scholarly journals Current Evidence and Limitation of Biomarkers for Detecting Sepsis and Systemic Infection

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 494
Author(s):  
Shang-Kai Hung ◽  
Hao-Min Lan ◽  
Shih-Tsung Han ◽  
Chin-Chieh Wu ◽  
Kuan-Fu Chen
Keyword(s):  
Study Design ◽  
Systemic Infection ◽  
Sampling Strategy ◽  
Case Control ◽  
Small Sample ◽  
Current Evidence ◽  
Synthesis Methods ◽  
Control Analysis ◽  
Small Sample Sizes ◽  
Meta Analyses

Sepsis was recently redefined as a life-threatening disease involving organ dysfunction caused by a dysregulated host response to infection. Biomarkers play an important role in early detection, diagnosis, and prognostication. We reviewed six promising biomarkers for detecting sepsis and systemic infection, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), CD64, presepsin, and sTREM-1. Among the recent studies, we found the following risks of bias: only a few studies adopted the random or consecutive sampling strategy; extensive case-control analysis, which worsened the over-estimated performance; most of the studies used post hoc cutoff values; and heterogeneity with respect to the inclusion criteria, small sample sizes, and different quantitative synthesis methods applied in meta-analyses. We recommend that CD64 and presepsin should be considered as the most promising biomarkers for diagnosing sepsis. Future studies should enroll a larger sample size with a cohort rather than a case-control study design. A random or consecutive study design with a pre-specified laboratory threshold, consistent sampling timing, and an updated definition of sepsis will also increase the reliability of the studies. Further investigations of appropriate specimens, testing assays, and cutoff levels for specific biomarkers are also warranted.

Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18600-e18600
Author(s):  
Maryam Alasfour ◽  
Salman Alawadi ◽  
Malak AlMojel ◽  
Philippos Apolinario Costa ◽  
Priscila Barreto Coelho ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Small Sample ◽  
Prediction Intervals ◽  
Invasive Ventilation ◽  
Newcastle Ottawa Scale ◽  
Small Sample Sizes ◽  
Meta Analyses

e18600 Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.

scholarly journals True and false positive rates for different criteria of evaluating statistical evidence from clinical trials

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Don van Ravenzwaaij ◽  
John P. A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Confidence Intervals ◽  
False Positive ◽  
Evaluation Criteria ◽  
Small Sample ◽  
Statistical Evidence ◽  
Bayes Factors ◽  
True Positive ◽  
Small Sample Sizes ◽  
Meta Analyses

Abstract Background Until recently a typical rule that has often been used for the endorsement of new medications by the Food and Drug Administration has been the existence of at least two statistically significant clinical trials favoring the new medication. This rule has consequences for the true positive (endorsement of an effective treatment) and false positive rates (endorsement of an ineffective treatment). Methods In this paper, we compare true positive and false positive rates for different evaluation criteria through simulations that rely on (1) conventional p-values; (2) confidence intervals based on meta-analyses assuming fixed or random effects; and (3) Bayes factors. We varied threshold levels for statistical evidence, thresholds for what constitutes a clinically meaningful treatment effect, and number of trials conducted. Results Our results show that Bayes factors, meta-analytic confidence intervals, and p-values often have similar performance. Bayes factors may perform better when the number of trials conducted is high and when trials have small sample sizes and clinically meaningful effects are not small, particularly in fields where the number of non-zero effects is relatively large. Conclusions Thinking about realistic effect sizes in conjunction with desirable levels of statistical evidence, as well as quantifying statistical evidence with Bayes factors may help improve decision-making in some circumstances.

scholarly journals Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

2019 ◽  
Author(s):  
Tianye Jia ◽  
Congying Chu ◽  
Yun Liu ◽  
Jenny van Dongen ◽  
Evangelos Papastergios ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nucleus Accumbens ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Association Studies ◽  
Meta Analysis ◽  
Hippocampal Volume ◽  
Small Sample ◽  
Small Sample Sizes ◽  
Meta Analyses

AbstractDNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

scholarly journals Relaxation therapy as a treatment for tics in patients with Tourette syndrome: a systematic literature review

2019 ◽  
Vol 41 (5) ◽  
pp. 1011-1017 ◽  
Author(s):  
Florence Tilling ◽  
Andrea E. Cavanna
Keyword(s):  
Literature Review ◽  
Tourette Syndrome ◽  
Systematic Literature Review ◽  
Treatment Strategies ◽  
Small Sample ◽  
Relaxation Therapy ◽  
Behavioural Treatment ◽  
Study Protocols ◽  
Small Sample Sizes ◽  
Meta Analyses

Abstract Background Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics, often associated with co-morbid behavioural problems. Tics can be modulated by environmental factors and are characteristically exacerbated by psychological stress, among other factors. This observation has led to the development of specific behavioural treatment strategies, including relaxation therapy. Objective This review aimed to assess the efficacy of relaxation therapy to control or reduce tic symptoms in patients with TS. Methods We conducted a systematic literature review of original studies on the major scientific databases, including Medline, EMBASE, and PsycInfo, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes measures included both tic severity and tic frequency. Results Our literature search identified three controlled trials, with a total number of 40 participants (range: 6–18 participants). In all three studies, relaxation therapy decreased the severity and/or the frequency of tic symptoms. However, the only trial comparing relaxation therapy to two other behavioural techniques found relaxation therapy to be the least effective intervention, as it reduced the number of tics by 32% compared to 44% with self-monitoring and 55% with habit reversal. Discussion The results of this systematic literature review provide initial evidence for the use of relaxation therapy as a behavioural treatment intervention for tics in patients with TS. Caution is needed in the interpretation of these findings, because the reviewed trials had small sample sizes and there was high heterogeneity across the study protocols.

scholarly journals Exercise and Nutrition Impact on Osteoporosis and Sarcopenia—The Incidence of Osteosarcopenia: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4499
Author(s):  
Sousana K. Papadopoulou ◽  
Konstantinos Papadimitriou ◽  
Gavriela Voulgaridou ◽  
Evridiki Georgaki ◽  
Eudoxia Tsotidou ◽  
...  
Keyword(s):  
Older Adults ◽  
Protective Role ◽  
Scientific Data ◽  
Bone Diseases ◽  
Small Sample ◽  
Narrative Review ◽  
Prevention Of Osteoporosis ◽  
Small Sample Sizes ◽  
Meta Analyses

Osteoporosis and sarcopenia are diseases which affect the myoskeletal system and often occur in older adults. They are characterized by low bone density and loss of muscle mass and strength, factors which reduce the quality of life and mobility. Recently, apart from pharmaceutical interventions, many studies have focused on non-pharmaceutical approaches for the prevention of osteoporosis and sarcopenia with exercise and nutrition to being the most important and well studied of those. The purpose of the current narrative review is to describe the role of exercise and nutrition on prevention of osteoporosis and sarcopenia in older adults and to define the incidence of osteosarcopenia. Most of the publications which were included in this review show that resistance and endurance exercises prevent the development of osteoporosis and sarcopenia. Furthermore, protein and vitamin D intake, as well as a healthy diet, present a protective role against the development of the above bone diseases. However, current scientific data are not sufficient for reaching solid conclusions. Although the roles of exercise and nutrition on osteoporosis and sarcopenia seem to have been largely evaluated in literature over the recent years, most of the studies which have been conducted present high heterogeneity and small sample sizes. Therefore, they cannot reach final conclusions. In addition, osteosarcopenia seems to be caused by the effects of osteoporosis and sarcopenia on elderly. Larger meta-analyses and randomized controlled trials are needed designed based on strict inclusion criteria, in order to describe the exact role of exercise and nutrition on osteoporosis and sarcopenia.

Effectiveness of Outdoor Exercise Parks on Health Outcomes in Older Adults—A Mixed-Methods Systematic Review and Meta-Analysis

2020 ◽  
pp. 1-13
Author(s):  
Yoke Leng Ng ◽  
Keith D. Hill ◽  
Pazit Levinger ◽  
Elissa Burton
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Older Adults ◽  
Meta Analysis ◽  
Small Sample ◽  
Activity Levels ◽  
Single Leg Stance ◽  
Small Sample Sizes ◽  
Meta Analyses

The objective of this systematic review was to examine the effectiveness of outdoor exercise park equipment on physical activity levels, physical function, psychosocial outcomes, and quality of life of older adults living in the community and to evaluate the evidence of older adults’ use of outdoor exercise park equipment. A search strategy was conducted from seven databases. Nine articles met the inclusion criteria. The study quality results were varied. Meta-analyses were undertaken for two physical performance tests: 30-s chair stand test and single-leg stance. The meta-analysis results were not statistically significant. It was not possible to conclude whether exercise parks were effective at improving levels of physical activity. The review shows that older adults value the benefits of health and social interaction from the use of exercise parks. Findings should be interpreted with caution due to the small sample sizes and the limited number of studies.

scholarly journals Efficacy of Dietary Supplements in Inflammatory Bowel Disease and Related Autoimmune Diseases

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2156 ◽  
Author(s):  
Priyanka Jadhav ◽  
Yan Jiang ◽  
Karolin Jarr ◽  
Cosima Layton ◽  
Judith F. Ashouri ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Psoriatic Arthritis ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Small Sample ◽  
Therapeutic Options ◽  
Current Evidence ◽  
Inflammatory Bowel ◽  
Small Sample Sizes

The microbiome is an important contributor to a variety of fundamental aspects of human health, including host metabolism, infection, and the immune response. Gut dysbiosis has been identified as a contributor to the errant immune response in a variety of immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriatic disease (psoriasis and psoriatic arthritis). Given this, probiotics and prebiotics have been investigated as therapeutic options in these disease states. In our review, we highlight the current evidence on prebiotics and probiotics as well as other supplements (such as fish oils, vitamin D, and curcumin) as therapies for IBD. Recommendations, however, regarding the specific use of such supplements in IBD have been lacking, particularly from professional societies, often due to study limitations related to small sample sizes and design heterogeneity. Hence, we additionally examine the literature on the use of prebiotics, probiotics, and other supplements in related IMIDs, namely RA and psoriasis/psoriatic arthritis, as these diseases share many approved therapeutic options with IBD. Based on these combined findings, we offer additional evidence that may help guide clinicians in their treatment of patients with IBD (and other IMIDs) and provide recommendations on potential next steps in therapeutic research in this area.

scholarly journals Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results From the D-Tect Study

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 924
Author(s):  
Thorsteinsdottir ◽  
Maslova ◽  
Jacobsen ◽  
Frederiksen ◽  
Keller ◽  
...  
Keyword(s):  
Vitamin D ◽  
Study Design ◽  
Childhood Asthma ◽  
Proportional Hazards ◽  
Epidemiological Studies ◽  
Vitamin D Insufficiency ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Increased Risk ◽  
Small Sample Sizes

Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0–9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90–1.04). When stratifying by sex and age, 0–3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67–0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0–9 years but seemed to reduce the risk among 0–3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

A Systematic Review and Meta-Analysis of Cognitive Performance among People with Chronic Use of Opioids for Chronic Non-Cancer Pain

Pain Medicine ◽  
2021 ◽  
Author(s):  
Jane Akhurst ◽  
Monica Lovell ◽  
Amy Peacock ◽  
Raimondo Bruno
Keyword(s):  
Working Memory ◽  
Cancer Pain ◽  
Cognitive Performance ◽  
Case Control ◽  
Small Sample ◽  
Effect Sizes ◽  
Attention And Memory ◽  
Small Magnitude ◽  
Meta Analyses

Abstract Objective Opioids, often prescribed for chronic non-cancer pain, may adversely affect cognition. Research has not been synthesised in recent years, during which time academic interest has increased. This study presents meta-analyses on cognitive performance in people taking opioids for CNCP. Methods We ran systematic literature searches in EMBASE, Medline, and PsycINFO. Eligible studies included people taking opioids for CNCP and an opioid-free group (i.e., case-control) or session (e.g., pre-post), and objective cognitive assessments. Using random-effects meta-analyses, we computed pooled effect sizes for differential task performance for each study design across five domains (motor performance, attention, working memory, executive functions, memory). Results Seventeen studies were included. Case-control studies covered 3 control types (healthy, CNCP, taper-off). Pre-post studies were grouped into 5 follow-ups (4–6 and 6–9 weeks; 3, 6, and 12 months). Effect sizes ranged from 0.02–0.62. Cases showed small magnitude impairments in attention and memory compared with healthy controls. Although limited by small sample sizes, there was no clear evidence of impairment in cases compared with opioid-free controls with CNCP. Cases showed some cognitive improvements from opioid-free baseline to follow-up. Effects were strongest for attention and working memory, and were apparent from 4 weeks to 6 months follow-up. Other effects were small and non-significant. Conclusions Opioid therapy for CNCP did not worsen cognitive performance and improved it for some domains. People who take opioids for CNCP may evidence deficits in attention and memory, but this is unlikely to translate to global impairment and likely relates to pain more so than opioids.

Imaging of depressive disorders

2020 ◽  
pp. 797-806
Author(s):  
Guy M. Goodwin ◽  
Michael Browning
Keyword(s):  
Depressive Disorders ◽  
Case Control ◽  
Structure And Function ◽  
Small Sample ◽  
Case Control Studies ◽  
Brain Structure And Function ◽  
Small Sample Sizes ◽  
And Function ◽  
Study Designs ◽  
And Control

Neuroimaging techniques have been used extensively to compare brain structure and function between patients with, or at risk of, depression and control subjects. The goal of this work has largely been to identify pathophysiological processes in depression. However, progress in this field has been limited by the heterogeneity of patient populations, the use of small sample sizes, and an overreliance on case-control studies. These limitations have increasingly been acknowledged with recent work collecting much larger samples and employing a variety of study designs, including those able to stratify patient populations. This chapter reviews imaging studies in depression, highlighting both outstanding questions and promising recent findings.

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