Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study
Abstract
:1. Introduction
- (a)
- To identify the inpatient management costs associated with the eight most common RVIs in the pediatric age group.
- (b)
- To specify costs associated with hospitalization in a general ward versus ICU, and/or mechanical ventilation, continuous positive airway pressure (CPAP), or oxygen support.
- (c)
- To assess the relationship between risk factors, disease severity, and SDHs (using surrogate markers) regarding clinical decisions to perform diagnostic tests in the emergency department (ED), to admit to non-ICU/ICU wards, and to start mechanical ventilation/CPAP/oxygen support, respectively.
2. Materials and Methods
2.1. Cohort Analysis
2.2. RT-PCR Analysis
2.3. Patients’ Baseline Demographics
2.4. Analysis of Clinical Decision Making
2.5. Cost Analysis
2.6. Analysis of Clinical Decision Making in Relation to Risk-Adjusted Disease Severity (raVIVI Score) vs. Social Determinants of Health (SDHs)
3. Results
3.1. Patients’ Baseline Demographics
3.2. Analysis of RVIs in Relation to Clinical Decision Making
- (a)
- Diagnostic Testing
- (b)
- Hospitalization and ICU admission
- (c)
- Mechanical Ventilation, CPAP, and Oxygen Supplementation
3.3. Cost Analysis
3.4. Clinical Decision Making in Relation to Risk-Adjusted Disease Severity (raVIVI Score) and Social Determinants of Health (SDHs)
3.4.1. Risk-Adjusted Disease Severity Score (‘raVIVI Score’) vs. SDHs
- (a)
- Diagnostic Testing
- (b)
- Non-ICU admission and ICU admission
- (c)
- Mechanical ventilation, CPAP, and O2 supplementation
3.4.2. Feature Importance Comprising the SDH Score
4. Discussion
4.1. RVI in Relation to Clinical Decision Making
4.2. Cost Analysis
4.3. Clinical Decision Making in Relation to Risk-Adjusted Disease Severity (raVIVI Score) and Social Determinants of Health (SDHs)
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CDISC | Clinical Data Interchange Standards Consortium |
COVID-19 | coronavirus disease 2019 |
CPAP | continuous positive airway pressure |
DRG | diagnosis-related group |
ED | emergency department |
hAdV | human adenovirus |
hBoV | human bocavirus |
hCoV | human coronavirus |
hMPV | human metapneumovirus |
hPIV | human parainfluenza virus |
hRV | human rhinovirus |
ICD | International Statistical Classification of Diseases and Related Health Problems |
ICU | intensive care unit |
ILI | influenza-like illness |
LMIC | low–middle-income country |
LRTI | lower respiratory tract infection |
QI | quality improvement |
raVIVI Score | risk-adjusted VIVI Score |
RSV | respiratory syncytial virus |
RV | respiratory virus |
RVI | respiratory viral infection |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
SDHs | social determinants of health |
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All Patients | Influenza Virus | hAdV | RSV | hRV | hMPV | hBoV | hPIV | hCoV | Co-Infection | No Virus Detected | p-Value * | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
n (% of total) | 4776 (100) | 409 (8.6) | 203 (4.3) | 492 (10.3) | 617 (12.9) | 131 (2.7) | 254 (5.3) | 190 (4.0) | 76 (1.6) | 969 (20.3) | 1435 (30.1) | |
Age (years) Median [IQR] | 1.6 [0.7–3.7] | 4.3 [1.6–7.9] | 1.8 [0.9–2.5] | 0.8 [0.3–1.8] | 1.6 [0.7–2.8] | 1.6 [0.7–2.8] | 1.5 [0.8–2.5] | 1.4 [0.6–2.6] | 1.2 [0.6–7.9] | 1.3 [0.6–2.4] | 2.1 [0.9–6.1] | 0.50 |
Gender Male (%) | 55.8 | 54.5 | 57.1 | 56.7 | 60.1 | 60.3 | 58.3 | 51.6 | 61.8 | 55.8 | 53.3 | 0.79 |
Chronic condition Pulmonary (95% CI) | 8.1% (7.4–8.9) | 7.3% (5.2–10.3) | 2.5% (1.1–5.6) | 8.5% (6.4–11.3) | 11.4% (9.1–14.1) | 8.4% (4.8–14.4) | 10.6% (7.4–15.0) | 10.0% (6.5–15.1) | 7.9% (3.7–16.2) | 7.4% (5.9–9.3) | 7.3% (6.1–8.8) | 0.20 |
Cardiac (95% CI) | 7.5% (6.7–8.2) | 5.9% (4.0–8.6) | 4.4% (2.4–8.2) | 6.9% (5.0–9.5) | 8.8% (6.8–11.2) | 6.9% (3.7–12.5) | 6.7% (4.2–10.5) | 9.5% (6.1–14.5) | 5.3% (2.1–12.8) | 5.9% (4.6–7.6) | 9.1% (7.7–10.7) | 0.54 |
Metabolic (95% CI) | 3.5% (3.0–4.1) | 5.6% (3.8–8.3) | 3.0% (1.4–6.3) | 2.4% (1.4–4.2) | 4.4% (3.0–6.3) | 2.3% (0.8–6.5) | 2.8% (1.3–5.6) | 4.7% (2.5–8.8) | 2.6% (0.7–9.1) | 2.5% (1.7–3.7) | 4.9% (3.9–6.1) | 0.42 |
Hepatorenal (95% CI) | 2.7% (2.3–3.3) | 1.2% (0.5–2.8) | 3.0% (1.4–6.3) | 2.6% (1.6–4.5) | 3.7% (2.5–5.5) | 1.5% (0.4–5.4) | 2.0% (0.8–4.5) | 2.6% (1.1–6.0) | 2.6% (0.7–9.1) | 2.4% (1.6–3.5) | 0.5% (0.2–1.0) | <0.05 |
Neurological (95% CI) | 5.0% (4.4–5.6) | 5.4% (3.6–8.0) | 2.0% (0.8–5.0) | 3.3% (2.0–5.2) | 4.9% (3.4–6.9) | 5.3% (2.6–10.6) | 3.9% (2.2–7.1) | 4.2% (2.2–8.1) | 9.2% (4.5–17.8) | 4.5% (3.4–6.0) | 6.3% (5.1–7.7) | 0.56 |
Haemato-oncological/immunological (95% CI) | 2.4% (2.0–2.9) | 2.7% (1.5–4.8) | 1.5% (0.5–4.3) | 1.6% (0.8–3.2) | 2.6% (1.6–4.2) | 3.8% (1.6–8.6) | 2.4% (1.1–5.1) | 2.6% (1.1–6.0) | 1.3% (0.2–7.1) | 1.9% (1.2–2.9) | 0.2% (0.1–0.6) | <0.05 |
Prematurity < 33 weeks GA (95% CI) | 5.2% (4.6–5.9) | 4.2% (2.6–6.6) | 3.0% (1.4–6.3) | 4.7% (3.1–6.9) | 6.0% (4.4–8.2) | 6.9% (3.7–12.5) | 5.1% (3.0–8.6) | 5.8% (3.3–10.1) | 9.2% (4.5–17.8) | 4.2% (3.1–5.7) | 5.9% (4.8–7.3) | 0.90 |
Any (95% CI) | 24.4% (23.2–25.7) | 19.3% (15.8–23.4) | 13.8% (9.7–19.2) | 12.4% (9.8–15.6) | 15.7% (13.1–18.8) | 22.1% (15.9–30.0) | 12.6% (9.1–17.2) | 19.5% (14.5–25.7) | 15.7% (9.3–25.6) | 16.3% (14.1–18.8) | 19.8% (17.8–21.9) | 0.10 |
O2 % of Total (95% CI) | CPAP % of Total (95% CI) | Mechanical Ventilation % of Total (95% CI) | |
---|---|---|---|
influenza virus | 7.8 (5.6;10.8) | 0.7 (0.3;2.1) | 1.0 (0.4;2.5) |
hAdV | 3.5 (1.7;7.0) | 0.0 (0.0;1.9) | 0.0 (0.0;1.9) |
RSV | 33.3 (29.3;37.6) | 1.8 (1.0;3.4) | 0.4 (0.1;1.5) |
hRV | 21.1 (18.0;24.5) | 0.7 (0.3;1.7) | 0.3 (0.1;1.2) |
hMPV | 24.4 (17.9;32.4) | 0.8 (0.1;4.2) | 0.0 (0.0;2.9) |
hBoV | 15.4 (11.4;20.3) | 0.0 (0.1;1.5) | 0.4 (0.1;2.2) |
hPIV | 12.1 (8.2;17.5) | 0.5 (0.1;2.9) | 0.0 (0.0;2.0) |
hCoV | 4.0 (1.4;11.0) | 1.3 (0.2;7.1) | 0.0 (0.0;4.8) |
p-value * | <0.05 | 0.82 | 0.98 |
Total n = 2372 | Diagnosis-Related Groups (DRGs) (Direct + Non-Direct Medical Cost) − Total Cost per Episode (EUR) | Summary of Individual Items (Direct + Non-Direct Medical Cost) − Total Cost per Episode (EUR) | Indirect Cost − Total Cost per Episode (EUR) | Total of Individual Items (Direct + Non-Direct Medical Cost) and Indirect Cost (EUR) | ||
---|---|---|---|---|---|---|
Influenza virus n = 409 | ||||||
ICU n = 54 | 7854.24 | 29,261.31 * | 680.40 | 29,941.71 | ||
0–5 years n = 32 | 5624.56 | 4262.32 | 680.40 | 4942.72 | ||
6–12 years n = 16 | 7943.44 | 30,632.53 | 907.20 | 31,539.73 | ||
13–18 years n = 6 | 3511.87 | 1500.98 | 1360.80 | 2861.78 | ||
Non-ICU n = 128 | 1668.35 | 1973.34 * | 793.80 | 2767.14 | ||
0–5 years n = 88 | 1761.25 | 1507.83 | 793.80 | 2301.63 | ||
6–12 years n = 19 | 1569.35 | 2419.47 | 992.25 | 3411.72 | ||
13–18 years n = 21 | 1533.18 | 1483.31 | 595.35 | 2078.66 | ||
Outpatient n = 227 | 85.00 | 88.33 * | 340.20 | 428.53 | ||
0–5 years n = 131 | 85.00 | 95.17 | 340.20 ** | 435.37 | ||
6–12 years n = 65 | 85.00 | 88.33 | 340.20 ** | 428.53 | ||
13–18 years n = 31 | 85.00 | 87.03 | 340.20 ** | 427.23 | ||
hAdV n = 203 | ||||||
ICU n = 23 | 3881.00 | 4260.40 | 680.40 | 4940.80 | ||
0–5 years n = 22 | 3893.12 | 3471.61 | 567.00 | 4038.61 | ||
6–12 years n = 0 | NA | NA | NA | NA | ||
13–18 years n = 1 | 3582.43 | 4247.96 | 680.40 | 4928.36 | ||
Non-ICU n = 82 | 1622.04 | 1498.38 | 595.35 | 2093.73 | ||
0–5 years n = 79 | 1611.92 | 1498.38 | 595.35 | 2093.73 | ||
6–12 years n = 2 | 1784.26 | 2357.88 | 992.25 | 3350.13 | ||
13–18 years n = 1 | 1581.10 | 2357.88 | 1984.50 | 4342.38 | ||
Outpatient n = 98 | 85.00 | 87.03 | 340.20 | 427.23 | ||
0–5 years n = 89 | 85.00 | 87.03 | 340.20 ** | 427.23 | ||
6–12 years n = 8 | 85.00 | 60.58 | 340.20 ** | 400.78 | ||
13–18 years n = 1 | 85.00 | 60.58 | 340.20 ** | 400.78 | ||
RSV n = 492 | ||||||
ICU n = 155 | 6487.58 | 15,817.06 | 1134.00 | 16,951.06 | ||
0–5 years n = 152 | 6356.71 | 14,436.10 | 907.20 | 15,343.30 | ||
6–12 years n = 1 | 7144.93 | 24,895.13 | 4082.40 | 28,977.53 | ||
13–18 years n = 2 | 5581.03 | 15,223.48 | 2494.80 | 17,718.28 | ||
Non-ICU n = 225 | 3584.00 | 1973.34 | 739.80 | 2713.14 | ||
0–5 years n = 223 | 3781.44 | 1973.65 | 793.80 | 2767.45 | ||
6–12 years n = 1 | 3544.82 | 1457.72 | 595.35 | 2053.07 | ||
13–18 years n = 1 | 3132.45 | 2848.09 | 1190.70 | 4038.79 | ||
Outpatient n = 112 | 85.00 | 87.57 | 340.20 | 427.77 | ||
0–5 years n = 108 | 85.00 | 95.17 | 340.20 | 435.37 | ||
6–12 years n = 4 | 85.00 | 86.81 | 340.20 | 427.01 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
hRV n = 617 | ||||||
ICU n = 89 | 6451.92 | 13,486.82 | 907.20 | 14,394.02 | ||
0–5 years n = 76 | 6684.73 | 13,486.31 | 907.20 | 14,393.51 | ||
6–12 years n = 13 | 6253.43 | 4269.72 | 680.40 | 4950.12 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
Non-ICU n = 306 | 1792.65 | 1973.53 | 793.80 | 2767.33 | ||
0–5 years n = 276 | 1852.98 | 1973.51 | 793.80 | 2767.31 | ||
6–12 years n = 24 | 1791.21 | 2438.78 | 992.25 | 3431.03 | ||
13–18 years n = 6 | 1782.43 | 1939.73 | 793.80 | 2733.53 | ||
Outpatient n = 222 | 85.00 | 87.57 | 340.20 | 427.77 | ||
0–5 years n = 185 | 85.00 | 88.33 | 340.20 ** | 428.53 | ||
6–12 years n = 30 | 85.00 | 87.57 | 340.20 ** | 427.77 | ||
13–18 years n = 7 | 85.00 | 60.58 | 340.20 ** | 400.78 | ||
hMPV n = 131 | ||||||
ICU n = 31 | 4259.31 | 5653.70 | 907.20 | 5653.70 | ||
0–5 years n = 31 | 4259.31 | 5653.70 | 907.20 | 6560.90 | ||
6–12 years n = 0 | NA | NA | NA | NA | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
Non-ICU n = 57 | 2133.87 | 1508.05 | 595.35 | 2103.40 | ||
0–5 years n = 53 | 2384.78 | 1508.01 | 595.35 | 2103.36 | ||
6–12 years n = 4 | 2044.68 | 1711.53 | 694.58 | 2406.11 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
Outpatient n = 43 | 85.00 | 87.57 | 340.20 | 427.77 | ||
0–5 years n = 38 | 85.00 | 87.57 | 340.20 | 427.77 | ||
6–12 years n = 5 | 85.00 | 86.81 | 340.20 | 427.01 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
hBoV n = 254 | ||||||
ICU n = 52 | 4231.89 | 5863.96 * | 680.40 | 6544.36 | ||
0–5 years n = 46 | 4287.90 | 5863.96 | 680.40 | 6544.36 | ||
6–12 years n = 4 | 4256.98 | 9067.01 | 1474.20 | 5728.92 | ||
13–18 years n = 2 | 4178.61 | 4254.72 | 680.40 | 9747.41 | ||
Non-ICU n = 131 | 2287.66 | 1973.40 * | 793.80 | 2767.20 | ||
0–5 years n = 114 | 2383.77 | 1507.98 | 595.35 | 2103.33 | ||
6–12 years n = 14 | 2159.62 | 1945.65 | 793.80 | 2739.45 | ||
13–18 years n = 3 | 2256.30 | 4209.63 | 1786.05 | 5995.68 | ||
Outpatient n = 71 | 85.00 | 87.57 * | 340.20 | 427.77 | ||
0–5 years n = 66 | 85.00 | 87.57 | 340.20 ** | 427.77 | ||
6–12 years n = 3 | 85.00 | 60.58 | 340.20 ** | 400.78 | ||
13–18 years n = 2 | 85.00 | 60.58 | 340.20 ** | 400.74 | ||
hPIV n = 190 | ||||||
ICU n = 46 | 3883.92 | 4274.76 | 680.40 | 4955.16 | ||
0–5 years n = 43 | 3973.11 | 4274.76 | 680.40 | 4955.16 | ||
6–12 years n = 0 | NA | NA | NA | NA | ||
13–18 years n = 3 | 3631.74 | 4247.12 | 680.40 | 4927.52 | ||
Non-ICU n = 77 | 1799.54 | 1973.14 | 793.80 | 2766.94 | ||
0–5 years n = 70 | 1832.85 | 1973.07 | 793.80 | 2766.87 | ||
6–12 years n = 7 | 1746.22 | 1938.67 | 793.80 | 2732.47 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
Outpatient n = 67 | 85.00 | 87.57 | 340.20 | 427.77 | ||
0–5 years n = 64 | 85.00 | 87.57 | 340.20 | 427.77 | ||
6–12 years n = 3 | 85.00 | 41.38 | 340.20 | 381.58 | ||
13–18 years n = 0 | NA | NA | NA | NA | ||
hCoV n = 76 | ||||||
ICU n = 15 | 4894.56 | 5644.87 | 907.20 | 6552.07 | ||
0–5 years n = 14 | 4174.00 | 5632.71 | 907.20 | 6539.91 | ||
6–12 years n = 0 | NA | NA | NA | NA | ||
13–18 years n = 1 | 6422.98 | 8370.77 | 1360.80 | 9731.57 | ||
Non-ICU n = 26 | 2464.31 | 1498.42 | 595.35 | 2093.77 | ||
0–5 years n = 23 | 2581.74 | 1498.42 | 595.35 | 2093.77 | ||
6–12 years n = 2 | 2478.73 | 3072.61 | 1289.93 | 4362.54 | ||
13–18 years n = 1 | 2347.91 | 3734.62 | 1587.60 | 5322.22 | ||
Outpatient n = 35 | 85.00 | 88.33 | 340.20 | 428.53 | ||
0–5 years n = 29 | 85.00 | 87.57 | 340.20 ** | 427.77 | ||
6–12 years n = 5 | 85.00 | 60.58 | 340.20 ** | 400.78 | ||
13–18 years n = 1 | 85.00 | 31.85 | 340.20 ** | 372.05 |
Predictor | Outcome | Coefficient | 95% CI | Odds Ratio | p-Value |
---|---|---|---|---|---|
raVIVI Score | Diagnostic Test | 0.12 | 0.10, 0.13 | 1.12 | 6.76−60 |
raVIVI Score | Non-ICU admission | 0.10 | 0.08, 0.11 | 1.10 | 4.23−49 |
raVIVI Score | ICU admission | 0.04 | 0.03, 0.06 | 1.04 | 8.30−11 |
raVIVI Score | O2 Supplementation | 0.10 | 0.08, 0.11 | 1.11 | 9.90−43 |
raVIVI Score | CPAP | −0.02 | −0.08, 0.06 | 0.98 | 0.76 |
raVIVI Score | Mechanical ventilation | −0.01 | −0.06, 0.09 | 0.99 | 0.71 |
SDH Score | Diagnostic Test | −0.02 | −0.07, 0.01 | 0.98 | 0.08 |
SDH Score | Non-ICU admission | 0.13 | 0.10, 0.17 | 1.14 | 1.86−11 |
SDH Score | ICU admission | 0.09 | 0.04, 0.13 | 1.09 | 3.47−4 |
SDH Score | O2 Supplementation | 0.19 | 0.14, 0.23 | 1.21 | 5.01−14 |
SDH Score | CPAP | 0.11 | −0.01, 0.38 | 1.12 | 0.07 |
SDH Score | Mechanical ventilation | −0.36 | −0.79, −0.00 | 0.70 | 4.84−2 |
Clinical Outcome | Ethnicity | Race | Migratory Background | Birth Rank | Number of Children | Individuals in the Household | Level of Education | SDH Score |
---|---|---|---|---|---|---|---|---|
Diagnostic Test | 0.08 | 0.08 | 0.09 | 0.15 | 0.09 | 0.14 | 0.07 | 0.31 |
Non-ICU admission | 0.07 | 0.09 | 0.10 | 0.12 | 0.10 | 0.17 | 0.05 | 0.30 |
ICU admission | 0.09 | 0.10 | 0.10 | 0.11 | 0.09 | 0.10 | 0.08 | 0.33 |
O2 Supplementation | 0.07 | 0.07 | 0.09 | 0.13 | 0.13 | 0.15 | 0.05 | 0.31 |
CPAP | 0.11 | 0.11 | 0.06 | 0.14 | 0.11 | 0.14 | 0.00 | 0.32 |
Mechanical ventilation | 0.01 | 0.27 | 0.13 | 0.08 | 0.03 | 0.16 | 0.00 | 0.32 |
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Alchikh, M.; Conrad, T.O.F.; Obermeier, P.E.; Ma, X.; Schweiger, B.; Opota, O.; Rath, B.A. Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study. Viruses 2024, 16, 507. https://doi.org/10.3390/v16040507
Alchikh M, Conrad TOF, Obermeier PE, Ma X, Schweiger B, Opota O, Rath BA. Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study. Viruses. 2024; 16(4):507. https://doi.org/10.3390/v16040507
Chicago/Turabian StyleAlchikh, Maren, Tim O. F. Conrad, Patrick E. Obermeier, Xiaolin Ma, Brunhilde Schweiger, Onya Opota, and Barbara A. Rath. 2024. "Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study" Viruses 16, no. 4: 507. https://doi.org/10.3390/v16040507
APA StyleAlchikh, M., Conrad, T. O. F., Obermeier, P. E., Ma, X., Schweiger, B., Opota, O., & Rath, B. A. (2024). Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study. Viruses, 16(4), 507. https://doi.org/10.3390/v16040507