Edward Litton

Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials

Objectives To evaluate the efficacy and safety of intravenous iron, focusing primarily on its effects on haemoglobin, requirement for transfusion, and risk of infection. Design Systematic review and meta-analysis of randomised controlled trials investigating the safety and efficacy of intravenous iron therapy. Data sources Randomised controlled trials from Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1966 to June 2013, with no language restrictions. Eligibility criteria for selecting studies Eligible trials were randomised controlled trials of intravenous iron compared with either no iron or oral iron. Crossover and observational studies were excluded. Main outcome measures Change in haemoglobin concentration and risk of allogeneic red blood cell transfusion (efficacy) and risk of infection (safety). Results Of the 75 trials meeting the inclusion criteria, 72 studies including 10 605 patients provided quantitative outcome data for meta-analysis. Intravenous iron was associated with an increase in haemoglobin concentration (standardised mean difference 6.5 g/L, 95% confidence interval 5.1 g/L to 7.9 g/L) and a reduced risk of requirement for red blood cell transfusion (risk ratio 0.74, 95% confidence interval 0.62 to 0.88), especially when intravenous iron was used with erythroid stimulating agents (ESAs) or in patients with a lower baseline plasma ferritin concentration. There were no significant interactions between the efficacy of intravenous iron and type or dose administered. Intravenous iron was, however, associated with a significant increase in risk of infection (relative risk 1.33, 95% confidence interval 1.10 to 1.64) compared with oral or no iron supplementation. The results remained similar when only high quality trials were analysed. Conclusions Intravenous iron therapy is effective in increasing haemoglobin concentration and reducing the risk of allogeneic red blood cell transfusion and could have broad applicability to a range of acute care settings. This potential benefit is counterbalanced by a potential increased risk of infection.

The Efficacy of Earplugs as a Sleep Hygiene Strategy for Reducing Delirium in the Icu: A Systematic Review and Meta-analysis*

Objective:A systematic review and meta-analysis to assess the efficacy of earplugs as an ICU strategy for reducing delirium. Data Sources:MEDLINE, EMBASE, and the Cochrane Central Register of controlled trials were searched using the terms “intensive care,” “critical care,” “earplugs,” “sleep,” “sleep disorders,” and “delirium.” Study Selection:Intervention studies (randomized or nonrandomized) assessing the efficacy of earplugs as a sleep hygiene strategy in patients admitted to a critical care environment were included. Studies were excluded if they included only healthy volunteers, did not report any outcomes of interest, did not contain an intervention group of interest, were crossover studies, or were only published in abstract form. Data Extraction:Nine studies published between 2009 and 2015, including 1,455 participants, fulfilled the eligibility criteria and were included in the systematic review. Studies included earplugs as an isolated intervention (n = 3), or as part of a bundle with eye shades (n = 2), or earplugs, eye shades, and additional sleep noise abatement strategies (n = 4). The risk of bias was high for all studies. Data Synthesis:Five studies comprising 832 participants reported incident delirium. Earplug placement was associated with a relative risk of delirium of 0.59 (95% CI, 0.44–0.78) and no significant heterogeneity between the studies (I2, 39%; p = 0.16). Hospital mortality was reported in four studies (n = 481) and was associated with a relative risk of 0.77 (95% CI, 0.54–1.11; I2, 0%; p < 0.001). Compliance with the placement of earplugs was reported in six studies (n = 681). The mean per-patient noncompliance was 13.1% (95% CI, 7.8–25.4) of those assigned to receive earplugs. Conclusions:Placement of earplugs in patients admitted to the ICU, either in isolation or as part of a bundle of sleep hygiene improvement, is associated with a significant reduction in risk of delirium. The potential effect of cointerventions and the optimal strategy for improving sleep hygiene and associated effect on patient-centered outcomes remains uncertain.

Cost-effectiveness of decompressive craniectomy as a lifesaving rescue procedure for patients with severe traumatic brain injury.

BACKGROUND Decompressive craniectomy has been traditionally used as a lifesaving rescue procedure for patients with refractory intracranial hypertension after severe traumatic brain injury (TBI), but its cost-effectiveness remains uncertain. METHODS Using data on length of stay in hospital, rehabilitation facility, procedural costs, and Glasgow Outcome Scale (GOS) up to 18 months after surgery, the average total hospital costs per life-year and quality-adjusted life-year (QALY) were calculated for patients who had decompressive craniectomy for TBI between 2004 and 2010 in Western Australia. The Corticosteroid Randomisation After Significant Head Injury prediction model was used to quantify the severity of TBI. RESULTS Of the 168 patients who had 18-month follow-up data available after the procedure, 70 (42%) achieved a good outcome (GOS-5), 27 (16%) had moderate disability (GOS-4), 34 (20%) had severe disability (GOS-3), 5 (3%) were in vegetative state (GOS-2), and 32 (19%) died (GOS-1). The hospital costs increased with the severity of TBI and peaked when the predicted risk of an unfavorable outcome was about 80%. The average cost per life-year gained (US

Delayed neurological recovery after decompressive craniectomy for severe nonpenetrating traumatic brain injury.

671,000 per life-year) and QALY (US

Long-term Clinical Outcomes and Health Care Utilization After Bariatric Surgery: A Population-Based Study

682,000 per QALY) increased substantially and became much more than the usual acceptable cost-effective limit (US

The use of pre-operative brain natriuretic peptides as a predictor of adverse outcomes after cardiac surgery: a systematic review and meta-analysis.

100,000 per QALY) when the predicted risk of an unfavorable outcome was >80%. Changing different underlying assumptions of the analysis did not change the results significantly. CONCLUSIONS Severity of TBI had an important effect on cost-effectiveness of decompressive craniectomy. As a lifesaving procedure, decompressive craniectomy was not cost-effective for patients with extremely severe TBI.

Effect of an injury awareness education program on risk-taking behaviors and injuries in juvenile justice offenders: a retrospective cohort study

Objective:This study aimed to assess the incidence and factors associated with delayed neurologic recovery after decompressive craniectomy for severe nonpenetrating traumatic brain injury. Design:Retrospective cohort study. Setting:Two major neurotrauma centers in Western Australia. Patients:One hundred and four adult neurotrauma patients who had had a decompressive craniectomy and remained moderately disabled or worse at 6-month follow-up. Measurements and Main Results:Glasgow Outcome Scale scores at 6, 12, and 18 months were used to assess the neurologic recovery of the patients, and logistic regression was used to identify the factors associated with delayed neurologic recovery between 6 and 18 months after surgery. Among a total of 176 patients who required decompressive craniectomy between 2004 and 2010, 104 (59%) had moderate to severe disability 6 months after surgery. Fifty of these patients (48%, 95% confidence interval: 39–58) had ≥1 grade of improvement in Glasgow Outcome Scale score between 6 and 18 months after surgery. Of the 59 patients who had an unfavorable outcome (severe disability or vegetative state) 6 months after surgery, 15 patients (25%, 95% confidence interval: 16–38) improved and had attained a favorable outcome (moderate disability or near normal neurologic function) by the 18-month follow-up. An absence of nonevacuated intracerebral hematoma (>1 cm in diameter) (odds ratio 6.67, 95% confidence interval: 1.12–33.3; p = .038) and a higher admission Glasgow Coma Scale (odds ratio per point increment 1.44, 95% confidence interval: 1.07–1.96; p = .018) were the only two factors significantly associated with a higher chance of delayed neurologic improvement from unfavorable to favorable neurologic outcome between 6 and 18 months after surgery. Conclusions:Delayed neurologic recovery after decompressive craniectomy for severe nonpenetrating traumatic brain injury was very common; absence of nonevacuated intracerebral hematoma and a high admission Glasgow Coma Scale were associated with a higher chance of delayed neurologic recovery after decompressive craniectomy.

Cost‐effectiveness of using recombinant activated factor VII as an off‐label rescue treatment for critical bleeding requiring massive transfusion

OBJECTIVE To determine the long-term outcomes, health care utilization, and risk factors for complications after bariatric surgery. BACKGROUND With the burgeoning problem of obesity and the consequential rise in bariatric surgery, uncertainty remains as to whether this has been matched by a reduction in long-term health care utilization. METHODS A population-based linked-data cohort study, utilizing a comprehensive set of data, including detailed comorbidity and complications, of each individual who had undergone bariatric surgery between 2007 and 2011 in Western Australia. Records were obtained via data linkage through the Western Australian Department of Health Data Linkage Unit. Every patient was followed for a minimum of 12-months after surgery or until death. RESULTS A total of 12062 patients underwent bariatric surgery during the study period with a mean follow-up period of 41 months. Hospitalization rates after bariatric surgery were substantially reduced for all-cause (361 vs 501 per 1000 patient-years, P = 0.002) and diabetes mellitus-related (7 vs 31 per 1000 patient-years, P < 0.001) diagnoses when compared with hospitalization rates before bariatric surgery. Complications occurred in 2171 (18.0%) patients during the follow-up period. Patient age, sex, open surgical procedures, and Charlson Comorbidity Index were associated with an increased risk of complications, with age the most important and accounting for 77% of the variability in the risk of complications. Long-term all-cause mortality rate after surgery was extremely low (0.54 deaths per 1000 patient-years). CONCLUSIONS When measured against long-term safety outcomes, bariatric surgery has low mortality and morbidity associated with a significant reduction in subsequent hospitalizations.

REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial

The objective of this systematic review was to assess whether pre-operative brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) are independent predictors of adverse outcomes after cardiac surgery. MEDLINE, Embase and the Cochrane Controlled Trials Register databases were searched. Eligible studies included observational or randomized control trials measuring natriuretic peptide concentrations before induction of anaesthesia for cardiac surgery. Two investigators independently extracted the data and assessed the validity of the included studies. The predictive ability of pre-operative BNP or NT pro-BNP on mortality, post-operative atrial fibrillation (AF) and intra-aortic balloon pump (IABP) requirement was meta-analysed. The association between BNP or NT pro-BNP and other outcomes was systematically summarized. A total of 4933 patients from 22 studies were considered in the systematic review. Ten studies with one or more outcomes of interest were included in the meta-analyses. The strength of association between pre-operative natriuretic peptide levels and adverse outcomes after surgery was variable, as was the size and quality of the included studies. The summary areas under the receiver operating characteristic curve for mortality, post-operative AF and post-operative IABP requirement were 0.61 (95% confidence interval [CI] 0.51-0.70), 0.61 (95% CI 0.58-0.64) and 0.81 (95% CI 0.73-0.89), respectively. With the limited data available, the associations between pre-operative natriuretic peptide levels and adverse outcomes after cardiac surgery were moderate. Future studies should assess whether pre-operative natriuretic peptides can provide additional independent predictive information to well-validated prognostic scores of cardiac surgery.

Mechanical Prostheses for Right Ventricular Outflow Tract Reconstruction: A Systematic Review and Meta-Analysis

Background Risk-taking behavior is a leading cause of injury and death amongst young people. Methodology and Principal Findings This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences. Significance Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders.