Publications by authors named "Laurence Chan"

Objective: Over the last 3 decades, group treatment researchers have become increasingly knowledgeable of the impact of within-group dependency on analyses of group treatment data and of mutual influence processes that occur within therapy groups. Despite these advancements, there remains a lack of consensus on the magnitude of mutual influence, or group effects, in group treatment research. As such, this study sought to estimate the size of group effects on members' posttreatment outcomes by meta-analyzing the intraclass correlation coefficients (ICCs) in group treatment research.

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Acculturation theories often describe how individuals in the United States adopt and incorporate dominant cultural values, beliefs, and behaviors such as individualism and self-reliance. Theorists tend to perceive dominant cultural values as "accessible to everyone," even though some dominant cultural values, such as preserving White racial status, are reserved for White people. In this article, the authors posit that White supremacist ideology is suffused within dominant cultural values, connecting the array of cultural values into a coherent whole and bearing with it an explicit status for White people and people of color.

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Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus.

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Background: Postkidney transplant donor-specific antibodies (DSA) have been identified as important contributors to graft loss. Few therapeutic options exist and have been met with limited success. We report outcomes in patients with de novo DSA and graft damage treated with a protocol of high-dose intravenous immunoglobulin (IVIG).

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MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations.

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Background: Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions.

Material And Methods: Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management.

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Kidney allograft damage resulting from donor-specific anti-HLA antibody (DSA) activity has been identified as a key component of long-term graft attrition. DSA that persists following acute antibody-mediated rejection (AMR) episodes and/or DSA associated with chronic graft dysfunction have been shown to be particularly pathogenic. Despite the significantly negative effects of DSA on graft survival, there are currently no accepted treatment modalities.

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Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four-yr data on 904 patients receiving tacrolimus and enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non-AA (n = 686) patients.

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Background: Prospective data regarding immunosuppression and rejection in African American patients receiving modern immunosuppressive regimens are sparse.

Methods: One-year data were analyzed from 901 tacrolimus-treated de novo kidney transplant patients in the prospective Mycophenolic Acid Observational Renal Transplant registry.

Results: Mean tacrolimus dose was significantly higher in African Americans (n=217) versus non-African Americans (n=684), but mean tacrolimus trough concentrations were similar.

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We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.

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Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored.

Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations.

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Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study, de novo RTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation.

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Background: Dose-finding studies for mycophenolic acid (MPA) in tacrolimus-treated kidney transplant patients are lacking.

Methods: Data from 901 de novo kidney transplant recipients enrolled in the prospective, non-interventional Mycophenolic acid Observational REnal (MORE) transplant registry were analyzed according to baseline daily MPA dose (<2000, 2000 or >2000 mg).

Results: The proportion of patients receiving 2000 and <2000 mg was 77.

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Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.

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Lai and colleagues demonstrate that pretreatment with N,N-dimethylsphingosine (DMS), a naturally occurring sphingosine derivative, provides renoprotection in ischemia/reperfusion injury. This DMS-induced renoprotection was abolished by the administration of agents that suppress regulatory T cells (Tregs) or by anti-CTLA-4 or anti-CD45 monoclonal antibodies, suggesting that Tregs played a critical role. The finding that Tregs are recruited to the kidney via DMS points to the exciting potential of new approaches to harnessing Tregs for therapeutic purposes.

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Background: Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes.

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Background: Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) significantly reduces gastrointestinal (GI) symptom burden and improves GI-specific health-related quality of life. Using a randomized design, this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment.

Methods: In this 4-week, multicenter, randomized, prospective, double-blind, parallel-group trial, renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitor ± corticosteroids were randomized to an equimolar dose of EC-MPS+MMF placebo or continue on their MMF-based regimen+EC-MPS placebo.

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We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specific anti-HLA antibodies (DSA) detected via post-transplant screening, were due to prior acute rejection (AR) episodes. In this report, we sought to identify DSA characteristics associated with poor outcomes in the absence of AR. All living and cadaveric donor kidney/ kidney-pancreas recipients from 9/07 to 10/09 were screened for class I and II DSA at 1, 6, 12, and 24 months post-transplant, in addition to whenever clinically indicated, using single antigen beads and Luminex technology.

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As part of the Spare-the-Nephron trial, we evaluated the combination mycophenolate mofetil (MMF) and sirolimus (SRL) as a calcineurin inhibitor (CNI)-free regimen for the preservation of renal function in renal allograft recipients. This 2-year, open-label, multicenter trial randomized 299 patients of which 151 were maintained on MMF and a CNI, 148 on MMF plus SRL (n=120, tacrolimus; n=31, cyclosporine). Baseline characteristics including measured (iothalamate) glomerular filtration rate (GFR) were similar between groups.

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In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care.

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Background: Everolimus (Evl) plus tacrolimus (Tac) in de novo renal transplantation is effective and safe. Whether the concentration of Evl affects efficacy and safety in a Tac-based regimen has not been previously reported.

Aim: To evaluate whether the concentration of Evl affects biopsy-proven acute rejection (BPAR), renal function, adverse events (AEs); and to assess for pharmacokinetic (PK) interactions.

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Background: Despite the prevalent use of rabbit antithymocyte globulin (rATG) as an induction agent in kidney transplantation, the appropriate dose for preventing acute rejection in high-risk patients is not known. Few studies have examined total exposure of rATG less than 6 mg/kg, with fewer studies examining lower dose rATG in patients with increased risk factors for acute rejection.

Methods: We retrospectively analyzed outcomes of 83 kidney transplant recipients at increased risk for acute rejection (repeat transplant, African American race, and panel reactive antibody > or =20%) from July 2004 to July 2007 who were treated with rATG 1.

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Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examines the changes in urine metabolite profiles as surrogate markers of renal cell metabolism and function after cyclosporine and/or sirolimus treatment employing a rat kidney transplantation model.

Methods: Using inbred Lewis rats, kidneys were transplanted into bilaterally nephrectomized recipients followed by treatment with either CsA (cyclosporine) 10, Rapa (sirolimus) 1, CsA10/Rapa1 or CsA25/Rapa1 mg/kg/day for 7 days.

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