scholarly journals A Systematic Review and Meta-Analysis of Combined Antibiotic Spacer with Ilizarov Methods in the Treatment of Infected Nonunion of Tibia

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhibo Deng ◽  
Yuexi Mu ◽  
Xianding Sun ◽  
Yongqing Xu ◽  
Fubing Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
High Rate ◽  
Sensitivity Analyses ◽  
Fixation Index ◽  
Cochrane Library ◽  
Infected Nonunion ◽  
Newcastle Ottawa Scale ◽  
Antibiotic Spacer ◽  
Infection Recurrence

Background. The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of infected nonunion of tibia and to perform meta-analysis of bone results and infection recurrence to assess the efficacy of an antibiotic spacer combined with Ilizarov methods. Methods. The MEDLINE, Embase, Cochrane Library, CNKI, and CBM (Chinese Biological Medicine) databases were searched for articles published between January 2000 and July 2020. Assessment of study quality was performed using a modified version of the Newcastle-Ottawa scale. Effect size and 95% confidence intervals were calculated for the main outcome. Heterogeneity was assessed. Fixed-effect modeling and Stata version 15.1 were used to analyze the data. Sensitivity analyses were conducted with the evidence of heterogeneity. Results. 11 studies involving 210 patients with infected nonunion of tibia were finally included in our meta-analysis. Bone results and infection recurrence were analyzed based on the single-arm meta-analysis. The average of external fixation index (EFI) was 46.88 days/cm in all studies included. The excellent rate in bone results and the rate of infection recurrence was 65% (95% CI: [0.22, 0.97], I 2 = 0.0 % , P = 0.932 ) and 6.99% (95% CI: [0.052, 0.325], I 2 = 0.0 % , P = 1.000 ) in patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods. Conclusions. Our meta-analysis revealed that the patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods had a high rate of excellent bone results and a low rate of infection recurrence. Therefore, combining the antibiotic spacer with Ilizarov methods may be an applicable choice for repairing and reconstructing infected nonunion of tibia.

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

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.

scholarly journals Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries: a systematic review and meta-analysis

2020 ◽  
Vol 4 (1) ◽  
pp. e000662 ◽  
Author(s):  
Nick Brown ◽  
Antti Juhani Kukka ◽  
Andreas Mårtensson
Keyword(s):  
Systematic Review ◽  
Treatment Failure ◽  
Low Income ◽  
Meta Analysis ◽  
Severe Pneumonia ◽  
Risk Of Bias ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Middle Income ◽  
Middle Income Countries

BackgroundDespite advances in vaccination and case management, pneumonia remains the single largest contributor to early child mortality worldwide. Zinc has immune-enhancing properties, but its role in adjunctive treatment of pneumonia in low-income and middle-income countries (LMICs) is controversial and research still active.MethodsSystematic review and meta-analysis of randomised controlled trials of zinc and placebo in pneumonia in children aged 2 to 60 months in LMICs. Databases included MEDLINE, the Cochrane Library, EMBASE, LILACS, SciELO, the WHO portal, Scopus, Google Scholar and ClinicalTrials.gov. Inclusion criteria included accepted signs of pneumonia and clear measure of outcome. Risk of bias was independently assessed by two authors. ORs with 95% CI were used for calculating the pooled estimate of dichotomous outcomes including treatment failure and mortality. Time to recovery was expressed as HRs. Sensitivity analyses considering risk of bias and subgroup analyses for pneumonia severity were performed.ResultsWe identified 11 trials published between 2004 and 2019 fulfilling the a priori defined criteria, 7 from South Asia and 3 from Africa and 1 from South America. Proportional treatment failure was comparable in both zinc and placebo groups when analysed for all patients (OR 0.95 (95% CI 0.80 to 1.14)) and only for those with severe pneumonia (OR 0.93 (95% CI 0.75 to 1.14)). No difference was seen in mortality between zinc and placebo groups (OR 0.64 (95% CI 0.31 to 1.31)). Time to recovery from severe pneumonia did not differ between the treatment and control groups for patients with severe pneumonia (HR 1.01 (95% CI 0.89 to 1.14)). Removal of four studies with high risk of bias made no difference to the conclusions.ConclusionThere is no evidence that adjunctive zinc treatment improves recovery from pneumonia in children in LMICs.Trial registration numberCRD42019141602.

scholarly journals Is dezocine effective and safe in preventing opioids-induced cough during general anaesthesia induction? A protocol for systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e035691
Author(s):  
Li-xian He ◽  
Ken Shao ◽  
Jie Ma ◽  
Yuan-yuan Zhao ◽  
Yun-tai Yao
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Sensitivity Analyses ◽  
Systemic Review ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Anaesthesia Induction

IntroductionCough is often observed when administrating a bolus of opioids. Opioid-induced cough (OIC) is mostly transient, benign and self-limiting, but could be associated with adverse effects. Numerous pharmacological and non-pharmacological interventions have been used to manage OIC with controversial efficacy and safety. Recent studies suggested that, pretreatment of intravenous dezocine (DZC) could completely suppress OIC during anaesthesia induction. To address this knowledge lack, we will perform a systemic review and meta-analysis to evaluate the efficacy of DZC on OIC and possible complications. We provide here a protocol that will outline the methods and analyses planned for the systematic review.MethodsPubMed, Embase, Cochrane Library, Web of Science as well as Chinese BioMedical Literature & Retrieval System (SinoMed), China National Knowledge Infrastructure, Wanfang Data and VIP Data will be searched from 1978 to 31 December 2019 to identify all randomised controlled trials comparing DZC with placebo on the incidence and severity of OIC. Primary outcomes of interest include the incidence and severity of OIC. Secondary outcomes of interest include possible complications or adverse effects of DZC. Two authors will independently extract relevant variables and outcome data. For continuous variables, treatment effects will be calculated as weighted mean difference and 95% CI. For dichotomous data, treatment effects will be calculated as OR and 95% CI. Each outcome will be tested for heterogeneity, and randomised-effects or fixed-effects model will be used in the presence or absence of significant heterogeneity. Sensitivity analyses will be done by examining the influence of statistical model and individual trial(s) on estimated treatment effects. Publication bias will be explored through visual inspection of funnel plots of the outcomes. Statistical significance will be defined as p<0.05.Ethics and disseminationThis study is a protocol of meta-analysis of previously published literatures, ethical approval was not necessary according to the Ethical Committee of Fuwai Hospital. The study will be submitted to a peer-reviewed journal and disseminated via research presentations.PROSPERO registration numberCRD42019141255.

scholarly journals Predictors of Postoperative Delirium in Elderly Patients Following Total Hip and Knee Arthroplasty: A Systematic Review and Meta‑Analysis

2021 ◽  
Author(s):  
Zhou Quan ◽  
Zhou Xin-feng ◽  
Zhang Jun-xin ◽  
Tian Xin ◽  
Yang Hui-lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Elderly Patients ◽  
Postoperative Delirium ◽  
Meta Analysis ◽  
Postoperative Recovery ◽  
Cochrane Library ◽  
Primary Analysis ◽  
Hip And Knee Arthroplasty ◽  
Newcastle Ottawa Scale ◽  
Potential Factors

Abstract Background: Postoperative delirium (POD) is widely reported as a very common postoperative complication following total joint arthroplasty (TJA) of the hip and knee in elderly patients, leading to a variety of adverse effects. We sought to investigate predictors of delirium after TJA.Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to May 2020 for studies examining POD following TJA in elderly patients. Pooled odds ratio (OR) and mean difference (MD) of those who experienced delirium compared to those who did not were calculated for each variable. The Newcastle-Ottawa Scale (NOS) was used for the study quality evaluation. Results: Fifteen studies with 31 potential factors were included in the meta-analysis. In the primary analysis, 9 factors were associated with POD, comprising advanced age (MD 3.81; 95% confidence interval (CI) 1.80–5.83), dementia (OR 24.85; 95% CI 7.26–85.02), hypertension (OR 2.26; 95% CI 1.31–3.89), diabetes (OR 2.02; 95% CI 1.15–3.55), stroke (OR 14.61; 95% CI 5.26–40.55), psychiatric illness (OR 2.72; 95% CI 1.45–5.08), use of sedative-hypnotics (OR 6.42; 95% CI 2.53–16.27), lower preoperative levels of hemoglobin (MD −0.56; 95% CI −0.89–−0.22), and lower preoperative mini-mental state examination score (MD −0.40; 95% CI −0.69–−0.12). Twelve studies were included in the systematic review, of which 24 factors were additionally correlated with POD using single studies.Conclusions: We identified predictors of POD in elderly patients following TJA. These findings may be used to identify patients with a high risk of delirium who are most likely to benefit from postoperative recovery.

scholarly journals Can Smartphone Apps Increase Physical Activity? Systematic Review and Meta-Analysis (Preprint)

2018 ◽  
Author(s):  
Amelia Romeo ◽  
Sarah Edney ◽  
Ronald Plotnikoff ◽  
Rachel Curtis ◽  
Jillian Ryan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Meta Analysis ◽  
Target Population ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Smartphone Apps ◽  
Intervention Effects ◽  
Randomized Controlled ◽  
Steps Per Day

BACKGROUND Smartphone apps are a promising tool for delivering accessible and appealing physical activity interventions. Given the large growth of research in this field, there are now enough studies using the “gold standard” of experimental design—the randomized controlled trial design—and employing objective measurements of physical activity, to support a meta-analysis of these scientifically rigorous studies. OBJECTIVE This systematic review and meta-analysis aimed to determine the effectiveness of smartphone apps for increasing objectively measured physical activity in adults. METHODS A total of 7 electronic databases (EMBASE, EmCare, MEDLINE, Scopus, Sport Discus, The Cochrane Library, and Web of Science) were searched from 2007 to January 2018. Following the Population, Intervention, Comparator, Outcome and Study Design format, studies were eligible if they were randomized controlled trials involving adults, used a smartphone app as the primary or sole component of the physical activity intervention, used a no- or minimal-intervention control condition, and measured objective physical activity either in the form of moderate-to-vigorous physical activity minutes or steps. Study quality was assessed using a 25-item tool based on the Consolidated Standards of Reporting Trials checklist. A meta-analysis of study effects was conducted using a random effects model approach. Sensitivity analyses were conducted to examine whether intervention effectiveness differed on the basis of intervention length, target behavior (physical activity alone vs physical activity in combination with other health behaviors), or target population (general adult population vs specific health populations). RESULTS Following removal of duplicates, a total of 6170 studies were identified from the original database searches. Of these, 9 studies, involving a total of 1740 participants, met eligibility criteria. Of these, 6 studies could be included in a meta-analysis of the effects of physical activity apps on steps per day. In comparison with the control conditions, smartphone apps produced a nonsignificant (P=.19) increase in participants’ average steps per day, with a mean difference of 476.75 steps per day (95% CI −229.57 to 1183.07) between groups. Sensitivity analyses suggested that physical activity programs with a duration of less than 3 months were more effective than apps evaluated across more than 3 months (P=.01), and that physical activity apps that targeted physical activity in isolation were more effective than apps that targeted physical activity in combination with diet (P=.04). Physical activity app effectiveness did not appear to differ on the basis of target population. CONCLUSIONS This meta-analysis provides modest evidence supporting the effectiveness of smartphone apps to increase physical activity. To date, apps have been most effective in the short term (eg, up to 3 months). Future research is needed to understand the time course of intervention effects and to investigate strategies to sustain intervention effects over time.

scholarly journals Global Incidence of Necrotizing Enterocolitis: a Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Amer Alsaied ◽  
Nazmul Islam ◽  
Lukman Thalib
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Publication Bias ◽  
Necrotizing Enterocolitis ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Vlbw Infants ◽  
Funnel Plots ◽  
Substantial Heterogeneity

Abstract Background: Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW).Methods: The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Data were extracted from the selected papers included incidence of NEC cases and size of population at risk, author and publication details, follow up period covered by the study, location and setting of the study and whether it was VLBW infants or preterm infants. Additionally, risk of bias assessment of the included studies were carried out using a validated tool. Bias adjusted Quality Effect Model (QEM) were used to pool the estimates. In the presence of substantial heterogeneity, Random Effect Models (REM) were used as an additionally sensitivity analyses. The heterogeneity between studies were evaluated using the Cochrane Q statistics and Higgin’s I2 value. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias. Results: A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The pooled estimate of the global incidence of NEC was 6.0% (95% CI: 4.0%-9.0%). There were substantial heterogeneity (I2 = 100%) between studies. Funnel plots showed no evidence of publication bias.Conclusion: Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted.

scholarly journals The Relationship Between Gambling Problems and the Five-Factor Model of Personality: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Rune Strømme ◽  
Karine Holthe Børstad ◽  
Andrea Eftang Rø ◽  
Eilin Kristine Erevik ◽  
Dominic Sagoe ◽  
...  
Keyword(s):  
Systematic Review ◽  
Personality Traits ◽  
Factor Model ◽  
Five Factor Model ◽  
Meta Analysis ◽  
Drop Out ◽  
Cochrane Library ◽  
Newcastle Ottawa Scale ◽  
Trim And Fill ◽  
Meta Analyses

Objectives: The aim of the present meta-analysis was to synthesize results from the association between problem gambling (PG) and dimensions of the five factor model of personality and to identify potential moderators (gambling diagnosis: yes/no, comorbidity: yes/no and trait assessment: four or fewer items vs. five items or more) of these associations in meta-regressions.Methods: Searches were conducted in six databases; Medline, Web of Science, PsychInfo, Google Scholar, OpenGrey, and Cochrane Library (conducted on February, 22, 2021). Included studies: (1) reported a relationship between PG and at least one of the personality traits in the five-factor model, (2) contained information of zero-order correlations or sufficient data for such calculations, and (3) were original articles published in any European language. Case-studies, qualitative studies, and reviews were excluded. All articles were independently screened by two authors. Final agreement was reached through discussion or by consulting a third author. Risk of bias of the included studies was assessed by the Newcastle-Ottawa Scale. Data were synthesized using a random effects model.Results: In total 28 studies, comprising 20,587 participants, were included. The correlations between PG and the traits were as follows: Neuroticism: 0.273 (95% CI = 0.182, 0.358), conscientiousness −0.296 (95% CI = −0.400, −0.185), agreeableness −0.163 (95% CI = −0.223, −0.101), openness −0.219 (95% CI = −0.308, −0.127), and extroversion −0.083 (95% CI = −0.120, −0.046). For all meta-analyses the between study heterogeneity was significant. Presence of gambling diagnosis was the only moderator that significantly explained between-study variance showing a more negative correlation to extroversion when participants had a gambling diagnosis compared to when this was not the case.Discussion: The results indicated some publication bias. Correcting for this by a trim-and-fill procedure showed however that the findings were consistent. Clinicians and researchers should be aware of the associations between personality traits and PG. Previous studies have for example showed neuroticism to be related to treatment relapse, low scores on conscientiousness to predict treatment drop-out and agreeableness to reduce risk of treatment drop-out.Systematic Review Registration: PROSPERO (CRD42021237225).

scholarly journals Association Between Irritable Bowel Syndrome and Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
XinYue Zhang ◽  
Zhen Svn ◽  
MengSi Liv ◽  
Yan Yang ◽  
Rui Zeng ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Irritable Bowel Syndrome ◽  
Meta Analysis ◽  
Underlying Mechanism ◽  
Cochrane Library ◽  
Bowel Diseases ◽  
Newcastle Ottawa Scale ◽  
Irritable Bowel

Background: Parkinson's disease (PD) and irritable bowel syndrome (IBS) are respectively one of the most common neurodegenerative diseases and functional bowel diseases in the world. Recent studies suggest that patients with IBS seem to have a higher risk of PD, which conflicts with the result of previous meta-analysis. Therefore, the purpose of this systematic review is to evaluate all available evidence, in order to clarify the association between PD and IBS.Methods: Two reviewers independently searched the PubMed, Embase, Web of Science, and Cochrane library on April 25, 2021 to identify all records that explore the association between IBS and PD. All reports that clearly define PD and IBS and analyze the relationship between the two were included. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies.Results: Five studies from four articles involving 2,044,110 subjects were included in this analysis. The pooled results demonstrated a significant association between PD and IBS (1.48; 95% CI: 1.35–1.62, P &lt; 0.001), with subtle heterogeneity (I2 = 0.0%, p = 0.585). The association was observed across genders and increased with age. However, the available evidence cannot allow a reliable analysis of the causal relationship between IBS and PD.Conclusion: This study demonstrates a higher risk of PD among subjects with IBS. Future studies are required to further clarify the causation and underlying mechanism of the association.

Depression and Anxiety in Patients with Primary Biliary Cholangitis: A Systematic Review and Meta-analysis (Preprint)

2020 ◽  
Author(s):  
Xiao Shi ◽  
Qi Chen ◽  
Fen Wang
Keyword(s):  
Systematic Review ◽  
Psychiatric Symptoms ◽  
Meta Analysis ◽  
Depression Scale ◽  
Cochrane Library ◽  
Primary Biliary Cholangitis ◽  
Depression And Anxiety ◽  
Pooled Prevalence ◽  
Newcastle Ottawa Scale ◽  
Underlying Mechanisms

BACKGROUND Previous studies have implicated the co-existence of psychological disorders and primary biliary cholangitis (PBC). However, the exact magnitude of the prevalence and related score of depression and anxiety in patients with PBC are still unclear. OBJECTIVE We aimed to assess the prevalence and Hospital Anxiety and Depression Scale (HADS) scores for depression and anxiety in patients with PBC. METHODS A comprehensive search of studies published before June 10, 2020 was performed in databases of PUBMED, EMBASE, Cochrane Library and Web of Science. Methodological quality was assessed based on the Newcastle - Ottawa Scale (NOS) tool. RESULTS Twelve studies were identified, representing 933 patients with PBC. Pooled prevalence estimates were 27.59% (95% CI 16.75%-38.43%) for depression and 19.87% (95% CI 14.12%-25.62%) for anxiety. The scores of HADS-D and HADS-A were 5.60 (95% CI 4.67-6.52) and 6.56 (95% CI 4.89-8.23) among PBC suffers, respectively. CONCLUSIONS This systematic review and meta-analysis indicates that depression and anxiety are prevalent in PBC patients. Physicians should be vigilant for psychiatric symptoms among PBC suffers and provide appropriate interventions for them. Exploration of underlying mechanisms and interactions in the future investigations is warranted.

scholarly journals Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Amir Shamshirian ◽  
Amirhossein Hessami ◽  
Keyvan Heydari ◽  
Reza Alizadeh-Navaei ◽  
Mohammad Ali Ebrahimzadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mortality Rate ◽  
Adverse Effects ◽  
Comparative Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Control Group ◽  
Mesh Terms

AbstractBackgroundCoronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine (HCQ) efficacy in the treatment of COVID-19. We aimed to overcome the controversies regarding the effectiveness of hydroxychloroquine in the treatment of COVID-19, using a systematic review and meta-analysis.MethodsA systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine. Two authors selected and assessed the quality of studies independently using related checklists. Data have been extracted from included studies and analyzed using CMA v. 2.2.064. heterogeneity was also assessed using the I-squared test. We also conducted different sensitivity analyses to examine the effect of studies that greatly influence the results.ResultsOut of 14 studies entered into our systematic review, 12 studies including seven comparative studies with control group and five observational studies containing 3,428 participants have entered into the study. The results of the meta-analysis on comparative studies indicated no significant clinical effectiveness (negative in RT-PCR evaluation) for HCQ regimen in the treatment of COVID-19 in comparison to control group (RR: 1.04, 95% CI, 0.83-1.31). The same result was observed for the combination of HCQ+azithromycin (RR: 2.15, 95% CI, 0.31-14.77). Approximately 1.7 times higher mortality rate was observed among the HCQ regimen group in comparison to control group (RR: 1.73, 95% CI, 1.06-2.81), which was not related to the age differences according to meta-regression analysis (P=0.305). No substantial difference was observed for disease exacerbation (RR: 1.87, 95% CI, 0.28-12.36) between HCQ group and controls. Also, radiological findings significantly improved in the HCQ group (OR: 0.32, 95% CI, 0.11-0.98). Odds of known HCQ adverse effects (diarrhea, vomiting, blurred vision, rash, headache, etc.) occurred in the HCQ regimen group was approximately 3.5 times of control group (OR: 3.55, 95% CI, 1.61-7.82), but no substantial differences were found regarding intubation odds between HCQ group and control group (OR: 2.11, 95% CI, 0.31-14.03).ConclusionThis systematic review and meta-analysis not only indicated no clinical benefits regarding HCQ treatment with/without azithromycin for COVID-19 patients, but the higher mortality rate and frequency of known HCQ adverse effects were observed for the HCQ regimen group. However, due to that most of the studies were non-randomized and results were not homogenous, selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings.

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