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Systematic review and meta-analysis on diagnostic accuracy of signs & symptoms
predicting uncomplicated urinary tract infection in women
Giesen LGMErasmus student Sept – Dec 2009 RCSI, Dublin
Cousins G, Dimitrov BD , Van de Laar FA, Fahey T
Outline
• Background/ Rationale
• Methods
• Results
• Conclusion
Background
• Prevalence– 5% asymptomatic– 50% symptomatic
• Pathogens
• Reference standard– Midstream urine culture– Thresholds >10², >10³, >105 CFU/ml
Diagnosis UTI
Diagnosis
Dipstick testing Culture urineSigns & symptoms
Diagnosis UTI
Diagnosis
Dipstick testing Culture urineSigns & symptoms
Rationale
• Bent 2002– Meta-analysis of 9 studies
– Reference standard > 104 CFU/ml
– Significant symptoms & signs
• What can we add?– 9 additional studies
– European guidelines
– Consideration of heterogeneity
Diagnostic accuracy signs & symptoms
Reference test :
Urine culture
> 10² CFU/ml
>10³ CFU/ml
>105 CFU/ml
Signs & symptoms
Dysuria
Frequency
Urgency
Hematuria
Fever
Flank pain
Absence vaginal discharge
& irritation
Participants Healthy women with symptoms of UTI
Setting Primary care
Index test Signs & symptoms
Reference test Urine culture (> 10², >103, >105 CFU/ml)
Outcome measure 2x2 tables
Methods – Identification of studies
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
Derivation of summary statistics
Little (2006)
UTI No UTI Total
Frequency 185 94 279
No frequency 69 60 129
Total 254 154 408
Sensitivity:
185/254 = 72.8%
Specificity: 60/154 = 39.0%
+ LR = sens/ (1- spec) =
72.8/ (1-39.0) = 1.19
Results: 16 studiesQuality assessment
Time period index and reference test
Blinding
Contamination reported
Pt selected consecutively
Data included 95%CI
Results: Meta-analysis (> 102)
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)
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%
Heterogeneity - threshold effect (> 102)Symptom (# studies) Correlation P-value Present
Frequency (13) 0.698 0.008 X
Dysuria (14) 0.679 0.008 X
Hematuria (7) -0.714 0.071
Nocturia (6) 0.257 0.623
Urgency (9) 0.933 0.000 X
Vaginal discharge (6) 1.000 0.000 X
Heterogeneity frequency - threshold effect
Frequency (# studies) Correlation P-value Present
> 102 CFU/ml (13) 0.698 0.008 X
> 103 CFU/ml (11) 0.673 0.023 X
> 105 CFU/ml (6)0.486 0.329
Heterogeneity 102 CFU/ml 103 CFU/ml
Figures: sensitivity frequency
I-square = 84.9% I-square = 85.2% I-square = 68.1%
105 CFU/ml
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
Conclusions
• Importance of considering heterogeneity– Variations in diagnostic threshold– Patient selection/ setting
• Future directions– Combinations of symptoms – clinical prediction rule– Severitiy of symptoms