Distal Technologies for Prediabetes: A Systematic Review and Meta-Analysis (Preprint)

2021 ◽  
Author(s):  
Mark Wing Loong Cheong ◽  
Chun Wie Chong ◽  
Siew Hua Gan ◽  
Lin Kooi Ong ◽  
Leong Seng Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Weight ◽  
Waist Circumference ◽  
Meta Analysis ◽  
Complex Interventions ◽  
Density Lipoprotein ◽  
Cochrane Library ◽  
Control Group ◽  
Lifestyle Interventions ◽  
Major Health Problem

BACKGROUND Prediabetes, where an individual’s glycaemic variables are significantly higher than normal but lower than the threshold for diabetes, is a major health problem. People with prediabetes experience a higher risk of developing chronic kidney disease, neuropathy, diabetic retinopathy, cardiac events, and stroke. The implementation of lifestyle-changing interventions or programs designed to monitor and adjust a prediabetic person’s lifestyle, daily activities, and diet has been demonstrated to substantially reduce the risk of developing diabetes.[4] Implementing these interventions, however, is not without its challenges. One way to overcome these challenges would be the use of distal technologies such as telehealth, mobile health, game‐based support, social platforms, patient portals, as well as wearable devices. To the best of our knowledge, no reviews have attempted to summarise the published research related to the use of distal technologies for the prevention of diabetes. OBJECTIVE The aim of this systematic review is to critically appraise studies where distal technologies have been applied in a prediabetic population. The systematic review also aimed to synthesize the evidence to determine the effectiveness of lifestyle interventions utilizing distal technologies in people with prediabetes. METHODS The systematic review was conducted on articles from database inception till 31st December 2020 within the PubMed/MEDLINE, EMBASE, SCOPUS, and The Cochrane Library databases. The databases were searched for published articles describing the use of distal technologies in prediabetes. The search terms related to digital health and prediabetes were used. The reference lists of included articles were also reviewed to identify any relevant articles that may have been missed. This study was registered with PROSPERO: CRD42020188051. Articles which met the following inclusion criteria were included: 1) the study included prediabetic individuals, 2) was a randomised controlled trial, 3) the intervention included the use of any distal technology, and 4) published in peer-reviewed journals. RESULTS The initial search identified a total of 364 articles. After the removal of duplicates and ineligible articles, 29 articles were selected for inclusion in this review. Meta-analysis of 15 of the studies showed that distal technologies was effective in reducing participants’ body weight by 1.24 kg [95% CI: -1.92, -0.56], their BMIs (MD: -0.64; -0.93 to -0.35) and waist circumference (MD: -1.27; -2.22 to -0.32), when compared to usual care/control. HbA1c levels were lowered marginally by 0.05% (95% CI: -0.09% to -0.02%) in the intervention group compared to the control group. However, distal technologies had limited impact on FPG (-0.11 mmol/l; -0.25 to 0.02), total cholesterol (-0.06 mmol/l; 95% CI: -0.14 to 0.03), low density lipoprotein (-0.04; -0.09 to 0.02), high density lipoprotein (0.03; -0.01 to 0.07) and triglyceride levels (-0.05; -0.13 to 0.02) compared to control group. CONCLUSIONS The evidence reviewed suggests that lifestyle interventions incorporating distal technologies can be effective in helping prediabetics reduce their body weight, body mass index, waist circumference, and blood glucose. The effectiveness of these interventions in improving lipid profile, blood pressure, and quality of life remains unclear. While the results are encouraging, more work is required to improve the evaluation and implementation of these complex interventions.

What Types of Exercise Are More Effective in Reducing Obesity and Blood Pressure for Middle-Aged Women? A Systematic Review With Meta-Analysis

2021 ◽  
pp. 109980042110154
Author(s):  
Seong-Hi Park ◽  
Chul-Gyu Kim
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Waist Circumference ◽  
Meta Analysis ◽  
Physical Activities ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Middle Aged

Background: A systematic review was performed to identify the types of physical activities effective as interventions in preventing metabolic syndrome in middle-aged women. Methods: Electronic databases (MEDLINE, EMBASE, the Cochrane Library, and CINAHL) served as the data sources. Cochrane’s Risk of Bias 2 was applied to assess the risk of bias of the randomized controlled trials. Meta-analyses were performed on selected studies using Review Manager 5.3. Thirty-one trials enrolling 2,202 participants were included. Results: Compared to controls, the effects of physical activity were indicated by pooled mean differences, which were −0.57 kg for body weight, −0.43 kg/m2 for body mass index, −1.63 cm for waist circumference, −4.89 mmHg for systolic blood pressure (BP), and −2.71 mmHg for diastolic BP. The effects were greater on the measurements of waist circumference and BP than on body weight and BMI. The types of physical activities were further analyzed according to sub-groups. Only aerobic exercise did not affect body weight and resistance exercise did not significantly change any results. Contrarily, combined exercises significantly reduced measurements of waist circumference and BP. Conclusion: This review can provide valuable information for research and implementation of measures to prevent metabolic syndrome in middle-aged women.

The effects of garlic supplementation on weight loss: A systematic review and meta-analysis of randomized controlled trials

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Manije Darooghegi Mofrad ◽  
Jamal Rahmani ◽  
Hamed Kord Varkaneh ◽  
Alireza Teymouri ◽  
Seyed Mohammad Mousavi
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Body Weight ◽  
Waist Circumference ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Online Databases

Abstract. Obesity is related to increase in the incidence of morbidity and mortality. Studies have suggested anti-obesity properties of garlic; however, results are inconsistent. This systematic review and meta-analysis is done to summarize the data obtained from available randomized clinical trials on the effect of garlic supplementation on body weight, Body Mass Index (BMI), and Waist Circumference (WC). The online databases of Scopus, PubMed, Google Scholar and Cochrane library were searched until March 2018 for related publications using relevant keywords. Effect sizes of eligible studies were pooled using random-effects models. Cochran’s Q-test and I2 index were used for assessing heterogeneity. We found 1241 records in our initial search, of which 13 randomized clinical trials (RCTs) with 15 treatment arms were included. Pooled analysis showed that garlic administration might significantly decrease WC (Weighed Mean Difference (WMD): −1.10 cm, 95% CI: −2.13, −0.07, P = 0.03, I2 = 0%). However, garlic intervention had no significant effect on body weight (WMD): −0.17 kg, 95% CI: −0.75 to 0.39, P = 0.54, I2 = 0%) and BMI (WMD: −0.17 kg/m2, 95% CI: −0.52, 0.16, P = 0.30, I2 = 44.5%) as compared to controls. From Subgroup analysis, it was ascertained that the effect of garlic supplementation on BMI was significant in trials with duration < 12 weeks (WMD: −0.58 kg/m2, 95% CI: −1.08, −0.08, I2 = 19.8%, P = 0.02) compared to those with higher duration (>12 weeks). The current meta-analysis results suggest that garlic supplementation seems to reduce waist circumference unlike body weight and BMI.

scholarly journals Whole grain food diet slightly reduces cardiovascular risks in obese/overweight adults: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Weihao Wang ◽  
Jianan Li ◽  
Xiaoxi Chen ◽  
Miao Yu ◽  
Qi Pan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Body Weight ◽  
Waist Circumference ◽  
Food Consumption ◽  
Meta Analysis ◽  
Control Group ◽  
Whole Grain ◽  
Cardiovascular Risks ◽  
Overweight Adults

Abstract Background: The effects of whole grain diet on cardiovascular risks in obese and overweight adults is not well established. Our goal was to conduct a systematic review and meta-analysis on the effect of whole grain diet on cardiovascular risks in obese/overweight adults. Methods: PubMed, Embase and Cochrane were systematically scanned for randomized controlled trials (RCTs), and studies were selected based on certain inclusion and exclusion criteria. The primary outcome was the effectiveness of whole grain food consumption in reducing body weight. The secondary outcomes were the effect of whole grain food consumption on cardiovascular disease (CVD) risk factors including plasma low-density lipoprotein cholesterol (LDL-C), insulin resistance index, blood pressure, body mass index (BMI), C-reactive protein (CRP), and waist circumference in obese/overweight adults. Results: Our results showed that whole grain consumption was associated with lower body weight (mean difference (MD) =-0.5, 95% confidence intervals (CI) [-0.74, 0.25], I2 = 35%, P < 0.0001) and lower CRP (MD =-0.36, 95% CI [-0.54, -0.18], I2=69%, P<0.0001), compared with the control group. However, there were no significant differences in LDL-C (MD =-0.08, 95% CI [-0.16, 0.00], I2 = 27%, P = 0.05), waist circumference (MD=-0.12, 95% CI [-0.92, 0.68], I2=44%, P=0.76), systolic blood pressure (MD=-0.11, 95% CI [-1.55, 1.33], I2=3%, P=0.88), diastolic blood pressure (MD=-0.44, 95% CI [-1.44, 0.57], I2=15%, P=0.39), and fasting glucose (MD=-0.05, 95% CI [-0.12, 0.01], I2=31%, P=0.11) between the two groups. Conclusion: This study suggests that whole grain food consumption can slightly reduce body weight and CRP in obese/overweight population.

scholarly journals Whole grain food diet slightly reduces cardiovascular risks in obese/overweight adults: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Weihao Wang ◽  
Jianan Li ◽  
Xiaoxi Chen ◽  
Miao Yu ◽  
Qi Pan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Body Weight ◽  
Waist Circumference ◽  
Food Consumption ◽  
Meta Analysis ◽  
Control Group ◽  
Whole Grain ◽  
Cardiovascular Risks ◽  
Overweight Adults

Abstract Background: The effects of whole grain diet on cardiovascular risks in obese and overweight adults is not well established. Our goal was to conduct a systematic review and meta-analysis on the effect of whole grain diet on cardiovascular risks in obese/overweight adults. Methods: PubMed, Embase and Cochrane were systematically scanned for randomized controlled trials (RCTs), and studies were selected based on certain inclusion and exclusion criteria. The primary outcome was the effectiveness of whole grain food consumption in reducing body weight. The secondary outcomes were the effect of whole grain food consumption on cardiovascular disease (CVD) risk factors including plasma low-density lipoprotein cholesterol (LDL-C), insulin resistance index, blood pressure, body mass index (BMI), C-reactive protein (CRP), and waist circumference in obese/overweight adults. Results: Our results showed that whole grain consumption was associated with lower body weight (mean difference (MD) =-0.5, 95% confidence intervals (CI) [-0.74, 0.25], I2 = 35%, P < 0.0001), lower LDL-C (MD =-0.08, 95% CI [-0.16, 0.00], I2 = 27%, P = 0.05), and lower CRP (MD =-0.36, 95% CI [-0.54, -0.18], I2=69%, P<0.0001), compared with the control group. However, there were no significant differences in waist circumference (MD=-0.12, 95% CI [-0.92, 0.68], I2=44%, P=0.76), systolic blood pressure (MD=-0.11, 95% CI [-1.55, 1.33], I2=3%, P=0.88), diastolic blood pressure (MD=-0.44, 95% CI [-1.44, 0.57], I2=15%, P=0.39), and fasting glucose (MD=-0.05, 95% CI [-0.12, 0.01], I2=31%, P=0.11) between the two groups. Conclusion: This study suggests that whole grain food consumption can slightly reduce body weight, LDL-C and CRP in obese/overweight population.

scholarly journals EXPRESS: Stroke risk following traumatic brain injury: systematic review and meta-analysis

2021 ◽  
pp. 174749302110042
Author(s):  
Grace Mary Turner ◽  
Christel McMullan ◽  
Olalekan Lee Aiyegbusi ◽  
Danai Bem ◽  
Tom Marshall ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stroke Risk ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Cochrane Library ◽  
Control Group ◽  
Large Sample Size ◽  
Hazard Ratios ◽  
Increased Risk ◽  
The Cochrane Library

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.

scholarly journals Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis

2021 ◽  
Vol 18 ◽  
pp. 147997312199456
Author(s):  
Peining Zhou ◽  
Jing Ma ◽  
Guangfa Wang
Keyword(s):  
Systematic Review ◽  
Interstitial Lung Disease ◽  
Confidence Interval ◽  
Lung Disease ◽  
Mortality Risk ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Anca Associated Vasculitis ◽  
Retrospective Cohort Studies

Several retrospectivee described the association of interstitial lung disease (ILD) and ANCA-associated vasculitis (AAV). However, the relationship between the ILD and mortality in AAV patients have not been established so far. This study aims to estimate the relevance of AAV-associated-ILD (AAV-ILD) and mortality risk by conducting a systematic review and meta-analysis.A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies. Summary estimates were derived with a random-effects model and reported as risk ratio (RR), tested for publication bias and heterogeneity. Ten retrospective cohort studies were included, comprising 526 AAV-ILD patients enrolled from 1974 to 2018. Meta-analysis yielded a pooled RR of 2.90 (95% confidence interval 1.77–4.74) for death among those with AAV-ILD compared to control group. UIP pattern was associated with an even poorer prognosis in comparison to non-UIP pattern (RR 4.36, 95% confidence interval 1.14–16.78). Sensitivity analysis suggested that the meta-RR result was not skewed by a single dominant study. ILD might be associated with a higher mortality risk in AAV patients.

scholarly journals Effect of workplace physical activity interventions on the cardio-metabolic health of working adults: systematic review and meta-analysis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Rubina Mulchandani ◽  
Ambalam M. Chandrasekaran ◽  
Roopa Shivashankar ◽  
Dimple Kondal ◽  
Anurag Agrawal ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Blood Pressure ◽  
Body Weight ◽  
Waist Circumference ◽  
Meta Analysis ◽  
Workplace Interventions ◽  
Working Adults ◽  
Reduced Body ◽  
Physical Activity Interventions

Abstract Background Adults in urban areas spend almost 77% of their waking time being inactive at workplaces, which leaves little time for physical activity. The aim of this systematic review and meta-analysis was to synthesize evidence for the effect of workplace physical activity interventions on the cardio-metabolic health markers (body weight, waist circumference, body mass index (BMI), blood pressure, lipids and blood glucose) among working adults. Methods All experimental studies up to March 2018, reporting cardio-metabolic worksite intervention outcomes among adult employees were identified from PUBMED, EMBASE, COCHRANE CENTRAL, CINAHL and PsycINFO. The Cochrane Risk of Bias tool was used to assess bias in studies. All studies were assessed qualitatively and meta-analysis was done where possible. Forest plots were generated for pooled estimates of each study outcome. Results A total of 33 studies met the eligibility criteria and 24 were included in the meta-analysis. Multi-component workplace interventions significantly reduced body weight (16 studies; mean diff: − 2.61 kg, 95% CI: − 3.89 to − 1.33) BMI (19 studies, mean diff: − 0.42 kg/m2, 95% CI: − 0.69 to − 0.15) and waist circumference (13 studies; mean diff: − 1.92 cm, 95% CI: − 3.25 to − 0.60). Reduction in blood pressure, lipids and blood glucose was not statistically significant. Conclusions Workplace interventions significantly reduced body weight, BMI and waist circumference. Non-significant results for biochemical markers could be due to them being secondary outcomes in most studies. Intervention acceptability and adherence, follow-up duration and exploring non-RCT designs are factors that need attention in future research. Prospero registration number: CRD42018094436.

scholarly journals Potential Biomarkers for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 23 (2) ◽  
pp. 602
Author(s):  
Ka Young Kim ◽  
Ki Young Shin ◽  
Keun-A Chang
Keyword(s):  
Systematic Review ◽  
Uric Acid ◽  
Cognitive Impairment ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Cochrane Library ◽  
Blood Proteins ◽  
Post Stroke

Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.

scholarly journals Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 939
Author(s):  
Jiaxin Chen ◽  
Yuangui Cai ◽  
Yicong Chen ◽  
Anthony P. Williams ◽  
Yifang Gao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Phase 1 ◽  
Cochrane Library ◽  
Categorical Variables ◽  
Control Group ◽  
Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

scholarly journals Effectiveness of Suprascapular Nerve Block in the Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yajing Hou ◽  
Yong Wang ◽  
Xiaojing Sun ◽  
Yake Lou ◽  
Ying Yu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Shoulder Pain ◽  
Nerve Block ◽  
External Rotation ◽  
Meta Analysis ◽  
Suprascapular Nerve ◽  
Cochrane Library ◽  
Control Group ◽  
Suprascapular Nerve Block ◽  
Secondary Endpoints

Purpose: We aimed to investigate the effectiveness of suprascapular nerve block (SSNB) in patients with hemiplegic shoulder pain (HSP).Background: SSNB is widely used in various shoulder pains, but whether it is effective in HSP remains unknown.Methods: PubMed, Cochrane Library, and Embase databases were searched to identify potential citations. Randomized controlled trials meeting the eligible criteria were included in our analysis. The primary endpoint was Visual Analog Scale (VAS) with a maximum value of 100 and a minimum value of 0. Secondary endpoints were passive range of motion (PROM) that pain starts, and the PROM mainly included abduction, flexion, and external rotation. In addition, the upper extremity Fugl-Meyer assessment (FMA) was also included in our secondary endpoints.Results: Eight studies with 281 patients were included in our analysis. For VAS, there was no obvious difference between SSNB group and control group regardless of the follow-up period (&lt;4 weeks or ≥4 weeks), which were −6.62 (−15.76, 2.53; p = 0.16) and 1.78 (−16.18, 19.74; p = 0.85). For shoulder function, the PROM of abduction, flexion, and external rotation was similar between groups. However, motor function indicator FMA is lower in SSNB control than that in control group, with a mean difference (and 95% CI) of −2.59 (−4.52, −0.66; p = 0.008).Conclusion: SSNB is an effective way for HSP patients.Systematic Review Registration: Registration ID: CRD42021252429.

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