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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.

Candida spp . infections are a major cause of morbidity and mortality in critically ill patients. Candida auris is an emerging multi-drug-resistant fungus that is rapidly spreading worldwide. Since the first reports in 2009, many isolates across five continents have been identified as agents of hospital-associated infections. Independent and simultaneous outbreaks of C. auris are becoming a major concern for healthcare and scientific community. Moreover, laboratory misidentification and multi-drug-resistant profiles, rarely observed for other non-albicans Candida species, result in difficult eradication and frequent therapeutic failures of C. auris infections. The aim of this review was to provide an updated and comprehensive report of the global spread of C. auris , focusing on clinical and microbiological characteristics, mechanisms of virulence and antifungal resistance, and efficacy of available control, preventive, and therapeutic strategies.

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.

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.

Background The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO 2 clearance after 2 h of treatment. Methods We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO 2  ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO 2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO 2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO 2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group ( p  = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO 2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p  = 0.0003). Both treatments had a significant effect on PaCO 2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO 2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration : The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Background Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia. Methods PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia. Results We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta- d -glucan) but more data is needed. Conclusions PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence.

The aim of this systematic review and meta-analysis was to estimate the pooled occurrence of ventilator-associated pneumonia (VAP) among patients admitted to an intensive care unit with COVID-19 and mortality of those who developed VAP. We performed a systematic search on PubMed, EMBASE and Web of Science from inception to 2nd March 2021 for nonrandomized studies specifically addressing VAP in adult patients with COVID-19 and reporting data on at least one primary outcome of interest. Random effect single-arm meta-analysis was performed for the occurrence of VAP and mortality (at the longest follow up) and ICU length of stay. Twenty studies were included in the systematic review and meta-analysis, for a total of 2611 patients with at least one episode of VAP. The pooled estimated occurrence of VAP was of 45.4% (95% C.I. 37.8–53.2%; 2611/5593 patients; I2 = 96%). The pooled estimated occurrence of mortality was 42.7% (95% C.I. 34–51.7%; 371/946 patients; I2 = 82%). The estimated summary estimated metric mean ICU LOS was 28.58 days (95% C.I. 21.4–35.8; I2 = 98%). Sensitivity analysis showed that patients with COVID-19 may have a higher risk of developing VAP than patients without COVID-19 (OR 3.24; 95% C.I. 2.2–4.7; P = 0.015; I2 = 67.7%; five studies with a comparison group).

In the past 10 years, anesthesiologists have been concentrating on opioid-free anesthesia (OFA) and utilizing locoregional anesthesia/analgesia to manage pain during open and laparoscopic surgeries. The goal is to reduce the negative effects of using opioids during and after surgery. This study aims to evaluate the efficacy and safety of OFA protocol with low doses of magnesium sulfate, Clonidine, and nonsteroidal anti-inflammatory drugs (NSAIDs) employing transversus abdominis plane (TAP) block and rectus sheath block (RSB) for intraoperative and postoperative pain control in laparoscopic abdominal surgery. We conducted a single-center unblinded randomized controlled trial (RCT) to compare the OFA protocol with bilateral TAP and RS block versus the conventional analgesic plan with opioids. We included all consecutive patients older than 18 who planned for laparoscopic scheduled abdominal surgery and underwent general anesthesia. We found a statistically significant lower numeric rating scale (NRS)score at each time point in the OFA group ( p  < 0.001). A significant statistical difference was also found in the mobilization recovery time, which occurred at 36.00 [18.00, 48.00] hours in the OFA group versus 48.00 [24.00, 72.00] hours in the control one ( p  < 0.001). The length of stay (LOS) was also in favor of the OFA group 4.00 [2.00, 6.00] days versus 6.00 [4.00, 9.00] days in the control one ( p  < 0.001). Concerning side effects, there was a reduced/null onset in the OFA group compared with the control. No ICU admissions were recorded in the first 24 h after the end of surgery. This study showed that the preoperative implementation of locoregional anesthesia techniques with our OFA protocols guarantees the adequacy of intraoperative antinociception, while low dose magnesium sulfate and clonidine ensure hemodynamic stability comparable to opioids during surgery. OFA eliminates the side effects of opioids and decreases patients’ length of stay and early mobilization without requiring additional drugs. Trial registration ISRCTN15228105. Retrospectively registered 02/12/2023.

High-quality chest compressions are pivotal to improve survival from cardiac arrest. Basic life support training of school students is an international priority. The aim of this trial was to assess the effectiveness of a real-time training software (Laerdal QCPR®) compared to a standard instructor-based feedback for chest compressions acquisition in secondary school students. After an interactive frontal lesson about basic life support and high quality chest compressions, 144 students were randomized to two types of chest compressions training: 1) using Laerdal QCPR® (QCPR group- 72 students) for real-time feedback during chest compressions with the guide of an instructor who considered software data for students' correction 2) based on standard instructor-based feedback (SF group- 72 students). Both groups had a minimum of a 2-minute chest compressions training session. Students were required to reach a minimum technical skill level before the evaluation. We evaluated all students at 7 days from the training with a 2-minute chest compressions session. The primary outcome was the compression score, which is an overall measure of chest compressions quality calculated by the software expressed as percentage. 125 students were present at the evaluation session (60 from QCPR group and 65 from SF group). Students in QCPR group had a significantly higher compression score (median 90%, IQR 81.9-96.0) compared to SF group (median 67%, IQR 27.7-87.5), p = 0.0003. Students in QCPR group performed significantly higher percentage of fully released chest compressions (71% [IQR 24.5-99.0] vs 24% [IQR 2.5-88.2]; p = 0.005) and better chest compression rate (117.5/min [IQR 106-123.5] vs 125/min [115-135.2]; p = 0.001). In secondary school students, a training for chest compressions based on a real-time feedback software (Laerdal QCPR®) guided by an instructor is superior to instructor-based feedback training in terms of chest compression technical skill acquisition. Australian New Zealand Clinical Trials Registry ACTRN12616000383460.