Figure 1
Flowchart of Study Selection for Meta-analysis.
Table 1
Summary of Quality Assessment of Diagnostic Accuracy Study (QUADAS-2) for Accepted Studies.
| No. | First Author (Year) | Risk of Bias | Applicability Concerns | |||||
|---|---|---|---|---|---|---|---|---|
| Patient Selection | Index Test | Reference Standard | Flow and Timing | Patient Selection | Index Test | Reference Standard | ||
| 1. | Wardi (2012) | U | L | L | L | L | L | L |
| 2. | Peng (2005) | L | H | L | L | L | L | L |
| 3. | Urita (2004) | L | H | L | L | L | L | L |
| 4. | Wong (2003) | L | L | L | L | L | L | L |
| 5. | Chua (2002) | L | L | L | L | L | L | L |
| 6. | Kato (2002) | L | H | L | L | L | L | L |
| 7. | Wong WM (2001) | L | H | L | L | L | L | L |
| 8. | Wong BCY (2001) | L | L | L | L | L | L | L |
| 9. | Peng (2000) | U | L | L | L | L | L | L |
| 10. | Wong (2000) | L | H | L | L | L | L | L |
| 11. | Wang (1998) | L | H | L | L | L | L | L |
[i] L = Low risk.
H = High risk.
U = Unclear risk.
Table 2
Summary Table of Accepted Studies.
| No. | First Author (Year) | Population & Country | Name of Test | Cut-off Threshold | Other Specific Features of Test | Gold Standard |
|---|---|---|---|---|---|---|
| 1. | Wardi (2012) | Adults, partial gastrectomy, Israel | 13C-BreathID | 5.0 δ over baseline | 75 mg, 4.5 g citric acid-based powder, breath sample at 10 to 15 minutes (delta time) | Histology |
| 2. | Peng (2005a) | Adults, routine upper scope, Taiwan | 13C-UBT (INER, Taiwan) | 2.0 δ over baseline | 50 mg, 6-hour fast, no test meal, breath sample at 15 minutes | Culture or histology + CLO |
| Peng (2005b) | Adults, routine upper scope, Taiwan | 13C-UBT (INER, Taiwan) | 5.0 δ over baseline | 100 mg, 6-hour fast, no test meal, breath sample at 15 minutes | Culture or histology + CLO | |
| 3. | Urita (2004) | Adults, diagnostic upper scope, Japan | Modified 13C-UBT (sample via nostril) | 2.5 δ over baseline | 100 mg, overnight fast, breath sample at 20 minutes | Histology + serology |
| 4. | Wong (2003) | Adults, referred to upper scope unit, Hong Kong | Tablet 13C-UBT (Diabact UBT) | 3.0 δ over baseline | 50 mg, overnight fast, 456 mg anhydrous citric acid, breath sample at 20 minutes | RUT + histology |
| 5. | Chua (2002) | Adults, referred to upper scope unit, Singapore | 13C-UBT (Hp-Plus, Sweden) | 3.5 δ over baseline | Amount of 13C-urea not stated, test meal with solution containing citric acid, breath sample at 30 minutes | Histology + CLO + serology (2/3) |
| 6. | Kato (2002) | Children, referred to upper scope unit, Japan | 13C-Urea Breath Test | 3.5 δ over baseline | 75 and 100 mg, 4-hour fast, no test meal, breath sample at 20 minutes | Culture or histology + RUT |
| 7. | Wong WM (2001a) | Adults, referred to upper scope unit, Hong Kong | 13C-Urea Breath Test | 7.5 δ over baseline | 50 mg, overnight fast, no test meal, breath sample at 20 minutes | Histology + CLO |
| Wong WM (2001b) | Adults, referred to upper scope unit, Hong Kong | 13C-Urea Breath Test | 3.0 δ over baseline | 50 mg, overnight fast, 2.4 g citrate solution as test meal, breath sample at 20 minutes | Histology + CLO | |
| 8. | Wong BCY (2001) | Adults, referred to upper scope unit, Hong Kong | 13C-Urea Breath Test | 5.0 δ over baseline | 75 mg, overnight fasting, 2.4 g citric acid 200 mL test meal solution, breath sample at 30 minutes | Histology + RUT + CLO + culture + PCR |
| 9. | Peng (2000) | Adults, non-ulcer dyspepsia, Taiwan | 13C-UBT (INER, Taiwan) | 3.0 δ over baseline | 100 mg, 6-hour fast, 100 mL fresh milk as test meal, breath sample at 15 minutes | Culture or histology + CLO |
| 10. | Wong (2000a) | Adults, referred to upper scope unit, Hong Kong | 13C-Urea Breath Test | 5.0 δ over baseline | 75 mg, overnight fast, 2.4 g citric acid solution as test meal, breath sample at 30 minutes | Histology + CLO |
| Wong (2000b) | Adults, referred to upper scope unit, Hong Kong | 13C-Urea Breath Test | 5.0 δ over baseline | 75 mg, overnight fast, no test meal, breath sample at 30 minutes | Histology + CLO | |
| 11. | Wang (1998a) | Adults, routine upper scope, Taiwan | 13C-UBT (INER, Taiwan) | 3.0 δ over baseline | 100 mg, 6-hour fast, 100 mL fresh milk as test meal, breath sample at 15 minutes | Histology or culture or urease test |
| Wang (1998b) | Adults, routine upper scope, Taiwan | 13C-UBT (INER, Taiwan) | 4.0 δ over baseline | 100 mg, 6-hour fast, 100 mL fresh milk as test meal, breath sample at 30 minutes | Histology or culture or urease test |
[i] PCR Polymerase chain reaction.
CLO Campylobacter-like organism test (rapid urease test).
RUT Rapid urease test.
Table 3
Summary Table of Accepted Studies with Indicators of Diagnostic Accuracy.
| No. | Author (Year) | Total, n | TP | TN | FP | FN | Sensitivity | Specificity | Overall Accuracy | PPV | NPV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1. | Wardi (2012) | 76 | i9 | i57 | i5 | i5 | 64.2 | 91.9 | 86.8 | 64.2 | 91.9 |
| 2. | Peng (2005a) | 50 | 27 | 22 | 0 | 1 | 96.4 | 100.0 | 98.0 | 100.0 | 95.6 |
| Peng (2005b) | 50 | 18 | 32 | 0 | 0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | |
| 3. | Urita (2004) | 127 | i42 | i85 | i0 | i0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
| 4. | Wong (2003) | 200 | i99 | i101 | i0 | i0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
| 5. | Chua (2002) | 100 | 65 | 31 | 0 | 4 | 94.2 | 100.0 | 96.0 | 100.0 | 88.6 |
| 6. | Kato (2002) | 220 | i87 | i129 | i2 | i2 | 97.8 | 98.5 | 98.2 | 97.8 | 98.5 |
| 7. | Wong WM (2001a) | 101 | i49 | i50 | i2 | i0 | 100.0 | 96.2 | 98.0 | 96.1 | 100.0 |
| Wong WM (2001b) | 105 | i50 | i54 | i1 | i0 | 100.0 | 98.2 | 99.1 | 98.0 | 100.0 | |
| 8. | Wong BCY (2001) | 294 | i151 | i127 | i4 | i12 | 92.6 | 96.9 | 94.5 | 97.4 | 91.2 |
| 9. | Peng (2000) | 136 | i76 | i49 | i6 | i5 | 93.8 | 89.1 | 91.9 | 92.7 | 90.7 |
| 10. | Wong (2000a) | 202 | i110 | i86 | i2 | i4 | 96.5 | 97.7 | 97.0 | 98.2 | 95.6 |
| Wong (2000b) | 202 | i108 | i86 | i2 | i6 | 94.7 | 97.7 | 96.0 | 98.2 | 93.5 | |
| 11. | Wang (1998a) | 352 | 197 | 143 | 10 | 2 | 99.0 | 93.4 | 96.6 | 95.2 | 98.6 |
| Wang (1998b) | 352 | 196 | 142 | 11 | 3 | 98.5 | 92.8 | 96.0 | 94.7 | 97.9 |
[i] i Figures indirectly derived from the original articles via deduction of other available figures.
TP True Positive.
TN True Negative.
FP False Positive.
FN False Negative.
PPV Positive Predictive Value.
NPV Negative Predictive Value.
Figure 2
Overall Pooled Sensitivity of 13C-UBT to Detect H. pylori Infection.
Figure 3
Overall Pooled Specificity of 13C-UBT to Detect H. pylori Infection.
Table 4
Summary Statistics for the Diagnostic Accuracy of 13C-Urea Breath Test.
| Sub-groups | Number of Studies | P-value (I2)a | P-value (I2)b | Sensitivity (95% CI) | Specificity (95% CI) |
|---|---|---|---|---|---|
| All studies* | 15 | <0.01 (72.8%) | <0.01 (64.5%) | 0.97 (0.96, 0.98) | 0.96 (0.95, 0.97) |
| By dose of 13C-urea** | |||||
| 50 mg | 4 | 0.24# (28.7%) | 0.17# (40.6%) | 1.00 (0.98, 1.00) | 0.99 (0.96, 1.00) |
| 75 mg | 4 | 0.01 (76.5%) | 0.28# (21.0%) | 0.93 (0.90, 0.96) | 0.96 (0.94, 0.98) |
| 100 mg | 5 | 0.07 (53.0%) | <0.01 (76.1%) | 0.98 (0.97, 0.99) | 0.94 (0.92, 0.96) |
| By cut-off threshold | |||||
| <5.0 δ over baseline | 9 | 0.02 (54.4%) | <0.01 (75.9%) | 0.98 (0.97, 0.99) | 0.96 (0.95, 0.97) |
| ≥5.0 δ over baseline | 6 | <0.01 (76.5%) | 0.30# (17.3%) | 0.94 (0.92, 0.96) | 0.97 (0.95, 0.98) |
| By breath sample collection time | |||||
| 10 to 15 minutes | 5 | <0.01 (83.0%) | 0.06 (55.4%) | 0.96 (0.94, 0.98) | 0.94 (0.90, 0.96) |
| 20 minutes | 5 | 0.26# (24.0%) | 0.15# (40.3%) | 0.99 (0.98, 1.00) | 0.99 (0.97, 1.00) |
| 30 minutes | 5 | 0.07 (54.6%) | 0.10# (48.4%) | 0.96 (0.94, 0.97) | 0.96 (0.94, 0.98) |
| By locality*** | |||||
| Hong Kong | 6 | <0.01 (75.5%) | 0.36# (8.4%) | 0.96 (0.94, 0.98) | 0.98 (0.96, 0.99) |
| Taiwan | 5 | 0.13# (44.0%) | 0.06 (54.8%) | 0.98 (0.96, 0.99) | 0.93 (0.91, 0.96) |
| By manufacturer | |||||
| 13C-UBT (INER, Taiwan) | 5 | 0.13# (44.0%) | 0.06 (54.8%) | 0.98 (0.96, 0.99) | 0.93 (0.91, 0.96) |
| Others | 10 | <0.01 (77.5%) | 0.05 (46.7%) | 0.96 (0.94, 0.97) | 0.98 (0.97, 0.99) |
[i] * Four articles had data for two sets of samples, tools and findings; a total of 15 studies were obtained.
** One study was not included in this sub-group due to absence of reported 13C-urea amount used, and another study was excluded due to use of multiple amounts in a single study (for different age groups in children).
*** Studies done in Japan, Israel and Singapore were excluded due to having only two or less studies per locality.
a P-value for heterogeneity (chi-squared) and I2 test for heterogeneity quantification for sensitivity analysis.
b P-value for heterogeneity (chi-squared) and I2 test for heterogeneity quantification for specificity analysis.
# P-value is not significant (≥0.1).