Potential Avoidable Costs of Low-Value Clinical Practices in Acute Injury Care in an Integrated Canadian Provincial Trauma System.

This economic evaluation estimated the direct health care costs associated with 11 low-value clinical practices in acute trauma care in the integrated health care system of Quebec, Canada.

The Efficacy of Glutamine Supplementation in Severe Adult Burn Patients: A Systematic Review With Trial Sequential Meta-Analysis.

OBJECTIVES: Evidence supporting glutamine supplementation in severe adult burn patients has created a state of uncertainty due to the variability in the treatment effect reported across small and large randomized controlled trials (RCTs). We aimed to systematically review the effect of glutamine supplementation on mortality in severe adult burn patients. DATA SOURCES: MEDLINE, Embase, CINAHL, and Cochrane Central were searched from inception to February 10, 2023. STUDY SELECTION: RCTs evaluating the effect of enteral or IV glutamine supplementation alone in severe adult burn patients were included. DATA EXTRACTION: Two reviewers independently extracted data on study characteristics, burn injury characteristics, description of the intervention between groups, adverse events, and clinical outcomes. DATA SYNTHESIS: Random effects meta-analyses were performed to estimate the pooled risk ratio (RR). Trial sequential analyses (TSA) for mortality and infectious complications were performed. Ten RCTs (1,577 patients) were included. We observed no significant effect of glutamine supplementation on overall mortality (RR, 0.65, 95% CI, 0.33-1.28; p = 0.21), infectious complications (RR, 0.83; 95% CI, 0.63-1.09; p = 0.18), or other secondary outcomes. In subgroup analyses, we observed no significant effects based on administration route or burn severity. We did observe a significant subgroup effect between single and multicenter RCTs in which glutamine significantly reduced mortality and infectious complications in singe-center RCTs but not in multicenter RCTs. However, TSA showed that the pooled results of single-center RCTs were type 1 errors and further trials would be futile. CONCLUSIONS: Glutamine supplementation, regardless of administration, does not appear to improve clinical outcomes in severely adult burned patients.

A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.

BACKGROUND: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.

OBJECTIVES: To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN: A multicenter randomized sham-controlled clinical trial. SETTING: Twelve ICUs in Canada. PATIENTS: We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS: Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS: The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS: Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.

Resource use for older people hospitalised due to injury in a Canadian integrated trauma system: a retrospective multicenter cohort study.

BACKGROUND: Injuries represent one of the leading causes of preventable morbidity and mortality. For countries with ageing populations, admissions of injured older patients are increasing exponentially. Yet, we know little about hospital resource use for injured older patients. Our primary objective was to evaluate inter-hospital variation in the risk-adjusted resource use for injured older patients. Secondary objectives were to identify the determinants of resource use and evaluate its association with clinical outcomes. METHODS: We conducted a multicenter retrospective cohort study of injured older patients (≥65 years) admitted to any trauma centres in the province of Quebec (2013-2016, N = 33,184). Resource use was estimated using activity-based costing and modelled with multilevel linear models. We conducted separate subgroup analyses for patients with trauma and fragility fractures. RESULTS: Risk-adjusted resource use varied significantly across trauma centres, more for older patients with fragility fractures (intra-class correlation coefficients [ICC] = 0.093, 95% CI [0.079, 0.102]) than with trauma (ICC = 0.047, 95% CI = 0.035-0.051). Risk-adjusted resource use increased with age, and the number of comorbidities, and varied with discharge destination (P < 0.001). Higher hospital resource use was associated with higher incidence of complications for trauma (Pearson correlation coefficient [r] = 0.5, 95% CI = 0.3-0.7) and fragility fractures (r = 0.5, 95% CI = 0.3-0.7) and with higher mortality for fragility fractures (r = 0.4, 95% CI = 0.2-0.6). CONCLUSIONS: We observed significant inter-hospital variations in resource use for injured older patients. Hospitals with higher resource use did not have better clinical outcomes. Hospital resource use may not always positively impact patient care and outcomes. Future studies should evaluate mechanisms, by which hospital resource use impacts care.

Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials.

OBJECTIVE: Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). SETTING: Primary care. PARTICIPANTS: Adults (≥18 years) who were iron deficient but non-anaemic. INTERVENTIONS: Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. COMPARATORS: Placebo or active therapy. RESULTS: We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO's International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) -0.38; 95% CI -0.52 to -0.23; I2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI -0.15 to 0.37; I2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I2 58%; 14 trials; 616 participants). CONCLUSION: In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia. PROSPERO REGISTRATION NUMBER: CRD42014007085.

A RandomizEd trial of ENtERal Glutamine to minimIZE thermal injury (The RE-ENERGIZE Trial): a clinical trial protocol.

BACKGROUND: Burn injury represents a significant public health problem worldwide. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies resulting in impaired immune function and increased risk of developing infection, organ dysfunction and death. Consequently, over the last few decades numerous trials have evaluated the impact of different nutritional strategies in severe burn injury. Glutamine is of particular interest, as it appears vital for a number of key stress-response pathways in serious illness. The purpose of the current manuscript is to provide the rationale and protocol for a large clinical trial of supplemental enteral glutamine in 2700 severe burn-injured patients. METHODS: We propose a multicentre, double-blind, pragmatic, randomized, clinical trial involving 80 tertiary intensive care unit (ICU) burn centres worldwide. We aim to enrol patients with deep second- and/or third-degree burns at moderate or high risk for death. We will exclude patients admitted > 72 h before screening and patients with advanced liver and kidney disease. The study intervention consists of enteral glutamine 0.5 g/kg/day vs. isocaloric maltodextran control delivered enterally. Primary outcome will be six-month mortality. Key secondary outcomes include time to discharge alive from hospital, ICU and hospital mortality, length of stay and health-related quality of life at six months. SIGNIFICANCE: This study will be the first large international multicentre trial examining the effects of glutamine in burn patients. Negative or positive, the results of this trial will inform the clinical practice of burns care worldwide.Clinicaltrials.gov ID #NCT00985205.

Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis.

IMPORTANCE: Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative. OBJECTIVE: To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA SOURCES: We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered. STUDY SELECTION: We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA EXTRACTION AND SYNTHESIS: Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index. MAIN OUTCOMES AND MEASURES: Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects. RESULTS: From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy. CONCLUSIONS AND RELEVANCE: Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.