Clinical trials traditionally aim to show a new treatment is superior to placebo or standard treatment, that is, superiority trials. There is an increasing number of trials demonstrating a new treatment is non-inferior to standard treatment. The hypotheses, design and interpretation of non-inferiority trials are different to superiority trials. Non-inferiority trials are designed with the notion that the new treatment offers advantages over standard treatment in certain important aspects. The non-inferior margin is a predetermined margin of difference between the new and standard treatment that is considered acceptable or tolerable for the new treatment to be considered ‘similar’ or ‘not worse’. Both relative difference and absolute difference methods can be used to define the non-inferior margin. Sequential testing for non-inferiority and superiority is often performed. Non-inferiority trials may be necessary in situations where it is no longer ethical to test any new treatment against placebo. There are inherent assumptions in non-inferiority trials which may not be correct and which are not being tested. Successive non-inferiority trials may introduce less and less effective treatments even though these treatments may have been shown to be non-inferior. Furthermore, poor quality trials favour non-inferior results. Intention-to-treat analysis, the preferred way to analyse randomised trials, may favour non-inferiority. Both intention-to-treat and per-protocol analyses should be recommended in non-inferiority trials. Clinicians should be aware of the pitfalls of non-inferiority trials and not accept non-inferiority on face value. The focus should not be on the p values but on the effect size and confidence limits.

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Background: Severe burn injuries are associated with hypermetabolism. This study aimed to compare the measured energy expenditure (mEE) with predicted energy requirements (pERs), and to correlate energy expenditure (EE) with clinical parameters in adults with severe burn injury. Methods: Data were retrospectively analysed on 29 burn patients (median (interquartile range) age: 46 (28-61) years, % total body surface area burn: 37% (18-46%)) admitted to an intensive care unit. Indirect calorimetry was performed on 1-4 occasions per patient to measure EE. mEE was compared with pER calculated using four prediction equations. Bland-Altman and correlation analyses were performed. Results: Mean AE SD mEE was 9752 AE 2089 kJ/day (143 AE 32% of predicted basal metabolic rate). Bland-Altman analysis demonstrated clinically important overestimation for three of the four prediction equations and wide 95% limits of agreement for all equations. Overestimation of EE was more marked early post-burn. mEE correlated with day post-burn (r = 0.42, P = 0.004) and number of operations prior to first EE measurement (r = 0.34, P = 0.016), but not with % total body surface area (r = 0.02, P = 0.9). Conclusions: Patients with severe burn injury exhibit hypermetabolism. The observed poor agreement between pER and mEE at an individual level indicates the value of indirect calorimetry in determining EE in burn injury.

Since its first description in the 1960s, three-dimensional echocardiography (3D echo) has gone through major advances. Initially, 3D echo was performed by acquiring a series of two-dimensional (2D) tomographic images, either by manual rotation of the transducer with external references or later by multi-plane transoesophageal echocardiography (TOE). Three-dimensional echo images were then generated by off-line reconstruction. The process was cumbersome and time consuming, thereby precluding its use in routine clinical practice. Through advances in ultrasound, electronic and computer technologies, real time display of 3D rendered images of the heart is possible with both transthoracic echo and TOE, enabling its more widespread use in routine clinical practice. Numerous studies have demonstrated the utility and, in many cases, the superiority of 3D over 2D echo in the assessment of almost all cardiac structures and function. These include assessment of left ventricular (LV) and right ventricular (RV) volume and function and wall motion, left and right atrial volume, LV mass, valvular heart disease, congenital heart disease, LV synchrony, guidance of interventional procedures and in volumetric colour Doppler imaging. In this article, we do not aim to give a full review of the technical aspects and all possible applications of 3D echo. Instead, we focus on areas where, in our opinions, 3D echo should be used in routine clinical practice in 2019. Three-dimensional (3D) echo has been around for almost five decades. Recent advances in ultrasound, electronic and computing technologies have moved 3D echo from the research environment to everyday clinical practice. Real time 3D echo and full volume acquisition are now possible with transthoracic as well as transoesophageal probes. The main advantages of 3D echo are the infinite cut planes possible, allowing direct, en face, and anatomical views of cardiac structures, avoiding foreshortening and circumventing the geometric assumptions of the cardiac chambers inherent in any 2D echo techniques. Three-dimensional echo is still dependent on image quality, subjected to ultrasound artifacts and faces the compromise between spatial and temporal resolution. In routine clinical practice in 2019, we recommend a focussed 3D examination after a full 2D echo study. The area where 3D echo has been consistently shown to have superior accuracy and reproducibility over 2D echo is in the assessment of left ventricular (LV) volumes and ejection fraction. We recommend obtaining a full volume 3D echo data set from the apical window, from which LV volumes and LV global longitudinal strain can be measured. Further 3D examination can be performed depending on the pathologies identified on 2D examination. Three-dimensional echo is superior to 2D echo in the assessment of mitral valve pathologies and atrial septal defects. Furthermore, real time 3D transoesophageal echo is a very useful technique in guiding structural cardiac intervention, both before, during and after the procedure. While 3D echo...

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