Analysis of clinical outcomes in elderly patients with impaired swallowing function.

Japan is the world's leading aging society, and increasing medical expenses for elderly people is an urgent issue. Since aspiration pneumonia in elderly people with impaired swallowing function is a huge problem in Japan, their expected long-term clinical course should be clarified. Accordingly, we collected data from 991 elderly (≥75 years old) patients whose swallowing function was evaluated by Kitasato Institute Hospital's speech therapists (January 1, 2010 to December 31, 2017). We analyzed the relationship between swallowing function and the subjects' long-term prognosis. To clarify the prognostic factors of patients with dysphagia, we obtained their clinical information (age, gender, activities of daily living, nutritional status, availability of alternative feeding pathways such as percutaneous endoscopic gastrostomy, and cognitive function). We confirmed 372 death cases and stratified the cases into three groups using Fujishima's swallowing ability grade, which is used to predict elderly people's real-world life expectancy. Results showed the median survival days were 331 and 952 days in Groups I (Grades 1-3, n = 308) and II (Grades 4-6, n = 153), respectively, whereas the median survival days for Group III (Grades 7-10, n = 530) could not be calculated. We conducted a multivariate analysis using the Cox proportional hazards model with Group I, which revealed that initial grade and percutaneous endoscopic gastrostomy were significant prognostic factors for the subjects' long-term survival. Nevertheless, further discussion is necessary, particularly to determine advanced care planning regarding indications for alternative feeding pathways in elderly patients with severe dysphagia, since percutaneous endoscopic gastrostomy could significantly prolong their survival.

Introduction

According to the Statistics Bureau of the Japanese Ministry of Internal Affairs and Communications, Japan has a rapidly aging society, with increasing life expectancy and decreasing birth rates [1]. According to a 2017 report, the proportion of the population aged 65 years and over was 27.7% and that of the population aged 75 years and over was 13.8% [2]. In 2016, life expectancy at birth was 80.98 and 87.14 years for men and women, respectively [3]. As a result, medical expenses for the elderly are increasing rapidly [4]. In the 2017 fiscal year, the medical costs to treat later-stage elderly were 16.0 trillion yen, comprising 37.9% of the national medical care expenditure [5]. Since pneumonia is one of the most common causes of death in the elderly, it is a significant cause of the increase in medical expenditures for this population Pneumonia in the elderly has often been correlated with reduced cognitive function and impaired swallowing function [6]. Further, earlier studies have revealed that aspiration pneumonia is common in patients aged 70 years and older; in some studies, 306 among 382 pneumonia patients were diagnosed with aspiration pneumonia [7, 8].

Once pneumonia occurs in the elderly, both the patients and their family members encounter multiple problems, such as ethical issues pertaining to life-prolonging treatments and increase in financial burden [2, 9–11] For effective decision-making, patients and their families require clinical evidence to determine the expected long-term prognosis. However, to date, most studies have only focused on the short-term prognosis or the recurrence rate of readmission for pneumonia; alternatively, they have reported the long-term prognosis in a limited number of patients who have undergone a percutaneous alternative feeding pathway procedure [12]. In other words, these studies do not discuss the prognoses of patients who did not undergo procedures to prolong their lives; however, from an ethical perspective, it is impossible to conduct randomized trials to assess the effectiveness of life-prolonging treatments. Therefore, we collected detailed medical records to obtain real-world data for all the elderly patients who were assessed for the possibility of impaired swallowing function.

The Kitasato Institute Hospital was founded in 1893 and is located in central Tokyo; its location enabled us to collect long-term medical records of a large proportion of patients who were living in the neighborhood. Furthermore, since this hospital cooperates with nearby nursing homes, home doctors, clinics, and university hospitals, we could obtain long-term follow-up data.

The current study reveals the effectiveness of an initial swallowing ability test in assessing elderly patients’ expected life span. Furthermore, it reveals a strong correlation between the prognosis and the existence of alternative nutritional pathways in elderly patients with severe dysphagia. Since it focuses on elderly people with impaired swallowing function, the study is expected to help the patients themselves and their families make decisions on care planning by clarifying the expected clinical courses after being diagnosed with severe dysphagia.

Materials and methods

Data acquisition

We conducted an observational study of long-term prognoses. The study adhered to the following inclusion (exclusion) criteria: The participants were all aged ≥ 75 years at the time of the study, and their swallowing function had been evaluated by a speech therapist (ST) at Kitasato Institute Hospital from 2010 to 2017. The following clinical data were collected from medical records retrospectively, until December 31, 2018, based on earlier reports [6, 13–15]: age, gender, initial swallowing ability grade (Fujishima’s swallowing ability grade), residence before admission, activities of daily living (ADL), existence of an alternative feeding pathway such as percutaneous endoscopic gastrostomy (PEG) or a central venous (CV) port, cognitive function, existence of close relatives as key persons (whether relatives of the third-degree of kinship are involved), and survival outcome. We determined ADL status by retrospectively assessing patients’ medical records on their ability to stand on their own without assistance. Regarding cognitive functioning, the attending physician’s judgment (whether the patient had cognitive impairment) was obtained from medical records.

This study was approved by the Ethics Committee of Kitasato University’s School of Medicine (approval number #17071). In accordance with the requirements of our institutional review board, participants were not required to provide written consent and were included on an opt-out basis. Information on the study was provided on the research website, and the patients and their relatives could terminate their participation whenever they wanted to. The study was conducted as per the principles expressed in the Declaration of Helsinki.

Fujishima’s swallowing ability grade

At initial evaluation, we classified the cases into three groups according to their Fujishima’s swallowing ability grade [16, 17]. Swallowing ability was assessed by the ST once the attending doctor suspected a swallowing dysfunction and consulted the rehabilitation department (Table 1). In this study, we focused on the initial evaluation of swallowing function during the study period, though some of the patients’ swallowing function was repeatedly evaluated. In the hospital, swallowing function was evaluated by one of two well-trained STs who shared information with each other. They made their evaluation of Fujishima’s swallowing ability grade by combining the results of several tests and observations.

Table 1

Fujishima’s swallowing ability grade and corresponding number of cases.

Grade	Method of Nutrition (n)	Groups
1	No therapy indication (n = 27)	I Severe dysphagia(n = 308)
2	Indirect therapy (n = 105)
3	Direct and indirect therapy (n = 176)
4	Minimal intakes for oral satisfaction (n = 32)	II Moderate dysphagia(n = 153)
5	Meals, once or twice a day (n = 36)
6	Meals, three times a day with alternative feeding (n = 85)
7	Dysphagia diet (n = 243)	III Mild dysphagia+Normal(n = 530)
8	Easy chewable diet (n = 154)
9	Normal food with observation (n = 73)
10	Normal swallowing ability (n = 60)

Statistical analyses

In this study, statistical analyses were performed using Prism version 8 for Mac (GraphPad Software, San Diego) and SPSS 19.0 for Mac (IBM SPSS Statistics, Chicago). Each group’s survival time was plotted as a Kaplan-Meier survival curve, and the groups’ survival times were compared using the log-rank test. The effects of several variables on survival time were investigated using Cox proportional hazards regression analysis. Serum albumin levels were compared using Student’s t-test. The significance level was determined as a p-value < 0.05.

Results

Overall impact of Fujishima’s swallowing ability grade on the elderly

Table 2 summarizes the baseline characteristics of patients. We confirmed 372 death cases among the 991 patients who had been evaluated for swallowing function by an ST in our hospital. We classified the cases into three groups according to the subjects’ Fujishima’s swallowing ability grades at the initial evaluation during the study period: Group I (Grades 1–3, severe dysphagia) with 308 people, Group II (Grades 4–6, moderate dysphagia) with 153 people, and Group III (Grades 7–10, mild dysphagia and normal) with 530 people (Table 2). By using the Kaplan-Meier method, we calculated the median survival days from initial evaluation to death of the cases in each group, which were 331 and 952 days for Groups I and II, respectively. Group III did not reach valid median survival values (Fig 1). Follow-up periods of patients who survived did not differ much among the groups, with an average of 518 days for Group I, 416 days for Group II, and 595 days for Group III. Further, as expected, the prognosis of Group I was worse than the prognoses of Groups II and III.

Table 2

Baseline characteristics of all patients evaluated for their swallowing ability by a speech therapist.

Variables	Numbers
Age at initial evaluation	75–103 years (mean 87.18)
Gender (M/F)	409/582
Fujishima’s grade at initial evaluation (Group I/II/III)	308/153/530
Median number of observation days (range)	Group I	129 (1–2297)
	Group II	110 (1–2345)
	Group III	317 (2–2364)
Median (average) number of observation days of patients who survived	Group I	215 (518)
	Group II	221 (416)
	Group III	382 (595)
Outcome (alive/dead)	619/372

Fig 1

Kaplan-Meier survival curve of all patients in this study.

Each point indicates days between initial evaluation and death in the death cases. All cases were divided into three groups according to the patients’ initial swallowing ability (*p < 0.05, ***p < 0.001). HR, hazard ratio; CI, confidence interval.

Characteristics of elderly patients with severe dysphagia

After obtaining the results of initial analysis, we focused on Group I to elucidate the prognostic factors of elderly patients with severe dysphagia since there were fewer deaths in Groups II and III. Table 3 summarizes the detailed clinical information collected from these patients. Further, we selected the following features as prognostic factors based on earlier reports [6, 13–15]: age, gender, initial swallowing ability grade (Fujishima’s swallowing ability grade), residence before admission, ADL, nutritional status (serum albumin), existence of an alternative feeding pathway such as PEG or a CV port, cognitive function, existence of close relatives as key persons, and survival outcome. Since multiple causes of dysphagia such as senility, dementia, and cerebrovascular disease simultaneously exist in some patients, it makes it difficult to collect this information unambiguously. Among the patients with severe dysphagia (n = 308), the mean age was 87.2 years, and 264 patients were considered cognitively impaired.

Table 3

Detailed clinical information of patients in Group I.

Variables	Numbers
Age at initial evaluation	75–103 years (mean 87.2)
	Grade 1 mean 80.8, median 84
	Grade 2 mean 84.9, median 86
	Grade 3 mean 85.7, median 86.5
Gender (M/F)	132/176
Initial Fujishima’s swallowing ability grade (1/2/3)	27/105/176
Residence before admission (nursing home/home)	194/114
Activities of daily living (not able to stand/able to keep standing with assistance)	202/106
Percutaneous endoscopic gastrostomy (yes/no)	65/243
Central venous port (yes/no)	19/289
Impaired cognitive function (yes/no)	244/64
Key persons are close relatives (yes/no)	290/18
Outcome (alive/dead)	110/198

Initial Fujishima’s swallowing ability grade and existence of PEG as significant prognostic factors in elderly patients with severe dysphagia

We performed multivariate analysis using the Cox proportional hazards model to determine the predictors of prognoses among the collected clinical information. Among the results, PEG and the initial Fujishima’s swallowing ability grade were identified as significant predictive markers for the prognosis (Table 4, Fig 2A and 2B). There were no other significant prognostic factors in our analysis, which suggests the utility of the swallowing ability function test in predicting the prognosis of elderly patients with severe dysphagia. Interestingly, Fujishima’s swallowing ability grade had significant efficiency in predicting the patients’ prognosis independently of the existence of an alternative feeding pathway.

Table 4

Results of the Cox regression analysis in Group I patients.

Variables	Partial regression coefficient	p-value	Hazard ratio (HR)	95% CI for HR
				Lower	Upper
Grade 1	0.89	0.001	2.431	1.448	4.083
Grade 2	0.48	0.003	1.619	1.179	2.222
PEG (-)	0.67	0.001	1.962	1.325	2.907

CI, confidence interval.

Fig 2

Group I patients’ survival curves classified by significant prognostic factors identified by Cox regression analysis.

(A) Patients were initially classified using Fujishima’s swallowing ability grade (*p < 0.05). (B) Patients were classified by the existence of PEG (**p < 0.01). PEG, percutaneous endoscopic gastrostomy.

The variables included in this analysis are as follows: age at initial evaluation, gender (male or female), initial Fujishima’s swallowing ability grade (Grade 3 vs Grade 1 or 2), residence before admission (nursing home or community living), ADL (yes or no), impaired cognitive function (yes or no), existence of percutaneous endoscopic gastrostomy (PEG; yes or no), existence of central venous port (yes or no), having key persons of close relatives (yes or no).

Significant impact of PEG on survival in Grade 1 and 2 patients

We performed a univariate analysis using the Kaplan-Meier method and correlated PEG with the prognosis alone in patients with initial swallowing ability Grades 1 and 2 (Fig 3A and 3B). We could not find any survival benefit of PEG in patients with Grade 3 swallowing ability, which suggests that PEG is necessary for only those patients with very severe dysphagia (Fig 3C). In contrast to the significant life-prolonging effect of PEG in patients with severe dysphagia, a CV port failed to improve the prognosis in our analysis regardless of the existence of PEG (Fig 3D and 3E). Based on the data we could collect, patients with a CV port had poorer nutritional status than did patients without a CV port (serum albumin level was 2.48 [with CV port] vs. 2.88 [without CV port]) (Fig 4). In addition, the initial swallowing grade was strongly correlated with the prognosis, particularly in patients without any alternative feeding pathway (PEG or a CV port) (Fig 5A and 5B).

Fig 3

Assessment of the survival benefit of an alternative feeding pathway (PEG or CV port).

(A), (B), and (C) Survival curves of patients in each initial grade. (D) and (E) Survival curves of patients with or without PEG. PEG, percutaneous endoscopic gastronomy; CV port, central venous port.

Fig 4

Correlation of nutritional status (serum albumin concentration) in patients with central venous port.

Serum albumin level of patients with or without central venous port (CV port). Student’s t-test was performed. *p < 0.05 for patients with CV port (n = 9) versus patients without CV port (n = 142).

Fig 5

Initial grade did not predict the prognosis of patients with an alternative feeding pathway.

(A) and (B) Survival curves of patients with or without PEG. Patients were classified into three groups according to their initial grade. PEG, percutaneous endoscopic gastronomy.

Discussion

The number of deaths from pneumonia has been increasing in Japan because of the increase in proportion and number of elderly people among the nation’s population. In most of the elderly patients with pneumonia, swallowing function is impaired and, hence, should be evaluated [2, 8]. Based on our findings, Fujishima’s swallowing ability grade helps predict the prognosis of elderly patients. We have shown that PEG significantly extended life expectancy in patients with very severe dysphagia alone. This observation is consistent with recent reports from Japan [12, 18] but inconsistent with earlier reports from other countries [19, 20]. The discrepancy regarding PEG’s utility in elderly patients between the findings of a recent Japanese paper and old reports from other countries can be explained by differences in the patients’ background characteristics, health insurance system, or use of sophisticated medical devices [12, 13, 18]. In general, the elderly do not prioritize prolonging their life over ensuring the quality of their life [21-23].

On the other hand, we did not find any survival advantage for the use of a CV port. This is probably because the general condition of patients requiring a CV port is severe. Hence, we should carefully select candidates requiring a CV port with thorough informed consent. Since PEG can improve the prognosis in elderly patients with severe dysphagia, we need to decide the indications for these patients, since euthanasia is not allowed in Japan and, once a life-prolonging device is started, it is very difficult to stop using it. Since most patients with severe dysphagia cannot decide on their medical procedures by themselves because of their decreased cognitive function, their families must face this decision and select appropriate procedures. This issue involves not only a medical problem but also ethical and social problems [24].

It is easy to speculate that lower nutrition levels in patients without oral intake may reduce their survival time. However, no previous study has clearly reported on the limitation of parenteral nutrition, which may increase family’s excessive expectation for the survival of the patient. It is often difficult for patients’ family or relatives to understand the connection between impaired swallowing function and their survival rate of elderly people. Although previous literature has suggested the utility of percutaneous endoscopic gastrostomy, our study revealed there is a limit, as we could not find any difference in prognosis in Grade 3 patients. Importantly, patients with severe dysphagia will die in a very short time if they are given only peripheral venous nutrition rather than a central venous port. Thus, our data may facilitate better decision-making by family members or close relatives in clinical settings. Furthermore, previous studies have suggested the utility of PEG, but our study revealed there might be a threshold, as we could not find any difference in the prognosis of Grade 3 patients.

The current study has certain limitations, since it was a retrospective study and all the patients’ data were obtained from a single institute. Previously, in our institution, one well-trained ST alone had been assessing the swallowing function for all patients since 2008. Since 2010, another ST collaborated with him to evaluate patients. Because the first ST mentored the second one, their evaluation criteria were similar. Thus, we need to consider the limitation of lack of inter-individual reproducibility.

However, issues surrounding an individual’s end of life are very sensitive and cannot be clarified by interventional trials. We successfully collected long-term follow-up data, since this study involved a hospital based in the study area. Despite these limitations, our study is expected to benefit clinical settings and, particularly, individuals involved in the terminal care of elderly people.

26 May 2020

PONE-D-20-09840

Analysis of clinical outcomes in elderly patients with impaired swallowing function

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Reviewer #1: The study entitled "Analysis of clinical outcomes in elderly patients with impaired swallowing function" is basically well written. However, some methodology information and some results presentations are unclear. Please see my comments below to improve the study.

1. The authors mentioned that they used the data from patients who had been estimated for their swallowing function between 2010 and 2017 to analyze survival hazard. However, it is unclear that when was the end of the present study. That is, when did the authors not follow up the survival status of the patients? If possible, I would also like to know, how many patients were lost to follow-up in the survival status. This is important information because the authors conducted survival analyses.

2. The authors have included several factors in the Cox model. However, the authors only describe how they measured swallow functioning. Some factors may not need to be described (e.g., age and gender). However, some factors need to be introduced because it is hard to know what information was obtained if the authors do not provide such information. For example, what instrument was used for the activities of daily living? Is it Barthel Index? How did the authors assess the cognitive function? There are so many different instruments on cognitive function, especially cognitive function included different aspects (e.g., memory, attention, executive function). Also, who did the assessments on ADL and cognitive function.

3. Although the authors introduced that Fujishima’s swallowing ability grade was used for swallow functions, the authors did not provide detailed information of it. Specifically, what is the psychometric properties of this measure?

4. Following the comment #3, the authors should notify the readers whether the speech therapists have been trained for assessing Fujishima's swallowing ability grade. Also, a limitation should be added if the authors have not information on the inter-rater reliability of the Fujishima's swallowing ability grade in their speech therapists. I assume that there were several speech therapists involved in this study because it is hard to believe that over 7 years, all the patients had their swallowing function assessed by the same therapist. However, I may be wrong and the authors need to explicitly mentioned that there was only one speech therapist in the Methods section if it is real condition.

5. I would recommend moving all the supplementary materials into the main text because to my understanding, Plos One does not have limitations in the number of figures and tables. This will allow potential readers to directly link the text information to figures/tables.

6. The presentation of Table S1 is somewhat mess. Specifically, the title of Grade and its following information are not aligned; the Group III (Mild dysphagia + mild) is not aligned with Groups I and II.

7. From the main text, I understand that Table S2 is presenting a multivariable Cox model. However, the authors only reported significant variables here. Please provide the information of all the included factors in Table S2. Additionally, please explicitly indicate the Grade 3 is the reference group of Grades 1 and 2.

Reviewer #2: This is an interesting and critical study exploring the prognostic factors in severe patients with dysphagia. Authors recruited 991 elderly patients and divided into three groups based on Fujishima’s swallowing ability grade. They investigated the relationship between clinical information and survival days. They described that the prognosis of patients with severe dysphagia was worse than the prognoses of others (moderate or mild dysphagia or normal). Further analysis revealed that Fujishima’s swallowing ability grade and PEG were significant prognostic factors for the long-term survival in severe patients with dysphagia. The concept is very clear and the analysis is appropriate. However, the new findings are very limited and there are several problems in methods, as indicated below.

General comments:

The new findings in the present study are very limited. It is not surprised that the patients with severe dysphagia which represents without oral intake with Fujishima’s grade had longer survival period than the other patients with moderate and mild dysphagia with oral intake. It is easy to imagine lower nutrition level in patients without oral intake than those with oral intake and this is important for survival time, unfortunately authors did not evaluate nutritional status. Previous literatures also suggested that PEG is useful to extend life expectancy. What is the new suggestion in this study compared with previous literatures? I felt the benefits of this study were very few.

This study emphasizes the importance of Fujishima’s swallowing ability grade for the long-term prognosis in patients with dysphagia. I am concerned that the reliability of the assessment of Fujishima’s swallowing ability grade. How to evaluate swallowing function and how to decide the grade? Did authors confirm the reliability of the grade in the present study? Although they described one speech therapist evaluated swallowing function, is this right? I felt this hospital might be not small. If some therapists evaluated swallowing function, the inter-individual reproducibility must be tested.

Authors speculated that the general condition of patients requiring a CV port was severe.

I recommend that they should evaluate subject’s nutritional status.

Why did authors focus on patients with severe dysphagia in the second analysis? How about moderate dysphagia?

Specific comments:

“dysphagic patients” should be replaced with “patients with dysphagia”.

“dysphasia” should be replaced with “dysphagia”.

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30 Jun 2020

PONE-D-20-09840R

Analysis of clinical outcomes in elderly patients with impaired swallowing function

We thank the reviewers for their thoughtful review and interest in our work. Their comments were incredibly insightful and helpful, and we feel that addressing the reviewer’s concerns has significantly strengthened the quality of the manuscript.

Our point-by-point response is as follows:

Reviewer #1: The study entitled "Analysis of clinical outcomes in elderly patients with impaired swallowing function" is basically well written. However, some methodology information and some results presentations are unclear. Please see my comments below to improve the study.

Thank you very much for your positive comment.

1. The authors mentioned that they used the data from patients who had been estimated for their swallowing function between 2010 and 2017 to analyze survival hazard. However, it is unclear that when was the end of the present study. That is, when did the authors not follow up the survival status of the patients? If possible, I would also like to know, how many patients were lost to follow-up in the survival status. This is important information because the authors conducted survival analyses.

We completely agree with the reviewer. We collected data until December 31, 2018. The median follow-up time of patients who survived was 215 days for Group I, 221 days for Group II, and 382 days for Group III. Similarly, the average follow-up period of patients who survived was 518 days for Group I, 416 days for Group II, and 595 days for Group III. We included these numbers in Table 2. The median follow-up period was shorter for Group I, but we do not think this shorter observation period is the reason for the shorter survival time in Group I since longer observation period usually results in lower survival ratio.

2. The authors have included several factors in the Cox model. However, the authors only describe how they measured swallow functioning. Some factors may not need to be described (e.g., age and gender). However, some factors need to be introduced because it is hard to know what information was obtained if the authors do not provide such information. For example, what instrument was used for the activities of daily living? Is it Barthel Index? How did the authors assess the cognitive function? There are so many different instruments on cognitive function, especially cognitive function included different aspects (e.g., memory, attention, executive function). Also, who did the assessments on ADL and cognitive function.

We appreciate this important suggestion by the reviewer. Since we retrospectively collected data from medical records, we could hardly obtain precise data on dementia using questionnaires or physical fitness examination for ADLs. Thus, we evaluated ADL according to whether patients could stand without assistance; we determined that a patient had impaired cognitive function by referring to medical records made by the doctor in charge of assessing cognitive function regardless of the method used. Moreover, we collected serum albumin data to assess patients’ nutritional status, although not all the patients were tested for serum albumin.

3. Although the authors introduced that Fujishima’s swallowing ability grade was used for swallow functions, the authors did not provide detailed information of it. Specifically, what is the psychometric properties of this measure?

We used Fujishima’s swallowing ability grade, since it is the most commonly-used scale in clinical settings in Japan. Another grading scale that is widely used in Japan, the Food Intake LEVEL Scale, has almost the same assessment items, and its reliability and validity have been evaluated. The latter is designed for practical use and does not need fluoroscopy or endoscopy for evaluation. We, however, adopted Fujishima’s swallowing ability grade, because it evaluates the ‘ability’ of patients, which seems more appropriate to our study that focuses on the survival period. For our study, two well-trained speech therapists evaluated Fujishima’s swallowing ability using multiple measurements including vocal status, patient posture, oral conditions, results of the modified water swallowing test, and videofluorography or videoendoscopic examination of swallowing. We have added this explanation in the revised manuscript (page 7, lines 125-128).

4. Following the comment #3, the authors should notify the readers whether the speech therapists have been trained for assessing Fujishima's swallowing ability grade. Also, a limitation should be added if the authors have not information on the inter-rater reliability of the Fujishima's swallowing ability grade in their speech therapists. I assume that there were several speech therapists involved in this study because it is hard to believe that over 7 years, all the patients had their swallowing function assessed by the same therapist. However, I may be wrong and the authors need to explicitly mentioned that there was only one speech therapist in the Methods section if it is real condition.

We agree with the reviewer. In our institution, originally, only one well-trained speech therapist began to assess the swallowing function for all patients in 2008. Since 2010, another speech therapist collaborated with him. Because the first speech therapist mentored the second therapist, their evaluation criteria were similar.

5. I would recommend moving all the supplementary materials into the main text because to my understanding, Plos One does not have limitations in the number of figures and tables. This will allow potential readers to directly link the text information to figures/tables.

We agree with the reviewer’s suggestion. We have added all supplementary information to the main text.

6. The presentation of Table S1 is somewhat mess. Specifically, the title of Grade and its following information are not aligned; the Group III (Mild dysphagia + mild) is not aligned with Groups I and II.

Thank you for your comment. We have corrected these errors.

7. From the main text, I understand that Table S2 is presenting a multivariable Cox model. However, the authors only reported significant variables here. Please provide the information of all the included factors in Table S2. Additionally, please explicitly indicate the Grade 3 is the reference group of Grades 1 and 2.

Thank you so much for the comment. We have added all the variables tested to the legend of Table 4. Additionally, we clarified that Grade 3 was used as a reference in the analysis in Table 4.

Reviewer #2: This is an interesting and critical study exploring the prognostic factors in severe patients with dysphagia. Authors recruited 991 elderly patients and divided into three groups based on Fujishima’s swallowing ability grade. They investigated the relationship between clinical information and survival days. They described that the prognosis of patients with severe dysphagia was worse than the prognoses of others (moderate or mild dysphagia or normal). Further analysis revealed that Fujishima’s swallowing ability grade and PEG were significant prognostic factors for the long-term survival in severe patients with dysphagia. The concept is very clear and the analysis is appropriate. However, the new findings are very limited and there are several problems in methods, as indicated below.

Thank you for your positive comments.

General comments:

The new findings in the present study are very limited. It is not surprised that the patients with severe dysphagia which represents without oral intake with Fujishima’s grade had longer survival period than the other patients with moderate and mild dysphagia with oral intake. It is easy to imagine lower nutrition level in patients without oral intake than those with oral intake and this is important for survival time, unfortunately authors did not evaluate nutritional status. Previous literatures also suggested that PEG is useful to extend life expectancy. What is the new suggestion in this study compared with previous literatures? I felt the benefits of this study were very few.

Thank you for your comments. We agree that it is easy to imagine lower nutrition levels in patients without oral intake matters in terms of survival time. We have added this issue to the revised manuscript (page 14, lines 268-271). However, no previous study has presented clinical data to support this idea, and sometimes it is difficult for patients’ relatives to correctly understand the connection between elderly people’s survival rate and impaired swallowing function. Importantly, patients with severe dysphagia would die in a very short time even if they were given a peripheral IV or a central venous port. Thus, our data can help decision-making by relatives in clinical settings. Furthermore, previous literature has suggested the utility of percutaneous endoscopic gastrostomy, but our study revealed there may be a threshold, as we could not find any difference in prognosis in Grade 3 patients.

This study emphasizes the importance of Fujishima’s swallowing ability grade for the long-term prognosis in patients with dysphagia. I am concerned that the reliability of the assessment of Fujishima’s swallowing ability grade. How to evaluate swallowing function and how to decide the grade? Did authors confirm the reliability of the grade in the present study? Although they described one speech therapist evaluated swallowing function, is this right? I felt this hospital might be not small. If some therapists evaluated swallowing function, the inter-individual reproducibility must be tested.

We agree with the reviewer. We used Fujishima’s swallowing ability grade as it is very commonly used in clinical settings in Japan; however, even though it is common, it has not been published frequently in international journals. For our study, Fujishima’s swallowing function was evaluated by well-trained speech therapists. These therapists usually evaluate Fujishima’s swallowing ability with multiple measurements including vocal status, patient posture, oral conditions, results of the modified water swallowing test, and videofluorography or videoendoscopic examination of swallowing. We have added this explanation to the modified manuscript (page 8, lines 125-128). Further, in our institution, originally, only one well-trained speech therapist began to assess the swallowing function for all patients nine years ago. During the last three years, another speech therapist collaborated with him to evaluate patients. Because the first speech therapist mentored the second one, their evaluation criteria were similar. We discussed this point in the limitations section of this study (page 15, lines 282-288).

Authors speculated that the general condition of patients requiring a CV port was severe.

I recommend that they should evaluate subject’s nutritional status.

We agree with the reviewer’s suggestion. Although there are multiple parameters for nutrition, it is not easy to evaluate nutritional status in a retrospective observational study. We analyzed the relationship between serum albumin and CV port, as it was the only available retrospective data for nutritional status. We found serum albumin levels of 2.48 for patients with a CV port (n = 9) and 2.88 for those without (n = 142), which was added to the result section (page 12, lines 219-221) and Figure 4 in the revised manuscript.

Why did authors focus on patients with severe dysphagia in the second analysis? How about moderate dysphagia?

We did not find that very many patients with moderate dysphagia had died. So, we considered it difficult to analyze the prognosis of patients with moderate dysphagia.

Specific comments:

“dysphagic patients” should be replaced with “patients with dysphagia”.

“dysphasia” should be replaced with “dysphagia”.

Thank you so much for your comment. We have corrected these.

Review comments, Reviewer 3:

L. 99~:

This paragraph is quite a few of lacking information in your subjects. I think you should add or rewrite more detail of the subjects' information, such as how Fujishima swallowing ability grade criteria were checked? Who did the exams it, an ST, or some STs? When did you check it? The checking was once and never, or sometimes like every month? And you should put the list of subjects' underlying disease. Generally, the survival days reflects the severity of the underlying disease. And also depending on the cause of the dysphagia, the dysphagia may recover (for example, sequela of cerebral infarction) or may not (for example, neuromuscular disease). It makes no sense to observe only life expectancy without distinguishing the underlying disease. And you only mentioned the age of the subjects "over 75". You should show the age distribution of every group. If subjects were too old at the start point, they could die just even with aging. The details of the cause of death and the breakdown should be shown.

Thank you for your comment. We have collected detailed information of the causes of death and underlying diseases of the patients included in the study. First, we did not have a large number of patients who had died in Groups II and III as compared with Group I. Thus, we only focused on Group I to analyze survival time. Second, elderly people normally have multiple complications, so it is quite difficult to stratify them according to the complications. By reviewing the information from the patients’ medical records, we found that the top three medical conditions for the physician to order evaluation of swallowing function were pneumonia, loss of appetite, and acute-subacute cerebral nerves system disorder. Even patients died because of aging might be determined to have died from such diseases. We also found that the same patient often had multiple reasons simultaneously for the speech therapist consultation. We focused on the initial evaluation of swallowing function because we aimed at providing useful data to informed consent on hospital admission. Specifically, patients’ families sometimes have to decide if percutaneous endoscopic gastrostomy should be performed, and our study can be used as a reference.

L. 132~:

Although there are supplementary materials, I cannot find Tables 1 and 2.

We apologize for this omission. We have added and modified the manuscript accordingly.

L.185~:

Why your hospital put PEG the patients who were classified grade 3? It seems a bit strange because grade 3 means the patients who has almost enough ability to swallowing.

Thank you for your comment. Patients with Grade 3 cannot start oral intake and just can be trained by food. Even patients with Grade 4 can easy-to swallow food less than the quantity of a meal (enjoyment level) is injested orally. Again, patients with Grade 3 cannot eat enough food; thus, alternative feeding pathway should be considered.

Case Number: 06648983

ref:_00DU0Ifis._5004P1ABcBd:ref

Submitted filename: PLOS_one_rebuttal_20200630.docx

Click here for additional data file.

4 Aug 2020

PONE-D-20-09840R1

Analysis of clinical outcomes in elderly patients with impaired swallowing function

PLOS ONE

Dear Dr. terai,

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

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Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Some minor questions are found in the revised manuscript. I prefer to recommend a minor revision.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: All comments have been addressed

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Reviewer #3: All comments have been addressed

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: The authors have satisfactorily responded to the previous comments made by both reviewers. I am comfortable to recommend publication for the present form.

Reviewer #2: The authors responded to all reviewer comments.

I am happy to recommend this paper for publication.

Reviewer #3:

Thank you for correcting the manuscript. The manuscript is very readable and useful. However, the reviewer has still some concerns.

L50 The speech therapist (ST) is common in Japan, but the speech language pathologist (SLP) is common in other countries. Please confirm the title.

L104 Were there any participants who constructed PEG or CV during the observation?

L122 The reviewer is still concerning what was the cause of dysphagia in this population. The prognosis of the disease (whether it is a progressive disease or not) is an important indicator for PEG construction. Information about the approximate cause of dysphagia of this population should be provided to the reader.

L145 The number of deaths is 373 in the text, but it is 372 in Table 1. The number of Grade I people is 308 in the text and Table 1, but in Figure 1 it is 309.

Table 4 "impaired cognitive function" is written twice in the legend.

**********

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Reviewer #3: No

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19 Aug 2020

PONE-D-20-09840R

Analysis of clinical outcomes in elderly patients with impaired swallowing function

We thank Reviewers #1 and #2 for recommending our paper for publication. We also appreciate Reviewer #3’s thoughtful feedback, which helped us enrich the quality of our manuscript.

Our point-by-point response is as follows:

Reviewer #1: The authors have satisfactorily responded to the previous comments made by both reviewers. I am comfortable to recommend publication for the present form.

We thank the reviewer for their positive comment and careful review, which helped improve the manuscript.

Reviewer #2: The authors responded to all reviewer comments. I am happy to recommend this paper for publication.

We thank the reviewer for their positive comment and careful review, which helped improve the manuscript.

Reviewer #3:

1. L50 The speech therapist (ST) is common in Japan, but the speech language pathologist (SLP) is common in other countries. Please confirm the title.

All speech therapists in Japan have passed the National License Examination for Speech-Language-Hearing Therapists. It is the only national certificate which officially prove the skill to engage in speech therapy in Japan and translated in English as ‘speech therapist’. We described the title of the therapists as ‘speech therapist’ because they possess the Japanese license which is not officially translated as ‘speech language pathologist’.

2. L104 Were there any participants who constructed PEG or CV during the observation?

Survival time of patients with PEG might be elongated by patients whose PEG was made during the observation, which suggests better health condition that did not need immediate construction of a parenteral route. Most of the patients with PEG or CV were made the parenteral nutritional route soon after their initial evaluation. Only five patients with severe dysphagia were constructed PEG 100 days or more after the initial evaluation. We analyzed survival time again after excluding those patients. The results of the analysis were the same (log-rank test: p < 0.05). Thus, we wish to retain the original analyses unchanged because the definition of ‘during the observation’ is not always clear.

3. L122 The reviewer is still concerning what was the cause of dysphagia in this population. The prognosis of the disease (whether it is a progressive disease or not) is an important indicator for PEG construction. Information about the approximate cause of dysphagia of this population should be provided to the reader.

We previously tried to divide patients by the causal disease of dysphagia such as brain infarction and by looking up the relevant ICD-10 codes. There were 801 pneumonia-related codes and 619 brain-related codes in the 912 patients. Then, we realized that a single patient often had multiple diseases, which made it difficult to presume the cause of dysphagia. Simple aging might not even be on the list of disease codes. Consequently, we focused on the direct relationship between swallowing function and survival time. For additional clarity, we added the following to the revised manuscript (page 10, lines 183-7 in the revised manuscript): “Since multiple causes of dysphagia such as senility, dementia, and cerebrovascular disease simultaneously exist in some patients, it makes it difficult to collect this information unambiguously. Among the patients with severe dysphagia (n = 308), the mean age was 87.2 years, and 264 patients were considered cognitively impaired.”

4. L145 The number of deaths is 373 in the text, but it is 372 in Table 1. The number of Grade I people is 308 in the text and Table 1, but in Figure 1 it is 309.

Thank you for your comment. We revised these errors.

5. Table 4 "impaired cognitive function" is written twice in the legend.

Thank you for your comment. We corrected this error.

Submitted filename: Response to Reviewers 20200819.docx

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7 Sep 2020

Analysis of clinical outcomes in elderly patients with impaired swallowing function

PONE-D-20-09840R2

Dear Dr. terai,

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Jason Chia-Hsun Hsieh, M.D. Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All the questions were answered adequately.

Reviewers' comments:

10 Sep 2020

PONE-D-20-09840R2

Analysis of clinical outcomes in elderly patients with impaired swallowing function

Dear Dr. terai:

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