self-care autonomy of these patients at the baseline and during the follow-up, with the help of some specific scales such as ADLs or IADLs. If it is not applicable, please report it in the limitation.

- Further information about cancer disease of these patients are needed, such as the presence of metastasis, palliative or chemotherapy treatments. Moreover, at least NYHA class of the patients affected by HF should be reported, at the baseline and during follow-up.

- Did any of these patients need re-hospitalization during follow-up?

**********

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: Himali Weerahandi

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.

8 Jun 2021

Reviewer #1, general comments:

Thank you for the opportunity to review this manuscript. This is an interesting retrospective cohort study using Danish nationwide registries to compare risk of needing domiciliary care or nursing home care between patients with HF, stroke, COPD, and cancer. The statistical methods that the authors employ appear to be appropriate, though I am not a statistician myself. I have a few comments/questions outlined below:

Thank you for this comment on our manuscript.

Reviewer #1, comment no 1:

- In terms of clarity, I suggest the authors start with describing the overall approach to this study. It appears to be a retrospective cohort study.

Thank you for this comment. We have tried to make the description of the study design more clear.

Changes made to the manuscript: Method section, (P 5, L11-13)

We designed a retrospective cohort study of all Danish residents with a first ever hospitalization for HF, stroke, COPD or cancer between January 1, 2008 and December 31, 2016, were identified and followed these patients for up to five years.

Reviewer #1, comment no 2:

- page 11 “ Comorbidities were identified by hospital discharge codes in a 10-year period prior to qualifying hospitalization”

o Please provide more details about this---do you mean ICD10 codes that are coded/associated with that particular admission?

Thank you for pointing this out. Yes, we used ICD codes from prior hospital admissions. A more detailed description and an appendix has now been included.

Changes made to the manuscript: Method section, (P 5, L19-20)

Comorbidities were identified by hospital discharge ICD-10 codes in a 10-year period prior to qualifying hospitalization; Appendix 1.

Appendix 1 ICD-10 codes

Comorbidity ICD-10 codes

Heart failure I420, I426, I427, I428, I429, I50, I110, I130, I132

Stroke I60-64

Chronic obstructive pulmonary disease J42-J44

Cancer C00-C97 (if not C44)

Ischemic heart disease I20-I25

Atrial fibrillation I48

Diabetes E10-14

Chronic kidney disease E102, E112, E132, E142, I120, N02-N08, N11, N12, N14, N18, N19, N26, N158-N160, N162-N164, N168, M300, M313, M319, M321B, Q612, Q613, Q615, Q619, T858, T859, Z992

Dementia F00-F03

Depression F31-34

ICD, International Classification of Diseases

Reviewer #1, comment no 3:

- page 11 “Diabetes mellitus, dementia and depression were additionally identified by at least one filled prescription for a disease-specific drug in the preceding 6 months.”

o Please provide an Appendix where details on which disease-specific drugs you used to define these co-morbidities.

An appendix with ATC codes has now been included.

Appendix 2. ATC classification codes

Pharmacotherapy ATC codes

Glucose lowering drugs

A10

Dementia N06D

Depression N06A

Antiplatelets

B01AC06, N02BA01, B01AC04, B01AC22, B01AC24, B01AC07

Lipid-lowering drugs

C10

Thiazides

C03A, C07B, C07D, C09XA52, C03EA01

Loop diuretics

C03C, C03EB01, C03EB02

Beta-blockers

C07, C09BX

Renin-angiotensin-system inhibitors

C09

ATC, Anatomical Therapeutic Chemical

Reviewer #1, comment no 4:

- page 11, “Ongoing use of medication was defined by at least one filled prescription of the drug in the preceding 6 months or 7 days after discharge but was not included in the adjusted Cox regression analyses.”

o Do you mean the variable reflecting filled prescription was not included in the model?

Thank for this comment. Yes, we chose not to include medication in our COX regression models. We believe that this is a very difficult issue as the information provided by medication use is complex. The information that a given medication is used indicates a need, but is also indicates ability to tolerate the medication and a clinical condition which has good compliance with medical advice.

Reviewer #1, comment no 5:

- Would be interesting to know how many patients in each cohort (HF/stroke/COPD/cancer) developed one of the other conditions of interest over the follow up period, and if development of additional conditions of interest affected risk of receiving domiciliary care or admission to nursing home. Patients at particularly high risk for needing receiving domiciliary care or admission to nursing home likely also have multimorbidity of these illnesses.

This is another very interesting question. However, this was the scope of this manuscript. The purpose of the manuscript was to provide the clinicians/physisians with risk estimates of nursing home admissions and need for domiciliary care when they sit in front of their patients and furthermore be able to put this risk into context with other chronic diseases.

Reviewer #1, comment no 6:

- The rate of nursing home admission in this study is surprisingly very low. In the US it is much more common (https://www.hcup-us.ahrq.gov/reports/statbriefs/sb205-Hospital-Discharge-Postacute-Care.jsp ). This may be because the differences in how domiciliary care and nursing home care is funded between the two countries. In the US, it is cheaper for insurance companies to pay for nursing home care rather than a home health aid 24/7. This doesn’t necessarily reflect patient or family preferences. It could also potentially provide an example of what utilization of these services might be if our healthcare/society in the US was different. I know you briefly mention that your findings may not be applicable to other countries, but might be interesting to discuss what might be learned from the differences.

This is a very good and important point which we have also mentioned in our limitation. We have now tried to elaborate on this point.

Changes made to the manuscript: Limitation section, (P 10, L12-15)

The main limitations are absence of certain clinical variables, such as HF severity; cancer type, stage and treatment; performance status, stroke score and pulmonary function tests which could help us identify the severity of the conditions of interest.

Reviewer #2, general comments

This is an interesting paper that describes the clinical management out of the hospital of patients affected by chronic diseases such as heart failure (HF), stroke, chronic obstructive pulmonary disease (COPD) and cancer.

Thank you.

Reviewer #2, comment no 1:

- It would be very interesting to evaluate the same outcomes in these two subgroups of patients: one of ‘’living alone’’ and other one ‘’supported by relatives’’. The family’s support could modify the necessity of domiciliary care initiation and nursing home admission.

The reviewer raises some very interesting points.

Living alone was included in all our model and shown to be a strong predictor of both the need for domiciliary care and nursinghome admissions. Further, there was no interaction between living alone and the respective chronic diseases.

Unfortunately, we don’t have data on support from relatives.

Reviewer #2, comment no 2:

- It would be very interesting a clinical evaluation of self-care autonomy of these patients at the baseline and during the follow-up, with the help of some specific scales such as ADLs or IADLs. If it is not applicable, please report it in the limitation.

We agree that information such as ADL could provide valuable extra information. Unfortunately we don’t have date on self-ca autonomy. We have now included this in the limitation section.

Changes made to the manuscript: Limitation section, (P 10, L19)

We did not have access to data on self-care autonomy such as activities of daily living

Reviewer #2, comment no 3:

- Further information about cancer disease of these patients are needed, such as the presence of metastasis, palliative or chemotherapy treatments. Moreover, at least NYHA class of the patients affected by HF should be reported, at the baseline and during follow-up.

We agree that information such as NYHA class, ejection fraction, performance status and other measures of disease severity could provide valuable information. Unfortunately, we don’t have information regarding this which we now have highlighted in the limitation section.

Changes made to the manuscript: Limitation section, (P 10, L 19-21)

Finally, our findings were based on the Danish healthcare and social systems and therefore may not be applicable to other countries.

Reviewer #2, comment no 4:

- Did any of these patients need re-hospitalization during follow-up?

This is another interesting question, which was not the scope of the manuscript.

Submitted filename: Itemised Response_Nursinhome_comorb_PlosONE_220521 (1).docx

Click here for additional data file.

15 Jul 2021

Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer

PONE-D-21-02090R1

Dear Dr. Rørth,

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,

Antonio Cannatà

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: All comments have been addressed

**********

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

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

Reviewer #1: Yes

**********

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

Reviewer #1: Yes

**********

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

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

Reviewer #1: 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: 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 do still think the discussion should be expanded as I recommended in comment 6. Otherwise, the authors' responses are adequate.

**********

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: Himali Weerahandi

26 Jul 2021

PONE-D-21-02090R1

Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer

Dear Dr. Rørth:

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. Antonio Cannatà

Academic Editor

PLOS ONE