Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients

Background Interleukin 2 receptor antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute rejection in kidney transplant recipients. Use of IL2Ra has increased steadily since their introduction, but the proportion of new transplant recipients receiving IL2Ra differs around the globe, with 27% of new kidney transplant recipients in the United States, and 70% in Australasia receiving IL2Ra in 2007. Objectives To systematically identify and summarise the effects of using an IL2Ra, as an addition to standard therapy, or as an alternative to another immunosuppressive induction strategy. Search methods We searched the Cochrane Renal Group’s specialised register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to identify new records, and authors of included reports were contacted for clarification where necessary. Selection criteria Randomised controlled trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or other antibody therapy. Data collection and analysis Data was extracted and assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). Main results We included 71 studies (306 reports, 10,520 participants). Where IL2Ra were compared with placebo (32 studies; 5,854 patients) graft loss including death with a functioning graft was reduced by 25% at six months (16 studies: RR 0.75, 95% CI 0.58 to 0.98) and one year (24 studies: RR 0.75, 95% CI 0.62 to 0.90), but not beyond this. At one year biopsy‐proven acute rejection was reduced by 28% (14 studies: RR 0.72, 95% CI 0.64 to 0.81), and there was a 19% reduction in CMV disease (13 studies: RR 0.81, 95% CI 0.68 to 0.97). There was a 64% reduction in early malignancy within six months (8 studies: RR 0.36, 95% CI 0.15 to 0.86), and creatinine was lower (7 studies: MD ‐8.18 µmol/L 95% CI ‐14.28 to ‐2.09) but these differences were not sustained. When IL2Ra were compared to ATG (18 studies, 1,844 participants), there was no difference in graft loss at any time point, or for acute rejection diagnosed clinically, but the was benefit of ATG therapy over IL2Ra for biopsy‐proven acute rejection at one year (8 studies:, RR 1.30 95% CI 1.01 to 1.67), but at the cost of a 75% increase in malignancy (7 studies: RR 0.25 95% CI 0.07 to 0.87) and a 32% increase in CMV disease (13 studies: RR 0.68 95% CI 0.50 to 0.93). Serum creatinine was significantly lower for IL2Ra treated patients at six months (4 studies: MD ‐11.20 µmol/L 95% CI ‐19.94 to ‐2.09). ATG patients experienced significantly more fever, cytokine release syndrome and other adverse reactions to drug administration and more leucopenia but not thrombocytopenia. There were no significant differences in outcomes according to cyclosporine or tacrolimus use, azathioprine or mycophenolate, or to the study populations baseline risk for acute rejection. There was no evidence that effects were different according to whether equine or rabbit ATG was used. Authors' conclusions Given a 38% risk of rejection, per 100 recipients compared with no treatment, nine recipients would need treatment with IL2Ra to prevent one recipient having rejection, 42 to prevent one graft loss, and 38 to prevent one having CMV disease over the first year post‐transplantation. Compared with ATG treatment, ATG may prevent some experiencing acute rejection, but 16 recipients would need IL2Ra to prevent one having CMV, but 58 would need IL2Ra to prevent one having malignancy. There are no apparent differences between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects

Working Together for Mental Health: Evaluation of a one-day mental health course for human service providers

BACKGROUND: The Working Together For Mental Health course is an 8-hour course designed to demystify mental illness and mental health services. The main target group for the course is people working in human service organisations who provide services for people with mental illness. METHODS: A questionnaire was administered to all participants attending the course during 2003 (n = 165). Participants completed the questionnaire before and immediately after the course, and at three month follow-up. RESULTS: A response rate of 69% was achieved with 114 people completing the questionnaire on all three occasions. The responses showed a significant improvement in the self-assessed knowledge and confidence of participants to provide human services to people with a mental health problem or disorder, three months after the course. There was no significant improvement in participants' attitudes or beliefs about people with a mental health problem or disorder at three month follow-up; however, participants' attitudes were largely positive before entering the course. CONCLUSION: The Working Together For Mental Health course was successful in improving participants' confidence and knowledge around providing human services to people with a mental health illness

Interventions for renal vasculitis in adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults.</p> <p>Methods</p> <p>We searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes.</p> <p>Results</p> <p>Twenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegener's granulomatosis.</p> <p>Conclusions</p> <p>Plasma exchange is effective in patients with severe ARF secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil are also effective. Azathioprine, methotrexate and leflunomide are effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.</p

Immunosuppressive agents in childhood nephrotic syndrome: A meta-analysis of randomized controlled trials

Immunosuppressive agents in childhood nephrotic syndrome: A meta-analysis of randomized trials.BackgroundMany children with steroid-sensitive nephrotic syndrome (SSNS) relapse frequently and receive immunosuppressive agents. In this systematic review of randomized controlled trials (RCTs), the benefits and harms of these immunosuppressive agents are evaluated.MethodsRCTs with outcome data at six months or more that evaluated noncorticosteroid agents in relapsing SSNS were included. A summary relative risk for relapse at 6 to 12 months was calculated using a random effects model.ResultsSeventeen trials involving 631 children were identified. Cyclophosphamide [3 trials; relative risk (RR) 0.44, 95% confidence interval (CI), 0.26 to 0.73] and chlorambucil (2 trials; RR 0.13, 95% CI, 0.03 to 0.57) significantly reduced the relapse risk at 6 to 12 months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI, 0.80 to 2.13). Cyclosporine was as effective as cyclophosphamide (1 trial; RR 1.07, 95% CI, 0.48 to 2.35) and chlorambucil (1 trial; RR 0.82, 95% CI, 0.44 to 1.53), but the effect was not sustained when cyclosporine was ceased. During treatment, levamisole (3 trials; RR 0.60, 95% CI, 0.45 to 0.79) was more effective than steroids alone, but the effect was not sustained.ConclusionsCyclophosphamide, chorambucil, cyclosporine, and levamisole reduce the risk of relapse in children with relapsing SSNS compared with prednisone alone. Clinically important differences in efficacy among these agents are possible, and further comparative trials are still needed. Meanwhile, the choice between these agents depends on physician and patient preferences related to therapy duration and complication type and frequency

Predictors of remission and relapse in idiopathic nephrotic syndrome : a prospective cohort study

Background: Although most children with idiopathic nephrotic syndrome will respond to corticosteroid therapy, 80-90 % suffer one or more relapses. Methods: Using Cox proportional hazard models, we analyzed predictors of remission and relapse in 1-year follow-up data on children aged below 15 years with new-onset nephrotic syndrome. Results: Of 129 children, 107 achieved remission with corticosteroid therapy and 86 subsequently relapsed. Boys achieved remission more often than girls (adjusted hazard ratio [AHR] 1.52, 95 % confidence interval (CI) 1.02-2.3). Boys relapsed significantly more frequently than girls (AHR 1.77, 95 % CI 1.11-2.83) and were more likely to have frequently relapsing disease (AHR 3.3, 95 % CI 1.18-9.23). The risk of first relapse increased with the number of days to first remission (AHR 1.02, 95 % CI 1.01-1.04). The risk for a frequently relapsing course increased with a shorter time from remission to first relapse (AHR 0.92, 95 % CI 0.87-0.97). Conclusions: In idiopathic nephrotic syndrome, boys are more likely to respond initially, more likely to relapse, and to be classified as having frequently relapsing nephrotic syndrome. A decrease in time from remission to first relapse predicts for a frequently relapsing course.8 page(s

Transforming growth factor-ß1 does not relate to hypertension in pre-eclampsia

Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-β1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-β1 is also an important factor in placental implantation. Alterations in TGF-β1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-β1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-β1 was determined by TGF-β1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-β1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 ± 0.4 weeks. There was no difference in TGF-β1 concentration between the two groups (mean (��SEM) 27.1 �� 1.0 vs 26.4 ± 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann–Whitney U -test). There was no correlation between systolic or diastolic blood pressure and TGF-β1 concentration (regression analysis P = 0.4 and 0.2)