scispace - formally typeset
Search or ask a question

Showing papers by "Leicester General Hospital published in 2001"


Journal ArticleDOI
01 Apr 2001-Gut
TL;DR: Using new meta-analysis techniques, the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children was determined and how risk varies with geography was estimated.
Abstract: BACKGROUND AND AIMS Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

2,627 citations


Journal ArticleDOI
TL;DR: A number of recommendations for the design and execution of studies within postoperative cognitive function are presented, and the critical reader may use these recommendations in the evaluation of the literature.
Abstract: Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature.

498 citations


Journal ArticleDOI
TL;DR: This review examines the current in vitro animal and human work underlying the use of rapamycin and comments on the pharmacokinetics and side-effect profile of this promising new agent.

427 citations


Journal ArticleDOI
TL;DR: The evidence linking CRP with atherosclerosis is outlined and it is proposed that elevated CRP concentrations may be involved in the initiation and progression of accelerated Atherosclerosis in uremia.

397 citations


Journal ArticleDOI
TL;DR: A need for caution when translating biopsy results between institutions is demonstrated, as it is obvious that evaluation of biopsies in multicenter trials must be done in one center.

262 citations


Journal ArticleDOI
TL;DR: It is concluded that gastrointestinal pathologists are no better than generalists when grading dysplasia in UC and that agreement is poor in both groups, and there is therefore no evidence that there would be any benefit in having specialist histopathology centres concentrating specifically on the interpretation of all surveillance colonoscopy biopsies from around the UK.
Abstract: Histological dysplasia is the cornerstone of colorectal cancer surveillance in ulcerative colitis (UC). Recently, pathologists have received unfavourable media attention concerning other cancer screening programmes. The aim of this study was to determine whether colonic biopsy specimens should be examined by gastrointestinal pathologists as opposed to generalists, by examining inter-observer variation between the two groups. Fifty-one coded slides showing varying degrees of dysplasia were mailed to seven gastrointestinal and six general histopathologists. Pathologists allocated each biopsy into one of four categories without the benefit of a clinical history or an opportunity to use the 'indefinite' category that is included in the Riddell classification. The responses were analysed using kappa statistics. The overall kappa statistic for gastrointestinal pathologists was 0.30 [95% confidence interval (CI)=0.26-0.34] and for general pathologists 0.28 (95% CI=0.23-0.32). Agreement was best for high-grade dysplasia (kappa of 0.54 and 0.61 for GI and general pathologists, respectively). There was total concordance of the 13 pathologists in only four of the 51 slides (7.8%) (95% CI=0.4-15.2%). It is concluded from these results that gastrointestinal pathologists are no better than generalists when grading dysplasia in UC and that agreement is poor in both groups. There is therefore no evidence that there would be any benefit in having specialist histopathology centres concentrating specifically on the interpretation of all surveillance colonoscopy biopsies from around the UK. It must be made clear to the public that surveillance and screening programmes carry a significant rate of histological error and that perfection cannot be expected or achieved with present methods.

231 citations


Journal ArticleDOI
TL;DR: The appearance of the disease in the older age groups together with the lack of evidence for an autosomal recessive pattern of inheritance would suggest that environmental factors are important in the cause of achalasia.

195 citations


Journal ArticleDOI
TL;DR: Long-term furosemide produces a significant increase in UV over 12 months when on CAPD and may result in clinically significant improvement in fluid balance, however, furoSemide has no effect on preserving residual renal function.

185 citations


Journal ArticleDOI
TL;DR: The depression and anxiety subscales of the HAD showed poor efficacy for screening when used alone and should be used as a combined scale, but low sensitivity and specificity may lead to poor efficacy as a screening tool.

142 citations


Journal ArticleDOI
TL;DR: Preliminary evidence is provided that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.

120 citations


Journal ArticleDOI
01 Jan 2001
TL;DR: Very elderly ESRD patients on RRT have a very poor outcome and, since they are the largest growing group of RRT patients, this has important implications for future health policies.
Abstract: BACKGROUND In a retrospective case-note and computer database analysis we assessed the outcome of very elderly patients (> or = 75 years old) with end-stage renal disease (ESRD) on renal replacement therapy (RRT). METHODS Fifty-eight individuals aged 75 or over (group 1) commenced RRT between 1 January 1991 and 31 December 1995. Comparisons were made with other patients commencing RRT who were divided into two groups: group 2 (201 individuals 65-74 years old) and group 3 (379 patients <65 years old). All subjects were followed up until the point of assessment (30 June 1998), the time of death, or withdrawal from dialysis. Survival rates in the three groups were compared using Kaplan-Meier method. The number of hospital admissions, length of in-patient stay, and complications rate on RRT were assessed for group 1. RESULTS One-year survival rates in groups 1, 2 and 3 were 53.5, 72.6, and 90.6% respectively and the 5-year survival rates were 2.4, 18.8, and 61.4% respectively. The very elderly spent 20% of their time in hospital, 46% had two co-morbid factors at the outset, and 26% developed multiple complications while on RRT. Withdrawal from dialysis remained the most common cause of death in this group of individuals (38%), followed by cardiovascular causes (24%) and infections (22%). CONCLUSION Very elderly ESRD patients on RRT have a very poor outcome and, since they are the largest growing group of RRT patients, this has important implications for future health policies.

Journal ArticleDOI
01 May 2001-Knee
TL;DR: The isolated atraumatic medial meniscal tear appeared to do particularly poorly and may be better treated by meniscectomy.
Abstract: A total of 62 arthroscopic meniscal repairs (60 knees in 59 patients) over a 5-year period were evaluated retrospectively to assess outcome and to identify factors that might improve future clinical results. The overall success rate was 66.1%. Early repair within 3 months of sustaining the tear gave better results (91%) than if carried out later (58%). Suture repair alone yielded better results (78%) than meniscal arrows or a T-fix device (56%). Healing rates of atraumatic meniscus tears were much lower than for traumatic tears (42 vs. 73%). The isolated atraumatic medial meniscal tear appeared to do particularly poorly (33% healing) and may be better treated by meniscectomy.

Journal ArticleDOI
TL;DR: The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB‐t and is an important advance in developing new treatment options for these patients.
Abstract: The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

Journal ArticleDOI
TL;DR: Patient satisfaction is dependent on many factors and mismatch between patient expectation and the service received is related to decreased satisfaction, which may increase as general practitioners delegate more out of hours care to cooperatives and deputising services.
Abstract: Objectives—To describe the relationship between patient satisfaction with out of hours care provided by deputising and practice doctors in four urban areas in England and characteristics of the service provided and patients, the care given, and health outcomes. Setting—Fourteen general practices in four urban areas in England. Participants—People who requested out of hours care. Design—Analysis of data from a study of out of hours care. Patients were interviewed within 5 days of their request for out of hours care. Data on the service provided were obtained from medical records and all other data were collected at interview. Satisfaction was measured using a valid reliable instrument. Results—2152 patients were recruited to the study and 1466 were interviewed. Satisfaction data were available on 1402 patients. “Overall satisfaction” was associated with age, doctor type, lack of access to a car at the time of the request, and health outcome. The relationships between satisfaction subscales and patient characteristics (age, sex, ethnicity, and access to a car at the time of the request), service characteristics (doctor type and delay between the request and visit), whether a prescription was given, and health outcome were variable. If an expected home visit was not received, “overall satisfaction” and satisfaction with “communication and management”, “doctor’s attitude”, and “initial contact person” were reduced. Conclusion—Patient satisfaction is dependent on many factors. Mismatch between patient expectation and the service received is related to decreased satisfaction. This may increase as general practitioners delegate more out of hours care to cooperatives and deputising services. (Quality in Health Care 2001;10:23‐28)

Journal Article
TL;DR: In the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk and the proportion of patients with BDI scores less than 11 at 16 weeks increased in the intervention group.
Abstract: BACKGROUND: Various methods are available for implementing change in the clinical behaviour of general practitioners (GPs). Although passive dissemination of information is generally ineffective, other methods can be variably effective. Few studies have investigated the impact of tailored methods. AIM: To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs. DESIGN OF STUDY: Randomised controlled trial. SETTING: Sixty general practices in England; 30 GPs in the control group, 34 in the intervention group. METHOD: Practitioners identified patients presenting with depression before and after the implementation of guidelines (control group n = 192 in the first data collection, n = 181 in the second; intervention group n = 210 in the first data collection and n = 197 in the second). The main outcome measures were: record of adherence to guideline recommendations in clinical records; proportion of patients with Beck Depression Inventory (BDI) score less than 11 at 16 weeks after diagnosis. RESULTS: In comparison with the control group, in the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk. In the intervention group, the proportion of patients with BDI scores of less than 11 at 16 weeks increased. CONCLUSION: Obstacles to implementation can be identified and strategies tailored to address them. The findings indicate a new approach for research to understand and develop methods of implementation.

Journal ArticleDOI
15 Jun 2001
TL;DR: NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD, and compared with matched heart-beating donor transplants as a case control analysis.
Abstract: Introduction The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. Methods In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. Results 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. Conclusion NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.

Journal ArticleDOI
TL;DR: Uptake of the screening test for DS was best in those with good knowledge compared to those with poor knowledge, and there is need for better education and counselling of women attending for antenatal care.
Abstract: The uptake of any screening test is influenced by knowledge of the condition being screened for. In the present study, the knowledge and the source of knowledge of women offered antenatal screening for Down syndrome (DS) was assessed by means of a self-administered questionnaire. The questionnaire was administered to 300 consecutive women booking for antenatal care, of the 245 (82%) women who completed and returned the questionnaire, 117 (48%) were Caucasian, 85 (35%) were Asian born outside the UK, 32 (13%) were Asian born in the UK and ten (4%) belonged to other categories. Only 30% of the cohort had a good understanding of the condition. Racial groups other than Caucasian had a poorer understanding of DS. The factors which affected knowledge of DS included quality of spoken English, knowing an affected child, parity and religion. The most significant factor affecting acceptance of screening was the woman's knowledge of DS. The source of information for the condition varied widely: 42% from a general practitioners (GP), 24% from the hospital and 16% from midwives. The proportion with good knowledge was similar in those women whose source of information was the GP (45%) and the midwife (41%). These proportions were, however, higher (though not significantly) when the source of information was from magazines and newspapers (67%) and from friends (53%). Uptake of the screening test was best in those with good knowledge (53%) compared to those with poor knowledge (23%) (p<0.02). Between 28% and 66% (depending on the ethnic group) of women had a screening blood test "allegedly" without knowing why it had been performed. In order to improve uptake of the screening test for DS there is need for better education and counselling of women attending for antenatal care.

Journal ArticleDOI
24 Mar 2001-BMJ
TL;DR: The case for the primacy of obtaining direct evidence of clinical competence of any doctor being revalidated is presented; the essential attributes of any process of obtaining such evidence are discussed; the ways in which such evidence can be gathered are described; the limitations of review tools currently available; and an appropriate model for performance review are suggested.
Abstract: It is now clear that revalidation and clinical governance will drive continuing professional development in medicine in the United Kingdom. 1 2 Thus patients, society, and the profession are to be assured that individual doctors not only are fit to practise but are providing high quality care for patients. The focus of professional revalidation is rightly moving from the requirement that practitioners merely provide evidence of participation in continuing education towards the requirement that they provide evidence that better reflects their clinical practice. 3 4 Nevertheless, the primary screening procedures that have been proposed for revalidation are indirect (see box).4 If used at all, tests of clinical competence come much later in the process, but few tests include direct observation of practice. We present the case for the primacy of obtaining direct evidence of clinical competence of any doctor being revalidated; discuss the essential attributes of any process of obtaining such evidence; describe the ways in which such evidence can be gathered; explore the limitations of review tools currently available; and suggest an appropriate model for performance review. #### Summary points The measures currently proposed for assessing competence in clinician revalidation are mainly indirect or proxy As the consultation is the single most important event in clinical practice, the central focus of revalidation should be the assessment of consultation competence Such assessment should be by direct observation and satisfy five criteria—reliability, validity, acceptability, feasibility, and educational impact Assessment of consultation competence would be followed by assessment of specific skills and regular performance review Such an assessment procedure is recommended for use in the revalidation of all clinicians #### Recent proposed components of revalidation in United Kingdom Indirect …

Journal ArticleDOI
TL;DR: Women in the experimental group had more home births, birth in a midwife-led suite and opted for early discharge home postnatally more often than the controls, and experienced much higher levels of continuity, particularly of a known midwife during labour and birth.

Journal ArticleDOI
TL;DR: Results indicate that substantial improvements in quality of intrapartum care can be achieved by a programme of clinical riskmanagement.
Abstract: Confidential Enquiries into Stillbirths and Deaths in Infancy (CESDI) have pointed to a high frequency of suboptimal intrapartum fetal care of a kind that, in the event of an adverse outcome, is hard to defend in court. In an effort to minimize liability, various strategies were applied in a district hospital labour ward—guidelines, cyclical audit, monthly feedback meetings and training sessions in cardiotocography (CTG). The effects of these interventions on quality of care was assessed by use of the CESDI system in all babies born with an Apgar score of 4 or less at 1 min and/or 7 or less at 5 min. 540 babies (4.3%) had low Apgar scores, and neither the percentage nor gestational age differed significantly between audit periods. In the baseline audit, care was judged suboptimal (grade II/III) in 14 (74%) of 19 cases, and in the next four periods it was 23%, 27%, 27% and 32%. In the latest audit period, after further educational interventions, it was 9%. Many of the failures to recognize or act on abnormal events were related to CTG interpretation. After the interventions there was a significant increase in cord blood pH measurement. There were no differences between audit periods in the proportion of babies with cord pH <7.2. These results indicate that substantial improvements in quality of intrapartum care can be achieved by a programme of clinical risk management.

Journal ArticleDOI
TL;DR: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia.
Abstract: Aims/hypothesis: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds.

Journal ArticleDOI
01 Jan 2001-Gut
TL;DR: Preliminary evidence is provided that EGF may be a novel approach for the prevention and/or treatment of multiorgan failure and reduced mortality, renal injury, and gastrointestinal damage.
Abstract: BACKGROUND—Multiorgan failure is a severe life threatening state where present therapeutic approaches are suboptimal. Epidermal growth factor (EGF) is a potent stimulant of repair in in vitro and in vivo models. We therefore examined its potential beneficial effect in reducing mortality and injury induced by the noxious agent thioacetamide (TAA). METHODS—Mice (20 per group) were fasted overnight and received a single intraperitoneal dose of human recombinant EGF at 10 or 30 µg/kg or saline (control). Either 30 minutes before or after EGF, all animals also received TAA (40 mg/kg intraperitoneally). Twenty four hours later, surviving animals were killed, tissues collected, and degree of organ injury assessed. RESULTS—Fifty per cent (10/20) of control animals died within the first 24 hour period. Mortality was almost completely prevented by the higher dose of EGF whether given before or after TAA (p<0.01) and was reduced by about 50% with the lower dose of EGF. In control animals, the entire length of the jejunum and ileum had necrosis with or without mucosal denudation. In contrast, necrosis affected only about 10-20% of the total length in EGF treated groups (both p<0.01 v control). Control animals showed marked glomerular tuft collapse, interstitial haemorrhage, and increased plasma creatinine levels. These effects were significantly reduced in animals given EGF (30 µg/kg; p<0.01). All groups showed similar changes in liver histology (centrilobular necrosis) and alanine transaminase levels (10-fold increase). CONCLUSIONS—Although EGF did not prevent the hepatotoxicity associated with TAA, it reduced mortality, renal injury, and gastrointestinal damage. These studies provide preliminary evidence that EGF may be a novel approach for the prevention and/or treatment of multiorgan failure. Keywords: gastrointestinal damage; nephrotoxicity; liver injury

Journal ArticleDOI
01 Feb 2001-Scopus
TL;DR: The new immunosuppressive agent rapamycin inhibits growth factordriven proliferation in a number of cells crucial to the development of fibrosis including smooth muscle cells, endothelial cells, and fibroblasts and has a potential role in the therapy of CAN.
Abstract: CHRONIC ALLOGRAFT nephropathy (CAN) remains a major cause of renal transplant failure. It is characterised by a progressive functional deterioration, which is associated histologically with graft fibrosis. Cyclosporin has no impact on the development of CAN, and its nephrotoxicity is a contributor to the functional and histological deterioration found in this condition. The new immunosuppressive agent rapamycin inhibits growth factordriven proliferation in a number of cells crucial to the development of fibrosis including smooth muscle cells, endothelial cells, and fibroblasts. It therefore has a potential role in the therapy of CAN. In this experiment, to further explore this role both cyclosporin and rapamycin were administered to a rodent model of renal ischaemia reperfusion injury, which has previously been shown to be associated with up-regulation of fibrosis-associated genes.

Journal Article
TL;DR: MRSA infection has a high mortality in vascular surgical patients in general, and following aorto-iliac reconstruction in particular, and strategies aimed at reducing the incidence of infection, including strict adherence to infection control procedures, may reduce the severity of this problem.
Abstract: BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is emerging as a major problem in vascular surgical practice. The aim of this study was to review the management of patients with MRSA infection complicating vascular surgical operations. METHODS: Data were obtained from the vascular audit, case notes, intensive therapy unit (ITU) notes, high dependency unit (HDU) notes and microbiological records of patients who underwent either arterial reconstruction (n = 464) or limb amputation (n = 110) between April 1994 and October 1998. RESULTS: Forty-nine vascular surgical patients developed clinical MRSA infection (9%). Clinical MRSA infection in patients who had undergone aorto-iliac reconstruction (n = 18) was associated with a 56% mortality (n = 10) and the most common infections were bacteraemia (55%) and pneumonia (50%). MRSA infection occurred in 17 patients who had undergone infra-inguinal bypass and was associated with a 29% mortality (n = 5). The most common site of MRSA infection was the groin wound (76%) leading to anastomotic dehiscence and death in one patient (11%) and necessitating wound debridement in 4 patients (22%). MRSA infection of the groin wound in the presence of a prosthetic graft (n = 3) led to anastomotic dehiscence in 2 patients, and graft excision in 2 patients. Similar complications were not observed in the presence of an underlying autogeneous long saphenous vein graft (n = 16). MRSA infection following major lower limb amputation (n = 14) was associated with death in 5 patients (36%). Wound infection in 10 amputees (71%) led to revision of the amputation to a higher level in 2 (14%) and wound debridement in 2 (14%). CONCLUSIONS: MRSA infection has a high mortality in vascular surgical patients in general, and following aorto-iliac reconstruction in particular. Autogeneous vein may confer some protection against local complications following groin wound infection. Strategies aimed at reducing the incidence of infection, including strict adherence to infection control procedures, may reduce the severity of this problem.

Journal ArticleDOI
TL;DR: The level of knowledge achieved by patients who have read a simple information sheet on gastroscopy and flexible sigmoidoscopy is determined, and the levels of information required by patients and solicitors specializing in clinical negligence are determined.
Abstract: Objective To determine the level of knowledge achieved by patients who have read a simple information sheet on gastroscopy and flexible sigmoidoscopy, and to determine the levels of information required by patients and solicitors specializing in clinical negligence.Design Self-administered questionn

Journal ArticleDOI
TL;DR: Support for the hypothesis that proteinuria may be an independent mediator of progression, rather than simply a marker of glomerular dysfunction, comes from the observations that strategies that reduce proteinuria, including control of hypertension, angiotensin-converting enzyme inhibition, and low-protein diets, reduce the rate of progression of renal failure.

Journal ArticleDOI
25 Aug 2001-BMJ
TL;DR: The new health promotion payment did not overcome general practitioners' resistance towards raising the issue of smoking when they felt that doing so could cause confrontation with patients, and policymakers should consider careful piloting and evaluation of future changes in health promotion payments.
Abstract: Objectives: To elicit general practitioners9 and practice nurses9 accounts of changes in their clinical practice or practice organisation made to claim a pilot health promotion payment. To describe attitudes towards the piloted and previous health promotion payments. Design: Qualitative, semistructured interview study. Setting: 13 general practices in Leicester. Participants: 18 general practitioners and 13 practice nurses. Results: Health professionals did not report substantially changing their clinical practice to claim the new payments and made only minimal changes in practice organisation. The new health promotion payment did not overcome general practitioners9 resistance towards raising the issue of smoking when they felt that doing so could cause confrontation with patients. General practitioners who made the largest number of claims altered the way in which they recorded patients9 smoking status rather than raising the topic of smoking more frequently with patients. Participants had strong negative views on the new payment, feeling it would also be viewed negatively by patients. They were, however, more positive about health promotion payments that rewarded “extra” effort — for example, setting up practice based smoking cessation clinics. Conclusions: General practitioners and practice nurses were negative about a new health promotion payment, despite agreeing to pilot it. Health promotion payments do not automatically generate effective health promotion activity, and policymakers should consider careful piloting and evaluation of future changes in health promotion payments.

Journal ArticleDOI
25 Aug 2001-BMJ
TL;DR: The feasibility and effectiveness of a payment scheme that aimed to increase general practitioners' antismoking advice in an uncontrolled before and after study were examined.
Abstract: See p 432 Since 1990, the UK government has tried to influence health promotion activity by general practitioners through payment schemes.1 These have never been rigorously evaluated.2 We examined the feasibility and effectiveness of a payment scheme that aimed to increase general practitioners' antismoking advice in an uncontrolled before and after study. The health promotion payment was piloted in a deprived area of Leicester. The recruitment of practices is described elsewhere.3 Thirty five general practitioners (out of 62 approached) from 13 general practices (out of 28 approached) were recruited, and 31 participated in the study. Before data collection began, we invited all members of primary healthcare teams to attend training in methods of stopping smoking. We then observed normal clinical behaviour over nine months (the control period). In the following nine months (the intervention period), practices could claim £15 from the health authority for identifying …

Journal ArticleDOI
01 Sep 2001
TL;DR: The data suggest that the pro-fibrotic effect of glucose dialysate on HPMC is mediated through stimulation of TGF-beta, which promotes FN gene expression and protein production.
Abstract: BACKGROUND Dialysate glucose has been implicated in the loss of peritoneal membrane function seen in long-term CAPD patients. METHODS In order to investigate this in vitro, human peritoneal mesothelial cells (HPMC) were cultured in a 50:50 mix of dialysis solution and M199 for 12 h. The dialysate was laboratory manufactured and designed to be identical in composition to PD4 (LAB). The final glucose concentration ranged between 5 and 40 mmol/l. Experiments were conducted in the presence and absence of an anti-transforming growth factor-beta (TGF-beta) antibody. Cell viability was measured by lactate dehydrogenase (LDH) release. Fibronectin (FN) and TGF-beta protein were measured by ELISA, and FN gene expression was measured by Northern analysis. Separately, the effects of recombinant TGF-beta(1) added to M199: dialysate at 5 mmol/l glucose were investigated. RESULTS Forty millimoles per litre d-glucose LAB caused a decrease in cell viability, as evidenced by an increase in LDH release (6.0+/-1.3 vs 2.6+/-0.7%). This effect was dependent on osmolality. Forty millimoles per litre d-glucose LAB stimulated a 15.4+/-4.6% increase in FN, a 46.5+/-18.3% increase in TGF-beta protein (both P<0.05), and 1.4+/-0.09-fold increase in FN mRNA compared with 5 mmol/l d-glucose LAB. Exogenous TGF-beta 0-1 ng/ml induced a dose-dependent increase in FN protein (280+/-45% increase at TGF-beta 1 ng/ml, P<0.0001), and FN mRNA levels (10.0+/-1.8-fold at TGF-beta 1 ng/ml). The increase in FN in response to 40 mmol/l glucose was significantly reduced by anti-TGF-beta antibody to levels not different from control (93.8+/-6.6%, P<0.05 vs no Ab). CONCLUSIONS These data suggest that the pro-fibrotic effect of glucose dialysate on HPMC is mediated through stimulation of TGF-beta, which promotes FN gene expression and protein production.

Journal ArticleDOI
TL;DR: An evaluation of a local clinical supervision scheme for practice nurses in Leicestershire, UK found that over half of the practice nurses remained undecided about their future involvement in the scheme, and obstacles that currrently hinder practice nurses' involvement need addressing.
Abstract: • This paper presents the findings of an evaluation of a local clinical supervision scheme for practice nurses in Leicestershire, UK. • A baseline and a follow-up postal questionnaire were sent to all practice nurses (including supervisors) and general practice senior partners to find out how far the objectives of the local scheme had been met during the first year of implementation. Two focus groups gathered qualitative data about the process of implementation. • Twelve months after implementation 12% of practice nurses and over two thirds of GPs reported that they were unaware of the scheme. Forty-three percent of practice nurses did not know who their local supervisor was; most reported that they would like to have known. • Eighteen percent of practice nurses reported uptake of supervision through the local scheme. The benefits of involvement were professional development tailored to individual learning needs and regular opportunities to share work-related problems with peers; about a third reported benefits for the practice as well. • The existing availability of peer support and time needed to undertake clinical supervision were common reasons given for non-involvement in the scheme. Misconceptions about the purpose of clinical supervision presented further obstacles. • At follow-up over half of the practice nurses remained undecided about their future involvement in the scheme. • If the benefits associated with clinical supervision are to be realized, the obstacles that currently hinder practice nurses’ involvement need addressing.