Association of Cachexia with Activities of Daily Living and Discharge Destinations among Inpatients with Dysphagia undergoing Convalescent Rehabilitation: A Multicenter Cohort Study
Article information
Abstract
Background
Although a recent study reported an association between cachexia, as defined by the Asian Working Group for Cachexia (AWGC), and lower functional recovery at discharge among post-stroke patients capable of oral intake during the convalescent rehabilitation phase, its impact on functional recovery in patients with dysphagia remains unclear. This study aimed to evaluate the association between cachexia, according to AWGC criteria, and both functional status and discharge destinations among inpatients with dysphagia.
Methods
This prospective cohort study enrolled 198 inpatients with dysphagia from eight convalescent rehabilitation hospitals. Cachexia was defined using the AWGC criteria at baseline. The primary outcome was the total Functional Independence Measure (FIM) at discharge, while the secondary outcomes were the Food Intake LEVEL Scale (FILS) score and discharge destinations. We applied generalized linear models to evaluate the association between cachexia and total FIM score at discharge, adjusting for age, sex, baseline FILS score, comorbidities, and use of enteral nutrition.
Results
Of 198 patients, the median age was 83.0 years (interquartile range, 77.0–88.0); 111 (56.1%) were women, and 33 (16.7%) had cachexia. After adjusting for covariates, cachexia was not significantly associated with total FIM score at discharge (β=0.03, 95% confidence interval [CI] -0.10 to 0.15, p=0.66), FILS (β=0.23, 95% CI -0.53 to 1.00, p=0.55), or discharge destinations including discharge to home (β=0.25, 95% CI -0.75 to 1.35, p=0.63).
Conclusion
Cachexia, as defined by the AWGC, was not significantly associated with either functional status at discharge or discharge destinations among inpatients with dysphagia undergoing convalescent rehabilitation.
INTRODUCTION
Cachexia is a serious yet under-recognized condition that is widespread globally.1,2) It is a complex metabolic syndrome characterized by muscle loss, with or without fat loss, typically associated with chronic diseases. This leads to fatigue, functional impairment, increased treatment toxicity, reduced quality of life (QOL), and lower survival rates.3,4) Cachexia affects approximately 1% of the general population; however, its prevalence increases significantly among patients with chronic diseases (3%–66%) and those with cancer (6%–93%), contributing to an estimated two million deaths annually, based on data from Europe, the USA, and Japan.5-7) However, cachexia often remains underrecognized by healthcare professionals.8-10) Early detection is therefore essential, as it may help maintain physical function, independence, and QOL in older adults, while also reducing the caregiving burden on families.4,11)
Dysphagia is also a serious health issue in older adults, affecting both the risk of aspiration pneumonia and overall QOL.12,13) It is a disorder resulting from disuse of the muscles involved in swallowing or from central nervous system impairment.12) The prevalence of dysphagia varies by setting, with rates ranging from 11%–34% among community-dwelling older adults and from 29%–47% among inpatients.13) Dysphagia is associated with several adverse outcomes, including aspiration pneumonia, dehydration, reduced functional performance, and diminished QOL.12,13) Therefore, developing effective management strategies for dysphagia in rehabilitation settings is essential for improving patient safety and functional outcomes.
Previous studies have reported inconsistent findings regarding the association between cachexia and functional recovery. A multicenter cohort study in Japan reported that neither malnutrition nor cachexia, as defined by the Asian Working Group for Cachexia (AWGC) criteria, was significantly associated with improvements in the Barthel Index at discharge among inpatients with sarcopenic dysphagia.14) In addition, a cohort study at a university hospital in Germany reported no significant differences in baseline Barthel Index scores between older inpatients with and without cachexia, as defined by the criteria of Evans, Fearon, and Bozzetti; however, follow-up functional status was not reported.15) Moreover, another cohort study from an inpatient rehabilitation facility in the United States found that gains in motor and cognitive Functional Independent Measure (FIM) scores were comparable between patients with and without cachexia (defined by Fearon’s criteria) among individuals with cancer.16) However, these studies had notable limitations. They focused on patients with cancer across various rehabilitation settings or examined those with sarcopenic dysphagia spanning both acute and rehabilitation phases, while also using different diagnostic criteria for cachexia. More recently, a recent study reported an association between AWGC-defined cachexia and reduced functional recovery at discharge among post-stroke patients capable of oral intake during the convalescent rehabilitation phase.17) Nevertheless, the impact of cachexia on functional recovery in patients with dysphagia remains unclear, highlighting a critical evidence gap. Furthermore, cachexia may directly impact key determinants of discharge outcomes. Patients with dysphagia often exhibit increased vulnerability and features of cachexia, making them a crucial population for studying cachexia-related outcomes in rehabilitation settings. Clarifying the relationship between cachexia, functional recovery, and discharge destination may provide a better understanding of the factors influencing rehabilitation outcomes in Asian populations and identify potential targets for multidisciplinary intervention.
Therefore, the present study aimed to evaluate the association between cachexia, as defined by the AWGC, and both functional status and discharge destination among inpatients with dysphagia in rehabilitation hospitals. We hypothesized that cachexia would be significantly associated with functional status at discharge and discharge destinations.
MATERIALS AND METHODS
Study Design
We conducted a secondary analysis of data from a prospective cohort study to evaluate the association between cachexia, as defined by the AWGC criteria, and outcomes among inpatients aged ≥20 years with dysphagia in eight convalescent rehabilitation hospitals. This study was conducted in accordance with the Declaration of Helsinki, was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038281), and was approved by the Institutional Review Board of Yokohama City University Medical Center (B190700074). This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. All participants provided written informed consent before enrollment or were given the right to refuse participation using an opt-out form.
Data Source
The data were obtained from the Japanese Sarcopenic Dysphagia Database, a multicenter prospective cohort study primarily aimed at assessing the risk and contributing factors associated with sarcopenic dysphagia18,19) using the REDCap application. In the database, we registered patients aged ≥20 years with dysphagia, as indicated by a Food Intake LEVEL Scale (FILS) score of ≤8,20) from nine acute‐care hospitals, eight convalescent rehabilitation hospitals, two long‐term care hospitals, and one home‐visit rehabilitation team between November 2019 and March 2021 using a standardized questionnaire for data collection.
Study Participants
We included non‐consecutive inpatients with dysphagia, defined by a FILS score ≤820) from eight convalescent rehabilitation hospitals in the database. Patients with dysphagia often exhibit increased vulnerability and features of cachexia,21) making them a key population for investigating cachexia-related outcomes in rehabilitation settings. The exclusion criterion was missing values in the diagnostic algorithm for cachexia based on the AWGC criteria.
Outcome
The primary outcome was functional status, as measured using the total FIM score.22,23) The FIM comprises 13 motor and five cognitive domains. Each item is scored from 1 (total assistance) to 7 (complete independence); therefore, the total FIM score ranges from 18 to 126 (integer variables). A previous quantitative review, which synthesized findings from 11 studies, reported median inter-rater reliability and test-retest reliability coefficients for the total FIM of 0.95 and 0.95, respectively.22) In addition to absolute values, we also calculated and analyzed the change in the total FIM (Δtotal FIM = total FIM at discharge – total FIM at baseline) within groups.
The secondary outcomes were FILS scores at discharge and discharge destinations. The FILS20) was used to evaluate swallowing function based on the patients’ level of food intake, using a 10‐point observer‐rating scale (discrete variable, ranging from 0 to 10). FILS levels 1–3 relate to various degrees of non-oral feeding; levels 4–6 to various degrees of oral food intake and alternative nutrition; levels 7–8 to various degrees of oral food intake alone; level 9 to no dietary restriction but with medical considerations; and level 10 indicates normal oral food intake. The weighted kappa coefficient for interrater reliability was 0.86 (95% confidence interval [CI], 0.82–0.90), and it showed high criterion-based validity against the Functional Oral Intake Scale (Spearman’s ρ = 0.93).20) Discharge destinations were classified as discharge to home, transfer to other hospitals/facilities, continued hospitalization, or in-hospital death.
Follow-up data were collected at discharge or 3 months after baseline, whichever came first. This is because the maximum stay in convalescent rehabilitation wards in Japan is 180 days for stroke and other neurological diseases with severe disability and cognitive disorders, while it is 90 days for orthopedic diseases and disuse syndrome. For instance, the mean length of stay (LOS) in a convalescent rehabilitation ward was 75 days overall and 90 days for patients with stroke.24)
Exposure
Cachexia was defined using the AWGC criteria2,25) at baseline. According to these criteria, the essential components were: (1) the presence of underlying chronic diseases such as cancer, chronic heart failure, chronic obstructive pulmonary disease, chronic kidney disease, rheumatoid arthritis, other collagen diseases, chronic respiratory failure, chronic liver failure, progressive worsening or uncontrolled chronic infections; and (2) either a weight loss of ≥ 2% over 3–6 months, or a low body mass index (BMI) of <21 kg/m². Additionally, at least one of the following items was also required: (1) subjective symptoms such as anorexia; (2) objective measures such as decreased grip strength (<28 kg in men and <18 kg in women); or (3) biomarkers such as elevated C-reactive protein (CRP) >0.5 mg/dL. Patients were categorized into two groups based on the presence or absence of cachexia.
Covariates
We collected the following data at baseline: age, sex, Charlson Comorbidity Index (CCI) score (integer variable), artificial nutrition (enteral nutrition and total parental nutrition), primary diagnosis based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10), dementia, and conditions leading to dysphagia. Conditions leading to dysphagia were identified by esophageal cancer (ICD-10 codes: C15x), laryngeal cancer (C32x), pharyngeal cancer (C14x), stroke (I630, I631–I636, I638, I639, I600–I611, I613–I616, I619, I629, and G459), Alzheimer’s disease (G20), head injury (S00x–S19x), Parkinson disease (G20x), and pneumonia (J15x, J18x, and J690).12,26)
Statistical Analysis
We described the patient characteristics using median and interquartile range (IQR) for continuous variables and number (%) for categorical variables. We used descriptive statistics to summarize and conduct a repeated-measures two-way analysis of variance (ANOVA) (time×cachexia) for total FIM between baseline and discharge.
For the primary outcome, we applied multivariate regression analysis for the total FIM score during the follow-up period using a complete case approach and obtained unstandardized regression coefficients and 95% CIs. We conducted four generalized linear regression models. Model 1 was unadjusted (crude); Model 2 adjusted for age, sex, baseline FIM, and baseline FILS; Model 3 additionally included the CCI score; and Model 4 further adjusted for enteral nutrition. These factors were selected to evaluate the association between cachexia and physical function, and were identified using a directed acyclic graph based on previous studies2,14,25,27-29) and discussions with our research team (nurses, occupational therapists, and medical doctors). In the multivariate model, we used the total FIM score at discharge (integer variable, ranging from 18 to 126) as the dependent variable, and cachexia, age, sex, and baseline FIM score as independent variables. For secondary outcomes, we analyzed FILS scores at follow-up using multivariate generalized regression. We also applied a logistic regression model to evaluate the potential association of cachexia with discharge destinations (binary as dummy variable; “discharge to home” and “transfer to other hospitals/facilities”). Additionally, we conducted sensitive analyses to verify the robustness of the results. First, we applied a multiple-imputation approach assuming data were missing at random. We generated 50 imputed datasets using the multiple imputation by chained equation (MICE) procedure and pooled the results (mice‐R‐package) using the standard Rubin’s rule.30) Second, we conducted subgroup analyses on conditions leading to dysphagia, dementia, age ≥65 years, and primary diagnosis (cerebrovascular disease, fracture, and other diseases). We also evaluated the overall fit of the regression models.
A formal a priori sample size calculation was not performed because this was a secondary analysis of a prospective cohort, and the sample size was determined by the number of patients enrolled during the study period. While we did not perform a post hoc power analysis,31) we calculated the effect size (Cohen’s d) with its 95% CI for the primary outcome to aid in the interpretation of the magnitude of the observed difference.
The significance level was set at p<0.05. R software (version 4.2.2; Foundation for Statistical Computing, Vienna, Austria) was used for all statistical analyses.
RESULTS
Of the total 212 patients aged ≥20 years with dysphagia who were hospitalized at eight rehabilitation hospitals in the database, 14 were excluded due to missing data on cachexia diagnosis. Finally, the analysis included 198 inpatients (44% male; median age, 83.0 years [IQR, 77.0–88.0]) (Fig. 1). Thirty-three (16.7%) patients had cachexia as defined by the AWGC criteria. While patients with cachexia had a higher prevalence of all diagnostic components, the prevalence of these components in those without cachexia was also notably high (e.g., 86% had low grip strength and 63% had low BMI/weight loss) (Supplementary Table S1). Table 1 and Supplementary Tables S2–S3 show the patient characteristics. Patients with cachexia were more likely to be women, older, have low BMI, cerebrovascular diseases, and weight loss, but were less likely to have other fractures and high BMI compared with those without cachexia. The median follow‐up period was 80.0 days (IQR, 59.0–92.0). Two patients in the cachexia group died; the causes of death were colon cancer and stroke.
Study flow.
The demographic and clinical data of patients with and without cachexia
Table 2, Supplementary Fig. S1 and Tables S1–S2 summarize the outcome measurements of patients with or without cachexia. In the descriptive summaries, both FIM and FILS scores at follow-up were higher than those at baseline. In the repeated-measures two-way ANOVA, the time factor showed a significant change in both FIM and FILS scores (p<0.05), whereas cachexia and the interaction term (time×cachexia) were not significant. Regarding discharge destinations, patients with cachexia showed a significant difference compared to those without cachexia (Fisher exact test, p<0.05). For example, discharge to home was 72.7% vs. 76.4%, transfer to other hospitals/facilities was 18.2% vs. 9.1%, continued hospitalization was 3.0% vs. 14.5%, and death was 6.1% vs. 0%. Regarding LOS, patients with cachexia were likely to have a shorter LOS for transfer to other hospitals/facilities compared with those without cachexia (48 days [IQR, 25.5–63] vs. 65 days [IQR, 47.5–91.5], p=0.22).
Description of outcome measurements with a complete case analysis
Table 3 and Supplementary Table S4 present the associations of cachexia with total FIM and FILS scores at discharge. After adjusting for covariates, cachexia was not significantly associated with total FIM (β = 0.03, 95% CI -0.10 to 0.15, p=0.66) or FILS (β=0.23, 95% CI -0.53 to 1.00, p=0.55) at discharge. The sensitivity analyses demonstrated similar results. The difference in the change in total FIM score between the cachexia and non-cachexia groups was not statistically significant (Cohen’s d=0.11, 95% CI -0.26 to 0.48).
Association of cachexia with FIM and FILS at follow-up
Table 4 and Supplementary Table S5 show the associations between cachexia and discharge destinations. After adjusting for covariates, cachexia was not significantly associated with discharge to home (β=0.25, 95% CI -0.75 to 1.34, p=0.64) or transfer to other hospitals/facilities (β=0.71, 95% CI -0.47 to 1.80, p=0.22). There may be differences in coefficients in the subgroup analyses, particularly for conditions leading to dysphagia, fractures, other diseases, and dementia. For patients with dementia, cachexia was associated with discharge to home (Model 3: β=-0.75, 95% CI -0.62 to 1.83, p=0.38) compared to those without dementia (Model 3: β=0.54, 95% CI -3.54 to 1.94, p=0.57), although this difference was not statistically significant. Supplementary Tables S6 and S7 present the overall fit of the regression models.
Association of cachexia with discharge destinations
DISCUSSION
This multicenter prospective cohort study primarily aimed to examine how cachexia, defined by AWGC criteria, is associated with functional status and discharge destinations among inpatients with dysphagia across eight convalescent rehabilitation hospitals. Our key findings were that cachexia was not significantly associated with FIM, FILS, or discharge destination in convalescent rehabilitation hospitals, in both multivariate and subsequent subgroup analyses.
First, contrary to our hypothesis, cachexia as defined by the AWGC criteria was not significantly associated with functional status at discharge among patients with dysphagia in convalescent rehabilitation hospitals. This result is similar to those previously reported.14,16) Although patients with cachexia presented with a higher prevalence of diagnostic factors, such as weight loss and low grip strength, those without cachexia could also present a high degree of vulnerability (Supplementary Table S1). For instance, many patients without cachexia have low grip strength and BMI. Thus, both groups may represent vulnerable populations. In the context of intensive multidisciplinary rehabilitation for vulnerable patient populations, cachexia may not have been sufficient to produce a statistically significant difference in the measured functional outcomes. However, our findings differ from those of some studies involving patients with sarcopenia. Nishioka et al.32) reported that sarcopenia was associated with poor recovery of swallowing function and lower FIM gains in post-stroke patients in a similar convalescent rehabilitation setting. This discrepancy may be attributable to differences in the definitions used (cachexia vs. sarcopenia) or the specific patient populations studied. Furthermore, Miura et al.33) suggested that differences in physical function may not manifest until 6 months post-discharge. Therefore, future research with long-term follow-up after discharge is required.
Second, cachexia was not significantly associated with discharge destination; however, patients with cachexia were likely to have a shorter LOS and more frequent transfers to other hospitals/facilities. This could reflect clinical efforts to initiate discharge planning at an early stage for patients with dysphagia and cachexia at convalescent rehabilitation hospitals. The goal of convalescent rehabilitation hospitals is to discharge patients to their homes once their activities of daily living have plateaued.24,34) Our results showed lower FIM scores at baseline and older age in patients with cachexia, which could lead to earlier consideration of transfer options. We did not collect information on the types of transfer destinations, such as long-term care hospitals or nursing facilities. Future studies examining the specific transfer destinations from convalescent rehabilitation hospitals may provide further insights into the reasons for transfer among patients with cachexia. Regarding mortality, previous studies have reported that cachexia is a poor prognostic factor for survival.25,35-37) In this present study, the target population comprised patients admitted to convalescent rehabilitation hospitals. As a result, the follow-up period was limited to 90 days, and most patients were likely in stable condition. These factors may explain why the proportion of deaths among patients with cachexia was lower compared to the previous studies mentioned above.25,35-37)
An interesting finding was the potential effect modification by dementia status, although the wide CIs indicated substantial uncertainty owing to the limited sample size in this subgroup. Patients with both cachexia and dementia represent a particularly vulnerable population for whom the benefits of convalescent rehabilitation may be limited, potentially requiring more aggressive care approaches or settings beyond standard rehabilitation interventions.38) However, as our study lacked information on pre-admission living conditions, some patients with dementia and cachexia may have been residing in care facilities prior to their acute hospitalization. This may have influenced the discharge planning decisions. Additionally, the shorter length of stay observed among patients with cachexia who were transferred to other hospitals/facilities (48 vs. 65 days) suggests earlier identification of alternative care needs in this population.
This study has some limitations. First, the generalizability of the findings may be limited, as this study was conducted in Japanese convalescent rehabilitation hospitals. However, the prevalence of dysphagia is high, at 29%–60% or more in hospitalized patients and 38%–92% in those hospitalized for community-acquired pneumonia.13) Second, this study did not collect information on the frequency, intensity, time, and type of rehabilitation program, which could have affected the improvement in functional status. Unmeasured variations in specific interventions between facilities or patients may have influenced our findings, potentially masking the subtle effects of cachexia. Furthermore, a stratified analysis using the FITT (frequency-intensity-time-type) program components, if available, could have provided additional clinically valuable insights. Therefore, future studies should focus on specific patient groups or employ designs with highly standardized protocols to minimize such variability. Third, due to the sparse data from the small sample size, we were unable to conduct comprehensive subgroup analyses to identify more specific subgroups that could show different associations. Fourth, the observed improvement in FILS scores could be partly attributed to a ceiling effect (Supplementary Fig. S2).
In conclusion, the results of this study demonstrated that cachexia, as defined by the AWGC criteria, was not significantly associated with functional status at discharge or discharge destination among inpatients with dysphagia in convalescent rehabilitation hospitals.
Notes
The authors thank Fuyuko Ogawa at the Library of the National Institute of Public Health for her help with the literature search, as well as all collaborators from the Japanese Working Group on Sarcopenic Dysphagia for their clinical work, data collection, and data registration.
During the preparation of this work, the authors used ChatGPT (Chat-4o, by OpenAI, San Francisco, CA, USA) and Claude (Claude3.5 Opus, Anthropic, San Francisco, CA, USA) to enhance readability and proofread the English text. After using these services, the authors reviewed and edited the content as required and take full responsibility for the content of the publication.
CONFLICT OF INTEREST
The researchers claim no conflicts of interest.
FUNDING
This study was supported by the Japan Society for the Promotion of Science, KAKENHI (Grant No. 19H03979).
AUTHOR CONTRIBUTIONS
Conceptualization, ST, HW; Data acquisition, collaborators from the Japanese Working Group on Sarcopenic Dysphagia; Data analysis and interpretation, ST, TM, HW; Funding acquisition, HW; Writing-original draft preparation, ST, TM; Writing-review and editing, ST, TM, HW, AS, SN, RM.
DATA AVAILABILITY STATEMENT
The datasets generated during the current study are not publicly available because of license agreements with the Japanese Association of Rehabilitation Nutrition. We previously published sample data as Supplemental Material in the report by Mizuno et al.
SUPPLEMENTARY MATERIALS
Supplementary materials can be found via https://doi.org/10.4235/agmr.25.0048.
Histogram for the total FIM at baseline and follow-up. We present stacked histograms showing the distribution of total FIM scores at baseline (upper panel; n=212) and follow-up (lower panel; n=210, with 2 patients deceased in hospital). We stratified patients by cachexia status: absent (red), present (blue), and missing assessment (orange). At baseline, the median FIM score was 51.5 (IQR, 37.0–71.8) and range of 18.0–112.0. At follow-up, the median FIM score increased to 82.0 (IQR, 56.8–104.0) and range of 18.0–125.0. The x-axis represents total FIM score (range, 18–126), and the y-axis represents patient count. FIM, Functional Independent Measure; IQR, interquartile range.
Histogram for the FILS at baseline and follow-up. We present stacked histograms showing the distribution of FILS scores at baseline (upper panel; n=212) and follow-up (lower panel; n=210, with 2 patients deceased in hospital). We stratified patients by cachexia status: absent (red), present (blue), and missing assessment (orange). At baseline, the median FILS score was 7 (IQR, 7–8) with a range of 1–8. At follow-up, the median FILS score improved to a median of 8 (IQR, 7–8.8) with a range of 1–10. The x-axis represents FILS score, and the y-axis represents patient count. Also, we provide accompanying tables on the right that display the detailed frequency distribution of each FILS score (1–10) at baseline (upper panel; n=212) and follow-up (lower panel; n=210, with 2 patients deceased in hospital). We stratified by cachexia status. We observed that a score of 7 was most common at baseline, with 13 and 57 patients with and without cachexia, respectively. We observed that higher scores were more common at follow-up, with 9 and 60 patients with and without cachexia achieving a score of 8, in addition 4 and 23 patients with and without cachexia reaching the maximum score of 10. FILS, Food Intake LEVEL Scale; BL, baseline; FU, follow-up; IQR, interquartile range.
Components of AWGC definition among study participants
Characteristics included missing of cachexia evaluation
Distribution of primary diagnoses within the "Other diseases" category
Subgroup analysis for association of cachexia with FIM and FILS at follow-up
Subgroup analysis for association of cachexia with discharge destinations
Coefficients of each variable on the final adjusted models for each outcome
Model fit statistics for regression analyses