Appendix A. Caprini risk factor analysis
TableA1. Complete Caprini risk factor distribution by cohort and relative risk for VTE events
(n=366)
Caprini risk factor / Caprini points / No VTE,(n = 342) (%) / VTE,
(n = 24)
(%) / RR (95% CI)
For VTE development / p value
Age Category / 0.08
40-59 years / 1 / 113 / (33.6) / 4 (16.7) / Ref
60-74 years / 2 / 161 / (47.9) / 17 / (70.8) / 2.8 / (1.0 – 8.1)
≥ 75 year / 3 / 62 / (18.5) / 3 / (12.5) / 1.4 / (0.3 – 5.8)
Minor surgery planned / 1 / 2 / (0.6) / 0 / - / -
BMI ≥30 kg/m2 / 1 / 85 / (24.9) / 8 / (33.3) / 1.5 / (0.6 – 3.3) / 0.37
History of prior major surgery (<1 month) / 1 / 11 / (3.2) / 0 / - / -
Swollen legs (current) / 1 / 21 / (6.1) / 5 / (20.8) / 3.4 / (1.4 – 8.5) / 0.02
Varicose veins / 1 / 25 / (7.3) / 6 / (25) / 3.6 / (1.5 – 8.4) / 0.01
Sepsis (<1 month) / 1 / 9 / (2.6) / 8 / (33.3) / 10.3 / (5.1 – 20.6) / <0.0001
Abnormal pulmonary function / 1 / 143 / (41.8) / 10 / (41.7) / 1.0 / (0.4 – 2.2) / 0.99
Acute myocardial Infarction / 1 / 2 / (0.6) / 1 / (4.2) / - / -
Congestive heart failure / 1 / 4 / (1.2) / 2 / (8.3) / 5.4 / (1.6 – 18.1) / 0.05
History of IBD / 1 / 1 / (0.3) / 0 / - / -
Serious acute lung disease (<1 month) / 1 / 48 / (14) / 10 / (41.7) / 3.8 / (1.8 – 8.1) / <0.01
Medical patient currently at bed rest / 1 / 1 / (0.3) / 0 / - / -
OC or HRT / 1 / 7 / (2.0) / 0 / - / -
History of recurrent spontaneous abortion / 1 / 1 / (0.3) / 0 / - / -
Major open surgery (> 45 minutes) / 2 / 221 / (64.6) / 19 / (79.2) / 2.0 / (0.8 – 5.2) / 0.13
Laparoscopic surgery (> 45 minutes) / 2 / 36 / (10.5) / 3 / (12.5) / 1.2 / (0.4 – 3.8) / 0.77
Prior cancer (except non-melanoma skin cancer / 2 / 69 / (20.2) / 7 / (29.2) / 1.6 / (0.7 – 3.6) / 0.31
Present cancer / 2 / 337 / (98.5) / 24 / (100.0)
Confined to bed (>72 hours) / 2 / 39 / (11.4) / 6 / (25) / 2.4 / (1.0 – 5.7) / 0.08
Central venous access / 2 / 110 / (32.2) / 17 / (70.8) / 4.6 / (1.9 – 10.7) / <0.001
History of VTE / 3 / 6 / (1.8) / 3 / (12.5) / 5.7 / (2.01 – 15.6) / 0.01
Family history of VTE / 3 / 4 / (1.2) / 1 / (4.2)
Present chemotherapy / 3 / 66 / (19.3) / 11 / (45.8) / 3.2 / (1.5 – 6.8) / <0.01
Positive Factor V Leiden / 3 / 1 / (0.3) / 0
Positive Lupus anticoagulant / 3 / 1 / (0.3) / 0
Elevated anticardiolipin antibodies / 3 / 1 / (0.3) / 0
Major surgery lasting > 6 hours / 5 / 83 / (24.3) / 12 / (50.0) / 2.8 / (1.3 – 6.1) / <0.01
Acute spinal cord fracture or paralysis (< 1 month) / 5 / 1 / (0.3) / 0
OC: Oral contraceptive HRT: Hormone replacement Therapy VTE = Venous Thromboembolism
Appendix B. Propensity score analysis
To balance the distribution of patient characteristics between the pre- and post-intervention groups of patients, we used propensity score with caliper matching to select 64 patients (same number as in the post-intervention group) from the pre-intervention group of 302 patients. The caliper width (~0.12) was set equal to 0.2 times the standard deviation of the logit of the propensity score. The propensity score was computed from a logistic regression model to predict presence in the post-intervention group; it included gender (male, female), histology (non-adenocarcinoma, adenocarcinoma), AJCC clinical N stage, surgical approach (lobectomy, non-lobectomy), Caprini risk score categories (low/medium, high) and length of stay (continuous). The mean propensity score for the post-intervention patients was 0.22, while in the original sample it was 0.18 for the pre-intervention patients and 0.22 in the matched sample. The standardized differences for the variables in the propensity model (Table B1) in the original sample ranged from 0.17 (surgical approach) to 1.01 (histology); in the matched sample, they ranged from 0.10 (histology) to 0.22 (length of stay), suggesting that all differences except for surgical approach were reduced in the matched sample. These variables were similarly distributed for both groups in the quintiles of propensity score. We then conducted an analysis on the matched sample of patients; however, these results should be interpreted cautiously due to small sample sizes.
In the matched sample, we had 5 patients (2 post- and 3 pre-intervention) with VTE, and 123 (62 post- and 61 pre-intervention) with no VTE. Given these small numbers, we were limited in what analyses we could conduct. The main variable of interest (presence of VTE in the pre- or post-intervention group), although not statistically significant at two-sided level of 0.05, still showed a higher relative risk (RR: 1.5; 95% CI: 0.3-8.7; p=0.65) of having VTE for a pre-intervention patient than for a post-intervention patient in the matched sample, consistent with results from the original sample (RR=2.3; 9% CI: 0.56 - 9.67; p=0.18) (Table B2). The risk of VTE was significantly associated for those patients with varicose veins at baseline in both the matched (RR: 8.8; 95% CI: 1.7 – 46.2; p=0.03) and original samples (RR: 3.6; 95% CI: 1.5 – 8.4; p=0.01) (Table B3). Similarly, the risk of VTE was significantly associated with the presence of sepsis at baseline in both the matched (RR: 15.7; 95% CI: 2.9 – 85.2; p=0.05) and original samples (RR: 10.3; 95% CI: 5.1 – 20.6; p<0.0001).
Table B1. Baseline patient characteristics by cohort
Characteristic / Post-intervention(N=64) / Pre-intervention / Standardized Differences / P-valuea
Original
(N=302) / Matched
(n=64) / Original / Matched / Original
Age in years: Mean (SD) / 63.6 (10.0) / 64.0 (10.8) / 62.6 (11.7) / 0.79
Length of stay: Mean (SD) / 10.6 (9.3) / 13.2 (11.6)) / 8.8 (5.9) / 0.25 / 0.22 / 0.05
N (%)
Gender / 0.30
Female / 26 (40.6) / 144 (47.7) / 28 (43.7) / 0.29 / 0.13
Male / 38 (59.4) / 158 (52.3) / 36 (56.3)
Histology / 0.01
Non-Adenocarcinoma / 13 (20.3) / 112 (37.1) / 14 (21.9) / 0.84 / 0.10
Adenocarcinoma / 51 (79.7) / 190 (62.9) / 50 (78.1)
AJCC clinical Nstageb / 0.42
pN0 / 44 (68.8) / 219 (73.7) / 46 (71.9) / 0.24 / 0.15
pN1-3 / 20 (31.3) / 78 (26.3) / 18 (28.1)
Surgical approach / 0.55
Non-lobectomy / 25 (39.1) / 106 (35.1) / 22 (34.4) / 0.17 / 0.20
Lobectomy / 39 (60.9) / 196 (64.9) / 42 (65.6)
Caprini Risk Score / 0.28
Low/Medium / 34 (53.1) / 138 (45.7) / 31 (48.4) / 0.30 / 0.19
High / 30 (46.9) / 164 (54.3) / 33 (51.6)
aBased on two-sided chi-square or Fisher’s exact test and t-test.
bAmerican Joint Committee on Cancer (AJCC), version 6 (2005-2010) and 7 (2010-2016).
SD = Standard Deviation.
Table B2. VTE events by cohort
Characteristic / Post-intervention(N=64) / Pre-intervention / P-valuea
Original
(N=302) / Matched
(n=64) / Original
N (%)
VTE / 2 (3.1) / 22 (7.3) / 3 (7.8) / 0.28
DVT / 26 (40.6) / 144 (47.7)
PE / 38 (59.4) / 158 (52.3)
Inpatient / 2 (100.0) / 18 (81.8) / 2 (66.7) / 1.00
Outpatient / 0 (0.0) / 4 (18.2) / 1 (33.3) / 1.00
Cancer Type / 1.00
Esophageal / 1 (50.0) / 10 (45.5) / 1 (33.3)
Lung / 1 (50.0) / 12 (54.5) / 2 (66.7)
aBased on two-sided chi-square or Fisher’s exact test.
VTE = Venous Thromboembolism DVT = Deep Vein Thromboembolism PE = Pulmonary Embolism.
Table B3. Caprini risk factor distribution by cohort and relative risk for VTE events.
Characteristic / VTE (Original) / VTE (Matched)No
(N=342) / Yes
(N=24) / RR* (95% CI) / No
(N=123) / Yes
(N=5) / RR* (95% CI)
N (%) / N (%)
Study (P-value) / 0.18 / 0.65
Prospective / 62 / 2 / Ref / 62 / 2 / Ref
Retrospective / 280 / 22 / 2.3 (0. 6,9. 7) / 61 / 3 / 1.5 (0.3,8.7)
Age in years (P-value) / 0.07
40 – 59 / 113 (33.6) / 4 (16.7) / Ref / 44 (35.8) / 0 (0.0) / -
60 – 74 / 161 (47.9) / 17 (70.8) / 2.9 (1.0,8.5) / 58 (47.2) / 4 (80.0)
>=75 / 62 (18.5) / 3 (12.5) / 1.4 (0.3,6.2) / 21 (17.1) / 1 (20.0)
BMI >=30 kg/m2 (P-value) / 0.37 / 0.85
No / 257 (75.1) / 16 (66.7) / Ref / 94 (76.4) / 4 (80.0) / Ref
Yes / 85 (24.9) / 8 (33.3) / 1.5 (0.6,3.3) / 29 (23.6) / 1 (20.0) / 0.8 (0.1,7.0)
Swollen legs (current) / 0.02 / 0.16
No / 321 (93.8) / 19 (79.2) / Ref / 119 (96.7) / 4 (80.0) / Ref
Yes / 21 (6.1) / 5 (20.8) / 3.4 (1.4,8.5) / 4 (3.3) / 1 (20.0) / 6.1 (0.8,45.5)
Varicose veins (P-value) / 0.01 / 0.03
No / 317 (92.7) / 18 (75.0) / Ref / 116 (94.3) / 3 (60.0) / Ref
Yes / 25 (7.3) / 6 (25.0) / 3.6 (1.5,8.4) / 7 (5.7) / 2 (40.0) / 8.8 (1.7,46.2)
Sepsis (<1 month) (P-value) / <0.0001 / 0.05
No / 333 (97.4) / 16 (66.7) / Ref / 122 (99.2) / 4 (80.0) / Ref
Yes / 9 (2.6) / 8 (33.3) / 10.3(5.1,20.6) / 1 (0.8) / 1 (20.0) / 15.7(2.9,85.2)
Congestive heart failure (P-value) / 0.05
No / 338 (98.8) / 22 (91.7) / Ref / 122 (99.2) / 5 (100.0) / -
Yes / 4 (1.2) / 2 (8.3) / 5.5 (1.6,18.1) / 1 (0.8) / 0 (0.0)
Serious acute lung disease (<1 month) (P-value) / 0.002 / 0.37
No / 294 (86.0) / 14 (58.3) / Ref / 114 (92.7) / 4 (80.0) / Ref
Yes / 48 (14.0) / 10 (41.7) / 3.8 (1.8,8.1) / 9 (7.3) / 1 (20.0) / 2.9 (0.4,23.9)
Major open surgery (>45 min) (P-value) / 0.13 / 0.37
No / 121 (35.4) / 5 (20.8) / Ref / 48 (39.0) / 1 (20.0) / Ref
Yes / 221 (64.6) / 19 (79.2) / 2.0 (0.8,5.2) / 75 (61.0) / 4 (80.0) / 2.5 (0.3,21.6)
Laparoscopic surgery (>45 min) (P-value) / 0.77
No / 306 (89.5) / 21 (87.5) / Ref / 112 (91.1) / 5 (100.0) / -
Yes / 36 (10.5) / 3 (12.5) / 1.2 (0.4,3.8) / 11 (8.9) / 0 (0.0)
Prior cancer (except non-melanoma skin cancer) (P-value) / 0.31 / 0.30
No / 273 (79.8) / 17 (70.8) / Ref / 99 (80.5) / 3 (60.0) / Ref
Yes / 69 (20.2) / 7 (29.2) / 1.6 (0.7,3.7) / 24 (19.5) / 2 (40.0) / 2.6 (0.5,14.9)
Present cancer (P-value)
No / 5 (1.5) / 0 (0.0) / - / 5 (4.1) / 0 (0.0) / -
Yes / 337 (98.5) / 24 (100.0) / 118 (95.9) / 5 (100.0)
Confined to bed (>72 hours) (P-value) / 0.08 / 0.29
No / 303 (88.6) / 18 (75.0) / Ref / 116 (94.3) / 4 (80.0) / Ref
Yes / 39 (11.4) / 6 (25.0) / 2.4 (1. 0,5. 7) / 7 (5.7) / 1 (20.0) / 3.7 (0.5,29.8)
Central venous access (P-value) / <0.001 / 0.95
No / Ref / 97 (78.9) / 4 (80.0) / Ref
Yes / 110 (32.2) / 17 (70.8) / 4.6 (1.9,10.7) / 26 (21.1) / 1 (20.0) / 0.9 (0.1,8.0)
History of VTE (P-value) / 0.01 / 0.007
No / 336 (98.2) / 21 (87.5) / Ref / 120 (97.6) / 3 (60.0) / Ref
Yes / 6 (1.8) / 3 (12.5) / 5.7 (2.1,15.6) / 3 (2.4) / 2 (40.0) / 16.4 (3.5,77.2)
Present chemotherapy (P-value) / 0.005 / 0.50
No / 276 (80.7) / 13 (54.2) / Ref / 111 (90.2) / 4 (80.0) / Ref
Yes / 66 (19.3) / 11 (45.8) / 3.2 (1.5,6.8) / 12 (9.8) / 1 (20.0) / 2.2 (0.3,18. 3)
Major surgery (>6 hours) (P-value) / 0.009 / 0.56
No / 289 (84.5) / 12 (50.0) / Ref / 89 (72.4) / 3 (60.0) / Ref
Yes / 83 (24.3) / 12 (50.0) / 2.9 (1. 3,6.1) / 34 (27.6) / 2 (40.0) / 1.7 (0.3,9. 8)
*Obtained from logistic regressions with only that variable in the model.
VTE = Venous Thromboembolism; RR=Relative Risk; CI=Confidence Intervals.