Renal Transplantation: Experience at a Single Centre

Background

Renal transplantation program in the Armed Forces commenced in Feb 1991 and till date 245 patients have undergone renal transplantation at INHS Asvini. We describe our protocols for donor and recipient evaluation and immunosuppression. Methods: 245 patients received renal transplants during this period, 243 (99.2%) being from live donors. Most of them were started on triple immunosuppression comprising of cyclosporine, azathioprine and prednisolone. Newer drugs like mycophenolate, tacrolimus and sirolimus were administered in a select population.

Result

69 (28.1%) of them had at least one episode of acute rejection, most of which were steroid responsive and 13 (18.8%) of them required either anti CD3 monoclonal or anti-thymocyte globulin (ATG). Complete recovery with normal renal function occurred in 54 (78.2%) cases and 15 (21.7%) recovered with residual dysfunction with maximum serum creatinine being 2.1mg/dl. There were three (1.2%) cases of accelerated rejection during the first week of transplantation and one had graft rupture. All three lost their grafts. There were eight (3.2%) cases of acute tubular necrosis, who recovered completely within 8–14 days. Immediate infections included wound sepsis, lower respiratory tract infection, disseminated candidiasis and disseminated aspergillosis. Late infections included pulmonary tuberculosis, disseminated tuberculosis, cytomegalovirus infection and recurrent urinary tract infection. 28 (11.4%) patients developed post transplant diabetes mellitus. At the end of one year and five years, graft and patient survival were 97.2%, 93%, 80.9% and 85.7% respectively.

Conclusion

Our outcomes show that the transplantation is a viable mode of renal replacement therapy in patients of end stage kidney disease with a near normal rehabilitation.Key Words: Kidney, Transplantation, Immunosuppression, Complications     

Direct healthcare costs and predictors of costs in patients with primary Sjogren's syndrome

OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sj?gren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.     

New guidelines on malaria prevention: A summary

Travellers to many tropical areas remain at risk of contracting malaria. Resistance of malaria parasites to a number of drugs continues to increase in degree and distribution, so that some older, trusted prophylactic drugs, such as chloroquine, are no longer useful in some parts of the world. Despite the introduction of new drugs and the reduction of malaria risk in some areas, such as parts of India, the number of people travelling continues to increase and malaria reports in the UK are not decreasing. New updated prevention guidelines from the Health Protection Agency Advisory Committee on Malaria Prevention (ACMP) in UK travellers (Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C, et al. Guidelines for malaria prevention in travellers from the United Kingdom. London: Health Protection Agency; January 2007. Available from: http://www.hpa.org.uk/infections/topics_az/malaria/default.htm) aim to raise awareness of the risks of malaria and help UK travel health advisors in giving malaria prevention advice to all those who need it. Together with the ACMP malaria treatment guidelines it is hoped that the risk of illness and death from malaria in UK travellers can be reduced. This article summarises the new ACMP malaria prevention guidelines.     

Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration

Aims/hypothesis We explored the epidemiology of hypoglycaemia in individuals with insulin-treated diabetes by testing the hypothesis that diabetes type and duration of insulin treatment influence the risk of hypoglycaemia. Materials and methods This was an observational study over 9–12 months in six UK secondary care diabetes centres. Altogether 383 patients were involved. Patients were divided into the following three treatment groups for type 2 diabetes: (1) sulfonylureas, (2) insulin for <2 years and (3) insulin for >5 years, and into two treatment groups for type 1 diabetes, namely <5 years disease duration and >15 years disease duration. Self-reported (mild and severe) and biochemical episodes (interstitial glucose <2.2 mmol/l using continuous glucose monitoring) were recorded. Results Mild hypoglycaemia in type 2 diabetic patients on insulin for <2 years was less frequent than in type 1 patients with <5 years disease duration (mean rate: 4 vs 36 episodes per subject-year, p < 0.001). In type 2 diabetic patients treated with sulfonylureas or insulin for <2 years, no differences were observed in the proportion experiencing severe hypoglycaemia (7 vs 7%, difference 0 [95% CI: −7 to 9%]), mild symptomatic (39 vs 51%, difference 12 [−3 to 25%]) or interstitial glucose <2.2 mol/l (22 vs 20%, difference 2 [−13 to 10%]). Severe hypoglycaemia rates were comparable in patients with type 2 diabetes on sulfonylureas or insulin < 2 years (0.1 and 0.2 episodes per subject-year) and far less frequent than in type 1 diabetes (<5 years group, 1.1; >15 years group, 3.2.episodes per subject-year). Conclusions/interpretation During early insulin use in type 2 diabetes, the frequency of hypoglycaemia is generally equivalent to that observed in patients treated with sulfonylureas and considerably lower than during the first 5 years of treatment in type 1 diabetes. UK Hypoglycaemia Study Group: For a list of the members of this group and their affiliations, see the Appendix. UK Hypoglycaemia Study Group: For a list of each author’s contribution to this study, see the Electronic supplementary material (ESM) which is available to authorised users at doi:. Send any feedback or comments on this article to Simon Heller at the Academic Unit of Diabetes, Endocrinology and Metabolism, School of Medicine and Biomedical Sciences, Room OU141, Beech Hill Road, Sheffield S10 2RX, UK. s.heller@sheffield.ac.uk.     

Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes

The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.     

Renal transplantation in the United Kingdom for patients from ethnic minorities

BACKGROUND: To investigate any differences in access to transplant and post-transplant outcomes for ethnic minority patients in the United Kingdom, national data on ethnicity of patients on the waiting list, those receiving a transplant, and deceased donors were analyzed. METHODS: Adult patients and donors were included. Ethnic origin was classified as white, Asian, black, or "other." National data were analyzed, and 2001 U.K. National census data were used for comparative purposes. Median waiting times to transplant were obtained from Kaplan-Meier estimates for patients registered 1998-2000. Transplant survival was estimated for patients transplanted from 1998 to 2003. RESULTS: A total of 92% of the U.K. population was white, compared with 77% of waiting list patients, 88% of transplant recipients, and 97% of deceased donors. Median waiting time to transplantation for white patients was 719 days (95% confidence interval 680-758) compared with 1368 (1131-1605) days for Asian patients and 1419 (1165-1673) days for black patients. The degree of human leukocyte antigen matching achieved was inferior for Asian and black patients. There is some evidence of inferior 3-year transplant survival for black patients compared with white and Asian patients (P=0.03). CONCLUSIONS: There are imbalances in the ethnic make up of the waiting list, the donor pool, and renal transplant recipients. There are significant differences in both post-transplant outcomes and time to transplantation between patients of different ethnic origin. Waiting times are influenced by allocation schemes, and the 2006 U.K. National Kidney Allocation Scheme is designed to achieve greater equity of access to transplant for all patients, regardless of geography, blood group, or ethnicity.     

Adult orthotopic liver transplantation in the United Kingdom and Ireland between 1994 and 2005

BACKGROUND: The UK and Ireland Liver Transplant Audit collects information on all liver transplantations that are carried out in both countries. In this paper, we describe these transplantations and their outcomes in adult patients according to primary liver disease diagnosis, type of transplantation and period. METHODS: A prospective cohort study of 7906 orthotopic liver transplantations carried out between April 1994 and June 2005 in the United Kingdom and Ireland. Multivariable logistic regression was used to investigate improvements in mortality according to period of transplantation adjusted for recipient and donor characteristics. RESULTS: A total of 6,850 transplantations were done in adults (patients 16 years or older). Of these, 836 (12.2%) were first super-urgent procedures (33.7% men; median age 36 years), and 5,072 (74.0%) first elective procedures (60.0% men; median age 52 years). The percentage of patients who received a donor organ with abnormal appearance gradually increased, especially in patients receiving an elective transplant. Mortality at 90 days after first super-urgent transplant decreased from 29.6% (95% confidence interval: 23.5% to 36.9%) before October 1, 1996 to 16.0% (11.7% to 21.7%) after October 1, 2002. Considering the same time periods, mortality at 90 days after first elective transplant decreased from 10.6% (8.9% to 12.7%) to 7.7% (6.3% to 9.3%). Multivariable analysis demonstrated that these improvements cannot be explained by changes in the risk profile of recipients and donors. CONCLUSIONS: Patients undergoing a liver transplantation in the most recent years had a better survival than patients with similar characteristics transplanted 10 years earlier. Posttransplant survival has improved despite a deteriorating quality of donor organs.     

What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?

OBJECTIVES To estimate the risk of death and examine the predictors of death and virological/immunological response, following diagnosis of multidrug-resistant (MDR) HIV-1 in a UK multicentre cohort of HIV-infected individuals. METHODS Five hundred and seventy-two patients were identified with MDR HIV-1 between 1997 and 2004. Factors associated with survival and virological/immunological response 24-48 weeks after MDR diagnosis were determined by the Poisson and linear regression, respectively. RESULTS Patient characteristics: 86% males; median age 39 years; median CD4 and viral load (VL) at MDR diagnosis 230 cells/mm3 and 4.2 log10 copies/mL; median number of antiretroviral drugs previously exposed to 8. Sixty patients died over a median follow-up of 31 months (IQR: 17-50), giving an estimated mortality rate of 3.7 deaths per 100 person-years (95% CI 2.9-4.7) following MDR diagnosis. In adjusted analysis, higher CD4 count, lower VL, more recent calendar year, lower number of antiretroviral drugs previously exposed to and greater age at MDR diagnosis were associated with an increased chance of survival. There was some evidence of a better virological response at 24-48 weeks after MDR diagnosis in patients who changed regimen compared with patients who did not change regimen. CONCLUSIONS The risk of death following MDR diagnosis may be at least 3-fold the risk observed overall in HIV-infected individuals. Changing antiretroviral therapy following emergence of MDR HIV-1 may be associated with improved short-term virological response.     

Screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics: a quality improvement programme

Objective: The aim was to evaluate a quality improvement programme designed to increase screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics. Method: Baseline audit against evidence‐based standards, followed by provision of benchmarked data and a range of change interventions, with re‐audit 1 year later. Results: At baseline, 48 assertive outreach teams across the UK submitted data on screening over the previous year for 1966 patients. At re‐audit, 35 of the teams submitted data for 1516 patients. Screening for all four aspects of the metabolic syndrome (measuring blood pressure, obesity, blood glucose and plasma lipids) had increased significantly by re‐audit. Clinical variables increasing the likelihood of full screening were clozapine treatment and a known diagnosis of diabetes or dyslipidaemia. Conclusion: The programme’s success may be partly attributed to the use of a widely‐accepted audit standard, and bespoke change interventions that directly addressed barriers to screening identified by the participating clinical teams.     

Primary malignant melanoma of the esophagus

Primary malignant melanoma of the esophagus is a rare neoplasm that accounts for approximately 0.1–0.2% of all esophageal tumors. Many cases are advanced at the time of diagnosis, and survival time is very short. The literature lists only four long‐term (> 5 years) survivors after optimal surgical excision. We present the case of a geriatric woman with a malignant melanoma of the esophagus that showed no pigment on gross inspection.