Carotid artery stenting vs carotid endarterectomy: meta-analysis and diversity-adjusted trial sequential analysis of randomized trials.

Background: The role of carotid artery stenting (CAS) when compared with carotid endarterectomy (CEA) is controversial, with recent trials showing an increased risk of harm with CAS.

Objective: To evaluate the periprocedural and intermediate to long-term benefits and harms of CAS compared with CEA.

Data Sources And Study Selection: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials searches for randomized clinical trials until June 2010 of CAS compared with CEA for carotid artery disease.

Evidence at a glance: error matrix approach for overviewing available evidence.

Background: Clinical evidence continues to expand and is increasingly difficult to overview. We aimed at conceptualizing a visual assessment tool, i.e.

[Reporting adverse reactions and events in randomised clinical trials].

"Good clinical practice" (GCP) is an international guideline on how to conduct clinical trials on medical products involving human participants. Danish statute follows the EU trial directive (2001/20/EF) including the GCP guidelines. This article summarises the practical implementation of reporting adverse events and adverse reactions to the Danish Medicines Agency and the regional ethics committee based on the protocol of the ongoing Copenhagen Insulin and Metformin Therapy (CIMT) trial.

Positive end-expiratory pressure (PEEP) during anaesthesia for the prevention of mortality and postoperative pulmonary complications.

Background: General anaesthesia causes atelectasis which can lead to impaired respiratory function. Positive end-expiratory pressure (PEEP) is a mechanical manoeuvre which increases functional residual capacity (FRC) and prevents collapse of the airways thereby reducing atelectasis. It is not known whether intra-operative PEEP alters the risk of postoperative mortality and pulmonary complications.

Aerosolized prostacyclin for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far.

Objectives: To systematically assess the benefits and harms of aerosolized prostacyclin in critically ill patients with ALI and ARDS.

Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults.

Background: Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has been used to improve oxygenation but its role remains controversial.

Hypothermia after cardiac arrest should be further evaluated--a systematic review of randomised trials with meta-analysis and trial sequential analysis.

Background: Guidelines recommend mild induced hypothermia (MIH) to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. Our objective was to systematically evaluate the evidence for MIH taking into consideration the risks of systematic and random error and to GRADE the evidence.

Methods: Systematic review with meta-analysis and trial sequential analysis of randomised trials evaluating MIH after cardiac arrest in adults.

Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis.

The pathophysiology of depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis and the use of salivary cortisol measures is increasingly being incorporated into research. The aim of the present study was to investigate whether salivary cortisol differs for patients with depression and control persons. We did a systematic review with sequential meta-analysis and meta-regression according to the PRISMA Statement based on comprehensive database searches for studies of depressed patients compared to control persons in whom salivary cortisol was measured.

Estimating required information size by quantifying diversity in random-effects model meta-analyses.

Background: There is increasing awareness that meta-analyses require a sufficiently large information size to detect or reject an anticipated intervention effect. The required information size in a meta-analysis may be calculated from an anticipated a priori intervention effect or from an intervention effect suggested by trials with low-risk of bias.

Methods: Information size calculations need to consider the total model variance in a meta-analysis to control type I and type II errors.

Trial sequential analyses of meta-analyses of complications in laparoscopic vs. small-incision cholecystectomy: more randomized patients are needed.

Objective: Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis.

Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.

Context: Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined.

Objective: To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery.

Pentoxifylline for alcoholic hepatitis.

Background: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects.

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression.

Background: Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients.

Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes.

This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this beneficial effect may be conserved with the combination of metformin and insulin treatment. However, the effect of glitazones on CVD is uncertain.

One-year results of total arterial revascularization vs. conventional coronary surgery: CARRPO trial.

Aims: To investigate clinical and angiographic outcomes after coronary surgery using total arterial revascularization (TAR).

Methods And Results: We randomized 331 patients with multivessel or isolated left main disease to TAR [internal thoracic (ITA) and radial arteries] vs. conventional revascularization (CR) using left ITA and vein grafts.

High body mass index is a weak predictor for difficult and failed tracheal intubation: a cohort study of 91,332 consecutive patients scheduled for direct laryngoscopy registered in the Danish Anesthesia Database.

Background: Previous studies have failed to detect high body mass index (BMI) as a risk factor for difficult tracheal intubation (DTI). BMI was investigated as a risk factor for DTI in patients planned for direct laryngoscopy.

Methods: A cohort of 91,332 consecutive patients planned for intubation by direct laryngoscopy was retrieved from the Danish Anesthesia Database.

Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis.

Background: American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative beta blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidence to assess the use of perioperative beta blockers in patients having non-cardiac surgery.

Methods: We searched Pubmed and Embase for randomised controlled trials investigating the use of beta blockers in non-cardiac surgery.

Perioperative oxygen fraction - effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial.

Background: A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO(2) = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO(2) = 0.

Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses?

Background: Results from apparently conclusive meta-analyses may be false. A limited number of events from a few small trials and the associated random error may be under-recognized sources of spurious findings. The information size (IS, i.

Apparently conclusive meta-analyses may be inconclusive--Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses.

Background: Random error may cause misleading evidence in meta-analyses. The required number of participants in a meta-analysis (i.e.

Antithrombin III for critically ill patients.

Background: Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown.

Objectives: To assess the benefits and harms of AT III in critically ill patients.

Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass surgery: systematic review with meta-analyses and trial sequential analyses.

Aims: To assess the clinical outcomes of off- vs. on-pump coronary artery bypass surgery in randomized trials.

Methods And Results: We searched electronic databases and bibliographies until June 2007.

Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses.

Objectives: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries analogous to interim monitoring boundaries in a single trial.