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.
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.
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.
The introduction of self-expandable metal stents has offered a promising alternative for palliation of malignant left-sided colonic obstruction. This randomized clinical trial aimed to assess whether ...a nonsurgical policy, with endoluminal stenting, is superior to surgical treatment in patients with stage IV left-sided colorectal cancer and imminent obstruction.
Patients with incurable left-sided colorectal cancer who fulfilled the study criteria were randomly assigned to nonsurgical or surgical treatment. The primary outcome measure was survival in good health out of hospital (World Health Organization performance scores 0 or 1).
A high number of serious adverse events in the nonsurgical arm led to premature closure of the trial. Ten patients were allocated to surgical treatment and 11 patients to nonsurgical palliation. The median survival in good health out of hospital during the first year was 56 days (interquartile range 7.5 - 338.5 days) in the surgical arm vs. 38 days (interquartile range 5.25 - 288.75 days) in the nonsurgical arm (P = 0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm vs. one adverse event in the surgical arm (P < 0.001). Of the six perforations, two were stent-related because they occurred at the proximal edge of the stent by erosion through a normal colon wall; one was probably stent-related (it was located in the region of the proximal half of the stent); one was a colon blowout; and two were late tumor perforations in patients on chemotherapy.
The unexpected high rate of perforation in the nonsurgical arm might be specifically WallFlex-related or enteral stent-related in patients on chemotherapy and warrants attention.
•A wide variety of definitions for hyperemesis gravidarum is currently in use.•An international definition for hyperemesis gravidarum was developed.•The consensus definition for hyperemesis ...gravidarum consisted of:•Symptoms start in early pregnancy, before a gestational age of 16 weeks.•Characterized by severe nausea and vomiting.•Inability to eat and/or drink normally.•Strongly limits daily activities.
To develop an international definition for hyperemesis gravidarum to assist in clinical diagnosis and harmonize hyperemesis gravidarum definition for study populations.
Study design: A mixed-methods approach was used to identify potential hyperemesis gravidarum definition criteria (i.e. systematic review, semi-structured interviews and closed group sessions with patients and Project Steering Committee input). To reach consensus on the definition we used a web-based Delphi survey with two rounds, followed by a face-to-face consensus development meeting, held in Windsor UK, and a web-based consultation round, in which the provisional hyperemesis gravidarum definition was fed back to the stakeholders. Four stakeholder groups were identified 1) researchers; 2) women with lived experience of hyperemesis gravidarum and their families; 3) obstetric health professionals (obstetricians, gynecologists, midwives); and 4) other health professionals involved in care for women with hyperemesis gravidarum (general practitioners, dieticians, nurses). To reflect the opinions of the international community, stakeholders from countries in all global regions were invited to participate.
Twenty-one identified potential criteria entered the Delphi survey. Of the 277 stakeholders invited, 178 completed round one, and 125 (70%) also completed round two. Twenty stakeholders attended the consensus development meeting, representing all stakeholder groups. The consultation round was completed by 96 (54%) stakeholders, of which 92% agreed with the definition as presented. The consensus definition for hyperemesis gravidarum consisted of: start of symptoms in early pregnancy (before 16 weeks gestational age); nausea and vomiting, at least one of which severe; inability to eat and/or drink normally; strongly limits daily living activities. Signs of dehydration were deemed contributory for the definition for hyperemesis gravidarum.
The proposed definition for hyperemesis gravidarum will help clinical studies to achieve more uniformity, and ultimately increasing the value of evidence to inform patient care.
The reported diagnostic accuracy of the D-dimer test for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE) varies. It is unknown to what extent this is due to differences in study ...design or patient groups, or to genuine differences between D-dimer assays.
Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of venous thromboembolism were systematically searched for in the MEDLINE and EMBASE databases up to March 2005. Reference lists of all included studies and of reviews related to the topic of the present meta-analysis were manually searched for other additional potentially eligible studies. Two reviewers independently extracted study characteristics using standardized forms.
In total, 217 D-dimer test evaluations for DVT and 111 for PE were analyzed. Several study design characteristics were associated with systematic differences in diagnostic accuracy. After adjustment for these features, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (DVT 96%; PE 97%), microplate enzyme-linked immunosorbent assay (ELISA) (DVT 94%; PE 95%), and latex quantitative assay (DVT 93%; PE 95%) were superior to those of the whole-blood D-dimer assay (DVT 83%; PE 87%), latex semiquantitative assay (DVT 85%; PE 88%) and latex qualitative assay (DVT 69%; PE 75%). The latex qualitative and whole-blood D-dimer assays had the highest specificities (DVT 99%, 71%; PE 99%, 69%).
Compared to other D-dimer assays, the ELFA, microplate ELISA and latex quantitative assays have higher sensitivity but lower specificity, resulting in a more confident exclusion of the disease at the expense of more additional imaging testing. These conclusions are based on the most up-to-date and extensive systematic review of the topic area, including 184 articles, with 328 D-dimer test evaluations.
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
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