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Background: Interdisciplinary pain treatment (IPT) is a complex intervention; its outcomes are very diverse, as are the methodologies for handling those outcomes. This diversity may hamper evidence-based decision making. Presently, there is no gold standard recommendation of how to select reported outcomes in published systematic reviews and meta-analyses to explicitly demonstrate the effectiveness of IPT., Objective: In this systematic overview, we aim to evaluate the reported outcome domains and measurements across published systematic reviews and meta-analyses and to identify any methods, considerations, and discussion regarding the handling of the chosen outcome domains and measurements., Methods: This article describes the protocol for a systematic overview of the outcomes reported in published systematic reviews and meta-analyses of randomized control trials for the effectiveness of IPT versus any control. To this end, we searched the PubMed, Cochrane Library, and Epistemonikos databases from inception to December 2019. Two independent investigators screened the titles, the abstracts of the identified records, and the full texts of the potentially eligible systematic reviews and meta-analyses, performed data extraction according to predefined forms, and rated the quality of the included systematic reviews and meta-analyses. The quality of the included systematic reviews and meta-analyses will be rated with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. Data will be analyzed descriptively and stratified by AMSTAR 2., Results: We introduced the rationale and design of a systematic overview to summarize and map the chosen IPT outcome domains and the methods of handling these outcomes reported in published systematic reviews and meta-analyses. As of December 2019, we collected 5229 systematic reviews, of which 147 (2.81%) were examined in-depth for eligibility. Topline results are anticipated by September 2020., Conclusions: The results of this study will be published as soon as they are available. Our results will fill a gap in the related literature and will be used to inform the development of a set of recommendations that can be applied in systematic reviews and hopefully serve as a gold standard., International Registered Report Identifier (irrid): PRR1-10.2196/17795., (©Elena Dragioti, Huan-Ji Dong, Britt Larsson, Björn Gerdle. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.05.2020.)

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.

Background: Since people with mental illness are more likely to die from cancer, we assessed whether people with mental illness undergo less cancer screening compared with the general population., Methods: In this systematic review and meta-analysis, we searched PubMed and PsycINFO, without a language restriction, and hand-searched the reference lists of included studies and previous reviews for observational studies from database inception until May 5, 2019. We included all published studies focusing on any type of cancer screening in patients with mental illness; and studies that reported prevalence of cancer screening in patients, or comparative measures between patients and the general population. The primary outcome was odds ratio (OR) of cancer screening in people with mental illness versus the general population. The Newcastle-Ottawa Scale was used to assess study quality and I 2 to assess study heterogeneity. This study is registered with PROSPERO, CRD42018114781., Findings: 47 publications provided data from 46 samples including 4 717 839 individuals (501 559 patients with mental illness, and 4 216 280 controls), of whom 69·85% were women, for screening for breast cancer (k=35; 296 699 individuals with mental illness, 1 023 288 in the general population), cervical cancer (k=29; 295 688 with mental illness, 3 540 408 in general population), colorectal cancer (k=12; 153 283 with mental illness, 2 228 966 in general population), lung and gastric cancer (both k=1; 420 with mental illness, none in general population), ovarian cancer (k=1; 37 with mental illness, none in general population), and prostate cancer (k=6; 52 803 with mental illness, 2 038 916 in general population). Median quality of the included studies was high at 7 (IQR 6-8). Screening was significantly less frequent in people with any mental disease compared with the general population for any cancer (k=37; OR 0·76 [95% CI 0·72-0·79]; I 2 =98·53% with publication bias of Egger's p value=0·025), breast cancer (k=27; 0·65 [0·60-0·71]; I 2 =97·58% and no publication bias), cervical cancer (k=23; 0·89 [0·84-0·95]; I 2 =98·47% and no publication bias), and prostate cancer (k=4; 0·78 [0·70-0·86]; I 2 =79·68% and no publication bias), but not for colorectal cancer (k=8; 1·02 [0·90-1·15]; I 2 =97·84% and no publication bias)., Interpretation: Despite the increased mortality from cancer in people with mental illness, this population receives less cancer screening compared with that of the general population. Specific approaches should be developed to assist people with mental illness to undergo appropriate cancer screening, especially women with schizophrenia., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder., Methods: We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704., Findings: 46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1·31, 95% CI 1·18-1·45), maternal chronic hypertension (odds ratio [OR] 1·48, 1·29-1·70), maternal gestational hypertension (OR 1·37, 1·21-1·54), maternal overweight before or during pregnancy (RR 1·28, 1·19-1·36), pre-eclampsia (RR 1·32, 1·20-1·45), prepregnancy maternal antidepressant use (RR 1·48, 1·29-1·71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1·84, 1·60-2·11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases., Interpretation: Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Staging in schizophrenia might be an important approach for the better treatment and rehabilitation of patients. The purpose of this study was to empirically devise a staging approach in a sample of stabilized patients with schizophrenia. One hundred and seventy patients aged ≥18 years (mean = 40.7, SD = 11.6) diagnosed by DSM-5 criteria were evaluated with the Positive and Negative Syndrome Scale (PANSS). Principal components analysis (PCA) with varimax rotation was used. The model was examined in the total sample and separately across a hypothesized stage of illness based on three age groups and between the two sexes. The PCA revealed a six factor structure for the total sample: 1) Negative, 2) Positive, 3) Depression and anxiety, 4) Excitement and Hostility, 5) Neurocognition and 6) Disorganization. The separate PCAs by stage of illness and sex revealed different patterns and quality of symptomatology. The Negative and Positive factors were stable across all examined groups. The models corresponding to different stages differed mainly in terms of neurocognition and disorganization and their interplay. Catatonic features appear more prominent in males while in females neurocognition takes two forms; one with disorganization and one with stereotype thinking with delusions. This study suggests that the three arbitrary defined stages of illness (on the basis of age) seem to reflect a progress from a preserved insight and more coherent mental functioning to disorganization and eventually neurocognitive impairment. Sexes differ in terms of the relationship of psychotic features with neurocognition. These results might have significant research and clinical implications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To investigate the effect of serum from patients with non-small cell lung cancer (NSCLC) on in vitro cytotoxicity of the clonal cell line NK-92., Materials and Methods: Twenty-six patients with NSCLC were included in this study. NK-92 cells were incubated in medium supplemented with 25% of each patient's serum (before and after chemotherapy) for 24 h, then washed and tested for cytotoxicity against NK-sensitive K562 targets., Results: The cytotoxicity of NK-92 cells exposed to serum from patients with NSCLC before chemotherapy initiation was significantly reduced compared to that upon incubated with serum from healthy individuals (p<0.001). NK-92 cytotoxicity was further reduced upon exposure to patient's serum after the first and third chemo therapy cycles (p<0.001)., Conclusion: The results of our in vitro study suggest that serum of patients with NSCLC may exert per se an inhibitory effect on the cytotoxicity of NK-92 cells and this negative regulation may be enhanced with chemotherapy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)