Contemporary roles of registries in clinical cardiology: when do we need randomized trials?

Clinical registries are established as tools for auditing clinical standards and benchmarking quality improvement initiatives. They also have an emerging role (as electronic health records) in cardiovascular research and, in particular, the conduct of RCTs. While the RCT is accepted as the most robust experimental design, observational data from clinical registries has become increasingly valuable for RCTs. Data from clinical registries may be used to augment results from RCTs, identify patients for recruitment and as an alternative when randomization is not practically possible or ethically desirable. Here the authors appraise the advantages and disadvantages of both methodologies, with the aim of clarifying when their joint use may be successful.     

Why do we need a trial on the effects of testosterone therapy in older men?

Development of innovative drugs has recently become more difficult. The case of rosiglitazone shows the extreme difficulty of making the regulatory decision that will best balance the benefits and risks of a drug. There is a high expectation that regulatory science (RS) can improve the situation. However, without user understanding of its basic characteristics, RS will not deliver what is expected.     

Outcome assessment for clinical trials: How many adjudicators do we need?

Considerable effort is often expended to adjudicate outcomes in clinical trials, but little has been written on the administration of the adjudication process and its possible impact on study results. As a case study, we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer. Up to five independent adjudicators independently determined two primary outcomes: tumor status at death or at final follow-up and the cause of death. Patients for whom there was any disagreement were discussed in committee until a consensus was achieved. We describe the pattern of agreement among the adjudicators and with the final consensus result. Additionally, we model the adjudication process and predict the results if a smaller committee had been used. We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10% of cases. Correspondingly, the effect on the final study results (comparing primary outcomes in both randomized arms) would have been altered very little. Even using a single adjudicator would not have affected the results substantially. About 90 minutes of person-time per patient was required for activities directly related to the adjudication process, or approximately 6 months of full time work for the entire study. This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results. Thus, we suggest that when high observer agreement is demonstrated or anticipated, adjudication committees should consist of no more than three members. Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower.     

Endosurgery: what do we need?

A paradigm shift in therapeutic endoscopy occurred with the advent of mucosectomy for the treatment of mucosal neoplasms and suture plication for gastroesophageal reflux disease. The objectives changed from finding simple, easy, and quick alternatives to surgery to reproducing surgical results. A radical version of flexible endoscopy has emerged to meet new goals of full-thickness resections, creation of anastomoses, and lumen reconfiguration. This will require a new generation of endosurgical tools that cut, stitch, and staple with added dimensions of multiaxis orientation and triangulation.     

Advanced endoscopy and endosurgical procedures: do we need a new subspecialty?

On the horizon is a new paradigm in minimally invasive therapy called natural orifice transluminal endoscopic surgery (NOTES). This new approach will most certainly disrupt both those living in the gut lumen with flexible endoscopes as well as those living in the peritoneal cavity using laparoscopes to perform surgical procedures. The question is what changes will need to occur in training and practice to accommodate this new paradigm? Those of us who consider ourselves to be gastrointestinal interventionalists are in a unique and exciting position because the answers to the question about training and practice in NOTES will unfold before us in the coming decade. For now however, we can only speculate on the course of these events.     

Intravenous urography in the emergency department: when do we need it?

Intravenous urography (IVU) is a useful radiographic study in the detection of renal and ureteral calculi. However, it is time consuming, expensive, and exposes the patient to i.v. contrast and radiation. To determine the impact of utilizing IVU less for the detection of renal calculi, criteria for ordering IVU in the emergency department (ED) were evaluated, and patients with high probability of positive IVU were identified. Variables included presence of acute flank pain with haematuria, prior history of renal calculus, degree of haematuria, and uncontrolled pain. We reviewed patients presenting with acute flank and abdominal pain with haematuria from May 1995 to May 1996 at a large urban university hospital. Charts were abstracted for prior history, reason for ordering IVU, time in the ED, laboratory results, IVU result, final diagnosis, and disposition. Data was analysed with Student's t-test, Wilcoxon rank-sum and receiver operating characteristic (ROC) analysis. A total of 302 patients were identified, and 185 underwent IVU during the study period. For patients with prior history of renal calculi 82% had positive IVU (sensitivity 51%, specificity 87%). For patients with both acute flank pain and haematuria, 92% had a positive IVU (sensitivity 93%, specificity 43%), and 19% of patients with abdominal pain of unclear aetiology with haematuria had a positive IVU. All patients with uncontrolled pain had evidence of high-grade obstruction on IVU. Degree of haematuria was not predictive of a positive IVU from ROC curve derivation. IVU is a useful study in the ED but may be overutilized, leading to lengthy patient stays. The combined objective findings of acute flank pain and haematuria are sensitive, and prior history is specific in identifying patients with renal calculi. Degree of haematuria was not useful in predicting renal calculi. By utilizing the criteria of acute flank pain and haematuria as a decision aid, 66% of all IVUs ordered could have been avoided.     

Spirituality in palliative care: what language do we need?

This article considers the language of spirituality in palliative care (Byrne, 2002; 2007), and focuses on the concepts of metaphor and story, demonstrated in practice by the art project and publication at The Prince & Princess of Wales Hospice (PPWH), Glasgow, UK. Metaphors have been used in everyday speech and literature throughout history. The word 'cancer' is a metaphor itself traced back to Hippocrates in the 5th century BC. Stanworth (2004) concluded that metaphor can draw attention to aspects of the patient's experience that might otherwise be overlooked. In palliative care the metaphor of the journey is often used to describe the experience of illness. Cicely Saunders (2000) described it as a spiritual journey, demonstrating opportunities for growth and development, hope and discovery. As professionals we share that journey. Stories often include metaphoric images and give an understanding of the uniqueness of individual fear and inner need. Cullen and Alcock describe creative expression as the process of unraveling a story (2007).The creative arts project at PPWH bears witness to this.