ORCID Profile
0000-0002-8656-9606
Current Organisations
North Middlesex University Hospital NHS Trust
,
Alexandria University Faculty of Medicine
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Publications
A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial
Publisher: Springer Science and Business Media LLC
Date: 25-08-2022
DOI: 10.1186/S13054-022-04120-Y
Abstract: Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30% 3.40%], − 0.39% [95% CrI − 3.46% 3.00%], and 0.64% [95% CrI − 2.53% 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38 − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.
Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study
Publisher: Springer Science and Business Media LLC
Date: 18-10-2022
DOI: 10.1186/S13054-022-04166-Y
Abstract: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55 74] male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.
The Effect of an Accelerated Renal Replacement Therapy Initiation Is Not Modified by Baseline Risk
Publisher: American Thoracic Society
Date: 09-2022
Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease: a secondary analysis of the STARRT-AKI trial
Publisher: Springer Science and Business Media LLC
Date: 04-11-2022
DOI: 10.1007/S00134-022-06912-W
Abstract: To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114-160) and 76 (64-90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05 95% CI, 0.79-1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8% aOR, 1.89 95% CI, 1.05-3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18 95% CI, 1.41-7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71 95% CI, 0.34-1.47, p value for interaction, 0.009). In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD however, no effect was observed in the absence of CKD.
Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury
Publisher: Massachusetts Medical Society
Date: 16-07-2020
Correction: Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease: a secondary analysis of the STARRT-AKI trial
Publisher: Springer Science and Business Media LLC
Date: 09-02-2023
Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT
Publisher: National Institute for Health and Care Research
Date: 02-2021
DOI: 10.3310/HTA25140
Abstract: Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An in idual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018 44 :12–21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients. To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60–65 mmHg) in older critically ill patients. A pragmatic, randomised clinical trial with integrated economic evaluation. Sixty-five NHS adult general critical care units. Critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension. Intervention – permissive hypotension (i.e. a mean arterial pressure target of 60–65 mmHg). Control (usual care) – a mean arterial pressure target at the treating clinician’s discretion. The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year. Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221 usual care, n = 1242) were analysed for the primary clinical outcome. Permissive hypotension resulted in lower exposure to vasopressors than usual care [mean duration 46.0 vs. 55.9 hours, difference –9.9 hours (95% confidence interval –14.3 to –5.5 hours) total noradrenaline-equivalent dose 31.5 mg vs. 44.3 mg, difference –12.8 mg (95% CI –18.0 mg to –17.6 mg)]. By 90 days, 500 (41.0%) patients in the permissive hypotension group and 544 (43.8%) patients in the usual-care group had died (absolute risk difference –2.85%, 95% confidence interval –6.75% to 1.05% p = 0.154). Adjustment for prespecified baseline variables resulted in an odds ratio for 90-day mortality of 0.82 (95% confidence interval 0.68 to 0.98) favouring permissive hypotension. There were no significant differences in prespecified secondary outcomes or subgroups however, patients with chronic hypertension showed a mortality difference favourable to permissive hypotension. At 90 days, permissive hypotension showed similar costs to usual care. However, with higher incremental life-years and quality-adjusted life-years in the permissive hypotension group, the incremental net monetary benefit was positive, but with high statistical uncertainty (£378, 95% confidence interval −£1347 to £2103). The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated. In critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. Future work should (1) update the in idual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials. Current Controlled Trials ISRCTN10580502. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 14. See the NIHR Journals Library website for further project information.
Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study
Publisher: Springer Science and Business Media LLC
Date: 02-2023
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Barts Health NHS Trust
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Queen Elizabeth Hospital
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North Middlesex University Hospital NHS Trust
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Royal College Of Physicians Of Edinburgh
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Royal College Of Physicians
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Broomfield Hospital
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Lewisham And Greenwich NHS Trust
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Ashraf Roshdy.