Cross-sectional Diagnostic Studies Research Articles

How good is the diagnostic test accuracy of telehealth assessment for dementia and mild cognitive impairment? A Cochrane Review summary with commentary.

It is estimated that 50% to 80% of people living with dementia worldwide remain undiagnosed and undocumented and have no access to care and treatment. Telehealth services can be utilized as one of the options to improve access to a diagnosis, especially for people living in rural areas or affected by COVID-19 containment measures. To assess the diagnostic accuracy of telehealth assessment for dementia and mild cognitive impairment (MCI). A summary of the Cochrane Review by McCleery et al. 2021, with comments from a rehabilitation perspective. Three cross-sectional diagnostic test accuracy studies (N = 136) were included. Participants were referred from primary care when presenting with cognitive symptoms or were identified as being at high risk of having dementia on a screening test in the care homes. The studies found that telehealth assessment correctly identified 80% to 100% of the people who were diagnosed with dementia during face-to-face assessment and also correctly identified 80% to 100% of people who did not have dementia. Only one study (N = 100) focused on MCI; 71% of participants who had MCI and 73% of participants who did not have MCI were correctly identified via telehealth assessment. Telehealth assessment in this study correctly identified 97% of the participants who had either MCI or dementia, but correctly identified only 22% of those who did not have either. Telehealth assessment for diagnosing dementia seems to have a good level of accuracy when compared to face-to-face assessment, although the small number of studies and small sample sizes and differences between the included studies indicate that the results are uncertain.

Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic women.

Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic women.

An Evaluation of The Diagnostic Value of Sputum Smears Microscopy and Pcr Relative to Sputum Culture in The Diagnosis of Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis in Iran.

Background: Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In many parts of the world, including Iran, the diagnosis of tuberculosis is based on the detection of acid-fast bacillus in sputum smear microscopy and PCR. this study aimed to synthesize evidence on the diagnostic accuracy of sputum smear and PCR compared to sputum culture for the diagnosis of PT in Iranian patients. Methods: This systematic review and meta-analysis was conducted based on PRISMA guideline for systematic review and meta-analysis. Eligible studies were cross-sectional original diagnostic studies published in English and Persian in Iran which examined the sensitivity or specificity(study outcome) of sputum smear microscopy or PCR( as the test) relative to sputum culture (as the gold standard/comparator) among Iranian patients suspected of having tuberculosis( study population). Studies whose data were not complete or extractable were excluded. Results: A total of 3518 subjects were evaluated from 15 eligible studies. The pooled sensitivity of sputum smear and PCR was 75.12 (95% CI: 66.68-83.56) and 88.02 (95% CI: 82.87-93.27), respectively. The specificity for sputum smear and PCR was 93.94 (95% CI: 91.26-96.63) and 91.82 (95% CI: 87.29-96.35) respectively. The sensitivity of both sputum smears was higher in studies published after 2010, and had higher quality. The specificity of sputum smear was a bit lower in studies published after2010 but higher in studies with higher quality. The specificity of PCR was higher in studies published after 2010 but higher in studies with higher quality. Conclusion:The increased sensitivity of sputum smear and PCR during recent years suggests the improvement of preparation and laboratory methods in recent years. However, the imperfect sensitivity of these tests highlights the need for a more accurate diagnostic method for the detection of pulmonary tuberculosis in Iran.

Trilostane monitoring in canine hyperadrenocorticism: can basal cortisol replace the ACTH stimulation test?

PICO question
 In dogs with hyperadrenocorticism that are being treated with trilostane, does the measurement of basal cortisol levels have comparable diagnostic performance to the adrenocorticotropic hormone (ACTH) stimulation test?
 
 Clinical bottom line
 Category of research question
 Diagnosis (effectiveness of treatment monitoring)
 The number and type of study designs reviewed
 Four cross-sectional diagnostic accuracy studies were critically reviewed
 Strength of evidence
 Weak to moderate (level 2)
 Outcomes reported
 There is evidence of moderate strength suggesting that basal cortisol measured at 4–6 hours (and possibly 2–3 hours) post-trilostane can be a good test to exclude adrenal oversuppression, while its use is not suggested for diagnostic confirmation of oversuppression. There is evidence of weak strength that basal cortisol might be helpful for identifying dogs with inadequate adrenal suppression, but cannot be used to rule it out
 Conclusion
 Although the evaluation of the available evidence is difficult due to its heterogeneity, there is moderate evidence that a basal cortisol measured at 4–6 hours (and possibly 2–3 hours) post-trilostane dose can be a good test to rule out adrenal oversuppression, but that it cannot be used to definitively diagnose oversuppression. The current evidence suggests that basal cortisol is less useful for identification of inadequate control. Based on one included study, neither ACTH-stimulated nor basal cortisol levels correlate optimally with the actual clinical response of the patient. In this context, it can be concluded that none of the currently used laboratory tests should be used as a sole monitoring tool in dogs with hyperadrenocorticism receiving trilostane and thus, the assessment of the clinical response is of utmost importance
 
 How to apply this evidence in practice
 The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
 Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Tests to detect and inform the diagnosis of root caries.

Root caries is a well-recognised disease, with increasing prevalence as populations age and retain more of their natural teeth into later life. Like coronal caries, root caries can be associated with pain, discomfort, tooth loss, and contribute significantly to poorer oral health-related quality of life in the elderly. Supplementing the visual-tactile examination could prove beneficial in improving the accuracy of early detection and diagnosis. The detection of root caries lesions at an early stage in the disease continuum can inform diagnosis and lead to targeted preventive therapies and lesion arrest. To assess the diagnostic test accuracy of index tests for the detection and diagnosis of root caries in adults, used alone or in combination with other tests. Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles. We included diagnostic accuracy study designs that compared one or more index tests (laser fluorescence, radiographs, visual examination, electronic caries monitor (ECM), transillumination), either independently or in combination, with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. In vitro and in vivo studies were eligible for inclusion but studies that artificially created carious lesions were excluded. Two review authors extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) specific to the review context. Estimates of diagnostic test accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each dataset. We planned to use hierarchical models for data synthesis and explore potential sources of heterogeneity through meta-regression. Four cross-sectional diagnostic test accuracy studies providing eight datasets with data from 4997 root surfaces were analysed. Two in vitro studies evaluated secondary root caries lesions on extracted teeth and two in vivo studies evaluated primary root caries lesions within the oral cavity. Four studies evaluated laser fluorescence and reported estimates of sensitivity ranging from 0.50 to 0.81 and specificity ranging from 0.40 to 0.80. Two studies evaluated radiographs and reported estimates of sensitivity ranging from 0.40 to 0.63 and specificity ranging from 0.31 to 0.80. One study evaluated visual examination and reported sensitivity of 0.75 (95% CI 0.48 to 0.93) and specificity of 0.38 (95% CI 0.14 to 0.68). One study evaluated the accuracy of radiograph and visual examination in combination and reported sensitivity of 0.81 (95% CI 0.54 to 0.96) and specificity of 0.54 (95% CI 0.25 to 0.81). Given the small number of studies and important differences in the clinical and methodological characteristics of the studies we were unable to pool the results. Consequently, we were unable to formally evaluate the comparative accuracy of the different tests considered in this review. Using QUADAS-2 we judged all four studies to be at overall high risk of bias, but only two to have applicability concerns (patient selection domain). Reasons included bias in the selection process, use of post hoc (data driven) positivity thresholds, use of an imperfect reference standard, and use of extracted teeth. We downgraded the certainty of the evidence due to study limitations and serious imprecision of the results (downgraded two levels), and judged the certainty of the evidence to be very low. Visual-tactile examination is the mainstay of root caries detection and diagnosis; however, due to the paucity of the evidence base and the very low certainty of the evidence we were unable to determine the additional benefit of adjunctive diagnostic tests for the detection and diagnosis of root caries.

Diagnosing serious infections in older adults presenting to ambulatory care: a systematic review.

to summarise all available evidence on the accuracy of clinical features and blood tests for diagnosing serious infections in older patients presenting to ambulatory care. systematic review, searching seven databases using a comprehensive search strategy. We included cross-sectional prospective diagnostic studies on (1) clinical features, (2) diagnostic prediction rules based on clinical features alone, (3) blood tests and (4) diagnostic prediction rules combining clinical features and blood tests. Study participants had to be community-dwelling adults aged ≥65years, in whom a physician suspected an infection. We used QUADAS-2 to assess risk of bias. We calculated measures of diagnostic accuracy and present descriptive statistics. out of 13,757 unique articles, only six studies with a moderate to high risk of bias were included. There was substantial clinical heterogeneity across these studies. Clinical features had LR- ≥0.61 and LR+ ≤4.94. Twelve prediction rules using clinical features had LR- ≥0.30 and LR+ ≤2.78. There was evidence on four blood tests of which procalcitonin was the most often investigated: levels <0.37ng/ml (LR- = 0.20; 95%CI 0.10-0.42) were suitable to rule out sepsis in moderately high prevalence situations. Two diagnostic prediction rules combining clinical features and procalcitonin had LR- of ≤0.12 (95%CI 0.05-0.33) and LR+ of maximum 1.39 (95%CI 1.30-1.49). we found few studies on the diagnostic accuracy of clinical features and blood tests to detect serious infections in older people presenting to ambulatory care. The risk of bias was mostly moderate to high, leading to substantial uncertainty.

Nucleic acid and antigen detection tests for leptospirosis.

Early diagnosis of leptospirosis may contribute to the effectiveness of antimicrobial therapy and early outbreak recognition. Nucleic acid and antigen detection tests have the potential for early diagnosis of leptospirosis. With this systematic review, we assessed the sensitivity and specificity of nucleic acid and antigen detection tests. To determine the diagnostic test accuracy of nucleic acid and antigen detection tests for the diagnosis of human symptomatic leptospirosis. We searched electronic databases including MEDLINE, Embase, the Cochrane Library, and regional databases from inception to 6 July 2018. We did not apply restrictions to language or time of publication. We included diagnostic cross-sectional studies and case-control studies of tests that made use of nucleic acid and antigen detection methods in people suspected of systemic leptospirosis. As reference standards, we considered the microscopic agglutination test alone (which detects antibodies against leptospirosis) or in a composite reference standard with culturing or other serological tests. Studies were excluded when the controls were healthy individuals or when there were insufficient data to calculate sensitivity and specificity. At least two review authors independently extracted data from each study. We used the revised Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) to assess risk of bias. We calculated study-specific values for sensitivity and specificity with 95% confidence intervals (CI) and pooled the results in a meta-analysis when appropriate. We used the bivariate model for index tests with one positivity threshold, and we used the hierarchical summary receiver operating characteristic model for index tests with multiple positivity thresholds. As possible sources of heterogeneity, we explored: timing of index test, disease prevalence, blood sample type, primers or target genes, and the real-time polymerase chain reaction (PCR) visualisation method. These were added as covariates to the meta-regression models. We included 41 studies evaluating nine index tests (conventional PCR (in short: PCR), real-time PCR, nested PCR, PCR performed twice, loop-mediated isothermal amplification, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, immunochromatography-based lateral flow assay, and dipstick assay) with 5981 participants (1834 with and 4147 without leptospirosis). Methodological quality criteria were often not reported, and the risk of bias of the reference standard was generally considered high. The applicability of findings was limited by the frequent use of frozen samples. We conducted meta-analyses for the PCR and the real-time PCR on blood products.The pooled sensitivity of the PCR was 70% (95% CI 37% to 90%) and the pooled specificity was 95% (95% CI 75% to 99%). When studies with a high risk of bias in the reference standard domain were excluded, the pooled sensitivity was 87% (95% CI 44% to 98%) and the pooled specificity was 97% (95% CI 60% to 100%). For the real-time PCR, we estimated a summary receiver operating characteristic curve. To illustrate, a point on the curve with 85% specificity had a sensitivity of 49% (95% CI 30% to 68%). Likewise, at 90% specificity, sensitivity was 40% (95% CI 24% to 59%) and at 95% specificity, sensitivity was 29% (95% CI 15% to 49%). The median specificity of real-time PCR on blood products was 92%. We did not formally compare the diagnostic test accuracy of PCR and real-time PCR, as direct comparison studies were lacking. Three of 15 studies analysing PCR on blood products reported the timing of sample collection in the studies included in the meta-analyses (range 1 to 7 days postonset of symptoms), and nine out of 16 studies analysing real-time PCR on blood products (range 1 to 19 days postonset of symptoms). In PCR studies, specificity was lower in settings with high leptospirosis prevalence. Other investigations of heterogeneity did not identify statistically significant associations. Two studies suggested that PCR and real-time PCR may be more sensitive on blood samples collected early in the disease stage. Results of other index tests were described narratively. The validity of review findings are limited and should be interpreted with caution. There is a substantial between-study variability in the accuracy of PCR and real-time PCR, as well as a substantial variability in the prevalence of leptospirosis. Consequently, the position of PCR and real-time PCR in the clinical pathway depends on regional considerations such as disease prevalence, factors that are likely to influence accuracy, and downstream consequences of test results. There is insufficient evidence to conclude which of the nucleic acid and antigen detection tests is the most accurate. There is preliminary evidence that PCR and real-time PCR are more sensitive on blood samples collected early in the disease stage, but this needs to be confirmed in future studies.

Tests to detect and inform the diagnosis of caries

Background Root caries is a well-recognised disease, with increasing prevalence as populations age and retain more of their natural teeth into later life. Like coronal caries, root caries can be associated with pain, discomfort, tooth loss, and contribute significantly to poorer oral health-related quality of life in the elderly. Supplementing the visual-tactile examination could prove beneficial in improving the accuracy of early detection and diagnosis. The detection of root caries lesions at an early stage in the disease continuum can inform diagnosis and lead to targeted preventive therapies and lesion arrest. Objectives To assess the diagnostic test accuracy of index tests for the detection and diagnosis of root caries in adults, used alone or in combination with other tests. Search methods Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles. Selection criteria We included diagnostic accuracy study designs that compared one or more index tests (laser fluorescence, radiographs, visual examination, electronic caries monitor (ECM), transillumination), either independently or in combination, with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. In vitro and in vivo studies were eligible for inclusion but studies that artificially created carious lesions were excluded. Data collection and analysis Two review authors extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) specific to the review context. Estimates of diagnostic test accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each dataset. We planned to use hierarchical models for data synthesis and explore potential sources of heterogeneity through meta-regression. Main results Four cross-sectional diagnostic test accuracy studies providing eight datasets with data from 4997 root surfaces were analysed. Two in vitro studies evaluated secondary root caries lesions on extracted teeth and two in vivo studies evaluated primary root caries lesions within the oral cavity. Four studies evaluated laser fluorescence and reported estimates of sensitivity ranging from 0.50 to 0.81 and specificity ranging from 0.40 to 0.80. Two studies evaluated radiographs and reported estimates of sensitivity ranging from 0.40 to 0.63 and specificity ranging from 0.31 to 0.80. One study evaluated visual examination and reported sensitivity of 0.75 (95% CI 0.48 to 0.93) and specificity of 0.38 (95% CI 0.14 to 0.68). One study evaluated the accuracy of radiograph and visual examination in combination and reported sensitivity of 0.81 (95% CI 0.54 to 0.96) and specificity of 0.54 (95% CI 0.25 to 0.81). Given the small number of studies and important differences in the clinical and methodological characteristics of the studies we were unable to pool the results. Consequently, we were unable to formally evaluate the comparative accuracy of the different tests considered in this review. Using QUADAS-2 we judged all four studies to be at overall high risk of bias, but only two to have applicability concerns (patient selection domain). Reasons included bias in the selection process, use of post hoc (data driven) positivity thresholds, use of an imperfect reference standard, and use of extracted teeth. We downgraded the certainty of the evidence due to study limitations and serious imprecision of the results (downgraded two levels), and judged the certainty of the evidence to be very low. Authors' conclusions Visual-tactile examination is the mainstay of root caries detection and diagnosis; however, due to the paucity of the evidence base and the very low certainty of the evidence we were unable to determine the additional benefit of adjunctive diagnostic tests for the detection and diagnosis of root caries.

Methods for Evaluating Medical Tests and Biomarkers

Joris de Groot, Christiana Naaktgeboren, Hans Reitsma, Carl Moons Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands Correspondence: Joris de Groot (j.degroot-17@umcutrecht.nl) A major contributor to the rising problem of overdiagnosis, with the subsequent risk of overtreatment, is the development of highly sensitive diagnostic technologies that challenge and sometimes expand prevailing disease definitions. Although the value of such new technology might be that it identifies new, milder, earlier or even other abnormalities, it is uncertain whether these “abnormalities” provide the same diagnostic and prognostic information, or require the same treatment as the original targeted disease. It is often unclear which of the newly detected abnormalities are benign and how many people might be diagnosed and treated unnecessarily as a result of widespread introduction of the new test. Failure to investigate the clinical relevance of broadening disease definitions which include these newly detected abnormalities may therefore lead to overdiagnosis and overtreatment. Spiral CT used in diagnosing pulmonary embolism, detecting small subsegmental embolisms, has been mentioned as an example of such situation. On-going technological advancements in medicine will only further increase the development of new diagnostic technologies that challenge existing disease definitions. We show why traditional cross-sectional diagnostic accuracy studies are insufficient to evaluate such new tests and how methodology for assessing their performance should catch up and keep pace with present-day technological developments. It is crucial to improve data analysis and presentation of current diagnostic studies, to make better use of existing data, or ultimately perform test-treatment trials to answer the question whether introduction of a new high sensitive test will in fact improve patient relevant outcomes, or rather induce overdiagnosis and overtreatment.

The diagnostic accuracy of the Kimberley Indigenous Cognitive Assessment (KICA) tool: a systematic review

The objective of this study was to conduct a systematic review of evidence for the accuracy of the Kimberley Indigenous Cognitive Assessment (KICA) tool in supporting the diagnosis of dementia in Indigenous Australian populations. Cross-sectional diagnostic accuracy studies of the KICA with an appropriate reference standard published to November 2015 were included. Comparison to an alternative cognitive assessment tool was required in non-remote populations. Case control analyses were excluded. Four studies were included: one of the KICA-Cog and KICA-Carer, one of the KICA Screen, and two of the modified-KICA. All tools developed for remote populations had a sensitivity of ≥76% and a specificity of ≥71% for the diagnosis of dementia. The KICA-Cog and KICA-Carer conducted in series had the highest sensitivity and specificity (91% and 94% respectively). In an urban and regional population, the mKICA had similar accuracy to the Mini-Mental State Examination (MMSE) (AUC 0.93, 95% CI 0.88-0.99 vs 0.94, 95% CI 0.89-0.99). Key risk of bias limitations related to lack of pre-determined cut-points and population selection methods. The use of the KICA in remote Indigenous Australians may assist in timely diagnosis of dementia in this population. Using the KICA-Cog and KICA-Carer in series may maximise specificity, decreasing false positive results without compromising sensitivity.

The Use of Enteric Contrast Media for Diagnostic CT, MRI, and Ultrasound in Infants and Children: A Practical Approach.

Enteric contrast media are commonly administered for diagnostic cross-sectional imaging studies in the pediatric population. The purpose of this manuscript is to review the use of enteric contrast media for CT, MRI, and ultrasound in infants, children, and adolescents and to share our experiences at a large tertiary care pediatric teaching hospital. The use of enteric contrast material for diagnostic imaging in infants and children continues to evolve with advances in imaging technology and available enteric contrast media. Many principles of enteric contrast use in pediatric imaging are similar to those in adult imaging, but important differences must be kept in mind when imaging the gastrointestinal tract in infants and children, and practical ways to optimize the imaging examination and the patient experience should be employed where possible.

Blood CEA levels for detecting recurrent colorectal cancer.

Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation. To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice. We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index & Conference Proceedings Citation Index - Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library. We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy. Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots. In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%). CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).

Adjunctive tests cannot replace scalpel biopsy for oral cancer diagnosis.

Medline, the Cochrane Diagnostic Test Accuracy Studies Register, the Cochrane Oral Health Groups Trials Register, Embase and MEDION. Two of the reviewers independently assessed titles abstracts and extracted data. Cross-sectional diagnostic test accuracy studies (or consecutive series) and randomised studies of diagnostic test accuracy that reported the diagnostic test accuracy of vital staining, oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis used as an adjunct to conventional oral examination in detecting PMD or oral squamous cell carcinoma of the lip or oral cavity were considered. Scalpel, punch or fine needle aspiration biopsy with histological diagnosis was the reference test. Study quality was assessed using a modified version of QUADAS-2. Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity. Meta-regressionanalysis was undertaken to explore possible sources of heterogeneity. Forty-one studies, recruiting 4002 patients were included. No single study could be classified as being at low risk of bias across all domains. Fourteen studies evaluated vital staining, 13 studies oral cytology and 13 studies light-based detection or oral spectroscopy, while six studies assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis. The overall quality of the included studies was poor. None of the adjunctive tests can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation.

Measuring GFR: A Systematic Review

No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. Systematic review with meta-analysis of cross-sectional diagnostic studies. Published original studies and systematic reviews in any population. Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. Renal inulin clearance measured under continuous inulin infusion and urine collection. Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

Acute HIV-related gastrointestinal disorders and complications in the antiretroviral era: spectrum of cross-sectional imaging findings

Emergency physicians and radiologists are increasingly confronted with aging HIV-positive or acquired immunodeficiency syndrome (AIDS) patients with acute abdominal symptoms, who often require immediate medical or surgical treatment. A wide spectrum of infectious and neoplastic HIV-related gastrointestinal diseases may be encountered, along with atypical presentations of common disorders. Since symptoms and physical findings are commonly nonspecific or masked by concurrent illnesses, medications, and weak immune response, prompt cross-sectional diagnostic imaging studies are needed to triage patients and choose treatment. Multidetector CT currently represents the mainstay modality to promptly investigate intra-abdominal opportunistic disorders in HIV/AIDS patients, and MRI is increasingly used to assess abnormalities involving the rectum. The spectrum of cross-sectional imaging appearances of HIV-related acute gastrointestinal disorders and complications observed in the antiretroviral era is reviewed, including acute intestinal infections, causes of right lower quadrant pain, bleeding, bowel obstruction, and perforation. State-of-the-art technology, knowledge of pertinent clinical information, and familiarity with the spectrum of opportunistic diseases are necessary to improve diagnostic confidence in the detection and characterization of gastrointestinal abnormalities on urgent cross-sectional abdominal studies performed in HIV-infected patients.

Accuracy of eucapnic hyperpnea or mannitol to diagnose exercise-induced bronchoconstriction: a systematic review

Exercise challenge testing is the typical method for diagnosing exercise induced bronchoconstriction; however, alternate tests have been developed. The purpose of this paper was to summarize the current literature comparing eucapnic voluntary hyperpnea and mannitol with standard exercise challenge testing to determine whether either test is a suitable alternative to standard exercise testing for the diagnosis of exercise-induced bronchoconstriction. Using valid systematic review methods, a comprehensive search strategy to avoid publication bias, we identified 10 studies that compared exercise challenge testing with either eucapnic voluntary hyperpnea or mannitol. For the 7 diagnostic cross-sectional studies that examined eucapnic voluntary hyperpnea, the sensitivity and specificity values were heterogeneous, ranging from 25 to 90% for sensitivity and 0 to 71% for specificity. In the 3 diagnostic cross-sectional studies that evaluated mannitol, the sensitivity and specificity ranged from 58 to 96% and 65 to 78%, respectively. For most studies, a representative spectrum of participants being tested was not used. Given the heterogeneity in sensitivity and specificity of eucapnic voluntary hyperpnea studies and the relatively small number of studies that have examined mannitol, insufficient evidence is available to conclude that either of these tests are suitable alternatives to exercise challenge testing to detect exercise-induced bronchoconstriction. Additional research is required.

Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis

The aim of this study was to assess the test performance and clinical effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC) in people suspected of new or recurrent bladder cancer. A systematic review was conducted of randomized controlled trials (RCTs), nonrandomized comparative studies, or diagnostic cross-sectional studies comparing PDD with WLC. Fifteen electronic databases and Web sites were searched (last searches April 2008). For clinical effectiveness, only RCTs were considered. Twenty-seven studies (2,949 participants) assessed test performance. PDD had higher sensitivity than WLC (92 percent, 95 percent confidence interval [CI], 80-100 percent versus 71 percent, 95 percent CI, 49-93 percent) but lower specificity (57 percent, 95 percent CI, 36-79 percent versus 72 percent, 95 percent CI, 47-96 percent). For detecting higher risk tumors, median range sensitivity of PDD (89 percent [6-100 percent]) was higher than WLC (56 percent [0-100 percent]) whereas for lower risk tumors it was broadly similar (92 percent [20-95 percent] versus 95 percent [8-100 percent]). Four RCTs (709 participants) using 5-aminolaevulinic acid (5-ALA) as the photosensitising agent reported clinical effectiveness. Using PDD at transurethral resection of bladder tumor (TURBT) resulted in fewer residual tumors at check cystoscopy (relative risk [RR], 0.37, 95 percent CI, 0.20-0.69) and longer recurrence-free survival (RR, 1.37, 95 percent CI, 1.18-1.59), compared with WLC. PDD detects more bladder tumors than WLC, including more high-risk tumors. Based on four RCTs reporting clinical effectiveness, 5-aminolaevulinic acid-mediated PDD at TURBT facilitates a more complete resection and prolongs recurrence-free survival.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Magnetic resonance imaging (MRI)-based volumetry of medial temporal lobe regions is among the best established biomarker candidates of Alzheimer's disease (AD) to date. This study assessed the effect of multicentre variability of MRI-based hippocampus and amygdala volumetry on the discrimination between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the association of morphological changes with ApoE4 genotype and cognition. We studied 113 patients with clinically probable AD and 150 patients with amnestic MCI using high-resolution MRI scans obtained at 12 clinical sites. We determined effect sizes of group discrimination and random effects linear models, considering multicentre variability. Hippocampus and amygdala volumes were significantly reduced in AD compared with MCI patients using data pooled across centres. Multicentre variability did not significantly affect the power to detect a volume difference between AD and MCI patients. Among cognitive measures, delayed recall of verbal and non-verbal material was significantly correlated with hippocampus and amygdala volumes. Amygdala and hippocampus volumes were not associated with ApoE4 genotype in AD or MCI. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for cross-sectional diagnostic studies, and they replicate essential findings from smaller scale monocentre studies.

Radiologic Monitoring of Hepatocellular Carcinoma Tumor Viability after Transhepatic Arterial Chemoembolization: Estimating the Accuracy of Contrast-enhanced Cross-sectional Imaging with Histopathologic Correlation

Cross-sectional diagnostic imaging studies such as contrast-enhanced quadruple-phase helical computed tomography (CT) and contrast-enhanced magnetic resonance (MR) imaging are routinely performed to evaluate tumor response to transhepatic arterial chemoembolization. However, the true correlation between imaging characteristics and histopathologic tumor viability is not known. The aim of the present retrospective study was to determine the sensitivity and specificity of contrast-enhanced CT and contrast-enhanced MR imaging with use of histopathologic analysis. Between February 2002 and October 2005, a total of 31 patients (age, 51-74 years; mean, 60 y) who had undergone chemoembolization underwent follow-up diagnostic cross-sectional imaging before transplantation. The mean time interval between the imaging study and transplantation was 32 days (range, 1-117 d). Imaging studies were assessed for residual or recurrent tumor and were then correlated to the findings of histopathologic analysis performed on the surgical specimens at the time of transplantation. The overall sensitivity and specificity rates of cross-sectional imaging studies were 35% and 64%, respectively. The overall accuracy rate of CT was 43%, with 36% sensitivity and 57% specificity. The overall accuracy rate of MR imaging was 55%, with 43% sensitivity and 75% specificity. Gross macroscopic disease was missed in one patient (9%) who underwent MR imaging and four patients (19%) who underwent CT. Contrast-enhanced CT and MR imaging after chemoembolization are associated with high error rates. Between the two modalities, MR has higher sensitivity and specificity and may be a preferable imaging tool for patients who have undergone chemoembolization.

Distraction From Randomization in Diagnostic Research

The ultimate goal of medical care, including diagnostic testing, is to improve patient outcome. Accordingly, it has been advocated widely that when establishing a test's diagnostic accuracy, the impact of the test on patient outcome subsequently must be quantified. When studying patient outcome in medical research, the use of randomized comparisons comes into perspective. In our view, randomized studies often are not necessary to validly estimate the effect of the diagnostic test on patient outcome. Results of cross-sectional diagnostic studies, combined with results from therapeutic studies, often will suffice.