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JAMA Pediatrics Mar 2019Concomitant urinary tract infection (UTI) is a frequent concern in febrile infants with bronchiolitis, with a prior meta-analysis suggesting a prevalence of 3.3%.... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Concomitant urinary tract infection (UTI) is a frequent concern in febrile infants with bronchiolitis, with a prior meta-analysis suggesting a prevalence of 3.3%. However, the definition of UTI in these studies has generally not incorporated urinalysis (UA) results.
OBJECTIVE
To conduct a systematic review and meta-analysis examining the prevalence of UTI in infants with bronchiolitis when positive UA results are incorporated into the UTI definition.
DATA SOURCES
Medline (1946-2017) and Ovid EMBASE (1976-2017) through August 2017 and bibliographies of retrieved articles.
STUDY SELECTION
Studies reporting UTI prevalence in bronchiolitis.
DATA EXTRACTION
Data were extracted in accordance with meta-analysis of observational studies in epidemiology guidelines via independent abstraction by multiple investigators. Random-effects models generated a weighted pooled event rate with corresponding 95% confidence intervals.
MAIN OUTCOMES AND MEASURES
Prevalence of UTI.
RESULTS
We screened 477 unique articles by abstract, with full-text review of 30 studies. Eighteen bronchiolitis studies reported a UTI prevalence and 7 of these reported UA data for inclusion in the meta-analysis. The overall reported prevalence of UTI in bronchiolitis from these 18 studies was 3.1% (95% CI, 1.8%-4.6%). With the addition of positive UA results (defined as the presence of pyuria or nitrites) as a diagnostic criterion, the prevalence of UTI as reported in the 7 studies in bronchiolitis was 0.8% (95% CI, 0.3%-1.4%). Sensitivity analyses yielded similar results, including for infants younger than 90 days. Heterogeneous definitions of UTI and UA criteria introduced uncertainty into prevalence estimates.
CONCLUSIONS AND RELEVANCE
When a positive UA result is added as a diagnostic criterion, the estimated prevalence of concomitant UTI is less than recommended testing thresholds for bronchiolitis.
Topics: Bronchiolitis; Global Health; Humans; Infant; Prevalence; Urinalysis; Urinary Tract Infections
PubMed: 30688987
DOI: 10.1001/jamapediatrics.2018.5091 -
BJU International Jul 2018To explore the efficacy of antibiotic prophylaxis and the different strategies used to prevent infection in ureteroscopic lithotripsy (URL) by conducting a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy of antibiotic prophylaxis and the different strategies used to prevent infection in ureteroscopic lithotripsy (URL) by conducting a systematic review and meta-analysis.
MATERIALS AND METHODS
A systematic literature search using Pubmed, Embase, Medline, the Cochrane Library, and the Chinese CBM, CNKI and VIP databases was performed to find comparative studies on the efficacy of different antibiotic prophylaxis strategies in URL for preventing postoperative infections. The last search was conducted on 25 June 2017. Summarized unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the efficacy of different antibiotic prophylaxis strategies.
RESULTS
A total of 11 studies in 4 591 patients were included in this systematic review and meta-analysis. No significant difference was found in the risk of postoperative febrile urinary tract infections (fUTIs) between groups with and without antibiotic prophylaxis (OR: 0.82, 95% CI 0.40-1.67; P = 0.59). Patients receiving a single dose of preoperative antibiotics had a significantly lower risk of pyuria (OR: 0.42, 95% CI 0.25-0.69; P = 0.0007) and bacteriuria (OR: 0.25, 95% CI 0.11-0.58; P = 0.001) than those who did not. Intravenous antibiotic prophylaxis was not superior to single-dose oral antibiotic prophylaxis in reducing fUTI (OR: 1.00, 95% CI 0.26-3.88; P = 1.00).
CONCLUSIONS
We concluded that preoperative antibiotic prophylaxis did not lower the risk of postoperative fUTI, but a single dose could reduce the incidence of pyuria or bacteriuria. A single oral dose of preventive antibiotics is preferred because of its cost-effectiveness. The efficacy of different types of antibiotics and other strategies could not be assessed in our meta-analysis. Randomized controlled trials with a larger sample size and more rigorous study design are needed to validate these conclusions.
Topics: Administration, Oral; Anti-Bacterial Agents; Antibiotic Prophylaxis; Fever; Humans; Infusions, Intravenous; Lithotripsy; Postoperative Complications; Research Design; Ureteroscopy; Urinary Calculi; Urinary Tract Infections
PubMed: 29232047
DOI: 10.1111/bju.14101 -
Open Forum Infectious Diseases 2017Mismanagement of asymptomatic patients with positive urine cultures (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes antimicrobial resistance...
BACKGROUND
Mismanagement of asymptomatic patients with positive urine cultures (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes antimicrobial resistance and results in unnecessary antimicrobial-related adverse events and increased health care costs.
METHODS
We conducted a systematic review and meta-analysis of studies that reported on the rate of inappropriate ASB treatment published from 2004 to August 2016. The appropriateness of antimicrobial administration was based on guidelines published by the Infectious Diseases Society of America.
RESULTS
A total of 2142 nonduplicate articles were identified, and among them 30 fulfilled our inclusion criteria. The pooled prevalence of antimicrobial treatment among 4129 cases who did not require treatment was 45% (95% CI, 39-50). Isolation of gram-negative pathogens (odds ratio [OR], 3.58; 95% CI, 2.12-6.06), pyuria (OR, 2.83; 95% CI, 1.9-4.22), nitrite positivity (OR, 3.83; 95% CI, 2.24-6.54), and female sex (OR, 2.11; 95% CI, 1.46-3.06) increased the odds of receiving treatment. The rates of treatment were higher in studies with ≥100 000 cfu/mL cutoff values compared with <10 000 cfu/mL for bacterial growth (, .011). The implementation of educational and organizational interventions designed to eliminate the overtreatment of ASB resulted in a median absolute risk reduction of 33% (range, 16-36%, median, 53%; range, 25-80%).
CONCLUSION
The mismanagement of ASB remains extremely frequent. Female sex and the overinterpretation of certain laboratory data (positive nitrites, pyuria, isolation of gram-negative bacteria and cultures with higher microbial count) are associated with overtreatment. Even simple stewardship interventions can be particularly effective, and antimicrobial stewardship programs should focus on the challenge of differentiating true urinary tract infection from ASB.
PubMed: 29226170
DOI: 10.1093/ofid/ofx207 -
Pediatrics Dec 2017Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist. (Review)
Review
CONTEXT
Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist.
OBJECTIVE
To assess the criteria used for patient selection and the efficacy end points in febrile pediatric UTI CTs.
DATA SOURCES
Medline, Embase, Cochrane central databases, and clinicaltrials.gov were searched between January 1, 1990, and November 24, 2016.
STUDY SELECTION
We combined Medical Subject Headings terms and free-text terms for "urinary tract infections" and "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086 articles.
DATA EXTRACTION
Two independent reviewers assessed study quality and performed data extraction.
RESULTS
We included 40 CTs in which a total of 4381 cases of pediatric UTIs were investigated. Positive urine culture results and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria, and colony thresholds were highly variable. Clinical and microbiological end points were assessed in 88% and 93% of the studies, respectively. Timing for end point assessment was highly variable, and only 3 studies (17%) out of the 18 performed after the Food and Drug Administration 1998 guidance publication assessed primary and secondary end points consistently with this guidance.
LIMITATIONS
Our limitations included a mixed population of healthy children and children with an underlying condition. In 6 trials, researchers studied a subgroup of patients with afebrile UTI.
CONCLUSIONS
We observed a wide variability in the microbiological inclusion criteria and the timing for end point assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is necessary.
Topics: Anti-Bacterial Agents; Child; Clinical Trials as Topic; Humans; Urinary Tract Infections
PubMed: 29187579
DOI: 10.1542/peds.2017-2209 -
Urologia Internationalis 2017Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in bladder cancer patients with asymptomatic bacteriuria (ABU) remains a matter of debate. The aim of this... (Review)
Review
Safety and Efficacy of Intravesical Bacillus Calmette-Guérin Immunotherapy in Patients with Non-Muscle-Invasive Bladder Cancer Presenting with Asymptomatic Bacteriuria: A Systematic Review.
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in bladder cancer patients with asymptomatic bacteriuria (ABU) remains a matter of debate. The aim of this systematic review was to present available evidence on the safety and efficacy of BCG immunotherapy in patients with ABU. A literature search within the Medline and the Embase databases was conducted with the following search terms: adverse events, bacteriuria, BCG, bladder cancer, cystitis, infection, pyuria, side effects and urinary tract infection (UTI). Sixteen relevant original articles were identified, including 6 articles directly presenting the safety or efficacy of BCG therapy in patients with ABU. None of them was a randomized controlled trial. Intravesical BCG instillations in patients with ABU were not associated with the increased risk of symptomatic UTI and did not affect negatively the recurrence- or progression-free survival. Routine urine analysis before BCG instillation created increased cost and potentially unnecessary delays in BCG therapy. ABU does not affect negatively the safety and efficacy of intravesical BCG immunotherapy. There is no evidence to support routine screening and treatment of ABU in patients scheduled for intravesical BCG instillations due to bladder cancer. However, this issue was not addressed adequately and needs further research.
Topics: Administration, Intravesical; Antineoplastic Agents; Asymptomatic Diseases; BCG Vaccine; Bacteriuria; Humans; Immunotherapy; Neoplasm Invasiveness; Risk Assessment; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 28601885
DOI: 10.1159/000477673 -
Surgical Infections Aug 2015To evaluate the effectiveness of prophylactic antibiotic therapy in reducing the incidence of post-ureteroscopic lithotripsy (URL) infections. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the effectiveness of prophylactic antibiotic therapy in reducing the incidence of post-ureteroscopic lithotripsy (URL) infections.
METHODS
A systemic search of PubMED was performed to identify all randomized trials that compared the incidence of post-operative infections in patients without pre-operative urinary tract infections who underwent URL with and without a single dose of prophylactic antibiotics. The data were analyzed using Cochrane Collaboration Review Manager (RevMan, version 5.2). The endpoints of the analysis were pyuria (>10 white blood cells/high-power field), bacteriuria (urine culture with bacteria >10(5) colony-forming units/mL), and febrile urinary tract infections (fUTIs), defined as a body temperature of >38°C with pyuria or meaningful bacteriuria within 1 wk after the operation.
RESULTS
In total, four trials enrolling 500 patients met the inclusion criteria and were subjected to meta-analysis. Prophylactic antibiotics significantly reduced post-URL pyuria (risk ratios [RR] 0.65; 95% confidence interval [CI] 0.51-0.82) and bacteriuria (RR 0.26; 95% CI 0.12-0.60; p=0.001). Patients who received prophylactic antibiotics tended to have lower rates of fUTI, although the difference was not statistically significant.
CONCLUSION
Prophylactic antibiotic therapy can reduce the incidence of pyuria and bacteriuria after URL. However, because of the low incidence of post-URL fUTIs, we failed to show that a single dose of prophylactic antibiotics can reduce the rate of such infections significantly.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Fever; Humans; Incidence; Lithotripsy; Postoperative Complications; Ureteroscopy; Urinary Tract Infections
PubMed: 26207401
DOI: 10.1089/sur.2014.013 -
The Cochrane Database of Systematic... Jul 2013Urinary tract infections account for about 40% of hospital-acquired (nosocomial) infections, and about 80% of urinary tract infections acquired in hospital are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urinary tract infections account for about 40% of hospital-acquired (nosocomial) infections, and about 80% of urinary tract infections acquired in hospital are associated with urinary catheters.
OBJECTIVES
To determine if certain antibiotic prophylaxes are better than others in terms of prevention of urinary tract infections, complications, quality of life and cost-effectiveness in short-term catheterisation in adults.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in Process, and handsearching of journals and conference proceedings (searched 31st October 2012). Additionally, we examined all reference lists of identified trials.
SELECTION CRITERIA
All randomised and quasi-randomised trials comparing antibiotic prophylaxis for short-term (up to and including 14 days) catheterisation in adults.
DATA COLLECTION AND ANALYSIS
Data were independently extracted by all review authors and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook for Systemtic Reviews of Interventions. Where data had not been fully reported, clarification was sought directly from the authors of the trial.
MAIN RESULTS
Six parallel-group randomised controlled trials with 789 participants met the inclusion criteria. All six trials compared antibiotic prophylaxis versus no prophylaxis. Studies presented a low to unclear risk of bias with similar interventions and measured outcomes.The primary outcome of bacteriuria was less common in the prophylaxis group amongst surgical patients with asymptomatic bacteriuria (I(2) = 0; risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) . Two non-surgical studies could not be combined in a meta-analysis due to heterogeneity and only one showed significantly fewer cases of bacteriuria (RR 0.19; 95% CI 0.09 to 0.37).Two trials of surgical patients with asymptomatic bacteriuria only (255 participants) compared one type of antibiotic prophylaxis with another and neither study showed a significant difference in cases of bacteriuria.One study (78 participants) compared antibiotic prophylaxis in patients at catheterisation only versus antibiotic prophylaxis throughout catheterisation period with asymptomatic bacteriuria. Antibiotics at catheterisation only, resulted in significantly fewer cases of bacteriuria than giving prophylaxis throughout the catheterisation period (RR 0.29 95% CI 0.09 to 0.91).Secondary data of pyuria were provided by two surgical studies (255 participants). When studies were pooled, pyuria occurred in significantly fewer cases in the prophylactic antibiotic group (RR 0.23, 95% CI 0.13 to 0.42). The number of gram-negative isolates in patients' urine just before catheter removal in one study (RR 0.05, 95% CI 0.00 to 0.79) and six weeks after hospital discharge (RR 0.36, 95% CI 0.23 to 0.56) were significantly lower. There were no events in the treatment group before catheter removal. When pooled data from two studies showed significantly reduced febrile morbidity in those receiving antibiotic prophylaxis (RR 0.53 95% CI 0.31 to 0.89).Although all studies assessed micro-organisms isolated from the urine specimens the data were too heterogenous to pool in a meta-analysis and have been provided in a narrative form. Further secondary data such as economic analysis, length of stay and quality of life were not covered in detail.
AUTHORS' CONCLUSIONS
The limited evidence indicated that receiving prophylactic antibiotics reduced the rate of bacteriuria and other signs of infection, such as pyuria, febrile morbidity and gram-negative isolates in patients' urine, in surgical patients who undergo bladder drainage for at least 24 hours postoperatively. There was also limited evidence that prophylactic antibiotics reduced bacteriuria in non-surgical patients.
Topics: Adult; Antibiotic Prophylaxis; Catheters, Indwelling; Drainage; Humans; Randomized Controlled Trials as Topic; Urinary Bladder; Urinary Catheterization; Urinary Tract Infections
PubMed: 23824735
DOI: 10.1002/14651858.CD005428.pub2 -
Health Technology Assessment... Oct 2006To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests... (Review)
Review
OBJECTIVES
To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals.
DATA SOURCES
Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field.
REVIEW METHODS
A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms.
RESULTS
The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year.
CONCLUSIONS
The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.
Topics: Algorithms; Child, Preschool; Cost-Benefit Analysis; Humans; Infant; Infant, Newborn; Models, Economic; United Kingdom; Urinalysis; Urinary Tract Infections; Urine
PubMed: 17014747
DOI: 10.3310/hta10360 -
The Cochrane Database of Systematic... Jul 2005Urinary tract infections account for about 40% of hospital-acquired (nosocomial) infections, and about 80% of urinary tract infections acquired in hospital are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urinary tract infections account for about 40% of hospital-acquired (nosocomial) infections, and about 80% of urinary tract infections acquired in hospital are associated with urinary catheters.
OBJECTIVES
To determine if certain antibiotic policies are better than others in terms of prevention of urinary tract infections, complications, quality of life and cost-effectiveness in short-term catheterised adults.
SEARCH STRATEGY
We searched the Cochrane Incontinence Group Specialised Register (searched 20 December 2004). Additionally, we examined all reference lists of identified trials.
SELECTION CRITERIA
All randomised and quasi-randomised trials comparing antibiotic policies for short-term (up to and including 14 days) catheterization in adults.
DATA COLLECTION AND ANALYSIS
Data were extracted by both reviewers independently and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. If data had not been fully reported, clarification was sought directly from the authors of the trial.
MAIN RESULTS
Six parallel-group randomised controlled trials met the inclusion criteria. In one trial comparing antibiotic prophylaxis with giving antibiotics when clinically indicated amongst female surgical patients who had a urethral catheter for more than 24 hours, symptomatic urinary tract infection was less common in the prophylaxis group (RR 0.20, 95% CI 0.06 to 0.66). Five trials compared antibiotic prophylaxis with giving antibiotics when microbiologically indicated, bacteriuria, pyuria and gram-negative isolates in patients' urine were less common in the prophylaxis group amongst surgical patients with bladder drainage for at least 24 hours postoperatively. Bacteriuria rates were also about five-fold lower in the prophylaxis group in trials involving urological surgery patients and non-surgical patients. No trial compared giving antibiotics when microbiologically indicated with giving antibiotics when clinically indicated.
AUTHORS' CONCLUSIONS
There was weak evidence that antibiotic prophylaxis compared to giving antibiotics when clinically indicated reduced the rate of symptomatic urinary tract infection in female patients with abdominal surgery and a urethral catheter for 24 hours. The limited evidence indicated that receiving antibiotics during the first three postoperative days or from postoperative day two until catheter removal reduced the rate of bacteriuria and other signs of infection such as pyuria and gram-negative isolates in patients urine in surgical patients with bladder drainage for at least 24 hours postoperatively. There was also limited evidence that prophylactic antibiotics reduced bacteriuria in non-surgical patients.
Topics: Adult; Antibiotic Prophylaxis; Catheters, Indwelling; Drainage; Humans; Randomized Controlled Trials as Topic; Urinary Bladder; Urinary Catheterization; Urinary Tract Infections
PubMed: 16034973
DOI: 10.1002/14651858.CD005428 -
BMC Pediatrics Apr 2005Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of... (Review)
Review
BACKGROUND
Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture.
METHODS
We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age.
RESULTS
The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful.
CONCLUSION
Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation.
Topics: Child, Preschool; Humans; Infant; Kidney; Predictive Value of Tests; Reagent Strips; Urinalysis; Urinary Tract Infections; Urine
PubMed: 15811182
DOI: 10.1186/1471-2431-5-4