Emotional sequelae during and following hospital admission for diabetic ketoacidosis

Increasingly patients are surviving admission to intensive care units (ICUs) with life-threatening, critical illness. This has led to a growing interest in longer-term patient outcomes, including their psychological health. This thesis consists of two discrete sections: 1) a systematic review of research that evaluated emotional outcomes between 3 and 12 months post-ICU discharge, and 2) a longitudinal cohort study of emotional sequelae among adults with Type 1 diabetes during and following admission for diabetic ketoacidosis (DKA). The systematic review identified seven studies that met inclusion criteria, and highlighted weaknesses in the existing literature. From the available evidence there appears to be elevated rates of clinically significant depression (11%), anxiety (15%) and post-traumatic stress disorder (PTSD) symptoms (23%) 3 months after discharge, and these remain high 9 months later (12%; 18%, and 27%, respectively). The prospective study of DKA admissions indicated substantial rates of clinically relevant depression (25%); anxiety (37.5%), and PTSD symptoms (37.5%) prior to discharge. However, 3 months later the rates of depression and PTSD had substantially attenuated (both 8.3%) although rates of anxiety (37.5%) remained higher than that found in the general population (7%) and the local Type 1 diabetes clinical community (11.9%). Those admitted with DKA had significantly poorer HbA1c compared to the overall Type 1 clinic population (10.9% vs. 8.9%; p < 0.0001), which indicates substantial difficulties in self managing their condition. It appears that psychological problems are elevated over time following ICU discharge. PTSD is notably high and enduring in general ICU survivors, whereas was observed to fall away in the DKA sample. Anxiety seems to be elevated and this persists over time following DKA; this is pertinent given the dearth of research on the role of anxiety in the efforts of people with type 1 diabetes to manage their condition. As far as the authors’ are aware, this is the first study tracking emotional outcomes post DKA discharge. There are clearly significant psychological issues that will likely impact on staff efforts to provide ward-based care aimed at improving post-discharge diabetes control, and on the future efforts of those admitted for DKA to self-manage a complex condition. A greater awareness of the psychological issues affecting people with type 1 diabetes who experience DKA is an important first step. More specifically, a better understanding among health professionals about the ways emotional distress can impact on self-management is needed, as well as a greater understanding of how best to communicate information and educational material in light of possible information processing deficits (which may be a result of emotional distress). Larger, multi-centre, higher quality studies are required in both general ICU settings and looking at specific disease complications (such as DKA). Psychological screening for ICU survivors and implementation of a care pathway to allow access to services post-ICU may be a useful development

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Optimization of adsorptive removal of α-toluic acid by CaO2 nanoparticles using response surface methodology

The present work addresses the optimization of process parameters for adsorptive removal of α-toluic acid by calcium peroxide (CaO2) nanoparticles using response surface methodology (RSM). CaO2 nanoparticles were synthesized by chemical precipitation method and confirmed by Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analysis which shows the CaO2 nanoparticles size range of 5–15 nm. A series of batch adsorption experiments were performed using CaO2 nanoparticles to remove α-toluic acid from the aqueous solution. Further, an experimental based central composite design (CCD) was developed to study the interactive effect of CaO2 adsorbent dosage, initial concentration of α-toluic acid, and contact time on α-toluic acid removal efficiency (response) and optimization of the process. Analysis of variance (ANOVA) was performed to determine the significance of the individual and the interactive effects of variables on the response. The model predicted response showed a good agreement with the experimental response, and the coefficient of determination, (R2) was 0.92. Among the variables, the interactive effect of adsorbent dosage and the initial α-toluic acid concentration was found to have more influence on the response than the contact time. Numerical optimization of process by RSM showed the optimal adsorbent dosage, initial concentration of α-toluic acid, and contact time as 0.03 g, 7.06 g/L, and 34 min respectively. The predicted removal efficiency was 99.50%. The experiments performed under these conditions showed α-toluic acid removal efficiency up to 98.05%, which confirmed the adequacy of the model prediction