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
|
aTotal population: N = 6,094,672
|
5,952,005 (97.7)
|
142,667 (2.3)
|
|
Females
|
3,280,823 (55.1)
|
63,912 (44.8)
|
0.208
|
Age groups
|
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
aTotal population presented in row percentage
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%), yet with marked differences between the two cohorts (SMD: 0.680). The prevalence for each Charlson comorbidity in the total population and the derivation 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%). However, the most pronounced difference between both cohorts was observed for metastatic cancer (4.0% vs. 26.5%; SMD: 0.657). 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 Swiss 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 with random effect on the hospital level. 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 Swiss 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) Swiss derivation sample and the van Walraven (VW) derivation sample [25]
Elixhauser comorbidities
|
Alive
cohort
(%)
|
Mortality cohort
(%)
|
SMD
|
Adjusted odds ratio (95% CI)
|
Weights
|
|
Swiss derivation sample
|
VWa
|
Swiss
|
VWa
|
Swiss
|
bDerivation 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, VWa van Walraven, `–` excluded in the final model, bRow percentage
Note: The total cohort percentages can exceed 100%, as each admission contributes to one or more comorbidities. Swiss weights are calculated by dividing the coefficient of each comorbidity by the coefficient in the model with the smallest absolute value (which is ‘diabetes uncomplicated’ with a coefficient of 0.084) and rounding to the nearest whole number.
Validation and comparison of weighted comorbidity models
All three comorbidity weighting systems (Charlson, Elixhauser van Walraven and Swiss) indicated higher in-hospital mortality risk than the base model, showing the conditional interpretation of weights for each of the weighted models. Each model performed similarly across all years in validation groups as in the derivation groups. Overall, the c-statistic for the 6-year cohort were: 0.757 (95% CI: 0.755–0.759) for the base model, 0.850 (95% CI: 0.849–0.851) for Charlson, 0.863 (95% CI: 0.862-0.864) for VW Elixhauser and 0.867 (95% CI: 0.865–0.868) with Swiss Elixhauser. These c-statistics were similar in the development and validation cohorts. All differences and the rankings they established among models were statistically significant. (Additional file 1, Table S5). In comparison, the model with Swiss weights discrimination was slightly better with some c-statistic variability across the six years’ data.
Additionally, 1% highest predicted value, showed the same order of the model’s performance from the observed mortality (base: 10.7%, Charlson: 18.5%, VW Elixhauser: 20.4%, Swiss Elixhauser: 20.9% (Table S6, Additional file 1). As shown in receiver-operating characteristic (ROC) curves (Fig. 1) the Swiss weights model’s discrimination was better than the Charlson’s or base model’s, and only slightly better than the van Walraven’s. The NRI confirm this picture (Table 3). Comparing the Swiss 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 3 Comparison of Swiss weights model with Base, Charlson and VW weights 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)
|
Swiss 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)
|
Swiss 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)
|
Swiss 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)
|
0.023
(0.023–0.024)
|
Abbreviations: NRI Net Reclassification Improvement with classification cut-off 0.023, 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
Swiss weights model: base and Elixhauser/ Swiss weights
Finally, the sensitivity analysis using MDCs did not offer any improvements in the models’ performance.