Bypass or Angioplasty for Severe Limb Ischaemia? A Delphi Consensus Study

AbstractObjectives: to examine the level of agreement among vascular surgeons and interventional radiologists regarding their preference for the surgical or endovascular management of severe limb ischaemia.Design: Delphi consensus study using 596 different hypothetical patient scenarios.Participants: Delphi consensus group for the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial.Methods: twenty consultant vascular surgeons and 17 interventional radiologists completed both rounds of the study. The scenarios detailed the anatomical extent of disease, whether the patients had rest pain only or had tissue loss, and whether or not a suitable vein for bypass was available. Panellists were asked to score their treatment preference for either surgery or angioplasty on an eight-point scale. Outliers (top 10% and bottom 10% responses) were removed. If the remaining 80% of responses fell within a 3-point range, this was defined as “agreement”. If they did not, this was considered “disagreement”.Results: there was substantial disagreement in 484 (81%) of scenarios in round 1 and 401 (67%) in round 2. This disagreement was greater among surgeon than radiologists in both round 1 (83 vs 65%) and round 2 (69 vs 42%). Surgeons also demonstrated less convergence between rounds.Conclusions: there is substantial disagreement between and among surgeons and radiologists with regard to the appropriateness of surgery or angioplasty for severe limb ischaemia. This lack of consensus stems from the absence of an evidence base and means that the same patient may receive entirely different treatment depending on which hospital and consultant they attend. Not only may this unexplained variation be clinically unsatisfactory, it has major implications for the planning and use of health service resources

Paying clinicians to join clinical trials : a review of guidelines and interview study of trialists

Background: The motivations of clinicians to participate in clinical trials have been little studied. This project explored the potential role of payment for participation in publicly funded clinical trials in the UK. The aims were to review relevant guidelines and to collate and analyse views of clinical trialists on the role of payments and other factors that motivated clinicians to join clinical trials. Methods: Review of guidelines governing payments to clinicians for recruitment to trials. Semistructured interviews with a range of NHS clinical trial leaders, analysed using qualititative methods. Results: While UK guidelines had little to say specifically on payments linked to recruitment, all payments have become highly regulated and increasingly transparent. Interview participants believed that expenses arising from research should be covered. Payments in excess of expenses were seen as likely to increase participation but with the risk of reducing quality. Motivations such as interest in the topic, the scope for patients to benefit and intellectual curiosity were considered more important. Barriers to involvement included bureaucracy and lack of time. Discussion: Limited scope exists for paying clinicians over-and-above the cost of their time to be involved in research. Most trialists favour full payment of all expenses related to research. Conclusion: Payment of clinicians beyond expenses is perceived to be a less important motivating factor than researching important, salient questions, and facilitating research by reducing bureaucracy and delay

Assessment of the face validity, feasibility and utility of a patient-completed questionnaire for polymyalgia rheumatica: a postal survey using the QQ-10 questionnaire.

BACKGROUND: The development of a patient-reported outcome measure (PROM) for polymyalgia rheumatica (PMR), a condition that causes pain, stiffness and disability, is necessary as there is no current validated disease-specific measure. Initial literature synthesis and qualitative research established a conceptual framework for the condition along with a list of symptoms and effects of PMR that patients felt were important to them. These findings were used to derive the candidate items for a patient-completed questionnaire. We aim to establish the face validity of this initial "long form" of a PROM. METHODS: People with a current or previous diagnosis of PMR were recruited both from the community and from rheumatology clinics. They were asked to complete the PMR questionnaire along with the QQ-10 questionnaire, which is a measure used to assess the face validity, feasibility and utility of patient healthcare questionnaires. RESULTS: A total of 28 participants with an age range of 59-85 years and a length of time since diagnosis from 4 months to 18 years completed the QQ-10. The overall mean "value" score was 79% (SD 12), and the mean "burden" score was 21% (SD 18). The free-text comments were analysed thematically and were found to focus on layout, content, where in the clinical pathway the questionnaire would be most beneficial, specific items missing and other areas for consideration. CONCLUSIONS: The high mean value score and low burden score indicate that the questionnaire has good face validity and is acceptable to patients. The questionnaire now needs to undergo further psychometric evaluation and refinement to develop the final tool for use in clinical practice and research

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Managing clinical trials

Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation

HcRed, a Genetically Encoded Fluorescent Binary Cross-Linking Agent for Cross-Linking of Mitochondrial ATP Synthase in Saccharomyces cerevisiae

Genetically encoded fluorescent cross-linking agents represent powerful tools useful both for visualising and modulating protein interactions in living cells. The far-red fluorescent protein HcRed, which is fluorescent only in a dimer form, can be used to promote the homo-dimerisation of target proteins, and thereby yield useful information about biological processes. We have in yeast cells expressed HcRed fused to a subunit of mitochondrial ATP synthase (mtATPase). This resulted in cross-linking of the large multi-subunit mtATPase complex within the inner-membrane of the mitochondrion. Fluorescence microscopy revealed aberrant mitochondrial morphology, and mtATPase complexes isolated from mitochondria were recovered as fluorescent dimers under conditions where complexes from control mitochondria were recovered as monomers. When viewed by electron microscopy normal cristae were absent from mitochondria in cells in which mATPase complexes were cross-linked. mtATPase dimers are believed to be the building blocks that are assembled into supramolecular mtATPase ribbons that promote the formation of mitochondrial cristae. We propose that HcRed cross-links mATPase complexes in the mitochondrial membrane hindering the normal assembly/disassembly of the supramolecular forms of mtATPase

Similarities in drinking behavior of twin's friends: moderation of heritability of alcohol use

Previous research has indicated that friends' drinking may influence alcohol use in adolescents and young adults. We explored whether similarities in the drinking behavior of friends of twins influence the genetic architecture of alcohol use in adolescence and young adulthood. Survey data from The Netherlands Twin Register were available for 1,526 twin pairs aged 16-25 years. We categorized the twin pairs as concordant (both report similar alcohol use in their friends) or discordant for the alcohol use of their friends. Genetic moderator models were tested by carrying out multi-group analyzes in Mplus. Findings showed a significant moderation effect. Genetic factors were more and common environment less important in the explanation of variation in alcohol use in twins discordant for alcohol use of friends than in twins concordant for alcohol use of friend

A centralised public information resource for randomised trials: a scoping study to explore desirability and feasibility

BACKGROUND: There are currently several concerns about the ways in which people are recruited to participate in randomised controlled trials, the low acceptance rates among people invited to participate, and the experiences of trial participants. An information resource about on-going clinical trials designed for potential and current participants could help overcome some of these problems. METHODS: We carried out a scoping exercise to explore the desirability and feasibility of establishing such a resource. We sought the views of a range of people including people who were considering taking part in a trial, current trial participants, people who had been asked but refused to participate in a trial, consumer group representatives and researchers who design and conduct trials. RESULTS: There was broad-based support for the concept of a centralised information resource for members of the public about on-going and recently completed clinical trials. Such an information resource could be based on a database containing standardised information for each trial relating to the purpose of the trial; the interventions being compared; the implications of participation for participants; and features indicative of scientific quality and ethical probity. The usefulness of the database could be enhanced if its search facility could allow people to enter criteria such as a disease and geographic area and be presented with all the trials relevant to them, and if optional display formats could allow them to view information in varying levels of detail. Access via the Internet was considered desirable, with complementary supported access via health information services. The development of such a resource is technically feasible, but the collation of the required information would take a significant investment of resources. CONCLUSION: A centralised participant oriented information resource about clinical trials could serve several purposes. A more detailed investigation of its feasibility and exploration of its potential impacts are required

Application of network traffic flow model to road maintenance

The study shows how the evolution of two-way traffic flows on a local highway network can be predicted over time using a network-level traffic flow model (NTFM) to model both urban and motorway road networks. After a brief review of the main principles of the NTFM and its associated sub-models, the paper describes how a maintenance worksite can be modelled using a roadwork-node sub-model and a network solution routine in the NTFM. In order to model the two-way traffic flow in the road network, an iterative simulation method is used to generate the evolution of dependent traffic flows and queues. The NTFM has been applied to model the traffic characteristics and the effects of maintenance activities on the local Loughborough–Nottingham highway network. The study has demonstrated that the methodology is useful in selecting various worksite arrangements in order to reduce the effects of maintenance on road users