Comparison of venovenous extracorporeal membrane oxygenation, prone position and supine mechanical ventilation for severely hypoxemic acute respiratory distress syndrome: a network meta-analysis.

PURPOSE: Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. METHODS: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. RESULTS: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59-0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57-0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66-0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63-1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72-1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. CONCLUSIONS: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Association of different positive end-expiratory pressure selection strategies with all-cause mortality in adult patients with acute respiratory distress syndrome.

BACKGROUND: The acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Positive end-expiratory pressure (PEEP) is commonly used in patients with ARDS but the best method to select the optimal PEEP level and reduce all-cause mortality is unclear. The primary objective of this network meta-analysis is to summarize the available evidence and to compare the effect of different PEEP selection strategies on all-cause mortality in adult patients with ARDS. METHODS: We will search MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and LILACS from inception onwards for randomized controlled trials assessing the effect of PEEP selection strategies in adult patients with moderate to severe ARDS. We will exclude studies that did not use a lung-protective ventilation approach as part of the comparator or intervention strategy. The primary outcome will be all-cause mortality (at the longest available follow-up and up to 90 days). Secondary outcomes will include barotrauma, ventilator-free days, intensive care unit and hospital length of stay, and changes in oxygenation. Two reviewers will independently screen all citations, full-text articles, and extract study-data. We will assess the risk of bias for each of the outcomes using version 2 of the Cochrane risk of bias tool for randomized controlled trials. If feasible, Bayesian network meta-analyses will be conducted to obtain pooled estimates of all potential head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and risk differences, together with the associated 95% credible intervals. We will assess certainty in effect estimates using GRADE methodology. DISCUSSION: The present study will inform clinical decision-making for adult patients with ARDS and will improve our understanding of the limitations of the available literature assessing PEEP selection strategies. Finally, this information may also inform the design of future randomized trials, including the selection of interventions, comparators, and predictive enrichment strategies. TRIAL REGISTRATION: PROSPERO 2020 CRD42020193302 .

Comparative Effectiveness of Protective Ventilation Strategies for Moderate and Severe Acute Respiratory Distress Syndrome. A Network Meta-Analysis.

Rationale: Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. Objectives: To compare the effects of low Vt, high Vt, high positive end-expiratory pressure (PEEP), prone ventilation, high-frequency oscillation, and venovenous extracorporeal membrane oxygenation (VV ECMO) on mortality in ARDS. Methods: We performed a network meta-analysis of randomized trials. We applied the Grading of Recommendations Assessment, Development and Evaluation methodology to discern the relative effect of interventions on mortality. Measurements and Main Results: We analyzed 34 trials including 9,085 adults with primarily moderate-to-severe ARDS (median baseline PaO2/FiO2, 118; interquartile range, 110-143). Prone positioning combined with low Vt was the best strategy (risk ratio [RR], 0.74 [95% confidence interval (CI), 0.60-0.92] vs. low Vt; high certainty). VV ECMO was also rated among the best (RR, 0.78 [95% CI, 0.58-1.05] vs. low Vt; RR, 0.66; [95% CI, 0.49-0.88] vs. high Vt) but was rated with lower certainty because VV ECMO was restricted to very severe ARDS (mean baseline PaO2/FiO2<75). High PEEP combined with low Vt was rated intermediately (RR, 0.91 [95% CI, 0.81-1.03] vs. low Vt; low certainty; RR, 0.77 [95% CI, 0.65-0.91] vs. high Vt; moderate certainty). High Vt was rated worst (RR, 1.19 [95% CI, 1.02-1.37] vs. low Vt; moderate certainty), and we found no support for high-frequency oscillation or high Vt with prone ventilation. Conclusions: These findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for critically ill adults with moderate-to-severe ARDS.

Subaxial Cervical Spine Injuries: Outcomes after Anterior Corpectomy and Instrumentation.

STUDY DESIGN: This is prospective study. PURPOSE: The purpose of this study is to assess the functional, neurological, and radiological outcomes of the patients of subaxial cervical spine injuries treated by anterior corpectomy and stabilization with anterior cervical locking plate and cage filled with bone. OVERVIEW OF THE LITERATURE: The principles in the treatment of unstable cervical spine injuries are reduction and stabilization of the injured segment, maintenance of cervical lordosis and decompression where indicated and ranges from nonoperative to combined anterior and posterior surgical fusion. There is, however, debate on the indications for anterior, posterior, or combined surgery. MATERIALS AND METHODS: The present study of 99 patients includes prospective patients of subaxial cervical spine injuries between February 2014 and February 2016 admitted and operated to Indira Gandhi Medical College, Shimla. Bony fusion, neurological recovery, Neck Disability Index and complication were studied in all patients. The mean follow-up period was 27 months (range 12-42 months). RESULTS: Of the 99 procedures, 77 (77.8%) involved a single vertebral level, 19 (19.2%) involved two levels, and 3 (3%) involved three levels corpectomy. The mean Neck Disability Index was 7.57 ± 5.42. Definitive Bridwell Grade 1 fusion was seen in 64.6% of the cases. No deterioration of neurological symptoms was seen. Dysphagia was the most common complication in 79 (79.8%) patients. One patient had minimal screw back out. CONCLUSIONS: Anterior cervical corpectomy and stabilization with cage filled with bone and cervical reflex locking plate are good method for subaxial cervical spine injuries with good fusion rates and probably procedure of choice for posttraumatic multiple disc prolapse with reduced hazards of multiple grafts.

Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome.

RATIONALE: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. OBJECTIVES: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV. METHODS: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. MEASUREMENTS AND MAIN RESULTS: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with PaO2/FiO2 among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04). CONCLUSIONS: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.

Functional outcome in unstable Hangman's fracture managed with anterior approach: A prospective study.

AIM: To study the functional outcome in unstable Hangman s fracture managed with anterior decompression and stabilization with cervical locking plate and tricortical bone graft. MATERIALS AND METHODS: Between 2010 and 2016, 44 patients (range: 19-75 years) with unstable Hangman's fracture underwent anterior decompression and stabilization with cervical locking plate and tricortical bone graft in our institution. RESULT: According to the Levine and Edwards classification, all patients were unstable with Type IA 6 (13.6), Type IIA 35 (79.5%), Type II (0), and Type III (6.8). The mean period of follow-up was 17 months (range: 6-48 months). Neurological recovery was observed in all nine patients. All patients were relieved from axial pain. None of the patients received blood transfusion. All patients showed solid fusion with no complication related to bone graft and plate. CONCLUSION: The anterior C2/C3 discectomy, fusion, and stabilization with cervical locking plate and tricortical bone graft are feasible and safe method in treating HangmanÊs fracture, with the benefit of high primary stability, anatomical reduction, and direct decompression of the spinal cord.

High-frequency oscillatory ventilation versus conventional ventilation for acute respiratory distress syndrome.

BACKGROUND: High-frequency oscillation (HFO) is an alternative to conventional mechanical ventilation that is sometimes used to treat people with acute respiratory distress syndrome, but effects on oxygenation, mortality and adverse clinical outcomes are uncertain. This review was originally published in 2004 and was updated in 2013 and again in 2015. OBJECTIVES: To determine the effects of HFO compared to conventional mechanical ventilation on physiological outcomes, clinical outcomes, and mortality when used for the treatment of acute respiratory distress syndrome (ARDS). SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid), MEDLINE (Ovid), EMBASE (Ovid), and ISI, from inception to December 2015. We conducted the original search in 2002. We manually searched reference lists from included studies and review articles; searched conference proceedings of the American Thoracic Society (1994 to 2015), Society of Critical Care Medicine (1994 to 2015), European Society of Intensive Care Medicine (1994 to 2015), and American College of Chest Physicians (1994 to 2015); contacted clinical experts in the field; and searched for unpublished and ongoing trials in clinicaltrials.gov and controlled-trials.com. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing treatment using HFO with conventional mechanical ventilation for children and adults diagnosed with ARDS. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. We used random-effects models in the analyses. MAIN RESULTS: We include 10 RCTs (n = 1850); almost all participants had moderate or severe ARDS. For the primary analysis, the risk of bias was low in three studies and unclear in five studies; the overall quality of evidence was very low due to imprecision, inconsistency, indirectness and methodologic limitations. In participants randomized to HFO, there was no significant difference in hospital or 30-day mortality (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.72 to 1.16; P = 0.46, I² = 66%; 8 trials, 1779 participants, 807 deaths) compared with conventional ventilation. One large multicentre RCT was terminated early because of increased mortality in participants randomized to HFO compared to mechanical ventilation with low tidal volume and high positive end expiratory pressure, with HFO reserved only as a rescue therapy. We found substantial between-trial statistical heterogeneity (I² = 0% to 66%) for clinical outcomes, including mortality.  AUTHORS' CONCLUSIONS: The findings of this systematic review suggest that HFO does not reduce hospital and 30-day mortality due to ARDS; the quality of evidence was very low. Our findings do not support the use of HFO as a first-line strategy in people undergoing mechanical ventilation for ARDS.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients.

IMPORTANCE: Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE: To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES: Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS: Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. CONCLUSIONS AND RELEVANCE: From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.

Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation. METHODS: We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses. RESULTS: We identified 11 RCTs (n=2341) that met our inclusion criteria. In the 6 trials (n=1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes. INTERPRETATION: Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation.

Glenoid fossa fractures: Outcome of operative and nonoperative treatment.

BACKGROUND: Glenoid fossa fractures are rare injuries having a prevalence of 0.1%. These fractures may be managed operatively if substantially displaced. However, several fractures of glenoid fossa are managed nonoperatively, even if displaced, due to high incidence of associated injuries which may render patient unfit to undergo major orthopaedic surgery. There is a relative paucity of articles reporting on outcome of treatment of glenoid fossa fractures. We present our experience of treating these injuries over past decade with operative and nonoperative methods. MATERIALS AND METHODS: 21 patients of glenoid fossa fractures were included in this series with 14 males and 7 females. Patients with displacement of >5 mm who were fit to undergo surgery within 3 weeks of injury were operated using a posterior Judet's approach. Overall 8 patients with displaced fractures were operated (Group A) while 9 patients with displaced fractures (Group B) and 4 patients with undisplaced fractures (Group C) were managed nonoperatively. RESULTS: The mean age and followup period in this series was 29 years and 7.3 years respectively. In group A, average constant score was 87.25. The least constant score was observed for group B (58.55) while group C had an average constant score of 86. Brachial plexus injury and fracture-dislocations had poorer outcome. CONCLUSION: Operative treatment for displaced glenoid fractures is a viable option at centers equipped to handle critically ill patients and subset of patients with fracture-dislocation as opposed to fracture alone should always be treated operatively due to persistent loss of function.

High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome.

BACKGROUND: High frequency oscillation is an alternative to conventional mechanical ventilation that is sometimes used to treat patients with acute respiratory distress syndrome, but effects on oxygenation, mortality and adverse clinical outcomes are uncertain. This review was originally published in 2004 and was updated in 2011. OBJECTIVES: To determine clinical and physiological effects of high frequency oscillation (HFO) in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) compared to conventional ventilation. SEARCH METHODS: We electronically searched CENTRAL (Ovid), MEDLINE (Ovid), EMBASE (Ovid), and ISI (from inception to March 2011). The original search was performed in 2002. We manually searched reference lists from included studies and review articles; searched conference proceedings of the American Thoracic Society (1994 to 2010), Society of Critical Care Medicine (1994 to 2010), European Society of Intensive Care Medicine (1994 to 2010), and American College of Chest Physicians (1994 to 2010); contacted clinical experts in the field; and searched for unpublished and ongoing trials in clinicaltrials.gov and controlled-trials.com. SELECTION CRITERIA: Randomized controlled clinical trials comparing treatment using HFO with conventional mechanical ventilation for children and adults diagnosed with ALI or ARDS. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. We used random-effects models in the analyses. MAIN RESULTS: Eight RCTs (n = 419) were included; almost all patients had ARDS. The risk of bias was low in six studies and unclear in two studies. The quality of evidence for hospital and six-month mortality was moderate and low, respectively. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24, 48, and 72 hours was 16% to 24% higher in patients receiving HFO. There were no significant differences in oxygenation index because mean airway pressure rose by 22% to 33% in patients receiving HFO (P < 0.01).  In patients randomized to HFO, mortality was significantly reduced (RR 0.77, 95% CI 0.61 to 0.98; P = 0.03; 6 trials, 365 patients, 160 deaths) and treatment failure (refractory hypoxaemia, hypercapnoea, hypotension, or barotrauma) was less likely (RR 0.67, 95% CI 0.46 to 0.99; P = 0.04; 5 trials, 337 patients, 73 events). Other risks, including adverse events, were similar. We found substantial between-trial statistical heterogeneity for physiological (I(2) = 21% to 95%) but not clinical (I(2) = 0%) outcomes.  Pooled results were based on few events for most clinical outcomes. AUTHORS' CONCLUSIONS: The findings of this systematic review suggest that HFO was a promising treatment for ALI and ARDS prior to the uptake of current lung protective ventilation strategies. These findings may not be applicable with current conventional care, pending the results of large multi-centre trials currently underway.

Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials.

BACKGROUND: The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up. FINDINGS: The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0.67, 95% CI 0.52-0.86; p=0.002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1.03, 0.77-1.37; p=0.78; I(2)=46%; 3790 patients, five trials; p interaction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity. INTERPRETATION: In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.

Understanding health economic analysis in critical care: insights from recent randomized controlled trials.

PURPOSE OF REVIEW: The article reviews the methods of health economic analysis (HEA) in clinical trials of critically ill patients. Emphasis is placed on the usefulness of HEA in the context of positive and 'no effect' studies, with recent examples. RECENT FINDINGS: The need to control costs and promote effective spending in caring for the critically ill has garnered considerable attention due to the high cost of critical illness. Many clinical trials focus on short-term mortality, ignoring costs and quality of life, and fail to change clinical practice or promote efficient use of resources. Incorporating HEA into clinical trials is a possible solution. Such studies have shown some interventions, although expensive, provide good value, whereas others should be withdrawn from clinical practice. Incorporating HEA into randomized controlled trials (RCTs) requires careful attention to collect all relevant costs. Decision trees, modeling assumptions and methods for collecting costs and measuring outcomes should be planned and published beforehand to minimize bias. SUMMARY: Costs and cost-effectiveness are potentially useful outcomes in RCTs of critically ill patients. Future RCTs should incorporate parallel HEA to provide both economic outcomes, which are important to the community, alongside patient-centered outcomes, which are important to individuals.

Screening and prevention of venous thromboembolism in critically ill patients: a decision analysis and economic evaluation.

RATIONALE: Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. OBJECTIVES: To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients. METHODS: A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios. MEASUREMENTS AND MAIN RESULTS: In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses. CONCLUSIONS: Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.

High frequency oscillation in patients with acute lung injury and acute respiratory distress syndrome (ARDS): systematic review and meta-analysis.

OBJECTIVE: To determine clinical and physiological effects of high frequency oscillation compared with conventional ventilation in patients with acute lung injury/acute respiratory distress syndrome (ARDS). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases to March 2010, conference proceedings, bibliographies, and primary investigators. STUDY SELECTION: Randomised controlled trials of high frequency oscillation compared with conventional ventilation in adults or children with acute lung injury/ARDS. Data selection Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. Analyses used random effects models. RESULTS: Eight randomised controlled trials (n=419 patients) were included; almost all patients had ARDS. Methodological quality was good. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24, 48, and 72 hours was 16-24% higher in patients receiving high frequency oscillation. There were no significant differences in oxygenation index because mean airway pressure rose by 22-33% in patients receiving high frequency oscillation (P

Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis.

BACKGROUND: Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe. OBJECTIVE: To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO(2))/inspired fraction of oxygen (FiO(2)) <100 mmHg] compared with moderate hypoxemia (100 mmHg < or = PaO(2)/FiO(2) < or = 300 mmHg). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (to November 2009) and conference proceedings. METHODS: Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO(2)/FiO(2) <100 mmHg. Meta-analyses used study-level random-effects models. RESULTS: Ten trials (N = 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO(2)/FiO(2) <100 mmHg [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74-0.96; p = 0.01; seven trials, N = 555] but not in patients with PaO(2)/FiO(2) > or =100 mmHg (RR 1.07, 95% CI 0.93-1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed significantly between subgroups (interaction p = 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO(2)/FiO(2) thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27-39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16-1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24-2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02-9.69). There was no statistical between-trial heterogeneity for most clinical outcomes. CONCLUSIONS: Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.