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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.06.031 Byline: Imad M. Tleyjeh (a)(b), Tarek Kashour (c)(d), Valerie Zimmerman (a), James M. Steckelberg (b), Walter R. Wilson (b), Larry M. Baddour (b) Abstract: The potential role of valve surgery in infective endocarditis (IE) management is controversial. No randomized trials have been conducted to date; accordingly, some studies use propensity score analysis (PSA) to minimize selection bias in observational studies. Author Affiliation: (a) Research Center, King Fahd Medical City, Riyadh, Saudi Arabia (b) Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN (c) Department of Cardiology, King Fahd Medical City, Riyadh, Saudi Arabia (d) Section of Cardiology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Article History: Received 14 April 2008; Accepted 26 June 2008 Article Note: (footnote) Dr Tleyjeh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Part of this work was presented at the Infectious Diseases Society of America Meeting, San Diego, CA, October 2007.

Post-acute COVID-19 syndrome (PACS) is an important healthcare burden. We examined persistent symptoms in COVID-19 patients at least four weeks after the onset of infection, participants' return to pre-COVID-19 health status and associated risk factors. Cross-sectional study was conducted (December 2020 to January 2021). A validated online questionnaire was sent to randomly selected individuals aged more than 14 years from a total of 1397,386 people confirmed to have COVID-19 at least 4 weeks prior to the start of this survey. This sample was drawn from the Saudi ministry of health COVID-19 testing registry system. Out of the 9507 COVID-19 patients who responded to the survey, 5946 (62.5%) of them adequately completed it. 2895 patients (48.7%) were aged 35–44 years, 64.4% were males, and 91.5% were Middle Eastern or North African. 79.4% experienced unresolved symptoms for at least 4 weeks after the disease onset. 9.3% were hospitalized with 42.7% visiting healthcare facility after discharge and 14.3% requiring readmission. The rates of main reported persistent symptoms in descending order were fatigue 53.5%, muscle and body ache 38.2%, loss of smell 35.0%, joint pain 30.5%, and loss of taste 29.1%. There was moderate correlation between the number of symptoms at the onset and post-four weeks of COVID-19 infection. Female sex, pre-existing comorbidities, increased number of baseline symptoms, longer hospital-stay, and hospital readmission were predictors of delayed return to baseline health state (p < 0.05). The symptoms of PACS are prevalent after contracting COVID-19 disease. Several risk factors could predict delayed return to baseline health state. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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 I2. We assessed the certainty of evidence using the GRADE approach. 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, I2 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), I2 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, I2 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, I2 76%). 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. [ABSTRACT FROM AUTHOR]

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. 18Fluorodeoxyglucose (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. [ABSTRACT FROM AUTHOR]

To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. 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. 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, I2 = 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, I2 = 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, I2 = 43.38%). 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. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.03.024 Byline: Ahmed Abdel-Latif (a), Roberto Bolli (a), Ewa K. Zuba-Surma (a), Imad M. Tleyjeh (b)(c), Carlton A. Hornung (d), Buddhadeb Dawn (a) Abstract: Small clinical studies of granulocyte colony-stimulating factor (G-CSF) therapy for cardiac repair after acute myocardial infarction (MI) have yielded divergent results. The effect of G-CSF therapy on left ventricular (LV) function and structure in these patients remains unclear. Author Affiliation: (a) Division of Cardiology and the Institute of Molecular Cardiology, University of Louisville, Louisville, KY (b) Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN (c) Department of Medicine, King Fahd Medical City, Riyadh, Saudi Arabia (d) Department of Epidemiology and Population Health, University of Louisville, School of Public Health and Information Sciences, Louisville, KY Article History: Received 14 January 2008; Accepted 29 March 2008 Article Note: (footnote) This meta-analysis and publication was supported in part by National Institutes of Health grants R01 HL-72410, HL-55757, HL-68088, HL-70897, HL-76794, and HL-78825.

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To provide a contemporary profile of epidemiological trends of infective endocarditis (IE) in Olmsted County, Minnesota. PATIENTS AND METHODS: This study consists of all definite or possible IE cases among adults in Olmsted County from January 1, 1970, through December 31,2006. Cases were identified using resources of the Rochester Epidemiology Project. RESULTS: We identified 150 cases of IE. The age- and sex-adjusted incidences of IE ranged from 5.0 to 7.9 cases per 100,000 person-years with an increasing trend over time differential with respect to sex (for interaction, P=.02); the age-adjusted incidence of IE increased significantly in women (P=.006) but not in men (P=.79). We observed an increasing temporal trend in the mean age at diagnosis (P=.04) and a decreasing trend in the proportion of cases with rheumatic heart disease as a predisposing condition (P=.02). There were no statistically significant temporal trends in the incidence of either Staphylococcus aureus or viridans group streptococcal IE. Data on infection site of acquisition were available for cases seen in 2001 and thereafter, with 50.0% designated as health care-associated, 425% community-acquired, and 7.5% nosocomiai. CONCLUSION: The incidence of IE among women increased from 1970 to 2006. Ongoing surveillance is warranted to determine whether the incidence change in women will be sustained. Subsequent analysis of infection site of acquisition and its impact on the epidemiology of IE are planned. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Survivor bias commonly weakens observational studies, even those published in premier journals. It occurs because patients who live longer are more likely to receive treatment than those who die early. We sought to quantify the effect of survivor bias on the association between valve surgery and mortality in infective endocarditis (IE). Study Design and Setting: The study cohort included 546 IE patients. We compared the hazard ratios (HR) resulting from two propensity score analysis approaches that adjusted for survivor bias (time-dependent variable and matching on follow-up time) with those achieved using the same models but without that adjustment (time-fixed variable). Results: In the total cohort, the HR of surgery in the time-dependent model was 1.9 (95% confidence interval [CI] = 1.1–3.2; P = 0.03) vs. 0.9 (95% CI = 0.5–1.4; P = 0.53) in the time-fixed model. In the propensity score–matched subset, the HR of surgery was 1.3 (95% CI = 0.5–3.1; P = 0.56) and 0.8 (95% CI = 0.4–1.7; P = 0.57) in the subset with and without matching on follow-up time, respectively. Conclusion: Adjusting for survivor bias changed the conclusion about the association between valve surgery and mortality in IE. Researchers should be aware of this bias when evaluating observational studies of treatment efficacy. [Copyright &y& Elsevier]

OBJECTIVE: To examine the effect of the 7-valent pneumococcal conjugate vaccine in a well-characterized population in Olmsted County, Minnesota, with a combination of urban and rural residents likely to have a relatively low risk of invasive pneumococcal disease (IPD). PATIENTS AND METHODS: This population-based study analyzed data from children younger than 5 years to determine the incidence of IPD from January 1, 1995, to December 31, 2007. RESULTS: From 1995 through 2007, 29 cases of IPD were identified in the study population, but 2 patients denied research authorization; thus, 27 cases were available for review. From 1995-1999 to 2001-2003, the incidence of IPD decreased from 33.5 (95% confidence interval [CI], 16.6-50.5) to 10.8 (95% CI, 0.0-23.0) cases per 100,000 person-years (68% decrease; P=.046). The incidence subsequently increased to 15.2 (95% CI, 3.0-27.4) cases per 100,000 person-years from 2004 through 2007; however this change was not significant (P=.62). All cases of IPD with available serotype data from 2002 through 2007 (n=5) were due to non-7-valent conjugate vaccine serotypes. CONCLUSION: Although the baseline incidence of IPD was much lower than that reported in other populations, the overall incidence of IPD decreased significantly in children younger than 5 years after introduction of a 7-valent conjugate vaccine. [ABSTRACT FROM AUTHOR]

Summary: Objective: Following the introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) for children in early 2000 in the United States, a decrease in the incidence of invasive pneumococcal disease (IPD) was seen in adults, likely due to a herd effect. However, there have been recent increases in IPD in adults caused by Streptococcus pneumoniae serotypes not included in PCV-7, so called “replacement disease”. We performed a population-based study to further investigate this emerging concern. Methods: Population-based incidence study in Olmsted County, Minnesota, United States, in adults aged ≥50 years. Results: From 1/1/1995 to 12/31/2007, 104 cases of IPD were identified in Olmsted County in adults aged ≥50 years. We found a 45% increase in the incidence rate of IPD from 2001–2003 (17.7 cases per 100,000 person-years) to 2004–2007 (32.1 cases per 100,000 person-years) (p =0.029). From 2002–2004 to 2005–2007, the incidence rate of IPD caused by S. pneumoniae serotypes not included in PCV-7 increased from 9.2 to 32.8 cases per 100,000 person-years (p <0.001). Conclusion: A recent increase in the incidence of IPD in adults aged ≥50 years was demonstrated in Olmsted County, Minnesota due to serotypes not found in PCV-7. These findings are unique and merit further investigation. [Copyright &y& Elsevier]

Background: Limited data exist regarding temporal trends in permanent pacemaker (PPM) implantation. To describe trends in incidence and comorbidities of PPM recipients, we conducted a retrospective population-based cohort study over a 30-year period.Methods: All 1291 adult residents of Olmsted County, Minnesota, undergoing PPM implantation between 1975 and 2004 were included in the study. Trends in PPM implantation incidence, pacing mode and indication, and comorbidities (via Charlson Comorbidity Index [CCI]) were assessed through the Rochester Epidemiology Project. Permanent pacemaker recipients were compared with age- and sex-matched PPM-free controls from the population.Results: Adjusted implantation incidence rates increased from 36.6 per 100,000 person-years during 1975 to 1979 to 99 per 100,000 person-years during 2000 to 2004 (P < .0001). After adjusting for age (hazard ratio [HR] 1.06 per year), male sex (HR 1.28), and implant year (HR 0.98), the HR for death among PPM recipients by CCI quartiles was 1.0, 1.79, 2.29, and 3.91 for CCI of 0 to 1 (reference), 2 to 3, 4 to 6, and > or = 7, respectively (P < .0001). Overall, PPM recipients had higher CCI than the population-based controls (P = .04), with higher mean CCI noted since 1990. Mean age-adjusted CCI increased from 3.15 to 4.60 among the cases (P < .0001) and from 3.06 to 3.54 among the age- and sex-matched controls (P = .047).Conclusions: There have been significant increases in incidence of PPM implantation over 30 years, and PPM recipients have had an age-independent increase in comorbidities relative to the underlying population, especially over the past 15 years. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate the association between antioxidant use and primary cancer incidence and mortality and to evaluate these effects across specific antioxidant compounds, target organs, and participant subgroups. METHODS: Multiple electronic databases (MEDLINE, Cochrane Controlled Clinical Trials Register, EMBASE, Science Citation index) were searched from their dates of inception until August 2005 to identify eligible randomized clinical trials. Random effects meta-analyses estimated pooled relative risks (RRs) and 95% confidence Intervais (CIs) that described the effect of antioxidants vs placebo on cancer incidence and cancer mortality. RESULTS: Twelve eligible trials, 9 of high methodological quality, were identified (total subject population, 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or mortality (RR, 1.03; 95% CI, 0.92.1.15) or any site-specific cancer incidence. Beta carotene supplementation was associated with an increase in the incidence of cancer among smokers (RR, 1.10; 95% CI, 1.03- 1.10) and with a trend toward increased cancer mortality (RR, 1.16; 95% CI, 0.98-1.37). Selenium supplementation was associated with reduced cancer incidence in men (RR, 037; 95% CI, 0.64-0.92) but not in women (RR, 1.00; 95% CI, 0.89-1.13, value for interaction, P<.001) and with reduced cancer mortality (RR, 0.78; 95% CI, 0.65-0.94). Vitamin E supplementation had no apparent effect on overall cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or cancer mortality (RR, 1.04; 95% CI, 0.97-1.12). CONCLUSION: Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects In men and thus requires further research. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the population-based incidence of lower-extremity cellulitis. METHODS: We performed a population-based survey with the resources of the Rochester Epidemiology Project in Olmsted County, Minnesota. We identified residents of Olmsted County who sought care for cellulitis from January 1, 1999, through December 31, 1999, reviewed medical records to ascertain agreement with a case definition of lower-extremity cellulitis, and calculated the population-based incidence of lower-extremity celluiltis. RESULTS: During 1999, 176 episodes met the case definition of lower-extremity celluiltis; the incidence of lower-extremity celluiltis in Olmsted County was 199 per 100,000 person-years. Sex-specific incidence was 197 per 100,000 person-years for women and 201 per 100,000 person-years for men. in a sex-adjusted model, the incidence increased 3.7% (95% confidence Interval, 2.9%–4.5%) per year Increment in age or 43.8% (95% confidence interval, 33.6%–54.7%) per 10-year increment. The incidence of celluiltis significantly increased with age (P<.001 in Poisson regression) but was not statistically significantly different between the sexes. CONCLUSION: The incidence of lower-extremity cellulitis in this population-based study was high and was affected by age in contrast, sex did not Influence infection incidence. The need for hospitalization and the prevalence of recurrence of lower-extremity celluiltis added to the burden of disease In Olmsted County. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. Background: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. Methods: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I2. Results: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). Conclusions: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The article discusses a report on a novel approach to Staphylococcus aureus Bacteremia (SAB) and Infective Endocarditis (IE) published within the issue.

Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome. To systematically review registered trials currently investigating therapeutic modalities for PACS. A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform. Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19. Data on trial characteristics and intervention characteristics were collected and summarized. After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed. We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment. [ABSTRACT FROM AUTHOR]

Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. Confirmed COVID-19 patients with post-mortem cardiovascular findings. None. Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%–100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%–92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%–92.1%) and fibrosis (median: 35.0%; IQR, 35.0%–90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19. [ABSTRACT FROM AUTHOR]

Post-acute coronavirus 2019 (COVID-19) syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity. To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods. Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed. Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness. Random-effect meta-analysis was performed to produce a pooled prevalence for each symptom at four different follow-up time intervals. Between-study heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study-level variables. Risk of bias was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively. After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257 348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder, and difficulty concentrating (32%, 25%, 24%, and 22%, respectively, at 3- to <6-month follow-up); effort intolerance, fatigue, sleep disorder, and dyspnea (45%, 36%, 29%, and 25%, respectively, at 6- to <9-month follow-up); fatigue (37%) and dyspnea (21%) at 9 to <12 months; and fatigue, dyspnea, sleep disorder, and myalgia (41%, 31%, 30%, and 22%, respectively, at >12-month follow-up). There was substantial between-study heterogeneity for all reported symptom prevalences. Meta-regressions identified statistically significant effect modifiers: world region, male sex, diabetes mellitus, disease severity, and overall study quality score. Five of six studies including a comparator group consisting of COVID-19–negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms. This systematic review found that a large proportion of patients experience post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of COVID-19. However, available studies of post-acute COVID-19 syndrome are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptom definitions and measurements, and longer follow-up. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the impact of prior antiplatelet and statin therapy on symptomatic embolic events in [corrected] infective endocarditis (IE).Patients and Methods: We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to Mayo Clinic (Rochester, MN) from January 1, 2003, to December 31, 2006. Patients were grouped into those who received treatment before infection or controls who did not receive treatment for both antiplatelet therapy and, separately, statin therapy. Because of the retrospective study design and thus the nonrandomized treatment groups, a propensity score approach was used to account for the confounding factors that may have influenced treatment allocation. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine or any combination of these agents. Statin therapy included atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin, or fluvastatin. The primary end point was a symptomatic embolic event that occurred before or during hospitalization. Multivariable logistic regression was used to assess the propensity-adjusted effects of continuous daily therapy with antiplatelet and statin agents on risk of symptomatic emboli. Likewise, Cox proportional hazards regression was used to test for an independent association with 6-month mortality for each of the treatments.Results: The study cohort comprised 283 patients with [corrected] IE. Twenty-eight patients (24.1%) who received prior continuous antiplatelet therapy developed a symptomatic embolic event compared with 66 (39.5%) who did not receive such treatment. After adjusting for propensity to treat, the effect of antiplatelet therapy on embolic risk was not statistically significant (odds ratio, 0.71; 95% confidence interval [CI], 0.37-1.36; P=.30). Only 14 patients (18.2%) who received prior continuous statin therapy developed a symptomatic embolic event compared with 80 (39.4%) of the 203 patients who did not. After adjusting for propensity to treat with statin therapy, the benefit attributable to statins was significant (odds ratio, 0.30; 95% CI, 0.14-0.62; P=.001). The 6-month mortality rate of the entire cohort was 28% (95% CI, 23%-34%). No significant difference was found in the propensity-adjusted rate of 6-month mortality between patients who had and had not undergone prior antiplatelet therapy (P=.91) or those who had and had not undergone prior statin therapy (P=.87).Conclusion: The rate of symptomatic emboli associated with IE was reduced in patients who received continuous daily statin therapy before onset of IE. Despite fewer embolic events observed in patients who received antiplatelet agents, a significant association was not found after adjusting for propensity factors. A continued evaluation of these drugs and their potential impact on subsequent embolism among IE patients is warranted. [ABSTRACT FROM AUTHOR]

Objective: To systematically assess the effect of the adjunctive administration of corticosteroids in the treatment of acute bacterial meningitis.Methods: We performed a systematic review and meta-analysis by searching several databases for reports (published from January 1966 through February 2008) of placebo-controlled randomized trials of corticosteroid use in the treatment of adolescents and adults with acute bacterial meningitis. We used random-effects models. Sources of heterogeneity were explored by preplanned subgroup analyses.Results: The 4 eligible trials (published between 1999 and 2007) were of high methodological quality and included 1261 adult patients. Overall, the short-term mortality rate associated with corticosteroid administration was not significantly lower than that associated with placebo (relative risk [RR], 0.81; 95% confidence interval [CI], 0.54-1.20; I(2)=54%). A significant interaction was found between the effect of corticosteroids and the income status of the country (P=.02) and the prevalence of infection with human immunodeficiency virus (HIV) among study populations (P=.03). The administration of corticosteroids resulted in a lower short-term mortality rate than did the administration of placebo in high-income countries (pooled RR, 0.5; 95% CI, 0.27-0.92; I(2)=0%) and in the studies with a low prevalence of infection with HIV (RR, 0.66; 95% CI, 0.44-0.99; I(2)=0%). In studies from high-income countries, the number needed to treat with corticosteriods to prevent 1 death and 1 neurologic sequela was 12.5 (95% CI, 7.1-100.0) and 11.0 (95% CI, 5.6-100.0), respectively.Conclusion: Our meta-analysis suggests that the adjunctive administration of corticosteroids is beneficial in the treatment of adolescents and adults with bacterial meningitis in patient populations similar to those seen in high-income countries and in areas with a low prevalence of HIV infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To systematically assess the effect of the adjunctive administration of corticosteroids in the treatment of acute bacterial meningitis. METHODS: We performed a systematic review and meta-analysis by searching several databases for reports (published from January 1966 through February 2008) of placebo-controlled randomized trials of corticosterold use In the treatment of adolescents and adults with acute bacterial meningitis. We used random-effects models. Sources of heterogeneity were explored by preplanned subgroup analyses. RESULTS: The 4 eligible trials (published between 1999 and 2007) were of high methodological quality and included 1261 adult patients. Overall, the short-term mortality rate associated with corticosterold administration was not significantly lower than that associated with placebo (relative risk ERR), 0.81; 95% confidence interval [CI], 0.54-1.20; P=54%). A significant interaction was found between the effect of corticosteroids and the Income status of the country (P=.02) and the prevalence of Infection with human immunodeficiency virus (HIV) among study populations (P=.03). The administration of corticosteroids resulted In a lower short-term mortality rate than did the administration of placebo in high-income countries (pooled RR, 0.5; 95% Cl, 0.27-0.92; P=0%) and In the studies with a low prevalence of infection with HIV (RR, 0.66; 95% Cl, 0.44-0.99; P=0%). In studies from high-income countries, the number needed to treat with corticosteriods to prevent 1 death and 1 neurologic sequela was 12.5 (95% CI, 7.1-100.0) and 11.0 (95% CI, 5.6-100.0), respectively. CONCLUSION: Our meta-analysis suggests that the adjunctive administration of corticosteroids is beneficial in the treatment of adolescents and adults with bacterial meningitis in patient populations similar to those seen In high-income countries and in areas with a low prevalence of HIV infection. [ABSTRACT FROM AUTHOR]

Abstract: To highlight the importance of intact skin infection syndromes caused by Stenotrophomonas maltophilia, we review 17 reported cases. Skin infection syndrome presentations included metastatic cellulitis (58%), primary cellulitis (23%), and ecthyma gangrenosum (17%). Associated risk factors were hematologic malignancies and chemotherapy (94%), neutropenia (94%), presence of central venous catheter (17%), and exposure to broad-spectrum antibiotics (84%). The diagnosis was supported by cultures of skin biopsy specimens (35%), blood cultures (24%), or both (41%). Trimethoprim–sulfamethoxazole was the treatment of choice (76%), and outcomes were favorable (71%). [Copyright &y& Elsevier]

Abstract: Objectives: Author contact can enhance the quality of systematic reviews. We conducted a systematic review of the practice of author contact in recently published systematic reviews to characterize its prevalence, quality, and results. Study Design and Setting: Eligible studies were systematic reviews of efficacy published in 2005–2006 in the 25 journals with the highest impact factor publishing systematic reviews in clinical medicine and the Cochrane Library, identified by searching MEDLINE, EMBASE, and the Cochrane Library. Two researchers determined whether and why reviewers contacted authors. To assess the accuracy of the abstracted data, we surveyed reviewers by e-mail. Results: Forty-six (50%) of the 93 eligible systematic reviews published in top journals and 46 (85%) of the 54 eligible Cochrane reviews reported contacting authors of eligible studies. Requests were made most commonly for missing information: 40 (76%) clinical medicine reviews and 45 (98%) Cochrane reviews. One hundred and nine of 147 (74%) reviewers responded to the survey, and reported a higher rate of author contact than apparent from the published record. Conclusion: Although common, author contact is not a universal feature of systematic reviews published in top journals and the Cochrane Library. The conduct and reporting of author contact purpose, procedures, and results require improvement. [Copyright &y& Elsevier]

Summary: Background: Because treatment outcomes of invasive aspergillosis (IA) remain suboptimal, clinicians have resorted to the use of combination antifungal therapy. We therefore sought to systematically review the evidence that addresses the role of combination antifungal therapy in the treatment of invasive aspergillosis. Methods: We retrieved the literature from MEDLINE, EMBASE, Web of Science, Cochrane Controlled Trials Register, and Scopus from inception up to March 2011 for cohort and randomized controlled trial (RCT) studies that assessed the efficacy of combination antifungal therapy for IA and reported on clinical outcomes. Results: Eight studies (one RCT and seven cohort studies) that enrolled a total of 1071 patients met our inclusion criteria. Six cohort studies examined the role of combination therapy for the primary treatment of IA and two for salvage therapy. Various antifungal combinations were used, mainly azoles with either an echinocandin or a polyene. Of the seven cohort studies, four reported adjusted effect estimates, one of which showed a better outcome with combination antifungal therapy and one a trend towards a better outcome, while the remaining two revealed that there was no added advantage of combination antifungal therapy over monotherapy or a better response with monotherapy, respectively. The randomized controlled trial revealed that the use of combination therapy was associated with a better outcome. Conclusion: Cumulative evidence supporting the use of combination antifungal therapy in IA is conflicting and of moderate strength. Well-designed RCTs are required to adequately address the issue of the usefulness of this approach. [Copyright &y& Elsevier]