Impact of COVID-19 on clinical trials and clinical research: A systematic review

Background: The World Health Organization has reported more than 31,186,000 confirmed cases of coronavirus disease-19 (COVID-19), including 962,343 deaths, worldwide as on September 21, 2020. The current COVID-19 pandemic is affecting clinical research activities in most parts of the world. The focus on developing a vaccine for SARS-CoV-2 and the treatment of COVID-19 is, in fact, disrupting many upcoming and/or ongoing clinical trials on other diseases around the globe. On March 18, 2020, the United States Food and Drug Administration (FDA) issued an updated guideline for the conduct of clinical trials during the current health emergency situation. The potential challenges, such as social distancing and quarantines, result in study participants’ inaccessibility and trial personnel for in-person scheduled study visits and/or follow-up. Due to the sudden onset and wide-spread impact of COVID-19, its influence on the management of clinical trials and research necessitates urgent attention. Therefore, our systematic review of the literature aims to assess the impact of the COVID-19 pandemic on the conduction of clinical trials and research. The search for the relevant articles for review included the keywords "COVID-19” AND "clinical trial" in PubMed, MEDLINE, Embase, Google scholar and Google electronic databases. Key findings include: delaying subject enrollment and operational gaps in most ongoing clinical trials, which in turn has a negative impact on trial programmes and data integrity. Globally, most sites conducting clinical trials other than COVID-19 are experiencing a delay in timelines and a complete halt of operations in lieu of this pandemic, thus affecting clinical research outcomes

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers. © 202

Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis

Background: Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. Methods: We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian�Laird�s random-effects model. Results: Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95 CI: � 0.51, � 0.02; I2 = 52.7), TG (SMD: -0.22; 95 CI: � 0.43, � 0.02; I2 = 36.0) and Malondialdehyde (MDA) levels (SMD: -0.91; 95 CI: � 1.29, � 0.54; I2 = 00.0) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95 CI: 0.27, 0.90; I2 = 00.0) and Glutathione peroxidase (GPx) (SMD: 0.50; 95 CI: 0.14, 0.86; I2 = 00.0) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field. © 2021, The Author(s)

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Effect of soy products and isoflavones on oxidative stress parameters: A systematic review and meta-analysis of randomized controlled trials

Soy products and isoflavones intake have been shown to exert antioxidant effects. There are several randomized control trials (RCTs) that evaluated the effect of soy products intake on oxidative stress (OS) parameters. The aim of the present systematic review and meta-analysis was to summarize the results of RCTs evaluating the effect of soy products and isoflavones intake on OS parameters. Randomized trials that assessed the effect of soy products and isoflavones intake on OS parameters in adults were identified through searching in electronic databases: Cochrane clinical trial center, Embase, PubMed, Scopus, and Web of Sciences up to April 2020. Random effects model was used to calculate the effects sizes of soy intake on OS parameters. Twenty-four trials with 1,852 participants were eligible and were included in the meta-analysis which measured OS parameters. Soy intake compared to control group significantly reduced MDA levels (SMD: �0.53; 95 CI: �0.86, �0.19; I2 = 88.3), increased GSH levels (SMD: 0.51; 95 CI: 0.13, 0.88; I2 = 72.4), SOD activity (SMD: 0.53; 95 CI: 0.08, 0.99; I2 = 84.1), TAC (SMD: 0.54; 95 CI: 0.27, 0.82; I2 = 49.3) and TRAP (SMD: 1.74; 95 CI: 0.82, 2.65; I2 = 81.3) significantly compared to control group. Soy products and isoflavones intake are effective in improving OS parameters in adults compared with controls; thus, it could be a valuable advise to control OS progress in chronic diseases. © 2020 Elsevier Lt

Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis

Aims: Several health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c) vs. control. Data synthesis: We pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: �0.07; 95% CI: �0.20, 0.07; I2 = 0.0%), insulin (SMD: �0.32; 95% CI: �0.70, 0.06; I2 = 38.0%), and HOMA-IR (SMD: �0.32; 95% CI: �0.75, 0.10; I2 = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results. Conclusion: Although EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters. © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II Universit

Effect of DASH diet on oxidative stress parameters: A systematic review and meta-analysis of randomized clinical trials

Background and aims: Oxidative stress (OS) is one of the main risk factors for several chronic diseases. The Dietary Approaches to Stop Hypertension (DASH) contain many antioxidants and may contribute to managing OS. Objective: To perform a systematic review and meta-analysis to examine the impacts of the DASH diet on OS parameters. Methods: A comprehensive electronic search in MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials was performed through September 2020 to find related studies evaluating the impact of the DASH diet on OS parameters. Standardized mean differences were pooled using random-effects meta-analysis. Results: Eight studies with a total of 317 subjects met our inclusion criteria. Four studies included in meta-analysis model with 200 participants (100 in treatment and 100 in control group). The DASH diet was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD: �0.53; 95 CI: �0.89, �0.16; I2 = 42.1), and a significant increase in glutathione (GSH) (SMD: 0.83; 95 CI: 0.36, 1.03; I2 = 42.1). Meta-analysis found no statistically significant effect of DASH diet on nitric oxide (NO) (SMD: �1.40; 95 CI: �0.12, 1.93; I2 = 92.6) or total antioxidant capacity (TAC) levels (SMD: 0.95; 95 CI: �0.10, 1.99; I2 = 87.6). Conclusion: Our results demonstrated that a DASH diet could significantly increase GSH and decrease MDA levels. Furthermore, there is a trend to improve TAC, NO, and f2-isoprostanes by the adherence to the DASH diet. However, long-term, large sample size and well-designed randomized clinical trials are still needed to draw concrete conclusions about DASH diet's effects on OS parameters. © 202