David Heney

INCREASED CIRCULATING ADHESION MOLECULE CONCENTRATIONS IN PATIENTS WITH THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME - A PROSPECTIVE COHORT STUDY

ObjectiveTo investigate the relationship between the soluble derivatives of endothelial adhesion molecules liberated by activated vascular endothelium and the development of the systemic inflammatory response syndrome and organ dysfunction in septic patients. DesignProspective cohort study with controls. SettingUniversity hospital intensive care unit. PatientsHealthy volunteers (controls, n = 85), patients with the systemic inflammatory response syndrome (n = 21), patients with systemic inflammatory response syndrome and organ dysfunction (n = 14), and miscellaneous, severely ill patients (n = 5). InterventionsPlasma samples were collected from consecutive patients who satisfied the criteria for inclusion in the groups listed above. Measurements and Main ResultsThe plasma was assayed by enzyme-linked immunosorbent assay (ELISA) for each of the three soluble adhesion molecules: sE-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. There were low basal amounts of these adhesion molecules in the healthy volunteers, while plasma concentrations of all three adhesion molecules were increased in the sepsis groups. The median soluble E-selectin concentration was higher in those patients with organ dysfunction compared with the concentrations in patients with uncomplicated sepsis (p < .01 at first and p < .001 when comparing peak values attained). No patient survived when the amount of soluble E-selectin was >30 units/mL. ConclusionsConcentrations of circulating vascular endothelial adhesion molecules, especially soluble E-selectin, are increased in patients with systemic inflammatory response syndrome and these concentrations are more increased in patients with organ dysfunction. High plasma concentrations of soluble E-selectin were closely associated with multiple-organ dysfunction and death. Measurement of adhesion molecules, especially soluble E-selectin, might be used to advantage in the management of patients with sepsis. (Crit Care Med 1994; 22:651–657)

A Systematic Review of Molecular and Biological Tumor Markers in Neuroblastoma

Purpose: The aim of this study was to conduct a systematic review, and where possible meta-analyses, of molecular and biological tumor markers described in neuroblastoma, and to establish an evidence-based perspective on their clinical value for the screening, diagnosis, prognosis, and monitoring of patients. Experimental Design: A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Results: A total of 428 papers studying the use of 195 different tumor markers in neuroblastoma were identified. Small sample sizes, poor statistical reporting, large heterogeneity across studies (e.g., in cutoff levels), and publication bias limited meta-analysis to the area of prognosis only; MYCN, chromosome 1p, DNA index, vanillylmandelic acid:homovanillic acid ratio, CD44, Trk-A, neuron-specific enolase, lactate dehydrogenase, ferritin, and multidrug resistance were all identified as potentially important prognostic tools. Conclusions: This systematic review forms a knowledge base of the tumor markers studied thus far in neuroblastoma, and has identified some of the most important prognostic markers, which should be considered in future research and treatment strategies. Importantly, the review has also highlighted some general problems across primary tumor marker studies, in particular poor and heterogeneous reporting. These need to be addressed to allow better clinical interpretation and enable more appropriate evidence-based reviews in the future. In particular, collaboration of cancer research groups is needed to enable bigger sample sizes, standardize methods of analysis and reporting, and facilitate the pooling of individual patient data.

Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future

Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers.The reporting of these studies was often inadequate, in terms of both statistical analysis and presentation, and there was considerable heterogeneity for many important clinical/statistical factors. These problems restricted both the extraction of data and the meta-analysis of results from the primary studies, limiting feasibility of the evidence-based approach.Guidelines for reporting the results of primary prognostic marker studies in cancer, and other diseases, are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic reviews, meta-analysis and, ultimately, evidence-based practice. General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered, including poorly reported summary statistics and variability in cutoff level, outcome assessed and adjustment factors used. It would also limit the problem of reporting bias, although publication bias will remain a concern until studies are prospectively registered. Such changes in practice would help important evidence-based reviews to be conducted in order to establish the most appropriate prognostic markers for clinical use, which should ultimately improve patient care.

Partnerships with children

Earlier this year a 15 year old girl had her decision to refuse a heart transplant overruled by the High Court,1 highlighting the issue of partnership with children. The case is the latest of several2 that have shown how childrens participation in decision making and recognising their autonomy and rationality 3 4 can conflict with the need to protect them from making decisions that are not in their long term interests.5 Court cases dramatically show the problems of involving children in decision making, but they tend to deal with extreme and unusual examples and have led to uncertainty and anxiety about routinely involving children in decision making. Away from the courts a movement is growing to promote childrens rights. Proponents have argued from a position of moral obligation and have called for a code of practice which would emphasise childrens rights to information, to express views, and to give or withhold consent provided the child is considered competent by a doctor.6 Professional bodies and others concerned with childrens wellbeing seem to have accepted many of these principles,7–10 which are based on ethical and moral principles of autonomy, free will, choice, and compassion and have the laudable aim of allowing childrens opinions to be voiced, heard, and acted on wherever possible. However, the evidence suggests that partnership with children enjoys only limited success. Children are given little voice in medical consultations 8 11 and are rarely consulted as partners in the evaluation and planning of health services.12 13 The …

Medical students benefit from learning about patient safety in an interprofessional team

Context  Safe clinical practice is inextricably linked to team‐working. Delivering patient safety education interprofessionally heightens students’ awareness of the importance of effective team‐working for safe care and care delivery.

A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family

The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewings sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFTs were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.

Tissue samples as 'gifts' for research: A qualitative study of families and professionals

Current policy in many countries, including the UK, is that tissue samples used for medical research should be treated as ‘gifts’ from patients. This approach is increasingly criticised. Among the solutions proposed is introducing an individual property rights regime for tissue donors. We report a qualitative study of the views of 79 family members of children with cancer and 54 health professionals in the area of paediatric oncology. We argue that systems of governance and regulation need to respect the values of donors. A charitable trust model might be more consistent with the values of solidarity and reciprocity expressed by the study participants than an individual property rights approach.

Consent for childhood cancer tissue banking in the UK: the effect of the Human Tissue Act 2004.

The obtainment, storage, and use of human tissue taken from children for research purposes is an area that is notable for its complexity and legal uncertainties. In the UK, the controversy surrounding organ retention prompted radical legislative change in the form of the Human Tissue Act 2004, which came into force from September, 2006. This Review paper explores the effect of the Human Tissue Act on consent, in the context of childhood tissue banking. We take as our case study the UK Childrens Cancer Study Group tumour bank. Although the Human Tissue Act provides a new, detailed statutory framework, it does not, by itself, resolve all the relevant issues in this area. Researchers and clinicians must, therefore, continue to work alongside the existing principles of common law relating to this issue. Consent for the removal of tumour tissue during a surgical procedure should be distinguished from consent for the retention of the tissue for future use in research or for other specified uses. Consent to surgery is regulated by the same common law procedures used for consent to treatment. By contrast, the requirements for consent to storage and specified uses of samples are predominantly, but not exclusively, regulated by the Human Tissue Act. Although the Human Tissue Act might, at first, seem to promote clarity, the new legislative provisions and resultant Codes of Practice on consent could possibly lead tumour banks to reassess the nature and process of obtaining consent for the use of samples from children in research.