Effect of cold ischaemia time on outcome after living donor renal transplantation.

BACKGROUND: The aim of the present study was to determine the effects of cold ischaemia time (CIT) on living donor kidney transplant recipients in a large national data set. METHODS: Data from the National Health Service Blood and Transplant and UK Renal Registry databases for all patients receiving a living donor kidney transplant in the UK between January 2001 and December 2014 were analysed. Patients were divided into three groups depending on CIT (less than 2 h, 2-4 h, 4-8 h). Risk-adjusted outcomes were assessed by multivariable analysis adjusting for discordance in both donor and recipient characteristics. RESULTS: Outcomes of 9156 transplants were analysed (CIT less than 2 h in 2662, 2-4 h in 4652, and 4-8 h in 1842). After adjusting for confounders, there was no significant difference in patient survival between CIT groups. Recipients of kidneys with a CIT of 4-8 h had excellent graft outcomes, although these were slightly inferior to outcomes in those with a CIT of less than 2 h, with risk-adjusted rates of delayed graft function of 8·6 versus 4·3 per cent, and 1-year graft survival rates of 96·2 versus 97·1 per cent, respectively. CONCLUSION: The detrimental effect of prolonging CIT for up to 8 h in living donation kidney transplantation is marginal.

Hand-assisted Laparoscopic Donor Nephrectomy and Cytokine Changes.

BACKGROUND: Laparoscopic living-donor nephrectomy (LDN) exerts systemic effects causing transaminitis and increased urinary neutrophil gelatinase-associated lipocalm (NGAL) excretion. Hand-assisted laparoscopic donor nephrectomy, which tends to be shorter with less pneumoperitoneum, may be hypothesized to produce less systemic stimulation than total laparoscopic LDN. METHODS: Serial urine and serum samples were collected from 15 patients undergoing HALDN. Samples were analyzed for NGAL and kidney injury molecule 1 (KIM-1) levels preoperatively and 24 hours post-surgery. Data relating to alanine aminotransferase, creatinine, and estimated glomerular filtration rate was also analyzed in 48 live donors preoperatively and at 24 hours and 48 hours post-surgery and compared to published data on LDN. RESULTS: Expected changes to creatinine and estimated glomerular filtration rates were observed in the donors. Compared to the preoperative levels, alanine aminotransferase levels showed a significant decrease at 24 hours (P = .004) and were not significantly different from baseline levels at 48 hours (P = .08). Serum KIM-1 and NGAL levels remained unchanged (P = .89 and P = .14, respectively) at 24 hours after donation. Similarly, urinary levels of KIM-1 and NGAL were not statistically significantly different after donation. Mean operating time for this cohort was 1 hour, 36 minutes. CONCLUSIONS: In contrast to other published data, our cohort did not exhibit changes to liver function tests or biomarker changes after donor nephrectomy. This could be because of the lower operative time (96 minutes vs. 216 minutes) or because of the intermittent release of the pneumoperitoneum in the hand-assisted method which may exert less of a systemic inflammatory response.

Evolution of Renal Transplant Practice Over the Past Decade: A U.K. Center Experience.

OBJECTIVE: As renal transplantation continues to evolve, there appears to be a change in both donor and recipient populations. Traditional markers of high-risk donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and recipient (e.g. obese, highly sensitized) operations appear to be more common without any noticeable worsening of patient outcome. The present study aimed to compare outcome and define the change in donor and recipient populations for cadaveric transplants over a 10-year period at a large U.K. center. METHODS: Single-center analysis of all adult patients undergoing cadaveric renal transplantation between January 2004 and January 2014 (n = 754). Transplants were divided into 3 groups (early, middle, and late) depending on the era, with donor, recipient and outcomes compared. RESULTS: There were considerable changes in both donor and recipient factors between the 3 eras, with a greater proportion of high-risk operations performed, as reflected by significant increases in Donor Risk Index (median: 1.11-1.16, P = .022), and the proportions of ECD (22.2%-33.9%, P = .003) and DCD kidneys (10.8%-19.4% P = .011). However, 1-year graft survival was comparable between the eras, with a decrease in the average 1-year serum creatinine between the early and late cohort (median: 161 µmol/L vs 132 µmol/L, P < .001). There was no significant increase in body mass index (BMI) in either the donor or recipient population across the eras. CONCLUSION: Improvement in transplant outcome continues despite a greater proportion of transplants previously considered as high risk being performed. This is likely to reflect a considerable improvement in pre- and postoperative management. BMI remains a major continuing block to transplantation.

Complex kidneys for complex patients: the risk associated with transplantation of kidneys with multiple arteries into obese patients.

Conflicting evidence surrounds clinical outcomes in obese individuals after transplantation; nonetheless, many are denied the opportunity to receive a transplant. Allografts with complex vascular anatomy are regularly used in both deceased and living donor settings. We established the risk of transplanting kidneys with multiple renal arteries into obese recipients. A retrospective analysis of data from 1095 patients undergoing renal transplantation between January 2004 and July 2013 at a single centre was conducted. Of these, 24.2% were obese (body mass index >30 kg/m(2)), whereas 25.1% of kidneys transplanted had multiple arteries, thereby making the transplantation of kidneys of complex anatomy into obese recipients a relatively common clinical occurrence. Vessel multiplicity was associated with inferior 1-year graft survival (85.8.% vs 92.1%, P = .004). Obese patients had worse 1-graft survival compared to those of normal BMI (86.8% vs 93.8%, P = .001). The risk of vascular complications and of graft loss within a year after transplantation were greater when grafts with multiple arteries were transplanted into obese recipients as compared to their nonobese counterparts (RR 2.00, CI 95% 1.07-3.65, and RR 1.95, CI 95% 1.02-3.65). Additionally, obese patients faced significantly higher risk of graft loss if receiving a kidney with multiple arteries compared to one of normal anatomy (RR 1.97, 95% CI 1.02-3.72). Thus, obese patients receiving complex anatomy kidneys face poorer outcomes, which should be considered when allocating organs, seeking consent, and arranging for aftercare.

The economic benefits of risk factor reduction in Canada: tobacco smoking, excess weight and physical inactivity.

OBJECTIVE: Tobacco smoking, excess weight and physical inactivity contribute substantially to the preventable disease burden in Canada. The purpose of this paper is to apply a recently developed approach in addressing the issue of double counting in estimating the combined current economic burden of these risk factors (RFs) and to estimate the economic benefits of long-term RF reduction in Canada. METHODS: We used an approach based on population attributable fractions (PAF) to estimate the economic burden associated with the various RFs. Sex-specific relative risk and age-/sex-specific prevalence data were used in the modelling when available. Excess weight was modelled as a trichotomous exposure (normal weight, overweight, obese) while tobacco smoking was modelled as a tetrachotomous exposure (non-smoker, light, medium or heavy smoker). All costs are given in constant 2012 Canadian dollars. RESULTS: The annual economic burden of the RFs of tobacco smoking, excess weight and physical inactivity in Canada are estimated at $50.3 billion in 2012. Sensitivity analysis suggests a range for the economic burden of $41.6 to $58.7 billion. Of the $50.3 billion, $21.3 ($20.0 to $22.6) billion is attributable to tobacco smoking, $19.0 ($13.8 to $24.0) billion to excess weight and $10.0 ($7.8 to $12.0) billion to physical inactivity. A 1% relative annual reduction in each of the three RFs would result in an $8.5 billion annual reduction in economic burden by 2031. CONCLUSION: A modest annual 1% relative reduction in the RFs of tobacco smoking, excess weight and physical inactivity can have a substantial health and economic impact over time at the population level.

Prehabilitation program for elective coronary artery bypass graft surgery patients: a pilot randomized controlled study.

OBJECTIVE: To determine the feasibility of a cardiac prehabilitation (Prehab) program for patients waiting for elective coronary artery bypass graft (CABG). DESIGN: A two-group parallel randomized controlled trial. SETTING: Medical fitness facility. SUBJECTS: Seventeen preoperative elective CABG surgery patients were randomized to standard care (n = 9) or Prehab (n = 8). INTERVENTION: Standard care: three-hour preassessment appointment. Prehab: exercise and education classes for 60 minutes/day, twice weekly for at least four weeks. MAIN MEASURES: Data were collected at baseline, one week preoperatively, and three months postoperatively. The primary outcome measure was walking distance using a 6-minute walk test. Secondary outcome variables included 5-meter gait speed, and cardiac rehabilitation attendance three months postoperatively. RESULTS: Fifteen patients (standard care, n = 7; Prehab, n = 8) completed the study. No Prehab patients developed cardiac symptoms during study participation. Walking distance remained unchanged in the standard care group; whereas, the Prehab group increased their walking distance to mean ± SD 474 ±101 and 487 ±106 m at the preoperative and three month postoperative assessments (p < 0.05). Gait speed was unchanged in the standard care group, but improved in the Prehab group by 27% and 33% preoperatively and three months postoperatively, respectively (p < 0.05). Enrollment in cardiac rehabilitation three months postoperatively was higher for Prehab participants (100%) than standard care participants (43%; p < 0.05). CONCLUSION: These data provide evidence for the feasibility of a Prehab intervention to improve the health status of patients waiting for elective CABG surgery. A larger trial of 92 patients will be utilized to demonstrate the safety and efficacy of Prehab.

Relationship of functional fitness with daily steps in community-dwelling older adults.

BACKGROUND: Walking is the main type of physical activity among community-dwelling older adults and it is associated with various health benefits. However, there is limited evidence about the relationship between functional fitness and walking performed under independent living conditions among older adults. PURPOSE: This study examined the relationship between functional fitness and steps walked per day among older adults, both assessed objectively, with performance-based measures accounting for the effect of age, gender, and chronic conditions. METHODS: In this cross-sectional study, 60 participants aged 65 years or older (mean = 76.9 ± 7.3 years, range 65-92 years) wore pedometers for 3 consecutive days. Functional fitness was measured using the Functional Fitness Test (lower and upper body strength, endurance, lower and upper body flexibility, agility/balance). The outcome measure was the mean number of steps walked for 3 days with participants classified into tertiles: low walkers (<3000 steps), medium walkers (≥3000 < 6500 steps), and high walkers (≥6500 steps). RESULTS: After controlling for age, gender, and the number of chronic conditions, none of the functional fitness parameters was significantly associated with steps taken per day when comparing medium walkers with low walkers. In contrast, all functional fitness parameters, except upper body flexibility, were significantly associated with steps taken per day when comparing high walkers with low walkers. CONCLUSION: In this sample of older adults, greater functional fitness was associated only with relatively high levels of walking involving 6500 steps per day or more. It was not related to medium walking levels. The findings point to the importance of interventions to maintain or enhance functional fitness among older adults.

Improved estimation of the health and economic burden of chronic disease risk factors in Manitoba.

INTRODUCTION: There are analytic challenges involved with estimating the aggregate burden of multiple risk factors (RFs) in a population. We describe a methodology to account for overlapping RFs in some sub-populations, a phenomenon that leads to "double-counting" the diseases and economic burden generated by those factors. METHODS: Our method uses an efficient approach to accurately analyze the aggregate economic burden of chronic disease across a multifactorial system. In addition, it involves considering the effect of body weight as a continuous or polytomous exposure that ranges from no excess weight through overweight to obesity. We then apply this method to smoking, physical inactivity and overweight/obesity in Manitoba, a province of Canada. RESULTS: The annual aggregate economic burden of the RFs in Manitoba in 2008 is about $1.6 billion ($557 million for smoking, $299 million for physical inactivity and $747 million for overweight/obesity). The total burden represents a 12.6% downward adjustment to account for the effect of multiple RFs in some individuals in the population. CONCLUSION: An improved estimate of the aggregate economic burden of multiple RFs in a given population can assist in prioritizing and gaining support for primary prevention initiatives.

TITRE: Meilleure estimation du fardeau que représentent les facteurs de risque de maladie chronique pour la santé et l'économie au Manitoba. INTRODUCTION: L'estimation du fardeau global que représentent les facteurs de risque multiples au sein d'une population présente certains défis d'ordre analytique. Nous décrivons une méthodologie permettant de tenir compte des facteurs de risque se chevauchant dans certaines sous-populations et entraînant un « double compte ¼ des maladies et du fardeau économique qu'ils engendrent. MÉTHODOLOGIE: Notre démarche permet d'analyser avec précision le fardeau économique global des maladies chroniques dans un cadre multifactoriel tout en tenant compte de l'incidence du poids en tant qu'exposition continue ou polytomique (allant de l'absence d'excédent de poids au surpoids et à l'obésité). Nous appliquons cette méthode au tabagisme, à l'inactivité physique et au surpoids et à l'obésité à la province du Manitoba (Canada). RÉSULTATS: En 2008, le fardeau économique global annuel des facteurs de risque au Manitoba était d'environ 1,6 milliard de dollars (557 millions pour le tabagisme, 299 millions pour l'inactivité physique et 747 millions pour le surpoids et l'obésité). Le fardeau total représente un rajustement à la baisse de 12,6 % lorsqu'on tient compte de l'effet des facteurs de risque multiples chez certaines personnes. CONCLUSION: Une meilleure estimation du fardeau économique global des facteurs de risque multiples au sein d'une population peut faciliter l'établissement des priorités et améliorer le soutien aux initiatives de prévention primaire.

Anti-tuberculosis prophylaxis following renal transplantation: acceptable variations?

BACKGROUND: Guidelines suggest tuberculosis (TB) prophylaxis in renal transplant recipients originating in endemic areas or in those at risk from non-endemic countries. Concern remains that these guidelines may fail to provide adequate prophylaxis for a cohort of patients who remain at potential risk. We aimed to determine variation patterns among different transplant units within the United Kingdom (UK) with regard to TB prophylaxis policy. METHODS: The renal pharmacist at each of the 25 UK renal transplant centers was contacted. Specific information was obtained relating to drug prophylaxis given, duration of treatment, as well as which transplant recipients were eligible for treatment. RESULTS: A 96% response rate (24/25 centers) was achieved. Prophylaxis regimens varied from no prophylaxis to isoniazid 300 mg given life-long. The most common duration of treatment was 6 months post transplantation (at 7 centers). Variations existed in the concurrent use of pyridoxine. A wide discrepancy was seen in the determination of who should receive prophylaxis, with no clear association with frequency of TB incidence in the region. CONCLUSIONS: A marked discrepancy exists among national renal transplant units in pharmacologic prophylaxis for TB, as well in the selection of individuals for this treatment.

Personal factors, perceived environment, and objectively measured walking in old age.

This study examined the associations between walking behavior and the perceived environment and personal factors among older adults. Sixty participants age 65 yr or older (mean 77 +/- 7.27, range 65-92) wore pedometers for 3 consecutive days. Perceived environment was assessed using the Neighborhood Environment Walkability Scale (abbreviated version). Physical function was measured using the timed chair-stands test. The mean number of steps per day was 5,289 steps (SD = 4,029). Regression analyses showed a significant association between personal factors, including physical function (relative rate = 1.05, p < .01) and income (RR = 1.43, p < .05) and the average daily number of steps taken. In terms of perceived environment, only access to services was significantly related to walking at the univariate level, an association that remained marginally significant when controlling for personal characteristics. These results suggest that among this sample of older adults, walking behavior was more related to personal and intrinsic physical capabilities than to the perceived environment.

Energy expenditure during golfing and lawn mowing in older adult men.

This study compared the intensity and energy cost of playing 9 holes of golf with 40 min of lawn mowing in older men and determined whether both met the current recommendations for health benefits. Eighteen men (age 71.2 +/- 4.4 yr, BMI 27.3 +/- 2.3; M +/- SD) completed a graded treadmill test. During golfing and lawn-mowing field tests, oxygen consumption and walking velocity and distance were measured using a portable metabolic system and global positioning system receiver. The net energy costs of golfing and lawn mowing were 310 and 246 kcal, respectively. The average intensities in metabolic equivalents of golfing and lawn mowing were 2.8 +/- 0.5 and 5.5 +/- 0.9, respectively. Both lawn mowing and golfing met the original intensity and energy expenditure requirements for health benefits specified by the American College of Sports Medicine in 1998, but only lawn mowing met the 2007 intensity recommendations.

Canada's physical activity guide recommendations are a low benchmark for Manitoba adults.

Canada's Physical Activity Guide to Healthy Active Living (CPAG) is the national reference for messaging on physical activity for health benefits, yet few studies have examined population activity levels in relation to its recommendations. As part of the province-wide in motion initiative, we obtained a baseline measurement of the physical activity levels of adult Manitobans. Physical activity levels were benchmarked against CPAG recommendations and were compared with criteria used in previous surveys. A stratified random sample of adults from the 9 Regional Health Authorities outside of Winnipeg, and from the 12 Community Areas within the Winnipeg Health Region, was surveyed by telephone. Respondents (n = 6,536) reported all light, moderate, and vigorous physical activity of 10 min or more in the previous week. Intensity levels were corrected to reflect standard MET equivalents, using the Ainsworth Compendium. A total of 69.5% of respondents met the minimum CPAG requirements; however, only 29.1% of those did so with vigorous activity. Relative to energy expenditure, 18.3% were classified as inactive (<1.50 kcal.kg-1.day-1 (KKD)), 16.4% as moderately active (1.50 to 2.99 KKD), and 65.3% as active (>or=3.00 KKD). When assessed against the CPAG recommendations, which promote integration of physical activity into one's daily routine, a higher proportion of Manitobans met recommended physical activity levels than that reported in previous surveys, which focused on leisure activity. Given the corresponding increase in levels of obesity and chronic disease, and equivocal nutrient intake data, we recommend that the CPAG recommendations be reviewed, especially with respect to the inclusion of routine baseline activities of daily living.

Internal iliac artery pseudoaneurysm following renal transplant biopsy successfully treated with endovascular stenting and thrombosis: a case report.

A 49-year-old man underwent living donor renal transplantation in November 2005. The transplant renal artery was anastomosed to the right internal iliac artery with an end-to-end anastomosis. The patient achieved immediate graft function and the allograft was normally perfused. Seven weeks later, renal allograft function deteriorated with a serum creatinine level increased to 244 micromol/L. An ultrasound scan revealed adequate perfusion to the kidney and the absence of hydronephrosis. A transplant biopsy revealed Banff IB rejection, which was treated with high-dose prednisolone. Following biopsy, the patient's renal function rapidly deteriorated with a serum creatinine level increased to 627 micromol/L, requiring hemodialysis. A computed tomography (CT) angiogram demonstrated a 6-cm diameter pseudoaneurysm arising from the internal iliac artery with absence of kidney perfusion. The aneurysm was accessed percutaneously with a 4-F catheter and 1000 U of human thrombin injected, resulting in partial thrombosis of the pseudoaneurysm. A balloon expandable covered metal stent was then placed across the site of the transplant renal artery anastomosis, resulting in successful occlusion of the aneurysm. Intrarenal blood flow was established by dilating 2 intrarenal branches with 3-mm diameter balloons. The serum creatinine level started to decrease within 24 hours of the procedure and renal function improved rapidly to a level achieved immediately after transplantation. Three months later the patient had a well-functioning allograft with a serum creatinine level of 176 micromol/L, follow-up CT scan demonstrated good perfusion of the transplanted kidney with no further change in the pseudoaneurysm. At 12 months follow-up the patient remains with a well-functioning allograft.

A systematic review and economic model of the clinical and cost-effectiveness of immunosuppressive therapy for renal transplantation in children.

OBJECTIVES: To review the clinical and cost-effectiveness of basiliximab, daclizumab, tacrolimus, mycophenolate mofetil (MMF), mycophenolate sodium (MPS) and sirolimus as possible immunosuppressive therapies for renal transplantation in children. DATA SOURCES: Electronic databases were searched up to November 2004. REVIEW METHODS: Data from selected studies were extracted and quality assessed. An economic model [Birmingham Sensitivity Analysis paediatrics (BSAp)] was produced based on an adaptation of a model previously developed for the assessment of the cost-effectiveness of immunosuppressants in adults following renal transplant. RESULTS: For the addition of basiliximab, one unpublished paediatric randomised control trial (RCT), reported that the addition of basiliximab to tacrolimus-based triple therapy (BTAS) failed to significantly improve 6-month biopsy-proven acute rejection (BPAR), graft function, graft loss and all-cause mortality. No significant difference between groups was seen in 6-month or 1-year or longer graft loss, all-cause mortality and side-effects. In a meta-analysis of adult RCTs, the addition of basiliximab to a ciclosporin, azathioprine and steroid regimen (CAS) significantly reduced short-term BPAR. There was no significant difference in short- or long-term graft loss, all-cause mortality or side-effects. One adult RCT was included for the addition of daclizumab to CAS, which reported reduced 1-year BPAR, although no difference between groups was seen in either 1- or 3-year graft loss, all-cause mortality and side-effects. For tacrolimus versus ciclosporin, one unpublished paediatric RCT found that a regimen of tacrolimus, azathioprine and a steroid (TAS) reduced 6-month BPAR and improved graft function [glomerular filtration rate (GFR)] compared with CAS. This improvement in BPAR with tacrolimus was as shown in the meta-analysis of adult RCTs. There was evidence, particularly in children, that in comparison with ciclosporin, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. The total level of withdrawal in children was reduced in children receiving tacrolimus. Adult RCTs showed an increase in post-transplant diabetes mellitus with tacrolimus. For MMF versus azathioprine, a meta-analysis of adult RCTs showed MMF [regimen of ciclosporin, MMF and a steroid (CMS)] to reduce 1-year BPAR compared with azathioprine (CAS). There was evidence, particularly in children, that in comparison with azathioprine, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. There was an increase in the level of cytomegalovirus infection with MMF, although the overall level of withdrawal due to adverse events was not different to that of azathioprine-treated adults. No study comparing MPS with azathioprine (CAS) was identified. In an adult RCT comparing MMF with MPS, there was no significant difference between groups in 1-year efficacy or side-effects. One unpublished paediatric RCT assessed the addition of sirolimus to CAS. BPAR, graft loss and all-cause mortality were not reported. In two adult RCTs, compared with azathioprine, sirolimus reduced 1-year BPAR, reduced graft function (as assessed by an increased serum creatinine) and increased the level of hyperlipidaemia. No significant differences were seen in other efficacy and side-effect outcomes. On an adult RCT comparing sirolimus with ciclosporin, there were no significant differences between groups in 1-year efficacy or side-effects with the exception of an increased level of hyperlipidaemia with sirolimus substitution. Both the assessment group and drug companies assessed the cost-effectiveness of the newer renal immunosuppressants currently licensed in children using an adaptation (BSAp) of the Birmingham Sensitivity Analysis (BSA) model. This model is based on a 10-year extrapolation of 1-year BPAR results sourced from paediatric RCTs or adult RCTs (where paediatric RCTs were not available). The addition of basiliximab and that of daclizumab to CAS was found to increase quality-adjusted life-years (QALYs) and decreased overall costs, a finding that was robust to sensitivity analyses. The incremental cost-effectiveness ratio (ICER) of replacing ciclosporin with tacrolimus was highly sensitive to the selection of the hazard ratio for graft loss from acute rejection, dialysis costs and the incorporation (or not) of side-effects. The ICERs for tacrolimus versus ciclosporin ranged from about 46,000 pounds/QALY to about 146,000 pounds/QALY. Although sensitive to varying the hazard ratio for graft loss with acute rejection, the ICER for replacing azathioprine with MMF remained in excess of 55,000 pounds/QALY. CONCLUSIONS: In general, compared with a regimen of ciclosporin, azathioprine and steroid, the newer immunosuppressive agents consistently reduced the incidence of short-term biopsy-proven acute rejection. However, evidence of the impact on side-effects, long-term graft loss, compliance and overall health-related quality of life is limited. Cost-effectiveness was estimated based on the relationship between short-term acute rejection levels from RCTs and long-term graft loss. Both the addition of daclizumab and that of basiliximab were found to be dominant strategies, that is, regarding cost savings and increased QALYs. The incremental cost-effectiveness of tacrolimus relative to ciclosporin was highly sensitive to key model parameter values and therefore may well be a cost-effective strategy. The incremental cost-effectiveness of MMF compared with azathioprine, although also sensitive to model parameter, was unattractive. There is a particular need for RCTs to assess the use of MMF, MPS and daclizumab for renal transplantation in children where no such evidence currently exists. Future comparative studies need to report not only on the impact of the newer immunosuppressants on short- and long-term clinical outcomes but also on side-effects, compliance, healthcare resource, costs and health-related quality of life.

Fitness centre membership is related to healthy behaviours.

AIM: Maximizing the health benefits associated with reducing inactivity levels requires an understanding of the individual and environmental determinants of physical activity. Membership in a fitness facility promotes physical activity, yet little is known of its relationship to health. The purpose of this study was to compare physical activity levels, and health status, behaviours, and beliefs, in members of a fitness centre, and non-member community residents. METHODS: Using a cross-sectional design, fitness centre members (n=236) and non-members (n=302) were compared with respect to perceived health status, use of health care services, fitness status, physical activity level, perceived control over health, and the likelihood of engaging in health promoting behaviours, using The Health-Promoting Lifestyle Profile. Questionnaires were mailed to adult members of a fitness centre, and a stratified (age, sex) sample of non-members randomly selected from the local community. RESULTS: Fitness centre members were more likely than the comparison group to have visited a general physician, dentist, athletic therapist, optometrist, or nutritionist during the previous year (p<0.05), to exercise regularly, and to rate their physical fitness as very fit. They scored significantly higher on the overall health promoting lifestyle score (p=0.0353) as well as on health responsibility (p=0.0053), exercise (p=0.0001), and nutrition (p=0.0166) subscales, even after adjusting for differences in activity levels between groups. CONCLUSIONS: Fitness centre membership is associated with increased health responsibility and health promoting behaviours. This finding appears to be related to membership in the fitness centre, and not to increased participation in physical activity.

Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. DATA SOURCES: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. REVIEW METHODS: The review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. RESULTS: For induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children (<18 years) were identified comparing ciclosporin to tacrolimus and sirolimus, respectively. CONCLUSIONS: The newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally, there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics.

Impact of a "direct approach" to live kidney donation in the British Indo-Asian community.

Although a general imbalance exists between the demand for renal transplants and the supply of suitable organs, the shortfall is particularly severe for patients from the Indo-Asian (I-A) community. It seems unlikely that this will be remedied by any increase in cadaveric donation. Our aim was to increase the rate of live donor transplantation (LDT) in the I-A population through a direct approach to patients and their families, in a culturally acceptable environment by an Asian transplant coordinator. Whereas an increase in LDT was seen in the I-A population over the period of review, 1997 to 2003, 15 compared with none prior to 1997, significant attrition was seen within the program, with only 10% of the original cohort coming to donation. There are multiple reasons for this including medical, social and psychological.

Living paid organ transplantation results in unacceptably high recipient morbidity and mortality.

The ethical debate surrounding the payment of living unrelated donors continues despite very little evidence regarding the outcome. The aim of this audit was to identify the scale of the problem and assess the results of patients undergoing these procedures. The large Indo-Asian population within our region has a high demand for renal replacement therapy and transplantation. These patients have a limited chance of receiving a transplant for several reasons and some resort to traveling abroad, against medical advice, to procure an unrelated donor kidney transplant. Following an initial audit in our region, a national audit was conducted within the UK. A total of 23 patients were identified, all of whom had done so against medical advice. Mortality from causes directly related to transplantation was high in this group (35%), as was graft loss. The overall rate of successful transplants was only 44% (overall graft loss was 56%) in the short term. The information regarding both donor and recipient, provided from the transplanting center, was inadequate in all cases. These results, which almost certainly represent an underestimate of an ongoing situation, reinforce the standpoint that organ trading is associated with unacceptable risks and poor outcomes. The basis of this trade in organs is based on monetary rather than clinical criteria and such exploitation of both donor and recipient lead us to conclude that this practice cannot be endorsed and even the most desperate dialysis patients should be reminded of the unacceptable risks involved in this practice.

Effects of a long-term, community-based cardiac rehabilitation program on middle-aged and elderly cardiac patients.

The purpose of this retrospective study was to compare the effects of a 2-year, community-based cardiac rehabilitation exercise program on cardiovascular fitness, body fatness, and blood lipids in middle-aged (65 years, n=40) male cardiac patients. Estimated maximal metabolic equivalents increased in both groups; however, the increase was greater for middle-aged patients (p=0.003). High-density lipoprotein cholesterol level increased significantly after 1 year in both groups, but the change was greater for the middle-aged subjects by Year 2 (p=0.02). The total cholesterol/high-density lipoprotein cholesterol ratio and serum triglyceride levels decreased in both groups, whereas total cholesterol and low-density lipoprotein cholesterol levels decreased only in the elderly group (p<0.01). Body fatness did not change in either group. These findings reinforce the importance of referring elderly as well as middle-aged patients to community-based cardiac rehabilitation exercise programs.