Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Abdominal aortic aneurysm repair and colonic infarction: a risk factor appraisal

OBJECTIVE: Colonic infarction is a recognized complication of abdominal aortic aneurysm (AAA) surgery. The clinical difficulty in establishing the diagnosis combined with the patient's poor physiological status is usually associated with a fatal outcome. We assessed our experience with this problem to identify a possible risk factor profile for these patients. METHOD: Patients records were identified from the operative logs, intensive care unit, Hospital Inpatient Enquiry system and vascular unit databases over a 6-year period. RESULTS: A total of 405 patients underwent AAA repair during this period; 140 as emergency ruptures. Nine patients were identified from the databases with known colonic infarction (2.2%). One was a woman. The mean age was 70 years. Seven patients had emergency ruptures (5%). Twenty independent risk factors were analysed using univariate and multivariate logistic regression models. Significant risk factors identified by using a multivariate analysis included the nature of the presenting patient, preoperative hypotension, prolonged cross-clamp time, intra-operative ischaemia and postoperative acidosis. Confirmatory diagnosis was made by colonoscopy in eight patients. One patient survived following the salvage surgery. The mean duration of survival was 10.5 days. The overall mortality was 89% of patients. CONCLUSION: In our unit infrarenal AAA repair has a 2.2% rate of colonic infarction. A definitive diagnosis is best made by colonoscopy. A risk factor profile for the development of colonic infarction may be constructed on the basis of specific clinical parameters. Earlier intervention on the basis of this profile may ultimately reduce the current excessive mortality.     

Constructing osteoarthritis through discourse – a qualitative analysis of six patient information leaflets on osteoarthritis

Background  

Health service policy in the United Kingdom emphasises the importance of self-care by patients with chronic conditions. Written information for patients about their condition is seen as an important aid to help patients look after themselves. From a discourse analysis perspective written texts such as patient information leaflets do not simply describe the reality of a medical condition and its management but by drawing on some sorts of knowledge and evidence rather than others help construct the reality of that condition. This study explored patient information leaflets on osteoarthritis (OA) to see how OA was constructed and to consider the implications for self-care.     

Perforation of a retrocaecal appendix presenting clinically as a right lumbar abscess.

Presentations of acute appendicitis represent an ongoing challenge to surgeons. This case of retrocaecal perforated appendicitis presented clinically as a right lumbar abscess, with the concomitant new diagnosis of type 2 diabetes mellitus in a 66-year-old male. This case emphasises the importance of an abdominal CT scan in any patient presenting with unusual sepsis near the abdomen.     

Usefulness of PCR Strategies For Early Diagnosis of Chagas'' Disease Reactivation and Treatment Follow-Up in Heart Transplantation

Heart transplantation (HTx) is a useful therapy for end‐stage Chaga? cardiomyopathy; however, Chagas reactivation remains a mayor complication. Parasitological methods offer poor diagnostic sensitivity, and use of more sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary. In the present study, reactivation incidence and PCR usefulness for early reactivation diagnosis, as well as for treatment response evaluation during follow‐up, were analyzed using Strout parasite detection test, in 10 of 222 consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and miniexon genes (SL‐DNA, 200 parasite/10 mL) were performed to compare parasite burdens between samples. No patients received prophylactic antiprotozoal therapy (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean period of 71.6 days; positive Strout results were observed in most cases presenting clinical manifestations. kDNA‐PCR was positive 38–85 days before reactivation, whereas SLDNA‐PCR became positive only 7–21 days later, revealing post‐HTx parasitic load enhancement present prior to clinical reactivation development. Reactivations were successfully treated with benznidazole and generated negative PCR results. Results observed in this study indicate the value of PCR testing for an early diagnosis of Chagas reactivation as well as for monitoring treatment efficacy.     

Options for Immunologic Support of Renal Transplantation Through the HLA and Immunology Laboratories

HLA and immunology laboratories are an integral part of clinical kidney transplant programs. They assist transplant clinicians with evaluating the immunological suitability of potential recipients for transplantation and selecting donor-recipient combinations with a low risk of immunological failure. With sophisticated new techniques becoming available for posttransplant immunological monitoring, laboratories play an increasing supporting role during posttransplant follow up. The level of precision at which immunological testing predicts clinical outcome, however, leaves room for improvement. In this article, we summarize the current state of diagnostics, discuss problems, and point out promising developments.     

Developing Organ Offer and Acceptance Measures: When 'Good' Organs Are Turned Down

Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs.