•Prenatal depression negatively affects offspring behavior.•Altered development of fetal stress systems has been proposed as underlying mechanism.•Stress reactivity reflects adaptive responding above ...resting function of stress systems.•Evidence of an association between prenatal depression and stress reactivity is limited.•Postnatal depression, caregiving behavior and partner support act as moderators.
Depression is a common condition affecting up to 20% of all pregnant women, and is associated with subsequent developmental and behavioral problems in children, such as conduct disorder and ADHD. One proposed mechanism underlying these associations is modification of the fetal hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system (ANS), resulting in altered responses to stress. This review examined the evidence regarding altered HPA-axis and ANS reactivity in children prenatally exposed to high maternal depressive symptoms. A systematic search was conducted in the electronic databases MEDLINE, EMBASE and PsycINFO, for studies published till 25 July 2017. A total of 13 studies comprising 2271 mother-infant dyads were included. None of the studies were suitable for meta-analysis. Risk of bias assessment showed low risk for four studies. Only three studies described an independent association between exposure to high maternal prenatal depressive symptoms and altered stress reactivity in children. There is limited evidence of an independent association between prenatal exposure to maternal depression and altered HPA or ANS reactivity in children.
To evaluate how diagnostic accuracy study reports published in 2012 adhered to the Standards for Reporting of Diagnostic Accuracy (STARD) statement and whether there were any differences in reporting ...compared with 2000 and 2004.
PubMed was searched for studies published in 12 high-impact-factor journals in 2012 that evaluated the accuracy of one or more diagnostic tests against a clinical reference standard. Two independent reviewers scored reporting completeness of each article with the 25-item STARD checklist. Mixed-effects modeling was used to analyze differences in reporting with previous evaluations from articles published in 2000 and 2004.
Included were 112 articles. The overall mean number of STARD items reported in 2012 was 15.3 ± 3.9 (standard deviation; range, 6.0-23.5). There was an improvement of 3.4 items (95% confidence interval: 2.6, 4.3) compared with studies published in 2000, and an improvement of 1.7 items (95% confidence interval: 0.9, 2.5) compared with studies published in 2004. Significantly more items were reported for single-gate studies compared with multiple-gate studies (16.8 vs 12.1, respectively; P < .001) and for studies that evaluated imaging tests compared with laboratory tests and other types of tests (17.0 vs 14.0 vs 14.5, respectively; P < .001).
Completeness of reporting improved in the 10 years after the launch of STARD, but it remains suboptimal for many articles. Reporting of inclusion criteria and sampling methods for recruiting patients, information about blinding, and confidence intervals for accuracy estimates are in need of further improvement.
The validity of a meta-analysis can be understood better in light of the possible impact of publication bias. The majority of the methods to investigate publication bias in terms of small ...study-effects are developed for meta-analyses of intervention studies, leaving authors of diagnostic test accuracy (DTA) systematic reviews with limited guidance. The aim of this study was to evaluate if and how publication bias was assessed in meta-analyses of DTA, and to compare the results of various statistical methods used to assess publication bias.
A systematic search was initiated to identify DTA reviews with a meta-analysis published between September 2011 and January 2012. We extracted all information about publication bias from the reviews and the two-by-two tables. Existing statistical methods for the detection of publication bias were applied on data from the included studies.
Out of 1,335 references, 114 reviews could be included. Publication bias was explicitly mentioned in 75 reviews (65.8%) and 47 of these had performed statistical methods to investigate publication bias in terms of small study-effects: 6 by drawing funnel plots, 16 by statistical testing and 25 by applying both methods. The applied tests were Egger's test (n = 18), Deeks' test (n = 12), Begg's test (n = 5), both the Egger and Begg tests (n = 4), and other tests (n = 2). Our own comparison of the results of Begg's, Egger's and Deeks' test for 92 meta-analyses indicated that up to 34% of the results did not correspond with one another.
The majority of DTA review authors mention or investigate publication bias. They mainly use suboptimal methods like the Begg and Egger tests that are not developed for DTA meta-analyses. Our comparison of the Begg, Egger and Deeks tests indicated that these tests do give different results and thus are not interchangeable. Deeks' test is recommended for DTA meta-analyses and should be preferred.
Background and purpose
Cardiac thrombi are an important cause of embolic stroke. We studied the diagnostic yield and diagnostic accuracy of cardiac CT angiography (CTA) compared to echocardiography ...for detection of cardiac thrombi in ischemic stroke patients.
Methods
We performed a systematic review and meta-analysis of the literature on cardiac CTA versus echocardiography for detection of cardiac thrombi in ischemic stroke patients. We included studies (
N
≥ 20) in which both cardiac CTA (index test) and echocardiography (reference test) were performed and data on cardiac thrombi were reported. Results were stratified for type of echocardiography: transesophageal (TEE) vs transthoracic (TTE).
Results
Out of 1530 studies, 14 were included (all single center cohort studies), with data on 1568 patients. Mean age varied between 52 and 69 years per study and 66% were men. Reported time intervals ranged from 0 to 21 days between stroke and first test, and from 0 to 199 days between tests. In ten studies that compared CTA to TEE, CTA detected cardiac thrombi in 87/1385 (6.3%) patients versus 68/1385 (4.9%) on TEE (
p
< 0.001). In four studies comparing CTA to TTE, CTA detected thrombi in 23/183 (12.5%) patients versus 12/183 (6.6%) on TTE (
p
= 0.010). Pooled sensitivity and specificity of CTA versus TEE were 86.0% (95% CI 65.6–95.2) and 97.4% (95% CI 95.0–98.7), respectively.
Conclusions
CTA may be a promising alternative to echocardiography for detection of cardiac thrombi in patients with ischemic stroke, especially now that CTA is standard care for patient selection for endovascular treatment. However, studies were too heterogeneous and of insufficient methodological quality to draw firm conclusions. Large, prospective studies on this topic are warranted.
Objective Currently, there is no consensus on the definition of hyperemesis gravidarum (HG; protracted vomiting in pregnancy) and no single widely used set of diagnostic criteria for HG. The various ...definitions rely on symptoms, sometimes in combination with laboratory tests. Through a systematic review, we aimed to summarize available evidence on the diagnostic value of biomarkers for HG. This could assist diagnosis and may shed light on the, as yet, not understood cause of the disorder. Study Design We searched Medline and Embase for articles about diagnostic biomarkers for either the presence or severity of HG or nausea and vomiting of pregnancy. We defined HG as any combination of nausea, vomiting, dehydration, weight loss, or hospitalization for nausea and/or vomiting in pregnancy, in the absence of any other obvious cause for these complaints. Results We found 81 articles on 9 biomarkers. Although 65% of all studies included only HG cases with ketonuria, we did not find an association between ketonuria and presence or severity of HG in 5 studies reporting on this association. Metaanalysis, with the use of the hierarchical summary receiver operating characteristics model, yielded an odds ratio of 3.2 (95% confidence interval, 2.0–5.1) of Heliobacter pylori for HG, as compared with asymptomatic control subjects (sensitivity, 73%; specificity, 55%). Studies on human chorionic gonadotropin and thyroid hormones, leptin, estradiol, progesterone, and white blood count showed inconsistent associations with HG; lymphocytes tended to be higher in women with HG. Conclusion We did not find support for the use of ketonuria in the diagnosis of HG. H pylori serology might be useful in specific patients.
Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) ...rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test.
To assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook.
We searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies.
We included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classification as reference standard.
Two review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment.
We included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%.
The optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.
How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this ...regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse.
The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as <50% reduction in total score on either the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) (corresponding to at least much improved) from baseline to endpoint (4-12 weeks), by <20% PANSS or BPRS improvement (corresponding to less than minimally improved) at week 2. Secondary outcomes were absent cross-sectional symptomatic remission and <20% PANSS or BPRS reduction at endpoint. Potential moderator variables were examined by meta-regression.
In 34 studies (N=9,460) a <20% PANSS or BPRS reduction at week 2 predicted nonresponse at endpoint with a specificity of 86% and a positive predictive value (PPV) of 90%. Using data for observed cases (specificity=86%, PPV=85%) or lack of remission (specificity=77%, PPV=88%) yielded similar results. Conversely, using the definition of <20% reduction at endpoint yielded worse results (specificity=70%, PPV=55%). The test specificity was significantly moderated by a trial duration of <6 weeks, higher baseline illness severity, and shorter illness duration.
Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.
Background & Aims Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. At present, there is no appropriate histologic scoring system available for PSC, evaluating both degree ...of necroinflammatory activity (grade) and fibrosis (stage). The aim of this study was to assess if three scoring systems, commonly used in different liver diseases could be applied for grading and/or staging of PSC. Methods Sixty-four PSC patients from a Dutch cohort, who underwent diagnostic liver biopsy, were included. Staging was scored using Ishak, Nakanuma, and Ludwig systems. Grading was scored using Ishak and Nakanuma systems. Three measures of outcome were defined; transplant-free survival, time to liver transplantation (LTx) and occurrence of cirrhosis related symptoms (CRS). Association of grade and stage with outcome was estimated using Kaplan–Meier log-rank test, and Cox regression analysis. Correlation with biochemistry was assessed by Spearman’s rank test. Results There were strong associations between disease stage measured by Ishak, Nakanuma, and Ludwig staging systems with both outcome measuring transplant-free survival (Hazard ratio (HR) 2.56; 95% CI 1.11–5.89, HR 6.53; 95% CI 2.01–21.22, HR 1.94; 95% CI 1.00–3.79, respectively), and time to LTx (HR 4.18; 95%CI 1.51–11.56, HR 7.05; 95% CI 1.77–28.11, HR 3.13; 95%CI 1.42–6.87, respectively). Ishak and Nakanuma grading systems were not associated with CRS. Weak correlations between histopathology and liver biochemistry were shown. Conclusion Applying the Nakanuma, Ishak, and Ludwig histopathological staging systems is feasible and clinically relevant given their association with transplant-free survival and time to LTx. This suggests that these staging systems could be likely candidates for surrogate endpoints and stratification purposes in clinical trials in PSC.
Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings ...potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables.
PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles.
Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders.
Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve.
Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79-92), pooled specificity of 92% (95% CI, 88-96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising-induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% 95% CI, 44-70 and specificity of 83% 95% CI, 68-92 vs sensitivity of 85% 95% CI, 78-90 and specificity of 92% 95% CI, 87-94, respectively; p < 0.001).
Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.
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