Please cite this paper as: Kleinrouweler C, Wiegerinck M, Ris‐Stalpers C, Bossuyt P, van der Post J, von Dadelszen P, Mol B, Pajkrt E, for the EBM CONNECT Collaboration. Accuracy of circulating ...placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis. BJOG 2012;119:778–787.
Background Biomarkers have been proposed for identification of women at increased risk of developing pre‐eclampsia.
Objectives To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms‐like tyrosine kinase‐1 (sFLT1) and soluble endoglin (sENG) to predict pre‐eclampsia.
Search strategy Medline and Embase through October 2010 and reference lists of reviews, without constraints.
Selection criteria We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre‐eclampsia.
Data collection and analysis Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained.
Main results We included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre‐eclampsia: standardised mean differences (SMD) −0.56 (95% CI −0.77 to −0.35) and −1.25 (95% CI −2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21–0.75) and SMD 0.54 (95% CI 0.24–0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6–14.5), sFLT1 6.6 (95% CI 3.1–13.7), sENG 4.2 (95% CI 2.4–7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% false‐positive rate.
Author’s conclusions PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre‐eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre‐eclampsia in clinical practice.
Objective
We previously showed that maternal under‐nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal ...adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren.
Design
Historical cohort study.
Setting
Web‐based questionnaire.
Population
The adult offspring (F2) of a cohort of men and women (F1) born around the time of the 1944–45 Dutch famine.
Methods
We approached the F2 adults through their parents. Participating F2 adults (n = 360, mean age 37 years) completed an online questionnaire.
Main outcome measures
Weight, body mass index (BMI), and health in F2 adults, according to F1 prenatal famine exposure.
Results
Adult offspring (F2) of prenatally exposed F1 fathers had higher weights and BMIs than offspring of prenatally unexposed F1 fathers (+4.9 kg, P = 0.03; +1.6 kg/m², P = 0.006). No such effect was found for the F2 offspring of prenatally exposed F1 mothers. We observed no differences in adult health between the F2 generation groups.
Conclusions
Offspring of prenatally undernourished fathers, but not mothers, were heavier and more obese than offspring of fathers and mothers who had not been undernourished prenatally. We found no evidence of transgenerational effects of grandmaternal under‐nutrition during gestation on the health of this relatively young group, but the increased adiposity in the offspring of prenatally undernourished fathers may lead to increased chronic disease rates in the future.
The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between ...undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944-1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI 1.09-1.70); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26-2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood.
Background
Invasive aspergillosis is the most common life‐threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive ...nor too great a burden for the already weakened patient. The serum galactomannan enzyme‐linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements.
Objectives
To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis.
Search methods
We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014.
Selection criteria
We included cross‐sectional studies, case‐control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).
Data collection and analysis
Two review authors independently assessed quality and extracted data. We carried out meta‐analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates.
Main results
We included 54 studies in the review (50 in the meta‐analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut‐off value, the sensitivity of the test was 78% (70% to 85%) and the specificity was 85% (78% to 91%). At a cut‐off value of 1.0 ODI, the sensitivity was 71% (63% to 78%) and the specificity was 90% (86% to 93%). At a cut‐off value of 1.5 ODI, the sensitivity was 63% (49% to 78%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity.
Authors' conclusions
If we used the test at a cut‐off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 11% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 78%, 22% false negatives), and 13 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 85%, 15% false negatives). If we used the test at a cut‐off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.
Abstract Objectives The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group developed an approach to assess the quality of evidence of diagnostic tests. Its use in ...Cochrane diagnostic test accuracy reviews is new. We applied this approach to three Cochrane reviews with the aim of better understanding the application of the GRADE criteria to such reviews. Study Design and Setting We selected reviews to achieve clinical and methodological diversities. At least three assessors independently assessed each review according to the GRADE criteria of risk of bias, indirectness, imprecision, inconsistency, and publication bias. Two teleconferences were held to share experiences. Results For the interpretation of the GRADE criteria, it made a difference whether assessors looked at the evidence from a patient-important outcome perspective or from a test accuracy standpoint. GRADE criteria such as inconsistency, imprecision, and publication bias were challenging to apply as was the assessment of comparative test accuracy reviews. Conclusion The perspective from which evidence is graded can influence judgments about quality. Guidance on application of GRADE to comparative test reviews and on the GRADE criteria of inconsistency, imprecision, and publication bias will facilitate the operationalization of GRADE for diagnostics.
BACKGROUND Various models have been developed for the prediction of pregnancy after in vitro fertilization (IVF). These models differ from one another in the predictors they include. We performed a ...systematic review and meta-analysis to identify the most relevant predictors for success in IVF. METHODS We systematically searched MEDLINE and EMBASE for studies evaluating IVF/ICSI outcome. Studies were included if they reported an unconditional odds ratio (OR) or whenever one could be calculated for one or more of the following factors: age, type of infertility, indication, duration of infertility, basal FSH, number of oocytes, fertilization method, number of embryos transferred and embryo quality. RESULTS Fourteen studies were identified. A summary OR could be calculated for five factors. We found negative associations between pregnancy and female age OR: 0.95, 95% confidence interval (CI): 0.94–0.96, duration of subfertility (OR: 0.99, 95% CI: 0.98–1.00) and basal FSH (OR: 0.94, 95% CI: 0.88–1.00). We found a positive association with number of oocytes (OR 1.04, 95% CI: 1.02–1.07). Better embryo quality was associated with higher pregnancy chances. No significant association was found for the type of infertility and fertilization method. A summary OR for IVF indication and number of embryos transferred could not be calculated, because studies reporting on these used different reference categories. CONCLUSIONS Female age, duration of subfertility, bFSH and number of oocytes, all reflecting ovarian function, are predictors of pregnancy after IVF. Better quality studies are necessary, especially studies that focus on embryo factors that are predictive of success in IVF.
Abstract Objective: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study's ...generalisability. Methods: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. Results: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both. Conclusions: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public. The Standards for Reporting of Diagnostic Accuracy (STARD) steering group aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy. The group describes and explains the development of a checklist and flow diagram for authors of reports
Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against ...colonoscopy.
Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20 μg Hb/g feces.
A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29-47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of 93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI: 36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml.
Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.
A study was undertaken to determine whether a short course of antibiotic treatment (< or = 5 days) is as effective as the conventional longer treatment in acute exacerbations of chronic bronchitis ...and chronic obstructive pulmonary disease (COPD).
MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to July 2006. Studies considered eligible were double-blind randomised clinical trials including adult patients > or = 18 years of age with a clinical diagnosis of exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment for < or = 5 days versus > 5 days. The primary outcome measure was clinical cure at early follow-up on an intention-to-treat basis.
21 studies with a total of 10 698 patients were included. The average quality of the studies was high: the mean (SD) Jadad score was 3.9 (0.9). At early follow-up (< 25 days), the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to 1.10) and the summary OR for bacteriological cure was 1.05 (95% CI 0.87 to 1.26). Similar summary ORs were observed for early cure in trials with the same antibiotic in both arms and in studies grouped by the antibiotic class used in the short-course arm.
A short course of antibiotic treatment is as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD.
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