Irritability as a Transdiagnostic Risk Factor for Functional Impairment in Autistic and Non-autistic Toddlers and Preschoolers.

Trait irritability in toddlerhood is a powerful risk factor for later internalizing and externalizing challenges in non-autistic children, but the predictive clinical utility of irritability is unknown in autism. Irritability is a trait-level emotional response (i.e., frustration) to a blocked goal and is one source of disruptive behavior. Irritability has two facets: Frustration is the degree to which emotion is elevated after a blocked goal, while soothability is the rate of recovery from peak distress. We aimed to: (1) compare and describe the two facets of irritability in non-autistic and young autistic children, and (2) assess whether children's reward sensitivity and executive function moderate the relation between irritability and clinical symptoms. Participants were 90 autistic (n=43) and non-autistic (n = 47) 2- and 4-year-olds. Autistic children did not have different levels of frustration but were more difficult to soothe compared to non-autistic children, according to parents. Further, frustration and soothability were less strongly correlated for autistic compared to non-autistic children. For all children, executive function (specifically, inhibition) moderated, or ameliorated the strength of, the relation between irritability (both soothability and frustration) and externalizing challenges. This study provides evidence for irritability as a transdiagnostic risk factor for clinically significant emotion regulation challenges. Further, the effect of trait irritability may be ameliorated by children's executive function in a transdiagnostic manner. Future work should examine the unique aspects of soothability to how irritability presents within autism, as well as evaluate and modify emotion regulation interventions for autistic toddlers and preschoolers.

Clinical characteristics and outcomes of 85 intensive care patients with Covid-19 in South London: A single centre observational study.

Background: In March 2020, Covid-19 secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic. Methods: This retrospective observational study included patients with Covid-19, managed in a single intensive care unit (ICU). We collected data on patient characteristics, laboratory and radiological findings and ICU management. Data are reported as median (interquartile range). Binary logistic regression modelling was used to identify variables at ICU admission associated with mortality. Results: 85 patients (age 57.3 years [49.4-64.2], 75.3% male) were followed up for 34 days (26-40). The commonest comorbidities were hypertension (51.8%), obesity (48.7%), and type 2 diabetes (31.8%). Covid-19 presented with shortness of breath (89.4%), fever (82.4%), and cough (81.2%), first noted 8 days (6-10) prior to ICU admission. PaO2/FiO2-ratios at ICU admission were 8.28 kPa (7.04-11.7). Bilateral infiltrates on chest X-ray, lymphopenia, and raised C-reactive protein and ferritin were typical. 81.2% received invasive mechanical ventilation (IMV). Acute kidney injury occurred in 62.4% with renal replacement therapy required in 20.0%. By the end of the follow-up period, 44.7% had died, 30.6% had been discharged from hospital, 14.1% had been discharged from ICU but remained in hospital and 10.6% remained in ICU. ICU length of stay was 14 days (9-23). Age was the only variable at admission which was associated with mortality. PaO2/FiO2-ratio, driving pressure and peak ferritin and neutrophil count over the first 72-hours of IMV all correlated with mortality. Conclusions: We report the clinical characteristics, ICU practices and outcomes of a South London cohort with Covid-19, and have identified factors which correlate with mortality. By sharing our insight, we hope to further understanding of this novel disease.

Severe Respiratory Failure, Extracorporeal Membrane Oxygenation, and Intracranial Hemorrhage.

OBJECTIVES: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Patients admitted between December 2011 and February 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (g/L) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%. CONCLUSIONS: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.

Healthcare-associated bloodstream infections in critically ill patients: descriptive cross-sectional database study evaluating concordance with clinical site isolates.

BACKGROUND: Healthcare-associated bloodstream infections are related to both increased antibiotic use and risk of adverse outcomes. An in-depth understanding of their epidemiology is essential to reduce occurrence and to improve outcomes by targeted prevention strategies. The objectives of the study were to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. METHODS: We conducted a descriptive cross-sectional study in critically ill adults admitted to a tertiary semi-closed intensive care unit in England to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. All nosocomial positive blood cultures over a 4-year study period were identified. Pathogens detected and concordances with clinical site are reported as proportions. RESULTS: Contaminant pathogens accounted for half of the isolates. The most common non-contaminant pathogens cultured were Pseudomonas spp. (8.0%), Enterococcus spp. (7.3%) and Escherichia coli (5.6%). Central venous catheter-linked bloodstream infections represent only 6.0% of the positive blood cultures. Excluding contaminants and central venous line infections, in only 39.5% of the bloodstream infections could a concordant clinical site source be identified, the respiratory and urinary tracts being the most common. CONCLUSIONS: Clinical practice should focus on a) improving blood culture techniques to reduce detection of contaminant pathogens and b) ensuring paired clinical site cultures are performed alongside all blood cultures to better understand the epidemiology and potential implications of primary and secondary discordant health-care associated bloodstream infections.