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COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed. •No specific pharmacological treatments are available to date for COVID-19.•Chloroquine is a widely used, safe and cheap, effective in viral infections in pre-clinical studies.•Specific pre-clinical evidence and expert opinions suggest potential use against SARS-CoV-2.•A search in trial registries shows that 23 clinical trials are ongoing in China.•There is a urgent need of high-quality clinical data from different geographic areas.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Environmental events, including military conflicts, may dramatically affect a hospital's ability to provide routine treatments while maintaining reasonable waiting times. To examine the impact of a military conflict (\"Protective Edge\", PE) on the volume of activity and waiting times for outpatient clinics in a tertiary medical center. Outpatient visits during PE (July-August 2014) were compared to outpatient visits during July-August 2013 (pre-conflict period) and 2015 (post-conflict period) with regards to the daily number of visits and waiting times. Clinics with at least 5,000 annual visits were included. Quantile regression adjusted for confounders was used for the multivariable models, in a stratified analysis by specialty. There were 87,495 outpatient visits during PE and 197,029 visits during the pre- and post-conflict periods. An 11% decrease in the daily number of visits was noted (ranging from 6% decrease in oncology and cardiology to 19-20% decrease in psychiatry and pediatrics). During PE, statistically significant longer waiting times were found for surgery (+1.0 day) and imaging (+1.1 days), while a 2.4 days decrease was noted in pediatrics, controlled for age, sex, ethnicity and the daily number of visits. Median waiting times were unchanged for cardiology, medicine, psychiatry and cardiology. In the midst of a continuing military conflict, there was a notable increase in outpatient visit waiting times in some disciplines, but not all, despite a reduction in the overall volume of visits. Investigating whether similar impacts on patient care occur during other military conflicts or pandemics necessitates further research.

Epidemiological differences between men and women have been reported with regards to sepsis, influenza and severe coronavirus infections including SARS-CoV and MERS-CoV. To systematically review the literature relating to men versus women on SARS-CoV-2 in order to seek differences in disease characteristics (e.g. infectivity, severity) and outcomes (e.g. mortality). We searched 3 electronic databases up or observational studies reporting differences between men and women in the SARS-CoV-2 disease characteristics stated. We identified and included 47 studies, reporting data for 21,454 patients mainly from China. The unadjusted mortality rates of men were higher than those of women, with a mortality OR 0.51 [0.42, 0.61] (p<0.001) for women. The proportion of men presenting with severe disease and admitted to the intensive care unit (ICU) was also higher than that of women (OR 0.75 [0.60-0.93] p<0.001 and OR 0.45 [0.40-0.52] p<0.001 respectively). Adjusted analyses could not be conducted due to lack of data. COVID-19 may be associated with worse outcomes in males than in females. However, until more detailed data are provided in further studies enabling adjusted analysis, this remains an unproven assumption.

Background The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. Main text PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle–Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH 2 O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH 2 O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with “classical” acute respiratory distress syndrome (ARDS). Conclusions Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for “classical” ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.

To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two ‘some concerns’ and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed. •As of June 2020 there is no high quality evidence regarding hydroxychloroquine (HCQ) as treatment or prophylaxis of COVID-19.•Treatment with HCQ may be associated with no reduction of in-hospital death compared to standard care.•High dosages, comorbidities and combinations with macrolides may increase the risk of death and cardiac adverse events.•Post-exposure prophylaxis with HCQ probably has no effect on preventing COVID-19-like symptoms.•HCQ should not be used outside high-quality RCTs in patients with COVID-19.

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume ( V T ) is a standard of care, further individualization of V T may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust V T and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

IntroductionThe term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs).Material and MethodsIn the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommendations and assign levels of evidence. The recommendations and their strength were decided by consensus and, if necessary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus.ConclusionsThe heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group’s main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised critically ill patients.

Table 1 Summary of findings in studies of the HFNT with regard to dyspnea, comfort, and respiratory rate Study Type Design Intervention (N) Control (N) Treatment methods Measurement method Dyspnea Comfort Respiratory rate Bell N. [6] Emerg Med Australas 2015 AHRF RCT HFNT (48) COT (52) HFNT: flow 50 L/m, FiO2 30% titrated to SpO2 95% COT: discretion of the treating physician Dyspnea: Borg Scale Comfort: Likert Scale HFNT§ HFNT§ (1 h) HFNT§ (2 h) Frat J.P. [7] N Engl J Med 2015 AHRF RCT HFNT (106) COT (94) NIV (110) HFNT: flow 50 L/m, FiO2 100% then titrated to SpO2 92% COT: O2 titrated to SpO2 94% Dyspnea: VAS Comfort: VAS HFNT§ (10, 15, 30 min) NS HFNT§ (5, 10, 15, 30 min) AHFR acute hypoxemic respiratory failure, ARF acute respiratory failure, CPAP continuous positive airway pressure, COT conventional oxygen therapy, HFNT high-flow nasal treatment, h hours, IPAP inspiratory positive airway pressure, N number of patients, NA not available, NIV noninvasive ventilation, NS not statistically significant, PES esophageal pressure, PSV pressure support ventilation, RCT randomized controlled trial, VAS visual analog scale §Comparison between intervention and control with a statistically significant p value in favor of (the specified intervention) Heterogeneity in case-mix, the tools used for outcome assessment and measurement time-points precluded performance of meta-analysis. N Engl J Med. 2015;372:2185–96.View ArticleGoogle Scholar Lemiale V, Mokart D, Mayaux J, Lambert J, Rabbat A, Demoule A, Azoulay E. The effects of a 2-h trial of high-flow oxygen by nasal cannula versus Venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial. Ann Emerg Med. 2017;70:465–472 e462.View ArticleGoogle Scholar Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Berrahil-Meksen L, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Theodose I, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bige N, Raphalen JH, Papazian L, Darmon M, Chevret S, Demoule A. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial.

Several mechanisms have been proposed to assume that CQ or hydroxychloroquine (HCQ) may be effective against SARS-CoV-2 (Fig. 1) [1, 2]: 1. a) Cell models of SARS-CoV-1 infection treated with CQ show interference with the glycosylation of ACE-2 receptors, proposed as the site of SARS-CoV-2 cell binding. 2. b) CQ/HCQ increases the pH of acidic cellular organelles, hindering the intermediate stages of endocytosis and virion transport and post-translational modification of newly synthesized viral proteins. 3. c) CQ/HCQ can counter the process of virion assembly and viral protein synthesis. [...]the indications for combined HCQ-azithromycin treatment were not described. On April 3, the International Society of Antimicrobial Chemotherapy (ISAC) declared that “The ISAC Board believes the article does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.” highlighting that “the need for fast release of new data should not reduce the quality of scientific scrutiny” [8].