The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

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The prognostic role of bone turnover markers in multiple myeloma patients: The impact of their assay. A systematic review and meta-analysis

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2015.05.001 ◽

2015 ◽

Vol 96 (1) ◽

pp. 54-66 ◽

Cited By ~ 7

Author(s):

Valentina Pecoraro ◽

Laura Roli ◽

Luca Germagnoli ◽

Giuseppe Banfi

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Meta Analysis ◽

Prognostic Role ◽

Turnover Markers ◽

The Impact

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Impact of remdesivir on 28 day mortality in hospitalized patients with COVID-19: February 2021 Meta-analysis

10.1101/2021.03.04.21252903 ◽

2021 ◽

Author(s):

Robert Robinson ◽

Vidhya Prakash ◽

Raad Al Tamimi ◽

Nour Albast ◽

Basma Al-Bast ◽

...

Keyword(s):

Usual Care ◽

English Language ◽

Meta Analysis ◽

Severity Of Illness ◽

Hospitalized Patients ◽

Randomized Controlled ◽

Analysis Process ◽

All Cause Mortality ◽

The Impact

AbstractBackgroundThe COVID-19 pandemic has stimulated worldwide investigation into a myriad of potential therapeutic agents, including antivirals such as remdesivir. The first RCT reporting results on the impact of remdesivir on COVID-19 in a peer reviewed journal was the ACTT-1 trial published in November, 2020. The ACTT-1 trial showed more rapid clinical improvement and a reduced risk of 28-day mortality in patients who received remdesivir.This study is a meta-analysis of peer reviewed RCTs aims to estimate the association of remdesivir therapy compared to the usual care or placebo on all-cause mortality in hospitalized patients with COVID-19. Software based tools to accelerate the analysis process.MethodsMeta-analysis of peer reviewed RCTs comparing remdesivir to usual care or placebo. The protocol for this meta-analysis was registered and published in the PROSPERO database (CRD42021229985) on February 5, 2021.ResultsFour English language RCTs were identified, including data from 7,333 hospitalized patients worldwide using remdesivir in COVID-19 positive patients.Meta-analysis of all identified RCTs showed no difference in survival in patients who received remdesivir therapy compared to usual care or placebo. The random effects meta-analysis has a summary odd ratio is 0.89 (95% CI 0.65-1.21, p = 0.30). Considerable variability in the severity of illness is noted with the rates of IMV at the time of randomization ranging from 0% to 27%.ConclusionsThis meta-analysis of randomized controlled trials published in peer-reviewed literature by February 1, 2021 did not show reduced mortality in hospitalized patients with COVID-19 who received remdesivir. Further research is needed to clarify the role of remdesivir therapy in the management of COVID-19.

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Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients

Blood ◽

10.1182/blood.2020008824 ◽

2020 ◽

Vol 136 (25) ◽

pp. 2881-2892

Author(s):

Abi Vijenthira ◽

Inna Y. Gong ◽

Thomas A. Fox ◽

Stephen Booth ◽

Gordon Cook ◽

...

Keyword(s):

Systematic Review ◽

Pediatric Patients ◽

Hematologic Malignancy ◽

Meta Analysis ◽

Hematologic Malignancies ◽

Hospitalized Patients ◽

Adult Patients ◽

Risk Of Death ◽

Dying Patients ◽

Pooled Prevalence

Abstract Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

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PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review

Acta Cytologica ◽

10.1159/000509095 ◽

2020 ◽

Vol 64 (6) ◽

pp. 547-555

Author(s):

Vasilios Pergialiotis ◽

Christina Nikolaou ◽

Dimitrios Haidopoulos ◽

Maximos Frountzas ◽

Nikolaos Thomakos ◽

...

Keyword(s):

Systematic Review ◽

Cervical Cancer ◽

Cancer Progression ◽

Meta Analysis ◽

Current Evidence ◽

Survival Outcomes ◽

Cochrane Central Register ◽

Wild Type ◽

Pik3ca Mutations ◽

The Impact

Introduction: Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. Methods: We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. Results: Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). Conclusion: Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

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The effect of ageing on presentation, management and outcomes in degenerative cervical myelopathy: a systematic review

Age and Ageing ◽

10.1093/ageing/afaa236 ◽

2020 ◽

Author(s):

Ben Grodzinski ◽

Rory Durham ◽

Oliver Mowforth ◽

Daniel Stubbs ◽

Mark R N Kotter ◽

...

Keyword(s):

Systematic Review ◽

Functional Status ◽

Cervical Myelopathy ◽

Older Patients ◽

Meta Analysis ◽

Current Evidence ◽

Clinical Aspects ◽

Similar Amount ◽

Degenerative Cervical Myelopathy ◽

The Impact

Abstract Objective Degenerative cervical myelopathy (DCM) is a disabling neurological condition. The underlying degenerative changes are known to be more common with age, but the impact of age on clinical aspects of DCM has never been synthesised. The objective of this study is to determine whether age is a significant predictor in three domains—clinical presentation, surgical management and post-operative outcomes of DCM. Methods a systematic review of the Medline and Embase databases (inception to 12 December 2019), registered with PROSPERO (CRD42019162077) and reported in accordance with preferred reporting items of systematic reviews and meta-analysis (PRISMA) guidelines, was conducted. The inclusion criteria were full text articles in English, evaluating the impact of age on clinical aspects of DCM. Results the initial search yielded 2,420 citations, of which 206 articles were eventually included. Age was found to be a significant predictor in a variety of measures. Within the presentation domain, older patients have a worse pre-operative functional status. Within the management domain, older patients are more likely to undergo posterior surgery, with more levels decompressed. Within the outcomes domain, older patients have a worse post-operative functional status, but a similar amount of improvement in functional status. Because of heterogenous data reporting, meta-analysis was not possible. Conclusion the current evidence demonstrates that age significantly influences the presentation, management and outcomes of DCM. Although older patients have worse health at all individual timepoints, they experience the same absolute benefit from surgery as younger patients. This finding is of particular relevance when considering the eligibility of older patients for surgery.

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Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽

10.1136/bmj.m2980 ◽

2020 ◽

pp. m2980 ◽

Cited By ~ 49

Author(s):

Reed AC Siemieniuk ◽

Jessica J Bartoszko ◽

Long Ge ◽

Dena Zeraatkar ◽

Ariel Izcovich ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Standard Care ◽

Interferon Beta ◽

Meta Analysis ◽

Risk Of Bias ◽

Drug Discontinuation ◽

Duration Of Symptoms ◽

Risk Of Death ◽

The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

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Long-Term Growth in Phenylketonuria: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu11092070 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2070 ◽

Cited By ~ 1

Author(s):

Fatma Ilgaz ◽

Alex Pinto ◽

Hülya Gökmen-Özel ◽

Julio César Rocha ◽

Esther van Dam ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Normal Growth ◽

Optimal Growth ◽

Current Evidence ◽

Eligibility Criteria ◽

Dietary Practices ◽

Dietary Treatments ◽

The Impact

There is an ongoing debate regarding the impact of phenylketonuria (PKU) and its treatment on growth. To date, evidence from studies is inconsistent, and data on the whole developmental period is limited. The primary aim of this systematic review was to investigate the effects of a phenylalanine (Phe)-restricted diet on long-term growth in patients with PKU. Four electronic databases were searched for articles published until September 2018. A total of 887 results were found, but only 13 articles met eligibility criteria. Only three studies had an adequate methodology for meta-analysis. Although the results indicate normal growth at birth and during infancy, children with PKU were significantly shorter and had lower weight for age than reference populations during the first four years of life. Impaired linear growth was observed until the end of adolescence in PKU. In contrast, growth impairment was not reported in patients with mild hyperphenylalaninemia, not requiring dietary restriction. Current evidence indicates that even with advances in dietary treatments, “optimal” growth outcomes are not attained in PKU. The majority of studies include children born before 1990s, so further research is needed to show the effects of recent dietary practices on growth in PKU.

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The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.364 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 364-364 ◽

Cited By ~ 4

Author(s):

J. J. Biagi ◽

M. Raphael ◽

W. D. King ◽

W. Kong ◽

W. J. Mackillop ◽

...

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Publication Bias ◽

Meta Analysis ◽

Disease Free Survival ◽

Significant Heterogeneity ◽

Risk Of Death ◽

The Impact ◽

The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

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Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death

BMJ Open ◽

10.1136/bmjopen-2017-018626 ◽

2017 ◽

Vol 7 (10) ◽

pp. e018626 ◽

Cited By ~ 5

Author(s):

Tatyana Mollayeva ◽

Chen Xiong ◽

Sara Hanafy ◽

Vincy Chan ◽

Zheng Jing Hu ◽

...

Keyword(s):

Systematic Review ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Status ◽

Medical Information ◽

Longitudinal Design ◽

Adverse Outcomes ◽

Current Evidence ◽

Risk Of Death ◽

The Impact

IntroductionReports on the association between comorbidity and functional status and risk of death in patients with traumatic brain injury (TBI) have been inconsistent; it is currently unknown which additional clinical entities (comorbidities) have an adverse influence on the evolution of outcomes across the lifespan of men and women with TBI. The current protocol outlines a strategy for a systematic review of the current evidence examining the impact of comorbidity on functional status and early-term and late-term mortality, taking into account known risk factors of these adverse outcomes (ie, demographic (age and sex) and injury-related characteristics).Methods and analysisA comprehensive search strategy for TBI prognosis, functional (cognitive and physical) status and mortality studies has been developed in collaboration with a medical information specialist of the large rehabilitation teaching hospital. All peer-reviewed English language studies with longitudinal design in adults with TBI of any severity, published from May 1997 to April 2017, found through Medline, Central, Embase, Scopus, PsycINFO and bibliographies of identified articles, will be considered eligible. Study quality will be assessed using published guidelines.Ethics and disseminationThe authors will publish findings from this review in a peer-reviewed scientific journal(s) and present the results at national and international conferences. This work aims to understand how comorbidity may contribute to adverse outcomes in TBI, to inform risk stratification of patients and guide the management of brain injury acutely and at the chronic stages postinjury on a population level.PROSPERO registration numberCRD42017070033.

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