Leicester General Hospital

About: Leicester General Hospital is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Transplantation. The organization has 2481 authors who have published 3034 publications receiving 107437 citations.

Formative assessment of the consultation performance of medical students in the setting of general practice using a modified version of the leicester assessment package.

Abstract: Objective To evaluate the use of a modified version of the Leicester Assessment Package (LAP) in the formative assessment of the consultation performance of medical students with particular reference to validity, inter-assessor reliability, acceptability, feasibility and educational impact. Design 180 third and fourth year Leicester medical students were directly observed consulting with six general practice patients and independently assessed by a pair of assessors. A total of 70 practice and 16 departmental assessors took part. Performance scores were subjected to generalizability analysis and students’ views of the assessment were gathered by questionnaire. Results Four of the five categories of consultation performance (Interviewing and history taking, Patient management, Problem solving and Behaviour and relationship with patients) were assessed in over 99% of consultations and Physical examination was assessed in 94%. Seventy-six percent of assessors reported that the case mix was ‘satisfactory’ and 20% that it was ‘borderline’; 85% of students believed it to have been satisfactory. Generalizability analysis indicates that two independent assessors assessing the performance of students across six consultations would achieve a reliability of 0·94 in making pass or fail decisions. Ninety-eight percent of students perceived that their particular strengths and weaknesses were correctly identified, 99% that they were given specific advice on how to improve their performance and 98% believed that the feedback they had received would have long-term benefit. Conclusions The modified version of the LAP is valid, reliable and feasible in formative assessment of the consultation performance of medical students. Furthermore, almost all students found the process fair and believed it was likely to lead to improvements in their consultation performance. This approach may also be applicable to regulatory assessment as it accurately identifies students at the pass/fail margin.

Distinguishing C1q nephropathy from lupus nephritis.

Abstract: Background 'Seronegative lupus nephritis' describes patients with renal histology typical of lupus nephritis who have no clinical or serological evidence of systemic lupus erythematosus (SLE). We report our experience in nine patients identified as having 'seronegative lupus nephritis' who met the diagnostic criteria for C1q nephropathy. Methods A retrospective review of clinical case notes and renal histology was carried out. Results We describe nine patients with C1q nephropathy in whom the diagnosis of 'seronegative lupus nephritis' was initially considered. All had renal histological features typical of lupus nephritis with 'wire loop' appearances on light microscopy, 'full house' immunoglobulin and complement deposition by immunoperoxidase, and electron-dense deposits in at least two glomerular locations. None of these nine patients developed clinical or serological evidence of SLE over a median follow-up of 6 years (range 0.1-9). There was no consistent evidence of a response to immunosuppressive therapy. In all cases, C1q staining was dominant on immunoperoxidase, and no tubuloreticular inclusions were seen. These appearances accord with previous descriptions of C1q nephropathy. Conclusions The implications of a diagnosis of lupus are considerable, and we propose that the term 'seronegative lupus nephritis' is unhelpful, and should be avoided when there is diagnostic uncertainty. The term C1q nephropathy should be preferred when these histological features are seen in the absence of overt lupus, when C1q deposition is dominant and when tubuloreticular bodies are absent. The clinical course in the cases reported here does not support the use of immunosuppressive therapy in C1q nephropathy.

Walking away from type 2 diabetes: trial protocol of a cluster randomised controlled trial evaluating a structured education programme in those at high risk of developing type 2 diabetes

Abstract: The prevention of type 2 diabetes is a recognised health care priority globally. Within the United Kingdom, there is a lack of research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. This study aims to establish the behavioural and clinical effectiveness of a structured educational programme designed to target perceptions and knowledge of diabetes risk and promote a healthily lifestyle, particularly increased walking activity, in a multi-ethnic population at a high risk of developing type 2 diabetes. Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is change in objectively measured ambulatory activity. Secondary outcomes include progression to type 2 diabetes, biochemical variables (including fasting glucose, 2-h glucose, HbA1c and lipids), anthropometric variables, quality of life and depression. 10 primary care practices will be recruited to the study (5 intervention, 5 control). Within each practice, individuals at high risk of impaired glucose regulation will be identified using an automated version of the Leicester Risk Assessment tool. Individuals scoring within the 90th percentile in each practice will be invited to take part in the study. Practices will be assigned to either the control group (advice leaflet) or the intervention group, in which participants will be invited to attend a 3 hour structured educational programme designed to promote physical activity and a healthy lifestyle. Participants in the intervention practices will also be invited to attend annual group-based maintenance workshops and will receive telephone contact halfway between annual sessions. The study will run from 2010–2014. This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme run within routine primary care in the United Kingdom. ClinicalTrials.Gov identifier: NCT00941954

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity.

Abstract: In the UK, bladder cancer is a common urological malignancy, affecting more than 12 500 individuals each year and causing nearly 5000 deaths per annum (CRC, 2001). In all, 90% of bladder cancers are transitional cell carcinomas (TCCs) and ∼30% of bladder tumours are muscle invasive at presentation, a feature that is associated with significant risk of metastasis (30–60%). Patients with organ-confined, muscle-invasive tumours, (T2/3/4a) who are deemed fit, are considered for potentially curative treatment in the form of radical surgery (cystectomy) or radiotherapy. Radical cystectomy (removal of the bladder and urinary diversion) is associated with significant morbidity and a mortality rate of ∼2% (Skinner et al, 1988; Studer et al, 1995). Furthermore, the necessary creation of an abdominal wall stoma (ileal conduit) may impact on quality of life, and erectile dysfunction is virtually universal. The outcome following radical cystectomy varies with tumour stage, with an overall 5-year survival of ∼40%. Radical radiotherapy (RT) is the mainstay of bladder-sparing treatment regimens. It avoids the trauma of major surgery and is considered a primary treatment for patients deemed unfit for surgery. However, RT is itself associated with dose-related complications arising from bowel and bladder being included in the radiation field. Furthermore, while for ∼50% of patients radical RT results in effective local tumour control and acceptable bladder function (Quilty et al, 1986; Jenkins et al, 1989), the remaining patients suffer local recurrence. For this latter group, the decision to treat with RT is disadvantageous, as these patients have been unnecessarily exposed to additional risks of ionising radiation. In addition, the time taken to recognise treatment failure (3–6 months) may provide further opportunity for metastatic spread, before secondary treatment (salvage cystectomy) is undertaken. Also, the morbidity in patients undergoing salvage cystectomy has been found to be significantly higher than in patients undergoing primary cystectomy (Rosario et al, 2000). Consequently, if a patient's bladder tumour RT response could be predicted in advance, RT could be promoted in patients with tumours that are predicted to respond. Conversely, patients with nonresponsive tumours could be identified and offered surgery at an earlier stage. In this way, the overall local control rates could be improved. While much work has been undertaken to develop assays capable of predicting tumour response to RT, none has been successfully applied to clinical practice. However, ex vivo measures of the surviving fraction of tumour cells at 2 Gy (SF2) suggest that intrinsic radiosensitivity (IRS) is a significant factor in determining tumour radiocurability (West, 1995; West et al, 1997). However, the SF2 assay fails to provide information on a time scale appropriate for treatment planning and also suffers from limited success rates; in an unpublished study, <10% of bladder tumours gave rise to colonies on soft agar (McKeown, McKelvey-Martin and Ho, personal communication). In addition, the relationship between clonogenic survival and clinical response is far from proven. The limitations of SF2 have stimulated research into methods to provide a more rapid and complete measure of IRS. DNA is the most important cellular target for the lethal effects of ionising radiation, with double-strand breaks (DSBs) proposed to be the principal lesions responsible for radiogenic cell killing (Ward, 1988; Iliakis, 1991). Unfortunately, the relative yield of radiogenic DSBs is low, and high radiation doses tend to be required to produce measurable levels; doses that are far greater than those used clinically. Indeed, while a recent study using the neutral comet assay to measure DSBs reports an association between DSB manifestation and survival (Price et al, 2000), the correlations were not definite, with one cell line yielding a false impression of radiosensitivity at the high doses (30 Gy) required for the assay. This highlights a benefit of conducting predictive tests of radiosensitivity at clinically relevant doses. In contrast with DSBs, the yield of radiation-induced single-strand breaks (SSBs) is far greater (Ward, 1988), and can be readily measured at low clinically relevant doses of radiation. Furthermore, the mechanisms that are proposed to vary the yield of radiation-induced DSBs formation are also expected to vary the yield of radiation-induced SSBs (Ward, 1990). Consequently, the extent of radiation-induced SSB formation can be considered a valid surrogate marker of radiogenic DSB formation. The alkaline comet assay (ACA) is a highly sensitive method for the assessment of SSBs and alkali labile sites (ALSs), and can readily detect levels of damage induced by clinically relevant doses of radiation (Singh et al, 1994; Singh, 1996). In a previous study of just three bladder cancer cell lines, an inverse correlation was obtained between clonogenic survival and mean tail moment (TM) for comet formation, suggesting that ACA could potentially be used to predict the radio response of the single cell lines (McKelvey-Martin et al, 1998). In the present study, we report our evaluation of ACA as a measure of bladder cancer cell radiosensitivity in vitro using a panel of six bladder cancer cell lines, and demonstrate that the extent of comet formation best reflects bladder cancer cell radiosensitivity; these results are supported by two independent, parallel studies using colorectal tumour cells (Dunne et al, 2003) and bladder tumour cells (McKeown et al, 2003). We also report on a preliminary study to determine the differing ACA radio response of epithelial cells isolated from human bladder tumour biopsies.

Outcome measures in intervention trials for adults with autism spectrum disorders: a systematic review of assessments of core autism features and associated emotional and behavioural problems

Abstract: A systematic review was conducted of outcome measures used in treatment trials for older adolescents and adults with autism spectrum disorders (ASDs). Of 818 titles only 30 articles (19 of which involved pharmacological treatments) were identified that met inclusion criteria (sample size > 5; mean age of group > 15 years; mean IQ > 30; ASD diagnosis confirmed; use of objective ASD outcome measures; focus on symptoms core to or typically associated with ASDs). Selected studies included randomized and placebo-controlled trials, retrospective assessment studies, case series and open label or case-control trials. Use of outcome measures varied with frequent use of non-standardized assessments, very little use of measures designed specifically for individuals with ASD or of instruments focusing on core ASD deficits, such as communication or social functioning. Most commonly used were the Clinical Global Impression (CGI) rating scale and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The strengths or deficiencies of the outcome measures used were not systematically evaluated. Although there are now many well controlled treatment trials for children with ASDs, adult intervention research is very limited. The lack of valid and reliable outcome measures for adults with ASDs compromises attempts at treatment evaluation.