Beginning with all patient encounters from 655 participating hospitals, the applied exclusion criteria resulted in 61,031 eligible patients [Figure 1]. ONS was provided in 267 (0.4%) of these patients. Of all patients eligible for ONS by POD 3, 5% had the diagnosis of malnutrition, 60% were aged ≥ 60 year, 48% were Medicare beneficiaries, 74% were Caucasian, 43% were from teaching hospitals, and 53% received care at mid-sized hospitals [Table 1]. Outcome analysis in the overall cohort revealed 4% of patients required ICU admission after POD 3, 15% required RBC transfusion, 5% experienced infectious complications, 2% experienced pneumonia, 15% experienced GI complications, and the median hospital cost was $24,954 [Table 2].
Propensity Score Matching
Propensity-score matching produced a sample of 801 hospitalizations that was more balanced than the pre-matched sample in terms of observed characteristics such as age, sex, race/ethnicity, and comorbidities [Table 3]. After matching, the two groups were comparable in terms of baseline characteristics (-0.1 < SMD < 0.1) [Figure 2].
Association Between Early ONS Exposure and Reduced Infectious Complications
Early ONS exposure was associated with significantly fewer infectious complications (6.7% vs 11.7%, P < 0.03) and pneumonia rates (2.6% vs 6.2%, P < 0.04) in the matched sample [Table 4]. Early ONS use was also associated with fewer ICU admissions (6% vs. 10%, P < 0.04) and fewer GI complications (16.5% vs 22.5%, P < 0.05). The matched sample did not, however, show a statistically significant difference in LOS and hospital costs associated with early ONS use.
Falsification Variable Analysis:
Falsification variable analysis was used as described previously to assess for residual confounding in health outcome research(23). As described in a recent JAMA publication, pre-specified falsification end points, when confirmed, assist in validating true observational associations(23). We believe that it is highly unlikely for red blood cell transfusions and myocardial infarction to be causally related to early ONS use, (i.e. we do not see an obvious causal pathway between early ONS use and these outcomes). Finding an association therefore would suggest possible residual confounding. We did not observe a statistically significant difference in RBC transfusion and myocardial infarction in the matched sample. This assists in supporting the validity of the biologically plausible finding that ONS was associated with decreased infectious complications.
Table 1. Baseline characteristics of colorectal surgery patients receiving oral nutritional supplement prior to matching.
Characteristics
|
Before matching
|
|
|
Overall Cohort (n=61,031)
|
Column Percentage
|
Malnutrition
|
3103
|
5%
|
Male
|
28047
|
46%
|
Age Group
|
|
|
<30
|
1142
|
2%
|
30 - 39
|
2783
|
5%
|
40 - 49
|
6734
|
11%
|
50 - 59
|
14042
|
23%
|
60 - 69
|
16507
|
27%
|
70 - 79
|
13248
|
22%
|
>=80
|
6575
|
11%
|
VW Score Category
|
|
|
<-5
|
897
|
1%
|
-5 to -1
|
7563
|
12%
|
-1 to 1
|
29018
|
48%
|
1 to 5
|
9133
|
15%
|
>5
|
14420
|
24%
|
Co-morbidities
|
|
|
Cancer
|
12333
|
20%
|
Renal failure
|
2444
|
4%
|
Chronic pulmonary disease
|
8440
|
14%
|
Payor Category
|
|
|
Managed care organization
|
21682
|
36%
|
Medicaid
|
2353
|
4%
|
Medicare
|
29018
|
48%
|
Other
|
7978
|
13%
|
Race
|
|
|
Black
|
4953
|
8%
|
Hispanic
|
1030
|
2%
|
Other
|
9808
|
16%
|
White
|
45240
|
74%
|
Open Colorectal Surgery
|
36371
|
60%
|
Hospital Bedsize
|
|
|
<200
|
5446
|
9%
|
200-499
|
32410
|
53%
|
≥500
|
23175
|
38%
|
Teaching hospital
|
26037
|
43%
|
Rural Hospital
|
5644
|
9%
|
Vasopressor
|
17381
|
28%
|
Table 2. Outcomes of colorectal sugery patient cohort receiving oral nutritional supplement prior to matching.
Outcome
|
Before matching
|
|
|
Overall Cohort (n=61,031)
|
Column Percentage
|
ICU admission after POD 3
|
2670
|
4%
|
In-hospital mortality
|
287
|
0%
|
Myocardial Infarction
|
872
|
1%
|
RBC Transfusion
|
9373
|
15%
|
Thrombosis (DVT, PE)
|
29
|
0%
|
Pneumonia
|
1501
|
2%
|
Infection
|
3133
|
5%
|
GI complication
|
9389
|
15%
|
30-day readmission
|
6797
|
11%
|
90-day readmission
|
10123
|
17%
|
|
|
|
|
Median
|
IQR
|
LOS
|
4
|
(3, 6)
|
Hospital Cost
|
$24,953.88
|
($7,472.57, $20,422.25)
|
ICU, intensive care unit; POD, postoperative day; RBC, red blood cell; DVT, deep vein thrombosis; PE, pulmonary embolism; GI, gastrointestinal; LOS, length of stay; IQR, interquartile range
Table 3. Baseline characteristics of colorectal surgery patient cohorts analyzed for ONS and non-ONS use after matching.
Characteristics
|
After Matching
|
|
|
ONS
|
Percentage
|
Non-ONS
|
Percentage
|
SMD
|
|
(n=267)
|
|
(n=534)
|
|
|
Malnutrition
|
57
|
21.3
|
109
|
20.4
|
0.02
|
Male
|
125
|
46.8
|
247
|
46.3
|
0.01
|
Age Group
|
|
|
|
|
0.13
|
<30
|
11
|
4.1
|
21
|
3.9
|
|
30 - 39
|
10
|
3.7
|
15
|
2.8
|
|
40 - 49
|
10
|
3.7
|
18
|
3.4
|
|
50 - 59
|
50
|
18.7
|
90
|
16.9
|
|
60 - 69
|
60
|
22.5
|
130
|
24.3
|
|
70 - 79
|
67
|
25.1
|
125
|
23.4
|
|
>=80
|
59
|
22.1
|
135
|
25.3
|
|
VW Score Category
|
|
|
|
|
0.17
|
<-5
|
3
|
1.1
|
|
|
|
5 to -1
|
32
|
12
|
57
|
10.7
|
|
-1 to 1
|
95
|
35.6
|
214
|
40.1
|
|
1 to 5
|
35
|
13.1
|
58
|
10.9
|
|
>5
|
102
|
38.2
|
205
|
38.4
|
|
Co-morbidities
|
|
|
|
|
0.00
|
Cancer
|
71
|
26.6
|
142
|
26.6
|
0.02
|
Renal failure
|
14
|
5.2
|
26
|
4.9
|
0.11
|
Chronic pulmonary disease
|
46
|
17.2
|
71
|
13.3
|
|
Payor Category
|
|
|
|
|
0.11
|
Managed care organization
|
61
|
22.8
|
114
|
21.3
|
|
Medicaid
|
15
|
5.6
|
23
|
4.3
|
|
Medicare
|
169
|
63.3
|
351
|
65.7
|
|
Other
|
22
|
8.2
|
46
|
8.6
|
|
Race
|
|
|
|
|
0.08
|
Black
|
25
|
9.4
|
38
|
7.1
|
|
Hispanic
|
2
|
0.7
|
3
|
0.6
|
|
Other
|
21
|
7.9
|
46
|
8.6
|
|
White
|
219
|
82
|
447
|
83.7
|
|
Open Colorectal Surgery
|
193
|
72.3
|
402
|
75.3
|
0.11
|
Hospital Bedsize
|
|
|
|
|
0.02
|
<200
|
76
|
28.5
|
157
|
29.4
|
|
200-499
|
132
|
49.4
|
255
|
47.8
|
|
≥500
|
59
|
22.1
|
122
|
22.8
|
|
Teaching hospital
|
69
|
25.8
|
138
|
25.8
|
0.00
|
Rural Hospital
|
50
|
18.7
|
99
|
18.5
|
0.00
|
Vasopressor
|
108
|
40.4
|
216
|
40.4
|
0.00
|
Table 4. Outcomes of colorectal surgery patient cohorts analyzed for ONS and non-ONS use after matching.
Outcome
|
After Matching
|
|
ONS (n=267)
|
Percentage
|
Non-ONS (n=534)
|
Percentage
|
p-value*
|
ICU after POD3
|
16
|
6
|
56
|
10.5
|
0.0384
|
In-hospital mortality
|
3
|
1.1
|
14
|
2.6
|
0.18
|
Myocardial Infarction
|
5
|
1.9
|
18
|
3.4
|
0.24
|
RBC Transfusion
|
87
|
32.6
|
147
|
27.5
|
0.14
|
Thrombosis (DVT, PE)
|
0
|
0
|
0
|
0
|
None
|
Pneumonia
|
7
|
2.6
|
33
|
6.2
|
0.034
|
Infection
|
18
|
6.7
|
63
|
11.8
|
0.027
|
GI complication
|
44
|
16.5
|
120
|
22.5
|
0.049
|
30-day readmission
|
34
|
12.7
|
68
|
12.7
|
1
|
90-day readmission
|
52
|
19.5
|
97
|
18.2
|
0.65
|
|
|
|
|
|
|
|
Median
|
IQR
|
Median
|
IQR
|
|
LOS
|
7
|
(4, 10)
|
6
|
(4, 9)
|
0.3471
|
Hospital Cost
|
16132.94
|
(11472.1, 22448.69)
|
14279.46
|
(10102.68, 19844.54)
|
0.3454
|
ICU, intensive care unit; POD, postoperative day; RBC, red blood cell; DVT, deep vein thrombosis; PE, pulmonary embolism; GI, gastrointestinal; LOS, length of stay; IQR, interquartile range.
* Univariable logistic regression for binary outcomes or paired t-test for continuous outcomes.