Introduction
Lower gastrointestinal bleeding (LGIB), defined as bleeding originating either from
the colon or rectum [1 ], accounts for substantial morbidity and mortality in the United States [2 ]. LGIB admissions accounted for approximately 109 per 100,000 emergency department
visits in the United States in year 2012 and are on rise [3 ]. With prevalent use of antithrombotics, LGIB will remain a common gastrointestinal
emergency. Although generally considered to have a better prognosis than upper gastrointestinal
bleeding (UGIB), it was reported in one study that LGIB was associated with a higher
mortality rate, longer length of stay (LOS), and higher healthcare resource utilization
compared to UGIB [4 ].
A cornerstone of LGIB management is colonoscopy, which has both diagnostic and therapeutic
potential [5 ]
[6 ]
[7 ]. Although colonoscopy has been accepted to have an important role in LGIB, the optimal
timing of it in LGIB is less clear. Currently, American College of Gastroenterology
(ACG) guidelines have recently encouraged colonoscopy within 24 hours of presentation
for patients with clinical features suggesting high risk [6 ]. In patients with severe acute LGIB, the American Society for Gastrointestinal Endoscopy
(ASGE) has recommended early colonoscopy (EC) within 24 hours of admission following
a rapid bowel preparation [8 ]
[9 ]. However, the evidence supporting these recommendations remains weak. Most of the
previously published studies on the effect of EC on outcomes have been small in sample
size or single-center, thus the impact of EC for clinical outcomes other than mortality
remains uncertain [10 ]
[11 ]
[12 ]
[13 ]
[14 ]. Consequently, the role of EC in LGIB has been the topic of debate in the gastroenterology
community with no single consensus regarding its effect on outcomes, and thus, EC
has not been adopted as the standard of care at many hospitals.
In this study, we hypothesized that because of improved care for patients with LGIB,
mortality is improving. We also aimed to evaluate recent real-world trends in hospitalization
and timing of colonoscopy in patients with LGIB. In addition, we explored factors
impacting inpatient mortality, cost of hospitalization, and LOS in this patient population.
Patients and methods
Design and data source
We performed a retrospective observational study using the National Inpatient Sample
(NIS) [15 ], which is the largest publicly available database drawn from more than 1000 hospitals
in 46 states. It is maintained by the Agency for Healthcare Research and Quality (AHRQ)-sponsored
Healthcare Cost and Utilization Project (HCUP). It includes more than 7 million hospital
admissions each year, which approximates a 20 % stratified sample of discharges from
US community hospitals (nonfederal, short-term, general, and specialty). With weight
adjustment, it estimates more than 35 million hospitalizations nationally. Each index
hospitalization is de-identified and maintained in the NIS with a unique identifier,
principal and secondary discharge diagnoses (up to 25), procedures (up to 15) along
with demographic details including age, sex, race, insurance status and type, comorbidities,
inpatient mortality, length of stay (LOS), cost of hospitalization and other hospital
characteristics. NIS data have been widely used to study trends and predictors of
health care usage, procedural adverse effects, cost, quality, and outcomes.
The NIS maintains internal validity in its database with annual data quality assessments,
while the external validity of the NIS is supported by comparisons against the following
data sources: The American Hospital Association Annual Survey Database, the National
Hospital Discharge Survey from the National Center for Health Statistics and the MedPAR
(Medicare Provider and Analysis Review) inpatient data from the Centers for Medicare
and Medicaid Services.
Population selection
We used a previously published algorithm to identify patients with LGIB using principle
and secondary discharge diagnoses [15 ]
[16 ]. Patients with a specific International Classification of Diseases, Ninth Revision,
Clinical Modification (ICD-9-CM) code for acute LGIB as principal discharge diagnosis
or secondary diagnosis of potential source of acute LGIB with concomitant principal
diagnosis of unspecified LGIB were identified from the NIS database from the years
2005 through 2014. The principal diagnosis was defined as the diagnosis determined
to be the principal reason for hospitalization. Diagnoses that were considered to
be specific for acute LGIB were: diverticulosis or diverticulitis of the colon with
hemorrhage, Dieulafoy lesion, internal, external or unspecified hemorrhoids with bleeding,
angiodysplasia of the intestine with hemorrhage, and hemorrhage of the rectum and
anus. We also included patients with a potential source of acute LGIB (malignant neoplasm
of the colon, rectum, rectosigmoid junction; benign neoplasm of colon or rectum, intestinal
ischemia, non-infectious colitis, inflammatory bowel disease, infectious enterocolitis,
colon ulcer, solitary rectal ulcer syndrome, vascular injury of the intestine, and
anal fissure), while having a concomitant principal diagnosis of “unspecified LGIB.”
ICD 9-CM codes used to identify principal and secondary discharge diagnoses are shown
in Supplementary Table 1 . Patients less than 18 years old and those missing the following data were excluded:
age, sex, or inpatient mortality. Admissions that were marked as “elective,” did not
receive a colonoscopy, or those who had concomitantly documented UGIB were also excluded.
Cases without colonoscopy were excluded as the question in our study was the timing
of the colonoscopy and not whether it was done or not; in that way, the patients we
selected were, in retrospect, stable and safe enough for them to undergo a colonoscopy
during the admission. Performance of colonoscopy during admission was determined by
querying all procedural codes for the ICD-9-CM codes corresponding to colonoscopy
(Supplementary Table 1 ). EC was defined as colonoscopy performed within 24 hours of admission (PRDAY 0–1)
and late colonoscopy was defined as having colonoscopy performed after 24 hours of
admission (PRDAY > 1). Subsequently, cases with invalid or missing data on procedure
days were excluded. Of note, Procedure Day is one of most accurate variable in NIS
and represents the day of the procedure rather than the day the procedure was ordered
or the claim was submitted [17 ]. [Fig. 1 ] summarizes the cohort selection. For sensitivity analysis, performance of esophagogastroduodenoscopy
were identified using codes delineated in Supplementary Table 2 . Institutional Review Board approval was not required as NIS is ade – identified
database available to the public.
Fig. 1 a Trends for acute lower gastrointestinal bleeding (LGIB). The figure depicts the number
of patients with LGIB admitted per 100,000 hospital discharges over the study period
from 2005 to 2014 and shows rising incidence of LGIB admissions (P trend < 0.001). b Trends for colonoscopy timing among patients with acute lower gastrointestinal bleeding
(LGIB). The proportion of patients having early or late colonoscopy over the study
period are shown. Both trends of timing are statistically non-significant (early colonoscopy
P trend = 0.07, late colonoscopy P trend = 0.06). c Trends for inpatient mortality in LGIB over the study period. The rates of inpatient
mortality from 2005 to 2014 in the study cohort are shown (P trend < 0.001).
Variables and outcomes
Each index hospitalization included patient demographics such as age, sex, race, and
insurance status. Hospital characteristics such as urban vs rural location, teaching
status of the hospital, hospital bed size, and hospital region (Northeast, Midwest,
South, or West Northeast, Midwest, South, or West) were also available. Insurance
status was categorized as Medicare, Medicaid, private insurance, and other. Utilization
of invasive support/monitoring that conventionally involves an intensive care unit
(ICU) setting was used as a surrogate to identify ICU admission (Supplementary Table 3 ). Use of blood transfusion during hospitalization was identified using ICD-9 CM codes
(Supplementary Table 3 ). We used the Charlson Comorbidity Index (CCI) to define the overall severity of
comorbidities, because comorbid conditions are known to negatively influence outcomes
of the hospitalization. The CCI is a widely-used index to measure the severity of
co-morbidity burden from administrative databases [18 ]
[19 ]. The CCI was calculated for each admission as described in Supplementary Table 4 . Hospitalization costs were calculated by multiplying cost-to-charge (CCR) ratios
provided by the Health Care Cost and Utilization Project (HCUP) by the TOTCHG (total
charges) variable, subsequently weighted for missing values and finally adjusted for
annual inflation using inflation calculator [20 ], with reference to year 2014.
The primary aim of this study was to assess trends for LGIB admission, timing of colonoscopy,
and mortality over the study period. The secondary aims were to assess factors affecting
inpatient all-cause mortality, cost of hospitalization, and LOS with particular interest
in timing of colonoscopy.
Statistical analysis
We calculated weighted means ± standard errors (SE) and % for continuous and categorical
variables, respectively, for both the groups: EC and late colonoscopy. Trend analyses
were conducted using mixed models (Hospital ID-Year as the random intercept), against
unit increase of year. Univariate analysis correlation tables were done to establish
significant associations between each covariate and the outcomes of inpatient mortality,
hospitalization costs and LOS, using mixed-effects logistic regression, mixed-effects
log-transformed linear regression and mixed-effects accelerated-failure-time (AFT)
with log-normal distribution model, respectively. AFT models can estimate LOS while
censoring inpatient deaths, as the event is defined “alive at discharge.” An additional
benefit of AFT models is the interpretability of the Time Ratio on (geometric mean
of) LOS, allowing to compare longer/shorter LOS by % at the level of each covariate,
while not being subject to the proportional hazards assumption. Covariates with clinical
merit and statistical significance at P < 0.1 on univariate analysis have been included in the multivariate models, taking
into account multicollinearity, possible interactions, and overfitting. Multicollinearity
was assessed by the Variance Inflation Factor (goal VIF < 10). The goodness of fit
of the logistic regression model was evaluated using the area under the curve (AUC,
i. e., c-statistic) and goodness of fit for linear regression (hospitalization costs)
was assessed using observed vs fitted plots and pseudo-R2 . Details of each analysis are shown in their respective multivariable analysis models.
Sensitivity analyses for each outcome were done by including the performance and timing
of esophagogastroduodenoscopy (EGD) as an interaction term with early and late colonoscopy,
therefore adjusting for potential selection bias for early vs. late colonoscopy, which
can result from the performance of an EGD itself, its timing, as well as its potential
findings.
Acknowledging the retrospective nature of the study and the risk of selection bias
for or against undergoing an early vs. late colonoscopy, we performed exact-matching
among patients who underwent colonoscopy, taking into account various confounders
that could potentially affect the following: 1. the decision of clinicians to choose
early vs. late colonoscopy for a patient; and 2. outcomes (inpatient mortality, hospitalization
costs and LOS). The exact-matching analysis estimated its own analytical weights according
to the total number of matched cases within each matched stratum, therefore the estimated
effects are by design not nationally-weighted. Continuous variables were semi-exact-matched,
i. e., matching groups were created to facilitate optimal balance between potential
residual mismatch (variability) and powering (number of cases) within matched strata;
these variables were then additionally included in the post-matching regression models
to adjust for any residual variability (i. e. double-robust regression). In addition
to the matching variables used, patients were matched to the same hospital within
the same year to account for inherent differences between hospitals and endoscopists.
Further details on the number of matched observations and number of matched strata,
matching variables used, and post-matching regression covariates are as described
in multivariable analysis models in results section. The advantage of using exact-matching
over other matching methods such as propensity score matching (PSM), is that in contrast
to PSM, exact-matching compares patients with exactly the same characteristics (instead
of having a similar propensity score potentially reflecting different characteristics),
thereby eliminating regression modeling caveats such as multicollinearity, overfitting,
miss-specification (i. e. unspecified covariates and/or interactions in the model).
National estimates were calculated using the TRENDWT (trend weight) variable, as recommended
by HCUP, while also adjusting for potentially missing hospitals from the LGIB subpopulation.
Complex-survey design commands (“svy”) were used to account for the NIS complex-survey
design, as recommended by HCUP. P values were considered significant a priori at < 0.05. All analyses were performed
with Stata MP 14.2 (Stata-Corp, College Station, Texas, United States).
Results
Baseline characteristics
A total of 1,643,235 patients with LGIB were identified during the study period and
after excluding patients based on exclusion criteria, we included 814,647 patient
with LGIB undergoing colonoscopy regardless of timing in the final analysis (Supplementary Fig. 1 ). The mean age of patients in the study population was 72 years, with equal sex distribution,
but with a predominance of White patients (518,395; 69 %) as shown in [Table 1 ]. One-fourth of patients (201,320; 25 %) were admitted on a weekend. AKI was present
in 66,208 (8 %) of patients. The majority of patients were admitted to urban (733,567;
90 %), large bed size (493,098; 61 %), and teaching hospitals (357,102; 44 %). Southern
hospitals accounted for the most patients (324,537; 40 %) of the four regions examined.
Although 0.6 % patients (5,401) were admitted to an ICU, 42 % of patients (344,760)
had a blood transfusion during hospitalization. The overall mortality rate was 0.6 %
(5,240). The mean LOS was 4.5 days, with a cost of hospitalization at $ 10,100. Of
note, 46 % (372,823) admitted for LGIB underwent simultaneous EGD.
Table 1
Baseline characteristics.
Variables
Late colonoscopy
Early colonoscopy
Total
P value
Patient characteristic
Age[1 ]
72
71
72
< 0.001
Female[1 ]
237,823 (53)
176,668 (48)
414,491 (51)
< 0.001
Weekend admission[1 ]
126,741 (28)
74,579 (20)
201,320 (25)
< 0.001
CCI [median; IQR][1 ]
1.4 ± 0.1
1.1± 0.1
1.2 ± 0.1
< 0.001[1 ]
Acute kidney injury[1 ]
43,244 (10)
22,963 (6)
66,208 (8)
< 0.001
Race
White
284,980 (68)
233,415 (69)
518,395 (69)
< 0.001
Black
77,789 (19)
55,777 (17)
133,566 (18)
Hispanic
34,991 (8)
28,005 (8)
62,996 (8)
Asian/Pacific Islander
8,899 (2)
10,669 (3)
19,568 (3)
Native American
1,749 (0.4)
1,380 (0.4)
3,129 (0.4)
Other
9,261 (2)
7,620 (2)
16,881 (2)
Insurance type
Medicare
329,134 (74)
255,182 (70)
584,316 (72)
< 0.001
Medicaid
25,686 (6)
17,275 (5)
42,961 (5)
Private
69,800 (16)
74,325 (20)
144,124 (18)
Self-pay
13,117 (3)
11,587 (3)
24,704 (3)
No charge
1,892 (0.4)
1,440 (0.4)
3,333 (0.4)
Other
7,457 (2)
6,606 (2)
14,063 (2)
Hospital location
Urban location
403,453 (90)
330,115 (90)
733,567 (90)
0.707
Teaching status
Teaching hospital
198,701 (44)
158,401 (43)
357,102 (44)
0.016
Hospital region
Northeast
125,767 (28)
70,593 (19)
196,359 (24)
< 0.001
Midwest
73,241 (16)
71,032 (19)
144,273 (18)
South
184,921 (41)
139,617 (38)
324,537 (40)
West
63,877 (14)
85,601 (23)
149,477 (18)
Hospital bed size
Small
51,324 (12)
46,679 (13)
98,003 (12)
< 0.001
Medium
121,583 (27)
97,990 (27)
219,573 (27)
Large
272,927 (61)
220,170 (60)
493,098 (61)
Resource utilization
ICU Admission
2,867 (0.6)
2,534 (0.7)
5,401 (0.6)
0.222
Inpatient mortality
2,863 (0.6)
2,377 (0.7)
5,240 (0.6)
0.829
Length of Stay [median]
4
2
3
< 0.001[2 ]
[Arithmetic mean]
5.3
3.5
4.5
< 0.001
[Geometric mean]
4.3
2.7
3.6
< 0.001
Cost [median; IQR]
8,240; 5,745–12,445
6,093; 4,157–9,482
7,258; 4,928–11,255
< 0.001[3 ]
[Arithmetic mean]
11,143
8,817
10,100
< 0.001
[Geometric mean]
8,559
6,613
7,739
< 0.001
Blood transfusion[1 ]
201,633 (45)
143,127 (39)
344,760 (42)
< 0.001
Colectomy/colostomy[1 ]
7.973 (1.8)
9,558 (2.6)
17,531 (2.2)
< 0.001
EGD
228,372 (51)
144,451 (39)
372,823 (46)
< 0.001
EGD timing[3 ]
Early EGD
71,706 (16)
127,224 (35)
198,930 (25)
< 0.001
Late EGD
150,447 (34)
11,473 (3)
161,921 (20)
< 0.001
% compared with weighted chi-square tests and continuous variables with weighted t-test,
unless otherwise specified
CI, confidence interval; EGD, esophagogastroduodenoscopy; CCI, Charlson Comorbidity
Index; ICU, intensive care unit; IQR, interquartile range.
1 Variables used for exact-matching analysis, which also matched same hospitals within
the same year.
2 Tested with generalized linear model with log-transform under Poisson distribution.
3 Tested with generalized linear model with log-transform under Normal distribution.
Forty-five percent of patients (366,842) with LGIB underwent EC while 55 % (447,805)
had LC ([Table 1 ]). Patients were slightly older (72 vs. 71 years) and more likely to be female in
the LC group [237,823 (53 %) vs. 176,668 (48 %)]. Weekend admissions were more common
in the LC group (126,741; 28 %) than EC group (74,579; 20 %) (χ2
P < 0.001]. The CCI was slightly higher in the LC group (1.4 vs. 1.1). Patients requiring
ICU level care were equally distributed between the two cohorts (0.6 %; 2,867 in LC
group and 0.7 %; 2,534 in EC group). Blood transfusion was more common in the LC group
(201,633; 45 % vs 143,127; 39 %). Though the proportion of patients undergoing EGD
was higher in the LC than in the EC group (228,372; 51 % vs 144,451;39 %), stratification
based on timing of EGD showed that the LC group had later EGDs (34 %; 150,447 vs.
3 %; 11,473) while the EC group had more early EGDs (35 %; 127,224 vs. 16 %; 71,706).
The median LOS was 2 days longer (5.3 vs. 3.5 days) and cost of hospitalization was
nearly $ 2,000 higher in LC group ($ 11,143 vs. $ 8,817). Mortality rates in the two
groups was identical (0.6 %; 2,863 in LC group vs. 0.7 %; 2,377 in EC group).
Trends in LGIB admissions, timing of colonoscopy and mortality
LGIB admissions increased from 472 in 2005 to 526 per 100,000 discharges in year 2014
[P trend < 0.001)([Fig. 1a ]). Of note, the timing of colonoscopy changed very little over the study period (LC
changed from 53.8 % to 55.4 %; P trend = 0.06 and EC from 46.2 % to 44.6 %; P trend = 0.07)([Fig. 1b ]). The inpatient mortality rate decreased slightly from 0.75 % in 2005 to 0.57 %
in 2014 P trend < 0.001]([Fig. 1c ]).
Causes of LGIB
The most common diagnosis associated with LGIB was diverticular bleeding (49 %; 398,487),
followed by anorectal hemorrhage (26.7 %; 217,446) and colonic polyps (11 %; 87,192)
([Table 2 ]). Of secondary etiologies with unspecified LGIB as linked diagnosis, polyps and
inflammatory lesion of the colon were most prominent ([Table 2 ]). It should be noted that some patients had more than one discharge diagnosis code
consistent with LGIB or a potential source of LGIB.
Table 2
Etiology of LGIB
Late colonoscopy
Early colonoscopy
Total
Primary diagnosis
Diverticular bleeding
193,938 (43.3)
204,549 (55.8)
398,487 (48.9)
Anorectal hemorrhage
119,761 (26.8)
97,685 (26.5)
217,446 (26.7)
Intestinal arteriovenous malformations
42,448 (9.5)
22,791 (6.2)
65,240 (8.0)
Dieulafoy lesion
1,808 (0.4)
1,842 (0.5)
3,650 (0.4)
Unspecified LGIB with secondary etiologies
89,850 (20.1)
39,974 (10.9)
129,824 (15.9)
Polyps
63,039 (14.1)
24,153 (6.6)
87,192 (10.7)
Non-infectious colitis
8,747 (1.9)
4,244 (1.2)
12,991 (1.6)
Colonic ulcer
5,683 (1.3)
3,946 (1.1)
9,629 (1.2)
Ischemic colitis
4,387 (0.9)
2,713 (0.7)
7,100 (0.8)
Inflammatory bowel disease
3,233 (0.7)
2,288 (0.6)
5,521 (0.7)
Solitary rectal ulcer
2,851 (0.6)
1,649 (0.4)
4,500 (0.5)
Colorectal cancer
2,148 (0.5)
1,296 (0.4)
3,443 (0.4)
Gastrointestinal vessel anomaly
1,227 (0.3)
567 (0.2)
1,795 (0.2)
Anal fissure
636 (0.1)
408 (0.1)
1,043 (0.1)
Infectious colitis
495 (0.1)
365 (0.1)
860 (0.1)
LGIB, lower gastrointestinal bleeding.
Factors associated with inpatient mortality
There was no statistically significant difference in odds of mortality between the
EC and LC group (OR:1.08, 95 % CI: 0.93–1.25, P = 0.336) ([Table 3 ]). In addition, results were similar after performing the exact matching (OR:1.77,
CI:0.70–4.50, P = 0.23). We also performed a sensitivity analysis focused on EGD (during the same
admission) and found that EGD (whether early or late) did not affect mortality odds
compared to no EGD ([Table 3 ]). Non-diverticular LGIB had no difference in odds of mortality compared to diverticular
LGIB (OR: 0.91, P = 0.185). A 10-year increase in patient age was associated with a 44 % increase in
odds of mortality (OR:1.44, P < 0.001). The odds of mortality was almost 17 % lower in women than in men (OR:0.83,
P = 0.006). Weekend admission did not appear to influence the mortality odds compared
to weekday admissions (OR:1.12, 95 % CI: 0.96–1.29, P = 0.149). Not surprisingly, increases in the CCI score of 1 point in patients with
LGIB was associated with an increase in odds of mortality by 33 % (OR:1.33, P < 0.001). ICU admission and surgery requirement were associated with 18-fold (OR:18.7,
P < 0.001) and 9-fold rise (OR:9.7, P < 0.001) in mortality odds, respectively. Blood transfusion during admission was
associated with a 30 % increase in odds of death (OR:1.3; P < 0.001). AKI in the setting of LGIB was associated with nearly 3-fold higher mortality
odds ([Table 3 ]). Compared to Northeast US hospitals, hospitals situated in the Midwest had 28 %
lower mortality odds while no difference existed for hospitals located in other parts
of the United States. Rural hospitals and teaching hospitals had no difference in
mortality odds compared to their counterparts. Moreover, hospital bed size did not
affect mortality.
Table 3
Factors associated with inpatient mortality in patients who underwent colonoscopy.
Variable
Odds Ratio
Lower 95 % CI
Upper 95 % CI
P value
Late colonoscopy
Referent
Early colonoscopy (< 24 h)
1.08
0.93
1.25
0.336
Early colonoscopy (< 24 h) [exact-matching][1 ]
1.77
0.70
4.50
0.23
No EGD
Referent
Early EGD
1.16
0.99
1.35
0.060
Late EGD
0.91
0.76
1.09
0.317
Age (per decade-increase)
1.44
1.35
1.55
< 0.001
Female
0.83
0.72
0.95
0.006
Weekend admission
1.12
0.96
1.29
0.149
CCI
1.33
1.30
1.36
< 0.001
Non-diverticular bleed
0.91
0.78
1.05
0.185
AKI
2.84
2.43
3.32
< 0.001
Colectomy/colostomy in same admission
9.76
8.02
11.88
< 0.001
ICU admission
18.78
14.66
24.06
< 0.001
PRBC Transfusion
1.30
1.13
1.50
< 0.001
Hospital region
Northeast
Referent
Midwest
0.72
0.57
0.89
0.003
South
0.85
0.71
1.02
0.080
West
0.86
0.70
1.05
0.132
Hospital location/teaching status
Rural
Referent
0.96
0.75
1.23
0.766
0.93
0.72
1.19
0.541
Hospital bed size
Small
Referent
Medium
0.90
0.71
1.15
0.390
Large
1.00
0.80
1.24
0.969
Analysis N = 798,720. Mean variance inflation factor: 2.76
Intraclass correlation coefficient: 0.116
Area under the curve ROC: 0.913
CI, confidence interval; EGD, esophagogastroduodenoscopy; AKI, acute kidney injury;
CCI, Charlson Comorbidity Index; ICU, intensive care unit; PRBC, packed red blood
cell.
These results are derived from multivariable analysis using mixed-effects logistic
regression.
1 Exact-Matched Analysis on variables marked [1 ] in Table 1, yielding 19,631 matched observations (early colonoscopies n = 10,001),
among 6,947 matching strata.
Factors associated with cost of hospitalization
After adjusting for LOS, the mean cost of hospitalization was approximately 12 % lower
in patients who underwent EC (OR:0.88, 95 % CI: 0.85–0.88, P < 0.001) ([Table 4 ]). Here, 12 % represents change over the geometric mean of cost of hospitalization,
which corresponds to $ 1,946 reduced cost with EC compared to late colonoscopy. Performance
of exact matching yielded similar results (OR: 0.87, 95 % CI: 0.85–0.88, P < 0.001). Sensitivity analysis showed that EGD either early or late minimally impacted
cost of hospitalization (cost decrease ranging from 1 %-7 %). Per day increase in
LOS was associated with 47 % increase in hospitalization cost. Weekend admissions
were associated with minimal increase in hospitalization cost (OR:1.01, P < 0.001). AKI, LGIB leading to ICU admission, and the need for surgery or blood transfusion
increased cost of hospitalization. Hospitals situated in the Western United States
had a 14 % higher cost of hospitalization, while the South and Midwest had 14 % and
2 % lower costs compared to hospitals in the Northeast United States, respectively.
Teaching hospitals and urban hospitals had an almost 5 % lower cost of hospitalization
compared to rural hospitals. Medium and large bed sizes were associated with lower
cost of hospitalization compared to small bed size.
Table 4
Factors affecting hospitalization costs in patients with LGIB who underwent colonoscopy.
Variable
Odds Ratio
Lower 95 % CI
Upper 95 % CI
P value
Late colonoscopy without EGD
Referent
Early colonoscopy (log(LOS)-adjusted)
0.88
0.87
0.88
< 0.001
Early colonoscopy [exact-matched][1 ]
0.87
0.85
0.88
< 0.001
No EGD†
Referent
Early EGD
0.99
0.98
0.99
0.04
Late EGD
0.93
0.92
0.94
< 0.001
Age (per decade-increase)
0.99
0.99
0.99
< 0.001
LOS (log-transformed)[2 ]
1.47
1.45
1.49
< 0.001
Weekend admission
1.01
1.005
1.014
< 0.001
CCI†
1.022
1.021
1.023
< 0.001
AKI
1.12
1.115
1.133
< 0.001
Colectomy/colostomy in same admission
1.93
1.89
1.97
< 0.001
ICU admission
1.58
1.52
1.63
< 0.001
PRBC transfusion
1.03
1.026
1.04
< 0.001
Hospital region
Northeast
Referent
Midwest
0.98
0.96
0.99
0.009
South
0.86
0.85
0.88
< 0.001
West
1.14
1.12
1.17
< 0.001
Hospital location/teaching status
Rural
Referent
Urban non-teaching
0.94
0.93
0.96
< 0.001
Urban teaching
0.93
0.92
0.95
< 0.001
Hospital bed size
Small
Referent
Medium
0.94
0.93
0.96
< 0.001
Large
0.90
0.89
0.92
< 0.001
Note: The model was fitted to the log of hospitalization costs.
Analysis N = 751,552. Geometric mean hospitalization costs: $ 7,718 USD.
Odds ratios reflect % change over the geometric mean hospitalization costs.
LGIB, lower gastrointestinal bleeding; CI, confidence Interval; EGD, esophagogastroduodenoscopy;
LOS, length of stay; CCI, Charlson Comorbidity Index; ICU, intensive care unit.
These results are derived from multivariable analysis using mixed-effects log-transformed
linear regression.
1 Exact-matched analysis on variables marked
2 in this Table as well as same hospital-year, yielding 13,662 matched observations
(early colonoscopies n = 6,940), among 5,127 matching strata. Log(LOS), colectomy/colostomy,
and ICU admission were added as confounders in the post-matching regression model.
Factors associated with length of stay
EC was associated with a 32 % shorter LOS compared to patients with late colonoscopy
(TR:0.68, 95 % CI:0.67–0.68, P < 0.001) ([Table 5 ]). Here, 32 % represents a change over the geometric mean of LOS, which corresponds
to a 1.6-day lower LOS with EC compared to late colonoscopy. Further analysis with
exact matching revealed similar results (OR:0.64, 95 % CI:0.63–0.65, P < 0.001). Other variables associated with a reduction in LOS included: (1) having
an early EGD; (2) male sex; and (3) being located in a rural area ([Table 5 ]). On the other hand, older age, requiring surgery or a blood transfusion, or developing
AKI were associated with a longer LOS ([Table 5 ]).
Table 5
Factors affecting length of stay in patients with LGIB who underwent colonoscopy.
Variable
Time Ratio
Lower 95 % CI
Upper 95 % CI
P value
Late colonoscopy
Referent
Early Colonoscopy ( < 24 h)
0.68
0.68
0.68
< 0.001
Early Colonoscopy ( < 24 h) [exact-matched][1 ]
0.64
0.63
0.65
< 0.001
No EGD
Referent
Early EGD
0.87
0.87
0.88
< 0.001
Late EGD
0.96
0.96
0.97
< 0.001
Age (per decade-increase)
1.05
1.048
1.053
< 0.001
Female
1.05
1.045
1.056
< 0.001
Weekend admission
0.99
0.980
0.991
< 0.001
CCI
1.04
1.036
1.039
< 0.001
AKI
1.20
1.19
1.21
< 0.001
Colectomy/colostomy in same admission
2.38
2.34
2.43
< 0.001
ICU admission
1.67
1.59
1.75
< 0.001
PRBC transfusion
1.06
1.05
1.07
< 0.001
Insurance
Medicare
Referent
Medicaid
1.04
1.03
1.05
< 0.001
Private
0.95
0.94
0.95
< 0.001
Self-pay
0.98
0.96
0.99
0.006
No charge
1.00
0.96
1.04
0.808
Other
1.00
0.98
1.02
0.709
Hospital region
Northeast
Referent
Midwest
0.94
0.93
0.95
< 0.001
South
0.96
0.95
0.97
< 0.001
West
0.86
0.85
0.87
< 0.001
Hospital location/teaching status
Rural
Referent
Urban non-teaching
1.05
1.04
1.07
< 0.001
Urban teaching
1.06
1.05
1.08
< 0.001
Hospital bed size
Small
Referent
Medium
1.04
1.03
1.05
< 0.001
Large
1.08
1.06
1.09
< 0.001
Analysis N = 794,455. Geometric mean length of stay: 3.5 days.
Area under the curve: 0.774
Time ratios reflect % change over the geometric mean length of stay
LGIB, lower gastrointestinal bleeding; CI, confidence interval; EGD, esophagogastroduodenoscopy;
CCI, Charlson Comorbidity Index; ICU, intensive care unit.
These results are derived from multivariable analysis using mixed-effects accelerated-failure-time
(AFT) model with log-normal distribution.
1 Exact-matched analysis on variables marked [1 ] in Table 1 and on number of diagnostic/operative procedures (in addition to colonoscopy),
yielding 14,903 matched observations (early colonoscopies n = 7,606), among 5,309
matching strata.
Discussion
We report here that between 2005 and 2014, the number of patients admitted with LGIB
has increased, but mortality among these patients is improving. In addition, despite
guidelines and non-randomized data supporting that EC may lead to more rapid identification
of colonic lesions [11 ] and shorter hospital LOS [15 ]
[20 ]
[21 ]
[22 ]
[23 ], EC has not been widely adopted. Finally, in patients admitted with LGIB, EC was
associated with decreased LOS and cost of hospitalization, but no significant difference
in mortality compared to LC. ICU admission, AKI, and surgery requirement are the strongest
predictors of mortality in LGIB.
This study represents a large, population-based, real-world examination of practice
patterns for colonoscopy in patients with acute LGIB in the United States. Despite
the fact that current guidelines recommend that colonoscopy be performed within 24
hours in patients admitted with LGIB [6 ]
[8 ], we found that as of 2014, in a real-world setting, only 45 % of patients had this
recommended management. We recognize that there may be multiple potential explanations
for this, including unavailability of robust randomized data showing improved outcomes,
difficulty with medical stabilization, and practicality of administering urgent bowel
prep older population with multiple comorbid conditions. We did not find any significant
trend toward performance of EC in LGIB patients. However, we noticed an increase in
hospital admission for LGIB over the years. A study from Spain looking at data from
10 different hospital also reported increased LGIB admissions [4 ]. One potential reason for increasing LGIB admissions could be secondary to the increase
in the aging population [24 ] and may be an increase in use of antithrombotics and/or anticoagulants, particularly
in elderly patients with multiple comorbidities (who are more prone to LGIB).
The possibility that earlier endoscopic intervention can lead to rapid identification
and control of culprit lesion bleeding and consequently could lead to reduced mortality
in patients with LGIB makes timing of colonoscopy a critical point and area of interest
in management of LGIB. Four RCTs [10 ]
[11 ]
[13 ]
[14 ], six observational studies [15 ]
[20 ]
[21 ]
[25 ]
[26 ]
[27 ] and seven meta-analyses [28 ]
[29 ]
[30 ]
[31 ]
[32 ]
[33 ]
[34 ] have been performed to evaluate this issue. One RCT showed that urgent colonoscopy
led to identification of a definitive source of bleeding more frequently, but it did
not lead to lower mortality [11 ]. Another RCT did not show any difference in clinical outcome with EC and it was
prematurely terminated [10 ]. Similarly, observational studies [20 ]
[21 ] showed that EC provided no mortality benefit. Results from seven meta-analyses [28 ]
[29 ]
[30 ]
[31 ]
[32 ]
[33 ]
[34 ] have yielded mixed results, with four reporting no difference in diagnostic yield
[28 ]
[30 ]
[32 ]
[34 ] while three report increased diagnostic yield [29 ]
[31 ]
[33 ]; all showed no difference in rebleeding rate; all reported no difference in LOS
except one [29 ]; no difference in transfusion requirement but one reported increased transfusion
for EC [33 ]; all showed no difference in mortality rate. All these meta-analyses differed in
the number of studies, and study designs included in quantitative synthesis along
with their primary aim of study. Given the low mortality in LGIB, it is likely that
RCTs with a very large sample size will be required to demonstrate a mortality benefit,
if in fact there is one. We also acknowledge that because our study was non-randomized,
it cannot definitively shed light on mortality benefit with EC.
The impact of timing of colonoscopy on clinical outcomes other than mortality is important
in clinical management. In one study, rapid colonoscopy with endoscopic therapy within
12 hours of presentation in patients with severe hematochezia and diverticulosis resulted
in reduced rebleeding rate and need for surgery [12 ]. One study reported lower transfusion requirement associated with early endoscopy
[21 ] and an NIS-based study showed that EC reduced LOS and cost of hospitalization [15 ]. A meta-analysis showed a decreased LOS and fewer complications with early endoscopy
[29 ]. A recent meta-analysis [32 ] that only included RCTs reported no change in LOS with EC. However, a statistical
analysis was not performed to specifically evaluate this result. Another recent meta-analysis
studied impact of timing on LOS for RCTs and observational studies separately: no
difference in LOS was found for RCTs only, but when only observational studies were
analyzed, LOS was statistically reduced [34 ]. In our study, we found that EC was associated with a substantially decreased hospital
LOS (by 1.6 days) in comparison to late colonoscopy, consistent with several other
studies [15 ]
[20 ]
[21 ]
[22 ]
[23 ]. Therefore, we presume that EC may lead to early triage of patients and shorter
wait time to get colonoscopy, and thus subsequently earlier discharge, which could
explain the short LOS. As expected, reduced LOS ultimately translates into cost reduction
and, as expected, our study showed a decrease in cost of hospitalization by $ 1,946
with EC even after adjusting for LOS.
Patients who are admitted on weekends for LGIB represent a challenging group because
in many hospitals, appropriate staffing to perform procedures such as colonoscopy
is limited or unavailable. The impact of weekend admission on patients with UGIB has
been variable in terms of mortality, LOS, and cost of hospitalization [35 ]
[36 ]. A previous NIS-based study reported no difference in mortality but increased LOS
with weekend admission in LGIB patients [15 ]. In our study, we also found that weekend admission did not affect mortality, LOS
or cost of hospitalization compared to weekday admission. The LC group had more weekend
admissions, implying that issues with logistics over the weekend may led to delays
in colonoscopy and increased costs. Arguing against this possibility is the finding
that weekend admission in our study was not associated with higher cost compared to
weekday admission. Thus, our study does not support a “weekend effect.”
In our multivariable regression analysis, increments in age and comorbidity were associated
with an increase in mortality. Both of these variables are well-known risk factors
for death and have been incorporated in risk stratification tools in UGIB [37 ]
[38 ]
[39 ]. Age > 70 years and more than two comorbidities have been identified as independent
predictors of mortality [37 ]
[38 ]
[39 ]. Our study reiterates impact of age and comorbidities in risk stratification for
this patient population. Diverticular bleeding represents the largest proportion of
LGIB cases [40 ]. After separating the diverticular bleeding and non-diverticular bleeding cohort,
we compared the mortality rate between the two and found no statistically significant
difference.
We recognize the limitations of our study. As with all population-based studies, the
diagnosis of LGIB is reliant on accurate diagnostic coding. Our study utilized ICD-9
coding methodology similar to a prior population-based study in this area [15 ]
[16 ]. In addition, given the nature of the NIS data, we were unable to evaluate rebleeding
rates, a relevant clinical outcome in LGIB. Similarly, because of unavailability of
Current Procedural Terminology codes and non-specific ICD-9 codes for endoscopic interventions,
we were unable to ascertain whether an intervention was performed during the colonoscopy
itself. Some results that are statistically significant on bivariate analysis may
not be clinically significant (i. e., age between the EC and LC groups), which may
suggest type II error. In addition, our study results are only applicable to patients
admitted with acute LGIB in the United States. However, our study has several strengths
and clinical applications. With this large NIS-based study encompassing data over
10 year, we studied the largest sample to date in this area, which is also free of
biases that may be introduced in studies from small individual centers. This suggests
that our results are likely generalizable across the entire US population.
Conclusion
In summary, our study demonstrated that practice patterns in terms of performance
of EC have not changed over the last decade. Admissions with acute LGIB are on the
rise with an improved all-cause inpatient mortality rate. Further, the data indicate
that timing of colonoscopy – early or late – does not appear to influence overall
inpatient mortality. However, the data indicated that EC was associated with decreased
healthcare costs compared with LC and suggest that EC may lead to more efficient patient
care.
