Early rehospitalizations of frail elderly patients – the role of medications: a clinical, prospective, observational trial

Figures & data

Figure 1 Flowchart of patients with a history of rehospitalizations.

Table 1 Baseline (index care episode) clinical and demographic characteristics of early readmitted patients (n=96) and patients not readmitted early (n=294), unadjusted analysis

Characteristics	Readmitted early (n = 96)	Not readmitted early (n = 294)	p-value
Age, mean (years) (SD)	85.7 (5.1)	85.7 (5.5)	0.960
Gender, male, n (%)	47 (49.0)	122 (41.5)	0.236
Charlson score, mean (SD)	6.8 (1.8)	6.8 (1.9)	0.984
ADL score, mean (SD)	4.9 (2.2)	4.4 (2.6)	0.064
Frailty score, mean (SD)	3.5 (0.95)	3.4 (0.84)	0.350
MNA, mean (SD)	10.2 (2.4)	10.2 (2.6)	0.968
Residential care,* n (%)	11 (11.5)	37 (12.6)	0.859
Own living with home help services, n (%)	38 (60.4)	146 (49.7)	0.078
Married/living in partnership, n (%)	26 (27.1)	105 (35.7)	0.136
Ischemic heart disease, n (%)	26 (27.0)	91 (31.0)	0.523
Chronic heart failure, n (%)	48 (50.0)	106 (36.1)	0.017
COPD, n (%)	18 (18.8)	57 (19.4)	1.000
Tumor, n (%)	12 (12.9)	52 (17.7)	0.269
Dementia, n (%)	7 (7.3)	37 (12.6)	0.194
Anemia, n (%)	64 (66.7)	138 (46.9)	0.001
Diabetes, n (%)	20 (20.8)	48 (16.3)	0.353
Renal function, GFR	38.9	53.1	0.155
Index diagnosis: acute heart failure, n (%)	37 (38.5)	85 (28.9)	0.077
Index diagnosis: bacterial infection, n (%)	46 (47.9)	129 (43.9)	0.555
Index diagnosis: myocardial infarction, n (%)	6 (6.2)	12 (4.1)	0.403
Reported cases with 10 or more drugs, n (%)	60 (62.5)	159 (54.0)	<0.001
LOS index, days, mean, n (SD)	10.5 (7.8)	10.0 (6.0)	0.552

Note:

* Living in care facilities.

Abbreviations: ADL, activities of daily living; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; LOS, length of stay; MNA, Mini Nutritional Assessment.

Table 2 Admission characteristics of early readmissions (n = 96)

Characteristics	N
Primary diagnosis at index hospitalization
Pneumonia/exacerbation/acute bronchitis	21
Heart failure	19
Urinary tract infection	11
Other infectious disease	9
Pain	5
Arrhythmia	5
Acute coronary syndrome	5
Vertigo	4
Anemia	4
Others	13
Cause of readmission, condition
Dyspnea	25
Worsened general condition/tiredness	18
Pain	15
Fever/infection	14
Vertigo/falling	10
Others	14
Primary diagnosis at early rehospitalization
Heart failure	17
Pneumonia/exacerbation/acute bronchitis	13
Other infectious disease	10
Urinary tract infection	8
Stroke/TIA	7
Fracture	7
Arrhythmia	5
Myocardial infarction/angina pectoris	3
Pain	3
Bleeding/anemia	3
Others	20

Abbreviation: TIA, transient ischemic attack.

Table 3 Early rehospitalizations probably due to ADRs according to clinical judgment and/or Naranjo scoring§

Case	Primary diagnosis at index discharge	Main reported cause of rehospitalization	Primary diagnosis at discharge from rehospitalization	ADR, clinical judgment*	ADR, Naranjo score**	Probably avoidable rehospitalization, clinical judgment	Probably avoidable rehospitalization, Hallas score	Drug/drug class
1	Back pain	Constipation	Constipation	Yes	Yes, 5	No	No	Oxycodon/opioid
2	Heart failure	Constipation	Abdominal pain	Yes	Yes, 5	No	No	Citalopram/antidepressant
3	Urinary tract infection	Falling	Falling	Yes	No, 3	No	No	Carbamazepine/antiepileptic
4	Orthostatism	Fainting	Orthostatism	Yes	Yes, 6	No	No	Metoprolol/beta-blocker
5	Depression	Falling	Fracture (collum chirurgicum)	Yes	No, 4	No	No	Duloxetine/antidepressant
6	Heart failure	GI bleeding	GI bleeding	Yes	Yes, 6	No	No	Warfarin/anticoagulant
7	Heart failure	Falling	Hip pain	Yes	Yes, 5	Yes	Yes	Digoxin/digitalis glycoside
8	NSTEMI	GI bleeding	Enterocolitis	Yes	Yes, 5	No	No	ASA/salicylate + clopidogrel/P2Y12 inhibitor
9	Supraventricular tachycardia	Vertigo, palpitations	Supraventricular tachycardia	Yes	Yes, 5	No	No	Metoprolol/beta-blocker + felodipine/calcium channel blocker
10	Heart failure	Fever, diarrhea	Enterocolitis	Yes	Yes, 5	No	No	Clindamycin/macrolide
11	Pneumonia	Abdominal pain	Muscle hemorrhage	Yes	No, 3	No	No	Warfarin/anticoagulant
12	Heart failure	Nausea, tiredness	Renal cancer	Yes	Yes, 6	Yes	Yes	Digoxin/digitalis glycoside
13	Bronchitis	Tiredness	Urinary tract infection	Yes	No, 1	No	No	Furosemide/loopdiuretic + spironolactone/potassium-sparing diuretic
				13	9	2	2

Notes:

§ Thirteen early rehospitalizations were classified as probably due to ADRs by clinical judgment and/or the Naranjo score. Among these cases, two rehospitalizations were classified as probably avoidable by clinical judgment and/or the Hallas score.

* Classified as probable ADR by two independent clinicians (Björn W Karlson and Göran Östberg). When the judgment was discordant, a third clinician (Niklas Ekerstad) performed judgment (case 6).

** ADR classified as probable according to the Naranjo score, i.e., >4. The figures denote Naranjo score. None of these patients died during the rehospitalization care episode.

Abbreviations: ADR, adverse drug reaction; ASA, acetylsalicylic acid; GI, gastrointestinal; NSTEMI, non ST elevation myocardial infarction.

Table 4 Early rehospitalization probably due to drug underuse, according to clinical judgment§

Case	Primary diagnosis at index discharge	Indication for drug treatment known at index care episode	Absence of treatment at discharge from index – drug class*	Main reported cause of rehospitalization	Primary diagnosis at discharge from rehospitalization
1	Pneumonia	Pneumonia	Antibiotics	Dyspnea, cough	Pneumonia
2	Heart failure	Atrial fibrillation, CHADS-VASC 5	Anticoagulant	Paresis	TIA
3	Heart failure	Known previous stroke	ASA	Stroke	Cerebral infarction
4	COPD with exacerbation	Heart failure	Beta-blocker	Worsened general condition	Worsened general condition
5	Heart failure	Heart failure	ACE/ARB	Dyspnea	Heart failure
6	Urinary tract infection	Heart failure	Beta-blocker	Dyspnea	Heart failure
7	Unstable angina	Unstable angina	DAPT	Progressive chest pain	Chest pain
8	Abnormal ADH sekretion	Heart failure	Beta-blocker	Dyspnea	Heart failure
9	Malnutrition	Heart failure	ACE/ARB	Dyspnea, back pain	Heart failure
10	Sick sinus syndrome	Heart failure	ACE/ARB	Dyspnea	Heart failure
11	Pyelonefritis	Heart failure	ACE/ARB; beta-blocker	Tiredness	Worsened general condition
12	Enterocolitis (C. difficile)	Enterocolitis (C. difficile)	Antibiotics	Diarrhea	Enterocolitis (C. difficile)
13	Pneumonia	Atrial fibrillation. CHADS-VASC	Anticoagulants	Paresis, aphasia	Cerebral infarction
14	Asthma	Heart failure	ACE/ARB	Dyspnea	Dyspnea
15	Heart failure	Heart failure	Beta-blocker	Dyspnea	Heart failure
16	COPD, exacerbation	Heart failure	ACE/ARB	Dyspnea	Heart failure
17	Heart failure	Heart failure	Beta-blocker	Tiredness	Infection, heart failure
18	COPD, exacerbation	COPD, exacerbation	Antibiotics	Dyspnea	COPD, exacerbation
19	Diverticulitis	Known paroxysmal atrial fibrillation	Anticoagulants	Dysarthria	Stroke

Notes:

§ Early rehospitalization classified as probably due to underuse of evidence-based drug treatment despite known indication at discharge from the index care episode. Classified as probably avoidable rehospitalization by two independent clinicians (Niklas Ekerstad and Björn W Karlson).

* Absence of evidence-based treatment constituting the probable cause of rehospitalization. Known indication and no known contraindication. Of these 19 early rehospitalizations probably due to underuse of evidence-based drug treatment, all were classified as probably avoidable by clinical assessment. None of these patients died during the rehospitalization care episode.

Abbreviations: ACE/ARB, angiotensin converting enzyme-inhibitor/angiotensin II receptor antagonist; ADH, antidiuretic hormone secretion; ASA, acetylsalicylic acid; C. difficile, Clostridium difficile; COPD, chronic obstructive pulmonary disease; DAPT, dual antiplatelet therapy; TIA, transient ischemic attack.

Table S1 Early rehospitalizations probably not due to ADRs or underuse of evidence-based drug treatment

Case	Primary diagnosis at index discharge	Main reported cause of rehospitalization	Primary diagnosis at discharge from rehospitalization	Probably avoidable rehospitalization	Death at rehospitalization
1	COPD with exacerbation	Dyspnea	COPD with exacerbation	No	No
2	Stroke	Dyspnea	Bronchitis	No	No
3	Septicemia	Dyspnea	Septicemia	No	No
4	Septicemia	Wound	Orthopedic care	No	No
5	Wound infection	Paresis	Cerebral infarction	No	Yes
6	Septicemia	Tiredness	Endocarditis	No	No
7	Pneumonia	Coughing	Pneumonia	No	No
8	Atrial fibrillation	Nausea	Atrial fibrillation	No	No
9	Myocardial infarction	Dyspnea	Heart failure	No	No
10	Nausea	Swollen urogenital organ	Paraphimosis	No	No
11	Atrial fibrillation	Dyspnea	Dyspnea	No	No
12	Urinary tract infection	Worsened general condition	Urinary tract infection	No	No
13	Urinary tract infection	Abdominal and back pain	Vertebral compression	No	No
14	Urinary tract infection	Falling	Tibia fracture	No	No
15	Heart failure	Dyspnea	Septicemia	No	Yes
16	Pain	Foot pain	Foot distorsion	No	No
17	Pneumonia	Fever	Pneumonia	No	No
18	Anemia	Tiredness	Calici infection	No	No
19	Nausea	Malnutrition	Hiatus hernia	No	No
20	Pneumonia	Dyspnea	Pneumonia	No	No
21	Heart failure	Chest pain	Cholecystitis	No	No
22	Anemia	Fainting	Pulmonary edema	No	Yes
23	Coughing	Headache	Blood pressure fall	No	No
24	Myocardial infarction	Chest pain	Myocardial infarction	No	No
25	Pulmonary hypertension	Heart failure	Heart failure	No	No
26	Pneumonia	Coughing	Urinary tract infection	No	No
27	Vertebral compression	Dysarthria	Cerebral infarction	No	No
28	Anemia	Worsened general condition	Septicemia	No	No
29	Septicemia	Tiredness	Urinary tract infection	No	No
30	Urinary tract infection	Hip fracture	Hip fracture	No	No
31	Endocarditis	Absence attack	Urinary tract infection	No	No
32	Anemia	Tiredness	Anemia	No	No
33	Heart failure	Tiredness	Heart failure	No	No
34	Heart failure	Falling	Heart failure	No	Yes
35	Headache	Atrial fibrillation	Atrial fibrillation	No	No
36	Heart failure	Fever	Diverticulitis	No	No
37	Pneumonia	Tiredness	Urinary bladder cancer	No	No
38	Dermal infection	Suspected infection	Dermal infection	No	No
39	Heart failure	Heart failure	ACE/ARB	Dyspnea	Heart failure
40	Pulmonary embolism	Abdominal pain	Pleural effusion	No	No
41	Vertigo	Worsened general condition	Vertigo	No	No
42	COPD with exacerbation	Dyspnea	COPD with exacerbation	No	No
43	Myocardial infarction	Paresis	Cerebral infarction	No	No
44	Heart failure	Chest pain	Angina pectoris	No	No
45	Erysipelas	Leg ulcers	Peripheral arterial insufficiency	No	No
46	Vertigo	Vertigo	Vertigo	No	No
47	Pneumonia	Coughing	Tiredness	No	No
48	Pneumonia	Dyspnea	Pulmonary embolism	No	No
49	Hip fracture	Abdominal pain	Ileus	No	No
50	COPD with exacerbation	Dyspnea	COPD with exacerbation	No	Yes
51	Urinary tract infection	Fever	Urinary tract infection	No	Yes
52	Pneumonia	Hand pain	Pneumonia	No	No
53	COPD, exacerbation	COPD, exacerbation	Antibiotics	Cough, dyspnea	COPD, exacerbation
54	COPD with exacerbation	Dyspnea	Heart failure	No	No
55	Pneumonia	Coughing	Pneumonia	No	Yes
56	Heart failure	Worsened general condition	Pneumonia	No	No
57	Cholecyctitis	Hip pain	Hip fracture	No	No
58	Heart failure	Cardiac arrest	Cardiac arrest	No	Yes
59	Atrial fibrillation	Chest pain	Chest pain	No	No
60	Vertebral compression	Bleeding	Vertebral fracture	No	No
61	Urinary tract infection	Fever	Utero-vaginal prolapsis	No	No
62	Orthostatism	Falling	Encephalopatia	No	No
63	Pleural effusion	Dyspnea	Dyspnea	No	No
64	Chest pain	Chest pain	Angina pectoris	No	No

Abbreviations: ADR, adverse drug reaction; COPD, chronic obstructive pulmonary disease.