Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective.

INTRODUCTION: Current low (stress) dose corticosteroid regimens may have therapeutic advantage in severe sepsis and septic shock despite conflicting results from two landmark randomised controlled trials (RCT). We systematically reviewed the efficacy of corticosteroid therapy in severe sepsis and septic shock. METHODS: RCTs were identified (1950-September 2008) by multiple data-base electronic search (MEDLINE via OVID, OVID PreMedline, OVID Embase, Cochrane Central Register of Controlled trials, Cochrane database of systematic reviews, Health Technology Assessment Database and Database of Abstracts of Reviews of Effects) and hand search of references, reviews and scientific society proceedings. Three investigators independently assessed trial inclusion and data extraction into standardised forms; differences resolved by consensus. RESULTS: Corticosteroid efficacy, compared with control, for hospital-mortality, proportion of patients experiencing shock-resolution, and infective and non-infective complications was assessed using Bayesian random-effects models; expressed as odds ratio (OR, (95% credible-interval)). Bayesian outcome probabilities were calculated as the probability (P) that OR ≥1. Fourteen RCTs were identified. High-dose (>1000 mg hydrocortisone (equivalent) per day) corticosteroid trials were associated with a null (n = 5; OR 0.91(0.31-1.25)) or higher (n = 4, OR 1.46(0.73-2.16), outlier excluded) mortality probability (P = 42.0% and 89.3%, respectively). Low-dose trials (<1000 mg hydrocortisone per day) were associated with a lower (n = 9, OR 0.80(0.40-1.39); n = 8 OR 0.71(0.37-1.10), outlier excluded) mortality probability (20.4% and 5.8%, respectively). OR for shock-resolution was increased in the low dose trials (n = 7; OR 1.20(1.07-4.55); P = 98.2%). Patient responsiveness to corticotrophin stimulation was non-determinant. A high probability of risk-related treatment efficacy (decrease in log-odds mortality with increased control arm risk) was identified by metaregression in the low dose trials (n = 9, slope coefficient -0.49(-1.14, 0.27); P = 92.2%). Odds of complications were not increased with corticosteroids. CONCLUSIONS: Although a null effect for mortality treatment efficacy of low dose corticosteroid therapy in severe sepsis and septic shock was not excluded, there remained a high probability of treatment efficacy, more so with outlier exclusion. Similarly, although a null effect was not excluded, advantageous effects of low dose steroids had a high probability of dependence upon patient underlying risk. Low dose steroid efficacy was not demonstrated in corticotrophin non-responders. Further large-scale trials appear mandated.

The efficacy of loop diuretics in acute renal failure: assessment using Bayesian evidence synthesis techniques.

OBJECTIVE: To quantify the therapeutic efficacy of loop diuretics in acute renal failure using Bayesian evidence synthesis, because despite widespread use, the role of diuretics is controversial. DATA SOURCE: Randomized controlled trials or nonrandomized studies, 1966 to January 2007, identified from MEDLINE and EMBASE databases and manual bibliographic search. STUDY SELECTION: Studies with assessable predefined end points, exclusive of those pertaining to acute renal failure prophylaxis or chronic renal failure. DATA EXTRACTION: Data extraction was performed jointly by the first two authors; independent study assessment was via standard checklist, unblinded. DATA SYNTHESIS: The primary outcome was mortality; secondary outcomes were time to renal function normalization and total number of dialyses. Bayesian hierarchical random effects estimates of treatment effects were determined as risk ratio for mortality, incidence rate ratio for dialysis number, and mean difference for continuous measures. Bayesian outcome probabilities were calculated as probability (P) that risk ratio or incidence rate ratio of loop diuretics >1 and probability that mean difference >0. Five randomized controlled trials and eight nonrandomized studies were identified. Loop diuretics were not associated with decreased mortality in either randomized controlled trials or nonrandomized studies: overall risk ratio 1.10; 95% credible interval 0.85, 1.42; P(risk ratio >1) > 83.8%. The oliguric period was decreased by loop diuretics: overall mean difference -7.70 days; 95% credible interval -12.51, -2.08; P (mean difference >0) = 0.7%. Although the dialysis rate credible interval, loop diuretics vs. control, spanned unity (incidence rate ratio 0.71; 95% credible interval 0.47, 1.06), the probability that the incidence rate ratio exceeded unity indicated a substantial benefit: P (incidence rate ratio >1 = 4.1%. Uremic duration was not substantially different, loop diuretics vs. control: overall mean difference -1.54 days; 95% credible interval -5.62, 2.46; P [mean difference >0] = 17.8%). CONCLUSIONS: Loop diuretics were not associated with improved survival benefit in acute renal failure, despite reduction in oliguric period and high probability of a significant reduction in dialysis numbers. Further studies to clarify this dichotomy appear mandated.

Chasing the sun: a virtual reference service between SAHSLC (SA) and SWICE (UK).

AIM: In 2002, a discussion in the United Kingdom (UK) between South-west Information for Clinical Effectiveness (SWICE) librarians and a member of the South Australian Department of Human Services Libraries' Consortium (SAHSLC) raised the possibility of developing an after-hours virtual reference service between the two consortium groups. The aim of the service is to put medical practitioners in contact with a librarian when urgent help is required in finding clinical medical information after hours. METHODS: A trial project has begun and has been given the name 'Chasing the Sun'. The service will make use of time-zone differences between the UK and Australia, so that librarians at work in another country will be able to answer urgent patient-related queries that cannot wait until normal office hours. RESULTS: This paper looks at the development of 'Chasing the Sun' from initial concept, funding proposal and trial project stage to implementation. It includes details of the groundwork, software evaluation, trials, outcomes, cost and benefits, future directions and potential problems yet to be experienced or overcome. CONCLUSION: This service is the first of its kind between health libraries in the world and offers potential for future worldwide expansion.