Objectives To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults. Data sources Electronic databases from inception to October 2003, updated in August 2004. Review methods A systematic review was undertaken according to published guidelines. Decision analytic modelling was undertaken, based on the findings of the review, expert opinion and additional information from the literature, to assess the relative cost-effectiveness of plausible alternative tests that are part of diagnostic algorithms for haematuria. Results A total of 118 studies met the inclusion criteria. No studies that evaluated the effectiveness of diagnostic algorithms for haematuria or the effectiveness of screening for haematuria or investigating its underlying cause were identified. Eighteen out of 19 identified studies evaluated dipstick tests and data from these suggested that these are moderately useful in establishing the presence of, but cannot be used to rule out, haematuria. Six studies using haematuria as a test for the presence of a disease indicated that the detection of microhaematuria cannot alone be considered a useful test either to rule in or rule out the presence of a significant underlying pathology (urinary calculi or bladder cancer). Forty-eight of 80 studies addressed methods to localise the source of bleeding (renal or lower urinary tract). The methods and thresholds described in these studies varied greatly, precluding any estimate of a 'best performance' threshold that could be applied across patient groups. However, studies of red blood cell morphology that used a cut-off value of 80% dysmorphic cells for glomerular disease reported consistently high specificities (potentially useful in ruling in a renal cause for haematuria). The reported sensitivities were generally low. Twenty-eight studies included data on the accuracy of laboratory tests (tumour markers, cytology) for the diagnosis of bladder cancer. The majority of tumour marker studies evaluated nuclear matrix protein 22 or bladder tumour antigen. The sensitivity and specificity ranges suggested that neither of these would be useful either for diagnosing bladder cancer or for ruling out patients for further investigation (cystoscopy). However, the evidence remains sparse and the diagnostic accuracy estimates varied widely between studies. Fifteen studies evaluating urine cytology as a test for urinary tract malignancies were heterogeneous and poorly reported. The calculated specificity values were generally high, suggesting some possible utility in confirming malignancy. However, the evidence suggests that urine cytology has no application in ruling out malignancy or excluding patients from further investigation. Fifteen studies evaluated imaging techniques [computed tomography (CT), intravenous urography (IVU) or ultrasound scanning (US)] to detect the underlying cause of haematuria. The target condition and the reference standard varied greatly between these studies. The diagnostic accuracy data for several individual studies appeared promising but meaningful comparison of the available imaging technologies was impossible. Eight studies met the inclusion criteria but addressed different parts of the diagnostic chain (e.g. screening programmes, laboratory investigations, full urological work-up). No single study addressed the complete diagnostic process. The review also highlighted a number of methodological limitations of these studies, including their lack of generalisability to the UK context. Separate decision analytic models were therefore developed to progress estimation of the optimal strategy for the diagnostic management of haematuria. The economic model for the detection of microhaematuria found that immediate microscopy following a positive dipstick test would improve diagnostic efficiency as it eliminates the high number of false positives produced by dipstick testing. Strategies that use routine microscopy may be associated with high numbers of false results, but evidence was lacking regarding the accuracy of routine microscopy and estimates were adopted for the model. The model for imaging the upper urinary tract showed that US detects more tumours than IVU at one-third of the cost, and is also associated with fewer false results. For any cause of haematuria, CT was shown to have a mean incremental cost-effectiveness ratio of pounds sterling 9939 in comparison with the next best option, US. When US is followed up with CT for negative results with persistent haematuria, it dominates the initial use of CT alone, with a saving of pounds sterling 235,000 for the evaluation of 1000 patients. The model for investigation of the lower urinary tract showed that for low-risk patients the use of immediate cystoscopy could be avoided if cystoscopy were used for follow-up patients with a negative initial test using tumour markers and/or cytology, resulting in a saving of pounds sterling 483,000 for the evaluation of 1000 patients. The clinical and economic impact on delayed detection of both upper and lower urinary tract tumours through the use of follow-up testing should be evaluated in future studies. Conclusions There are insufficient data currently available to derive an evidence-based algorithm of the diagnostic pathway for haematuria. A hypothetical algorithm based on the opinion and practice of clinical experts in the review team, other published algorithms and the results of economic modelling is presented in this report. This algorithm is presented, for comparative purposes, alongside current US and UK guidelines. The ideas contained in these algorithms and the specific questions outlined should form the basis of future research. Quality assessment of the diagnostic accuracy studies included in this review highlighted several areas of deficiency.

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Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation

Objective

To assess the accuracy of fetal echocardiography in the prenatal diagnosis of cardiosplenic syndromes and the spectrum of associated anomalies.



Methods

This was a retrospective survey of fetuses in our databases over a period of 10 years with postnatally confirmed prenatal diagnosis of cardiosplenic syndromes.



Results

In 32 of 35 fetuses the prenatal diagnosis of cardiosplenic syndromes was confirmed postpartum. Twenty-two fetuses had left isomerism. Their main prenatal ultrasound features were interrupted inferior vena cava (n = 21), complete atrioventricular septal defect (n = 15), viscerocardiac heterotaxy (n = 15), persistent bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema (n = 12). Twelve pregnancies were terminated, two fetuses were stillborn and eight infants survived. Ten fetuses had right isomerism. Their main sonographic features were juxtaposition of the descending aorta and inferior vena cava (n = 7), complete atrioventricular septal defect (n = 7), left persistent superior vena cava (n = 6) and viscerocardiac heterotaxy (n = 6). In this group there was one stillbirth, five infant deaths and four survivors. The overall survival rate and spectrum of other cardiac malformations were similar between the two groups. Prenatal diagnosis of other visceral features of cardiosplenic syndromes was inconsistent.



Conclusion

Cardiosplenic syndromes can be diagnosed with high accuracy by prenatal sonography. A diagnosis of left isomerism should be strongly suggested in the presence of a combination of at least two of the following: (1) complete atrioventricular septal defect or other structural heart disease; (2) interruption of inferior vena cava with azygos continuation; (3) early fetal heart block; (4) viscerocardiac heterotaxy. Right isomerism should be suspected in the presence of a combination of at least two of the following: (1) structural heart disease, namely complete atrioventricular septal defect; (2) juxtaposition of inferior vena cava and descending aorta; (3) viscerocardiac heterotaxy. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Prenatal diagnosis of cardiosplenic syndromes: a 10-year experience.

Congenital Abnormalities of Intrathoracic Airways

Excellent inherent tissue contrast is one of the great promises of clinical magnetic resonance (MR) imaging, but functional information is relatively limited. However, MR imaging complemented by the administration of contrast agents can provide such functional assessment. The perfusion status of the myocardium is one of the most important functional information in cardiovascular imaging. Because the clinical acceptance of a contrast agent is measured by its ability to improve patient outcome and to guide therapy, it is unlikely that detection of myocardial infarction, the final stage of ischemic heart disease, should be the target for contrast media development. It would obviously be better if occult regional myocardial perfusion deficits could be reliably detected. The current article was prepared to help the clinical radiologist to keep pace with new strategies for myocardial enhancement and their potential clinical applicability for detection of early perfusion deficits.

Assessment of myocardial perfusion using contrast-enhanced MR imaging: current status and future developments.

IODINATED CONTRAST MATERIAL IN URORADIOLOGY: Choice of Agent and Management of Complications

A prospective, randomized, physician-blinded study was conducted to determine whether a smaller dose of low-osmolar, nonionic contrast medium can provide diagnostic information on excretory urograms equivalent to that obtained with higher doses of ionic and nonionic contrast agents. One hundred fifty adult patients who underwent excretory urography received a high-dose ionic contrast medium (diatrizoate sodium), high-dose nonionic contrast medium (iohexol), or low-dose nonionic contrast medium (iohexol). All urograms were scored for diagnostic quality. No difference in urographic quality was detected among the different doses of contrast media. The lower dose of low-osmolar nonionic contrast medium provided equivalent diagnostic information. The quality of the nephrotomograms, ureteral image, and overall image was slightly greater with diatrizoate than with a small dose of iohexol, but the difference was not significant. This study suggests that excretory urograms obtained in relatively healthy, well-prep...

Diagnostic efficacy of excretory urography with low-dose, nonionic contrast media.

Left thoracic isomerism may present as an isolated anomaly without symptoms. The chest radiograph demonstrates characteristic right hilar findings that may be misinterpreted as a hilar mass. Computed tomography of the chest is recommended to confirm the correct diagnosis.

Isolated left thoracic isomerism.

Because of improved patient tolerance and decreased risks of idiosyncratic reaction, low-osmolarity contrast media are increasingly used for excretory urography. However, physiologic differences among patients may affect the optimal time for acquiring diagnostic radiographs during the pyelographic phase of the examination. A prospective, randomized, physician-blinded comparative study of 60 adult patients was undertaken to determine if the time to peak opacification of the pyelocaliceal systems differs with different doses of nonionic and ionic contrast media. Three doses of contrast media were used: a high dose (based on body weight) of a high-osmolarity ionic contrast medium, a high dose (based on body weight) of a low-osmolarity non-ionic contrast medium and a lower, fixed dose of a low-osmolarity nonionic contrast medium. The diagnostic quality of the radiographs did not differ statistically with the dose or the contrast medium. However, acquiring an additional radiograph during abdominal compression greatly increased the chance of obtaining at least one radiograph with maximal diagnostic information during the pyelographic phase. Despite potential differences among contrast media in the degree of pyelocaliceal opacification or distension and diuresis, it is not necessary to modify the timing of film acquisitions during excretory urography when lower doses of low-osmolarity agents are administered.

J. V. Ellis

Papers

Diagnostic efficacy of excretory urography with low-dose, nonionic contrast media.

Isolated left thoracic isomerism.

Maximizing opacification during excretory urography: effect of low-osmolarity contrast media.