ABSTRACT The diagnosis of tuberculous meningitis (TBM) is difﬁcult and poses a signiﬁcant challenge to physicians worldwide. Recently, nucleic acid ampliﬁcation (NAA) tests have shown promise for the diagnosis of TBM, although their perfor- mance has been variable. We undertook a systematic review and meta-analysis to evaluate the diagnostic accuracy of NAA tests with cerebrospinal ﬂuid (CSF) samples against that of culture as the reference standard or a combined reference standard (CRS) for TBM. We searched the Embase, PubMed, Web of Science, and Cochrane Li- brary databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and speciﬁcity) were pooled with a random-effects model. All statistical analyses were performed with STATA (version 14 IC; Stata Corporation, College Station, TX, USA), Meta-DiSc (ver- sion 1.4 for Windows; Cochrane Colloquium, Barcelona, Spain), and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) soft- ware. Sixty-three studies comprising 1,381 cases of conﬁrmed TBM and 5,712 non-TBM controls were included in the ﬁnal analysis. These 63 studies were divided into two groups comprising 71 data sets (43 in-house tests and 28 commercial tests) that used culture as the reference standard and 24 data sets (21 in-house tests and 3 commercial tests) that used a CRS. Studies which used a culture reference standard had better pooled summary estimates than studies which used CRS. The overall pooled estimates of sensitivity, speciﬁcity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the NAA tests against culture were 82% (95% conﬁdence interval [CI], 75 to 87%), 99% (95% CI, 98 to 99%), 58.6 (95% CI, 35.3 to 97.3), and 0.19 (95% CI, 0.14 to 0.25), re- spectively. The pooled sensitivity, speciﬁcity, PLR, and NLR of NAA tests against CRS were 68% (95% CI, 41 to 87%), 98% (95% CI, 95 to 99%), 36.5 (95% CI, 15.6 to 85.3), and 0.32 (95% CI, 0.15 to 0.70), respectively. The analysis has demonstrated that the diagnos- tic accuracy of NAA tests is currently insufﬁcient for them to replace culture as a lone di- agnostic test. NAA tests may be used in combination with culture due to the advantage of time to result and in scenarios where culture tests are not feasible. Further work to improve NAA tests would beneﬁt from the availability of standardized reference stan- dards and improvements to the methodology.
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Search strategies were developed by a medical librarian with expertise in designing systematic review searches. Our search algorithm consisted of the following components: hepatitis C, diagnostic tests, and diagnostic accuracy. We searched MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1947 onwards), the Cochrane Central Register of Controlled Trials (Wiley interface, current issue), Science Citation Index Expanded (Web of Science interface, 1970 onwards), Conference Proceedings Citation Index-Science (Web of Science interface, 1990 on- wards), SCOPUS (1960 onwards), Literatura Latino- Americana e do Caribe em Ciências da Saúde (LILACS) (BIREME interface) and WHO Global Index Medicus. The search was supplemented by searching for ongoing studies in WHO’s International Clinical Trials Registry. The litera- ture search was limited to English language and human subjects that available until April 30th, 2015. In addition to searching databases, we contacted individual researchers and authors of major trials to address whether any relevant manuscripts are in preparation or in press. The references of published articles found in the above databases were searched for additional pertinent materials.
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Articles reporting the diagnostic accuracy of non-invasive prenatal diagnostic (NIPD) tests for RHD genotyping using fetal material extracted from maternal blood have been published steadily for over a decade. Health care providers in Europe have started to use this technology for management of the small number of sensitised pregnancies (ca. 220–600 per annum in the Netherlands, Germany, France and the UK). Scientists and clinicians are also advocating widespread implementation for the far larger number of non-sensitised RhD-negative pregnancies (ca. 34,000–125,000 per annum in the same countries). Large- scale, prospective trials are only now underway. Estimates of the technical performance of these tests are currently based on results from small-scale studies, together with formal meta-analysis. The issue of early assessment of test performance is one faced by many new genetic tests. As part of a wider study we have investigated the quality of reporting of diagnostic accuracy in publications and produced guidelines for future studies.
In the trial by Lewin et al. , the investigators used a standard analysis to compare the full areas under the receiver operating characteristic curves. The standard analysis includes all participants, even those whose dis- ease status is not verified with the reference standard test. Because some cases may be misclassified, the estimates of diagnostic accuracy may be biased, causing decision errors . If the bias is severe enough, investigators can detect a difference between screening tests when there is none, or conclude incorrectly that the inferior test is superior. Choosing the inferior test can delay diagnosis, increasing morbidity and mortality.
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In this article, we systematically evaluated the site-speci ﬁ c diagnostic performance of both gFOBT and iFOBT with a single test for detecting colorectal neoplasms. For gFOBT, the diagnostic accuracy of detecting colorectal lesions located in the two different colon sites were similar, with comparable pooled sensitivities and areas under the SROC curves. For iFOBT, we found that the diagnostic perfor- mance of iFOBT for detecting advanced adenomas and advanced neoplasia varied according to the anatomical sites of the colorectum, with better sensitivities for the detection of these lesions in the distal colon/rectum than in the proximal colon. As the evidences have shown that iFOBT is superior to gFOBT for CRC screening, iFOBT has been one of the most widely used non-invasive tests for CRC screening. However, the different diagnostic accuracy
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independently (ML, HS) we read the full text of 489 studies, performed data-extraction on 122 studies and finally included 75 unique published articles (Fig. 1). Fifty-seven of these had a case-control design, compar- ing a group of well-defined cases with a group of healthy controls or controls with diseases that could lead to cross-reactivity of the tests [8–64]. Eighteen had a cross- sectional design in which a more homogeneous sample of patients underwent both the serological assay(s) and the reference standard [65–82]. Three studies were not used in the meta-analyses, either because they used im- munoblot as a reference standard [76, 79], or included asymptomatic cross-country runners with high IgG titers as controls .
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Our study was retrospective, and longitudinal in nature leaving us unable to control for significant variables, such as the EORTC risk scores, that predict the prob- ability of recurrence and progression of bladder cancer. With 19 % of cystoscopies in the cytology cohort classi- fied as positive, this cohort was at higher risk for bladder cancer than the average US population. Additionally, while the sensitivity could have been improved with nar- row band imaging or fluorescent cystoscopy, these tech- nologies were not available at our institution for the entirety of the study period. For the purposes of our analyses, suspicious lesions on cystoscopy were classified as positive. When we correlated this classification with pathology, only 59 % of pathology specimens were found to have cancer, reflecting a limitation of this classifica- tion. However, when we performed a sensitivity analysis with suspicious cystoscopies classified as negative, our results were not significantly different, indicating a minimal impact of this limitation on the interpretation of the results. The data were collected over a 10 year time frame; so indications for using the tests have chan- ged over time as have technique of verification of test results. Furthermore, more than one cytopathologist was involved over the period examined and literature sug- gests high inter-observer discrepancy, but this reflects the real world. Urine cytology has a low sensitivity and is highly operator-dependent in the setting of low grade disease . In experienced hands, however, specificity is about 90 % . Indeed, our own data supports this
Kyonggi-do - South Korea), Dengue NS1 Ag STRIP™ (Bio-Rad), and SD BIOLINE™ Dengue Duo (Standard diagnostic Inc.). The characteristics of the tests are sum- marized in table 2. The Platelia™ Dengue NS1 Ag Test and Dengue NS1 Ag STRIP™ were purchased from the local distributor while the rest were kindly donated by the manufacturers. All tests were run following the cor- responding manufacturer ’ s instructions. Dengue NS1 Ag STRIP ™ was read at 15 min and 30 min. Three separate results were obtained from SD BIOLINE ™ Dengue Duo test based on the results of NS1 only (dengue if NS1 was positive and non-dengue if NS1 was negative, regardless of IgM/IgG results), NS1/IgM combined (dengue if one of NS1 or IgM was positive and non- dengue if both were negative, regardless of IgG results), and NS1/IgM/IgG combined (dengue if at least one of NS1, IgM or IgG was positive and non-dengue if all three were negative). Batches of samples were analyzed by all the NS1-based diagnostic tests on the same day and by the same persons who were two experienced lab scientists. Both observers were blind to the samples den- gue status and each other results. Results of the ELISA- based format tests given as “ equivocal ” were repeated once. Persistent equivocal results were excluded from the analysis. Those results of the immunochromatogra- phy-based format tests given as “ weak ” were considered as positive results.
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Our results differ from a recent UK case – control study that assessed the diagnostic value of clinical features of colorectal cancer before diagnosis. This study identified cases from a cancer registry and controls selected and matched in terms of age and registration with a general practice (Hamilton et al, 2005). In this case – control study, PLRs were considerably higher than found in this systematic review of cohort studies. For example, PLRs for weight loss (5.1), abdominal pain (4.5) and anaemia o10 g per 100 ml (9.5) would all be associated with definitive shifts in the probability of colorectal cancer (Grimes and Schulz, 2005). The most likely explanation for this discordant finding is that recall bias amongst controls may have produced a comparison group that did not remember having colorectal symptoms in the past, thus inflating estimates of diagnostic utility for symptoms, signs and diagnostic tests when compared with individuals with colorectal cancer (Grimes and Schulz, 2002).
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D.A. is one of a group of coinvestigators who invented molecular beacon technology and who receive income from licensees, including a license to Cepheid forM. tuberculosis detection. To manage this conflict of interest, the income attributable to the Xpert MTB/RIF assay, which he may receive, has been irrevocably capped at $4,999 per year. D.A. also reports receiving two research contracts from Cepheid. E.V., C.M.D., D.L.D., and C.B. are employed by FIND, a nonprofit organization that TABLE 3 Diagnostic accuracy clinical study: accuracy of single rapid tests using as a gold standard four cultures performed from two sputum samples
Thirteen studies evaluated the diagnostic accuracy of tests to detect renal scarring. Four studies evaluated the diag- nostic accuracy of IVP: positive likelihood ratios were high (10.0 to 171.3), but corresponding negative likelihood ratios were poor (0.15 to 0.80)[80,82-84]. Only one study included an appropriate patient spectrum, and this reported a much lower positive likelihood ratio (10.0 compared to next lowest of 58.8), and higher negative likelihood ratio (0.80 compared to next highest of 0.42) than the others. Seven studies evaluated standard ultra- sound techniques[60,85-90]. Figure 4 shows estimates of sensitivity and specificity for these studies plotted in ROC space. Performance characteristics varied greatly, although positive likelihood ratios were generally moderate to high (1.3–35.9). Negative likelihood ratios showed poorer performance for ruling out scarring (0.14–0.99). Three studies assessed the diagnostic accuracy of indirect radio- nuclide cystography[78,84,91]; positive likelihood ratios were moderate and ranged from 3.3 to 12.6, and negative likelihood ratios ranged from 0.15 to 0.63.
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In accordance with our published protocol , we systematically searched Medline (using PubMed) and ISI Web of Science for studies published between 1 January 2005 and 22 April 2015 that evaluated the diagnostic accuracy of fourth-generation RDTs for acute HIV-1 (Supplementary Table 1: Search Strategy, http:// links.lww.com/QAD/A767). Studies were eligible if they evaluated the field performance of at least one fourth-generation RDT for acute HIV-1 in adults (aged >15 years). We defined field performance as the RDT being used on an unselected population, at the point of care (defined as being conducted in the presence of the patient ), in the setting of intended use and carried out by the intended user. Cross-sectional studies, cohort studies and randomized control trials were included. Studies that evaluated fourth-generation RDTs within laboratories or retrospectively against specimen panels were excluded. We placed no restrictions on assay manufacturer, language or country.
The major strength of this study was the comprehensive search strategy used, along with rigorous methods for study selection and quality appraisal. Both QUADAS and STARD checklists were examined, which provide a complementary assessment of both methodological quality and quality of reporting. The overall conclusion is that the quality of reporting of the diagnostic accuracy of perimetric tests in glaucoma is sub-optimal and appears not to have improved substantially following the development of the STARD initiative. Adoption and enforcement of STARD by ophthalmic journals is likely to lead to quality improvements in reporting of these studies.
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Study characteristics were extracted, including design, year, country and patient eligibility criteria. Patient characteristics that were extracted included age, comorbidities, diabetic status, location of osteomyelitis and reason for referral. Data on study intervention (e.g. characteristics of imaging test used, radioisotope, contrast agent, diagnostic cut-off point and thresholds), unit of analysis (e.g. patient, body part) and data on exclusions from study/analysis with reasons were recorded. Types of reference standards used for confirming positive and negative cases were recorded. The numbers of patients confirmed to be positive or negative in accordance with the reference standard, and the numbers of true-positive, true-negative, false-positive and false-negative test results, were extracted, if reported. If not reported, sensitivity and specificity estimates [with their 95% confidence intervals (CIs)] or other reported diagnostic accuracy data were extracted. Where possible, sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and checked against reported values in the publications to check for any discrepancies. When more than one test was performed for the same participant in the same body part (i.e. repeat test, or follow-up test), only the result of the first test was used.
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All three diagnostic tests – the two comparator refer- ence tests and the and POC index test – were performed and analyzed independently. The index POC test was not a component of the reference test. All tests were administered on a blinded basis; different providers conducted different tests. In addition, no clinical infor- mation was provided to persons conducting the Sickle SCAN® test. All subjects were initially diagnosed by a single national reference test, a strict monitoring process insuring control for verification bias. Our CRF contains dedicated space for ambiguous results, and after moni- toring, no such results were reported during the study period. After test reading, each device was photographed to allow a control quality process. Finally, sensitivity and specificity estimates were precisely assessed for each phenotype. Thus, we conclude that our study findings are robust.
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Actually, with the introduction of new diagnostic methods, there have been many cases and much uncer- tainty about the interpretation of positive cultures with these new techniques. Some authors reported a higher sensitivity from standard cultures than from sonicate fluid cultures  while others agree that sonication in- creases the diagnostic accuracy for implant-related infec- tion [13, 20]. Several studies observed that antibiotic intake prior to prosthetic removal negatively affected the microbial detection of tissue and sonication cultures [20 – 22], while others had no influence [18, 23, 24]. We found differences in bacteria detection when antibiotics had been previously used for all types of infection. It was also found that more than one-half (55.5%) of early PJI patients had received antibiotic therapy within 14 days before the surgery date according to the discretion of the treating physician.
Background: Malaria rapid diagnostic tests (RDTs) are commonly used in Médecins Sans Frontières (MSF) programmes to detect acute malaria infection. Programmes in regions with both Plasmodium falciparum and non-falciparum malaria (i.e. Plasmodium ovale, Plasmodium malariae and Plasmodium vivax) use a three-band P. falciparum/Pan test such as the SD Bioline Malaria Ag P.f/Pan 05FK60 (Standard Diagnostics, Kyonggi, Republic of Korea), hereafter referred to as SD 05FK60, as used by the MSF-Holland clinics in Rakhine state, Myanmar. In spite of published reports of generally good test performance, medical and paramedical staff on the ground often doubt the diagnostic accuracy of these RDTs.
This study prospectively assessed the diagnostic accuracy of one of the tuberculosis RDTs locally available in the market. The choice for the assessed RDT was based on its simplicity which was determined by the technicians that work in the health facilities where the suspected pulmonary tuberculosis patients were recruited. Like most immunochromatographic tests, this point of care device is a direct binding, double sandwich antigen immunochromatographic test for the detection of antibodies to TB present in human serum or plasma. The device has recombinant TB antigens immobilized on the membrane. According to the manufacturer (Clinotech Diagnostics and Pharmaceuticals Inc, Canada), anti-TB antibodies in serum or plasma binds colloidal gold particle conjugated antigens which form sandwich complexes. The complexes migrate through the membrane which has been pre-coated with recombinant TB antigens on the test line and anti-TB antibodies on the control line.
As RDT cassette design is fairly standardized, the parameters governing the appropriateness of design of the transfer device should be common to various RDT kits. Identifying the best design should therefore improve the overall diagnostic accuracy and safety of all RDT cassettes. Five devices were evaluated: four were typical examples of the main types of devices currently provided with commercially-available malaria RDTs, while the fifth was developed specifically for the study, based on an earlier promising design that had not been deployed with commercially-available tests. The study reported here evaluated blood transfer devices in terms of accuracy and consistency of blood volume trans- ferred, blood safety, and ease of use in the hands of health workers, to identify the most appropriate blood transfer devices for use with malaria RDTs in routine clinical care.
Finally, the use of a qualitative POC FIT in the way that we did in this study, although easily implemented in primary care, also has limitations. First, as the qualitative POC FIT yields a positive or a negative test result (with a detection limit of 6 μg Hb/g faeces), the diagnostic informa- tion that would be available by quantitatively assessing the amount of Hb present in faeces is lost. Second, patients collected faecal samples in regular blue-capped containers without Hb stabilizing buffer (so each patient needed to fill only one faecal container for both calprotectin and Hb analysis). Samples were kept refrigerated, and – if not fro- zen before further processing – 90 % were tested within 3 days of collection. Additional data-analysis showed that the chance of a positive POC FIT slightly decreased with increasing time between collection and testing (0.3 % absolute decrease per day; P = 0.19), and that frozen samples were more likely to be POC FIT negative than non-frozen samples (absolute 8.6 % decrease in POC FIT positivity; P = 0.017; calprotectin results seemed not to be affected). Some patients have thus likely tested falsely nega- tive for the POC FIT because of Hb degradation in our study. However, in none of the models with POC FIT did its odds ratio for SCD significantly differ in patients whose faecal samples were and were not frozen. Furthermore, the POC FIT performed well in our study despite these limita- tions, and the sensitivity and discriminatory performance of faecal Hb testing in primary care will thus likely be even better when using Hb stabilizing buffers in faecal sample collection devices and using a quantitative FIT.
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