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Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496 -
Annals of Medicine and Surgery (2012) Sep 2023The multisystem inflammatory syndrome in adults (MIS-A) has emerged, similar to those in children associated with SARS-CoV-2 (severe acute respiratory syndrome... (Review)
Review
A global systematic review and meta-analysis on the emerging evidence on risk factors, clinical characteristics, and prognosis of multisystem inflammatory syndrome in adults (MIS-A).
BACKGROUND
The multisystem inflammatory syndrome in adults (MIS-A) has emerged, similar to those in children associated with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) [multisystem inflammatory syndrome in children (MIS-C)]. This review aimed to analyze the risk factors, clinical course, and prognosis of MIS-A.
METHODS
A comprehensive literature search was conducted using several databases for cases reporting MIS-A from 1 December 2019 till 9 September 2021. The case definitions used to identify potential cases were those recommended by the World Health Organization, Center for Disease Control, and individual country/physician classification. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) 2.2.027 and Review Manager (RevMan) 5.4.1, employing 95% confidence intervals (CI).
RESULTS
Seventy studies were assessed for full-text eligibility, out of which 37 were included. The mean age of the study population was 32.52±10.29 years. The most common symptoms were fever (89.8%, 95% CI: 77.7-95.7%) and diarrhea (49%, 95% CI: 35.4-62.7%). Ventricular tachycardia (57.1%, 95% CI: 43.1-70.1%) was the most common electro-cardiac abnormality. The most common inflammatory marker was elevated C-reactive protein (89.8%, 95% CI: 77.7-95.7%). Abnormal echocardiogram was the most common imaging test result (commonly, ventricular dysfunction and arrhythmias), while steroids were the most administered treatment. Severe cases had a higher need for vasopressor and inotropic support and antibiotic therapy compared to the non-severe cases. One death was reported due to cardiovascular failure.
CONCLUSION
Our collated findings will help clinicians identify the typical presenting symptoms and optimal management of MIS-A. Further research is required to understand the long-term prognosis and the correlation between coronavirus disease 2019 (COVID-19) and MIS-A to understand its pathogenesis and clinical spectrum.
PubMed: 37663717
DOI: 10.1097/MS9.0000000000000732 -
Journal of Medical Internet Research Aug 2023Digital therapeutics (DTx), a class of software-based clinical interventions, are promising new technologies that can potentially prevent, manage, or treat a spectrum of... (Review)
Review
BACKGROUND
Digital therapeutics (DTx), a class of software-based clinical interventions, are promising new technologies that can potentially prevent, manage, or treat a spectrum of medical disorders and diseases as well as deliver unprecedented portability for patients and scalability for health care providers. Their adoption and implementation were accelerated by the need for remote care during the COVID-19 pandemic, and awareness about their utility has rapidly grown among providers, payers, and regulators. Despite this, relatively little is known about the capacity of DTx to provide economic value in care.
OBJECTIVE
This study aimed to systematically review and summarize the published evidence regarding the cost-effectiveness of clinical-grade mobile app-based DTx and explore the factors affecting such evaluations.
METHODS
A systematic review of economic evaluations of clinical-grade mobile app-based DTx was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Major electronic databases, including PubMed, Cochrane Library, and Web of Science, were searched for eligible studies published from inception to October 28, 2022. Two independent reviewers evaluated the eligibility of all the retrieved articles for inclusion in the review. Methodological quality and risk of bias were assessed for each included study.
RESULTS
A total of 18 studies were included in this review. Of the 18 studies, 7 (39%) were nonrandomized study-based economic evaluations, 6 (33%) were model-based evaluations, and 5 (28%) were randomized clinical trial-based evaluations. The DTx intervention subject to assessment was found to be cost-effective in 12 (67%) studies, cost saving in 5 (28%) studies, and cost-effective in 1 (6%) study in only 1 of the 3 countries where it was being deployed in the final study. Qualitative deficiencies in methodology and substantial potential for bias, including risks of performance bias and selection bias in participant recruitment, were identified in several included studies.
CONCLUSIONS
This systematic review supports the thesis that DTx interventions offer potential economic benefits. However, DTx economic analyses conducted to date exhibit important methodological shortcomings that must be addressed in future evaluations to reduce the uncertainty surrounding the widespread adoption of DTx interventions.
TRIAL REGISTRATION
PROSPERO International Prospective Register of Systematic Reviews CRD42022358616; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022358616.
Topics: Humans; Cost-Benefit Analysis; COVID-19; Mobile Applications; Pandemics; Clinical Trials as Topic
PubMed: 37526973
DOI: 10.2196/47094 -
Brain, Behavior, and Immunity Mar 2024While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents.
METHODS
We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker.
RESULTS
The systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge's g = 0.40, 95 % CI 0.17 - 0.64), tumor necrosis factor (Hedge's g = 0.38, 95 % CI 0.06 - 0.69), C-reactive protein (Hedge's g = 0.38, 95 % CI 0.05 - 0.70), interleukin-6 (Hedge's g = 0.35; 95 % CI 0.11 - 0.64), and total white blood cell count (Hedge's g = 0.29, 95 % CI 0.12 - 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous.
CONCLUSION
Results from several studies are consistent with the hypothesis that signals often classified as "proinflammatory" are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.
Topics: Adolescent; Humans; Child; Psychotic Disorders; Biomarkers; C-Reactive Protein; Interleukin-6; Oxidative Stress
PubMed: 38141839
DOI: 10.1016/j.bbi.2023.12.019 -
BMC Pediatrics Nov 2023Neonatal near-miss (NNM) can be considered as an end of a spectrum that includes stillbirths and neonatal deaths. Clinical audits of NNM might reduce perinatal adverse...
BACKGROUND
Neonatal near-miss (NNM) can be considered as an end of a spectrum that includes stillbirths and neonatal deaths. Clinical audits of NNM might reduce perinatal adverse outcomes. The aim of this review is to evaluate the effectiveness of NNM audits for reducing perinatal mortality and morbidity and explore related contextual factors.
METHODS
PubMed, Embase, Scopus, CINAHL, LILACS and SciELO were searched in February/2023. Randomized and observational studies of NNM clinical audits were included without restrictions on setting, publication date or language.
PRIMARY OUTCOMES
perinatal mortality, morbidity and NNM.
SECONDARY OUTCOMES
factors contributing to NNM and measures of quality of care. Study characteristics, methodological quality and outcome were extracted and assessed by two independent reviewers. Narrative synthesis was performed.
RESULTS
Of 3081 titles and abstracts screened, 36 articles had full-text review. Two studies identified, rated, and classified contributing care factors and generated recommendations to improve the quality of care. No study reported the primary outcomes for the review (change in perinatal mortality, morbidity and NNM rates resulting from an audit process), thus precluding meta-analysis. Three studies were multidisciplinary NNM audits and were assessed for additional contextual factors.
CONCLUSION
There was little data available to determine the effectiveness of clinical audits of NNM. While trials randomised at patient level to test our research question would be difficult or unethical for both NNM and perinatal death audits, other strategies such as large, well-designed before-and-after studies within services or comparisons between services could contribute evidence. This review supports a Call to Action for NNM audits. Adoption of formal audit methodology, standardised NNM definitions, evaluation of parent's engagement and measurement of the effectiveness of quality improvement cycles for improving outcomes are needed.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Clinical Audit; Near Miss, Healthcare; Perinatal Death; Perinatal Mortality; Stillbirth
PubMed: 37978460
DOI: 10.1186/s12887-023-04383-6 -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
Indian Journal of Dermatology 2023is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics,... (Review)
Review
is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics, immunosuppressant agents, and other immunocompromising conditions. Currently, bLf and antifungal drugs have been known to have synergistic effects, increasing the drug's efficacy. This study aims to investigate the efficacy of the synergistic effect of bLf and antifungal drugs. This review addressed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We conducted literature searches to assess the association of lactoferrin and current antifungal therapy against in ProQuest, PubMed, MEDLINE, EBSCOhost, SAGE, JSTOR, GARUDA, and Open Gray with no date restriction (until March 5, 2021). We used Jeffry's Amazing Statistical Program (JASP) to measure the overall size effect of MIC (minimum inhibitory concentration) between studies. A total of 7 studies retained were experimental in vitro studies. Based on the available data, 4 out of 7 studies were included in the quantitative analysis. This systematic review showed that bovine lactoferrin could help inhibit the development of azole-susceptible and azole-resistant . Furthermore, there was synergistic activity between lactoferrin and various antifungals. Our meta-analysis showed that lactoferrin could significantly inhibit the growth than the control group. Bovine lactoferrin and its peptide derivatives isolated from bovine milk can significantly inhibit the growth of , both susceptible to azoles and those with azole resistance.
PubMed: 38371540
DOI: 10.4103/ijd.ijd_275_22 -
Neuroscience and Biobehavioral Reviews May 2024The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health... (Meta-Analysis)
Meta-Analysis Review
Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis.
The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support.
Topics: Child; Humans; Female; Pregnancy; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Antipsychotic Agents; Prenatal Exposure Delayed Effects; Mothers
PubMed: 38499117
DOI: 10.1016/j.neubiorev.2024.105635 -
Translational Psychiatry Dec 2023Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high... (Meta-Analysis)
Meta-Analysis
Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high frequencies and reduced power for middle frequencies. However, these differences have yet to be quantified using effect sizes and probed robustly for consistency, which are critical next steps for clinical translation. Following PRISMA guidelines, we conducted a systematic review of published and gray literature on resting-state EEG power in autism. We performed 10 meta-analyses to synthesize and quantify differences in absolute and relative resting-state delta, theta, alpha, beta, and gamma EEG power in autism. We also conducted moderator analyses to determine whether demographic characteristics, methodological details, and risk-of-bias indicators might account for heterogeneous study effect sizes. Our literature search and study selection processes yielded 41 studies involving 1,246 autistic and 1,455 neurotypical individuals. Meta-analytic models of 135 effect sizes demonstrated that autistic individuals exhibited reduced relative alpha (g = -0.35) and increased gamma (absolute: g = 0.37, relative: g = 1.06) power, but similar delta (absolute: g = 0.06, relative: g = 0.10), theta (absolute: g = -0.03, relative: g = -0.15), absolute alpha (g = -0.17), and beta (absolute: g = 0.01, relative: g = 0.08) power. Substantial heterogeneity in effect sizes was observed across all absolute (I: 36.1-81.9%) and relative (I: 64.6-84.4%) frequency bands. Moderator analyses revealed that age, biological sex, IQ, referencing scheme, epoch duration, and use of gold-standard autism diagnostic instruments did not moderate study effect sizes. In contrast, resting-state paradigm type (eyes-closed versus eyes-open) moderated absolute beta, relative delta, and relative alpha power effect sizes, and resting-state recording duration moderated relative alpha power effect sizes. These findings support further investigation of resting-state alpha and gamma power as potential biomarkers for autism.
Topics: Humans; Electroencephalography; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Autistic Disorder
PubMed: 38097538
DOI: 10.1038/s41398-023-02681-2 -
Frontiers in Psychiatry 2023Metacognition is the ability to reflect on one's own cognitive processes, monitor and regulate them to enhance mental performance. Social cognition involves the capacity...
INTRODUCTION
Metacognition is the ability to reflect on one's own cognitive processes, monitor and regulate them to enhance mental performance. Social cognition involves the capacity to perceive and respond to social cues from others. The study of metacognition and social cognition is an expanding research field in psychiatry. Both domains are related to neurocognition, symptoms and psychosocial functioning in schizophrenia. Understanding the relationship between social cognition and metacognition may be pivotal for enhancing the treatment of cognitive symptoms in schizophrenia.
METHODS
We conducted a PRISMA systematic review and meta-analysis on quantitative studies comparing metacognition to social cognitive outcomes in adult outpatients with a schizophrenia spectrum disorder. Reports were retrieved from the Medline, ScienceDirect and PsycINFO databases up to July 13th, 2023. Risk of bias was assessed with the Cochrane tool.
RESULTS
Our review included 1,036 participants across 17 reports, with 12 reports included in the meta-analysis. We found a significant positive correlation ( = 0.28, 95% CI: [0.14, 0.41]) between social cognition and metacognition. Subgroup analyses indicated that metacognition was specifically associated with theory of mind, attribution, and emotion processing. Different patterns of correlations were observed according to the assessment of metacognition and its subdimensions.
CONCLUSION
Despite discrepancies among the included studies, no publication bias was detected. The results suggest that metacognition and social cognition are distinct but related constructs. Those processes should be assessed and treated together, along with neurocognition, in schizophrenia.
PubMed: 38188042
DOI: 10.3389/fpsyt.2023.1285993