SUPPLEMENTAL DIGITAL CONTENT 1
Results of Sensitivity analyses
Inverse probability of treatment weight analysis
The probability of treatment received for each patient corresponds to the propensity score
(for early group) or, 1 minus the propensity score (for delayed group). Weighting on the inverse
of the probability of treatment received created a synthetic study sample that was well-balanced
with respect to observed covariates (Table S1). The operative outcome results from the weighted
analysis are similar to the matched analysis (Table S2). Total hospital length of stay remained
shorter with early surgery (mean difference 1.9 days, 95% confidence interval 1.8-2.1 days).
Defining early cholecystectomy as occurring within 3 days of emergency department
presentation
When narrowing the timeframe for early cholecystectomy to 3 days from ED
presentation, 13,087 (59% of 22,202) were considered to have undergone early cholecystectomy.
Using the same propensity score model and matching algorithm as the primary analysis, 7,865
well-balanced matched pairs were formed. The results with the new exposure definition remain
consistent with the primary analysis (Table S3). Total hospital length of stay remained shorter
with early surgery (mean difference 2.6 days, 95% confidence interval 2.5-2.8 days).
Excluding patients who underwent delayed cholecystectomy later than 1 year after
discharge
When excluding patients who underwent delayed cholecystectomy later than 1 year after
discharge, the cohort was reduced to 21,937 patients. Applying the same propensity score model
and matching algorithm as the primary analysis resulted in 6,864 well-balanced matched pairs.
The results for this cohort are similar to the primary analysis (Table S4). Total hospital length of
stay remained shorter with early surgery (mean difference 1.9 days, 95% confidence interval 1.72.1 days).
Defining major bile duct injury based on repair or reconstruction of the biliary tract within
12 months of cholecystectomy
When using a 12 month window, as opposed to 6 months, to capture biliary tract repair
for major bile duct injury, the cohort was reduced to 20,442 patients since the minimum postcholecystectomy follow-up was increased to 12 months. Applying the same propensity score
model and matching algorithm as the primary analysis resulted in 6,577 well-balanced matched
pairs. The results for major bile duct injury and major bile duct injury or death for this cohort are
similar to the primary analysis (Table S5).
E1
Table S1. Baseline characteristics of patients and their surgeon in synthetic cohort after
weighting on the inverse probability of treatment received
Characteristic a
Early
cholecystectomy
(n=14,948)
Delayed
cholecystectomy
(n=7,254)
54 (21)
4,700 (31)
8,999 (60)
54 (31)
2,252 (31)
4,366 (60)
3,207 (21)
3,219 (22)
2,939 (20)
2,922 (20)
2,661 (18)
1,563 (22)
1,563 (22)
1,419 (20)
1,419 (20)
1,290 (18)
3.2±16.3
3,697 (25)
1522 (10)
709 (5)
3.2±23.3
1,772 (24)
736 (10)
344 (5)
21±12
3,731 (25)
21±17
1,711 (24)
72 (59)
3,661 (24)
72 (85)
1,841 (25)
Patient
Age, y
mean (SD)
≥65 years, no. (%)
Female sex, no. (%)
Income Quintile, no. (%)
1
2
3
4
5b
ADG c comorbidity index
mean (SD)
highest quartile, no. (%)
Common bile duct obstruction, no. (%)
Pancreatitis, no. (%)
Surgeon
Years since medical school graduation
mean (SD)
highest quartile (≥29) , no. (%)
Number of cholecystectomies in
preceding year
mean (SD)
highest quartile (≥90), no. (%)
a
All characteristics were well balanced (standardized differences of at most 3% as well as
similar distributions of continuous variables when verified graphically).
b
Highest income level
c
Aggregated Diagnostic Group
E2
Table S2. Relative risk of outcome after weighting on inverse probability of treatment
Outcome
a
Relative risk b
Major bile duct injury
0.56 (0.36 – 0.89)
Major bile duct injury or death
0.71 (0.56 – 0.90)
30-day post-cholecystectomy mortality
0.67 (0.45 – 1.01)
Cholecystectomy completed open
1.03 (0.98 – 1.08)
Conversion among laparoscopic cases
0.99 (0.91 – 1.08)
a
Total study sample (n=22,202) included in analysis. Conversion was compared within the
21,936 laparoscopic cases
b
Relative risk (early compared to delayed cholecystectomy) is presented with the corresponding
95% confidence interval.
Table S3. Relative risk of outcomes when defining early cholecystectomy as occurring within 3
days of emergency department presentation
E3
Outcome a
Relative risk b
Major bile duct injury
0.48 (0.26 – 0.91)
Major bile duct injury or death
0.57 (0.42 – 0.77)
30-day post-cholecystectomy mortality
0.61 (0.36 – 1.03)
Cholecystectomy completed open
1.04 (0.96 – 1.13)
Conversion among laparoscopic cases
0.93 (0.84 – 1.02)
a
The outcome results reflect 7,865 well-balanced matched pairs from a total study sample of
22,202. Conversion was compared within the 7,165 well-balanced matched pairs that began with
a laparoscopic approach.
b
Relative risk (early compared to delayed cholecystectomy) is presented with the corresponding
95% confidence interval.
Table S4. Relative risk of outcome when excluding delayed cholecystectomy later than 1 year
after discharge
Outcome a
Relative risk b
E4
Major bile duct injury
0.49 (0.28 – 0.84)
Major bile duct injury or death
0.73 (0.56 – 0.96)
30-day post-cholecystectomy mortality
0.70 (0.45 – 1.11)
Cholecystectomy completed open
1.07 (0.99 – 1.16)
Conversion among laparoscopic cases
1.05 (0.95 – 1.16)
a
The outcome results reflect 6,864 well-balanced matched pairs from a starting sample of
21,937. Conversion was compared between the 6,242 well-balanced matched pairs that began
with a laparoscopic approach.
b
Relative risk (early compared to delayed cholecystectomy) is presented with the corresponding
95% confidence interval.
Table S5. Relative risk of outcome when capturing major bile duct injury as operative repair
within 12 months of cholecystectomy
Outcome a
Relative risk b
0.42 (0.23 – 0.76)
Major bile duct injury
E5
0.70 (0.53 – 0.92)
Major bile duct injury or death
a
The outcome results reflect 6,577 well-balanced matched pairs from a starting sample of
20,4421.
b
Relative risk (early compared to delayed cholecystectomy) is presented with the corresponding
95% confidence interval.
E6