A Novel Approach to Analyze Disparities in Colorectal Cancer Screening and Mortality.

INTRODUCTION: Reducing disparities in colorectal cancer (CRC) screening rates and mortality remains a priority. Mitigation strategies to reduce these disparities have largely been unsuccessful. The primary aim is to determine variables in models of healthcare utilization and their association with CRC screening and mortality in North Carolina. METHODS: A cross-sectional analysis of publicly available data across North Carolina using variable reduction techniques with clustering to evaluate association of CRC screening rates and mortality was performed. RESULTS: Three million sixty-five thousand five hundred thirty-seven residents (32.1%) were aged 50 y or more. More than two-thirds (68.8%) were White, while 20.5% were Black. Approximately 61% aged 50 y or more underwent CRC screening (range: 44.0%-80.5%) and had a CRC mortality of 44.8 per 100,000 (range 22.8 to 76.6 per 100,000). Cluster analysis identified two factors, designated social economic education index (factor 1) and rural provider index (factor 2) for inclusion in the multivariate analysis. CRC screening rates were associated with factor 1, consisting of socioeconomic and education variables, and factor 2, comprised of the number of providers per 10,000 individuals aged 50 y or more and rurality. An increase in both factors 1 and 2 by one point would result in an increase in CRC screening rated by 6.8%. CRC mortality was associated with factor 2. An increase in one point in factor 1 results in a decrease in mortality risk by 10.9%. CONCLUSIONS: In North Carolina, using variable reduction with clustering, CRC screening rates were associated with the inter-relationship of the number of providers and rurality, while CRC mortality was associated with the inter-relationship of social, economic, and education variables.

Disparities in Access to Bariatric Surgery in North Carolina.

BACKGROUND: This study sought to identify factors that contribute to disparities in access to bariatric surgery in North Carolina (NC). METHODS: Using the rate of bariatric surgery in the county with the best health outcome as the reference, we calculated the Surgical Equity Index (SEI) in the remaining counties in NC. RESULTS: Approximately 2.95 million individuals (29%) were obese in NC. There were 992 (.5%) bariatric procedures performed on a population of 194 209 individuals with obesity in the Reference County (RC). The mean SEI for bariatric surgery in NC was .47 (SD .17, range .15-.95). A statistically significant difference was observed in 89 counties. Univariable analyses identified the following variables to be significantly associated with the SEI: percent of population living in rural areas (% rural) (relative rate change in SEI [RR] = .994, 95% CI .92-.997; <.0001), median household income (RR = 1.0, 95% CI = 1.0-1.0; P = .0002), prevalence of diabetes (RR = .947, 95% CI .917-.977; .0006), the primary care physician ratio (RR = .995, 95% CI .991-.998; P = .006), and percent uninsured adults (RR = .955, 95% CI .927-.985; P = .003). By multivariable hierarchical regression analysis, only the % rural remained statistically associated with a low SEI (RR = .995 per 1% increase in % rural, 95% CI = .992, .998; P = .0002). DISCUSSION: The percent rural is the most significant predictor of disparities in access to bariatric surgery. For every 1% increase in % rural, the rate of surgery decreased by .5%. Understanding the characteristics of rurality that are barriers to access is crucial to mitigate disparities in bariatric surgical access in NC.

Racial Differences in Stage IV Colorectal Cancer Molecular Profiling and Mutation Rates.

INTRODUCTION: Despite advances in colorectal cancer (CRC) treatment, racial disparities persist. The primary aims of the study were to: evaluate differences in molecular testing rates over time by race; and measure the incidence of tumor mutations by race in patients with metastatic CRC. METHODS: A retrospective cohort study was performed of all adult patients with stage IV CRC (2008-2018) identified within the cancer registry of a large regional health system. Demographic/clinical characteristics were collected through primary data abstraction of the electronic health record. Molecular profiling results were obtained directly from Caris Molecular Intelligence and electronic health record. RESULTS: Three hundred eighty-three patients were included: 40.5% (n = 155) were Black and 59.5% (n = 228) were White. Significant increases were observed in microsatellite instability (MSI), KRAS, and BRAF testing rates during the study period (P < 0.0001). The odds of testing over time increased more significantly in Black compared to White patients for MSI testing (White: odds ratio [OR] 1.26 [95% confidence interval [CI] 1.12-1.41], Black: OR 1.69 [95% CI 1.41-2.02], P = 0.005) and BRAF testing (White: OR 1.42 [95% CI 1.26-1.62], Black: OR 1.89 [95% CI 1.51-2.36], P = 0.027). An increase in KRAS testing over time was observed for both cohorts and was independent of race (P = 0.58). Mutation rates did not differ by race: KRAS (Black 55.8% versus White 45.6%, P = 0.13) and BRAF (Black 4.8% versus White 10.0%, P = 0.33). CONCLUSIONS: Within a large regional health system, molecular testing rates in patients with metastatic CRC increased significantly following National Comprehensive Cancer Network guideline changes for both Black and White patients. Black and White patients who underwent molecular testing had similar rates of MSI, KRAS, and BRAF mutations.

A Statewide Analysis of Predictors of Trauma Center Transfer: The Burden of Non-Clinical Factors.

OBJECTIVES: There is a perception, with mixed literary support, that patients are transferred from community hospitals to tertiary medical centers for non-clinical reasons (ie, payor, race, and admission time). Over-triage risks unequally burdening the tertiary medical centers within a trauma system. This study aims to identify potential non-clinical factors associated with the transfer of injured patients. METHODS: Using the 2018 North Carolina State Inpatient Database, patients with a primary diagnosis of spine, rib or extremity fractures, or TBI were identified using ICD-10-CM code and admission type of "Urgent," "Emergency," or "Trauma." Patients were divided into cohorts of "retained" (at community hospital) or "transferred" (Level-1 or 2 trauma centers). RESULTS: 11,095 patients met inclusion criteria; 2432 (21.9%) patients made up the transfer cohort. The mean ISS for all retained patients was 2.2 (±.9) and 2.9 (±1.4) for all transferred patients. The transfer cohort was younger (mean age 66 v 75.8), underinsured, and more likely to be admitted after 1700 (P < .001). Similar differences were seen regardless of injury pattern. CONCLUSIONS: Patients transferred to trauma centers were more likely to be underinsured and be admitted outside of normal business hours. These transferred patients had longer lengths of stay and higher mortality rates. Across all cohorts, similar ISS suggests that a portion of the transfers could be managed at a community hospital. After hours transfers suggest a need for more robust community hospital coverage. Intentional triage of the injured patient encourages appropriate utilization of resources and is crucial to maintaining high-functioning trauma centers and systems.

A population health assessment of screening mammography on breast cancer mortality in North Carolina.

PURPOSE: To identify predictors of screening mammography use and the effect of screening mammography on breast cancer mortality in North Carolina. METHODS: This cross-sectional study integrated publicly available data from government and private data repositories to model predictors of screening mammography and breast cancer mortality in North Carolina. RESULTS: In North Carolina during 2008-2010, on average, 68.1% of women aged 40-74 years underwent a screening mammogram in the previous two years (range: 38.7%-82.1). The ordinary least squares (OLS) regression demonstrated counties experiencing persistent poverty have mammography screening rates that are 4.3% less, on average, than counties without persistent poverty (estimate (SE) = - 4.283 (2.105), p = 0.045). As the percentage of women with a college education increases, the mammography screening rates increase by approximately 0.3% (estimate (SE) = 0.319 (0.078), P < .001) and as the health literacy score increases, the mammography screening rate decreases by 0.3% (estimate (SE) = - 0.318 (0.104), p = 0.003). These variables explain 7.0% of the variability in mammographic screening rates. The OLS regression analysis demonstrated that age-adjusted breast cancer incidence (Estimate (SE) = 0.074 (0.024), p = 0.003) and health literacy score (estimate (SE) = - 0.175 (0.083), p = 0.039) are significantly related to breast cancer mortality. CONCLUSIONS: Demographic, socioeconomic, and environmental variables explain only a small percentage of the variability in the rates of screening mammography and breast cancer mortality in North Carolina. Advances in the available treatments are likely the major contributor to improving breast cancer mortality.

Disparate Access to Surgery for Operable Carcinoma of the Lung in North Carolina.

PURPOSE: Disparities in access to surgical care are associated with poorer outcomes in patients with cancer. We sought to determine whether vulnerable populations undergo an expected rate of surgery for Stage I-IIIA lung cancer in North Carolina (NC). METHODS: We calculated the proportional surgical ratio (PSR) to identify a potential disparity in surgery rates for early stage (I-IIIA) lung cancer, first in the five counties with the worst health outcomes (LRC) and subsequently the entire state. The reference was the five healthiest counties (HRC), initially, and then the single county with the best health outcomes. RESULTS: In 2016, 3,452 individuals with Stage I-IIIA lung cancer were diagnosed in NC of which 246,854 resided in LRC, whereas 1,865,588 resided in HRC. A total of 453 operable lung cancers were diagnosed in the HRC and 107 in the LRC. The observed lobectomy rate in HRC was 40.1% (range 20.2-58.3%) of early-stage lung cancer and 19% (range 12-36%) for LRC. The PSR was 0.65 (95% confidence interval [CI] = 0.35, 0.90). For all 99 counties across NC, the PSR ranged from 0.33 to 0.96 (mean = 0.49, standard deviation [SD] = 0.10). In a multivariable model, only other primary care provider ratio (relative rate per 100 increase = 0.997; 95% CI = 0.994, 0.999) was significantly associated with PSR. CONCLUSIONS: Individuals residing in LRC in NC are 42% less likely to undergo surgery for operable lung cancer than patients living in HRC. Understanding how factors impact access is key to designing informed interventions.

Real-world retrospective analysis of outcomes in patients undergoing bariatric surgery with class 1 obesity.

BACKGROUND: NIH-established indications for bariatric surgery were set close to 3 decades ago. OBJECTIVES: The purpose of this study was to evaluate outcomes in patients undergoing bariatric surgery with class I obesity, a class that does not fall into current indications. SETTING: University Hospital. METHODS: De-identified records from a clinic system's Electronic Health Record database were accessed to identify adult patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 566) and sleeve gastrectomy (SG) (n = 730). Patients were compared in terms of resolution of co-morbidities and weight loss outcomes at 3 years following surgery. A mixed effects model was used, adjusting for the type of surgery, the number of quarters after the surgery when the averaged measurements were taken, and the interaction between these two variables. RESULTS: Patients lost up to 20% of their initial body mass index (BMI). Being of younger age, female, and having an obesity-related co-morbidity were associated with greater weight loss. At around 2 years after the surgery, the likelihood of being in remission from type 2 diabetes reached 45%. Remission probabilities for hypertension are 60% for RYGB and 50% for SG, 3 years after the surgery. On the other hand, the probabilities of remission from hyperlipidemia are close to 50% and 25% for RYGB and SG at 2 years. There was no difference between the BMI trajectories and remission from type 2 diabetes (T2D) when comparing the 2 groups. CONCLUSIONS: Bariatric surgery is effective in weight loss and resolution of comorbidities in patients with class I obesity. This data further supports the need to revisit the current indication criteria.

Changes in the Proportion of Patients Presenting With Early Stage Colon Cancer Over Time Among Medicaid Expansion and Nonexpansion States: A Cross-sectional Study.

BACKGROUND: The 2010 Patient Protection and Affordable Care Act mandated preventive screening coverage and provided support to participating states for Medicaid coverage. The association of Medicaid expansion with colon cancer stage at diagnosis is unknown. OBJECTIVE: This study aimed to determine whether the proportion of patients diagnosed with early stage colon cancer changed over time within states that expanded Medicaid compared with nonexpansion states. DESIGN: This is a cross-sectional cohort study. SETTING: This study evaluated multicenter registry data from the National Cancer Database (2006-2016). PATIENTS: There were 25,462 uninsured or Medicaid-insured patients with newly diagnosed colon cancer who resided in 2014 Medicaid expansion or nonexpansion states. MAIN OUTCOME MEASURES: This study assessed the annual proportion of patients with early stage (I-II) versus late stage (III-IV) colon cancer. RESULTS: A total of 10,289 patients were identified in expansion states and 15,173 patients in nonexpansion states. Cohorts were similar in age (median 55 years) and sex (46.7% female). A greater proportion of patients in nonexpansion states were Black (33.4% vs 24.0%) and resided in a zip code with median income <$38,000 (39.7% vs 28.2%) and lower educational status (37.4% vs 28.1%). In 2006, the proportions of patients with early stage colon cancer in expansion and nonexpansion cohorts were similar (33.2% vs 32.5%). The proportion of patients with early stage colon cancer within nonexpansion states declined by 0.8% per year after 2014, whereas the proportion within expansion states increased by 0.9% per year after 2014 ( p < 0.05). By 2016, the absolute difference in the propensity-adjusted proportion of early stage colon cancer was 8.8% (39.7% vs 30.9%, p < 0.001). LIMITATIONS: National Cancer Database data are obtained only from Commission on Cancer-accredited sites and are not population based. CONCLUSIONS: After Medicaid expansion in 2014, the proportion of patients diagnosed and treated at Commission on Cancer-accredited facilities with early stage colon cancer increased within expansion states and decreased in nonexpansion states. Increase in insurance coverage may have facilitated earlier diagnosis among patients in expansion states. See Video Abstract at http://links.lww.com/DCR/B804 . CAMBIOS EN LA PROPORCIN DE PACIENTES QUE PRESENTAN CNCER DE COLON EN ESTADIO TEMPRANA A LO LARGO DEL TIEMPO ENTRE LOS ESTADOS DE EXPANSIN Y NO EXPANSIN DE MEDICAID UN ESTUDIO TRANSVERSAL: ANTECEDENTES:La Ley del Cuidado de Salud a Bajo Precio del 2010 ordenó la cobertura de exámenes preventivos y brindó apoyo a los estados participantes para la cobertura de Medicaid. Se desconoce la asociación de la expansión de Medicaid con el estadio del cáncer de colon en el momento del diagnóstico.OBJETIVO:Determinar si la proporción de pacientes diagnosticados con cáncer de colon en estadio temprano cambió con el tiempo dentro de los estados que expandieron Medicaid en comparación con los estados sin expansión.DISEÑO:Estudio de cohorte transversal.ENTORNO CLINICO:Datos de registro multicéntrico de la Base de datos nacional de cáncer (2006-2016).PACIENTES:Había 25,462 pacientes sin seguro o asegurados por Medicaid con cáncer de colon recién diagnosticado. Exposición: Residencia en estados de expansión o no expansión de Medicaid en el 2014.PRINCIPALES MEDIDAS DE RESULTADO:Proporción anual de pacientes con cáncer de colon en estadio temprano (I-II) versus tardío (III-IV).RESULTADOS:Se identificaron un total de 10.289 pacientes en estados de expansión y 15.173 pacientes en estados de no expansión. Las cohortes fueron similares en edad (mediana de 55 años) y sexo (46,7% mujeres). Una mayor proporción de pacientes en estados sin expansión eran de raza negra (33,4% vs 24,0%) y residían en un código postal con ingresos medios <$38 000 (39,7% vs 28,2%) y un nivel educativo más bajo (37,4% vs 28,1%). En el 2006, las proporciones de pacientes con cáncer de colon en estadio temprano en cohortes en expansión y sin expansión fueron similares (33,2% vs 32,5%). La proporción de pacientes con estadio temprano dentro de los estados sin expansión disminuyó en un 0,8% por año después del 2014, mientras que la proporción dentro de los estados de expansión aumentó en un 0,9% por año después del 2014 (p <0,05). Para el 2016, la diferencia absoluta en la proporción ajustada por propensión de cáncer de colon en estadio temprano fue de 8.8% (39.7% vs 30.9%, p <0.001).LIMITACIONES:Los datos de la Base de datos nacional de cáncer se obtienen únicamente de los sitios acreditados por la Comisión de cáncer y no se basan en la población.CONCLUSIONES:Después de la expansión de Medicaid en el 2014, la proporción de pacientes diagnosticados y tratados en instalaciones acreditadas por la Comisión de Cáncer en pacientes con cáncer de colon en estadio temprano aumentó dentro de los estados de expansión y disminuyó en los estados de no expansión. El aumento de la cobertura del seguro puede haber facilitado un diagnóstico más temprano entre los pacientes en estados de expansión. Consulte Video Resumen en http://links.lww.com/DCR/B804 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Retrospective comparative study of the effectiveness of bariatric surgery on 3-year outcomes in the real-world clinical setting.

BACKGROUND: Bariatric surgery has shown an improvement in obesity and obesity-related disease in many clinical trials and single center studies. However, real-world data, including data from non-centers of excellence, is sparse. OBJECTIVES: To provide clinical outcomes of patients who underwent bariatric surgery in real-world clinical setting. SETTING: Academic Institution. METHODS: Adults with obesity undergoing Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and a control group (CG) between 2007 and 2019 were identified. The CG represented patients with a previous visit to a bariatric surgeon without a subsequent surgery. Cohorts were matched on age, gender, ethnicity, baseline body mass index (BMI), and presence of diabetes and hypertension. Groups were compared in terms of co-morbidities, weight loss, and chronic conditions for three years. RESULTS: A total of 61 313 patients were identified. From these, 14 916 RYGB and 20 867 SG patients were matched to the CG (n = 16 562). The median BMI loss three years after surgery was 28.7% (interquartile range [IQR] 20.8%-36.2%) and 20.5% (IQR 13.5%-28.6%) for RYGB and SG groups, respectively. The CG had a median BMI loss of 6.7% with IQR of 20.4% decrease to 1.78% gain. At three years postoperatively, HbA1C decreased by 13% for RYGB and 5.9% for the SG group. The probabilities of remission from diabetes, hypertension, and low high-density lipoprotein cholesterol were significantly higher among patients who had surgery compared to the CG. For both RYGB and SG, the estimated probabilities of remission were similar. CONCLUSION: This study shows that bariatric surgery performed in the real-world clinical setting is an effective therapy for various expressions of the metabolic syndrome with results that are comparable to randomized control trials.

Development and Assessment of a Systematic Approach for Detecting Disparities in Surgical Access.

Importance: Although optimal access is accepted as the key to quality care, an accepted methodology to ascertain potential disparities in surgical access has not been defined. Objective: To develop a systematic approach to detect surgical access disparities. Design, Setting, and Participants: This cross-sectional study used publicly available data from the Health Cost and Utilization Project State Inpatient Database from 2016. Using the surgical rate observed in the 5 highest-ranked counties (HRCs), the expected surgical rate in the 5 lowest-ranked counties (LRCs) in North Carolina were calculated. Patients 18 years and older who underwent an inpatient general surgery procedure and patients who underwent emergency inpatient cholecystectomy, herniorrhaphy, or bariatric surgery in 2016 were included. Data were collected from January to December 2016, and data were analyzed from March to July 2020. Exposures: Health outcome county rank as defined by the Robert Wood Johnson Foundation. Main Outcomes and Measures: The primary outcome was the proportional surgical ratio (PSR), which was the disparity in surgical access defined as the observed number of surgical procedures in the 5 LRCs relative to the expected number of procedures using the 5 HRCs as the standardized reference population. Results: In 2016, approximately 1.9 million adults lived in the 5 HRCs, while approximately 246 854 lived in the 5 LRCs. A total of 28 924 inpatient general surgical procedures were performed, with 4521 being performed in those living in the 5 LRCs and 24 403 in those living in the 5 HRCs. The rate of general surgery in the 5 HRCs was 13.09 procedures per 1000 population. Using the 5 HRCs as the reference, the PSR for the 5 LRCs was 1.40 (95% CI, 1.35-1.44). For emergent/urgent cholecystectomy, the PSR for the 5 LRCs was 2.26 (95% CI, 2.02-2.51), and the PSR for emergent/urgent herniorrhaphy was 1.83 (95% CI, 1.33-2.45). Age-adjusted rate of obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 30), on average, was 36.6% (SD, 3.4) in the 5 LRCs vs 25.4% (SD, 4.6) in the 5 HRCs (P = .002). The rate of bariatric surgery in the 5 HRCs was 33.07 per 10 000 population with obesity. For the 5 LRCs, the PSR was 0.60 (95% CI, 0.51-0.69). Conclusions and Relevance: The PSR is a systematic approach to define potential disparities in surgical access and should be useful for identifying, investigating, and monitoring interventions intended to mitigate disparities in surgical access that effects the health of vulnerable populations.

The Association of Tacrolimus Formulation Switching with Trough Concentration Variability: A Retrospective Cohort Study of Tacrolimus Use Post-Kidney Transplantation Based on National Drug Code (NDC) Numbers.

INTRODUCTION: It was hypothesized that patients experiencing at least one tacrolimus formulation switch may require more frequent therapeutic drug monitoring, subsequent dose adjustments, and a potential for untoward clinical outcomes than patients who remain on a single formulation. METHODS: Eligible patients were adult kidney transplant recipients with stable renal function at month 3 post-transplant and no evidence of acute rejection, receiving an oral, tacrolimus-based regimen. Patients were categorized into two groups (fixed or variable formulation) using the US National Drug Code (NDC) on the basis of tacrolimus formulation usage over the 12-month period. RESULTS: A total of 305 patients were enrolled from four US transplant centers; 44 (14.4%) received multiple formulations and 261 (85.6%) received a single formulation. Mean number of tacrolimus dose adjustments and mean cumulative milligram dose change were not statistically different between the two groups. Mean trough-to-dose ratio, frequency of trough level measurements, and mean number of excursions above 120% or below 80% of the patient's mean trough concentration were significantly higher in the variable compared to the fixed formulation group. CONCLUSION: A variable tacrolimus formulation regimen was associated with a higher frequency of trough level measurements and a greater number of excursions in trough levels compared with continuing on a fixed formulation regimen of tacrolimus in this retrospective chart review study. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Assessing Consequences of Intraaortic Balloon Counterpulsation Versus Left Ventricular Assist Devices at the Time of Heart Transplantation.

The proportion of heart transplant recipients bridged with durable, intracorporeal left ventricular assist devices (dLVADs) has dramatically increased; however, concern exists regarding obligate repeat sternotomy, increased bleeding risk because of anticoagulation and acquired von Willebrand disease, and increased rates of allosensitization. Whether dLVAD patients have impaired posttransplant outcomes compared with equivalent patients with less invasive intraaortic balloon pump counterpulsation (IABP) at the time of transplant is unknown. Therefore, we analyzed adult, first time, heart-only transplant procedures with dLVAD (n = 2,636) compared with IABP (n = 571) at the time of transplant based on data from the United Network for Organ Sharing (UNOS) July 2004 to December 2011. There was clear geographic variation in IABP and dLVAD at transplant. Multivariable analysis demonstrated equivalent cumulative risk of death (adjusted Cox proportional hazard ratio, 1.08; 95% confidence interval, 0.87-1.33; p = 0.51). There was no significant difference in adjusted comparison of perioperative morality, length of stay, postoperative renal failure requiring dialysis, or early acute rejection (p ≥ 0.14 for all). Therefore, data from UNOS suggest that the presence of dLVAD at the time of heart transplantation does not have a detrimental effect on postoperative outcomes compared with IABP, which must be considered in the context of pretransplant mortality and locoregional organ availability.

Outcomes in kidney transplant recipients from older living donors.

BACKGROUND: Previous studies demonstrate that graft survival from older living kidney donors (LD; age>60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD. METHODS: Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60-64, 65-69, ≥70 years). Adjusted models, controlling for donor and recipient risk factors, evaluated graft and recipient survivals. RESULTS: Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n=4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients. CONCLUSIONS: As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys.

Epidemiologic critique of literature on post-transplant neoplasms in solid organ transplantation.

As survival of transplant recipients improves, long-term complications become more important. We reviewed epidemiologic literature on real-world risks of de novo neoplasia post-transplant. We searched the Medline/PubMed, Cochrane, and Embase databases for population-based studies on risk of neoplasia from 1998 to 2005. Selection criteria included: solid organ transplants, neoplastic outcomes, n > 500 subjects, age > or = 18 yr, and study design. Of 187 abstracts, 64 met criteria for study size, age range, topic, and design. We classified the articles by quality of reporting on components of cohort studies. Twelve of 64 studies reported cohort eligibility and exclusion criteria, defined time at risk, and ascertained incident neoplasms. Twenty-one studies reported prevalence of neoplasms for unspecified time periods, and only eight incidence studies reported person yr at risk. Three studies of all types of neoplasms in kidney recipients reported incidence ranging from 11.0 to 17.3 cases per 1000 person yr. Two studies of post-transplant lymphoproliferative disorders reported incidence of 0.4 to 2.5 cases per 1000 person yr in kidney recipients. More precise estimation of risks and rates, better description of study population, and more attention to confounding in comparisons of rates would make studies more meaningful. Reports should adhere to established guidelines for presenting methods and results in epidemiologic studies.

Lifetime cost-effectiveness of calcineurin inhibitor withdrawal after de novo renal transplantation.

After renal transplantation, immunosuppressive regimens associated with high short-term survival rates are not necessarily associated with high long-term survival rates, suggesting that regimens may need to be optimized over time. Calcineurin inhibitor (CNI) withdrawal from a sirolimus-based immunosuppressive regimen may maximize the likelihood of long-term graft and patient survival by minimizing CNI-associated nephrotoxicity. In this study, a lifetime Markov model was created to compare the cost-effectiveness of a sirolimus-based CNI withdrawal regimen (sirolimus plus steroids) with other common CNI-containing regimens in adult de novo renal transplantation patients. Long-term graft survival was estimated by renal function and data from published studies and the US transplant registry, including short- and long-term outcomes, utility weights, and health-state costs were incorporated. Drug costs were based on average daily consumption and wholesale acquisition costs. The model suggests that treatment with sirolimus plus steroids is more efficacious and less costly than regimens consisting of a CNI, mycophenolate mofetil, and steroids; therefore, CNI withdrawal not only shows potential for long-term clinical benefits but also is expected to be cost-saving over a patient's life compared with the most commonly prescribed CNI-containing regimens.

Influence of early posttransplantation prednisone and calcineurin inhibitor dosages on the incidence of new-onset diabetes.

Risk for new-onset diabetes (NOD) after renal transplantation is higher with tacrolimus (Tac) than with cyclosporine (CsA), but the extent to which the diabetogenic effect of Tac is dosage dependent or steroid dependent remains uncertain. Patients who received a transplant between 1995 and 2002 were drawn from the United Network for Organ Sharing registry and prescription records and NOD diagnoses from Medicare claims, both provided by the United States Renal Data System. Patients were divided into six groups of steroid and Tac doses at 30 d after transplantation and referenced against CsA. Relative hazards of NOD with Cox proportional hazards regression were estimated incorporating propensity scores for Tac and nonimmunosuppressive factors related to NOD. A total of 8839 patients with valid immunosuppression records and without pretransplantation evidence of diabetes were included in the study. Unadjusted, cumulative, NOD incidence 1 yr after transplantation was 14.6% with CsA and 22.2% with Tac and at 3 yr after transplantation was 23.4% with CsA and 32.9% with Tac (P < 0.0001). Neither higher CsA nor higher steroid dosages were associated with NOD in CsA-treated patients. However, NOD hazard was significantly higher with Tac than with CsA in all six steroid/Tac dosing groups, including the cohort with the lowest dosages of Tac (dosage thresholds at 30 d after transplantation <0.12 mg/kg per d [mean 0.07 mg/kg per d] and steroids (<0.75 mg/kg per d; hazard ratio 1.28; 95% confidence interval 1.10 to 1.48; P = 0.0012). Whereas the incidence of NOD is greatest with high Tac dosages, the increased risk versus CsA is sustained with lower Tac dosages. Higher steroid dosages increase the early diabetogenic effect of Tac but not of CsA.

Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients.

BACKGROUND: Data are scarce regarding the incidence and risk factors for complications of new-onset diabetes mellitus (NODM) in renal transplant patients. METHODS: United States Renal Data System (USRDS) data from primary renal transplant recipients during 1995-2001 who developed NODM was used to examine diabetic complications over the first three years posttransplant. Prognostic models were used to evaluate patient characteristics and treatment choices associated with risk of each class of complications. Propensity scores for choice of calcineurin inhibitor were included in multivariate analyses. RESULTS: The analysis included 21,489 patients, of whom 4,105 developed NODM by 3 years posttransplant. One or more NODM complications developed in 2,393 patients (58.3% of all patients with NODM), comprising ketoacidosis (334, 8.1%), hyperosmolarity (131, 3.2%), renal complications (1,286, 31.3%), ophthalmic complications (340, 8.3%), neurological complications (665, 16.2%), peripheral circulatory disorders (170, 4.1%) and hypoglycemia/shock (301, 7.3%). Complications developed within a mean of 500 to 600 days from diagnosis of NODM. Multivariate analysis showed that increased recipient age, higher body mass index, African-American race, hepatitis C infection, hypertension as cause of end-stage renal disease, cold ischemia >or=30 hours, and use of tacrolimus each increased risk of complications. CONCLUSION: NODM is associated with similar complications to those seen in the general population, but these appear to develop at an accelerated rate. Obesity and use of tacrolimus are the only modifiable factors that appear to affect risk of NODM or its complications.