scholarly journals Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review

2021 ◽  
Vol 14 (8) ◽  
pp. 736
Author(s):  
Victoria Gil Gil Martínez ◽  
Ana Avedillo Avedillo Salas ◽  
Sonia Santander Santander Ballestín
Keyword(s):  
Systematic Review ◽  
Clinical Improvement ◽  
Demographic Data ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Increased Risk ◽  
Prisma Statement ◽  
Comparison Groups ◽  
Gastrointestinal Adverse Events

Background: Due to the lack of an etiologic treatment for SARS-CoV-2 and the difficulties involved in developing new drugs, some drugs already approved for other diseases or with efficacy against SARS and MERS, have been used in patients with COVID-19. This systematic review aims to summarize evidence on the efficacy and safety of five antivirals applied to patients with COVID-19, that have proven to be effective either in vitro studies or in studies on SARS-CoV and MERS.; Methods: An intensive search of different databases (Pub Med, WoS, MEDLINE and Cochrane COVID-19 Study Register) has been carried out until the end of April 2021. This systematic review has been conducted according to the PRISMA statement. From each of the included studies, the characteristics of the intervention and comparison groups, demographic data and results were extracted independently; Results: Remdesivir is well tolerated and helps to accelerate clinical improvement but is ineffective in reducing mortality. Favipiravir is safe and shows promising results regarding symptom resolution but does not improve viral clearance. The use of lopinavir/ritonavir has been associated with an increased risk of gastrointestinal adverse events and it has not proven to be effective. No significant differences were observed between patients treated with ribavirin or umifenovir and their respective control groups; Conclusions: Remdesivir and favipiravir are well tolerated and effective in accelerating clinical improvement. This systematic review does not support the use of lopinavir/ritonavir, ribavirin and umifenovir in hospitalized patients with COVID-19.

Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

2019 ◽  
Vol 25 (22) ◽  
pp. 2474-2479 ◽  
Author(s):  
Alisson Diego Machado ◽  
Gustavo Rosa Gentil Andrade ◽  
Jéssica Levy ◽  
Sara Silva Ferreira ◽  
Dirce Maria Marchioni
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Serum Levels ◽  
Antioxidant Compounds ◽  
Increased Risk ◽  
Coronary Events ◽  
Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

scholarly journals MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii406-iii406
Author(s):  
Kübra Taban ◽  
David Pauck ◽  
Mara Maue ◽  
Viktoria Marquardt ◽  
Hua Yu ◽  
...  
Keyword(s):  
New Drugs ◽  
Current Therapy ◽  
Cancer Drug ◽  
Mrna Levels ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Group 3 ◽  
Novel Therapeutic

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

scholarly journals Does the etiology of infertility have any effect on perinatal outcomes?

2021 ◽  
Vol 29 ◽  
Author(s):  
Songül Alemdaroğlu ◽  
Gülşen Doğan Durdağ ◽  
Şafak Yılmaz Baran ◽  
Tayfun Çok ◽  
Erhan Şimşek ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Multinomial Logistic Regression ◽  
Demographic Data ◽  
Control Group ◽  
Male Factor ◽  
Retrospective Case ◽  
Increased Risk ◽  
Confounding Variables ◽  
Adverse Pregnancy

Objective: Pregnancies after in vitro fertilization (IVF) are associated with a less favorable outcome compared to natural conception as consistently shown in various studies. However, etiologic factors behind this issue remain to be elucidated. We aimed to demonstrate whether the etiology of infertility has a role on poor pregnancy outcomes in IVF pregnancies. Methods: In this retrospective case control study; IVF and spontaneous singleton pregnancies were investigated. The infertile patients were divided into six groups according to the etiology of their infertility (anovulation, male factor, tubal factor, endometriosis, unexplained infertility and poor ovarian reserve). The incidence of preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, preterm birth and birth weight discrepancies was examined between the groups and subgroups. After adjusting the confounding variables for each infertility subgroup such as demographic data, embryo stage in transfer (blastocyst against cleavage stage) and fresh and frozen embryo transfer status, the effect on pregnancy outcomes was investigated using multinomial logistic regression analysis. Results: The study included 934 patients in the IVF group and 1009 patients in the control group. While adverse pregnancy outcomes were more frequent in the general infertility group in comparison to the control group, after elimination of the confounding variables, the direct effect of the etiology of infertility on these outcomes could not be shown. Conclusion: In the IVF pregnancies, most of the increased risk of poor pregnancy outcomes appeared to be explained by maternal characteristics (such as age, body mass index) and by treatment protocols rather than infertility etiology. Physicians should consider these risks while counselling patients.

scholarly journals Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

2022 ◽  
Vol 9 ◽  
Author(s):  
Maria Veronica Lipreri ◽  
Nicola Baldini ◽  
Gabriela Graziani ◽  
Sofia Avnet
Keyword(s):  
Extracellular Matrix ◽  
Bone Structure ◽  
Dynamic Network ◽  
Cell Types ◽  
New Drugs ◽  
Culture Methods ◽  
Increased Risk ◽  
Multiple Cell

As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.

scholarly journals Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review

2020 ◽  
Author(s):  
Sonal Singh ◽  
Thomas J Moore
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Poor Quality ◽  
Hospitalized Patients ◽  
Efficacy And Safety ◽  
Treatment Benefits ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Newcastle Ottawa Scale

BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of ≥ 500 ms or an increase of ≥ 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.

scholarly journals Effect of various treatment modalities on the novel coronavirus (nCOV-2019) infection in humans: a systematic review & meta-analysis

2020 ◽  
Author(s):  
Shubham Misra ◽  
Manabesh Nath ◽  
Vijay Hadda ◽  
Deepti Vibha
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Clinical Improvement ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Treatment Modalities ◽  
Cochrane Library ◽  
Effect Model ◽  
Novel Coronavirus

AbstractBackground and aimSeveral therapeutic agents have been investigated for the treatment of novel Coronavirus-2019 (nCOV-2019). We aimed to conduct a systematic review and meta-analysis to assess the effect of various treatment modalities in nCOV-2019 patients.MethodsAn extensive literature search was conducted before 22 May 2020 in PubMed, Google Scholar, Cochrane library databases. Quality assessment was performed using Newcastle Ottawa Scale. A fixed-effect model was applied if I2 <50%, else the results were combined using random-effect model. Risk Ratio (RR) or Standardized Mean Difference (SMD) along-with 95% Confidence Interval (95%CI) were used to pool the results. Between study heterogeneity was explored using influence and sensitivity analyses & publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.ResultsEighty-one studies involving 44 in vitro and 37 clinical studies including 8662 nCOV-2019 patients were included in the review. Lopinavir-Ritonavir compared to controls was significantly associated with shorter mean time to clinical improvement (SMD -0.32; 95%CI -0.57 to -0.06) and Remdesivir compared to placebo was significantly associated with better overall clinical improvement (RR 1.17; 95%CI 1.07 to 1.29). Hydroxychloroquine was associated with less overall clinical improvement (RR 0.88; 95%CI 0.79 to 0.98) and longer time to clinical improvement (SMD 0.64; 95%CI 0.33 to 0.94), It additionally had higher all-cause mortality (RR 1.6; 95%CI 1.26 to 2.03) and more total adverse events (RR 1.84; 95% CI 1.58 to 2.13).ConclusionOur meta-analysis suggests that except in vitro studies, no treatment till now has shown clear-cut benefit on nCOV-2019 patients. Lopinavir-Ritonavir and Remdesivir have shown some benefits in terms less time to clinical improvement and better overall clinical improvement. Hydroxychloroquine use has a risk of higher mortality and adverse events. Results from upcoming large clinical trials must be awaited to draw any profound conclusions.

scholarly journals Dementia and Hospital Readmission Rates: A Systematic Review

2017 ◽  
Vol 7 (3) ◽  
pp. 346-353 ◽  
Author(s):  
Sabrina Pickens ◽  
Aanand D. Naik ◽  
Angela Catic ◽  
Mark E. Kunik
Keyword(s):  
Systematic Review ◽  
Hospital Readmission ◽  
Patient Discharge ◽  
Community Dwelling ◽  
Case Control Studies ◽  
Readmission Rates ◽  
Absolute Increase ◽  
Hospital Readmission Rates ◽  
Increased Risk ◽  
Comparison Groups

Background: Although community-dwelling persons with dementia have an increased risk of hospital readmission, no systematic review has examined the contribution of dementia to readmissions. Summary: We examined articles in English, with no restrictions on publication dates, from Medline, PubMed, PsycINFO, CINAHL, and EMBASE. Keywords used were dementia, Alzheimer disease, frontotemporal lobar degeneration, elderly, frontotemporal dementia, executive function, brain atrophy, frontal lobe atrophy, cognitive impairment, readmission, readmit, rehospitalization, patient discharge, and return visit. Of 404 abstracts identified, 77 articles were retrieved; 12 were included. Four of 5 cohort studies showed significantly increased readmission rates in patients with dementia. On average the absolute increase above the comparison groups was from 3 to 13%. Dementia was not associated with readmission in 7 included case-control studies. Key Message: Findings suggest a small increased risk of hospital readmission in individuals with dementia. More study is needed.

scholarly journals Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

2021 ◽  
Vol 13 (2) ◽  
pp. 186-220
Author(s):  
André Santos ◽  
◽  
Érica Gonçalves ◽  
Ananda Oliveira ◽  
Douglas Lima ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Standard Of Care ◽  
P Value ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

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