Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-analysis

Abstract Objectives This systematic review and meta-analysis synthesized the evidence on the impact of demographics and comorbidities with clinical outcomes of COVID-19, including severe illness, admission to the intensive care unit (ICU), and death.MethodsThe PRISMA guidelines were followed to conduct and report this meta-analysis. The protocol is registered in PROSPERO International prospective register of systematic reviews (ID=CRD42020184440). Two authors independently searched literature from PubMed, Embase, Cochrane library and CINHAL on May 6, 2020; removed duplicates; screened titles, abstracts and full text using criteria; and extracted data from eligible articles. A random-effects model was used to estimate the summary odds ratio (OR). Variations among studies were examined using Cochrane Q and I2.ResultsOut of 4,275 articles obtained from the databases and screened, 71 studies that involved 216,843 patients were abstracted and then, where appropriate, analyzed by meta-analysis. The COVID-19 related outcomes reported were death in 26 studies, severe illness in 41 studies, and admission to ICU in 11 studies. Death was significantly correlated with hypertension (OR 2.60, 95% CI 1.95–3.25, I2 = 52.6%, n= 13 studies), cardiovascular disease (5.16, 4.10–6.22, 0.0%, 6), diabetes (2.11, 1.35–2.87, 67.4%, 12), chronic respiratory disease (2.83, 2.14–3.51, 0.0%, 9), cerebrovascular diseases (5.14, 1.08–9.19, 0.0%, 2), male sex (1.34, 1.18 – 1.50, 38.7%, 16), age older than 60 (6.09, 3.53 – 8.66, 95.5%, 6) or 65 years (3.56, 1.21 – 5.90, 18.2%, 6). Severe illness was also significantly associated with hypertension (1.70, 1.30 –2.10, 47.8%, 21), cardiovascular diseases (2.04, 1.01–3.08, 30.6%, 10), diabetes (1.65, 1.23–2.08, 24.9%, 18), male sex (1.35, 1.23 – 1.47, 0.0%, 32) and age at least 60 (4.91, 1.35 – 8.47, 0.0%, 4) or 65 (2.55,1.94 – 3.17, 24.5%, 9) years. Among hospitalized patients, the odds of admission to ICU was greater in individuals who had cardiovascular diseases (1.36,1.04–1.69, 0.0%, 4), diabetes (1.55, 1.20–1.90, 0.0%, 5) and chronic respiratory disease (1.52, 1.09–1.94, 0.0%, 5) than those who were not having these comorbidities. ConclusionsOlder age and chronic diseases increase the risk of developing severe illness, admission to ICU and death among COVID-19 patients. Special strategies are warranted to prevent SARS-CoV-2 infection and manage COVID-19 cases in those with vulnerabilities.

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Risk factors for severe illness and death in COVID-19: a systematic review and meta-analysis

10.1101/2020.12.03.20243659 ◽

2020 ◽

Author(s):

Abraham Degarege ◽

Zaeema Naveed ◽

Josiane Kabayundo ◽

David Brett-Major

Keyword(s):

Systematic Review ◽

Cardiovascular Diseases ◽

Respiratory Disease ◽

Meta Analysis ◽

Chronic Respiratory Disease ◽

Cerebrovascular Diseases ◽

Cochrane Library ◽

Severe Illness ◽

Male Sex ◽

The Impact

AbstractObjectivesThis systematic review and meta-analysis synthesized the evidence on the impact of demographics and comorbidities with clinical outcomes of COVID-19, including severe illness, admission to the intensive care unit (ICU), and death.MethodsThe PRISMA guidelines were followed to conduct and report this meta-analysis. The protocol is registered in PROSPERO International prospective register of systematic reviews (ID=CRD42020184440). Two authors independently searched literature from PubMed, Embase, Cochrane library and CINHAL on May 6, 2020; removed duplicates; screened titles, abstracts and full text using criteria; and extracted data from eligible articles. A random-effects model was used to estimate the summary odds ratio (OR). Variations among studies were examined using Cochrane Q and I2.ResultsOut of 4,275 articles obtained from the databases and screened, 71 studies that involved 216,843 patients were abstracted and then, where appropriate, analyzed by meta-analysis. The COVID-19 related outcomes reported were death in 26 studies, severe illness in 41 studies, and admission to ICU in 11 studies. Death was significantly correlated with hypertension (OR 2.60, 95% CI 1.95–3.25, I2 = 52.6%, n= 13 studies), cardiovascular disease (5.16, 4.10–6.22, 0.0%, 6), diabetes (2.11, 1.35–2.87, 67.4%, 12), chronic respiratory disease (2.83, 2.14–3.51, 0.0%, 9), cerebrovascular diseases (5.14, 1.08–9.19, 0.0%, 2), male sex (1.34, 1.18 1.50, 38.7%, 16), age older than 60 (6.09, 3.53 8.66, 95.5%, 6) or 65 years (3.56, 1.21 5.90, 18.2%, 6). Severe illness was also significantly associated with hypertension (1.70, 1.30 –2.10, 47.8%, 21), cardiovascular diseases (2.04, 1.01–3.08, 30.6%, 10), diabetes (1.65, 1.23–2.08, 24.9%, 18), male sex (1.35, 1.23 1.47, 0.0%, 32) and age at least 60 (4.91, 1.35 8.47, 0.0%, 4) or 65 (2.55,1.94 3.17, 24.5%, 9) years. Among hospitalized patients, the odds of admission to ICU was greater in individuals who had cardiovascular diseases (1.36,1.04–1.69, 0.0%, 4), diabetes (1.55, 1.20–1.90, 0.0%, 5) and chronic respiratory disease (1.52, 1.09–1.94, 0.0%, 5) than those who were not having these comorbidities.ConclusionsOlder age and chronic diseases increase the risk of developing severe illness, admission to ICU and death among COVID-19 patients. Special strategies are warranted to prevent SARS-CoV-2 infection and manage COVID-19 cases in those with vulnerabilities.

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The Impact of CKD on the Prognosis of COVID-19: A Protocol for Systematic Review and Meta-analysis

10.21203/rs.3.rs-130917/v1 ◽

2020 ◽

Author(s):

Ruiqi Liu ◽

Ruiyu Mou ◽

Xinyao Jin ◽

Kang Yang ◽

Junli Chen ◽

...

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Meta Analysis ◽

Journal Citation Report ◽

Cochrane Library ◽

Primary Study ◽

Severe Illness ◽

Study Approach ◽

Registration Number ◽

The Impact

Abstract Background: COVID-19 is a serious respiratory disease currently causing a global pandemic. However, few studies have evaluated the prognosis of chronic kidney disease (CKD) patients infected with COVID-19. Given the comorbidities evident in CKD patients, we speculate that they are more likely to be susceptible to COVID-19 infection relative to healthy individuals. However, a systematic study is necessary to confirm the relationship between these two conditions.Methods: The Wanfang, China Science Journal Citation Report (VIP database), EMBASE, CNKI, Web of Science, PubMed, and Cochrane Library databases will be reviewed to identify relevant studies. The PRISMA-P and Cochrane Handbook guidelines were used to prepare a standardized table to extract data from all relevant studies in a uniform manner. Risk and quality assessment analyses will be conducted for all included studies, with Revman 5.3 and Stata 13.0 being used for all data analyses. The primary study outcome is the assessment of whether CKD is a risk factor associated with COVID-19 infection, and to establish whether CKD increases the risk of severe illness in those infected with COVID-19. Secondary outcomes include mortality rates in CKD patients with COVID-19.Results: This study approach will synthesize extant studies into a single systematic review and meta-analysis in order to establish whether or not CKD is a risk factor associated with the development of critical COVID-19 illness, and whether CKD patients are at a higher risk of being infected by COVID-19.Conclusion: These results will provide a basis for the clinical treatment of COVID-19 in those with CKD.Systematic Review registration: CRD42020216330（PRORPERO registration number）

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Impact of Treatment for Nasal Cavity Disorders on Sleep Quality: Systematic Review and Meta-analysis

Otolaryngology ◽

10.1177/01945998211029527 ◽

2021 ◽

pp. 019459982110295

Author(s):

Jacob Fried ◽

Erick Yuen ◽

Kathy Zhang ◽

Andraia Li ◽

Nicholas R. Rowan ◽

...

Keyword(s):

Systematic Review ◽

Sleep Quality ◽

Nasal Obstruction ◽

Meta Analysis ◽

Mean Difference ◽

Cochrane Library ◽

Life Questionnaire ◽

Subjective Sleep Quality ◽

Subjective Sleep ◽

The Impact

Objective To determine the impact of treatment for patients with nasal obstruction secondary to allergic rhinitis (AR) and nasal septal deviation (NSD) on sleep quality. Data Sources Primary studies were identified though PubMed, Scopus, Cochrane Library, and Web of Science. Review Methods A systematic review was performed by querying databases for articles published through August 2020. Studies were included that reported on objective sleep parameters (apnea-hypopnea index) and sinonasal and sleep-specific patient-reported outcome measures: Rhinoconjunctivitis Quality of Life Questionnaire, Nasal Obstruction Symptom Evaluation, Epworth Sleepiness Scale (EpSS), and Pittsburgh Sleep Quality Index (PSQI). Results The database search yielded 1414 unique articles, of which 28 AR and 7 NSD studies were utilized for meta-analysis. A total of 9037 patients (8515 with AR, 522 with NSD) were identified with a mean age of 35.0 years (35.3 for AR, 34.0 for NSD). Treatment for AR and NSD significantly improved subjective sleep quality. For AR, the EpSS mean difference was −1.5 (95% CI, –2.4 to –0.5; P = .002) and for the PSQI, –1.7 (95% CI, –2.1 to –1.2; P < .00001). For NSD, the EpSS mean difference was −3.2 (95% CI, –4.2 to –2.2; P < .00001) and for the PSQI, –3.4 (95% CI, –6.1 to –0.6; P = .02). Conclusion Subjective sleep quality significantly improved following treatment for AR and NSD. There were insufficient data to demonstrate that objective metrics of sleep quality similarly improved.

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Efficacy of hydrofibre dressing following total joint arthroplasty: a meta-analysis of randomised controlled trials

Hip International ◽

10.1177/11207000211012669 ◽

2021 ◽

pp. 112070002110126

Author(s):

Raman Mundi ◽

Harman Chaudhry ◽

Seper Ekhtiari ◽

Prabjit Ajrawat ◽

Daniel M Tushinski ◽

...

Keyword(s):

Systematic Review ◽

Total Joint Arthroplasty ◽

Meta Analysis ◽

Joint Infection ◽

The United States ◽

Joint Arthroplasty ◽

Cochrane Library ◽

Controlled Trials ◽

Observable Effect ◽

The Impact

Introduction: In the United States, over 1,000,000 total joint arthroplasty (TJA) surgeries are performed annually and has been forecasted that this number will exceed 4,000,000 by the year 2030. Many different types of dressing exist for use in TJA surgery, and it is unclear if any of the newer, hydrofibre dressings are superior to traditional dressings at reducing rates of infections or improving wound healing. Thus, the aim of this systematic review and meta-analysis was to assess the impact of hydrofiber dressings on reducing complications. Methods: A systematic review and meta-analysis was performed using the online databases MEDLINE and the Cochrane Library. Randomized controlled trials (RCTs) comparing hydrofibre dressings to a standard dressing were included. Summary measures are reported as odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Our primary outcome was prosthetic joint infection (PJI). Secondary outcomes included blisters, dressing changes and wound irritation. Results: 5 RCTs were included. Hydrofibre dressing had no observable effect on PJI or wound irritation (OR 0.53; 95% CI, 0.14–1.98; p = 0.35). Hydrofibre dressings reduced the rate of blisters (OR 0.36; 95% CI, 0.14–0.90; p = 0.03) and number of dressing changes (MD -1.89; 95% CI, -2.68 to -1.11). Conclusions: In conclusion, evidence suggests hydrofibre dressings have no observable effect on PJI and wound irritation. Evidence for reduction in blisters and number of dressings is modest given wide CIs and biased trial methodologies. Use of hydrofibre dressings should be considered inconclusive for mitigating major complications in light of current best evidence.

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The Use of Seton as a Bridge to Definitive Ligation of the Intersphincteric Fistula Tract Procedure for Fistula-in-ano: A Systematic Review and Meta-analysis

Journal of Coloproctology ◽

10.1055/s-0041-1730039 ◽

2021 ◽

Author(s):

Carlos Placer-Galán ◽

Jose Mª Enriquez-Navascués ◽

Tania Pastor-Bonel ◽

Ignacio Aguirre-Allende ◽

Yolanda Saralegui-Ansorena

Keyword(s):

Systematic Review ◽

Anal Fistula ◽

Meta Analysis ◽

Fistula Tract ◽

Cochrane Library ◽

Fistula In Ano ◽

Intersphincteric Fistula ◽

The Impact ◽

Seton Placement ◽

Primary Healing

Abstract Background There is still controversy over the usefulness of seton placement prior to the ligation of the intersphincteric fistula tract (LIFT) surgery in the management of anal fistula. Objective To evaluate the impact of preoperative seton placement on the outcomes of LIFT surgery for the management of fistula-in-ano. Design systematic review and meta-analysis. Data Sources A search was performed on the MEDLINE (PubMed), EMBASE, Scopus, Web of Science, Cochrane Library and Google Scholar databases. Study Selection Original studies without language restriction reporting the primary healing rates with and without seton placement as a bridge to definitive LIFT surgery were included. Intervention The intervention assessed was the LIFT with and without prior seton placement. Main Outcome Measures The main outcome was defined as the primary healing rate with and without the use of seton as a bridge to definitive LIFT surgery. Results Ten studies met the criteria for systematic review, all retrospective, with a pooled study population of 772 patients. There were no significant differences in the percentages of recurrence between patients with and without seton placement (odds ratio [OR] 1.02; 95% confidence interval [CI] 0.73–1.43: p = 0.35). The I2 value was 9%, which shows the homogeneity of the results among the analyzed studies. The 10 included studies demonstrated a weighted average overall recurrence of 38% (interquartile range [IQR] 27–42.7%), recurrence with the use of seton was 40% (IQR 26.6–51.2%), and without its use, the recurrence rate was 51.3% (IQR 31.3–51.3%) Limitations The levels of evidence found in the available literature were relatively fair, as indicated after qualitative evaluation using the Newcastle-Ottawa scale and the Attitude Heading Reference System (AHRS) evidence levels. Conclusions Our meta-analysis suggests that the placement of seton as a bridge treatment prior to LIFT surgery does not significantly improve long-term anal fistula healing outcomes. Ligation of the intersphincteric fistula tract surgery can be performed safely and effectively with no previous seton placement.International prospective register of systematic reviews—PROSPERO registration number: CDR42020149173.

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Risk of nodal disease in patients with MRI-detected extramural vascular invasion in rectal cancer: a systematic review and meta-analysis

Tumori Journal ◽

10.1177/0300891620975867 ◽

2020 ◽

pp. 030089162097586

Author(s):

Pratik Tripathi ◽

Zhen Li ◽

Yaqi Shen ◽

Xuemei Hu ◽

Daoyu Hu

Keyword(s):

Systematic Review ◽

Rectal Cancer ◽

Lymph Node ◽

Vascular Invasion ◽

Literature Search ◽

Meta Analysis ◽

Adjuvant Chemoradiotherapy ◽

Cochrane Library ◽

Nodal Disease ◽

The Impact

Background: The impact of magnetic resonance imaging–detected extramural vascular invasion (mrEMVI) in distant metastasis is well known but its correlation with prevalence of lymph node metastasis is less studied. The aim of this systematic review and meta-analysis was to assess the prevalence of nodal disease in mrEMVI–positive and negative cases in rectal cancer. Methods: Following guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic literature search in PubMed, Web of Science, Cochrane Library, and EMBase was carried out to identify relevant studies published up to May 2019. Results: Our literature search generated 10 studies (863 and 1212 mrEMVI–positive and negative patients, respectively). The two groups (mrEMVI–positive and negative) were significantly different in terms of nodal disease status (odds ratio [OR] 3.15; 95% confidence interval [CI] 2.12–4.67; p < 0.001). The prevalence of nodal disease was 75.90% vs 52.56% in the positive mrEMVI vs negative mrEMVI group, respectively ( p < 0.001). The prevalence of positive lymph node in positive mrEMVI patients treated with neoadjuvant/adjuvant chemoradiotherapy (nCRT/CRT) (OR 2.47; 95% CI 1.65–3.69; p < 0.001) was less compared with the patients who underwent surgery alone (OR 6.25; 95% CI 3.74–10.44; p < 0.001). Conclusion: The probability of positive lymph nodes in cases of positive mrEMVI is distinctly greater compared with negative cases in rectal cancer. Positive mrEMVI indicates risk of nodal disease prevalence increased by threefold in rectal cancer.

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Effects of exercise training on physical and psychosocial health in children with chronic respiratory disease: a systematic review and meta-analysis

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2018-000409 ◽

2018 ◽

Vol 4 (1) ◽

pp. e000409 ◽

Cited By ~ 14

Author(s):

Barbara Joschtel ◽

Sjaan R Gomersall ◽

Sean Tweedy ◽

Helen Petsky ◽

Anne B Chang ◽

...

Keyword(s):

Systematic Review ◽

Lung Function ◽

Exercise Training ◽

Respiratory Disease ◽

Effect Size ◽

Meta Analysis ◽

Chronic Respiratory Disease ◽

Cardiovascular Fitness ◽

Standard Mean Difference ◽

Children With Asthma

IntroductionChronic disease in children is increasing, including the prevalence of chronic respiratory diseases such as asthma, cystic fibrosis (CF), bronchiectasis and bronchopulmonary dysplasia (BPD). The aim of this systematic review and meta-analysis was to evaluate the effects of exercise training on health outcomes in children with chronic respiratory disease.MethodFive databases were searched for randomised controlled trials investigating the effects of exercise training on children with chronic respiratory disease. Following the PRISMA guidelines, eligible studies were identified and data were extracted. A meta-analysis was conducted for the outcomes cardiovascular fitness, lung function and quality of life (QoL).ResultsThe initial search returned 3688 papers. Twenty-seven (17 in children with asthma, 10 in children with CF) were included in the systematic review and 24 of these were included in the meta-analysis. No studies were identified in children with bronchiectasis or BPD. Included papers had a total of 1009 participants aged 8–20 years. In addition to cardiovascular fitness, lung function and QoL, studies also assessed pulmonary function, respiratory muscle strength, muscular strength and inflammation. Meta-analysis showed a large significant effect size in favour of exercise for cardiovascular fitness (peak VO2) (standard mean difference (SMD)=1.16, 95% CI 0.61 to 1.70) and QoL (SMD=1.27, 95% CI 0.72 to 1.82) as well as a small, non-significant effect size for lung function (FEV1) (SMD=0.02, 95% CI -0.38 to 0.42).ConclusionExercise training significantly improves cardiovascular fitness and QoL in children with asthma and CF. Further research is needed, particularly in children with bronchiectasis and BPD.

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Impact of eating disorders on paid or unpaid work participation and performance: a systematic review and meta-analysis protocol

Journal of Eating Disorders ◽

10.1186/s40337-021-00525-2 ◽

2022 ◽

Vol 10 (1) ◽

Author(s):

Fatima Safi ◽

Anna M. Aniserowicz ◽

Heather Colquhoun ◽

Jill Stier ◽

Behdin Nowrouzi-Kia

Keyword(s):

Systematic Review ◽

Eating Disorders ◽

Meta Analysis ◽

Experimental Studies ◽

Work Participation ◽

Unpaid Work ◽

Cochrane Library ◽

And Performance ◽

The Impact

Abstract Background Eating disorders (ED) can reduce quality of life by limiting participation and performance in social and occupational roles, including paid or unpaid work. The association between ED pathologies and work participation and performance must be well understood to strengthen vocational rehabilitation programmes and prevent occupational disruptions in the ED population. The aims of this study are: (1) to examine the degree of association between ED pathologies and work participation and performance in 15-year-olds and older; (2) to highlight the specific ED symptoms that are most correlated with changes in work performance and participation; (3) to compile the most common metrics and assessments used to measure work participation and performance with ED. Methods Medline, Embase, CINAHL, Web of Science, PsycINFO, and Cochrane Library will be searched for observational and experimental studies that meet the following criteria: (1) a clinical sample of typical or atypical ED; (2) paid or unpaid employment or training; (3) an association between ED pathologies and work participation or performance. Unpublished data will also be examined. Title and abstract, and full-text screening will be conducted in duplicate. Risk of bias and quality of evidence assessments will be completed. A random-effect meta-analysis will be performed. Discussion This synthesis can clarify knowledge and gaps around the impact of ED on work functioning, thereby allowing better evaluation, improvements and development of current workplace assessments, interventions, and policies. Trial registration The registration number for this systematic review on PROSPERO is CRD42021255055.

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Effects of mouth breathing on facial skeletal development and malocclusion in children: A systematic review and meta-analysis.

10.21203/rs.3.rs-28100/v1 ◽

2020 ◽

Author(s):

Ziyi Zhao ◽

Leilei Zheng ◽

Xiaoya Huang ◽

Caiyu Li ◽

Jing Liu ◽

...

Keyword(s):

Systematic Review ◽

Skeletal Development ◽

Meta Analysis ◽

Mouth Breathing ◽

Occlusal Plane ◽

Cochrane Library ◽

Nasal Breathing ◽

Anterior Teeth ◽

Newcastle Ottawa Scale ◽

The Impact

Abstract BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Methodological quality assessments of the selected articles were performed using the Newcastle-Ottawa Scale. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 7 studies (387 mouth-breathing subjects and 433 nasal-breathing controls) were included in the final quantitative synthesis; they were all high-quality. The included indicators were SNA (p>0.050), ANS-PNS (p>0.050), 1.NB (p>0.050), MP-H (p>0.050), FMA (p>0.050), SNB (MD: -1.99, P <0.0001), ANB (MD: 0.95, P = 0.0005), SN-OP (MD: 3.20, P < 0.0001), SNGoGn (MD: 4.34, P < 0.0001), 1-NA (MD: 0.72, P = 0.004), 1. NA (MD: 1.98, P = 0.020), 1-NB (MD: 1.06, P < 0.0001), SPAS (MD: -5.23, P < 0.0001), PAS (MD: -2.11, P < 0.0001), and C3-H (MD: -1.34, P < 0.0001). CONCLUSIONS: The results showed that mouth breathing can cause underdevelopment of the mandible. The mandible rotated backward and downward, and the occlusal plane was steep. However, there was little effect on the maxilla. In addition, mouth breathing presented a tendency of lip inclination of the upper and lower anterior teeth. Airway stenosis was common in mouth-breathing children. TRIAL REGISTRATION: [email protected]; registration number CRD42019129198 KEYWORDS: Mouth breathing; Facial skeletal development; Children; Systematic review, Meta-analysis.

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"Effectiveness of Robotics Intervention in Education for Children and Healthcare of Elderly People: A Systematic Review and Meta-Analysis Protocol" (Preprint)

10.2196/preprints.32942 ◽

2021 ◽

Author(s):

Ramesh Athe ◽

Vidushi Varma ◽

Shivendra Pandey ◽

Ayush Gupta ◽

Sravanthi Chaitanya

Keyword(s):

Systematic Review ◽

Elder Care ◽

Meta Analysis ◽

Educational Institution ◽

Humanoid Robots ◽

Outcome Data ◽

Population Characteristics ◽

Cochrane Library ◽

Test Procedures ◽

The Impact

UNSTRUCTURED A systematic review will be carried out to examine the use of robots in early childhood and lower-level education, elder care, and learning/teaching in an educational institution(s). Present study to critically review the currently available evidence of studies carried out and look at the impact of humanoid robots on children, elder care, and education. Four major factors will be considered – the type of studies carried on the influence of robots on children’s behavior and growth, elder care, the understanding of stakeholders (parents, children, and educators) on educational robots, and finally, the reactions of the children and elderly population on robot design or presence. This review will reveal the validating of their use of robots including experimental and non-experimental trials. The steps in this process will be conducted according to the PRISMA-P (Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocols) guidelines for meta-analysis. A comprehensive review of the literature search from Medline, the Cochrane Library, Scopus, PubMed, ProQuest, and secondary references will be performed from inception to April 15, 2021. Analyses will be done to calculate summary estimates on awareness indicators and test procedures by using fixed/random-effects models. Meta-regression and covariate analyses will be performed to explore the influence of confounders on the net pooled effect. Titles and abstracts will be assessed by three independent reviewers for potential relevance. Using study-specific data forms, predetermined data will be extracted for each study. Data extracted will include: 1) study characteristics, 2) study design, 3) population characteristics, 4) details of the comparison group(s), 5) awareness indicators, 6) skills development, 7) progressive, 8) outcome data, and 9) Study year. Other classifications to be considered are a type of skill and specific age.

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