Publications by authors named "Imad M Tleyjeh"

96 Publications

Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up.

J Infect Public Health 2021 Nov 18;15(1):21-28. Epub 2021 Nov 18.

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Prince Abdullah Ben Khaled Celiac Disease Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.

Background: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19.

Methods: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up.

Results: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score.

Conclusions: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.
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http://dx.doi.org/10.1016/j.jiph.2021.11.016DOI Listing
November 2021

Predictors of Complications Secondary to Infective Endocarditis and Their Associated Outcomes: A Large Cohort Study from the National Emergency Database (2016-2018).

Infect Dis Ther 2021 Nov 24. Epub 2021 Nov 24.

Division of Pulmonary and Critical Medicine, Detroit Medical Center Wayne State University, Detroit, MI, USA.

Introduction: Literature regarding outcomes and predictors of complications secondary to infective endocarditis (IE) is limited. We aimed to study the outcomes and predictors of complications of IE.

Methods: Data from a national emergency department sample, which constitutes 20% sample of hospital-owned emergency departments in the USA, were analyzed for hospital visits for IE. Complications of endocarditis were obtained by using ICD codes. Multivariable generalized linear method was used to evaluate predictors of in-hospital mortality and complications.

Results: Out of 255,838 adult IE patients (mean age 60.3 ± 20.1 years, 48.5% females), 97,803 (38.2%) patients developed one or more major complications. The major complications were cardiovascular system complications [57,900 (22.6%)], neurologic [42,851 (16.7%)] complications, and renal [16,236 (6.4%)] complications. These included cardiogenic shock [3873 (1.5%)], septic shock [25,798 (10.1%)], acute heart failure [35,602 (14%)], systemic thromboembolism (STE) [21,390 (8.36%)], heart block [11,430 (4.47%)], in-hospital dialysis [2880 (1.1%)], and disseminated intravascular coagulation (DIC) [2704 (1.1%)]. Patients with complicated IE had risk of mortality (adjusted RR 1.12, 95% CI 1.11-1.13, p < 0.001). The complications strongly associated with mortality were septic shock (RR 1.29, 95% CI 1.27-1.30, p < 0.001), cardiogenic shock (RR 1.24, 95% CI 1.20-1.29, p < 0.001), DIC (RR 1.4, 95% CI 1.35-1.46, p < 0.001), and STE (RR 1.07, 95% CI 1.05-1.08, p < 0.001). Staphylococci were the predominant causative organisms (30.8%) among the complicated IE subgroups with higher associated mortality (42.8%). The main predictors of complications from IE were congenital heart disease, history of congestive heart failure, high Elixhauser comorbidity profile, staphylococcal infection, and fungal infections. The prevalence of cardiogenic shock increased over the study years from 1.13 to 1.98% (p-trend 0.04).

Conclusion: Complicated IE is not uncommon and is associated with significant mortality. Staphylococcal infections were associated with high mortality rates. There has been an increasing trend of cardiogenic shock among IE patients across the US. Further research is needed to improve the outcomes of complicated endocarditis.
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http://dx.doi.org/10.1007/s40121-021-00563-yDOI Listing
November 2021

Escalating incidence of infective endocarditis in Europe in the 21st century.

Open Heart 2021 Oct;8(2)

Taunton and Somerset NHS Foundation Trust, Taunton, UK.

Aim: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe.

Methods: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence.

Results: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%.

Conclusion: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase.

Trial Registeration Number: CRD42020191196.
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http://dx.doi.org/10.1136/openhrt-2021-001846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529987PMC
October 2021

Which are the best coronavirus disease 2019 vaccines?

Clin Microbiol Infect 2021 Dec 21;27(12):1729-1732. Epub 2021 Aug 21.

Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379816PMC
December 2021

Overlooked Shortcomings of Observational Studies of Interventions in Coronavirus Disease 2019: An Illustrated Review for the Clinician.

Open Forum Infect Dis 2021 Aug 1;8(8):ofab317. Epub 2021 Jul 1.

Department of Biomedical Informatics, University of Arizona College of Medicine, Phoenix, Arizona, USA.

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection across the globe triggered an unprecedented increase in research activities that resulted in an astronomical publication output of observational studies. However, most studies failed to apply fully the necessary methodological techniques that systematically deal with different biases and confounding, which not only limits their scientific merit but may result in harm through misleading information. In this article, we address a few important biases that can seriously threaten the validity of observational studies of coronavirus disease 2019 (COVID-19). We focus on treatment selection bias due to patients' preference on goals of care, medical futility and disability bias, survivor bias, competing risks, and the misuse of propensity score analysis. We attempt to raise awareness and to help readers assess shortcomings of observational studies of interventions in COVID-19.
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http://dx.doi.org/10.1093/ofid/ofab317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339279PMC
August 2021

Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.

Front Immunol 2021 30;12:686029. Epub 2021 Jun 30.

Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia.

More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.
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http://dx.doi.org/10.3389/fimmu.2021.686029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278217PMC
July 2021

Prior Statin Use and Risk of Mortality and Severe Disease From Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

Open Forum Infect Dis 2021 Jul 28;8(7):ofab284. Epub 2021 May 28.

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Background: Statins up-regulate angiotensin-converting enzyme 2, the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while also exhibiting pleiotropic antiviral, antithrombotic, and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statin use and outcomes of patients with coronavirus disease 2019 (COVID-19).

Methods: We searched Ovid Medline, Web of Science, Scopus, and the preprint server medRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted relative risk (aRRs) of the association between prior statin use and outcomes of patients with COVID-19 using the DerSimonian-Laird random-effects model and assessed heterogeneity using the index.

Results: Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395 513 patients. Sixteen of 19 studies had low or moderate risk of bias. Among 109 080 patients enrolled in 13 separate studies, prior statin use was associated with a lower risk of mortality (pooled aRR, 0.65 [95% confidence interval {CI}, .56-.77], = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48 110 patients enrolled in 9 studies (pooled aRR, 0.73 [95% CI, .57-.94], = 82.8%), with no evidence of publication bias.

Conclusions: Cumulative evidence suggests that prior statin use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic.
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http://dx.doi.org/10.1093/ofid/ofab284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244756PMC
July 2021

The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review.

J Nucl Cardiol 2021 Aug 6;28(4):1545-1552. Epub 2021 Jul 6.

Houston Methodist Debakey Heart & Vascular Center, 6550 Fannin Street, Smith Tower - Suite 1801, Houston, TX, 77030, USA.

Purpose: Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. Fluorodeoxyglucose (FDG) positron emission tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. The aim of this review is to summarize evidence on the prognostic role of FDG PET.

Methods: Studies were identified by searching MEDLINE from inception to October 2020. Medical subject headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done.

Results: A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported major adverse cardiovascular events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used left ventricular ejection fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake.

Conclusion: Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.
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http://dx.doi.org/10.1007/s12350-021-02681-zDOI Listing
August 2021

Combination of (interferon beta-1b, lopinavir/ritonavir and ribavirin) versus favipiravir in hospitalized patients with non-critical COVID-19: A cohort study.

PLoS One 2021 10;16(6):e0252984. Epub 2021 Jun 10.

Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia.

Objectives: Our study aims at comparing the efficacy and safety of IFN-based therapy (lopinavir/ritonavir, ribavirin, and interferon β-1b) vs. favipiravir (FPV) in a cohort of hospitalized patients with non-critical COVID-19.

Methods: Single center observational study comparing IFN-based therapy (interferon β-1b, ribavirin, and lopinavir/ritonavir) vs. FPV in non-critical hospitalized COVID-19 patients. Allocation to either treatment group was non-random but based on changes to national treatment protocols rather than physicians' selection (quasi-experimental). We examined the association between IFN-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate.

Results: The study cohort included 222 patients, of whom 68 (28%) received IFN-based therapy. Antiviral therapy was started at a median of 5 days (3-6 days) from symptoms onset in the IFN group vs. 6 days (4-7 days) for the FPV group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FPV (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.27 (0.08-0.88)). No difference in hospitalization duration between the 2 groups, 9 (7-14) days vs. 9 (7-13) days, P = 0.732 was found. IFN treated group required less use of systemic corticosteroids (57%) as compared to FPV (77%), P = 0.005 after adjusting for disease severity and other confounders. Patients in the IFN treated group were more likely to have nausea and diarrhea as compared to FPV group (13%) vs. (3%), P = 0.013 and (18%) vs. (3%), P<0.0001, respectively.

Conclusion: Early IFN-based triple therapy was associated with lower 28-days mortality as compared to FPV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252984PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191942PMC
June 2021

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update.

Clin Microbiol Infect 2021 Aug 27;27(8):1076-1082. Epub 2021 Apr 27.

Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Objectives: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to update the data in a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.

Methods: Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google from 8th October 2020 till 24th February 2021. Eligible studies were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. The participants were hospitalized COVID-19 patients, and intervention was tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs with a random effects model and evaluated inconsistency between studies with I. We assessed the certainty of evidence using the GRADE approach.

Results: Of 1600 citations, eight RCTs and 28 cohorts were eligible. The eight RCTs had low risk of bias, and with 6311 patients they examined the effect of tocilizumab on short-term mortality; pooled RR was 0.91 (95%CI 0.78-1.07, I 25%). Only the REMAP-CAP and RECOVERY trials, with the majority of their patients on concomitant corticosteroids, showed lower 30-day mortality with tocilizumab use: RR 0.74 (95%CI 0.59-0.93) and 0.89 (95%CI 0.81-0.97), respectively. Seven RCTs, with 5391 patients, examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.84 (95%CI 0.76-0.93), I 0%, with a corresponding number needed to treat of 20 (95%CI 14.3-33.3). Eight RCTs, with 5340 patients, examined the effect of tocilizumab on a composite of poor outcome; pooled RR was 0.82 (95%CI 0.76-0.90, I 3%). Data from the RCTs showed a lower risk of infections and no higher risk of serious adverse events with tocilizumab: pooled RR 0.67 (95%CI 0.45-0.99, eight RCTs) and 0.85 (95%CI 0.63-1.16, seven RCTs), respectively. Among 28 cohorts with 15 484 patients, the pooled adjusted RR for mortality was 0.53 (95%CI 0.43-0.67, I 76%).

Conclusions: Cumulative high-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized patients with severe COVID-19. Moderate-certainty evidence shows that tocilizumab reduces the risk of poor outcome and the risk of secondary infections in hospitalized COVID-19 patients. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.
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http://dx.doi.org/10.1016/j.cmi.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076756PMC
August 2021

Association Between Chronic Statin Use and 30-Day Mortality in Hospitalized Patients With COVID-19.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 14;5(2):442-446. Epub 2021 Mar 14.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Objective: To determine the association between chronic statin use and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19).

Patients And Methods: We identified a retrospective cohort of patients requiring admission at the Mayo Clinic using our enterprise-wide COVID-19 registry from March 1, 2020, through September 30, 2020. Available information included age, sex, use of statins, medical comorbidities, and 30-day mortality. We estimated the association of statins with 30-day mortality using odds ratios and 95% CIs from logistic regression modeling.

Results: Patients (N=1295) between the ages of 30 and 80 years tested positive for COVID-19 and required admission during the study period, of whom 500 (38.6%) were taking statins at admission. Patients taking statins were older and more likely to have diabetes mellitus or congestive heart failure. Within 30 days of diagnosis, 59 (4.6%) died. In multivariable analysis, statin users did not have statistically different odds of death within 30 days with an odds ratio of 1.14 (95% CI, 0.64 to 2.03; =.67) compared to nonusers.

Conclusion: Patients with COVID-19 taking statins had similar 30-day mortality to those not taking statins after adjusting for relevant covariates. Although this is partly influenced by a higher prevalence of risk factors for more severe COVID-19 presentation not entirely adjusted for by the Charlson comorbidity index, these data would not support statins as a likely therapeutic intervention for COVID-19 in the hospital setting.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955930PMC
April 2021

Temporal Trends of Infective Endocarditis in Olmsted County, Minnesota, Between 1970 and 2018: A Population-Based Analysis.

Open Forum Infect Dis 2021 Mar 27;8(3):ofab038. Epub 2021 Jan 27.

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Background: A population-based study of infective endocarditis (IE) in Olmsted County, Minnesota, provides a unique opportunity to define temporal and seasonal variations in IE incidence over an extended time period.

Methods: This was a population-based review of all adults (≥18 years) residing in Olmsted County, Minnesota, with definite or possible IE using the Rochester Epidemiology Project from January 1, 1970, through December 31, 2018. Poisson regression was used to characterize the trends in IE incidence; models were fitted with age, sex, calendar time, and season, allowing for nonlinearity and nonadditivity of their effects.

Results: Overall, 269 cases of IE were identified over a 49-year study period. The median age of IE cases was 67.2 years, and 33.8% were female. The overall age- and sex-adjusted incidence of IE was 7.9 cases per 100 000 person-years (95% CI, 7.0-8.9), with corresponding rates of 2.4, 2.4, 0.9, and 0.7 per 100 000 person-years for , viridans group streptococci (VGS), species, and coagulase-negative staphylococci IE, respectively. Temporal trends varied by age, sex, and season, but on average IE incidence increased over time ( = .021). Enterococcal IE increased the most ( = .018), while IE appeared to increase but mostly in the winter months ( = .018). Between 1996 and 2018, the incidence of VGS IE was relatively stable, with no statistically significant difference in the trends before and after the 2007 AHA IE prevention guidelines.

Conclusions: Overall, IE incidence, and specifically enterococcal IE, increased over time, while IE was seasonally dependent. There was no statistically significant difference in VGS IE incidence in the periods before and after publication of the 2007 AHA IE prevention guidelines.
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http://dx.doi.org/10.1093/ofid/ofab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944350PMC
March 2021

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis - Author's reply.

Clin Microbiol Infect 2021 08 8;27(8):1177-1178. Epub 2021 Mar 8.

Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938745PMC
August 2021

Mortality, viral clearance, and other clinical outcomes of hydroxychloroquine in COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

Clin Transl Sci 2021 05 2;14(3):1101-1112. Epub 2021 May 2.

Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia.

Many meta-analyses have been published about the efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID-19). Most of them included observational studies, and few have assessed HCQ as a prophylaxis or evaluated its safety profile. We searched multiple databases and preprint servers for randomized controlled trials (RCTs) that assessed HCQ for the treatment or prevention of COVID-19. We summarized the effect of HCQ on mortality, viral clearance, and other clinical outcomes. Out of 768 papers screened, 21 RCTs with a total of 14,138 patients were included. A total of 9 inpatient and 3 outpatient RCTs assessed mortality in 8596 patients with a pooled risk difference of 0.01 (95% confidence interval [CI] 0.00-0.03, I  = 1%, p = 0.07). Six studies assessed viral clearance at 7 days with a pooled risk ratio (RR) of 1.11 (95% CI 0.86-1.42, I  = 61%, p = 0.44) and 5 studies at 14 days with a pooled RR of 0.96 (95% CI 0.89-1.04, I  = 0%, p = 0.34). Several trials showed no significant effect of HCQ on other clinical outcomes and. Five prevention RCTs with 5012 patients found no effect of HCQ on the risk of acquiring COVID-19. Thirteen trials showed that HCQ was associated with increased risk of adverse events. We observed, with high level of certainty of evidence, that HCQ is not effective in reducing mortality in patients with COVID-19. Lower certainty evidence also suggests that HCQ neither improves viral clearance and other clinical outcomes, nor prevents COVID-19 infection in patients with high-risk exposure. HCQ is associated with an increased rate of adverse events.
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http://dx.doi.org/10.1111/cts.13001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013604PMC
May 2021

Letter About: Risk Factors for Mortality in Patients with COVID-19 in New York City.

J Gen Intern Med 2021 03 11;36(3):811-812. Epub 2021 Jan 11.

Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1007/s11606-020-06369-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799422PMC
March 2021

Statins as an adjunctive therapy for COVID-19: the biological and clinical plausibility.

Immunopharmacol Immunotoxicol 2021 Feb 6;43(1):37-50. Epub 2021 Jan 6.

Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has infected millions of individuals and has claimed hundreds of thousands of human lives worldwide. Patients with underlying cardiovascular conditions are at high risk for SARS-CoV-2 infection, and COVID-19 patients have high incidence of cardiovascular complications such as acute cardiac injury, arrhythmias, heart failure, and thromboembolism. The disease has no approved proven effective therapy and hence repurposing of existing approved drugs has been considered as the fastest treatment approach. Statins have been shown to exhibit lipid lowering dependent and independent cardiovascular protective effects as well as favorable effects in various other pathophysiological states. These beneficial properties of statins are a result of their multiple pleotropic effects that include, anti-inflammatory, immunomodulatory, antithrombotic and antimicrobial properties. In this review, we provide a comprehensive description of the mechanisms of the pleotropic effects of statins, the relevant pre-clinical and clinical data pertinent to their role in infections and acute lung injury, the possible cardiovascular benefits of statins in COVID-19, and the implications of the therapeutic potential of statins in COVID-19 disease. We conclude with the rationale for conducting randomized controlled trials of statins in COVID-19 disease.
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http://dx.doi.org/10.1080/08923973.2020.1863984DOI Listing
February 2021

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Risk of SARS-CoV-2 Infection or Hospitalization With COVID-19 Disease: A Systematic Review and Meta-Analysis.

Am J Ther 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Department of Medical Specialties, Infectious Diseases Section, King Fahad Medical City, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Swedish Heart and Vascular Institute, Swedish Medical Center, Seattle, WA; Department of Intensive Care, King Abdulaziz Medical City, King Saud bin Abdulaziz for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Houston Methodist DeBakey Heart and Vascular Center, Houston, TX; Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Mayo Clinic Libraries, Mayo Clinic, Rochester, MN; Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Poland; and Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Background: SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold.

Areas Of Uncertainty: These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease.

Data Sources: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020.

Therapeutic Advances: Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%.

Conclusion: Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.
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http://dx.doi.org/10.1097/MJT.0000000000001319DOI Listing
December 2020

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

J Am Coll Cardiol 2020 12;76(25):2982-3021

University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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http://dx.doi.org/10.1016/j.jacc.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755038PMC
December 2020

It is time to drop hydroxychloroquine from our COVID-19 armamentarium.

Med Hypotheses 2020 Nov 17;144:110198. Epub 2020 Aug 17.

Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Department of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; College of Medicine, Al Faisal University, Riyadh, Saudi Arabia. Electronic address:

Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.
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http://dx.doi.org/10.1016/j.mehy.2020.110198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430273PMC
November 2020

The Misleading "Pooled Effect Estimate" of Crude Data from Observational Studies at Critical Risk of Bias: The Case of Tocilizumab in Coronavirus Disease 2019 (COVID-19).

Authors:
Imad M Tleyjeh

Clin Infect Dis 2021 06;72(12):e1154-e1155

Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1093/cid/ciaa1735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717230PMC
June 2021

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Mortality Among COVID-19 Patients: A Systematic Review and Meta-Analysis.

Am J Ther 2020 Nov 10. Epub 2020 Nov 10.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2).

Areas Of Uncertainty: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease.

Data Sources: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data.

Therapeutic Advances: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42-0.94) (I = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58-1.04) (I = 0%) and 0.97, 95% CI (0.73-1.30) (I = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis.

Conclusion: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.
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http://dx.doi.org/10.1097/MJT.0000000000001281DOI Listing
November 2020

Cardiac Toxicity of Chloroquine or Hydroxychloroquine in Patients With COVID-19: A Systematic Review and Meta-regression Analysis.

Mayo Clin Proc Innov Qual Outcomes 2021 Feb 2;5(1):137-150. Epub 2020 Nov 2.

Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Objective: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19).

Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences.

Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; =96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; =98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; =97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity.

Conclusion: Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605861PMC
February 2021

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis.

Clin Microbiol Infect 2021 Feb 5;27(2):215-227. Epub 2020 Nov 5.

Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Objectives: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.

Methods: Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I. We assessed the certainty of evidence using the GRADE approach.

Results: Of 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80-1.49, I = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52-0.96, I = 0%), with a corresponding number needed to treat of 17 (95%CI 9-100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51-0.66, I = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38-1.06, five RCTs) and 0.83 (95%CI 0.55-1.24, five RCTs), respectively.

Conclusions: Cumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.
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http://dx.doi.org/10.1016/j.cmi.2020.10.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644182PMC
February 2021

Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.

J Antimicrob Chemother 2021 01;76(1):30-42

Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia.

Objectives: Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients.

Methods: We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization.

Results: Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00-1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19.

Conclusions: Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.
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http://dx.doi.org/10.1093/jac/dkaa403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665543PMC
January 2021

Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis.

J Infect Public Health 2020 Nov 29;13(11):1652-1663. Epub 2020 Sep 29.

College of Medicine, Al Faisal University, Riyadh, Saudi Arabia; Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

Background: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients.

Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach.

Results: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I = 43.38%).

Conclusion: In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST.
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http://dx.doi.org/10.1016/j.jiph.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522674PMC
November 2020

Fluoroquinolones and the risk of aortopathy: A systematic review and meta-analysis.

Int J Cardiol 2019 Jan 21;274:299-302. Epub 2018 Sep 21.

Division of Cardiovascular Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address:

Objective: To investigate the association between fluoroquinolones use and development of aortopathy.

Methods: A systematic review and meta-analysis was conducted following PRISMA and MOOSE guidelines for reporting systematic reviews of observational studies. Multiple databases were searched and two authors independently screened studies for eligibility. Newcastle Ottawa scale was used to assessed the quality of included studies. Primary outcome of interest was development of aortic aneurysm or dissection among fluoroquinolones users in comparison to non-users. An inverse variance model meta-analysis was used to pool odds ratio or hazards ratio from included studies to calculate the overall effect estimate. Pre specified subgroups analyses were also conducted to explore sources of heterogeneity.

Results: Three observational studies that enrolled 941,639 subjects met the inclusion criteria and were included in the final analysis. All studies were of a good methodological quality. Current use of fluoroquinolones, defined as within 60 days from development of the primary outcome, was associated with significantly elevated risk of developing aortic aneurysm and/or dissection in comparison to controls, (OR = 2.04; 95% CI [1.67, 2.48]). There was only a mild degree of between study heterogeneity, I = 33%. The association remains robust among all subgroups analyses.

Conclusion: Our findings indicate that current fluoroquinolone use was significantly associated with increased risk of aortic aneurysm and dissection. Health care providers need to be aware of this serious association and use fluoroquinolones judiciously in order to minimize the risk of the serious sequela of aortopathy.
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http://dx.doi.org/10.1016/j.ijcard.2018.09.067DOI Listing
January 2019

Workup and Management of Native and Prosthetic Valve Endocarditis.

Curr Treat Options Cardiovasc Med 2018 Aug 7;20(9):73. Epub 2018 Aug 7.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA.

Infective endocarditis (IE) is associated with significant serious adverse outcomes including death. IE usually presents with diverse clinical picture and syndromic diagnoses including heart failure, stroke, and peripheral embolization. Given variable, vague, and syndromic presentations, the diagnosis of IE may be delayed for days to weeks. Maintaining a high index of suspicion among clinicians is the key to early recognition of the disease and prompt initiation of antimicrobial therapy to prevent IE-associated mortality and morbidity. Blood culture and echocardiography remain essential tools in the diagnosis of infective endocarditis. However, advances in molecular techniques, serology testing, computed tomography scan, and nuclear medicine have led to growth in the available tools that may aid in early diagnosis of infective endocarditis. Antimicrobial agents are the mainstay of IE therapy; however, as many as 50% of endocarditis cases will undergo valve surgery, even on an urgent or emergent basis.
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http://dx.doi.org/10.1007/s11936-018-0668-1DOI Listing
August 2018

Indications of Surgery in Infective Endocarditis.

Curr Infect Dis Rep 2017 Mar;19(3):10

Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA.

Purpose Of The Review: Infective endocarditis (IE) is a serious disease with significant morbidity and mortality. Valve surgery is fundamental in the standard of care of selected IE patients. Indeed, valve surgery can be a lifesaving procedure in critically ill endocarditis patients. Our goal from this review is to discuss the indications of surgery in IE population and international cardiac societies' guideline recommendations.

Recent Findings: Though IE is an uncommon disease, its incidence is noted to be on rise in some parts of the world, and the disease is expected to continue to be a major health problem. Antimicrobials remain the mainstay of IE therapy, but as many as 50% of endocarditis patients will undergo surgical intervention. Heart failure most commonly from acute valvular insufficiency, uncontrolled and persistent infection, and recurrent embolic events are the major indications for valve surgery in IE population. Heart failure is by far the most common indication for surgery in IE patients. Despite the fact that many IE patients will require surgical interventions, most of the international societies' recommendations to perform valve surgery are based on observational studies or experts' opinion. Surgery plays a major role in the management of IE patients, and it is most commonly performed in patients with heart failure, persistent or uncontrolled infection, and recurrent emboli. Most of the current evidence supporting surgical intervention in IE patients is based on observational studies and experts' opinion. Randomized clinical trials are urgently needed to guide surgical therapy in IE.
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http://dx.doi.org/10.1007/s11908-017-0569-6DOI Listing
March 2017

Temporal trends in infective endocarditis epidemiology from 2007 to 2013 in Olmsted County, MN.

Am Heart J 2015 Oct 17;170(4):830-6. Epub 2015 Jul 17.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Background: The aim of this study is to determine if there have been contemporary shifts in infective endocarditis (IE) epidemiology in our local population; an analysis of cases from 2007 to 2013 was conducted.

Methods: This is a population-based review of all adults (≥18 years) residing in Olmsted County, MN, with definite or possible IE using the Rochester Epidemiology Project from January 1, 2007, to December 31, 2013.

Results: We identified 51 cases of IE in Olmsted County, MN, between 2007 and 2013. Median age of IE cases was 68.8 years (interquartile range 55.6-76.5), and 41% were females. Age- and sex-adjusted incidence of IE was 7.4 (95% CI 5.3-9.4) cases per 100,000 person-years. From a multivariable Poisson regression model, incidence of IE did not change significantly during the study period (P = .222) but was significantly higher in males and those of older age (P < .001). The annual incidences (per 100,000 person-years) were 2.5 for Staphylococcus aureus, 1.1 for viridans group streptococci, 1.6 for Enterococcus species, and 0.8 for coagulase-negative staphylococci. Only 19.6% (10/51) of Olmsted County patients underwent valve surgery between 2007 and 2013 as compared with 44.4% (197/444) of non-Olmsted County patients treated at Mayo Clinic Rochester.

Conclusion: In this population-based study, no significant change in the overall incidence of IE in Olmsted County, MN, between 2007 and 2013 was seen, and it was similar to that seen between 1970 and 2006. Male gender and older age were associated with increased IE risk. With a lesser extent of cases attributable to viridans group streptococcal IE compared with previous years, S aureus was the predominant pathogen in IE cases during 2007 to 2013. The relatively low valve surgery rate was disparate from that reported from large, tertiary care centers (including our own) with non-population-based cohorts, which are subject to referral bias and can influence the expected characterization of IE.
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http://dx.doi.org/10.1016/j.ahj.2015.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677064PMC
October 2015

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Circulation 2015 Oct 15;132(15):1435-86. Epub 2015 Sep 15.

Background: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.

Methods And Results: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.

Conclusions: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.
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http://dx.doi.org/10.1161/CIR.0000000000000296DOI Listing
October 2015
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