1. Systematic review and meta-analysis on diagnostic accuracy of signs & symptoms predicting uncomplicated urinary tract infection in women Giesen LGM Erasmus student Sept – Dec 2009 RCSI, Dublin Cousins G, Dimitrov BD, Van de Laar FA, Fahey T

2. Outline Background/ Rationale Methods Results Conclusion

3. Background Prevalence –5% asymptomatic –50% symptomatic Pathogens Reference standard –Midstream urine culture –Thresholds >10², >10³, >10 5 CFU/ml

4. Diagnosis UTI Diagnosis Dipstick testingCulture urine Signs & symptoms

5. Diagnosis UTI Diagnosis Dipstick testingCulture urine Signs & symptoms

6. Rationale Bent 2002 – Meta-analysis of 9 studies – Reference standard > 10 4 CFU/ml – Significant symptoms & signs What can we add? – 9 additional studies – European guidelines – Consideration of heterogeneity

7. Diagnostic accuracy signs & symptoms Reference test : Urine culture > 10² CFU/ml >10³ CFU/ml >10 5 CFU/ml Signs & symptoms Dysuria Frequency Urgency Hematuria Fever Flank pain Absence vaginal discharge & irritation

8. ParticipantsHealthy women with symptoms of UTI SettingPrimary care Index testSigns & symptoms Reference testUrine culture (> 10², >10 3, >10 5 CFU/ml) Outcome measure2x2 tables Methods – Identification of studies

9. Methods Quality assessment (QUADAS) Meta-analysis 1.Derivation of summary statistics of each study (2x2 tables) 2.Pooling the summary statistics across studies 3.Examine the pattern of variability (heterogeneity) observed in the results

10. Derivation of summary statistics Little (2006) UTINo UTITotal Frequency18594279 No frequency6960129 Total254154408 Sensitivity: 185/254 = 72.8% Specificity: 60/154 = 39.0% + LR = sens/ (1- spec) = 72.8/ (1-39.0) = 1.19

11. Results: 16 studies Quality assessment Time period index and reference test Blinding Contamination reported Pt selected consecutively Data included 95%CI

12. Results: Meta-analysis (> 10 2 ) Symptom (# studies)Sens (95%CI)Spec (95%CI)+ LR (95%CI) Frequency (13)0.88 (0.83-0.92)0.20 (0.14-0.28)1.10 (1.04-1.16) Dysuria (14)0.80 (0.74-0.86)0.38 (0.31-0.46)1.30 (1.20-1.41) Hematuria (7)0.25 (0.21-0.29)0.85 (0.81-0.89)1.72 (1.30-2.27) Nocturia (6)0.59 (0.50-0.68)0.55 (0.49-0.61)1.30 (1.08-1.56) Urgency (9)0.67 (0.52-0.80)0.45 (0.31-0.60)1.22 (1.11-1.34) Vaginal discharge (6)0.15 (0.08-0.26)0.77 (0.62-0.88)0.65 (0.51-0.83)

13. Pretest & posttest probability Pretest Probability = 50% Posttest Probability Frequency LR+ = 1.10 Hematuria LR+ = 1.72 Dysuria LR+ = 1.30 Nocturia LR+ = 1.30 Urgency LR+ = 1.22 Vaginal discharge LR+ = 0.65 52,4% 56.5% 63.2% 55.0% 39.4% 56.5%

14. Heterogeneity - threshold effect (> 10 2 ) Symptom (# studies)CorrelationP-valuePresent Frequency (13)0.6980.008X Dysuria (14)0.6790.008X Hematuria (7)-0.7140.071 Nocturia (6)0.2570.623 Urgency (9)0.9330.000X Vaginal discharge (6)1.0000.000X

15. Heterogeneity frequency - threshold effect Frequency (# studies)CorrelationP-valuePresent > 10 2 CFU/ml (13)0.6980.008X > 10 3 CFU/ml (11)0.6730.023X > 10 5 CFU/ml (6) 0.4860.329

16. Heterogeneity 10 2 CFU/ml10 3 CFU/ml Figures: sensitivity frequency I-square = 84.9%I-square = 85.2%I-square = 68.1% 10 5 CFU/ml

17. Conclusions 5 symptoms increase the probability of UTI when present (frequency/ dysuria/ hematuria/ nocturia/ urgency) – Vaginal discharge decreased probability of UTI However only modest ability to ‘rule in’ or ‘rule out’ UTI – High pre-test probability

18. Conclusions Importance of considering heterogeneity – Variations in diagnostic threshold – Patient selection/ setting Future directions – Combinations of symptoms – clinical prediction rule – Severitiy of symptoms