scholarly journals ICODE: the international COVID-19 thrombosis biomarkers colloquium—novel soluble biomarkers: circulating cell-free nucleic acids and other molecules

2021 ◽  
Author(s):  
Krystin Krauel ◽  
Daniel Duerschmied
Keyword(s):  
Sample Preparation ◽  
Nucleic Acids ◽  
Clinical Studies ◽  
Observational Studies ◽  
Prognostic Value ◽  
Technical Details

AbstractThis article summarizes the evidence derived from clinical (observational) studies describing novel soluble biomarkers in COVID-19. Our goal was to stimulate further research (preclinical as well as clinical studies) and therefore we discuss potential prognostic value, but also technical details, such as sample preparation. A table provides an overview of the described biomarkers measured in plasma, serum or other (namely bronchoalveolar) fluids.

scholarly journals Prognostic Value of Serum Magnesium in Mortality Risk among Patients on Hemodialysis: A Meta-Analysis of Observational Studies

2020 ◽  
pp. 1-10
Author(s):  
Hongwei Wu ◽  
Qiang Li ◽  
Lijing Fan ◽  
Dewang Zeng ◽  
Xianggeng Chi ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Cardiovascular Mortality ◽  
Observational Studies ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Serum Magnesium ◽  
Cochrane Library ◽  
Lower Serum ◽  
All Cause Mortality ◽  
End Stage

<b><i>Background:</i></b> Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. <b><i>Methods:</i></b> We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). <b><i>Results:</i></b> We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (<i>I</i><sup>2</sup> = 79.6%, <i>p</i> &#x3c; 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. <b><i>Conclusion:</i></b> A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.

scholarly journals Current Perspectives on High-Throughput Sequencing (HTS) for Adventitious Virus Detection: Upstream Sample Processing and Library Preparation

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 566 ◽  
Author(s):  
Siemon Ng ◽  
Cassandra Braxton ◽  
Marc Eloit ◽  
Szi Feng ◽  
Romain Fragnoud ◽  
...  
Keyword(s):  
Sample Preparation ◽  
Nucleic Acids ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Virus Detection ◽  
Extraction Methods ◽  
Control Measures ◽  
Acid Extraction ◽  
Library Preparation ◽  
Sample Processing

A key step for broad viral detection using high-throughput sequencing (HTS) is optimizing the sample preparation strategy for extracting viral-specific nucleic acids since viral genomes are diverse: They can be single-stranded or double-stranded RNA or DNA, and can vary from a few thousand bases to over millions of bases, which might introduce biases during nucleic acid extraction. In addition, viral particles can be enveloped or non-enveloped with variable resistance to pre-treatment, which may influence their susceptibility to extraction procedures. Since the identity of the potential adventitious agents is unknown prior to their detection, efficient sample preparation should be unbiased toward all different viral types in order to maximize the probability of detecting any potential adventitious viruses using HTS. Furthermore, the quality assessment of each step for sample processing is also a critical but challenging aspect. This paper presents our current perspectives for optimizing upstream sample processing and library preparation as part of the discussion in the Advanced Virus Detection Technologies Interest group (AVDTIG). The topics include: Use of nuclease treatment to enrich for encapsidated nucleic acids, techniques for amplifying low amounts of virus nucleic acids, selection of different extraction methods, relevant controls, the use of spike recovery experiments, and quality control measures during library preparation.

scholarly journals High-cited favorable studies for COVID-19 treatments ineffective in large trials

2022 ◽  
Author(s):  
John P.A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Clinical Studies ◽  
Observational Studies ◽  
Randomized Trials ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Wide Dissemination ◽  
Highly Cited Articles ◽  
Highly Cited

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

scholarly journals Fluid Overload

2021 ◽  
Vol 8 ◽  
Author(s):  
Bernie Hansen
Keyword(s):  
Fluid Therapy ◽  
Clinical Studies ◽  
Observational Studies ◽  
Fluid Intake ◽  
Fluid Overload ◽  
Body Cavity ◽  
Positive Fluid Balance ◽  
Intravenous Fluid Therapy ◽  
Maintenance Fluid ◽  
Resuscitation Fluid

Fluid overload (FO) is characterized by hypervolemia, edema, or both. In clinical practice it is usually suspected when a patient shows evidence of pulmonary edema, peripheral edema, or body cavity effusion. FO may be a consequence of spontaneous disease, or may be a complication of intravenous fluid therapy. Most clinical studies of the association of FO with fluid therapy and risk of harm define it in terms of an increase in body weight of at least 5–10%, or a positive fluid balance of the same magnitude when fluid intake and urine output are measured. Numerous observational clinical studies in humans have demonstrated an association between FO, adverse events, and mortality, as have two retrospective observational studies in dogs and cats. The risk of FO may be minimized by limiting resuscitation fluid to the smallest amount needed to optimize cardiac output and then limiting maintenance fluid to the amount needed to replace ongoing normal and pathological losses of water and sodium.

scholarly journals The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational studies

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191972 ◽  
Author(s):  
Hui Luo ◽  
Xiaohui Xu ◽  
Miaomiao Ye ◽  
Bo Sheng ◽  
Xueqiong Zhu
Keyword(s):  
Ovarian Cancer ◽  
Observational Studies ◽  
Prognostic Value ◽  
Meta Analysis

scholarly journals Electrokinetically Assisted Paper-Based DNA Concentration for Enhanced qPCR Sensing

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 33
Author(s):  
Md Nazibul Islam ◽  
Jarad Yost ◽  
Zachary Gagnon
Keyword(s):  
Sample Preparation ◽  
Nucleic Acids ◽  
Pore Size ◽  
Fluid Transport ◽  
Low Cost ◽  
Quantitative Polymerase Chain Reaction ◽  
Pressure System ◽  
Bulk Fluid ◽  
Paper Based Microfluidics ◽  
Copper Tape

Paper-based microfluidics have gained widespread attention for use as low-cost microfluidic diagnostic devices in low-resource settings. However, variability in fluid transport due to evaporation and lack of reproducibility with processing real-world samples limits their commercial potential and widespread adoption. We have developed a novel fabrication method to address these challenges. This approach, known as “Microfluidic Pressure in Paper” (μPiP), combines thin laminating polydimethylsiloxane (PDMS) membranes and precision laser-cut paper microfluidic structures to produce devices that are low-cost, scalable, and exhibit controllable and reproducible fluid flow dynamics similar to conventional microfluidic devices. We present a new μPiP DNA sample preparation and processing device that reduces the number of sample preparation steps and improves sensitivity of the quantitative polymerase chain reaction (qPCR) by electrophoretically separating and concentrating nucleic acids (NAs) continuously on paper. Our device was assembled using two different microfluidic paper channels: one with a larger pore (25 microns) size for bulk fluid transport and another with a smaller pore size (11 microns) for electrophoretic sample concentration. These two paper types were aligned and laminated within PDMS sheets, and integrated with adhesive copper tape electrodes. A solution containing a custom DNA sequence was introduced into the large pore size paper channel using a low-cost pressure system and a DC voltage was applied to the copper tape to electrophoretically deflect the solution containing NAs into the paper channel with the smaller pore size. Samples were collected from both DNA enriched and depleted channels and analyzed using qPCR. Our results demonstrate the ability to use these paper devices to process and concentrate nucleic acids. Our concentration device has the potential to reduce the number of sample preparation steps and to improve qPCR sensitivity, which has immediate applications in disease diagnostics, microbial contamination, and public health monitoring.

scholarly journals Equivalency of Protection from Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis

2021 ◽  
Author(s):  
Mahesh B Shenai ◽  
Ralph Rahme ◽  
Hooman Noorchasm
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Observational Studies ◽  
Individual Preference ◽  
Pooled Analysis ◽  
Case Control ◽  
Number Needed To Treat ◽  
Clinical Equipoise ◽  
Natural Immunity ◽  
Randomized Controlled Studies

BACKGROUND: We present a systematic review and pooled analysis of clinical studies to date, that (1) specifically compare the protection of natural immunity in the COVID-recovered versus the efficacy of full vaccination in the COVID-naive, and (2) the added benefit of vaccination in the COVID-recovered, for prevention of subsequent SARS-CoV-2 infection. METHODS: Using the PRISMA 2020 guidance, we first conducted a systematic review of available literature on PubMed, MedRxIV and FDA briefings to identify clinical studies either comparing COVID vaccination to natural immunity or delineating the benefit of vaccination in recovered individuals. After assessing for eligibility, studies were qualitatively appraised and formally graded using the NOS system for observational, case-control and RCTs. Incidence rates were tabulated for the following groups: never infected (NI) and unvaccinated (UV), NI and vaccinated (V), previously infected (PI) and UV, PI and UV. Pooling was performed by grouping the RCTs and observational studies separately, and then all studies in total. Risk ratios and risk differences are reported for individual studies and pooled groups, in 1) NPI/V vs. PI/UV and 2) PI/UV vs. PI/V analysis. In addition, number needed to treat (NNT) analysis was performed for vaccination in naive and previously infected cohorts. RESULTS: Nine clinical studies were identified including three randomized controlled studies, four retrospective observational cohorts, one prospective observational cohort, and a case-control study. The NOS quality appraisals of these articles ranged from four to nine (out of nine stars). All of the included studies found at least statistical equivalence between the protection of full vaccination and natural immunity; and, three studies found superiority of natural immunity. Four observational studies found a statistically significant incremental benefit to vaccination in the COVID-recovered individuals. In total pooled analysis, incidence in NPI/V trended higher than PI/UV groups (RR=1.86 [95%CI 0.77-4.51], P=0.17). Vaccination in COVID-recovered individuals provided modest protection from reinfection (RR=1.82 [95%CI 1.21-2.73], P=0.004), but the absolute risk difference was extremely small (AR= 0.004 person-years [95% CI 0.001-0.007], P=0.02). The NNT to prevent one annual case of infection in COVID-recovered patients was 218, compared to 6.5 in COVID-naive patients, representing a 33.5-fold difference in benefit between the two populations. CONCLUSIONS: While vaccinations are highly effective at protecting against infection and severe COVID-19 disease, our review demonstrates that natural immunity in COVID-recovered individuals is, at least, equivalent to the protection afforded by full vaccination of COVID-naive populations. There is a modest and incremental relative benefit to vaccination in COVID-recovered individuals; however, the net benefit is marginal on an absolute basis. COVID-recovered individuals represent a distinctly different benefit-risk calculus. Therefore, vaccination of COVID-recovered individuals should be subject to clinical equipoise and individual preference.

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