Vision for Transformation Strengths: The SHSIP describes a holistic transformation plan and ensures connections between various plan components. The State’s Plan seeks to reward health care providers for better care, smarter spending, and healthier people through higher quality, instead of quantity of services by utilizing valuebased purchasing across public and private payers. The SHSIP provides a well-detailed description of the proposed value-based models of care through the Patient-Centered Medical Home (PCMH) model, resulting in the statewide implementation of Accountable Health Communities (AHCs). The SHSIP outlines a long-term vision of building and expanding the PCMH model into a Community Centered Health Homes (CCHHs) model, which will focus on prevention and collaboration with other communitybased organizations. Another strength identified is the amount of existing PCMHs operating within the State. The SHSIP provides a course of action to assist non-PCMH practices to become nationally certified, as well as, goals for a single, statewide PCMH model to be used by all providers and payers within the state. The implementation of the AHCs will be key in addressing social determinants of health within various communities and seems to align well with the PCMH goals. This focus on population and community health will enable the State to make a broader impact and support the long-term goal of moving towards a CCHH model. The focus on the improvement of clinical, behavioral, and oral health care within the urban, rural, and frontier communities is well aligned and consistent with the SIM goals and the overall Triple Aim initiative. Figure 18: Driver Diagram clearly shows how the State plans to achieve the Triple Aim by 2020.

Department of health & human services

This article provides a comprehensive, up-to-date review of methods to prevent early and late renal-allograft loss and to improve long-term outcomes in patients. The authors focus particular attention on the problem of late graft loss and discuss current antirejection therapy, including calcineurin blockers such as cyclosporine and tacrolimus, the interleukin-2 signal-transduction inhibitor sirolimus, and the purine-synthesis inhibitor mycophenolate mofetil, which inhibits the proliferation of T cells and B cells.

Strategies to improve long-term outcomes after renal transplantation.

From the Hematology Branch (P.S., O.N., B.W., P.S., N.S.Y.) and Office of Biostatis- tics Research (C.O.W.), National Heart, Lung, and Blood Institute; and the Trans- NIH Center for Human Immunology, Auto- immunity, and Inflammation, National In- stitutes of Health (A.B., N.S.Y.) — both in Bethesda, MD. Address reprint requests to Dr. Scheinberg at 10 Center Dr., Bldg. 10 CRC, Rm. 3E-5140, MSC 1202, Bethes- da, MD 20892-1202, or at scheinbp@mail .nih.gov. A B S T R AC T A large, unexpected difference was observed in the rate of hematologic response at 6 months in favor of horse ATG (68%; 95% confidence interval (CI), 56 to 80) as compared with rabbit ATG (37%; 95% CI, 24 to 49; P<0.001). Overall survival at 3 years also differed, with a survival rate of 96% (95% CI, 90 to 100) in the horse- ATG group as compared with 76% (95% CI, 61 to 95) in the rabbit-ATG group (P = 0.04) when data were censored at the time of stem-cell transplantation, and 94% (95% CI, 88 to 100) as compared with 70% (95% CI, 56 to 86; P = 0.008) in the re- spective groups when stem-cell-transplantation events were not censored. Conclusions In a randomized study, rabbit ATG was inferior to horse ATG as a first treatment for severe aplastic anemia, as indicated by hematologic response and survival. (Funded by the Intramural Research Program of the National Institutes of Health; ClinicalTrials.gov number, NCT00260689.)

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Horse versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia

Background The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse-derived polyclonal antibody) for induction in adult renal transplant recipients Methods Transplant recipients (n=72) were ran domized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 15 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraopera tively, then daily for at least 6 days Recipients were observed for at least 1 year of follow-up Results By 1 year after transplantation, 4% of Thymoglobulin-treated patients experienced acute rejection compared with 25% of Atgam-treated patients (P=0014) The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=009; P=0009) Rejection was less severe with Thymoglobulin than Atgam (P=002) No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS) Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the event-free survival, was superior with Thymoglobulin (94%) compared with Atgam (63%; P=00005) Fewer adverse events occurred with Thymoglobulin (P=0013) Leukopenia was more common with Thymoglobulin than Atgam (56% vs 4%; P<00001) during induction The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0007), but with Atgam, significant lymphocyte reductions occurred only at day 7 The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs 33%; P=0025) Conclusions Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam These results may in fact be explained by a more profound and durable beneficial lymphopenia

A randomized, double-blinded comparison of thymoglobulin versus atgam for induction immunosuppressive therapy in adult renal transplant recipients

Background. The mechanisms of action of polyclonal antithymocyte globulins (ATGs) are still poorly understood and the selection of doses used in different clinical applications (prevention or treatment of acute rejection in organ allografts, treatment of graft-versus-host disease, or conditioning for allogeneic stem cell transplantation) remains empirical. Low T-cell counts are usually achieved in peripheral blood during ATG treatment but the extent of T-cell depletion in lymphoid tissues is unknown. Methods. Experiments were conducted in cynomolgus monkeys using Thymoglobuline at low (1 mg/kg), high (5 mg/kg), and very high (20 mg/kg) doses. Results. ATG treatment induced a dose-dependent lymphocytopenia in the blood and a dose-dependent T-cell depletion in spleen and lymph nodes but not in the thymus, indicating a limited access of ATG to this organ. T-cell apoptosis in peripheral lymphoid tissues was the main mechanism of depletion. Remaining T cells in peripheral lymphoid organs were coated by antibodies and had down-modulated surface expression of CD2, CD3, CD4, and CD8 molecules, whereas their responsiveness in mixed leukocyte reaction was impaired. The survival of MHC-mismatched skin and heart allografts was prolonged in a dose-dependent fashion, despite the occurrence of a strong anti-ATG antibody response resulting in the rapid clearance of circulating ATGs. Conclusion. The results indicate that T-cell depletion is achieved rapidly and primarily in peripheral lymphoid tissues at high ATG dosage. Short ATG treatments could therefore be clinically evaluated when major peripheral T-cell depletion is required.

Mechanisms involved in antithymocyte globulin immunosuppressive activity in a nonhuman primate model.

Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011).

Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation

Kathleen R. Lamborn

Papers

Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation