Risk of Recurrence after Stopping Anticoagulants in Women with Combined Oral Contraceptive-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

Abstract Background Although combined oral contraceptives (COC) are considered a transient risk factor for venous thromboembolism (VTE), the risk of recurrence after discontinuation of anticoagulation is unclear. Few studies have focused on the risk of recurrence in this group; studies report variable results and are limited by small sample size. The risk of recurrence appears to be low, but this could relate to the young age of affected women. Deciphering the absolute VTE recurrence risk after a COC-associated VTE is crucial in helping clinicians and patients decide if anticoagulation could be discontinued after the initial treatment period. Objectives The objectives of this systematic review and meta-analysis are to estimate the incidence of recurrent VTE among women with COC-associated VTE, compared with women with unprovoked VTE. Methods We searched the following databases: Cochrane Central Register of Controlled Trial, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform, from the database's inception to July 2020. Additional studies were identified by screening citations from included studies. Prospective cohort studies, randomized controlled trials (RCTs), and meta-analyses of prospective cohort studies or RCTs were reviewed by two authors for study inclusion (Figure 1). Studies were included if women had objectively confirmed COC-associated VTE, received a minimum of three months of anticoagulation, discontinued COC prior to or at time of discontinuation of anticoagulation, time of follow-up began after anticoagulation was stopped, and recurrent VTE data was available. Studies were excluded if patients were systematically treated with an alternative pharmacologic agent intended to reduce the risk of recurrent VTE such as aspirin. Authors of identified papers were contacted for additional data on critical variables. If there were multiple publications from a cohort, the study with the longest follow up was included. Two authors extracted study data and assessed included studies for risk of bias using the Newcastle Ottawa Scale. Meta-analysis was done using a random effects Poisson regression model. Heterogeneity was assessed using the I-squared measure. Results Our systematic review included 19 studies with a total of 1,537 women (5,828 patient years of follow up) with an index COC-associated VTE, and 1,974 women (7,798 patient years of follow up) with an index unprovoked VTE. Authors contributed additional unpublished data in 16 of the 19 studies. Overall, studies were at low risk of bias, with a mean of 7 stars (out of a possible 9) in the Newcastle Ottawa Scale. Among the 19 studies, the incidence rate of VTE recurrence in women with COC-associated VTE was 1.22 per patient year (95% confidence interval (CI) 0.94 to 1.59, I 2 = 6.4%, 95% prediction interval (PI) 0.81 to 1.85) (Figure 2). The incidence rate of VTE recurrence in women with an index unprovoked VTE not associated with COC was 3.89 per patient year (95% CI 2.98 to 5.07, I 2 =74.2%, 95% PI 1.37 to 11.03). The unadjusted incidence rate ratio of recurrent VTE comparing women with COC-associated events to women with unprovoked events was 0.34 (95% CI 0.26 to 0.45, I 2 = 2.6%, 95% PI 0.26 to 0.46). Only three studies had age-adjusted comparisons, but each with a different effect measure so they could not be combined, with a relative risk ratio 0.4 (95% CI 0.2 to 0.8) (also adjusted for site of VTE and congenital thrombophilia) (Eischer 2014), a hazard ratio of 0.11 (95% CI 0.01 to 0.85) (Kearon 2019), and an incidence rate ratio of 1 (95% CI 0.3 to 3.2) (Le Moigne 2013). Conclusions The estimated risk of VTE recurrence after a COC-associated VTE is low, and is lower compared to women with unprovoked VTE, however this comparison may be confounded by age. With only a minority of studies providing age adjusted analyses, the true difference remains unknown. Our meta-analysis is strengthened by the substantial contribution of unpublished data from individual study authors. This can help to guide clinicians and patient shared decision-making on the duration of anticoagulation. Figure 1 Figure 1. Disclosures Le Gal: LEO Pharma: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Aspen: Honoraria; Sanofi: Honoraria. Schulman: Boehringer-Ingelheim: Research Funding; Octapharma: Research Funding. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

Download Full-text

Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies

Evidence-Based Mental Health ◽

10.1136/ebmental-2018-300037 ◽

2018 ◽

Vol 21 (4) ◽

pp. 146-154 ◽

Cited By ~ 23

Author(s):

Amparo Díaz-Román ◽

Junhua Zhang ◽

Richard Delorme ◽

Anita Beggiato ◽

Samuele Cortese

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorders ◽

Evidence Synthesis ◽

Meta Analysis ◽

Autism Spectrum ◽

Newcastle Ottawa Scale ◽

Spectrum Disorders ◽

Sleep Alterations ◽

The Impact ◽

Ottawa Scale

BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2 statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted using Review Manager and Comprehensive Meta-Analysis.FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.

Download Full-text

Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8120162 ◽

2021 ◽

Vol 8 (12) ◽

pp. 162

Author(s):

Sergio Rico-Martín ◽

Julián F. Calderón-García ◽

Belinda Basilio-Fernández ◽

María Zoraida Clavijo-Chamorro ◽

Juan F. Sánchez Muñoz-Torrero

Keyword(s):

Systematic Review ◽

Metabolic Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Meta Analysis ◽

Risk Of Bias ◽

Newcastle Ottawa Scale ◽

Abstract Screening ◽

The Relationship ◽

Metabolic Comorbidities ◽

Ottawa Scale

Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients. Methods: A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88–3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16–4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71–2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed. Conclusions: this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components.

Download Full-text

Efficacy and safety of tocilizumab in the management of COVID-19: A systematic review and meta-analysis of observational studies

10.1101/2021.01.27.21250599 ◽

2021 ◽

Author(s):

Gollapalle L Viswanatha ◽

CH K V L S N Anjana Male ◽

Hanumanthappa Shylaja

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Standard Of Care ◽

Efficacy And Safety ◽

Risk Of Mortality ◽

Significant Difference ◽

Newcastle Ottawa Scale ◽

Soc Control ◽

Ottawa Scale

AbstractBackgroundThis systematic review and meta-analysis was aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19).MethodsThe electronic search was performed using PubMed, Scopus, CENTRAL, and Google scholar to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th September 2020. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo/standard of care. The comparison will be between TCZ versus standard of care (SOC)/placebo. Inconsistency between the studies was evaluated with I2 and quality of the evidences were evaluated by Newcastle-Ottawa scale.ResultsBased on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (M-H,RE-OR −0.11(−0.18 to −0.04) 95% CI, p =0.001, I2 =88%) and increased the incidences of super-infections (M-H, RE-OR 1.49(1.13 to 1.96) 95% CI, p=0.004, I2=47%). However, there is no significant difference in ICU admissions rate (M-H, RE-OR −0.06(−0.23 to 0.12), I2=93%), need of MV (M-H, RE-OR of 0.00(−0.06 to 0.07), I = 74%), LOS (IV −2.86(−0.91 to 3.38), I2=100%), LOS-ICU (IV: −3.93(−12.35 to 4.48), I2=100%), and incidences of pulmonary thrombosis (M-H, RE-OR 1.01 (0.45 to 2.26), I2=0%) compared to SOC/control.ConclusionBased on cumulative low to moderate certainty evidence shows that TCZ could reduce the risk of mortality in hospitalized patients. However, there is no statistically significant difference observed between the TCZ and SOC/control groups in other parameters.

Download Full-text

Cranial Base Angle in Patients With Cleft Lip and Palate—A Systematic Review and Meta-Analysis

The Cleft Palate-Craniofacial Journal ◽

10.1177/10556656211053545 ◽

2021 ◽

pp. 105566562110535

Author(s):

Chandnee Murugan ◽

Vignesh Kailasam

Keyword(s):

Systematic Review ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Meta Analysis ◽

Cranial Base ◽

Class I ◽

Base Angle ◽

Registration Number ◽

Newcastle Ottawa Scale ◽

Ottawa Scale

Background: Diverse findings have been reported for the cranial base angle (CBA) in patients with CLP (cleft lip and palate) and non-CLP controls. Objective: The aim of this study is to assess and evaluate the CBA in patients with CLP and non-CLP controls. Methods: Data from PubMed, OVID Technologies, Inc., Cochrane, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scopus, Web of Science, and EMBASE for Excerpta Medica dataBASE (EMBASE) with relevant terms was extracted until December 31, 2020. Inclusion criteria were data of patients with non-syndromic unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP). In the case of UCLP and BCLP, patients with craniofacial syndromes were excluded. The study proposal was registered with PROSPERO (Registration number: CRD42021228632). Results: Fifteen studies with a total of 2032 participants were included for the systematic review and 14 studies with a total of 1972 participants were included for the meta-analysis. The risk of bias was assessed using the Modified Newcastle Ottawa scale under seven domains by two authors. Thirteen studies were graded as “good” and two as “satisfactory.” The CBA in patients with CLP were greater than the non CLP Class I controls in six of the 15 studies. CBA was greater in patients with CLP than non-CLP controls by 1.21° (95% CI of 0.19-2.22). Meta-analysis reported considerable heterogeneity (I2 = 86%). Anterior (ACB) and posterior cranial base (PCB) lengths were shorter in patients with CLP than in the non-cleft Class I controls by 2.14 mm (95% CI of 0.99-3.30) and 2.06 mm (95% CI of 1.52-2.60), respectively. Conclusion: Most studies were graded as good. Patients with CLP had greater CBA and shorter ACB and PCB lengths when compared to non-CLP controls.

Download Full-text

Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis

F1000Research ◽

10.12688/f1000research.27334.1 ◽

2020 ◽

Vol 9 ◽

pp. 1316

Author(s):

Endang Mutiawati ◽

Syahrul Syahrul ◽

Marhami Fahriani ◽

Jonny Karunia Fajar ◽

Sukamto S. Mamada ◽

...

Keyword(s):

Systematic Review ◽

Web Of Science ◽

Viral Infections ◽

Meta Analysis ◽

Global Prevalence ◽

Newcastle Ottawa Scale ◽

Adults And Children ◽

Respiratory Viral Infections ◽

Cumulative Prevalence ◽

Ottawa Scale

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020)

Download Full-text

Socioeconomic Factors and Caries in People between 19 and 60 Years of Age: An Update of a Systematic Review and Meta-Analysis of Observational Studies

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081775 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1775 ◽

Cited By ~ 15

Author(s):

Simone Costa ◽

Carolina Martins ◽

Mânia Pinto ◽

Mara Vasconcelos ◽

Mauro Abreu

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Socioeconomic Indicators ◽

Effect Model ◽

Statistical Heterogeneity ◽

Newcastle Ottawa Scale ◽

Meta Regression ◽

Ottawa Scale

This study is aimed to perform an update of a systematic review and meta-regression to evaluate the effect modification of the socioeconomic indicators on caries in adults. We included studies that associated social determinants with caries, with no restriction of year and language. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. With regard to the meta-analysis, statistical heterogeneity was evaluated by I2, and the random effect model was used when it was high. A subgroup analysis was conducted for socioeconomic indicators, and a meta-regression was performed. Publication bias was assessed through Egger’s test. Sixty-one studies were included in the systematic review and 25 were included in the meta-analysis. All of the studies were published between 1975 and 2016. The most frequent socioeconomic indicators were schooling, income, and socioeconomic status (SES). In the quantitative analysis, the DMFT (decayed, missing, filled teeth) variation was attributed to the studies’ heterogeneity. The increase of 10.35 units in the proportion of people with lower SES was associated with an increase of one unit in DMFT, p = 0.050. The findings provide evidence that populations with the highest proportions of people with low SES are associated with a greater severity of caries. The results suggest the need for actions to reduce the inequalities in oral health (PROSPERO [CRD42017074434]).

Download Full-text

Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis

10.1101/2020.07.04.20146381 ◽

2020 ◽

Cited By ~ 1

Author(s):

Arunmozhimaran Elavarasi ◽

Manya Prasad ◽

Tulika Seth ◽

Ranjit Kumar Sahoo ◽

Karan Madan ◽

...

Keyword(s):

Systematic Review ◽

Randomized Trials ◽

Meta Analysis ◽

Standard Of Care ◽

Efficacy And Safety ◽

Quality Of Evidence ◽

Newcastle Ottawa Scale ◽

Ecg Abnormalities ◽

Ottawa Scale

Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.

Download Full-text

Effect of retirement on cognitive function: a systematic review and meta-analysis

Occupational and Environmental Medicine ◽

10.1136/oemed-2020-106892 ◽

2020 ◽

pp. oemed-2020-106892

Author(s):

Celia Alvarez-Bueno ◽

Ivan Cavero-Redondo ◽

Estela Jimenez-Lopez ◽

Maria Eugenia Visier-Alfonso ◽

Irene Sequi-Dominguez ◽

...

Keyword(s):

Systematic Review ◽

Cognitive Function ◽

Longitudinal Studies ◽

Meta Analysis ◽

Negative Effects ◽

Longitudinal Association ◽

Study Characteristics ◽

Newcastle Ottawa Scale ◽

Global Cognition

The study aimed to determine the longitudinal association between retirement and cognitive function, including global cognition and memory-related skills. This is a systematic review of longitudinal studies on the association between retirement and cognitive function, using Medline (via PubMed), Scopus, Web of Science and PsycINFO databases from inception to April 2020 and longitudinal studies on the association between retirement and cognitive function. The Newcastle-Ottawa Scale was used to assess risk of bias of included studies. Effect size (ES) and 95% CI were calculated using Cohen’s d index. Meta-regressions were calculated on the basis of sample characteristics: percentage of women, years of follow-up and age at baseline. A total of 23 longitudinal studies were included in this systematic review. The pooled ES for the association of retirement with global cognition and memory-related skills was −0.01 (95% CI −0.02 to 0.00; I2: 0.0%) and −0.09 (95% CI −0.16 to 0.01; I2: 93%), respectively. Meta-regression analyses showed that length of follow-up, percentage of women in the sample and mean age at baseline did not influence the longitudinal association between retirement and adults’ memory-related skills. The results of this study indicate that retirement has no negative effects on adults’ global cognition and slightly adversely influences memory-related skills. Moreover, this association does not seem to be influenced by some demographic and study characteristics.

Download Full-text

Epidemiology of placenta previa accreta: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-031193 ◽

2019 ◽

Vol 9 (11) ◽

pp. e031193 ◽

Cited By ~ 9

Author(s):

Eric Jauniaux ◽

Lene Grønbeck ◽

Catey Bunce ◽

Jens Langhoff-Roos ◽

Sally L Collins

Keyword(s):

Systematic Review ◽

Placenta Previa ◽

Data Extraction ◽

Meta Analysis ◽

Eligibility Criteria ◽

Registration Number ◽

Newcastle Ottawa Scale ◽

Placenta Accreta Spectrum ◽

Obstetric Population ◽

Ottawa Scale

ObjectiveTo estimate the prevalence and incidence of placenta previa complicated by placenta accreta spectrum (PAS) and to examine the different criteria being used for the diagnosis.DesignSystematic review and meta-analysis.Data sourcesPubMed, Google Scholar, ClinicalTrials.gov and MEDLINE were searched between August 1982 and September 2018.Eligibility criteriaStudies reporting on placenta previa complicated by PAS diagnosed in a defined obstetric population.Data extraction and synthesisTwo independent reviewers performed the data extraction using a predefined protocol and assessed the risk of bias using the Newcastle-Ottawa scale for observational studies, with difference agreed by consensus. The primary outcomes were overall prevalence of placenta previa, incidence of PAS according to the type of placenta previa and the reported clinical outcomes, including the number of peripartum hysterectomies and direct maternal mortality. The secondary outcomes included the criteria used for the prenatal ultrasound diagnosis of placenta previa and the criteria used to diagnose and grade PAS at birth.ResultsA total of 258 articles were reviewed and 13 retrospective and 7 prospective studies were included in the analysis, which reported on 587 women with placenta previa and PAS. The meta-analysis indicated a significant (p<0.001) heterogeneity between study estimates for the prevalence of placenta previa, the prevalence of placenta previa with PAS and the incidence of PAS in the placenta previa cohort. The median prevalence of placenta previa was 0.56% (IQR 0.39–1.24) whereas the median prevalence of placenta previa with PAS was 0.07% (IQR 0.05–0.16). The incidence of PAS in women with a placenta previa was 11.10% (IQR 7.65–17.35).ConclusionsThe high heterogeneity in qualitative and diagnostic data between studies emphasises the need to implement standardised protocols for the diagnoses of both placenta previa and PAS, including the type of placenta previa and grade of villous invasiveness.PROSPERO registration numberCRD42017068589

Download Full-text

Extracorporeal membrane oxygenation (ECMO) in patients with severe COVID-19 adult respiratory distress syndrome: a systematic review and meta-analysis

The Cardiothoracic Surgeon ◽

10.1186/s43057-021-00046-3 ◽

2021 ◽

Vol 29 (1) ◽

Author(s):

Hany Hasan Elsayed ◽

Aly Sherif Hassaballa ◽

Taha Aly Ahmed ◽

Mohammed Gumaa ◽

Hazem Youssef Sharkawy

Keyword(s):

Systematic Review ◽

Risk Ratio ◽

Mortality Risk ◽

Distress Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Registration Number ◽

Newcastle Ottawa Scale ◽

Venovenous Ecmo ◽

Ottawa Scale

Abstract Background COVID 19 is the most recent cause of adult respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for COVID-associated ARDS to study its outcome. Main body CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from inception to May 28, 2020. Studies reporting five or more patients with COVID-19 infection treated venovenous with ECMO were included. The main outcome assessed was mortality and ICU/hospital discharge. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. The validity of all the included observational studies was appraised with the Newcastle Ottawa scale. Meta-regression and publication bias were tested. This trial was registered with PROSPERO under registration number CRD42020183861. From 1647 initial citations, 34 full-text articles were analyzed and 12 studies were selected, including 194 patients with confirmed COVID-19 infection requiring ICU admission and venovenous ECMO treatment. Median Newcastle-Ottawa scale was 6 indicating acceptable study validity. One hundred thirty-six patients reached an endpoint of weaning from ECMO with ICU/hospital discharge or death while the rest were still on ECMO or in the ICU. The median Berlin score for ARDS prior to starting ECMO was III. Patients received mechanical ventilation before ECMO implementation for a median of 4 days and ECMO was maintained for a median of 13 days. In hospital and short-term mortality were highly variable among the included studies ranging between 0 and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.49 (95% confidence interval 0.259 to 0.721; I2 = 94%). Subgroup analysis according to country of origin showed persistent heterogeneity only in the 7 Chinese studies with pooled estimate mortality risk ratio of 0.66 (I2 = 87%) (95% CI = 0.39-0.93), while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.41 (95% CI 0.28-0.53) with homogeneity (p=0.67) similar to France with a pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86). Meta-regression showed only younger age as a predictor of mortality (p=0.02). Publication bias was excluded by visualizing the funnel plot of standard error, Egger’s test with p=0.566, and Begg and Mazumdar test with p=0.373. Conclusion The study included the largest number of patients with outcome findings of ECMO in this current pandemic. Our findings showed that the use of venovenous ECMO at high-volume ECMO centers may be beneficial for selected COVID 19 patients with severe ARDS. However, none of the included studies involve prospective randomized analyses; and therefore, all the included studies were of low or moderate quality according to the Newcastle-Ottawa scale. In the current era and environment of the pandemic, it will likely be very challenging to conduct a prospective randomized trial of ECMO versus no-ECMO for COVID-19. Therefore, the information contained in this systematic review of the literature is valuable and provides important guidance. Trial registration The study protocol link is at www.crd.yorl.ac.uk/PROSPERO under registration number CRD42020183861.

Download Full-text