Impact of initiating insulin glargine disposable pen versus vial/syringe on real-world glycemic outcomes and persistence among patients with type 2 diabetes mellitus in a large managed care plan: a claims database analysis.

BACKGROUND: Diabetes accounts for almost 15% of all direct healthcare expenditures. Managed care organizations try to reduce costs and improve patient outcomes. Increasing patient persistence with antidiabetes treatment could help achieve these goals. SUBJECTS AND METHODS: A retrospective study was conducted using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical and economic outcomes associated with initiation of insulin glargine via a disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts were assessed for persistence with insulin therapy, glycated hemoglobin (A1C), hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid amount of adjudicated claims) after follow-up at 1 year. RESULTS: In 1,308 matched patients, persistence was significantly higher (P=0.011) and longer (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038), and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all-cause and diabetes-related healthcare costs were similar. CONCLUSIONS: In insulin-naive patients with T2DM, initiation of insulin glargine using the disposable pen rather than the vial and syringe is associated with higher persistence, better A1C control, and lower rates of hypoglycemia. The higher study drug costs associated with pen use do not increase total all-cause or diabetes-related healthcare costs. This may help treatment selection for patients with T2DM in a managed care setting.

Predicting long-term graft survival in adult kidney transplant recipients.

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons.

BACKGROUND: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. METHODS: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. RESULTS: All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. CONCLUSIONS: Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.

Increased risk of graft failure in kidney transplant recipients after a diagnosis of dyspepsia or gastroesophageal reflux disease.

BACKGROUND: Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS: We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. RESULTS: The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). CONCLUSIONS: Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.

Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality.

BACKGROUND: Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. STUDY DESIGN: Historic cohort study. SETTING & PARTICIPANTS: We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. PREDICTORS: Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. OUTCOMES: Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. RESULTS: We enrolled 41,442 patients. Mean follow-up was 758 +/- 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). LIMITATIONS: Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. CONCLUSIONS: Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death.

Flow cytometry crossmatch before kidney transplantation in contemporary practice: target cell utilization, results patterns, and associated long-term graft survival.

The flow cytometry crossmatch (FXCM) is an increasingly common method for pre-transplant crossmatching. We examined FCXM use in a national sample of kidney transplants, characterizing target cell utilization, results patterns, and associated graft outcomes. We queried Organ Procurement and Transplant Network Registry to identify kidney transplants performed in 1995-2007 with prospective FCXM testing for IgG antibodies against T-cells, B-cells or undifferentiated lymphocytes. FCXM was categorized according to target utilization and target-specific results. We modeled associations of FCXM testing-results patterns with risk of five-year graft loss and with projected graft survival by multivariable survival analysis. Sixty-five percent of the deceased donor transplants were performed with negative T-cell and B-cell FCXM, 16% with negative T-cell/unmeasured B-cell FCXM, 9% with negative undifferentiated lymphocyte FCXM, and < 0.5% with negative B-cell/unmeasured T-cell FCXM. Test results for at least one target were positive in 7.6% of transplants, most commonly in the form of B-cell positive/T-cell negative. Allograft survival was most favorable when both T-cell and B-cell FCXM targets were included and yielded negative results. Notably, B-cell positive/T-cell negative FCXM predicted elevated graft loss risk, with approximately 16% and 32% relative risk increases for deceased and living donor grafts, respectively, compared to negative T-cell and B-cell FCXM. Negative FCXM results with undifferentiated targets alone also predicted inferior graft survival. These data support the importance of using differentiated B-cell and T-cell targets for FCXM. Transplants that proceeded with positive FCXM experienced decrements in long-term graft survival - the decision to accept such risk must be individualized.

The impact of human leukocyte antigen matching on transplant complications and immunosuppression dosage.

Administrative claims data facilitate ascertainment of outcomes not collected by the transplant registry and provide the opportunity to examine prescribed doses of immunosuppressive medications. Here, we examine the impact of human leukocyte antigen (HLA) matching on traditional outcomes, rejection and survival, and use novel methods to examine immunosuppresion doses and complication rates. The central hypothesis tested in this analysis is that HLA-matched recipients receive lower doses of immunosuppression and have fewer posttransplant complications. We break from tradition by examining HLA matching in both living and deceased donor kidney transplants. As secondary aims, we compare the relative impact of class I and II mismatches and describe outcomes achieved with older donors. Medicare claims linked to the United States Renal Data System database for 23,443 kidney transplants were included in the study. A total of 15,793 transplants were DR mismatched (DRMM), 5,340 manifested no DR mismatches (NODRMM), and 2,310 manifested no ABDR mismatches (NOABDRMM). Patients with NOABDRMM experienced lower adjusted risk of rejection (0.66, 95% confidence interval 0.59-0.74, P < 0.001) and lower hazard of graft loss (0.69, 0.61-0.77, P < 0.001) and death (0.76, 0.63-0.92, P < 0.001) compared with those with DRMM. The hazard of cardiac and diabetic complications was similar between recipients of NOADRMM and DRMM transplants, but the hazard of diarrhea was significantly lower (0.82, 0.73-0.92, P < 0.001) in patients with NOABDRMM. The 6-month dose of mycophenolate mofetil was lower in patients with NOABDRMM. This study validates previous studies that indicated significantly lower risks of rejection, graft loss, and death among patients with 0 HLA-A,B,DR mismatches. Use of administrative claims revealed similar rates of cardiovascular complications. However, HLA-matched deceased donor recipients received lower dosages of mycophenolate mofetil and manifested a lower risk of developing posttransplant diarrhea.

Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure.

BACKGROUND: Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. METHODS: Using the United States Renal Data System, we identified 3,675 adult recipients (age >or=18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced >or=50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. RESULTS: Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction >or=50% (HR=2.36, 95% CI 1.23-4.54) and those with MMF discontinuation (2.72, CI 1.60-4.64). CONCLUSION: Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.