Marie Westwood

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis

IMPORTANCE Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. OBJECTIVE To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. DATA SOURCES Twenty-eight databases from inception to April 2015. STUDY SELECTION Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. DATA EXTRACTION AND SYNTHESIS Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. RESULTS A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. CONCLUSIONS AND RELEVANCE There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review

Objective: To determine the accuracy of guaiac and immunochemical faecal occult blood tests (FOBTs) for the detection of colorectal cancer in an average-risk screening population. Methods: Fifteen electronic databases, the internet, key journals and reference lists of included studies were searched. We included diagnostic accuracy studies that compared guaiac or immunochemical FOBTs with any reference standard, for the detection of colorectal cancer in an average-risk adult population, with sufficient data to construct a 2 × 2 table. Results: Fifty-nine studies were included. Thirty-three evaluated guaiac FOBTs, 35 immunochemical FOBTs and one evaluated sequential FOBTs. Sensitivities for the detection of all neoplasms ranged from 6.2% (specificity 98.0%) to 83.3% (specificity 98.4%) for guaiac FOBTs, and 5.4% (specificity 98.5%) to 62.6% (specificity 94.3%) for immunochemical FOBTs. Specificity ranged from 65.0% (sensitivity 44.1%) to 99.0% (sensitivity 19.3%) for guaiac FOBTs, and 89.4% (sensitivity 30.3%) to 98.5% (sensitivity 5.4%) for immunochemical FOBTs. Diagnostic case–control studies generally reported higher sensitivities. Sensitivities were higher for the detection of CRC, and lower for adenomas, in both the diagnostic cohort and diagnostic case–control studies for both guaiac and immunochemical FOBTs. Conclusions Immudia HemSp appeared to be the most accurate immunochemical FOBT, however, there was no clear evidence to suggest whether guaiac or immunochemical FOBTs performed better, either from direct or indirect comparisons. Poor reporting of data limited the scope of this review, and the use the Standards for Reporting of Diagnostic Accuracy guidelines is recommended for reporting future diagnostic accuracy studies.

Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

BackgroundUrinary 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.MethodsWe conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age.ResultsThe 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.ConclusionDipstick 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.

A systematic review of continuous positive airway pressure for obstructive sleep apnoea–hypopnoea syndrome

We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea-hypopnoea syndrome (OSAHS). The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline. CPAP significantly reduced ESS score compared to control (MD -2.7, 95% CI -3.45, -1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD -5.0, -6.5, -3.5); moderate (MD -2.3, -3.0, -1.6); mild (MD -1.1, -1.8, -0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control. CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms.

Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis.

In publicly funded health systems with finite resources, management decisions are based on assessments of clinical effectiveness and cost-effectiveness. The UK National Institute for Health and Clinical Excellence commissioned a systematic review to inform their 2009 update to guidance on the use of antiviral drugs for the treatment of influenza. We searched databases for studies of the use of neuraminidase inhibitors for the treatment of seasonal influenza. We present the results for healthy adults (ie, adults without known comorbidities) and people at-risk of influenza-related complications. There was an overall reduction in the median time to symptom alleviation in healthy adults by 0.57 days (95% CI -1.07 to -0.08; p=0.02; 2701 individuals) with zanamivir, and 0.55 days (95% CI -0.96 to -0.14; p=0.008; 1410 individuals) with oseltamivir. In those at risk, the median time to symptom alleviation was reduced by 0.98 days (95% CI -1.84 to -0.11; p=0.03; 1252 individuals) with zanamivir, and 0.74 days (95% CI -1.51 to 0.02; p=0.06; 1472 individuals) with oseltamivir. Little information was available on the incidence of complications. In view of the advantages and disadvantages of different management strategies for controlling seasonal influenza in healthy adults recommending the use of antiviral drugs for the treatment of people presenting with symptoms is unlikely to be the most appropriate course of action.

A systematic review classifies sources of bias and variation in diagnostic test accuracy studies

OBJECTIVE To classify the sources of bias and variation and to provide an updated summary of the evidence of the effects of each source of bias and variation. STUDY DESIGN AND SETTING We conducted a systematic review of studies of any design with the main objective of addressing bias or variation in the results of diagnostic accuracy studies. We searched MEDLINE, EMBASE, BIOSIS, the Cochrane Methodology Register, and Database of Abstracts of Reviews of Effects (DARE) from 2001 to October 2011. Citation searches based on three key papers were conducted, and studies from our previous review (search to 2001) were eligible. One reviewer extracted data on the study design, objective, sources of bias and/or variation, and results. A second reviewer checked the extraction. RESULTS We summarized the number of studies providing evidence of an effect arising from each source of bias and variation on the estimates of sensitivity, specificity, and overall accuracy. CONCLUSIONS We found consistent evidence for the effects of case-control design, observer variability, availability of clinical information, reference standard, partial and differential verification bias, demographic features, and disease prevalence and severity. Effects were generally stronger for sensitivity than for specificity. Evidence for other sources of bias and variation was limited.

How does study quality affect the results of a diagnostic meta-analysis?

BackgroundThe use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies.The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies.MethodsThis study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns.ResultsMany of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations.ConclusionFurther work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited.

Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: a systematic review and cost-effectiveness analysis

BACKGROUND Patients with substantive bleeding usually require transfusion and/or (re-)operation. Red blood cell (RBC) transfusion is independently associated with a greater risk of infection, morbidity, increased hospital stay and mortality. ROTEM (ROTEM® Delta, TEM International GmbH, Munich, Germany; www.rotem.de), TEG (TEG® 5000 analyser, Haemonetics Corporation, Niles, IL, USA; www.haemonetics.com) and Sonoclot (Sonoclot® coagulation and platelet function analyser, Sienco Inc., Arvada, CO) are point-of-care viscoelastic (VE) devices that use thromboelastometry to test for haemostasis in whole blood. They have a number of proposed advantages over standard laboratory tests (SLTs): they provide a result much quicker, are able to identify what part of the clotting process is disrupted, and provide information on clot formation over time and fibrinolysis. OBJECTIVES This assessment aimed to assess the clinical effectiveness and cost-effectiveness of VE devices to assist with the diagnosis, management and monitoring of haemostasis disorders during and after cardiac surgery, trauma-induced coagulopathy and post-partum haemorrhage (PPH). METHODS Sixteen databases were searched to December 2013: MEDLINE (OvidSP), MEDLINE In-Process and Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (SCI) (Web of Science), Conference Proceedings Citation Index (CPCI-S) (Web of Science), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Latin American and Caribbean Health Sciences Literature (LILACS), International Network of Agencies for Health Technology Assessment (INAHTA), National Institute for Health Research (NIHR) HTA programme, Aggressive Research Intelligence Facility (ARIF), Medion, and the International Prospective Register of Systematic Reviews (PROSPERO). Randomised controlled trials (RCTs) were assessed for quality using the Cochrane Risk of Bias tool. Prediction studies were assessed using QUADAS-2. For RCTs, summary relative risks (RRs) were estimated using random-effects models. Continuous data were summarised narratively. For prediction studies, the odds ratio (OR) was selected as the primary effect estimate. The health-economic analysis considered the costs and quality-adjusted life-years of ROTEM, TEG and Sonoclot compared with SLTs in cardiac surgery and trauma patients. A decision tree was used to take into account short-term complications and longer-term side effects from transfusion. The model assumed a 1-year time horizon. RESULTS Thirty-one studies (39 publications) were included in the clinical effectiveness review. Eleven RCTs (n=1089) assessed VE devices in patients undergoing cardiac surgery; six assessed thromboelastography (TEG) and five assessed ROTEM. There was a significant reduction in RBC transfusion [RR 0.88, 95% confidence interval (CI) 0.80 to 0.96; six studies], platelet transfusion (RR 0.72, 95% CI 0.58 to 0.89; six studies) and fresh frozen plasma to transfusion (RR 0.47, 95% CI 0.35 to 0.65; five studies) in VE testing groups compared with control. There were no significant differences between groups in terms of other blood products transfused. Continuous data on blood product use supported these findings. Clinical outcomes did not differ significantly between groups. There were no apparent differences between ROTEM or TEG; none of the RCTs evaluated Sonoclot. There were no data on the clinical effectiveness of VE devices in trauma patients or women with PPH. VE testing was cost-saving and more effective than SLTs. For the cardiac surgery model, the cost-saving was £43 for ROTEM, £79 for TEG and £132 for Sonoclot. For the trauma population, the cost-savings owing to VE testing were more substantial, amounting to per-patient savings of £688 for ROTEM compared with SLTs, £721 for TEG, and £818 for Sonoclot. This finding was entirely dependent on material costs, which are slightly higher for ROTEM. VE testing remained cost-saving following various scenario analyses. CONCLUSIONS VE testing is cost-saving and more effective than SLTs, in both patients undergoing cardiac surgery and trauma patients. However, there were no data on the clinical effectiveness of Sonoclot or of VE devices in trauma patients. STUDY REGISTRATION This study is registered as PROSPERO CRD42013005623. FUNDING The NIHR Health Technology Assessment programme.

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review

AbstractBackgroundFurther investigation of confirmed UTI in children aims to prevent renal scarring and future complications.MethodsWe conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age.Results73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation.ConclusionThere is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.