Learning to speak in a second language: Does multiple talker production training benefit production of English vowels in Arabic children?

High-variability phonetic training (HVPT) has been shown to be highly effective in improving secondlanguage (L2) perception in adults, and to also benefit production. In contrast, recent studies have suggested that children may benefit more from low-variability phonetic training (LVPT), in particular for production. The present study compares HVPT and LVPT articulatory training for production and perception of Standard Southern British English (SSBE) vowels in children in a non-immersion context. Forty-six monolingual Arabic children aged 8-12 years were randomly assigned to single- (LVPT) or multi-talker (HVPT) training. Both groups completed five articulatory training sessions on 18 vowels and a battery of perception and production tests evaluated improvement. The results showed that the LVPT group performed better not only in production, but also in category discrimination. The results support previous studies that have suggested that LVPT training might be more successful with children

Formulaic Language in People with Probable Alzheimer's Disease: A Frequency-Based Approach

BACKGROUND: Language change can be a valuable biological marker of overall cognitive change in Alzheimer's disease (AD) and other forms of dementia. Previous reports have described increased use of language formulas in AD, i.e., combinations likely processed in a holistic manner. Words that commonly occur together are more likely to become a formula. OBJECTIVE: To determine if frequency of co-occurrence as one indicator for formulaic language can distinguish people with probable AD from controls and if variables are sensitive to time post-symptom onset. METHODS: We developed the Frequency in Language Analysis Tool (FLAT), which indicates degrees of formulaicity in an individual language sample. The FLAT accomplishes this by comparing individual language samples to co-occurrence data from the British National Corpus (BNC). Our analysis also contained more conventional language variables in order to assess novel contributions of the FLAT. We analyzed data from the Pitt Corpus, which is part of DementiaBank. RESULTS: Both conventional and co-occurrence variables were able to distinguish AD and control groups. According to co-occurrence data, people with probable AD produced more formulaic language than controls. Only co-occurrence variables correlated with disease progression. DISCUSSION: Frequency of word co-occurrences is one indicator for formulaicity and a valuable contribution to characterizing language change in AD

Intensive care doctors and nurses personal preferences for intensive Care, as compared to the general population: a discrete choice experiment

Background To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. Methods Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. Results A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. Conclusion The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival

Airway pressure release ventilation in mechanically ventilated patients with COVID-19: a multicenter observational study

Background Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation. Methods A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated. Results Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03–0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation. Conclusions Based on the findings of this study, we urge caution with the use of APRV in COVID-19

Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: The multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT)

Introduction The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain. Methods and analysis The 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 dissemination ROCIT 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 number Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial

Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. Trial registration: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471. Registered on 20 December 2015

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570