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This longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support.

Abstract Patients diagnosed with diabetes mellitus (DM) who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) belong to the most vulnerable patient subgroups. Emerging data has shown increased risks of severe infections, increased in ICU admissions, longer durations of admission, and increased mortality among coronavirus disease 2019 (COVID-19) patients with diabetes. We performed a subgroup analysis comparing the outcomes of patients diagnosed with DM (n = 2191) versus patients without DM (n = 8690) on our data from our study based on a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from around the Philippines. We determined distribution differences between two independent samples using Mann–Whitney U and t tests. Data on the time to onset of mortality, respiratory failure, intensive care unit (ICU) admission were used to build Kaplan–Meier curves and to compute for hazard ratios (HR). The odds ratios (OR) for longer ventilator dependence, longer ICU stay, and longer hospital stays were computed via multivariate logistic regression. Adjusted hazard ratios (aHR) and ORs (aOR) with 95% CI were calculated. We included a total of 10,881 patients with confirmed COVID-19 infection (2191 have DM while 8690 did not have DM). The median age of the DM cohort was 61, with a female to male ratio of 1:1.25 and more than 50% of the DM population were above 60 years old. The aOR for mortality was significantly higher among those in the DM group by 1.46 (95% CI 1.28–1.68; p

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children. Methods This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March–June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes. Results Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3–41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5–14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5–30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p

This longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lanzara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Patients diagnosed with diabetes mellitus (DM) who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) belong to the most vulnerable patient subgroups. Emerging data has shown increased risks of severe infections, increased in ICU admissions, longer durations of admission, and increased mortality among coronavirus disease 2019 (COVID-19) patients with diabetes. We performed a subgroup analysis comparing the outcomes of patients diagnosed with DM (n = 2191) versus patients without DM (n = 8690) on our data from our study based on a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from around the Philippines. We determined distribution differences between two independent samples using Mann–Whitney U and t tests. Data on the time to onset of mortality, respiratory failure, intensive care unit (ICU) admission were used to build Kaplan–Meier curves and to compute for hazard ratios (HR). The odds ratios (OR) for longer ventilator dependence, longer ICU stay, and longer hospital stays were computed via multivariate logistic regression. Adjusted hazard ratios (aHR) and ORs (aOR) with 95% CI were calculated. We included a total of 10,881 patients with confirmed COVID-19 infection (2191 have DM while 8690 did not have DM). The median age of the DM cohort was 61, with a female to male ratio of 1:1.25 and more than 50% of the DM population were above 60 years old. The aOR for mortality was significantly higher among those in the DM group by 1.46 (95% CI 1.28–1.68; p < 0.001) as compared to the non-DM group. Similarly, the aOR for respiratory failure was also significantly higher among those in the DM group by 1.67 (95% CI 1.46–1.90). The aOR for developing severe COVID-19 at nadir was significantly higher among those in the DM group by 1.85 (95% CI 1.65–2.07; p < 0.001). The aOR for ICU admission was significantly higher among those in the DM group by 1.80 (95% CI 1.59–2.05) than those in the non-DM group. DM patients had significantly longer duration of ventilator dependence (aOR 1.33, 95% CI 1.08–1.64; p = 0.008) and longer hospital admission (aOR 1.13, 95% CI 1.01–1.26; p = 0.027). The presence of DM among COVID-19 patients significantly increased the risk of mortality, respiratory failure, duration of ventilator dependence, severe/critical COVID-19, ICU admission, and length of hospital stay. [ABSTRACT FROM AUTHOR]

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132–2.435) and by 1.352 (95% CI 1.042–1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346–2.722), by 1.614 (95% CI 1.260–2.068), and by 1.234 (95% CI 1.089–1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457–2.673) and by 1.831 (95% CI 1.506–2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772–1.179), longer ICU stay (aOR 0.983, 95% CI 0.772–1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947–1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection.

Objective: Long-term changes in burnout and its predictors in hospital staff during the COVID-19 pandemic were investigated in an international study., Methods: Two online surveys were distributed to hospital staff in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) between May and October 2020 (T1) and between February and April 2021 (T2), using the following variables: Burnout (emotional exhaustion and depersonalization), job function, age, gender, and contact with COVID-19 patients; individual resources (self-compassion, sense of coherence, social support) and work-related resources and demands (support at the workplace, risk perception, health and safety at the workplace, altruistic acceptance of risk). Data were analyzed using linear mixed models repeated measures, controlled for age., Results: A total of 612 respondents were included (76% women). We found an increase in burnout from T1 to T2. Burnout was high among personnel with high contact with COVID-19 patients. Individual factors (self-compassion, sense of coherence) and work-related factors (support at the workplace, risk perception, health and safety at the workplace) showed associations with burnout. Low health and safety at the workplace at T1 was associated with an increase in emotional exhaustion at T2. Men showed an increase in depersonalization if they had much contact with COVID-19 patients., Conclusion: Burnout represents a potential problematic consequence of occupational contact with COVID-19 patients. Special attention should be paid to this group in organizational health management. Self-compassion, sense of coherence, support at the workplace, risk perception, and health and safety at the workplace may be important starting points for interventions., Registration: Müller, M. M. (2020, August 30). Cope-Corona: Identifying and strengthening personal resources of hospital staff to cope with the Corona pandemic. Open Science Foundation., Competing Interests: Declaration of Competing Interest The authors have no competing interests to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Susceptibility of children and adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and persistence of antibody response to the virus after infection resolution remain poorly understood, despite their significant public health implications., Methods: A prospective cross-sectional seroprevalence study with volunteer families that included at least 1 first-reported adult case positive by SARS-CoV-2 by polymerase chain reaction (PCR) and at least 1 child aged <15 years living in the same household under strict home confinement was conducted in the metropolitan Barcelona Health Region, Spain, during the pandemic period 28 April 2020-3 June 2020. All household members were tested at home using a rapid SARS-CoV-2 antibody assay with finger prick-obtained capillary blood., Results: A total of 381 family households including 381 first-reported PCR-positive adult cases and 1084 contacts (672 children, 412 adults) were enrolled. SARS-CoV-2 seroprevalence rates were 17.6% (118 of 672) in children and 18.7% (77 of 335) in adult contacts (P = .64). Among first-reported cases, seropositivity rates varied from 84.0% in adults previously hospitalized and tested within 6 weeks since the first positive PCR result to 31.5% in those not hospitalized and tested after that lag time (P < .001). Nearly all (99.9%) positive children were asymptomatic or had mild symptoms., Conclusions: Children appear to have similar probability as adults to become infected by SARS-CoV-2 in quarantined family households but remain largely asymptomatic. Adult antibody protection against SARS-CoV-2 seems to be weak beyond 6 weeks post-infection confirmation, especially in cases that have experienced mild disease., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children., Methods: This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March-June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes., Results: Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3-41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5-14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5-30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively)., Conclusions: Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.

Objectives: This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers., Background: Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy., Methods: From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide. Interactions with statin treatment were also assessed., Results: The two models-model 1 (endostatin, interleukin 8, soluble ST2, troponin T, galectin 3, and chemokine [C-C motif] ligand 21) and model 2 (troponin T, soluble ST2, galectin 3, pentraxin 3, and soluble tumor necrosis factor receptor 2)-significantly improved the CORONA and Seattle HF models but added only modestly to their Harrell's C statistic and net reclassification index. In addition, rosuvastatin had no effect on the levels of a wide range of inflammatory and extracellular matrix markers, but there was a tendency for patients with a lower level of biomarkers in the 2 panels to have a positive effect from statin treatment., Conclusions: In the specific HF patient population studied, a multimarker approach using the particular panel of biomarkers measured was of limited clinical value for identifying future risk of adverse outcomes., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study., Methods and Results: Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (≥60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality., Conclusions: Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.

Aims: To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective., Methods and Results: Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (≤ 19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.46-0.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50-0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54-0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16-0.67; P= 0.002)., Conclusion: Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.

Objectives: The purpose of this study was to determine whether coenzyme Q₁₀ is an independent predictor of prognosis in heart failure., Background: Blood and tissue concentrations of the essential cofactor coenzyme Q₁₀ are decreased by statins, and this could be harmful in patients with heart failure., Methods: We measured serum coenzyme Q₁₀ in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes., Results: Patients with lower coenzyme Q₁₀ concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q₁₀ tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q₁₀ was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q₁₀ but there was no interaction between coenzyme Q₁₀ and the effect of rosuvastatin., Conclusions: Coenzyme Q₁₀ is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q₁₀, but even in patients with a low baseline coenzyme Q₁₀, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310)., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In patients with heart failure (HF), statin treatment might improve myocardial perfusion, but could also have detrimental effects on myocardial metabolism. A predefined substudy of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial sought to determine the effects of statin treatment on myocardial blood flow reserve and cardiac metabolism. Sixteen patients with HF (New York Heart Association class II or III) were randomized to rosuvastatin 10 mg/day (n = 8) or placebo treatment (n = 8). At baseline and after 6 months of treatment, nitrogen-13 ammonia at rest and after dipyridamole stress and 18-fluorodeoxyglucose positron emission tomography were performed. Rosuvastatin treatment significantly lowered total (-36%, p <0.01) and low-density lipoprotein (-47%, p <0.001) cholesterol and C-reactive protein levels (-36%, p <0.05). Myocardial perfusion reserve (ratio) changed from 1.64 +/- 0.90 to 1.30 +/- 0.37 in placebo-treated and from 1.51 +/- 0.18 to 1.55 +/- 0.34 in rosuvastatin-treated patients (p = NS). Metabolic mismatch changed from 4.25 +/- 2.37% to 4.38 +/- 3.81% in placebo-treated and from 5.13 +/- 2.75% to 3.50 +/- 2.73% in rosuvastatin-treated patients (p = NS). In conclusion, changes regarding myocardial perfusion and metabolic mismatch after 6 months of rosuvastatin treatment in patients with HF did not suggest any beneficial or adverse effects in this pilot study, although due to the small numbers of patients small effects might have been missed., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims: To estimate the cost-effectiveness of 10 mg rosuvastatin daily for older patients with systolic heart failure in the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) trial., Methods and Results: This within trial analysis of CORONA used major cardiovascular (CV) events as the outcome measure. Resource use was valued and the costs of hospitalizations, procedures, and statin use compared. Cost-effectiveness was estimated as cost per major CV event avoided. There were significantly fewer major CV events in the rosuvastatin group compared with the placebo group (1.04 vs. 1.20 per patient; difference 0.164; 95% CI: 0.075-0.254, P < 0.001). The average cost of CV hospitalizations and procedures was significantly lower for those receiving rosuvastatin ( pound1531 vs. pound1769; difference pound238; 95% CI: pound73-403, P = 0.005); the additional cost of the statin resulted in significantly higher total costs for the rosuvastatin group ( pound1769 vs. pound2072; difference pound303; 95% CI: pound138-468, P < 0.001). Overall, rosuvastatin was found to cost pound1840 (95% CI: pound562-6028) per major CV event avoided., Conclusion: This economic analysis showed that a significant reduction in major CV events with rosuvastatin led to significantly reduced costs of CV hospitalizations and procedures. The reduction in associated costs for major CV events was found to offset partially (by 44%) the cost of rosuvastatin treatment in patients with systolic heart failure.

Objectives: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective., Background: Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile., Methods: In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke., Results: Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin., Conclusions: Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin., (2009 by the American College of Cardiology Foundation)

Aims: Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all-cause mortality., Methods and Results: We built a series of models for nine different fatal and non-fatal outcomes. For each outcome, a model was first built using demographic and clinical variables (Step 1), then with the addition of biochemical measures (serum creatinine, alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A-1 and B, and triglycerides) (Step 2) and finally with the incorporation of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Ranked according to the Wald chi(2) value, age (56), ejection fraction (44), and body mass index (42) were most predictive of all-cause mortality in Step 1 (total model chi(2) 343). Creatinine was the most powerful predictor at Step 2 (48) and ApoA-1 ranked fifth (25), with the overall chi(2) increasing to 440. Log NT-proBNP (167) was the most powerful of the 14 independently predictive variables identified at Step 3 and the overall chi(2) increased to 600. NT-proBNP was the most powerful predictor of each other outcome. hsCRP was not a predictor of all-cause mortality but did predict the composite atherothrombotic outcome., Conclusion: Of the two new biomarkers studied in prognostic models in heart failure, NT-proBNP, but not hsCRP, added substantial and independent predictive information, for a range of clinical outcomes, to that provided by simple demographic, clinical, and biochemical measures. ApoA-1 was more predictive than LDL or HDL.

Background: Previous prospective outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure., Aim: The primary objective is to determine whether rosuvastatin (10 mg) reduces the combined endpoint of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke (time to first event). The first secondary endpoint is all-cause mortality., Methods: CORONA is a randomized, double-blind, placebo-controlled trial. Briefly, men and women, aged > or =60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or =0.40 (NYHA class III and IV) or < or =0.35 (NYHA class II) were eligible if they were not using or in need of cholesterol lowering drugs., Results: Mean age was 73 years (n=5016; 24% women), with 37% in NYHA II and 62% in NYHA III, ejection fraction 0.31, total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infarction, 63% hypertension, and 30% diabetes. Patients are well treated for heart failure with 90% on loop or thiazide diuretics, 42% aldosterone antagonists, 91% ACE inhibitor or AT-I blocker, 75% beta-blockers, and 32% digitalis., Conclusion: CORONA is important for three main reasons: (1) A positive result is very important because of the high risk of the population studied, the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society, and the health economic issues involved. (2) If negative, new mechanistic questions about heart failure have to be raised. (3) If neutral we can avoid unnecessary polypharmacy.

Background: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. Methods: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. Results: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49–3.3, p < 0.01). Conclusions: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. [ABSTRACT FROM AUTHOR]

Owing to coronavirus disease 2019 (COVID-19), lung damage is seen as an important problem in patients after recovery. In this study, evaluation of respiratory symptoms and lung ultrasonography (LUS) findings of those who have had symptomatic and asymptomatic COVID-19 disease in children was aimed. A total of 81 patients with positive and 18 healthy children with negative COVID-19 antibodies were included to the study. The most common late presentation symptoms were cough (85.2%), shortness of breath (77.8%), and chest pain (60.5%). In LUS, 2 or less B lines, 3 or more B lines, and Z line were seen in 66.7%, 33.3%, and 9.9% of patients, respectively. There was no significant difference between control and patients in terms of these parameters (P >.05). Pleural effusion was detected in 2 patients in the late period. Respiratory system findings may develop in the late period in patients infected with COVID-19. Therefore, patients should be followed closely. [ABSTRACT FROM AUTHOR]

Background: The global pandemic caused by the coronavirus disease 2019 (COVID-19) resulted in many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on the COVID-19 illness. Methods: Data from the Philippine CORONA study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. Results: A total of 10,881 patients were included in this study, and 156 (1.4%) patients had been diagnosed with COPD. A majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients were 2.0× more likely to present with severe to critical COVID-19 disease. COVID-19 patients with COPD in our study have a 1.7× increased mortality, 1.6× increased respiratory failure, and 2.0× increased risk for ICU admission. Smokers with COVID-19 were 1.8× more likely to present with more severe disease and have a 1.9× increased mortality. Conclusion: Our study supports the growing evidence that COPD among COVID-19 patients is a risk factor for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS‐induced pathology. Methods and results: The study included 20 females [median age 65 years; interquarile range (IQR) = 58–70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed‐rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5–28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31–48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)‐1 receptor antagonist and soluble T‐cell immunoglobulin mucin domain‐3 (sTIM‐3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL‐6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor‐15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N‐terminal‐pro‐brain‐natriuretic peptide, while the correlations of IL‐6 and sTIM‐3 with N‐terminal‐pro‐brain‐natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase‐9 increased during follow‐up to reach levels higher than those in the healthy controls. Conclusion: The median IMR was only slightly elevated in this study, but about one‐third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM‐3 as a potential novel marker. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 pneumonia in children has a lower incidence and severity compared to adults. Risk factors are adolescence and comorbidities. Our aims were to describe the characteristics of children admitted with SARS-CoV-2 pneumonia, identify risk factors associated with severity and compare the cases according to the variant of SARS-CoV-2. This was a descriptive and retrospective study, including patients aged 0–18 years hospitalized in a tertiary-care hospital between 1 March 2020 and 1 March 2022. Epidemiological, clinical, diagnostic and therapeutic data were analyzed. Forty-four patients were admitted; twenty-six (59%) were male and twenty-seven (61%) were older than 12 years. Thirty-six (82%) had comorbidities, the most frequent of which were obesity and asthma. Seven (15.9%) patients required high-flow oxygen, eleven (25%) non-invasive ventilation and four (9.1%) conventional mechanical ventilation. In critically ill patients, higher levels of anemia, lymphopenia, procalcitonin, lactate dehydrogenase (LDH) and hypoalbuminemia and lower levels of HDL-cholesterol were detected (all p < 0.05). Prematurity (p = 0.022) was associated with intensive care unit admission. Patients were younger during the Omicron wave (p < 0.01); no variant was associated with greater severity. In conclusion, pediatric patients with a history of prematurity or with anemia, lymphopenia, elevated procalcitonin, elevated LDH levels, hypoalbuminemia and low HDL-cholesterol levels may require admission and present more severe forms. Apart from age, no notable differences between SARS-CoV-2 variant periods were found. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of mortality and disability worldwide, with low and middle-income countries bearing the greatest burden. This article focuses on stroke prevention and awareness in the Philippines, a country grappling with high stroke incidence and limited healthcare resources. The two-pronged approach presented by the authors aims to address the challenges of stroke care by combining community-based prevention and targeted public awareness campaigns. The community-based stroke prevention component involves personalized risk factor assessments and tailored interventions conducted at local health centers. By identifying modifiable risk factors such as hypertension, diabetes, smoking, and elevated cholesterol levels, healthcare professionals can provide targeted education and interventions to individuals at risk. Additionally, the decentralized targeted stroke awareness campaigns emphasize public education through culturally adapted materials, engagement with local stakeholders, and media campaigns. These initiatives seek to increase awareness of stroke symptoms and prompt presentation in medical facilities. By implementing this comprehensive approach, we aim to mitigate the burden of stroke in the Philippines, improve stroke outcomes, and raise public awareness about stroke recognition and prevention. [ABSTRACT FROM AUTHOR]

Aims: It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure. Methods and results: Aldosterone, cystatin C, high‐sensitivity troponin T (hs‐TnT), galectin‐3, growth differentiation factor‐15 (GDF‐15), kidney injury molecule‐1, matrix metalloproteinase‐2 and ‐9, soluble suppression of tumourigenicity‐2, tissue inhibitor of metalloproteinase‐1 (TIMP‐1) and urinary albumin to creatinine ratio were measured in 1559 of PARADIGM‐HF participants. We tested whether these biomarkers, individually or collectively, improved the performance of the PREDICT‐HF prognostic model, which includes clinical, routine laboratory, and natriuretic peptide data, for the primary endpoint and cardiovascular and all‐cause mortality. The mean age of participants was 67.3 ± 9.9 years, 1254 (80.4%) were men and 1103 (71%) were in New York Heart Association class II. During a mean follow‐up of 30.7 months, 300 patients experienced the primary outcome and 197 died. Added individually, only four biomarkers were independently associated with all outcomes: hs‐TnT, GDF‐15, cystatin C and TIMP‐1. When all biomarkers were added simultaneously to the PREDICT‐HF models, only hs‐TnT remained an independent predictor of all three endpoints. GDF‐15 also remained predictive of the primary endpoint; TIMP‐1 was the only other predictor of both cardiovascular and all‐cause mortality. Individually or in combination, these biomarkers did not lead to significant improvements in discrimination or reclassification. Conclusions: None of the biomarkers studied individually or collectively led to a meaningful improvement in the prediction of outcomes over what is provided by clinical, routine laboratory, and natriuretic peptide variables. [ABSTRACT FROM AUTHOR]

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Lung ultrasound (LUS) can detect lower respiratory tract involvement in children with acute SARS-CoV-2 infection. However, its role in follow-up assessments is still unclear. To describe LUS findings in children after SARS-CoV-2 infection, we conducted a prospective study in a population of pediatric patients referred to the post-COVID unit in a tertiary center during the study period from February 2021 to May 2022. Children were classified as recovered from acute infection or with persisting symptoms. LUS was performed in all children and a LUS score (ranging from 0 to 36 points) was calculated according to the Italian Academy of Thoracic Ultrasound. Six hundred forty-seven children (304 females, 47%) were enrolled. The median follow-up evaluation was two months. The median age was 7.9 (IQR: 6) years. At the follow-up evaluation, 251 patients (38.8%) had persistent symptoms, of whom 104 (16.1%) had at least one respiratory symptom. The median LUS level was 2 (IQR: 4). LUS findings and LUS scores did not differ in children with Long COVID compared to the group of children fully recovered from the initial infection. In conclusion, after SARS-CoV-2 infection, LUS was mostly normal or showed minimal artifacts in all groups of children. [ABSTRACT FROM AUTHOR]

Background: Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. Methods: This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan–Meier methods. Results: A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow‐up of 32 months (IQR: 26–41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P < 0.001). Cox regression showed that 1‐SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024–1.242)], cardiovascular mortality [1.112 (1.032–1.198)], all‐cause mortality [1.142 (1.057–1.234)], and HF rehospitalization [1.122 (1.030–1.224)] after adjustment for potential confounders including NT‐proBNP. Kaplan–Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all‐cause mortality (all P values < 0.001). Furthermore, both Kaplan–Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT‐proBNP were more likely to predict all‐cause or cardiovascular mortality (both P < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. Conclusions: Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT‐proBNP, suggesting that sAXL is a promising prognostic marker for further study. [ABSTRACT FROM AUTHOR]