Objectives The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. Trial design REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. Participants The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. Inclusion criteria Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria:  • Moderate – PaO2/FiO2 100–200 mmHg;  • Severe – PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. Exclusion criteria Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history:  a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days;  b) Systemic corticosteroid use before hospitalization;  c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment;  d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g.  • intractable hyperglycaemia;  • active gastrointestinal bleeding;  • adrenal gland disorders;  • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. Intervention and comparator Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1–5, followed by dexamethasone 10 mg intravenously once daily on day 6–10. Patients in the control group will receive dexamethasone 6 mg day 1–10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. Main outcomes Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. Secondary endpoints a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. Randomisation Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. Blinding (masking) This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. Numbers to be randomised (sample size) The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. Trial Status This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. Trial registration The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. Full protocol The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Clocked manufacturing processes such as sheet metal forming and cutting processes pose a challenge for process monitoring approaches due to inaccessibility of tool components and high production rates which make direct measurement of the physical process conditions unfeasible. Auxiliary data such as force signals are acquired and assessed, often still relying on control and run charts or even visual control in order to monitor the process. The data of these signals are high-dimensional and contain a large amount of redundant information. Therefore, the processing of such signals focuses on compressing information into as few variables as possible that still represent the important information for the manufacturing process. Due to repeatability in clocked sheet metal processing, the data generated consist of a series of time series of the same operation with varying physical conditions due to wear and variations in lubrication or material properties. In this paper two major research objectives are identified: (i) the theoretical evaluation of representation learning methods in context of clocked sheet metal processing, and the connection with (ii) the practical evaluation of the learned representations with a given use case to track the wear progression in series of strokes. The contribution of this paper is the comparison of varying time series representation learning techniques and their performance evaluation in a theoretical and practical scenario.

Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality. Objective It is known that the closed tracheal suction system (CTSS) produces less hemodynamic and gasometric deterioration than an open tracheal suction system (OTSS). Use is limited because no decrease in the incidence of ventilator-associated pneumonia (VAP) was found and also because it is more expensive. But, is daily periodic change of the CTSS necessary? The aim of this study was to analyze the incidence of VAP using a CTSS without periodic change versus an OTSS. Methods It is a prospective study of ICU patients from 1 January 2004 to 31 October 2004. Patients who required mechanical ventilation (MV) were randomized into two groups: one group was suctioned with CTSS without periodic change and another group with OTSS. An aspirate tracheal swab and a throat swab on admission and afterwards twice weekly were taken. VAP was classified based on throat flora in endogenous and exogenous samples. The statistical analysis was performed by chi-square test and Student's t test, and w...