Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Prevention of ventilator-associated pneumonia through care bundles: A systematic review and meta-analysis.

Background: Ventilator-associated pneumonia (VAP) represents a common hospital-acquired infection among mechanically ventilated patients. We summarized evidence concerning ventilator care bundles to prevent VAP. Methods: A systematic review and meta-analysis were performed. Randomized controlled trials and controlled observational studies of adults undergoing mechanical ventilation (MV) for at least 48 h were considered for inclusion. Outcomes of interest were the number of VAP episodes, duration of MV, hospital and intensive care unit (ICU) length of stay, and mortality. A systematic search was conducted in the MEDLINE, the Cochrane Library, and the Web of Science between 1985 and 2022. Results are reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI). The PROSPERO registration number is CRD42022341780. Results: Thirty-six studies including 116,873 MV participants met the inclusion criteria. A total of 84,031 participants underwent care bundles for VAP prevention. The most reported component of the ventilator bundle was head-of-bed elevation (n=83,146), followed by oral care (n=80,787). A reduction in the number of VAP episodes was observed among those receiving ventilator care bundles, compared with the non-care bundle group (OR=0.42, 95% CI: 0.33, 0.54). Additionally, the implementation of care bundles decreased the duration of MV (MD=-0.59, 95% CI: -1.03, -0.15) and hospital length of stay (MD=-1.24, 95% CI: -2.30, -0.18) in studies where educational activities were part of the bundle. Data regarding mortality were inconclusive. Conclusions: The implementation of ventilator care bundles reduced the number of VAP episodes and the duration of MV in adult ICUs. Their application in combination with educational activities seemed to improve clinical outcomes.

Impact of air pollution on respiratory microbiome: A narrative review.

BACKGROUND: Respiratory microbiome composition depends on an intricate balance between host characteristics, diet, and environmental factors. Some studies indicate a bidirectional relationship between respiratory microbiota and disease. Air pollution is consistently associated with increased respiratory morbidity and mortality in different populations and across different ages. The aim of this review was to report a summary of the evidence regarding the impact of air pollution on the upper and lower respiratory tract microbiome. METHODS: A literature search from interaction between air pollution and respiratory microbiome was performed (2010-2022). RESULTS: Sixteen studies demonstrated changes in microbiome with both environmental and household air pollution. Increasing levels of air pollutants are associated with lower relative abundance of Corynebacterium and increasing levels of pathogen colonization, such as Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa and Acinetobacter baumannii, altering the incidence and clinical course of respiratory infections. This ultimately leads to an excess of morbidity and mortality due to antimicrobial resistance. CONCLUSION: Changes of air pollution on the respiratory microbiome may influence respiratory infections in critical care. Use of probiotics may restore the diversity of baseline microbiome, preventing infections by resistant organisms in the critical care setting. Using protective equipment decreased the effect of air pollutants on increasing potentially pathogenic microorganisms.

The effect of sex inequality on solid organ transplantation: A systematic review and meta-analysis.

BACKGROUND: Sex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT). METHODS: A systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615. RESULTS: After retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83-0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86-0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76-0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males. CONCLUSIONS: Females represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management.

Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights.

INTRODUCTION: Varicella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown. METHODS: We conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms "varicella zoster" and "COVID-19″. PROSPERO Register Number: CRD42021289399. RESULTS: The search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42-70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3-10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found. CONCLUSION: This study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.

Ribavirin for Treatment of Subjects with Respiratory Syncytial Virus-Related Infection: A Systematic Review and Meta-Analysis.

INTRODUCTION: Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower respiratory tract infections (LRTIs) in all age groups, adults with comorbidities, and immunocompromised patients. The aim was to summarize the evidence concerning efficacy and safety of ribavirin in subjects diagnosed with RSV associated with LRTI. METHODS: A systematic review and meta-analysis were performed. Eligible studies were observational (> 10 subjects) and randomized-controlled trials of subjects with aerosol/oral ribavirin for RSV-LRTI. Comparator was supportive care or placebo. Systematic search on PubMed, Cochrane Library, and Web of Science databases was conducted between January 2001 and January 2022. PROSPERO register number: CRD42022308147. RESULTS: After retrieving 907 studies, 10 observational studies and 1 randomized controlled trial were included (4/11 high quality of evidence). Seven studies included subjects with haematological malignancy/stem cell transplant, two lung transplants, and two healthy individuals. A total of 788 subjects diagnosed with RSV infection were included; 14.3% of them presented with only LRTI. Among 445 subjects treated with ribavirin, 195 (43.8%) received an aerosolized formulation. Pooled meta-analysis showed no differences in mortality [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.28-1.42] in all subjects treated with aerosol/oral ribavirin compared to supportive care. In subgroup analysis, mortality was significantly lower in haematological subjects (RR: 0.32; 95% CI: 0.14-0.71), but did not differ significantly in lung transplant recipients (RR: 0.89; 95% CI 0.31-2.56). Oral ribavirin (vs. supportive care) was associated with increased viral clearance (RR: 2.60; 95% CI: 1.35-4.99). Seventeen adverse events were reported among 119 subjects, but none were severe. CONCLUSION: Ribavirin should be considered for treatment of RSV-LRTI in haematological subjects. There is a lack of evidence to support its use in lung transplant recipients. Oral formulation appears to be an easier, safe, and cost-effective alternative to aerosolized ribavirin. Further advances needs to focus on newer antivirals.

Solid organ transplantation from donors with recent or current SARS-CoV-2 infection: A systematic review.

BACKGROUND: Solid-organ transplantation (SOT) from SARS-CoV-2 positive donors could be a life-saving opportunity worth grasping. We perform a systematic review to evaluate the recipient outcomes of SOT from donors with recent or current SARS-CoV-2 infection. METHODS: Search strategy was performed in PubMed, Cochrane COVID-19 Study Register, and Web of Science databases from the 1st of January 2019 to the 31st of December 2021. SOT adult recipients from a donor with past or current SARS-CoV-2 infection were elegible for inclusion. Outcomes were viral transmission, COVID-19 symptoms, mortality, hospital stay, and complications. PROSPERO Register Number: CRD42022303242 FINDINGS: Sixty-nine recipients received 48 kidneys, 18 livers and 3 hearts from 57 donors. Six additional transplants from positive lungs were identified. IgG+ anti-SARS-CoV-2 titers were detected among 10/16 recipients; only 4% (3/69) recipients were vaccinated. Non-lung transplant recipients received organs from 10/57 (17.5%) donors with persistent COVID-19. In 18/57 donors, SARS-CoV-2 RNA was detected (median 32 Cycle threshold [Ct]) at procurement. Among non-lung transplant recipients, SARS-CoV-2 viral transmission was not documented. Four patients presented delayed graft dysfunction, two patients acute rejection, and two patients died of septic shock. The median (IQR) hospital stay was 18 (11-28) days in recipients from symptomatic donors. Viral transmission occurred from three lung donors to their recipients, who developed COVID-19 symptoms. One of the recipients subsequently died. CONCLUSION: Use of non-lung (kidney, liver and heart) organs from SARS-CoV-2 positive donors seem to be a safe practice, with a low risk of transmission irrespective of the presence of symptoms at the time of procurement. Low viral replication (Ct > 30) was safe among non-lung donors, even if persistently symptomatic at procurement.

Ventilator-associated events in children: A multicentre prospective cohort study.

BACKGROUND: The Centres for Disease Control and Prevention (CDC) broadened the focus of surveillance from ventilator-associated pneumonia to ventilator-associated event (VAE) for quality purposes. No paediatric definition of VAE (PaedVAE) has been accurately validated. We aimed to analyse the incidence and impact on patient outcomes resulting from the application of the adult and two paediatric VAE (PaedVAE) criteria. SECONDARY OBJECTIVE: to evaluate VAE/PaedVAE as factors associated with increased duration of mechanical ventilation (MV) and Paediatric Intensive Care Unit (PICU) stay. METHODS: Multicentre observational prospective cohort study in 15 PICUs in Spain. VAEs were assessed using the 2013/2015 CDC classification. PaedVAE were assessed using the CDC definition based on mean airway pressure (MAP-PaedVAE) versus a paediatric definition based on positive end-expiratory pressure (PEEP-PaedVAE). Children who underwent MV ≥ 48 h were included. RESULTS: A total of 3626 ventilator-days in 391 patients were analysed. The incidence of VAE, MAP-PaedVAE and PEEP-PaedVAE was 8.55, 5.24 and 20.96 per 1000 ventilator-days, respectively. The median time [IQR] for VAE, MAP-PaedVAE and PEEP-PaedVAE development from the MV onset was 4 [3-12.5], 4 [3-14], and 5 [3-7.75] days, respectively. Among survivors, all three were associated with increased MV duration (> 7 days) and PICU stay (> 10 days) at univariate analysis. Multivariate analysis showed that PEEP-PaedVAE was the only definition independently associated with MV above 7 days [OR = 4.86, 95% CI (2.41-10.11)] and PICU stay [OR = 3.49, 95% CI (1.68-7.80)] above ten days, respectively. CONCLUSIONS: A VAE definition based on slight PEEP increases should be preferred for VAE surveillance in children.

Antiseptic barrier caps in central line-associated bloodstream infections: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the evidence concerning the effectiveness of antiseptic barrier caps vs. manual disinfection in preventing central line-associated bloodstream infection (CLABSI). METHODS: The protocol of this systematic review and meta-analysis was pre-registered in PROSPERO (CRD42021259582). PubMed, Cochrane Library and Web of Science databases were searched from 2011 to 2021. Randomized-controlled trials (RCT) and observational studies on hospitalized patients of any age were included. RESULTS: Fourteen studies were included. Compared with manual disinfection, antiseptic barrier caps significantly reduced CLABSI rate per 1000 line-days (Standardized Mean Difference [SMD]: -0.02; 95%CI: -0.03 to -0.01) and number of CLABSI per patient (RR: 0.60; 95%CI: 0.41-0.89). Subgroup analysis showed that antiseptic barrier caps were more effective in reducing CLABSI rate per 1000 line-days in ICU (SMD: -0.02; 95%CI: -0.03 to -0.01) and non-ICU patients (SMD: -0.03; 95%CI: -0.05 to -0.01), adults (SMD: -0.02; 95%CI: -0.04 to -0.01), as in observational studies (SMD: -0.02; 95%CI: -0.02 to -0.01). Antiseptic barrier caps also significantly reduce CLABSI risk in ICU patients (RR: 0.65, 95%CI: 0.42-1.00), adults (RR: 0.50, 95%CI: 0.29-0.86), and observational studies (RR: 0.54; 95%CI: 0.32-0.91). No differences were found when only children or RCTs were taken into account. Median cost savings amongst studies were $21,890 [IQR 16,350-45,000] per CLABSI. CONCLUSIONS: Antiseptic barrier caps appear to be effective in reducing CLABSI. The real-world impact needs to be confirmed by RCTs.

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis.

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3-139.7) and quality of life (MD -7.52; 95% CI -13.06 to -1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV1% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements.

Systemic infections associated with tattoos or permanent makeup: A systematic review

IntroductionThe aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture.MethodsA literature search was performed in PubMed database (2009–2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews.ResultsWe identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis.ConclusionsBacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

Introducción:El objetivo de este artículo es resumir la información publicada sobre las complicaciones infecciosas sistémicas de los tatuajes para tener una actualización de la situación actual.Métodos:Se realizó una búsqueda de literatura en la base de datos PubMed (2009-2019), que se comparó con una búsqueda sin restricción de año. Los criterios de elegibilidad fueron estudios sobre infecciones sistémicas relacionadas con tatuajes, incluidos informes de casos, series de casos, investigaciones de brotes, revisiones y revisiones sistemáticas.Resultados:Se identificaron 17 manuscritos con infecciones sistémicas entre 2009 y 2019, y se informó de una muerte. A diferencia de los registros históricos, no se notificaron informes de tuberculosis sistémica, sífilis ni infecciones viíricas (hepatitis o VIH) durante el período de estudio. Se identificaron algunos casos esporádicos de Mycobacterium leprae (India) o de linfadenopatías regionales asociadas con lesiones cutáneas en micobacterias no tuberculosas. La fiebre persistente con escalofríos era común en las infecciones bacterianas del torrente sanguíneo. Se informó un episodio de síndrome de choque tóxico estafilocócico y varios episodios de choque séptico, asociados con celulitis o fascitis necrosante dentro de las 2 semanas posteriores al procedimiento, predominantemente causada por bacterias piógenas (S. aureus o estreptococo). La identificación de embolias pulmonares o sistémicas en ausencia de síntomas locales fue indicativa de endocarditis infecciosa (derecha o izquierda).Conclusiones:Las infecciones bacterianas deben considerarse en sujetos que desarrollen fiebre y escalofríos después de los tatuajes, independientemente de los síntomas locales. Se ha documentado un cambio en los organismos causales y las micobacterias no tuberculosas constituyen organismos emergentes. Las condiciones higiénicas adecuadas son fundamentales a la hora de realizar un tatuaje. (AU)

Critical appraisal of international adult bronchiectasis guidelines using the AGREE II tool.

BACKGROUND: Guidelines aim to standardize and optimize diagnosis and management. We evaluated the quality of evidence supporting recommendations from different international adult guidelines on bronchiectasis, and classified with the GRADE system. METHODS: Quality of eligible clinical practice guidelines was assessed for six domains using the AGREE II tool, with ≥ 80% rating as excellent. RESULTS: Seven guidelines (283 recommendations) were analyzed, and four of them were considered "recommended for use" (three reported after 2017 as excellent). Overall, 144 (50.9%) recommendations were based on low-quality evidence, representing 81.5% in diagnosis and 36.2% in therapy. In contrast, 5/92 (5.4%) and 40/191 (20.9%) recommendations regarding diagnostic and treatment (respectively) were based on high-quality evidence. Quality agreement ratings were significantly (p< 0.05) higher for guidelines delivered after 2015, progressing from 27.7% to 58.3%, qualifying as excellent. Highest scores were documented in the domains of "scope and purpose" followed by "clarifying of presentation" and "editorial independence". CONCLUSION: Updated guidelines reported after 2017 improved quality, although well-designed randomized clinical trials remain an unmet need. AGREE II quality assessment identified four guidelines qualified as recommended for use. Improvements are required in stakeholder involvement and applicability.

Systemic infections associated with tattoos or permanent makeup: A systematic review.

INTRODUCTION: The aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture. METHODS: A literature search was performed in PubMed database (2009-2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews. RESULTS: We identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis. CONCLUSIONS: Bacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations. METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154. RESULTS: Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70-5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81-18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28-1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82-0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35-3.27) at the end of therapy, with a number needed to treat of 6. CONCLUSIONS: IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.

Neuraminidase inhibitors and single dose baloxavir are effective and safe in uncomplicated influenza: a meta-analysis of randomized controlled trials.

BACKGROUND: Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found. METHODS: PubMed, Cochrane Library, and Web of Science databases were searched through December 2020. Randomized-controlled trials (RCT) that enrolled patients with laboratory-confirmed influenza receiving neuraminidase inhibitors (NAI) or baloxavir comparing to placebo were assessed. PROSPERO Registration-number: CRD42021226854. RESULTS: Twenty-one RCTs (11,697 patients) were included. Antiviral administration significantly reduced time to clinical resolution (mean difference: -21.3 hours) and total influenza-related complications (OR:0.55, 95%CI: 0.42-0.73). Specifically, antivirals significantly decreased bronchitis (OR:0.54, 95%CI: 0.38-0.75), sinusitis (OR:0.51, 95%CI: 0.33-0.78), acute otitis media (OR:0.48, 95%CI: 0.30-0.77), and antibiotic prescription (OR:0.62; 95%CI: 0.48-0.80). A positive trend favored antivirals administration to reduce pneumonia (OR:0.47, 95%CI: 0.16-1.33), or hospitalization rates (OR:0.65; 95%CI: 0.34-1.24) compared to placebo, but did not reach statistical significance. Adverse events (AE) were reported in 11%, 8.9%, and 5.1% of NAIs, placebo and baloxavir recipients, respectively. Compared with NAIs, administration of baloxavir showed non-significantly reduced AEs (OR:0.74, 95%CI: 0.53-1.04). CONCLUSIONS: Single-dose baloxavir and NAIs were superior to placebo to reduce complications in uncomplicated influenza, with 40% significant reduction in antibiotic prescription. Safety and efficacy of single-dose baloxavir were non-inferior to NAIs.

Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.

The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.

Neuraminidase inhibitors are effective and safe in reducing influenza complications: meta-analysis of randomized controlled trials.

BACKGROUND: There is scarce evidence verifying the impact of neuraminidase inhibitors (NAIs) in reducing influenza complications. The aim was to evaluate the available evidence from randomized-controlled trials (RCT) regarding the efficacy and safety of NAIs in reducing influenza complications. METHODS: A systematic search of the literature was performed in the Cochrane Library, PubMed and Web of Science databases (2006-2019). Eligibility criteria were RCT that enrolled patients of any age or clinical severity with seasonal influenza (H1N1, H3N2, or B) or influenza-like syndrome and receiving NAIs comparing to placebo therapy. RESULTS: Eighteen RCTs (9004 patients) were included: nine focused on oral oseltamivir, six on inhaled zanamivir, and three on intravenous peramivir. Administration of NAIs therapy significantly decreased the time to clinical resolution (median difference: -17.7 hours; and total influenza-related complications (OR: 0.64, 95%CI: 0.51-0.82). In addition, NAIs significantly decreased acute otitis media complication (OR: 0.50, 95%CI: 0.31-0.82) and need for antibiotic treatment (OR: 0.64, 95%CI: 0.46-0.90); and showed a trend towards a reduced occurrence of pneumonia (OR: 0.44, 95%CI: 0.10-2.00), bronchitis (OR: 0.80, 95%CI: 0.43-1.48), sinusitis (OR: 0.73, 95%CI: 0.40-1.32), asthma exacerbations (OR: 0.57, 95%CI: 0.28-1.16), and hospitalizations (OR: 0.57, 95%CI: 0.24-1.38). The overall proportion of AEs tend to increase with NAIs treatment (OR: 1.16, 95%CI: 0.92-1.47). Use of NAIs was associated with a significant increase of nausea and vomiting (OR: 1.61, 95%CI: 1.04-2.50) and a decrease on diarrhea (OR: 0.81, 95%CI: 0.65-1.00). CONCLUSIONS: NAIs are effective in reducing time to clinical resolution, total influenza-related complications, otitis media, and need of antibiotic administration. Reductions on mortality, pneumonia, asthma exacerbations or hospitalization rates only did demonstrate a trend benefit in favor of NAIs. The only significant AE is the increased occurrence of nausea and vomiting.

Update in COVID-19 in the intensive care unit from the 2020 HELLENIC Athens International symposium.

The 2020 International Web Scientific Event in COVID-19 pandemic in critically ill patients aimed at updating the information and knowledge on the COVID-19 pandemic in the intensive care unit. Experts reviewed the latest literature relating to the COVID-19 pandemic in critically ill patients, such as epidemiology, pathophysiology, phenotypes of infection, COVID-19 as a systematic infection, molecular diagnosis, mechanical ventilation, thromboprophylaxis, COVID-19 associated co-infections, immunotherapy, plasma treatment, catheter-related bloodstream infections, artificial intelligence for COVID-19, and vaccination. Antiviral therapy and co-infections are out of the scope of this review. In this review, each of these issues is discussed with key messages regarding management and further research being presented after a brief review of available evidence.

Evaluation of the quality of evidence supporting guideline recommendations for the nutritional management of critically ill adults.

AIMS: The primary aim of this study was to evaluate the quality of evidence supporting the 2019 European Society for Clinical Nutrition and Metabolism (ESPEN) and 2016 American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations for medical nutrition therapy in critically ill patients. Secondary objectives are to assess the differences between 2019 ESPEN and 2016 ASPEN recommendations and to inform relevant stakeholders of areas requiring improvement in the research. METHODS: The 2019 ESPEN and 2016 ASPEN guidelines were identified and downloaded from the official websites. The level of evidence and strength of recommendations from the guidelines were standardised to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Level of evidence was classified as high-quality (randomised controlled trials (RCTs) without important limitations), moderate-quality (downgraded RCTs or upgraded observational studies) or low-quality (observational studies without specific strengths or important limitations, case series, case reports). In addition, good practice points (GPP; recommendations based on the clinical experience of the guideline development group) were considered. Strength of recommendation was reported as strong or weak. RESULTS: From 152 total recommendations, only five (3.3%) were supported by high-quality evidence, with 14 being strong recommendations. A total of 79 (52.0%) recommendations were GPPs. Overall, the proportion of recommendations supported by high-quality (7% [ESPEN] vs. 1.1% [ASPEN], p < 0.05) and moderate-quality evidence (33.3% [ESPEN] vs. 8.4% [ASPEN], p < 0.01) was significantly higher in ESPEN guidelines. On the other hand, ASPEN guidelines reported a greater proportion of recommendations supported by GPPs (58.9% [ASPEN] vs. 40.4% [ESPEN], p = 0.03). In enteral and parenteral nutrition, the proportion of recommendations supported by moderate-quality evidence (50% [ESPEN] vs. 15.8% [ASPEN], p < 0.01) was significantly higher in ESPEN guidelines. CONCLUSION: Published guideline recommendations for the nutritional management of critically ill adults remain largely supported by expert opinion and only a minority by high-quality evidence. An urgent unmet clinical need for high-quality clinical trials is warranted.

Quality of evidence supporting Surviving Sepsis Campaign Recommendations.

INTRODUCTION: The Surviving Sepsis Campaign (SSC) guidelines, released in 2017, are a combination of expert opinion and evidence-based medicine, adopted by many institutions as a standard of practice. The aim was to analyse the quality of evidence supporting recommendations on the management of sepsis. METHODS: The strength and quality of evidence (high, moderate, low-very low and best practice statements) of each recommendation were extracted. Randomised controlled trials were required to qualify as high-quality evidence. RESULTS: A total of 96 recommendations were formulated, and 87 were included. Among thirty-one (43%) strong recommendations, only 15.2% were supported by high-quality evidence. Overall, thirty-seven (42.5%) recommendations were based on low-quality evidence, followed by 28 (32.2%) based on moderate-quality, 15 (17.2%) were best practice statements and only seven (8.0%) were supported by high-quality evidence. Randomised controlled trials supported 21.4%, 9.5% and 8.6% recommendations on mechanical ventilation, resuscitation, and management/adjuvant therapy, respectively. In contrast, none high-quality evidence recommendation supported antimicrobial/source control (82.4% were low-very low evidence or best practice statements), and nutrition. CONCLUSIONS: In the SSC guidelines most recommendations were informed by indirect evidence and non-systematic observations. While awaiting trials results, Delphi-like approaches or multi-criteria decision analyses should guide recommendations.