scholarly journals Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Hany Hasan Elsayed ◽  
Aly Sherif Hassaballa ◽  
Taha Aly Ahmed ◽  
Mohamed Gumaa ◽  
Hazem Youssef Sharkawy

Abstract Background: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries.Methods: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from June 8 2019 to June 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365Findings: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p=0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p= 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p=0.714 and Begg&Mazumdar test with p=0.334Interpretation: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252760
Author(s):  
Hany Hasan Elsayed ◽  
Aly Sherif Hassaballa ◽  
Taha Aly Ahmed ◽  
Mohammed Gumaa ◽  
Hazem Youssef Sharkawy ◽  
...  

Background COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries. Methods CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365. Findings Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94–1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08–0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43–0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger’s test with p = 0.714 and Begg&Mazumdar test with p = 0.334. Interpretation The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.


2020 ◽  
Author(s):  
Hany Hasan Elsayed ◽  
Aly Sherif Hassaballa ◽  
Taha Aly Ahmed ◽  
Mohammed Gumaa ◽  
Hazem Youssef Sharkawy

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.Materials and Methods: 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. 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 CRD42020183861Results: From 1647 initial citations, 34 full text articles were analysed and 12 studies were selected, including 194 patients with confirmed COVID 19 infection requiring ICU admission and venovenous ECMO treatment. Median New Castle Ottawa scale was 6 indicating acceptable study validity. 136 patients reached an endpoint of weaning from ECMO or death while the rest were still on ECMO. The median Berlin score for ARDS prior to starting ECMO was III. Patients received mechanical ventilation before ECMO implementation for a median of four 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&Mazumdar test with p=0.373Conclusion: 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 centres 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.


2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Hany Hasan Elsayed ◽  
Aly Sherif Hassaballa ◽  
Taha Aly Ahmed ◽  
Mohammed Gumaa ◽  
Hazem Youssef Sharkawy

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.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030407 ◽  
Author(s):  
Kimberley A Lewis ◽  
Dipayan Chaudhuri ◽  
Gordon Guyatt ◽  
Karen E A Burns ◽  
Karen Bosma ◽  
...  

IntroductionTimely liberation from invasive mechanical ventilation is important to reduce the risk of ventilator-associated complications. Once a patient is deemed ready to tolerate a mode of partial ventilator assist, clinicians can use one of multiple ventilatory modes. Despite multiple trials, controversy regarding the optimal ventilator mode to facilitate liberation remains. Herein, we report the protocol for a systematic review and network meta-analysis comparing modes of ventilation to facilitate the liberation of a patient from invasive mechanical ventilation.Methods and analysisWe will search MEDLINE, EMBASE, PubMed, the Cochrane Library from inception to April 2019 for randomised trials that report on critically ill adults who have undergone invasive mechanical ventilation for at least 24 hours and have received any mode of assisted invasive mechanical ventilation compared with an alternative mode of assisted ventilation. Outcomes of interest will include: mortality, weaning success, weaning duration, duration of mechanical ventilation, duration of stay in the acute care setting and adverse events. Two reviewers will independently screen in two stages, first titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, two investigators will extract all data, and assess risk of bias in all eligible studies using the Modified Cochrane Risk of Bias tool. Reviewers will resolve disagreement by discussion and consultation with a third reviewer as necessary. Using a frequentist framework, we will perform random-effect network meta-analysis, including all ventilator modes in the same model. We will calculate direct and indirect estimates of treatment effect using a node-splitting procedure and report effect estimates using OR and 95% CI. We will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation methodology.Ethics and disseminationResearch ethics board approval is not necessary. The results will be disseminated through publication in a peer-reviewed journals.PROSPERO registration numberCRD42019137786


Author(s):  
Zhipeng Yan ◽  
Zhipeng Yan ◽  
Ka Shing Cheung ◽  
Eric Ho-Yin Lau ◽  
Ching-Lung Lai

Background: Coronavirus Disease in 2019 (COVID-19) is a pandemic caused by SARS-CoV-2 infection. Over 53 million people have been infected with over 1.3 million deaths. However, there is no standard treatment or vaccines to date. Recently, several randomized controlled trials and cohort studies have demonstrated the efficacy of remdesivir for the treatment of severe COVID-19 patients. This is a systematic review and meta-analysis to define its efficacy. Methods: A systematic review was done on databases (PubMed, Embase, Medline, Cochrane) on 9 Nov 2020. Search keywords were remdesivir, COVID-19, SARS-CoV-2, randomized controlled trials and cohort studies. Studies with high-evidence values were selected to evaluate its clinical efficacy in terms of risk ratio, time to clinical improvement, and mortality risk. Subgroup analysis was performed based on baseline hospitalization status, age and ethnicity. Results: Of the 1328 studies, 6 studies were selected and pooled for meta-analysis. Remdesivir was associated with clinical improvement (risk ratio 1.14, 95% CI 1.02-1.28, p=0.02). It shortened the mean time of clinical improvement by 3.32 days (95% CI -4.37 to -2.28, p<0.001). However, its use was not associated with reduced mortality risk (risk ratio 0.75, 95% CI 0.40–1.40). In subgroup analysis, remdesivir was associated with clinical improvement in patients without the need of invasive ventilation (risk ratio 1.90, 95% CI 1.58-2.29, p<0.001; hazard ratio 2.22, 95% CI, 1.64-3.02), and age less than 70 years (risk ratio 2.14, 95% CI 1.39-3.28, p<0.001). Conclusion: Remdesivir is effective in the treatment of severe COVID-19 patients, in particular those without invasive ventilation


2020 ◽  
Author(s):  
Hossein Dabiriyan Tehrani ◽  
Sara Yamini

This systematic review aimed to find attitudes toward Altruistic and Game-playing love styles across individualistic and collectivistic cultures. Addressing major moderators concerning Altruistic and Game-playing love styles are the secondary objectives of this review. This review included 102 articles comprising samples from 37 countries (N = 41997). The findings of this meta-analysis show that there is a collectivistic and individualistic difference in Game-playing but not in the Altruistic love style. Collectivistic and individualistic cultures, on average, demonstrate the same perception concerning the Altruistic love style, whereas collectivistic culture shows the Game-playing love style more strongly. To explain the role of moderators in key measures, the subgroup analysis and meta-regression show that both Game-playing and Altruistic love styles decline by increasing the length of the relationship. Likewise, having children affects these love styles such that the Altruistic love style is improved, and the Game-playing love style is reduced by the presence of children in families.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
I Giacchetta ◽  
M Chiavarini ◽  
G Naldini ◽  
R Fabiani

Abstract Background The probability of developing invasive cutaneous malignant melanoma (CMM) is higher in women than in men up until the age of 49. Several studies investigated the association between hormonal factors and CMM. The aim of this systematic review and meta-analysis is to summarize the evidence on the association between Oral Contraceptives (OC) and the risk of CMM. Methods This review and meta-analysis follow the PRISMA guidelines. A systematic literature search was conducted on Medline and Web of Science until December 2019. Studies were eligible if reported a risk estimate for the association between OC and CMM. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using random effect model. Results The results of the pooled analysis of all 32 studies showed no significant association between OC and the risk of CMM (OR 1.02; 95% CI 0.94-1.11; I2=39.32%, p = 0.013). The stratified analyses by study design found no significant association between OC and the risk of CMM neither in the 18 case-control studies (OR 1.02; 95% CI 0.87-1.21; I2=56.91%, p = 0.002) nor in the 14 cohort studies (OR 1.04; 95% CI 0.98-1.11; I2=0.00%, p = 0.557). No significant publication bias could be detected by Egger's test or Begg's test. Conclusions This meta-analysis of available literature suggests no significant association between OC and the risk of developing CMM. Further investigations are needed to evaluate the possible relationship of OC use and other hormonal factors potentially contributing to the increased risk of CMM in women during their reproductive years. Key messages Oral contraceptives (OC) do not significantly contribute to the risk of Cutaneous Malignant Melanoma (CMM). Further studies are needed to investigate the potential role of other hormonal factors in the increased probability of developing CMM in women during their reproductive years.


2020 ◽  
Vol 30 (8) ◽  
pp. 3073-3083 ◽  
Author(s):  
Walid El Ansari ◽  
Ayman El-Menyar ◽  
Brijesh Sathian ◽  
Hassan Al-Thani ◽  
Mohammed Al-Kuwari ◽  
...  

Abstract Background This systematic review and meta-analysis searched, retrieved and synthesized the evidence as to whether preoperative esophagogastroduodenoscopy (p-EGD) should be routine before bariatric surgery (BS). Methods Databases searched for retrospective, prospective, and randomized (RCT) or quasi-RCT studies (01 January 2000–30 April 2019) of outcomes of routine p-EGD before BS. STROBE checklist assessed the quality of the studies. P-EGD findings were categorized: Group 0 (no abnormal findings); Group 1 (abnormal findings that do not necessitate changing the surgical approach or postponing surgery); Group 2 (abnormal findings that change the surgical approach or postpone surgery); and Group 3 (findings that signify absolute contraindications to surgery). We assessed data heterogeneity and publication bias. Random effect model was used. Results Twenty-five eligible studies were included (10,685 patients). Studies were heterogeneous, and there was publication bias. Group 0 comprised 5424 patients (56%, 95% CI: 45–67%); Group 1, 2064 patients (26%, 95% CI: 23–50%); Group 2, 1351 patients (16%, 95% CI: 11–21%); and Group 3 included 31 patients (0.4%, 95% CI: 0–1%). Conclusion For 82% of patients, routine p-EGD did not change surgical plan/ postpone surgery. For 16% of patients, p-EGD findings necessitated changing the surgical approach/ postponing surgery, but the proportion of postponements due to medical treatment of H Pylori as opposed to “necessary” substantial change in surgical approach is unclear. For 0.4% patients, p-EGD findings signified absolute contraindication to surgery. These findings invite a revisit to whether p-EGD should be routine before BS, and whether it is judicious to expose many obese patients to an invasive procedure that has potential risk and insufficient evidence of effectiveness. Further justification is required.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
GF Romiti ◽  
D Pastori ◽  
JM Rivera-Caravaca ◽  
WY Ding ◽  
YX Gue ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with Atrial Fibrillation (AF), standing on three main pillars: ‘A’ Avoid stroke (with Anticoagulants); ‘B’ Better symptom management; ‘C’ Cardiovascular and Comorbidity management. The ABC pathway is now recommended in several clinical guidelines, including the recent European Society of Cardiology (ESC) AF management guidelines. We performed a systematic review of the current evidence for use of the ABC pathway on clinical outcomes. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. Pubmed and EMBASE were searched for studies reporting the prevalence of ABC pathway adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Metanalysis of odds ratio (OR) was performed with random-effect models; subgroup analysis and meta-regression were performed to account for heterogeneity; a CHA2DS2-VASc-stratified sensitivity analysis was also performed. Results Among 2862 records retrieved from the literature search, 8 studies were included. The pooled prevalence of ABC adherent management was 21% (95% confidence intervals (CI), 13-34%), with a high grade of heterogeneity; in a multivariable meta-regression model, adherence to each criteria of the ABC pathway explained most part of the heterogeneity (R2 = 98.9%). Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR:0.42, 95%CI 0.31-0.56), cardiovascular death (OR:0.37, 95%CI 0.23-0.58), stroke (OR:0.55, 95%CI 0.37-0.82) and major bleeding (OR:0.69, 95%CI 0.51-0.94), with moderate heterogeneity. Meta-regressions showed that the increasing prevalence of diabetes mellitus, coronary artery disease, chronic heart failure and history of stroke were associated with a reduced effectiveness of the ABC pathway for all-cause and cardiovascular death; each comorbidity was able to explain a significant proportion of heterogeneity at univariate meta-regression. Conversely, longer follow-up time was associated with more effectiveness of the ABC pathway for all outcomes. Adherence to ABC pathway was associated with a progressively greater reduction of the all-cause death risk amongst patients with higher CHA2DS2-VASc scores; no difference in ABC pathway effectiveness was found across CHA2DS2-VASc strata for CV death and stroke occurrence. Conclusions Adherence to the ABC pathway was suboptimal, being adopted in 1 in every 5 patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes. Our data supports extensive application of the ABC pathway for the management of AF. Abstract Figure.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16506-e16506
Author(s):  
Ce Cheng ◽  
Iloabueke Gabriel Chineke ◽  
Ali McBride ◽  
Juan Chipollini ◽  
Edward Paul Gelmann ◽  
...  

e16506 Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I2= 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I2= 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I2= 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I2= 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I2= 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I2= 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I2= 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I2= 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I2= 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I2= 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I2= 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.


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