Biomarkers for Psychosis: Are We There Yet? Umbrella Review of 1478 Biomarkers
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PROVIDER: S-EPMC11369642 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: Indicated primary prevention in young people at Clinical High Risk for Psychosis (CHR-P) is a promising avenue for improving outcomes of one of the most severe mental disorders but their effectiveness has recently been questioned. Methods: Umbrella review. A multi-step independent literature search of Web of Science until January 11, 2019, identified interventional meta-analyses in CHR-P individuals. The individual randomised controlled trials that were analysed by the meta-analyses were extracted. A review of ongoing trials and a simulation of living meta-analysis complemented the analysis. Results: Seven meta-analyses investigating preventive treatments in CHR-P individuals were included. None of them produced pooled effect sizes across psychological, pharmacological, or other types of interventions. The outcomes analysed encompassed risk of psychosis onset, the acceptability of treatments, the severity of attenuated positive/negative psychotic symptoms, depression, symptom-related distress, social functioning, general functioning, and quality of life. These meta-analyses were based on 20 randomised controlled trials: the vast majority defined the prevention of psychosis onset as their primary outcome of interest and only powered to large effect sizes. There was no evidence to favour any preventive intervention over any other (or control condition) for improving any of these clinical outcomes. Caution is required when making clinical recommendations for the prevention of psychosis in individuals at risk. Discussion: Prevention of psychosis from a CHR-P state has been, and should remain, the primary outcome of interventional research, refined and complemented by other clinically meaningful outcomes. Stagnation of knowledge should promote innovative and collaborative research efforts, in line with the progressive and incremental nature of medical knowledge. Advancements will most likely be associated with the development of new experimental therapeutics that are ongoing along with the ability to deconstruct the high heterogeneity within CHR-P populations. This would require the estimation of treatment-specific effect sizes through living individual participant data meta-analyses, controlling risk enrichment during recruitment, statistical power, and embedding precision medicine within youth mental health services that can accommodate sequential prognosis and advanced trial designs. Conclusions: The evidence-based challenges and proposed solutions addressed by this umbrella review can inform the next generation of research into preventive treatments for psychosis.
| S-EPMC6917652 | biostudies-literature
Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) leads to the majority of cancer-related deaths due to its morbidity with similar mortality. Lack of effective prognostic biomarkers are the main reason for belated post-operative intervention of recurrence which causes high mortality. Numerous systematic reviews and meta-analyses have explored the prognostic value of biomarkers in PDAC so far. In this article, we performed an umbrella review analyzing these studies to provide an overview of associations between prognostic biomarkers and PDAC survival outcome and synthesized these results to guide better clinical practice. Methods: Systematic reviews and meta-analyses investigating the associations between PDAC survival outcomes and prognostic biomarkers were acquired via the PubMed and Embase databases from inception till February 1, 2020. Associations supported by nominally statistically significant results were classified into strong, highly suggestive, suggestive, and weak based on several critical factors such as the statistical significance of summary estimates, the number of events, the estimate of the largest study included, interstudy heterogeneity, small-study effects, 95% predictive interval (PI), excess significance bias, and the results of credibility ceiling sensitivity analyses. Results: We included 41 meta-analyses containing 63 associations between PDAC survival outcomes and prognostic biomarkers. Although, none was supported by strong evidence among these associations, an association between C-reactive protein to albumin ratio (CAR) and PDAC overall survival (OS) and an association between neutrophil-lymphocyte ratio (NLR) and PDAC OS were supported by highly suggestive evidence. Otherwise, the association between lactate dehydrogenase (LDH) and PDAC OS was supported by suggestive evidence. The remaining 60 associations were supported by weak or not suggestive evidence. Conclusion: Associations between CAR or NLR and PDAC OS were supported by highly suggestive evidence. And the association between LDH and PDAC OS was supported by suggestive evidence. Although the methodological quality of the included systematic reviews and meta-analyses which were evaluated by AMSTAR2.0 is generally poor, the identification of the relatively robust prognostic biomarkers of PDAC may guide better post-operative intervention and follow-up to prolong patients' survival.
| S-EPMC7527774 | biostudies-literature
Project description:Exposure to childhood trauma is a well-known risk factor for severe mental disorders including schizophrenia and other non-affective psychoses. Beyond childhood trauma, there is increasing evidence that bullying, social exclusion, and discrimination during adolescence and adulthood may increase the risk of developing a psychotic disorder, and that such forms of traumatization may also underlie the elevated psychosis risk among migrants or persons with a visible minority status. In this umbrella review, we systematically assess meta-analyses regarding trauma and social adversity. A systematic literature review yielded 11 meta-analyses that met inclusion criteria and could be summarized quantitatively with a random effect model. Furthermore, six meta-analyses were evaluated qualitatively. Heterogeneity and publication bias were apparent in several meta-analyses. We observed that most significant social risk factors for psychosis were vulnerability for racist discrimination [OR = 3.90 (3.25-4.70)], migration [OR = 2.22 (1.75-2.80)], and childhood adversities [OR = 2.81 (2.03-3.83)]. Furthermore, social factors increasing the risk for psychosis were variation/impairment of parental communication, aversive adult life events, bullying, and factors associated with social isolation and discrimination. In spite of these environmental risk factors, there is a lack of evidence regarding treatment of trauma and psychosis, although some psychotherapeutic and art therapy approaches appear to be promising. Beyond individual interventions, stigmatization, racism, and other forms of discrimination need to be targeted to increase solidarity and communal support.
| S-EPMC8569921 | biostudies-literature
Project description:Introduction: Biomarkers are biological molecules entirely or partially participating in cancerous processes that function as measurable indicators of abnormal changes in the human body microenvironment. Aiming to provide an overview of associations between prognostic biomarkers and gastric cancer (GC), we performed this umbrella review analyzing currently available meta-analyses and grading the evidence depending on the credibility of their associations. Methods: A systematic literature search was conducted by two independent investigators of the PubMed, Embase, Web of Science, and Cochrane Databases to identify meta-analyses investigating associations between prognostic biomarkers and GC. The strength of evidence for prognostic biomarkers for GC were categorized into four grades: strong, highly suggestive, suggestive, and weak. Results: Among 120 associations between prognostic biomarkers and GC survival outcomes, only one association, namely the association between platelet count and GC OS, was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence. Four associations were considered suggestive and the remaining 108 associations were supported by weak or not suggestive evidence. Discussion: The association between platelet count and GC OS was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence, however, the results should be interpreted cautiously due to inadequate methodological quality as deemed by AMSTAR 2.0.
| S-EPMC6895018 | biostudies-literature
Project description:Black people and People of Color are disproportionately affected by racism and show increased rates of psychosis. To examine whether racialized migrant groups are particularly exposed to racism and therefore have higher risks for psychosis, this paper (1) systematically assesses rates of psychosis among racialized migrant groups concerning the country of origin, and (2) analyzes interviews regarding the association of racism experiences with psychosis-related symptoms in racialized Black people and People of Color populations in Germany. We present an umbrella review of meta-analyses that report the incidence of positive symptoms (e.g., hallucinations and delusions) and negative symptoms (e.g., apathy and incoherent speech) of diagnosed schizophrenia, other non-affective psychotic disorders (e.g., schizoaffective disorder) or first-episode psychosis among migrants by country of origin. We also report 20 interviews with first- and second-generation migrants racialized as Black and of Color in Germany to capture and classify their experiences of racism as well as racism-associated mental health challenges. In the umbrella review, psychosis risk was greatest when migration occurred from developing countries. Effect size estimates were even larger among Caribbean and African migrants. In the qualitative study, the application of the constant comparative method yielded four subordinate themes that form a subclinical psychosis symptomatology profile related to experiences of racism: (1) a sense of differentness, (2) negative self-awareness, (3) paranoid ideation regarding general persecution, and (4) self-questioning and self-esteem instability. We here provide converging evidence from a quantitative and qualitative analysis that the risk of poor mental health and psychotic experiences is related to racism associated with minority status and migration.
| S-EPMC9400567 | biostudies-literature
Project description: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.
| S-EPMC7235270 | biostudies-literature
Project description:Several associations between non-genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations are not confirmed. We aimed to evaluate the evidence of these associations and integrate results from different approaches to assess causal inference. We searched Medline and Embase for meta-analyses of observational studies, meta-analyses of randomized clinical trials (RCTs), and Mendelian randomization (MR) studies measuring the associations between non-genetic biomarkers and CRC risk and meta-analyses of RCTs on supplementary micronutrients. We repeated the meta-analyses using random-effects models and categorized the evidence based on predefined criteria. We described each MR study and evaluated their credibility. Seventy-two meta-analyses of observational studies and 18 MR studies on non-genetic biomarkers and six meta-analyses of RCTs on micronutrient intake and CRC risk considering 65, 42, and five unique associations, respectively, were identified. No meta-analyses of RCTs on blood level biomarkers have been found. None of the associations were classified as convincing or highly suggestive, three were classified as suggestive, and 26 were classified as weak. For three biomarkers explored in MR studies, there was evidence of causality and seven were classified as likely noncausal. For the first time, results from both observational and MR studies were integrated by triangulating the evidence for a wide variety of non-genetic biomarkers and CRC risk. At blood level, lower vitamin D, higher homeostatic model assessment-insulin resistance, and human papillomavirus infection were associated with higher CRC risk while increased linoleic acid and oleic acid and decreased arachidonic acid were likely causally associated with lower CRC risk. No association was found convincing in both study types.
| S-EPMC7333850 | biostudies-literature
Project description:BackgroundThe etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.MethodsWe performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.ResultsWe identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.ConclusionsWe identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
| S-EPMC7805241 | biostudies-literature
Project description:BackgroundThe utilization of basket trials in oncology has gained popularity because of the drive for precision medicine and the increasing ease of genetically profiling tumors. However, it is unknown if this has translated into patient benefit, either through higher response rates because of precision treatment or because of increasing options for less-common tumor types that are less represented in oncology drug trials. We sought to characterize basket studies for oncology drugs targeting a genetic biomarker, determine the responses for various tumor types and genetic biomarkers, and test for correlation between the number of participants in each tumor basket and the incidence of the respective tumor.MethodsWe conducted a retrospective cross-sectional review of oncology basket trials on Embase or clinicaltrials.gov with published data. We included studies that reported on oncology drugs that target a genetic biomarker. We examined the response for basket trial participants, stratified by tumor type and genetic biomarker and the correlation between the number of participants in each tumor basket and the incidence of the respective tumor.ResultsThe overall response rate for all 25 included trials was 23%. The response for each genetic biomarker ranged from 0 to 69%, and for half of the genetic biomarkers, the response rate ranged from 0 to 100%, depending on tumor type. There is low correlation between the number of participants in each tumor basket and the incidence of the respective tumor (66.41 + -0.20x, R2 = 0.003, p = 0.75).ConclusionWhile there has been an increase in the number of published basket trials and individuals included in these trials, the response rate is low, but varies widely, depending on tumor type and genetic biomarker.
| S-EPMC9840247 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease that imposes a significant impact on the health and wellbeing of patients and a financial burden on individuals, their families, and society. Development of new methods of testing other than an overnight sleep study, such as measurement of serum or plasma biomarkers, may provide an easier diagnostic process to identify patients with OSA and allow earlier initiation of treatment, which might prevent serious comorbidities. We conducted a systematic review and quality assessment of available meta-analyses regarding potential diagnostic and monitoring biomarkers of obstructive sleep apnea. A total of 14 sets of candidate biomarkers displayed differences in levels or concentrations in OSA patients compared to non-OSA controls, and decreased after OSA treatment: CRP, IL-6, TNF-α, Il-8, HCY, ICAM-1, VCAM-1, VEGF, TC, LDLc, HDLc, TG, leptin, MDA, ALT, AST, IGF-1, adiponectin, and cortisol. This review summarizes the evidence for OSA-associated potential biomarkers and demonstrates that the quality of available studies, as measured by AMSTAR2, is often low and associated with a high risk of bias.
| S-EPMC9821668 | biostudies-literature