Chapter 4: Effective Search Strategies for Systematic Reviews of Medical Tests

This article discusses techniques that are appropriate when developing search strategies for systematic reviews of medical tests. This includes general advice for searching for systematic reviews and issues specific to systematic reviews of medical tests. Diagnostic search filters are currently not sufficiently developed for use when searching for systematic reviews. Instead, authors should construct a highly sensitive search strategy that uses both controlled vocabulary and text words. A comprehensive search should include multiple databases and sources of grey literature. A list of subject-specific databases is included in this article

Age-related differences in selection by visual saliency

We examined the ability of older adults to select local and global stimuli varying in perceptual saliency – a task requiring non-spatial visual selection. Participants were asked to identify in separate blocks a target at either the global or local level of a hierarchical stimulus, while the saliency of each level was varied (across different conditions either the local or the global form was the more salient and relatively easier to identify). Older adults were less efficient than young adults in ignoring distractors that were higher in saliency than targets, and this occurred across both the global and local levels of form. The increased effects of distractor saliency on older adults occurred even when the effects were scaled by overall differences in task performance. The data provide evidence for an age-related decline in non spatial attentional selection of low-salient hierarchical stimuli, not determined by the (global or local) level at which selection was required. We discuss the implications of these results for understanding both the interaction between saliency and hierarchical processing and the effects of aging on non-spatial visual attention

Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I(2 )production by rat liver cells

BACKGROUND: Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. METHODS: Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [(3)H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I(2 )produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. RESULTS: Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I(2 )production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I(2 )production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. CONCLUSIONS: Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. DISCUSSION: The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia

Fluorescence-Based Methods for Detecting Caries Lesions: Systematic Review, Meta-Analysis and Sources of Heterogeneity

Background Fluorescence-based methods have been proposed to aid caries lesion detection. Summarizing and analysing findings of studies about fluorescence-based methods could clarify their real benefits. Objective We aimed to perform a comprehensive systematic review and meta-analysis to evaluate the accuracy of fluorescence-based methods in detecting caries lesions. Data Source Two independent reviewers searched PubMed, Embase and Scopus through June 2012 to identify papers/articles published. Other sources were checked to identify non-published literature. Study Eligibility Criteria, Participants and Diagnostic Methods The eligibility criteria were studies that: (1) have assessed the accuracy of fluorescence-based methods of detecting caries lesions on occlusal, approximal or smooth surfaces, in both primary or permanent human teeth, in the laboratory or clinical setting; (2) have used a reference standard; and (3) have reported sufficient data relating to the sample size and the accuracy of methods. Study Appraisal and Synthesis Methods A diagnostic 2×2 table was extracted from included studies to calculate the pooled sensitivity, specificity and overall accuracy parameters (Diagnostic Odds Ratio and Summary Receiver-Operating curve). The analyses were performed separately for each method and different characteristics of the studies. The quality of the studies and heterogeneity were also evaluated. Results Seventy five studies met the inclusion criteria from the 434 articles initially identified. The search of the grey or non-published literature did not identify any further studies. In general, the analysis demonstrated that the fluorescence-based method tend to have similar accuracy for all types of teeth, dental surfaces or settings. There was a trend of better performance of fluorescence methods in detecting more advanced caries lesions. We also observed moderate to high heterogeneity and evidenced publication bias. Conclusions Fluorescence-based devices have similar overall performance; however, better accuracy in detecting more advanced caries lesions has been observed

A Systematic Review on the Diagnosis of Pediatric Bacterial Pneumonia: When Gold Is Bronze

In developing countries, pneumonia is one of the leading causes of death in children under five years of age and hence timely and accurate diagnosis is critical. In North America, pneumonia is also a common source of childhood morbidity and occasionally mortality. Clinicians traditionally have used the chest radiograph as the gold standard in the diagnosis of pneumonia, but they are becoming increasingly aware that it is not ideal. Numerous studies have shown that chest radiography findings lack precision in defining the etiology of childhood pneumonia. There is no single test that reliably distinguishes bacterial from non-bacterial causes. These factors have resulted in clinicians historically using a combination of physical signs and chest radiographs as a 'gold standard', though this combination of tests has been shown to be imperfect for diagnosis and assigning treatment. The objectives of this systematic review are to: 1) identify and categorize studies that have used single or multiple tests as a gold standard for assessing accuracy of other tests, and 2) given the 'gold standard' used, determine the accuracy of these other tests for diagnosing childhood bacterial pneumonia.Search strategies were developed using a combination of subject headings and keywords adapted for 18 electronic bibliographic databases from inception to May 2008. Published studies were included if they: 1) included children one month to 18 years of age, 2) provided sufficient data regarding diagnostic accuracy to construct a 2x2 table, and 3) assessed the accuracy of one or more index tests as compared with other test(s) used as a 'gold standard'. The literature search revealed 5,989 references of which 256 were screened for inclusion, resulting in 25 studies that satisfied all inclusion criteria. The studies examined a range of bacterium types and assessed the accuracy of several combinations of diagnostic tests. Eleven different gold standards were studied in the 25 included studies. Criterion validity was calculated for fourteen different index tests using eleven different gold standards. The most common gold standard utilized was blood culture tests used in six studies. Fourteen different tests were measured as index tests. PCT was the most common measured in five studies each with a different gold standard.We have found that studies assessing the diagnostic accuracy of clinical, radiological, and laboratory tests for bacterial childhood pneumonia have used a heterogeneous group of gold standards, and found, at least in part because of this, that index tests have widely different accuracies. These findings highlight the need for identifying a widely accepted gold standard for diagnosis of bacterial pneumonia in children

Spatially explicit poisoning risk affects survival rates of an obligate scavenger

Obligate scavengers such as vultures provide critical ecosystem services and their populations have undergone severe declines in Asia and Africa. Intentional poisoning is a major threat to vultures in Africa, yet the impact on vulture populations of where poisoned carcasses are positioned is not known. We used re-sightings of 183 African white-backed vultures captured and tagged in two regions of South Africa, some 200 km apart, to estimate spatial differences in relative survival rates across life stages. Juvenile survival rates were similar in the two regions, whilst subadult and adult survival rates differed significantly. Using agent-based modelling, we show that this pattern of relative survival rates is consistent between regions that differ in intensity of poisoning, despite the proximity of the two regions. This may have important consequences for vulture conservation and the targeting of conservation efforts, particularly with regard to the efficacy of “vulture safe zones” around vulture breeding populations

Performance of Polymerase Chain Reaction Techniques Detecting Perforin in the Diagnosis of Acute Renal Rejection: A Meta-Analysis

BACKGROUND: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients

Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease

<p>Abstract</p> <p>Aim</p> <p>Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD) through meta-analysis of the available data.</p> <p>Methodology</p> <p>Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral) using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1) used a [greater than or equal to] 1.5 Tesla MR scanner; (2) employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3) provided sufficient data to permit analysis.</p> <p>Results</p> <p>From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%), and a specificity of 80% (95% CI: 78-83%). Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92%) versus 86% (80-90%), P = 0.022), and a tendency to a better specificity (81% (78-84%) versus 77% (71-82%), P = 0.065).</p> <p>Conclusion</p> <p>Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate.</p