Population characteristics
Overall, the adult inpatient population between 2012 and 2017 in all Swiss general hospitals (102) consisted of 6,094,672 cases. Among all hospitalized cases in our study population mortality was 2.3%. The characteristics of the adult inpatient cases are presented in Table 1. Inpatient cases had between 0 and 9 Charlson comorbidities (median 0, interquartile range (IQR): 0-1) and between 0 and 16 Elixhauser comorbidities (median 1, IQR: 0-2). The different categories of three comorbidity weightings are presented in supplementary table S2 (Additional file 1).
Table 1 General characteristics of the total study population
Parameters
|
Alive cohort (%)
|
Mortality cohort (%)
|
SMD
|
Total population: N = 6,094,672
|
5,952,005 (97.7)
|
142,667 (2.3)
|
|
Female
|
3,280,823 (55.1)
|
63,912 (44.8)
|
0.208
|
Age group
|
1.006
|
20–24 years
|
215,672 (3.6)
|
292 (0.2)
|
|
25–29 years
|
327,562 (5.5)
|
375 (0.3)
|
|
30–34 years
|
415,022 (7.0)
|
526 (0.4)
|
|
35–39 years
|
348,591 (5.9)
|
718 (0.5)
|
|
40–44 years
|
299,985 (5.0)
|
1,368 (1.0)
|
|
45–49 years
|
350,899 (5.9)
|
2,503 (1.8)
|
|
50–54 years
|
408,028 (6.9)
|
4,312 (3.0)
|
|
55–59 years
|
430,721 (7.2)
|
6,503 (4.6)
|
|
60–64 years
|
466,543 (7.8)
|
9,068 (6.4)
|
|
65–69 years
|
528,374 (8.9)
|
13,322 (9.3)
|
|
70–74 years
|
554,612 (9.3)
|
16,899 (11.8)
|
|
75–79 years
|
535,543 (9.0)
|
19,888 (13.9)
|
|
80–84 years
|
509,225 (8.6)
|
24,853 (17.4)
|
|
85–89 years
|
365,924 (6.1)
|
24,042 (16.9)
|
|
90–94 years
|
161,236 (2.7)
|
14,156 (9.9)
|
|
95+ years
|
34,068 (0.6)
|
3,842 (2.7)
|
|
Hospital types
|
0.157
|
University (level 1)
|
1,078,612 (18.1)
|
29,379 (20.6)
|
|
Tertiary care (level 2)
|
3,274,382 (55.0)
|
83,686 (58.7)
|
|
Basic care (level 3)
|
736,465 (12.4)
|
14,863 (10.4)
|
|
Basic care (level 4)
|
671,182 (11.3)
|
10,695 (7.5)
|
|
Basic care (level 5)
|
191,364 (3.2)
|
4,044 (2.8)
|
|
Number of Charlson comorbidities
|
1.234
|
0
|
3,642,650 (61.2)
|
17,465 (12.2)
|
|
1–2
|
1,907,761 (32.1)
|
80,876 (56.7)
|
|
>= 3
|
401,594 (6.7)
|
44,326 (31.1)
|
|
Number of Elixhauser comorbidities
|
1.039
|
0
|
2,509,169 (42.2)
|
11,036 (7.7)
|
|
1–2
|
2,106,780 (35.4)
|
43,494 (30.5)
|
|
>= 3
|
1,336,056 (22.4)
|
88,137 (61.8)
|
|
Abbreviations: SMD standardized mean difference between alive and mortality cohort
Prevalence of Charlson and Elixhauser comorbidity indices
The most common Charlson comorbidity was any malignancy (including lymphoma and leukaemia, except malignant neoplasm of the skin) in both cohorts, alive (10.2 %) and mortality (37.6%). The prevalence for each Charlson comorbidity in the total population and the derivation, group is presented in supplementary table S3 (Additional file 1).
The most common Elixhauser comorbidities were uncomplicated hypertension (22.7 %) in the alive cohort, whereas in the mortality cohort, it was solid tumour without metastasis (33.7%). The prevalence for each Elixhauser comorbidity from the total population and derivation group is presented in the supplementary table S4 (Additional file 1).
Derivation of population-based weights
In the derivation group, two of the 31 Elixhauser comorbidities showed no association with hospital mortality and were removed, leaving 29 in the final model. Sixteen were associated with increased mortality risk, with the strongest associations coming from metastatic cancer (OR: 4.09, 95% CI: 3.98–4.21) and liver disease (OR: 3.83, 95% CI: 3.70–3.97). At the other end of the spectrum, thirteen comorbidities were associated with a decreased risk of hospital mortality. The strongest of these were deficiency anaemia (OR: 0.54, 95% CI: 0.51–0.56) and obesity (OR: 0.59, 95% CI: 0.56–0.63). The adjusted coefficients were used to derive population-based weights with a new maximum weight of 17, for metastatic cancer, and a new minimum of -7, for deficiency anaemia (Table 2).
Table 2 Prevalence, adjusted odds ratio and weights from the (new) population-based derivation sample and the van Walraven (VW) derivation sample [25]
Elixhauser comorbidities
|
Alive
cohort
(%)
|
Mortality cohort
(%)
|
SMD
|
Adjusted odds ratio (95% CI)
|
Weights
|
|
Population-based derivation sample
|
VWa
|
Newb
|
VWa
|
Newb
|
Derivation group
|
2,975,887 (97.7)
|
71,449 (2.3)
|
|
|
|
|
|
Congestive heart failure
|
163,685 (5.5)
|
16,333 (22.9)
|
0.514
|
1.96 (1.85–2.07)
|
3.07 (3.00–3.14)
|
7
|
13
|
Cardiac arrhythmias
|
341,280 (11.5)
|
20,754 (29.0)
|
0.448
|
1.71 (1.62–1.80)
|
1.69 (1.66–1.73)
|
5
|
6
|
Valvular disease
|
117,450 (3.9)
|
6,568 (9.2)
|
0.213
|
0.91 (0.82–0.99)
|
0.92 (0.89–0.95)
|
-1
|
-1
|
Pulmonary circulation disorders
|
53,292 (1.8)
|
4,813 (6.7)
|
0.247
|
1.48 (1.34–1.62)
|
1.62 (1.57–1.68)
|
4
|
6
|
Peripheral vascular disorders
|
141,051 (4.7)
|
6,912 (9.7)
|
0.192
|
1.26 (1.17–1.36)
|
1.27 (1.24–1.31)
|
2
|
3
|
Hypertension (uncomplicated)
|
676,609 (22.7)
|
15,692 (22.0)
|
0.019
|
–
|
0.69 (0.68–0.70)
|
0
|
-4
|
Hypertension (complicated)
|
218,656 (7.3)
|
11,003 (15.4)
|
0.256
|
–
|
0.79 (0.77–0.81)
|
0
|
-3
|
Paralysis
|
61,546 (2.1)
|
5,153 (7.2)
|
0.246
|
1.93 (1.75–2.12)
|
2.60 (2.52–2.69)
|
7
|
11
|
Other neurological disorders
|
120,045 (4.0)
|
8,011 (11.2)
|
0.273
|
1.83 (1.70–1.96)
|
2.45 (2.39–2.52)
|
6
|
10
|
Chronic pulmonary disease
|
170,770 (5.7)
|
8,269 (11.6)
|
0.209
|
1.36 (1.29–1.44)
|
1.31 (1.27–1.34)
|
3
|
3
|
Diabetes, uncomplicated
|
245,817 (8.3)
|
9,059 (12.7)
|
0.145
|
–
|
1.09 (1.06–1.11)
|
0
|
1
|
Diabetes, complicated
|
66,161 (2.2)
|
2,763 (3.9)
|
0.096
|
–
|
0.89 (0.86–0.93)
|
0
|
-1
|
Hypothyroidism
|
126,062 (4.2)
|
3,454 (4.8)
|
0.029
|
–
|
0.76 (0.74–0.79)
|
0
|
-3
|
Renal failure
|
289,047 (9.7)
|
20,526 (28.7)
|
0.497
|
1.63 (1.54–1.73)
|
2.06 (2.02–2.11)
|
5
|
8
|
Liver disease
|
49,916 (1.7)
|
5,822 (8.1)
|
0.303
|
2.97 (2.73–3.22)
|
3.83 (3.7–3.97)
|
11
|
16
|
Peptic ulcer disease, excluding bleeding
|
5,808 (0.2)
|
258 (0.4)
|
0.032
|
–
|
–
|
0
|
0
|
AIDS/HIV
|
2,300 (0.1)
|
85 (0.1)
|
0.013
|
–
|
–
|
0
|
0
|
Lymphoma
|
25,049 (0.8)
|
1,759 (2.5)
|
0.127
|
2.55 (2.31–2.81)
|
2.19 (2.07–2.31)
|
9
|
9
|
Metastatic cancer
|
119,667 (4.0)
|
18,907 (26.5)
|
0.657
|
3.30 (3.10–3.52)
|
4.09 (3.98–4.21)
|
12
|
17
|
Solid tumour without metastasis
|
268,298 (9.0)
|
24,046 (33.7)
|
0.631
|
1.47 (1.39–1.56)
|
2.36 (2.3–2.42)
|
4
|
10
|
Rheumatoid arthritis/collagen vascular diseases
|
47,305 (1.6)
|
1,254 (1.8)
|
0.013
|
–
|
0.91 (0.86–0.97)
|
0
|
-1
|
Coagulopathy
|
90,551 (3.0)
|
9,528 (13.3)
|
0.382
|
1.30 (1.22–1.40)
|
2.12 (2.07–2.18)
|
3
|
9
|
Obesity
|
68,155 (2.3)
|
1,011 (1.4)
|
0.065
|
0.64 (0.53–0.77)
|
0.59 (0.56–0.63)
|
-4
|
-6
|
Weight loss
|
98,545 (3.3)
|
9,527 (13.3)
|
0.369
|
1.85 (1.67–2.04)
|
1.67 (1.63–1.71)
|
6
|
6
|
Fluid and electrolyte disorders
|
257,618 (8.7)
|
17,440 (24.4)
|
0.434
|
1.61 (1.53–1.69)
|
1.58 (1.55–1.61)
|
5
|
5
|
Blood loss anaemia
|
19,759 (0.7)
|
685 (1.0)
|
0.033
|
0.81 (0.70–0.93)
|
0.66 (0.60–0.71)
|
-2
|
-5
|
Deficiency anaemia
|
72,290 (2.4)
|
1,886 (2.6)
|
0.013
|
0.80 (0.71–0.90)
|
0.54 (0.51–0.56)
|
-2
|
-7
|
Alcohol abuse
|
96,708 (3.2)
|
3,086 (4.3)
|
0.056
|
–
|
0.75 (0.72–0.78)
|
0
|
-3
|
Drug abuse
|
38,044 (1.3)
|
583 (0.8)
|
0.045
|
0.50 (0.42–0.60)
|
0.67 (0.61–0.73)
|
-7
|
-5
|
Psychoses
|
29,598 (1.0)
|
404 (0.6)
|
0.049
|
–
|
0.72 (0.65–0.79)
|
0
|
-4
|
Depression
|
173,898 (5.8)
|
3,715 (5.2)
|
0.028
|
0.73 (0.67–0.80)
|
0.73 (0.70–0.75)
|
-3
|
-3
|
Abbreviations: SMD standardized mean difference between alive and mortality cohort, Newb population-based, VWa van Walraven, `–` excluded in the final model
Note: Total cohort % exceed 100% for each cohort, as comorbidities are mutually inclusive, New weights are calculated dividing the coefficient of each comorbidity by the coefficient in the model with the smallest absolute value
Validation and comparison of weighted comorbidity models
All three comorbidity weighting systems (Charlson, Elixhauser van Walraven and population-based) indicated higher in-hospital mortality risk than the base model. They also showed equivalent discrimination in the derivation and validation groups (Table 3). Overall, the Charlson weighting model’s c-statistic was 0.850 (95% CI: 0.849–0.851), the van Walraven model was 0.863 (95% CI: 0.862–0.864) and population-based weights model was 0.867 (95% CI: 0.865–0.868) in the total sample. There were similar results for both, the derivation and validation groups except the slight change on c statistic and CI on six validation samples as shown in Table 3. Additionally, c statistics for the validation sample is shown in supplementary table S5 (Additional file 1). In comparison, the model with population-based weights discrimination was slightly better with some c-statistic variability across the six years’ data.
Table 3 Performance measures of the base, Charlson, van Walraven and population-based weights models for in-hospital mortality in derivation, validation and all cases groups
C Statistic (95% CI)
|
|
Derivation group
|
Validation groups
|
All cases
|
|
n = 3,047,336
|
n1 = 491,962
|
n2 = 496,684
|
n3 = 504,741
|
n4 = 514,267
|
n5= 520,277
|
n6 = 519,405
|
N= 6,094,672
|
|
|
All years
(2012–2017)
|
Year 1
|
Year 2
|
Year 3
|
Year 4
|
Year 5
|
Year 6
|
All years
(2012–2017)
|
|
Base model
|
0.757
(0.755–0.759)
|
0.758
(0.752–0.759)
|
0.758
(0.754–0.762)
|
0.756
(0.753–0.760)
|
0.752
(0.748–0.756)
|
0.756
(0.752–0.759)
|
0.750
(0.746–0.754)
|
0.757
(0.755–0.759)
|
|
Charlson weights model
|
0.850
(0.847–0.851)
|
0.849
(0.846–0.852)
|
0.852
(0.849–0.855)
|
0.854
(0.851–0.857)
|
0.849
(0.846–0.852)
|
0.854
(0.851–0.857)
|
0.844
(0.841–0.847)
|
0.850
(0.849–0.851)
|
|
VW weights model
|
0.863
(0.862–0.864)
|
0.862
(0.859–0.865)
|
0.866
(0.863–0.869)
|
0.867
(0.864–0.869)
|
0.863
(0.860–0.866)
|
0.869
(0.866–0.872)
|
0.862
(0.859–0.864)
|
0.863
(0.862–0.864)
|
|
Population-based weights model
|
0.867
(0.865–0.868)
|
0.865
(0.862–0.868)
|
0.869
(0.866–0.871)
|
0.871
(0.868–0.873)
|
0.866
(0.863–0.869)
|
0.872
(0.869–0.874)
|
0.865
(0.862–0.867)
|
0.867
(0.865–0.868)
|
|
Abbreviations: VW van Walraven, CI confidence interval
Base model: age groups, sex, hospital types
Charlson weights model: base and Charlson weights
VW weights model: base and Elixhauser/ van Walraven weights
Population-based weights model: base and Elixhauser/ Population-based weights
As shown in Fig. 1, the population-based weights model’s discrimination was clearly better than the Charlson’s or base model’s, and only slightly better than the van Walraven’s. The NRI confirm this picture (Table 4). Comparing the population-based weights with VW weights showed an NRI of 1.6% (95%-CI: 1.3–2.0) with differences in predicted probabilities of mortality (among those who died) of 1.4% and differences in predicted probabilities of alive (among those who lived) by 0.02%.
Table 4 Comparison of population-based weights model with Base, Charlson and VW models based on the Net Reclassification Improvement (NRI)
Derivation group
|
Comparison models
|
NRI
(95% CI)
|
Mortality increased Pr(Up|Case)
|
Alive
increased Pr(Up|Ctrl)
|
Mortality decreased
Pr(Down|Case)
|
Alive
decreased
Pr(Down|Ctrl)
|
Population-based weights
vs.
Base model
|
0.355
(0.352–0.357)
|
0.448
(0.445–0.450)
|
0.074
(0.074–0.074)
|
0.134
(0.133–0.136)
|
0.115
(0.115–0.116)
|
Population-based weights
vs.
Charlson weights model
|
0.049
(0.044–0.052)
|
0.297
(0.294–0.299)
|
0.058
(0.058–0.059)
|
0.251
(0.250–0.253)
|
0.062
(0.061–0.062)
|
Population-based weights
vs.
VW weights model
|
0.016
(0.013–0.020)
|
0.157
(0.155– 0.159)
|
0.021
(0.021–0.022)
|
0.143
(0.140–0.145)
|
0.024
(0.023–0.024)
|
Abbreviations: NRI Net Reclassification Improvement, CI confidence interval
Pr(Up, Down) | (Case, Ctrl) represents the proportion of patients whose predicted probabilities increased or decreased for in-hospital mortality and alive cohorts respectively
NRI= (Pr(Up|Case) - Pr(Down|Case)) + (Pr(Down|Ctrl) - Pr(Up|Ctrl))
Base model: age group, sex, hospital types
Charlson weights model: base and Charlson weights
VW weights model: base and Elixhauser/ van Walraven weights
Population-based weights model: base and Elixhauser/ Population-based weights
Finally, the sensitivity analysis using MDCs did not offer any improvements in the models’ performance.