Limited effect of rehabilitation for preventing a decrease in functional status after community-acquired pneumonia in elderly patients

Background: Functional status (FS) is often decreased after hospitalization in elderly community-acquired pneumonia (CAP) survivors. Rehabilitation has frequently been used to prevent decreased FS. This study was designed to evaluate the effect of rehabilitation for preventing decreased FS. Methods: This retrospective, observational study was conducted in two medical facilities from January 2016 to December 2018, and hospitalized CAP patients >64 years of age were enrolled. FS was assessed by the Barthel Index (BI) (range, 0–100, in 5-point increments) at admission and before discharge and graded into three categories: independent, BI 80–100; semi-dependent, BI 30–75; and dependent, BI 0–25. Multivariable analysis of factors contributing to decreased FS was conducted with two groups: with a decrease of at least one category (decreased group), or without a decrease of a category (maintained group). Then, the effect of rehabilitation was examined by propensity score analysis by adjusting factors contributing to decreased FS determined in the previous multivariable analysis. Results: The maintained group included 400 patients, and the decreased group included 138 patients. The decreased group had a high frequency of rehabilitation therapy (189 (47.3%) vs 104 (75.4%); p<0.001). Multivariable analysis showed that factors affecting FS were length of stay, aspiration pneumonia, age, and Pneumonia Severity Index (PSI) of category V (odds ratio 1.05, 95%CI 1.04–1.07; 2.66, 95%CI 1.58–4.49; 1.05, 95%CI 1.02–1.09; and 1.92, 95%CI 1.29-3.44; respectively). After adjusting for factors contributing to decreased FS, rehabilitation showed a limited effect in preventing a decreased FS in 166 matched pairs (p=0.327). Conclusions: The effect of rehabilitation was still unclear in CAP, and further research is warranted to �nd an effective way to conduct rehabilitation.


Background
Pneumonia is causing an increasingly higher proportion of deaths worldwide, with 3.2 million estimated deaths globally each year, exceeding all other infections including tuberculosis, HIV infection, and malaria.[1] Community-acquired pneumonia (CAP) is one of the most common medical causes of admission in most healthcare institutions in the USA.[2] In Japan, pneumonia is the third highest cause of death among elderly patients.[3] Besides the high mortality in elderly CAP patients, these patients also experience deterioration of functional status (FS), an important component of quality of life for older adults and their caregivers, both during and after treatment [4].Decreased FS prolongs length of stay (LOS) in elderly CAP patients [5], and the prevalence of functional decline was reported to be 8.6%-20% in CAP [5,6].Early rehabilitation therapy might improve activities of daily living (ADL) during hospitalization in patients with aspiration pneumonia, but it may increase LOS [7].The effect of rehabilitation in preventing decreased FS in CAP has remained unclear.Therefore, this study was designed to identify factors related to decreased FS and evaluate the effect of rehabilitation in preventing decreased FS in elderly CAP patients.

Methods
This was a retrospective, cohort study of inpatients admitted to a community-based hospital and a teaching hospital in Japan from January 2015 to December 2018.This study was approved by the institutional review boards of the hospitals and conformed to the provisions of the Declaration of Helsinki (as revised in Brazil 2013).

De nitions
FS was evaluated at admission and before discharge by the Barthel Index (BI) [8] (range, 0-100, in 5point increments) of ADL and was graded into three categories according to the BI: independent, BI 80-100; semi-dependent, BI 30-75; and dependent, BI 0-25 [9].A decreased FS was considered a reduction in ADL of at least one category.Disorder of conscious (DOC) was de ned as a Glasgow Coma Scale [10] score below 15, and for dementia patients, DOC was considered only if their consciousness was worse than their normal status.The key person (representing the main individual supporting the patient during and after admission) was classi ed as a child, spouse, or others.Rehabilitation included any type and intensity of physical rehabilitation program administered by physicians, physical therapists, and occupational therapists.The need for rehabilitation was determined during admission based on the risk of disuse syndrome or aspiration pneumonia.For survival patients, sites of acquisition were classi ed as home discharge (without nursing), home nursing, facility and transfer to another hospital.

Patients
Elderly hospitalized CAP patients were divided into two groups: maintained group, without deterioration of FS; and decreased group, with decreased FS.All enrolled cases had been diagnosed with CAP according to the de nitions of the American Thoracic Society/Infectious Diseases Society of America guideline [11].Patients who ful lled all of the following inclusion criteria were enrolled in the study: 1) age >64 years; 2) symptoms compatible with pneumonia (e.g., fever, cough, sputum, pleuritic chest pain, or dyspnea); and 3) appearance of new pulmonary in ltrates consistent with pneumonia on chest X-ray or computed tomography.To ensure that all eligible cases were enrolled, the study investigators screened the hospital database for International Classi cation of Diseases, 10th revision (ICD-10) codes (J13-18, J69) and reviewed hospital medical records.Repeated episodes of pneumonia in the same patient within a 2-week period were regarded as a single episode.

Exclusion criteria
Cases of healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP) were excluded [12].Cases with complications that occurred during admission (myocardial infarction, femoral fracture, cerebral infarction, etc.) that would have affected FS were also excluded.

Outcomes
The primary outcome was the effect of rehabilitation in preventing decreased FS.Demographic information, vital signs, including DOC and body mass index (BMI), laboratory values, and comorbidities were collected on admission.Comorbidities were identi ed according to the Charlson Comorbidity Index (CCI) [13].The Pneumonia Severity Index (PSI) [14] score was calculated based on data obtained at the time of admission.Information regarding the key person was con rmed soon after admission.Information about acquisitions for survivors was also collected, and all patients who died were considered in-hospital deaths.Information of medical costs were collected at discharge.

Statistical analyses
The results are presented as numbers and percentages or medians and interquartile ranges unless otherwise indicated.Groups were compared using Wilcoxon rank-sum tests.In order to evaluate the effect of rehabilitation on FS, risk factors for decreased FS were determined using stepwise regression analysis.
Confounding variables of decreased FS, age, sex, BMI, aspiration, dementia, DOC, undergoing rehabilitation, pre-admission ADL, PSI, CCI, and LOS were chosen as candidates with p values below 0.2 on univariable analysis.Using the model of the minimum corrected Akaike's information criterion (AICc) in the backward direction, the nal variables were determined.The effect of rehabilitation was evaluated by propensity score analysis by adjustment with variables determined on multivariable analysis.
McNemar's test was performed to evaluate the effect of rehabilitation on preventing decreased FS in matched pairs.In all instances, two-tailed values of p<0.05 were considered signi cant.Data analysis was performed using JMP software (version 15.0; SAS Institute, Cary, NC).

Results
A total of 1854 patients diagnosed with pneumonia were identi ed.Of these, the following were excluded: 278 due to age <65 years; 612 due to outpatient treatment; 113 due to HCAP or HAP; and 215 due to incomplete data such as PSI, BI, etc.Of the 636 elderly patients with CAP, treatment was prolonged in 98 patients due to complications, even if pneumonia had resolved.The remaining 538 cases were included in the study, including 400 patients in the maintained group and 138 patients in the decreased group (Figure 1).The participants were 370 men (68.8%) and 168 women (31.2%), with a median age of 79 years (73, 84 years; rst and third quartile, respectively).The background characteristics of these patients are summarized in Table 1.Sex, bedsores, and CCI were not signi cantly different between the groups.
Patients in the decreased group were older, with higher rates of DOC and aspiration, and higher PSI categories.Patients in the decreased group had longer LOS (13 vs 27 days, respectively; p<0.001).
In order to check the effect of rehabilitation on preventing decreased FS, 166 cases were matched after propensity score analysis using variables identi ed on multivariate analysis (Table 3).Age, BMI, aspiration, DOC, LOS, and PSI category V showed no signi cant differences.For the matched cases, McNemar's test was performed and showed no signi cant differences in preventing decreased FS between the two groups (p=0.327;Table 4).

Discussion
In this retrospective cohort study, prolonged LOS was observed in the decreased FS group.After multivariable regression analysis, LOS, aspiration pneumonia, age, and category V PSI were identi ed as independent factors contributing to decreased FS.There were 138 (25.7%) elderly CAP patients who showed decreased FS in this study, which was higher than in previous studies [5,6].On propensity score analysis, after adjusting for age, BMI, aspiration pneumonia, DOC, LOS, and PSI, rehabilitation showed a limited effect in preventing decreased FS in elderly CAP patients.
The effects of rehabilitation have been evaluated from various aspects, but there was no de nite conclusion.Some studies showed that early rehabilitation reduced LOS [15,16] in pneumonia, but another study showed that it would prolong LOS [7].The effects of rehabilitation on mortality and readmission rates were also unclear [17,18].The present study showed that rehabilitation had a limited effect in preventing decreased FS in elderly CAP patients.This does not mean that rehabilitation is useless in CAP.Further research is warranted to nd a more cost-effective approach to rehabilitation with adjustment for patient background and hospital characteristics.
There were other factors affecting decreased FS.Age-associated alterations not only decrease innate and adaptive immune responses, but they also involve structural and functional deteriorations of most physiological systems, which may negatively impact the ability of the individual to carry out ADL [19].
Aging is a major risk factor for the development of virtually every lung disease, with increased morbidity and mortality, whereas morbidities and mortalities from other prevalent diseases have decreased or remained stable [20].
In the process of aging, aspiration pneumonia, a subclass of CAP, is an increasing signi cant problem in elderly persons, and it is expected to contribute increasingly to mortality and morbidity in the elderly population over the coming decades [21].Diagnosing aspiration pneumonia has been notoriously problematic because there have not been any established criteria for its diagnosis.Aspiration pneumonia is often diagnosed clinically, relying on the history and physical examination.Aspiration pneumonia accounts for 7-24% of CAP cases [22].The rate of aspiration in the patients was 22.5% (overall), and up to 44.9% in the decreased group.Aspiration independently increased the risk of in-hospital mortality [23], and was also an independent factor related to decreased FS.
The PSI is considered the best predictor of mortality of CAP [14,24].Most patients who die from pneumonia are elderly, with multiple comorbidities and signi cant limitations in care put in place at or during admission.Surviving patients face the additional problem of decreased FS.According to the present study, FS tended to easily decrease in severe pneumonia.Decreased FS and LOS are important risk factors for unplanned re-hospitalization [25].A prolonged LOS would result in a higher hospitalization cost.The average medical cost for the decreased group was almost double that of the maintained group.
In addition to nding an effective method of rehabilitation, discharge planning might be necessary to decrease hospitalization costs.
Limitations Some limitations to this study need to be considered when interpreting the present results.First, this study was limited to two medical facilities.Second, only CAP patients were included, and FS in HCAP or HAP is also important for elderly patients, but it remained unclear.Third, due to lack of information about cognitive function, a tool such as the Functional Independence Measure (FIM) [26] was not applicable.Fourth, FS was divided into three categories, whereas continuous variables might be more informative.
Fifth, there were other factors, such as exercise, social issues, and economic situation, that could affect FS other than rehabilitation, but they were not included in the present study due to lack of information about them in the medical record.

Conclusions
The effect of rehabilitation is still unclear in CAP, and further research is warranted to analyze the costeffectiveness of rehabilitation.

Tables
Flowchart of the study HCAP, healthcare-associated pneumonia; HAP, hospital-acquired pneumonia; CAP, community-acquired pneumonia.

Table 2 .
Table and outcomes of the maintained and decreased functional status groups Multivariable analyses of factors affecting decreased functional status CI, confidence interval; LOS, length of stay; PSI, Pneumonia Severity Index; DOC, disorder of consciousness; BMI, body mass index.

Table 3 .
Detailed information of cases matched by propensity

Table 4 .
The of rehabilitation in elderly CAP patients