Consent to participate: Written informed consent was obtained from all subjects or their legally authorised representatives. Consent for publication: Not applicableAvailability of data and material: De-identified data collected during the trial will be made available upon reasonable request to researchers who provide a methodologically sound proposal, after approval by the study authors, and with a signed data access agreement. Questions about data are handled by the corresponding author.

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In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home. Methods: A multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH 60). Secondary outcomes included nosocomial infections. Results: The median [interquartile range (IQR)] number of DAOH 60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0-53.0) and 49.0 (IQR 43.8-53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) − 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51-5.10), P = 0.57. There were no serious, or probiotic-associated adverse events. Conclusion: Early and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.

Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The ‘Prophylactic Melatonin for Delirium in Intensive Care’ study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. Discussion The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647, registration date: 06 April 2016. WHO Trial Number – U1111-1175-1814

IntroductionThe effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain.Methods and analysisThe Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60.Ethics and disseminationROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results.

16 patients were admitted to a tertiary intensive care in 2019 for viral pneumonia. 11 were prescribed corticosteroids for vasopressor resistant shock, and 9 received intravenous vitamin C (1.5 g QID) at the discretion of the treating clinician. Data was collected prospectively to examine the change in PaO2/FiO2 ratios after administration of Vitamin C, and the association with mortality. Vitamin C did not change oxygenation, but combined with corticosteroids there was trend towards a beneficial separation in the P/F ratio over time. The use of corticosteroids was associated with a mortality benefit. These findings need confirmation in a larger study. Wordcount 99

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Asse ssment o f ACTH d ef i cie nc y in chi l dren wit h hypo t halami c -pituit ary dys func t ion .Insulin hy pog l yc emi a ( IH ) i s one of t he mos t va l ua bl e pro cedures to t e st the pi t ui tary ACTH re serve -es pe c ially a s part of t h e combined t e st o f hypothalami c -pitui tary f uncti on. The ACTH re sponse t o IH is a steep