The challenges faced in the design, conduct and analysis of surgical randomised trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials

Humanitarian Crisis looms in Kachin conflict: Implications for Myanmar’s reform process

Recent reports of reforms in Myanmar have been overwhelmingly positive. However there remain some serious concerns around them. The current conflict in Kachin state is one significant challenge to reform and human security in Myanmar. In June 2011 the 17 year ceasefire between the Kachin Independence Army and tatmadaw broke down with a return to fighting and the forced displacement of civilians. Over the past nineteen months, access to the internally displaced people has been stymied by restrictions on the movement of humanitarian assistance in territory controlled by the KIA. While many local civil society organisations found ways and means to deliver some assistance, it is unsustainable if the basic needs of this population at risk are to be met. While a United Nations humanitarian assistance convoy suffered delays but eventually arrived in Kachin State in mid February 2013, the Myanmar government met with the United Nationalities Federation Council for their second round of talks in Chiang Mai, Thailand. At the peace talks, the issue of humanitarian assistance was addressed but without the attendance of military officials raises questions about whether word will be met with deed

Investigating engineering students' learning for global preparedness in curricular and cocurricular engineering education

2019 Spring.Includes bibliographical references.Engineering as a profession has a significant impact globally in the creation and maintenance of the infrastructure and technology on which humanity relies. As resource constraints and dramatic global population growth challenge engineering's ability to support sustainable, appropriate development globally, the education provided for engineers is increasingly important for preparing engineering students to face the challenges of the present and future. Therefore, it is essential to understand how engineering students can become more globally prepared in their studies. The purpose of this study is to compare, through student experiences, different classes, and programs in engineering education designed to develop students' capabilities in global preparedness. The data for this project were collected through interviews with students who were taking part in different learning curricular and cocurricular classes and programs. In addition, data were collected through pre/post/retrospective-pre-student surveys when possible (for participant groups of greater than 30). The outcomes of this study are presented in three articles. The first article is a structured literature review of the global and professional competencies recognized by academia and engineering practitioners as key experiences and learning designed to improve undergraduate engineering students' global preparedness. The second article is a mixed methods analysis, comparing on-campus classroom development of global preparedness and the impact of changing the context of the engineering class (from local to global) on student's global preparedness and professional competence development. The final article reports on the results of interviews with students participating in different study abroad and volunteer programs, to compare and contrast their experiences in and the impact of those programs. The value of this study is that universities and students may be able to use these results to better understand how to more effectively design and deliver classes and programs to increase the global and professional preparedness of engineering students

Using the literature to quantify the learning curve: a case study

Objective: To assess whether a literature review of a technology can allow a learning curve to be quantified. Methods: The literature for fibreoptic intubation was searched for studies reporting information relevant to the learning curve. The Cochrane Librar y, Medline, Embase and Science Citation index were searched. Studies that reported a procedure time were included. Data were abstracted on the three features of learning: initial level, rate of learning and asymptote level. Random effect meta-analysis was performed. Results: Only 21 studies gave explicit information concerning the previous experience of the operator(s). There were 32 different definitions of procedure time. From 4 studies of fibreoptic nasotracheal intubation, the mean starting level and time for the 10th procedure (95% confidence interval) was estimated to be 133s (113, 153) and 71s (62, 79) respectively. Conclusions: The review approach allowed learning to be quantified for our example technology. Poor and insufficient reporting constrained formal statistical estimation. Standardised reporting of non-drug techniques with adequate learning curve details is needed to inform trial design and costeffectiveness analysis

The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?

Acknowledgements The authors would like to acknowledge helpful discussions on this topic held with various colleagues in connection with a variety of projects. Funding No funding was received for this work.Peer reviewedPublisher PD

Randomised controlled trial comparing rubber band ligation with stapled haemorrhoidopexy for Grade II circumferential haemorrhoids : Long-term results

Peer reviewedPostprin

Proliferation and lineage potential in fetal thymic epithelial progenitor cells

The thymic stroma primarily comprises epithelial, mesenchymal and endothelial cells, interspersed with those of haematopoietic origin. Thymic epithelial cells (TECs) are highly heterogeneous, but can be divided into two broad lineages, cortical and medullary, based on phenotype, functionality and location. A population of Plet1+ TEC progenitors have been identified which, when isolated from mouse E12.5 or E15.5 fetal thymus, reaggregated, and grafted, can produce a functional thymus. However, the potential of individual progenitors to form cortex and/or medulla is undefined. The main aim of this thesis was to use retrospective clonal analysis to ascertain the point during thymus ontogeny at which the cortical and medullary lineages diverge. To this end, I used transgenic mice carrying a ubiquitous ROSA26laacZ reporter gene (where a duplication within lacZ encodes non-functional b-galactosidase). Here, rare, random laacZ-lacZ genetic recombinations result in heritable expression of functional b-gal, producing labelled clones. As this occurs at a known frequency, determination of TEC numbers would enable calculation of the expected number of TEC clones present throughout ontogeny. Due to the lack of quantitative data on all thymic cell populations, I determined the size not only of TEC (lin-EpCAM+), but also haematopoietic (CD45+), mesenchymal (lin-PDGFRa+ and/or lin-PDGFRb+) and endothelial (lin-CD31+) populations from E12.5 until E17.5. I then showed that the absolute number of Plet1+ TECs remains constant during this time, although the proportion of Plet1+ cells in cycle decreases. From these collective data, I propose a model for the role of the Plet1+ population in thymus development, in which Plet1+ cells continually give rise to Plet1- TECs in a self-renewing manner. Finally, I present a ‘dual origin coefficient’ strategy for analysis of a library of prospective TEC clones. I calculated the number of TEC lacZ+ clones expected to be present throughout thymus ontogeny, selecting an appropriate developmental stage for analysis. Although I observed several clones of apparent mesenchymal origin, supporting a single origin for intrathymic and capsular mesenchyme at E15.5, I observed no TEC clones in this extensive analysis. The CpG content of the ROSA26 promoter suggests a possibility of methylation-induced silencing brought about by de novo methylation of the lacZ reporter gene

64-slice computed tomography angiography in the diagnosis and assessment of coronary artery disease : systematic review and meta-analysis

Objective To assess whether 64-slice computed tomography (CT) angiography might replace some coronary angiography (CA) for diagnosis and assessment of coronary artery disease (CAD). Methods We searched electronic databases, conference proceedings and scanned reference lists of included studies. Eligible studies compared 64-slice CT with a reference standard of CA in adults with suspected/known CAD, reporting sensitivity and specificity or true and false positives and negatives. Data were pooled using the hierarchical summary receiver operating characteristic model. Results Forty studies were included; 28 provided sufficient data for inclusion in the meta-analyses, all using a cutoff of ≥ 50% stenosis to define significant CAD. In patient-based detection (n=1286) 64-slice CT pooled sensitivity was 99% (95% credible interval (CrI) 97 to 99%), specificity 89% (95% CrI 83 to 94%), median positive predictive value (PPV) across studies 93% (range 64 to 100%) and negative predictive value (NPV) 100% (range 86 to 100%). In segment-based detection (n=14,199) 64-slice CT pooled sensitivity was 90% (95% CrI 85 to 94%), specificity 97% (95% CrI 95 to 98%), median positive predictive value (PPV) across studies 76% (range 44 to 93%) and negative predictive value (NPV) 99% (range 95 to 100%). Conclusions 64-slice CT is highly sensitive for patient-based detection of CAD and has high NPV. An ability to rule out significant CAD means that it may have a role in the assessment of chest pain, particularly when the diagnosis remains uncertain despite clinical evaluation and simple non-invasive testing.UK National Institute for Health Research Health Technology Assessment programme (project number 06/15/01). The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedAuthor versio

Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.The Balliol Colloquium has been supported by Ethicon UK with unrestricted educational grants and by the National Institute of Health Research Health Technology Assessment Programme. The Balliol Colloquium was administratively and financially supported by the Nuffield Department of Surgery at the University of Oxford and the Department of Surgery at McGill University. JAC holds a Medical Research Council UK special training fellowship. The University of Aberdeen’s Health Services Research Unit is core funded by the Chief Scientist Offi ce of the Scottish Government Health Directorates. IB is supported by a grant from the Société Française de Rhumatologie and Lavoisier Program (Ministère des Aff aires Etrangères et Européennes). PLE is a DPhil Candidate in Evidence-Based Health Care at Oxford University

Outcomes of stenting after uncomplicated ureteroscopy: systematic review and meta-analysis.

Objective To investigate the potential beneficial and adverse effects of routine ureteric stent placement after ureteroscopy. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Cochrane controlled trials register (2006 issue 2), Embase, and Medline (1966 to 31 March 2006), without language restrictions. Review methods We included all randomised controlled trials that reported various outcomes with or without stenting after ureteroscopy. Two reviewers independently extracted data and assessed quality. Meta-analyses used both fixed and random effects models with dichotomous data reported as relative risk and continuous data as a weighted mean difference with 95% confidence intervals. Results Nine randomised controlled trials (reporting 831 participants) were identified. The incidence of lower urinary tract symptoms was significantly higher in participants who had a stent inserted (relative risk 2.25, 95% confidence interval 1.14 to 4.43, for dysuria; 2.00, 1.11 to 3.62, for frequency or urgency) after ureteroscopy. There was no significant difference in postoperative requirement for analgesia, urinary tract infections, stone free rate, and ureteric strictures in the two groups. Because of marked heterogeneity, formal pooling of data was not possible for some outcomes such as flank pain. A pooled analysis showed a reduced likelihood of unplanned medical visits or admission to hospital in the group with stents (0.53, 0.17 to 1.60), although this difference was not significant. None of the trials reported on health related quality of life. Cost reported in three randomised controlled trials favoured the group without stents. The overall quality of trials was poor and reporting of outcomes inconsistent. Conclusions Patients with stents after ureteroscopy have significantly higher morbidity in the form of irritative lower urinary symptoms with no influence on stone free rate, rate of urinary tract infection, requirement for analgesia, or long term ureteric stricture formation. Because of the marked heterogeneity and poor quality of reporting of the included trials, the place of stenting in the managementof patients after uncomplicated ureteroscopy remains unclear.Peer reviewedPublisher PD