Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Invasive melanoma in vivo can be distinguished from basal cell carcinoma, benign naevi and healthy skin by canine olfaction: a proof-of-principle study of differential volatile organic compound emission.

BACKGROUND: Volatile organic compounds (VOCs) are continuously released by the body during normal metabolic processes, but their profiles change in the presence of cancer. Robust evidence that invasive melanoma in vivo emits a characteristic VOC signature is lacking. OBJECTIVES: To conduct a canine olfactory, proof-of-principle study to investigate whether VOCs from invasive melanoma are distinguishable from those of basal cell carcinoma (BCC), benign naevi and healthy skin in vivo. METHODS: After a 13-month training period, the dog's ability to discriminate melanoma was evaluated in 20 double-blind tests, each requiring selection of one melanoma sample from nine controls (three each of BCC, naevi and healthy skin; all samples new to the dog). RESULTS: The dog correctly selected the melanoma sample on nine (45%) occasions (95% confidence interval 0·23-0·68) vs. 10% expected by chance alone. A one-sided exact binomial test gave a P-value of < 0·01, supporting the hypothesis that samples were not chosen at random but that some degree of VOC signal from the melanoma samples significantly increased the probability of their detection. Use of a discrete-choice model confirmed melanoma as the most influential of the recorded medical/personal covariates in determining the dog's choice of sample. Accuracy rates based on familiar samples during training were not a reliable indicator of the dog's ability to distinguish melanoma, when confronted with new, unknown samples. CONCLUSIONS: Invasive melanoma in vivo releases odorous VOCs distinct from those of BCC, benign naevi and healthy skin, adding to the evidence that the volatile metabolome of melanoma contains diagnostically useful biomarkers.

Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

INTRODUCTION: The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. AIMS: The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. METHODS: Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. DISCUSSION: If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.

The effects of a diet rich in inulin or wheat fibre on markers of cardiovascular disease in overweight male subjects.

BACKGROUND: Previous studies suggest that the beneficial health effects of a diet rich in whole grains could be a result of the individual fibres found in the grain. The present study aimed to investigate the influence of a diet high in either wheat fibre (as an example of an insoluble fibre) or inulin (a nondigestible carbohydrate) on markers of cardiovascular disease. METHODS: Ten male participants classified as at higher risk of cardiovascular disease [mean (SD) body mass index 30.2 (3) kg m(-2) , mean (SD) waist circumference 106.4 (7) cm, mean (SD) age 39.8 (9) years] were recruited to a randomised, controlled, cross-over study comparing the consumption of bespoke bread rolls containing either inulin, wheat germ or refined grain (control) (15 g day(-1) ) for 4 weeks with a 4-week washout period between each regime. At the end of each regime, participants underwent an oral glucose tolerance test (OGTT), measures of pulse wave velocity (PWV), 24-h ambulatory blood pressure (AMBP), plasma lipid status and markers of glucose control. RESULTS: There was no difference in measures of glucose control, lipid status, 24-h AMBP or PWV after the intervention periods and no changes compared to baseline. There was no significant difference between OGTT glucose and insulin time profiles; however, there was a significant difference in area under the curves between the wheat fibre and control interventions when comparing change from baseline (control +10.2%, inulin +4.3%, wheat fibre -2.5%; P = 0.03). CONCLUSIONS: Only limited differences between the interventions were identified, perhaps as a consequence of the amount of fibre used and intervention length. The wheat germ intervention resulted in a significant reduction in glucose area under the curve, suggesting that this fibre may aid glucose control.

Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.

The long-term quality of life of living kidney donors: a multicenter cohort study.

Previous studies that described the long-term quality of life of living kidney donors were conducted in single centers, and lacked data on a healthy nondonor comparison group. We conducted a retrospective cohort study to compare the quality of life of 203 kidney donors with 104 healthy nondonor controls using validated scales (including the SF36, 15D and feeling thermometer) and author-developed questions. Participants were recruited from nine transplant centers in Canada, Scotland and Australia. Outcomes were assessed a median of 5.5 years after the time of transplantation (lower and upper quartiles of 3.8 and 8.4 years, respectively). 15D scores (scale of 0 to 1) were high and similar between donors and nondonors (mean 0.93 (standard deviation (SD) 0.09) and 0.94 (SD 0.06), p = 0.55), and were not different when results were adjusted for several prognostic characteristics (p = 0.55). On other scales and author-developed questions, groups performed similarly. Donors to recipients who had an adverse outcome (death, graft failure) had similar quality of life scores as those donors where the recipient did well. Our findings are reassuring for the practice of living transplantation. Those who donate a kidney in centers that use routine pretransplant donor evaluation have good long-term quality of life.

Fate of the mate: the influence of delayed graft function in renal transplantation on the mate recipient.

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of -11.2 mL/min, while the control group had a mean change of -0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these'at-risk'recipients should be developed and tested.

Intermittent versus continuous renal replacement therapy for acute renal failure in adults.

BACKGROUND: Renal replacement therapy (RRT) for acute renal failure (ARF) can be applied intermittently (IRRT) or continuously (CRRT). It has been suggested that CRRT has several advantages over IRRT including better haemodynamic stability, lower mortality and higher renal recovery rates. OBJECTIVES: To compare CRRT with IRRT to establish if any of these techniques is superior to each other in patients with ARF. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL). Authors of included studies were contacted, reference lists of identified studies and relevant narrative reviews were screened. Search date: October 2006. SELECTION CRITERIA: RCTs comparing CRRT with IRRT in adult patients with ARF and reporting prespecified outcomes of interest were included. Studies assessing CAPD were excluded. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: We identified 15 studies (1550 patients). CRRT did not differ from IRRT with respect to in-hospital mortality (RR 1.01, 95% CI 0.92 to 1.12), ICU mortality (RR 1.06, 95% CI 0.90 to 1.26), number of surviving patients not requiring RRT (RR 0.99, 95% CI 0.92 to 1.07), haemodynamic instability (RR 0.48, 95% CI 0.10 to 2.28) or hypotension (RR 0.92, 95% CI 0.72 to 1.16) and need for escalation of pressor therapy (RR 0.53, 95% CI 0.26 to 1.08). Patients on CRRT were likely to have significantly higher mean arterial pressure (MAP) (WMD 5.35, 95% CI 1.41 to 9.29) and higher risk of clotting dialysis filters (RR, 95% CI 8.50 CI 1.14 to 63.33). AUTHORS' CONCLUSIONS: In patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. Future research should focus on factors such as the dose of dialysis and evaluation of newer promising hybrid technologies such as SLED. Triallists should follow the recommendations regarding clinical endpoints assessment in RCTs in ARF made by the Working Group of the Acute Dialysis Quality Initiative Working Group.

Risk of Thromboembolism Following Body-Contouring Surgery After Massive Weight Loss.

BACKGROUND: "Postbariatric" patients are at significant risk for increased postoperative complications. This study aimed to define the risk of venous thromboembolism following body-contouring surgery after massive weight loss. METHODS: A retrospective analysis was performed on all patients who had undergone all forms of body-contouring procedures after massive weight loss between January 2005 and August 2012 at St George's Hospital, South West London, United Kingdom. Data were collected on patient demographics, comorbidities, risks factors for thromboembolism, preoperative and postoperative body mass index, and type of surgery. RESULTS: A total of 135 operations were performed on 53 patients (43 females, 10 male), with an average age of 44.8 years (range, 26-56 years). Most had staged procedures including 55 abdominoplasties, 23 brachioplasties, 31 thigh lifts, 14 lower-body lifts, and 12 mastopexies. All patients received venous thromboembolism prophylaxis postoperatively including low-molecular-weight heparin (dalteparin) within an average of 22.5 hours after surgery and the application of intraoperative graduated compression stockings. Patients received dalteparin for an average of 4 days (range, 2-14 days), which correlated to their length of stay. One patient had a deep venous thrombosis 14 days postoperatively and then 2 days later developed a nonfatal pulmonary embolus, giving a venous thromboembolism prevalence of 0.74% (1/135). CONCLUSIONS: The clinically apparent venous thromboembolism prevalence was low among patients undergoing body-contouring procedures after massive weight loss in this study. We provide evidence of a successful algorithm to prevent venous thromboembolism for patients undergoing body-contouring procedures after massive weight loss.

Increased sensitivity of adenylate cyclase activity in the striatum of the rat to calmodulin and GppNHp after chronic treatment with haloperidol.

Chronic treatment of rats with haloperidol causes behavioral supersensitivity to dopaminergic agonists and an increase in the sensitivity of adenylate cyclase activity in the striatum to stimulation by dopamine. In this study the authors examined whether chronic treatment with haloperidol could elicit a change in sensitivity of adenylate cyclase in the striatum of the rat for guanyl nucleotides and the endogenous Ca2+-binding protein, calmodulin. These agents increase the activation of adenylate cyclase activity by dopamine but act beyond the level of the dopamine receptor. Male, Sprague-Dawley rats were injected subcutaneously with either 0.6 mg/kg haloperidol or vehicle for 14 days. Four days after the last injection, the animals were sacrificed and the activity of adenylate cyclase was measured in a EGTA-washed particulate preparation of the striatum. There was an increase in the activation of adenylate cyclase activity by calmodulin and GppNHp but not by guanosine triphosphate (GTP) in particulate fractions of the striatum from rats treated with haloperidol as compared to controls. The sensitivity of adenylate cyclase to calmodulin was increased 5-fold in particulate fractions from rats treated with haloperidol as opposed to vehicle-treated rats. The lack of change in activation by GTP was not due to an altered activity of GTPase in rats treated with haloperidol. In animals treated for 14 days but not withdrawn from haloperidol there was no statistically significant increase in the sensitivity of adenylate cyclase to calmodulin. There was no change in activation of the enzyme by GppNHp or GTP as compared to control. The activation of adenylate cyclase by calmodulin was not affected when haloperidol was added in vitro to the assay or after the acute injection of rats with haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)

The outcome of pregnancy following renal transplantation--the experience of a single center.

Many centers still recommend avoidance of pregnancy after renal transplantation because of fears for the safety of both mother and fetus. These fears are in part based on a lack of information concerning the effects of newer immunosuppressive drugs such as cyclosporine on the course and outcome of pregnancy. The present study examines the experience of first pregnancies following renal transplantation in a single center, with emphasis on the role of CsA. Data on the first pregnancies of 22 women transplanted between 1977 and 1988 were studied. The mean age of patients at the time of transplant was 23.4 +/- 3.1 years and interval from transplant to pregnancy was 34.5 +/- 24.5 months (range 1-75 months). Twelve patients received CsA alone or in combination with other immunosuppressives, while the remaining 10 patients received azathioprine and prednisone. Mean serum creatinine fell progressively during pregnancy in both CsA- and azathioprine-treated mothers. Mean CsA dose rose during pregnancy while mean CsA blood concentration fell during the 2nd trimester (P = 0.042). The gestation period ranged from 27 to 40 weeks (35.5 +/- 3.3) with 14 pregnancies ending prematurely prior to 37 weeks. Thirteen deliveries occurred by Caesarian section. Hypertension complicated 10 pregnancies. Birth weight correlated directly with both maternal weight gain (r = 0.57; P less than 0.02) and gestational age (r = 0.9; P less than 0.01). Ten of 23 offspring were below the 10th percentile for weight. Mean birth weight ranged from 0.72 to 3.7 kg (2.3 +/- 0.84 kg). The mean birth weight and gestational age of children born to mothers taking CsA were lower than those in azathioprine treated mothers but these differences were not statistically significant. Successful pregnancy is possible following renal transplantation, although there is a high rate of prematurity, low birth weight, and intrauterine growth retardation. CsA dose requirements may be increased. Maternal risks including hypertension require that such pregnancies be handled by a multidisciplinary team approach.

A randomized, prospective multicenter pharmacoepidemiologic study of cyclosporine microemulsion in stable renal graft recipients. Report of the Canadian Neoral Renal Transplantation Study Group.

BACKGROUND: The safety, tolerability, and pharmacokinetics of conventional cyclosporine (ConCsA) and cyclosporine microemulsion (MeCsA) were compared under conditions of normal clinical practice in a prospective, randomized, concentration-controlled, pharmacoepidemiologic study. METHODS: Between September 1994 and March 1995, 1097 stable renal transplant recipients in 14 Canadian centers were randomized 2:1 to treatment with MeCsA or ConCsA. Patients were commenced on each study drug at a dose equal to their previous therapy with ConCsA, and the dose was adjusted to maintain predose whole blood cyclosporine concentrations within the therapeutic range established for each center. Prednisone and azathioprine were continued unless dose adjustment was required for clinical reasons. RESULTS: The mean cyclosporine concentration was comparable in both treatment groups at all time points throughout the 6 months of follow-up. The mean dose of cyclosporine was 3.6 mg/kg/day in both treatment groups at entry to the study, and declined by 0.3% and by 2.8% in patients receiving ConCsA and MeCsA, respectively. The nature and severity of adverse events were similar in both treatment groups, but there was a transient increase in neurological and gastrointestinal complications in the group receiving MeCsA within the first month after conversion (P<0.05). Serum creatinine and creatinine clearance did not change in either treatment group throughout the study. Biopsy-proven acute rejection occurred in three patients (0.8%) receiving ConCsA and in seven patients (0.9%) receiving MeCsA, with non-histologically proven acute rejection in an additional three patients (0.8%) receiving ConCsA and five patients (0.6%) receiving MeCsA (P=NS). Serum creatinine rose transiently in 35 patients (9.8%) receiving ConCsA and 138 patients (18.7%) receiving MeCsA (P<0.05) and resolved either spontaneously or after a reduction in the cyclosporine dose. One graft was lost in the MeCsA group due to irreversible rejection, and seven patients died, three in the group receiving ConCsA and four of those receiving MeCsA (P=NS). Absorption of cyclosporine was more rapid and complete from MeCsA than from ConCsA during the first 4 hr of the dosing interval, resulting in almost 40% greater exposure to the drug (P<0.001). There was close correlation between area under the time-concentration curve (AUC) over the first 4 hr of the 12-hr dosage interval and AUC over the entire 12-hr dosage interval for both formulations, making AUC over the first 4 hr a good predictor of total cyclosporine exposure. Using this parameter, patients with low absorption randomized to receive MeCsA showed a marked increase in drug exposure by months 3 and 6, whereas there was no change in those who continued on ConCsA. A limited sampling strategy utilizing samples at the predose and postdose trough levels provided an excellent correlation with drug exposure, particularly for patients receiving MeCsA (r2=0.94 MeCsA vs. r2=0.89 ConCsA). CONCLUSIONS: MeCsA appears to be a safe and effective therapy in stable renal transplant patients and provides superior and more consistent absorption of cyclosporine when compared with ConCsA. Transient toxicity after conversion to MeCsA occurs in some patients, and may reflect the increased exposure to cyclosporine. Use of a limited sampling approach combining trough and 2-hr postdose concentrations may provide an effective way to monitor this exposure.

Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.

BACKGROUND: There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. METHODS: The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up. RESULTS: No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035). CONCLUSIONS: Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.

Idiopathic thrombocytopenia after cytomegalovirus infection in a renal transplant recipient.

Infection with cytomegalovirus (CMV) is a frequent complication of organ transplantation and presents a spectrum of disease ranging from asymptomatic viremia to life-threatening tissue-invasive disease. CMV is also lymphotrophic, with the potential to induce autoimmune disease, although immunosuppressive therapy may prevent or attenuate the clinical course in transplant patients. We report a case of idiopathic thrombocytopenic purpura occurring in a renal transplant recipient after primary CMV infection and discuss the possible mechanisms involved.

Management of idiopathic membranous nephropathy: evidence-based recommendations.

Membranous nephropathy is a frequent cause of nephrotic syndrome in adults, and in one third of these patients, it leads to end-stage renal disease. Based on an extensive critical review of the literature, the following recommendations are offered. Oral high-dose corticosteroids are ineffective in producing either a sustained remission of nephrotic syndrome or in preserving renal function in patients with membranous nephropathy, and should not be used as the sole therapy (grade A recommendation). The use of azathioprine is not associated with any significant benefits, so its use is not justified (grade C). The alkylating agents cyclophosphamide and chlorambucil are both effective in the management of membranous nephropathy. Because of growing concern about long-term toxicity, especially with cyclophosphamide, these drugs should be reserved for patients who exhibit clinical features, such as severe or prolonged nephrosis, renal insufficiency, or hypertension, that predict a high likelihood of progression to end-stage renal disease. Chlorambucil in conjunction with oral steroids is the drug of first choice (grade A). Cyclophosphamide and oral steroids are alternatives (grade B). Cyclosporine may, in the future, become the agent of choice for membranous nephropathy. Currently, it is recommended (grade B) that cyclosporine use be considered in patients at high risk for progression in membranous nephropathy or if alkylating agents are contraindicated or ineffective.

Erythropoietin and renal transplantation.

The advent of erythropoietin (rHuEPO) has revolutionized the treatment of anemia in end-stage renal disease. While many studies indicate beneficial effects of rHuEPO in hemodialysis, peritoneal dialysis and predialysis patients, the impact of the drug in renal transplantation is less clear. Treatment with rHuEPO may reduce the degree of allosensitization produced by random blood transfusion while still allowing the possibility of the transplant survival benefit derived from deliberate transfusion. Recovery from anemia post-transplantation is hastened by treatment with rHuEPO, while patients with failing allografts respond to rHuEPO in a fashion similar to dialysis patients, despite the concomitant use of immunosuppressives. The erythropoietic response to rHuEPO is abrogated during episodes of acute rejection, and restored when successful treatment of rejection has occurred. Iron therapy is a critical factor for support of erythropoiesis and prevention of absolute iron deficiency posttransplantation. In patients presenting for renal transplant, the balance of evidence suggests that there is no increase in the rate of delayed graft function, graft loss or vascular thrombosis for patients who had received prior rHuEPO therapy.

The impact of recombinant human erythropoietin on medical care costs for hemodialysis patients in Canada.

Recombinant human erythropoietin (r-HuEPO) is an established and effective therapy for anemia related to end stage renal disease. In addition to its clinical effects, it has been associated with significant improvements in quality of life for anemic hemodialysis patients. The therapy's impact on overall medical care expenditures for these patients remains uncertain, however. In this study, we examine the costs of r-HuEPO as well as potential offsetting reductions in other medical care costs that might result from the therapy. We used data from a randomized clinical trial, a longitudinal study of hemodialysis patients and the clinical literature to estimate the impact of r-HuEPO on transfusion requirements, transfusion-related illness, hospitalization and transplant success for these patients. We estimate that for patients that otherwise would be transfused, the therapy would reduce blood requirements by nearly 10 units per patient annually and hospital use by 8 days per year. In addition, increased transplant success due to r-HuEPO might result in 150 fewer patient months of dialysis treatments each year. Comparing the dollar value of these reductions with the cost of therapy yields a base case net increase in medical care expenditures of $3425 per patient year. Under varying assumptions, the estimates range from a net cost of $8320 to a net saving of $1775 per patient year.

Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients.

The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history. These patients had not been prescribed EPO as they had started hemodialysis prior to the clinical availability of EPO. There were 21 pairs without hospitalization and 46 pairs with at least 1 member of the pair experiencing hospitalization. Among the latter group, the median follow-up was 174 and 184 days for the EPO and control patients respectively. For all hospitalizations, those treated with EPO were hospitalized 15.3 days per year compared to 23.2 days for the control patients. The difference (EPO-control) was -7.9 days (95% CI: -21.0; 7.8) for all cause hospitalization. For hospitalizations due to cardiac, infectious disease and gastrointestinal disease, the differences were 1.6, 1.8 and 1.2 days favouring EPO treated patients. For hospitalizations related to vascular access complications, the difference was 0.9 days favoring the control group. All other causes favoured EPO treated patients by 4 days. There had been 58 hospitalizations in the EPO group compared to 97 in the control group. The mean duration of hospitalization was 8.0 days for the EPO and 9.6 for the control group. The direction and magnitude of the change in all cause hospitalization represents an improvement in morbidity and an important decrease in health resource utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey.

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

A comparison between cyclosporine and tacrolimus-based immunosuppression for renal allografts: renal function and blood pressure after 5 years.

The choice of initial immunosuppressive therapy (IST) following solid organ transplant remains a source of some controversy. Cyclosporine A (CsA) has been the basis of most IST protocols over the past two decades but has recently been supplanted in many centers by the use of tacrolimus (TAC)-based protocols. Renal allograft recipients in London may receive either CsA or TAC based IST, along with prednisone and azathioprine or (since 1999) mycophenolate mofetil (MMF). The decision is based on criteria such as age, gender, diabetic status, and lipid levels, which are felt to be impacted by the delivery of CsA or TAC based IST. The present analysis focuses on the results of BP and renal function in renal transplant patients receiving CsA or TAC based initial therapy during the period January 1, 1996 to June 30, 2002. Patients receiving TAC based IST were significantly younger than those receiving CsA (44 +/- 13.9 vs 50.5 +/- 12.3 years; P < .004). Mean arterial pressure (MAP) was lower in the TAC patients at 1 month (97.8 +/- 13.1 vs 103.2 +/- 11.8 mm Hg; P = .035), but became equivalent to CsA-treated patients for the balance of the follow-up period of up to 60 m. Serum creatinine was not significantly different between groups at any time during up to 60 months of follow-up. Based on these results, it seems apparent that the choice of calcineurin inhibitor may not influence renal function or blood pressure in long-term renal allograft survivors.