Article

Prognosis of non-severely comorbid elderly patients admitted to emergency departments: A prospective study

Journal logoUnlabelled imageAmerican Journal of Emergency Medicine 38 (2020) 2034-2040

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Prognosis of non-severely comorbid elderly patients admitted to emergency departments: A prospective study

Laura Maarek, M.D. a,b, Florent Maillet, M.D. a, Aicha Turki, M.D. a, Adrien Altar, M.D. a, Hichem Hamdi, M.D. a, Mouna Berroukeche, M.D. a, Didier Haguenauer, M.D. b, Myriam Chemouny, M.D. a,

Pierre-Emmanuel Cailleaux, M.D. b, Nicolas Javaud, M.D., Ph.D. a,?

a AP-HP, Urgences, CreAk, Hopital Louis Mourier, Universite Paris Diderot, Universite de Paris, Colombes, France

b AP-HP, Geriatrie aigue, Hopital Louis Mourier, Universite Paris Diderot, Universite de Paris, Colombes, France

Introduction

The ageing of the population leads to a rising demand for urgent care among elderly patients, namely patients >75 years [1]. Visits to emer- gency department (ED) for elderly patients increased by 34% during a ten years period (1993-2003) and this trend is growing [1]. In a Retro- spective analysis of prospectively collected data of 120,123 patients, the absolute number and the proportion of patients aged over 80 years admitted to intensive care unit (ICU) significantly increased annually during the 6-year study period and those with comorbid illnesses had lower ICU and hospital survival [2]. In a cross-sectional analysis of a national dataset in the UK, the prevalence of multimorbidity, the presence of two or more long-term conditions, rose substantially with age, and were present in most people aged 65 years and older [3]. Moreover, in a prospective cohort, multimorbidity was strongly linked to frailty, itself associated with mortality after a median follow-up dura- tion of 7 years [4]. Frailty, a state of impaired resolution to homeostasis following a stress, increases the risk of long-term adverse outcomes including mortality, falls, disability, hospitalization and nursing home admission in cohorts of Elderly people [5]. Recently, a retrospective study of a Swedish cohort enrolled 1115 subjects 60 years or older without multimorbidity who were robust, prefrail and frail for 672 (60%), 424 (38%) and 19 (2%) of them respectively [6]. This study showed an increased mortality risk within the first five years for prefrail and frail subjects in comparison with robust subjects [6]. Thus, several studies have studied the frailty in patients visiting the emergency room [7-9]. Two studies had evaluated prevalence of frailty (between 25% to 58% of the included population) and one study impact of frailty at 6 months but no study has been performed exclusively in non-severe comorbid patients.

Even though elderly patients are Frequent attenders to the ED, no prospective observational study on the short-term all-causes outcomes of non-severely comorbid elderly patients admitted through the ED ex- ists. To fill this perceived need, in the current prospective observational study, we aimed to determine if the presence of frailty is an

* Corresponding author at: Urgences, Hopital Louis Mourier, 92 700 Colombes, France.

E-mail address: [email protected] (N. Javaud).

independent factor associated with 30-day all-causes mortality in non-severely comorbid elderly patients admitted to the ED.

Patients and methods

Design and setting

We conducted this prospective observational study including all consecutive non-severely comorbid elderly patients who visited the ED of a Parisian Academic Public Hospital (Louis Mourier Hospital, Co- lombes) and did not exclude any patient presenting to the ED. This hospital is a teaching hospital including an ED and a geriatric unit. The ED receives patients from North West of Paris. The ED receives a total of 35,600 patients in one year, therefore close to 100 patients per day. The >75 years patients’ rate is close to 10% to the global visits. The geriatric unit is a department in which cut-off age of 75 years is necessary to hospitalize patients. Recruitment took place in the ED during a 6-month period from January 2019 to June 2019. A team of fifteen ED physicians were trained to perfume geriatric as- sessments and were treating clinicians in the ED. Follow-up was pro- vided by the geriatrics team.

Our study complied with the Strengthening the Reporting of Observa- tional Studies in Epidemiology guidelines for observational studies [10]. The protocol was approved by the local ethics committee. According to French legislation, no written informed consent was required because of the observational nature of the study and all patients were informed of the study plan. None voiced any opposition.

Participant inclusion and exclusion criteria

The study inclusion criteria were patients of 75 years of age or older who presented to the ED. They were required to have a weighted index of comorbidity (Charlson index) strictly lower than 3. The exclusion criteria were patients who had a severely comorbidity defined by a weighted index of comorbidity (Charlson index) equal to or higher than 3 and any disability.

https://doi.org/10.1016/j.ajem.2020.06.064

0735-6757/(C) 2020

Outcomes and data collection

The primary outcome was the 30-day all-cause mortality (in-hospi- tal or out-hospital) collected by a geriatrics investigator through a tele- phone call to the patients or to a relative authorized by the patients at the inclusion date if the patients were not hospitalized. The date of death was also collected.

Secondary outcomes comprised the length of stay and emergency readmission within 30 days of initial discharge (excluding patients who died at the hospital). The secondary outcomes were collected by a geriatrics investigator through a telephone call if the patients were not hospitalized.

For each emergency visit, the emergency physician collected the fol- lowing data on standardized forms immediately after the baseline visit:

(1) demographical: age, sex, current smoking and current alcohol con- sumption, number of medications, Charlson Comorbidity Index (esti- mating the mortality risk from comorbid diseases at a specified timepoint in longitudinal studies) [11]; (2) clinical: vital signs (arterial blood pressure, cardiac rate, pulse oximetry, Coma Glasgow Scale and respiratory rate), functional status as defined by an Index of Indepen- dence in activities of daily living score, [12] frailty status as originally defined by Fried and colleagues (weight loss, exhaustion, measure of physical activity, walking speed and grip strength) [13], Initial diagnosis at the ED, including surgical and medical pathology, and listing in the Appendix 1. The geriatric assessment that included frailty phenotype and baselines of Index of Independence in Activities of Daily Living (ADL) score was performed by a trained emergency physician during the first 12 h of care in the ED. The principal investigator (NJ) double checked the database.

Definitions

The Charlson comorbidity index is a weighted index of comorbidity who is a significant predictor of 1-Year survival. This weighted index ex- plained a higher proportion of the variance than the initial model based on the number of comorbid diseases. The Charlson index has been rec- ommended for measuring comorbidity when mortality is the outcome of interest. It is the sum of the weights of the patient’s current comorbid- ities for a given subject (Appendix 2). All comorbidities were cumula- tive except for diabetes and tumor [11].

Frailty phenotype is based on the co-occurrence of at least three of five features including unintentional weight loss (of 5 kg or > 5% of body weight on prior year), self-reported exhaustion (“Did you feel that everything you did was an effort?”), low grip strength stratified by sex and BMI cutoffs as originally proposed by Fried (handgrip strength was measured in kilograms using a JAMAR hand-held dyna- mometer, < 20 kg for women and 30 kg for men), slow walking speed stratified by sex and standing height as originally proposed by Fried (the slowest 20% of the population was defined at baseline, based on time to walk 15 ft) and low weekly physical activity was defined as a weekly physical activity <383 kcals/week in males and < 270 kcals/ week in females). Patients were defined prefrail if they met one or two criteria and robust otherwise. Prefrail patients were combined with robust patients. Patients unable to perform the handgrip strength or walking test were considered as having weakness or slow gait speed, respectively [13].

The index of Independence in Activities of Daily Living (ADL) is based on an evaluation of the functional independence or dependence of patients in bathing, dressing, toileting, transferring, continence and feeding and ranges from 0 (totally dependent) to 6 (independent) [9].

Statistical analysis

Quantitative variables are presented as mean +/- standard devia- tion (SD) if normally distributed, with the addition of median and inter- quartile ranges (IQR) for skewed distributed variables. Qualitative data

are expressed as numbers with percentages. Data were compared be- tween two groups using t-test for normally quantitative variables or Mann-Whitney-test for skewed quantitative variables. Data were com- pared between two groups using Chi-square or Fisher’s exact test for qualitative variables. The effect of the frailty on 30-day mortality and re- admission was expressed as crude Hazard ratios, with 95% confidence intervals, and then adjusted HR for all potential confounding factors (p < .20), using a direct Cox regression analysis. The proportionality of hazards and the collinearity were analyzed using the proportional haz- ards assumption test based on Schoenfeld residuals. survival curves were constructed using Kaplan-Meier method on day 30 after ED visit and global differences between the different groups were determined using the log-rank statistics. All tests were 2-sided. A p-value <.05 was considered significant. We used R statistical software version

3.5.2 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Among 1636 patients who presented to ED of 75 years of age or older, 1338 patients had a Charlson index greater than or equal to 3 and were non-eligible (Fig. 1).

Description of patients

Two hundred ninety-eight patients with a Charlson index lower than 3 were included. One-hundred and ninety-five (65%) were women with a median age of 85 (79-89) years. The main patient char- acteristics are summarized in Table 1 and Fig. 2. A large majority had no multimorbidity (89%) and lived at home (90%) with a median number of medications and ADL score of 4 (2-6) and 6.0 (5.0-6.0), respectively. The prevalence of frailty grew with increasing multimorbidity, since it concerned from 48%, 49% and 81% of the patients with zero, one and two coexisting conditions (Fig. 2), respectively.

Characteristics of acute episode

Clinical characteristics of the acute episode are given in Table 2.A large majority of the emergency visits were motived by medical rea- sons. More than half of the patients had a cardiac disorder, a fall or a re- spiratory disorder (a complete list is available in Appendix 1).

Comparisons of patients and acute episode

We did not find any significant differences between the two groups in terms of sex and initial clinical data. Patients with frailty were older, had greater multimorbidity, had lower Index of independence and lived more often with home assistance. They were more frequently hos- pitalized after the ED visit.

Primary and secondary outcomes

The overall rate of 30-day all-cause mortality was 6%. The rate of 30- day mortality was significantly higher in the frailty group than in the non-frailty group, 11% versus 1%, respectively (p = .0002). The rate of 30-day readmission was also significantly higher in the frailty group than in the non-frailty group, 18% versus 10%, respectively (p = .04). The median length of stay was significantly higher in the frailty group than in the non-frailty group, 5 (0-12) day versus 0 (0-3) day, respec- tively (p < .0001). Fig. 3A and B showed the survival curves of the 30- days all-cause survival rate and the 30-days emergency readmission rate in the 2 groups, by frailty status.

Death was due to hemorrhagic stroke in 1 (1%) patient in the non- frail group. Death was caused by acute heart failure in 4 (3%) patients, by ischemic stroke in 3 (2%) patients, by pulmonary embolism and acute coronary syndrome in 2 (1%) patients respectively, by pneumonia in 3 (2%) patients, by hemorrhagic stroke, comatose, and septic shock in

14932 patients presented to ED during the study period

1636 patients presented to ED who had 75 years of age or older

Fig. 1. Flow chart of patients.

Non eligible patients

Patients who were 75 years of age or older who presented to the ED with a Charlson index greater than or equal to 3

N = 1338

13 patients were robust

131 patients were prefrail

154 patients were frail

298 patients were included

1 death

17 deaths

0 death

1 (1%) patient respectively, and by an unknown cause in 2 (1%) patients, in the frail group.

After adjusting for all potential confounding factors (age, sex, index of Charlson, number of medications, index of independence,

Table 1 Clinical baseline and characteristics of acute episode of 298 elderly patients admitted to ED according to frailty status.

multimorbidity, living situation), the presence of frailty was indepen- dently associated with 30-day mortality: HR = 10.20; 95% CI =

Characteristics Patients.

n = 298

Frailty.

n = 154

Non-frailty. p

n = 144

1.28-81.44; p = .03 (Table 3). Without adjustment, the presence of frailty was associated with readmission: OR = 2.06; CI = 1.04-4.10;

Female patients, no. (%) 195 (65) 103 (67) 92 (64) 0.58

Age (yr), median (IQR) 85 (79-89) 87 (82-92) 82 (78-85) <0.0001

Number of medications, median

p = .038 and after adjusting for the same potential confounding factors, Multimorbidity, no. (%)

the presence of frailty was independently associated with readmission: No long-term conditions

148 (50)

70 (45)

78 (54)

0.02

One long-term conditions

117 (39)

57 (37)

60 (42)

OR = 2.28; 95% CI = 1.06-4.96; p = .036. Two long-term conditions

33 (11)

27 (18)

6 (4)

Charlson index, median score

1 (0

1 (0-1)

0 (0-1)

0.02

3.5. Follow-up (IQR)

[1-4]-1)

4 (2-6)

4 (3-6)

3 (2-5)

0.004

(IQR)

No patients were lost to follow-up and primary and secondary end- Index of Independence in ADL

6.0

5.5

6.0

<0.0001

points were available for all patients. score, median (IQR)

Home without assistance

(5.0-6.0)

149 (50)

(3.5-6.0)

55 (36)

(6.0-6.0)

94 (65)

<0.0001

4. Discussion Home with assistance

118 (40)

75 (48)

43 (30)

Long-term care facility

Acute episode clinical data

31 (10)

24 (16)

7 (5)

Living situation, no. (%)

In our prospective study, we describe a series of 298 patients with non-severely comorbid diseases of 75 years or older, which represents

SBP, median (IQR)

145

(129-164)

145

(126-165)

145

(131-161)

0.33

only 20% of over 75 years old patients in the ED. Half of the patients Cardiac rate, median (IQR) 80 (68-91) 80 (69-92) 78 (68-91) 0.48

who visited the ED for an acute episode were frail. In our study, the

Temperature, median 36,8

36,8

36,7

0.23

probability of short-term mortality, rate of readmission and length of stay were significantly higher in the frail group than in the non-frail

(36,4-37,1) (36,5-37,2) (36,4-37)

Pulse oximetry, median (IQR) 97 (97-98) 97 (96-98) 97 (96-98) 0.02

Respiratory rate, median (IQR) 17 (15-18) 17 (15-18) 17 (15-18) 0.52

group. We found that the risk of 30-day all-cause mortality was 10 times higher for non-severely comorbid frail patients over 75 years than for non-frail patients. Frailty must be assessed in elderly patients, including non-comorbid patients who visit the ED and should ulti- mately lead to an intervention.

Prevalence of frailty was high (52%) in our included population, slightly higher than that of the Martin-Sanchez study (36%), whose study population also included severe comorbid patients (51%) in acute setting [15]. This prevalence was much higher than that of the Zucchelli study (2%), whose study population included subjects without multimorbidity [6]. The acute clinical setting of ED patients probably

Primary medical ED admission, no. (%)

Initial clinical diagnosis, no. (%)

Cardiac disorder

66 (22)

35 (23)

31 (22)

<0.0001

Fall

66 (22)

11 (7)

55 (38)

Respiratory disorder

44 (15)

37 (24)

7 (5)

Exhaustion

41 (14)

26 (17)

15 (10)

neurologic disorder

40 (13)

23 (15)

17 (12)

Urinary tract disorder

24 (8)

15 (10)

9 (6)

Gastrointestinal disorder

8 (3)

2 (1)

6 (4)

Other

9 (3)

5 (3)

4 (3)

Hospitalization after ED visit,

154 (52)

99 (64)

56 (39)

<0.0001

no. (%)

280 (94) 134 (45) 146 (49) 0.53

overestimated the prevalence of frailty in our study. These were

no., number of patients; yr, year; IQR, interquartile range; SD, standard deviation.

Image of Fig. 2

Fig. 2. Prevalence of frailty status categorised by number of long-term conditions.

consistent with frailty significantly more common than non-frailty for respiratory disorder and significantly less common after mechanic fall. Frailty is described, as a state of increased vulnerability, more fre- quently present in older patients with chronic diseases [4,6,15]. In the retrospective Swedish cohort study of 1115 enrolled subjects, frail pa- tients were significantly older than non-frail patients [6]. The Spanish retrospective study of a prospective cohort study enrolled 465 non- severely disabled older patients with acute heart failure attending the ED. Compared to non-frail patients, those who were frail were older in

this study too [15]. This is consistent with our results.

Patients who had long-term conditions were more likely to de- velop frailty. In a large prospective cohort study which enrolled 493.737 participants aged 40-49 years between 2006 and 2010, the prevalence of frailty increased with increasing multimorbidity [4]. These findings are consistent with our study that identifies higher multimorbidity (the presence of two or more long-term conditions) in the frailty group despite the fact that patients had a maximum of 2 long-term conditions given in our inclusion criteria [4]. This is the main reason why we included only patients of 75 years of age or older with a weighted index of comorbidity strictly lower than 3, i.e. non-severely comorbid elderly patients. We could have imagined a larger proportion of frail patients in our study if all multimorbid pa- tients older than 75 years were included without severity restrictions. Indeed, in a cross-sectional analysis of a national dataset of 1.751.841 patients, the number of morbidities and the proportion of people with multimorbidity increased significantly with age. By age 75 years, 65% of the population was multimorbid [3].

There was only small concordance between frailty and disability. In Fried’s study, frailty and disability had a prevalence of 6% [13]. This is why patients initially disabled patients were not excluded. This finding provides support for frailty as an independent concept, distinct from disability even though recent works suggest that the overlap is more frequent and disability increases with greater frailty [5]. Despite a high Index of independence level in our study, patients who were frail had

Table 2

Outcomes of 298 elderly patients admitted to ED according to frailty status.

a lower basal level of dependence, as in the Spanish retrospective study of 465 non-severely disabled older patients with acute heart fail- ure attending the ED [15].

Previous studies have suggested that frailty in older patients admit- ted to the hospital is a predictor of adverse short and long-term out- comes [6,7,15,16]. However, our study provides additional evidence of the effect of frailty on 30-day all-cause mortality in non-severely comor- bid older patients attending the ED. In our study, the mortality rate (6%) is close to that of the Spanish study who found a mortality rate of 7% in 465 patients >65 years with severe comorbidity in approximatively 50% of cases attended with acute heart failure in ED. In this Spanish retro- spective study of a prospective observational Multicenter cohort study, the frailty phenotype was an independent factor associated with 30-day mortality in 465 non-severely disabled older patients with acute heart failure attending the ED [15].

However, our rate is lower than the mortality rate of 15% found in a recent observational study using electronic hospital records [14]. This recent observational study using electronic hospital records and the In- ternational Statistical Classification of Diseases and Related Health Prob- lems, Tenth Revision (ICD-10) showed that people with high frailty risk had a higher odds of 30-day mortality (OR 1.71, 95% CI 1.68-1.75), of a long hospital stay (6.03, 5.92-6.10) and of emergency readmission within 30 days (1.48, 1.46-1.50) than those in the low-risk group [14]. Moreover, our 14% readmission rate is lower than the 25% readmission in the same study using electronic records [14] and the 32% readmission in the study using the ‘Identification of Seniors at Risk” (ISAR) screening in which the ED re-visits by seniors were fairly predictable with the pos- itive ISAR screening tool [17]. However, this study, using ICD-10, does not capture disease severity and might also miss out on weakness, polypharmacy and need for support in everyday living [14]. In the cur- rent study, the selection of patients with non-severely comorbid pa- tients with preserved Baseline functional status may explain the observed low rates of 30-day all-cause mortality and of readmission. This is also the reason why we chose the frailty phenotype rather than the Clinical Frailty Scale , which is easy to use and may readily be administered in an acute clinical setting, like in intensive care unit in which CFS had adequate properties to evaluate frailty in very old inten- sive care patients (not in the ED) [18,19].

Outcomes Patients

n = 298

Frailty

n = 154

Non-frailty p

n = 144

4.1. Limitations

30 day-Mortality, no. (%) 18 (6) 17 (11) 1 (1) 0.0002

Secondary outcome

Length of stay, day median (IQR) 1 (0-8) 5 (0-12) 0 (0-3) <0.0001

This study has several strengths. First, participants were patients without severe comorbidity, so as to avoid inclusion of patients with

Emergency readmission within 30-day, no. (%)

42 (14) 28 (18) 14 (10) 0.04

very high Expected mortality. Second, this study was pragmatic, which contributes to the generalizability of the results. Third, no patients

no., number of patients; IQR, interquartile range.

were lost to follow-up.

A

Non- frail

Frail

p = .0002 by log-rank test

Non- frail

p = .02 by log-rank test

Frail

No. at risk

Non-frail

144

144

144

144

144

144

143

Frail

154

147

143

142

141

139

138

B

No. at risk

Non-frail

144

143

141

140

138

136

135

Frail

154

137

133

129

126

126

122

Fig. 3. A.Survival, according to frailty status. Fig. 3A shows the Kaplan-Meier estimates of the 30-days survival rate in the two groups. The Probability of survival was significantly higher in the non-frail group than in the frail group. Fig. 3B Emergency readmission, according to frailty status. Fig. 3B shows the Kaplan-Meier estimates of the 30-days emergency readmission rate in the two groups. The probability of emergency readmission was significantly higher in the frail group than in the non-frail group.

Table 3

Multivariate Logistic Regression Analysis of Factors Associated with 30-day mortality.

OR

p

[95% CI]

Age

1.06 [0.97-1.17]

0.19

Female sex

1.05 [0.36-3.09]

0.91

Pre-existing condition

Index of Charlson

1.93 [0.36-10.29]

0.43

Index of Independence in ADL score

0.91 [0.67-1.21]

0.49

Multimorbidity

2.11 [0.49-9.08]

0.31

Home without assistance

2.19 [0.28-17.34]

0.46

Baseline in ED

Number of medications

1.11 [0.94-1.32]

0.20

Frailty

10.21 [1.28-81.44]

0.03

OR, Odds Ratio; CI, confidence interval; ADL, Activities of Daily Living; ED, emergency department.

This study also has several limitations. First, the sample size was cal- culated a priori but was based on the 15% 30-day mortality rate [14]. This may have limited the statistical power of the analysis, showed by large confidence intervals despite significant results. Second, our analy- sis only included non-comorbid older patients. Therefore, the findings cannot be directly compared with most of the cited studies. Third, de- spite the absence of clinical missing values, the one-month mortality (6%) is difficult to analyze without any severity score, like SOFA for ex- ample. Fourth, the proportion of frail patients might be overestimated because of transient impairments of their functional performances, caused by Acute diseases leading to the emergency department. Finally, we used unadvised cox analyses for the readmission outcome with high possibility of a competing risk with mortality.

Conclusion

Presence of frailty is an independent risk factor associated with all causes 30-day all-cause mortality in patients >75 years with non- severely comorbidity attending the ED. Frailty should be accounted in the decision-making process of non-severely comorbid patients who visit the ED. A pragmatic interventional trial should be conducted to study if intervention on frailty in an emergency condition could increase survival of non-severely comorbid elderly patients.

Author contributions

    • NJ, LM, DH and PEC initiated and coordinated the research.
    • NJ and PEC designed the study.
    • NJ, DH and LM managed and analyzed data.
    • NJ, LM, FM, AT, AA, HH, MB, MC participated in the data collection, in- terpretation.
    • LM and NJ wrote the article.

All authors contributed substantially to the study and approved the

final version of the article.

NJ take responsibility for the paper as a whole.

Funding

None.

Declaration of Competing Interest

None.

Acknowledgment

We thank Virginie Panayotopoulos for the editorial support.

Appendix 1. List of the emergency conditions for diagnosis

List of the emergency conditions for diagnosis

Cardiac disorder Congestive heart failure Arrhythmia

Syncope

Falls Falls

Respiratory disorder Chronic obstructive pulmonary disease

Pulmonary embolism Pneumonia

Exhaustion Exhaustion

Neurologic disorder Coma

Confusion

Urinary tract disorder Acute renal failure Urinary tract infection

Gastrointestinal disorder Digestive bleeding Constipation

Others Others

Appendix 2. The Charlson comorbidity index

Charlson comorbidity index Points

Myocardial infarct 1

Cerebrovascular disease Congestive heart failure Peripheral vascular disease

Dementia (Mini-mental state Examination <27/30) Connective tissue disease

Chronic pulmonary disease Ulcer disease

Mild liver disease Diabetes

Diabetes with end organ damage 2

Hemiplegia

Moderate or severe renal disease Any tumor

Leukemia Lymphoma

Moderate or severe liver disease 3

Metastatic solid tumor 6

AIDS

Total of the score

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