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PurposeTo assess the effect of low dose corticosteroids on outcomes in adults with septic shock.MethodsWe systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.ResultsThere were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89–1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91–1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90–1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03–2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) −1.52 days; 95% CI −1.71 to −1.32, p < 0.0001], duration of mechanical ventilation (MD −1.38 days; 95% CI −1.96 to −0.80, p < 0.0001), and ICU stay (MD −0.75 days; 95% CI −1.34 to −0.17, p = 0.01) were shorter with corticosteroids versus placebo.ConclusionsIn adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced.PROSPERO registration no. CRD42017084037.

PurposeTo determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.MethodsWe conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.ResultsWe obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p = 0.86), self-care (24.7% vs. 26.0%, p = 0.44), usual activities (44.5% vs. 46.8%, p = 0.28), pain/discomfort (42.4% vs. 41.6%, p = 0.54) and anxiety/depression (36.9% vs. 37.7%, p = 0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p = 0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1 ± 11.9 vs. 8.0 ± 9.8 days (p < 0.0001) and 22.8 ± 21.2 vs. 19.1 ± 19.0 days, (p = 0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345 ± 46,263 (€35,109 ± 35,043) versus 34,844 ± 38,281 (€28,223 ± 31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517 ± 10,254), p < 0.001 as was the total cost of hospital treatment to 2 years: A$74,120 ± 60,750 (€60,037 ± 49,207) versus A$65,806 ± 59,856 (€53,302 ± 48,483), p = 0.005.ConclusionsCritically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

Background Over the last two decades, there have been several improvements in the management of diabetes. Whether this has impacted on the epidemiology and outcome of diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission is unknown. Method This was a retrospective study of 8533 patients with the diagnosis of DKA admitted to 171 ICUs in Australia and New Zealand between 2000–2013 with separate independent analysis of those on established insulin (Group I) or not on insulin (Group NI) at the time of hospitalisation. Results Of the 8553 patients, 2344 (27 %) were identified as NI. The incidence of ICU admission with DKA progressively increased fivefold from 0.97/100,000 (95 % CI 0.84–1.10) in 2000 to 5.3/100,000 (95 % CI 4.98–5.53) in 2013 ( P  < 0.0001), with the proportions between I and NI remaining stable. Rising incidences were observed mainly in rural and metropolitan hospitals ( P  < 0.01). In the first 24 hours in the ICU, mean worst pH increased over the study period from 7.20 ± 0.02 to 7.24 ± 0.01 ( P  < 0.0001), and mean lowest plasma bicarbonate from 12.1 ± 6.6 to 13.8 ± 6.6 mmol/L ( P  < 0.0001). In contrast, mean highest plasma glucose decreased from 26.3 ± 14 to 23.2 ± 13.1 mmol/L ( P  < 0.0001). Hospital mortality was significantly greater in NI as compared to I (2.4 % vs 1.1 %, P  > 0.0001). Elevated plasma urea in the first 24 hours (≥25 mmol/L, adjusted odds ratio 20.6 (6.54–65.7), P  < 0.0001) was the strongest individual predictor of mortality. Conclusions The incidence of ICU admission of patients with DKA in Australia and New Zealand has increased fivefold over the last decade, with a significant proportion of patients not on insulin at presentation. Overall physiological status in the first 24 hours of ICU admission has progressively improved and mortality rates have remained stable. However, DKA patients not on established insulin therapy at presentation had significantly worse outcomes. This notion has epidemiologic, diagnostic and management implications.

Host immune dysregulation is thought to contribute to much of the harm associated with coronavirus disease 2019 (COVID-19) [1, 2]. Accordingly, significant focus has been directed toward finding immunomodulatory therapies to offset this host-mediated damage, leading to the beneficial effects of corticosteroids being demonstrated [3]. As elevated concentrations of interleukin-6 (IL-6) have been found to be an important prognostic factor in COVID-19 [4], attention has also focused on targeted IL-6 receptor antagonism. Tocilizumab, a recombinant humanised monoclonal antibody, is one such agent.

In the ADRENAL trial, among adult patients with septic shock, hydrocortisone did not lead to lower mortality than placebo. Now, a prespecified secondary analysis shows that hydrocortisone did not affect mortality 6 months after randomization.

To determine the association between intensive care unit (ICU) characteristics and clinicians' decision to decline eligible patients for randomization into a multicentered pragmatic comparative-effectiveness controlled trial. Screening logs from the Adjunctive Glucocorticoid Therapy in Septic Shock Trial (ADRENAL) and site-level data from the College of Intensive Care Medicine and Australia New Zealand Intensive Care Society were examined. The effects of ICU characteristics such as tertiary academic status, research coordinator availability, number of admissions, and ICU affiliations on clinicians declining to randomize eligible patients were calculated using mixed effects logistic regression modelling. There were 21,818 patients screened for inclusion in the ADRENAL trial at 69 sites across five countries, out of which 5,501 were eligible, 3,800 were randomized and 659 eligible patients were declined for randomization by the treating clinician. The proportion of eligible patients declined by clinicians at individual ICUs ranged from 0 to41%. In the multivariable model, none of the ICU characteristics were significantly associated with higher clinician decline rate. Neither tertiary academic status, nor other site-level variables were significantly associated with increased rate of clinicians declining eligible patients.

Shirodhara is a brain relaxation therapy. The treatment induces a relaxed state with awareness that results in treating neurological conditions like mental stress (depression/anxiety/hypertension) and some of its beneficial side effects are soothing the central nervous system. In the present study, the investigation aimed to analyze the ratios of brain waves, particularly focusing on the frontal region. In this study, Shirodhara with “Ksheerabala thailam” medicinal oil was conducted on 16 participants and pre-post treatment brain signals were collected using an EEG acquisition tool and it was found that treatment induced relaxation aspects were observed among participants. Welch's Fast Fourier transform (FFT) was used to analyze the EEG signals in order to obtain power spectral density (PSD) features, which indicated a signal's power dispersed across a range of frequencies. The effectiveness of treatment has been evaluated by examining the spectral power ratios of alpha/beta, theta/beta in the frontal region of the brain and physiological and psychological parameters.

PurposeTo determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis.MethodsWe conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ − 3 mEq/L at 48 h.ResultsNinety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48 h, mean fluid administration was 6798 ± 4850 ml vs 6574 ± 3123 ml, median anion gap 6 mEq/L (IQR 5–7) vs 7 mEq/L (IQR 5–7) and median blood ketones 0.3 mmol/L (IQR 0.1–0.5) vs 0.3 (IQR 0.1–0.5) in the PL and SC groups. DKA resolution at 48 h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73–21.16, p = 0.111). At 24 h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68–10.72, p = 0.002). The median ICU and hospital lengths of stay were 49 h (IQR 23–72) vs 55 h (IQR 41–80) and 81 h (IQR 58–137) vs 98 h (IQR 65–195) in the PL and SC groups.ConclusionPlasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.