Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Introduction: A hypercoagulable condition was described in patients with COVID-19 and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods: In a retrospective observational study, 2,574 unselected patients hospitalised in 30 clinical centres in Italy from February 19, 2020 to May 23, 2020 with laboratory-confirmed SARS-CoV-2 infection, were analysed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (HR=0.60; 95%CI: 0.49 to 0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusions: In-hospital heparin treatment was associated with lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomised clinical trials are eagerly awaited to provide clear-cut recommendations.

Propofol in combination with fentanyl or midazolam gives better sedation and ease of endoscopy than propofol alone.

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n¼5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO 2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]¼1.16; 95% confidence interval [CI], 1.04e1.28

We investigated whether intervention with antioxidant vitamins C and E in enteral feeding influenced oxidative stress and clinical outcome in critically ill patients. Two-hundred-sixteen patients expected to require at least 10 days of enteral feeding completed the study. One-hundred-five patients received enteral feeding supplemented with antioxidants, and 111 control patients received an isocaloric formula. Plasma lipoperoxidation (by thiobarbituric acid reactive substances [TBARS] and prostaglandin F(2alpha) isoprostane levels), low-density lipoprotein (LDL) oxidizability, and LDL tocopherol content were determined at baseline and at the end of the 10-day period. The clinical 28-day outcome was also assessed. Plasma TBARS and isoprostanes were 5.33 +/- 1.26 nM/mL and 312 +/- 68 pg/mL, respectively, before treatment and 2.42 +/- 0.61 nM/mL and 198 +/- 42 pg/mL after intervention (P < 0.01 for both comparisons). Antioxidants improved LDL resistance to oxidative stress by approximately 30% (the lag time before treatment was 87 +/- 23 min and was 118 +/- 20 min after treatment; P < 0.04). There was a significantly reduced 28-day mortality after antioxidant intervention (45.7% in the antioxidant group and 67.5% in the regular-feeding group; P < 0.05). Isoprostanes may provide a sensitive biochemical marker for dose selection in studies involving antioxidants.