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Biomedical subjects

Dawn M Dykstra

Publications and source records attributed to Dawn M Dykstra.

At least 19 recordsLinked to original sources

Preemptive transplantation for patients with diabetes-related kidney disease.

BACKGROUND: Preemptive kidney transplantation (PreKT) before initiation of chronic dialysis has been examined recently with favorable results as the most effective treatment for kidney failure. Given that few of these studies are disease specific, the present analyses investigated the outcomes of PreKT by transplantation option and diabetes type. METHODS: The impact of PreKT on posttransplantation mortality and graft failure was examined in 23 238 adults with type 1 and type 2 diabetes mellitus (DM), receiving either living or deceased donor kidneys or undergoing simultaneous pancreas-kidney (SPK) transplantation between January 1, 1997, and December 31, 2002. RESULTS: The PreKTs were provided to 14.4% of patients with type 1 DM and 6.7% of patients with type 2 DM. Cox regression models were used to estimate the effect of PreKT on the adjusted risk ratio (RR) of graft failure and mortality. After adjusting for multiple factors, PreKT in this era was associated with lower RR of mortality only among type 1 and type 2 diabetic recipients of transplants from living donors and SPK transplant recipients with type 1 DM (RR, 0.50-0.65; P<.007 for each). The effect on graft failure was less pronounced, significant only for preemptive SPK transplant recipients (RR, 0.79; P=.01 vs nonpreemptive SPK transplant recipients). CONCLUSIONS: These analyses suggest that PreKT has significant benefits for subsets of patients with types 1 and 2 DM and end-stage renal disease. It also suggests a time trend toward less benefit from preemptive transplants from deceased donors in more recent years compared with the early 1990s. This observation and the discrepancies between RR of graft loss and RR of mortality deserve further study.

Adolescent↗

Analytical approaches for transplant research, 2004.

This article provides detailed explanations of the methods frequently employed in outcomes analyses performed by the Scientific Registry of Transplant Recipients (SRTR). All aspects of the analytical process are discussed, including cohort selection, post-transplant follow-up analysis, outcome definition, ascertainment of events, censoring, and adjustments. The methods employed for descriptive analyses are described, such as unadjusted mortality rates and survival probabilities, and the estimation of covariant effects through regression modeling. A section on transplant waiting time focuses on the kidney and liver waiting lists, pointing out the different considerations each list requires and the larger questions that such analyses raise. Additionally, this article describes specialized modeling strategies recently designed by the SRTR and aimed at specific organ allocation issues. The article concludes with a description of simulated allocation modeling (SAM), which has been developed by the SRTR for three organ systems: liver, thoracic organs, and kidney-pancreas. SAMs are particularly useful for comparing outcomes for proposed national allocation policies. The use of SAMs has already helped in the development and implementation of a new policy for liver candidates with high MELD scores to be offered organs regionally before the organs are offered to candidates with low MELD scores locally.

Data Interpretation, Statistical↗

Transplant data: sources, collection and research considerations, 2004.

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.

Graft Survival↗

The survival benefit of liver transplantation.

Demand for liver transplantation continues to exceed donor organ supply. Comparing recipient survival to that of comparable candidates without a transplant can improve understanding of transplant survival benefit. Waiting list and post-transplant mortality was studied among a cohort of 12 996 adult patients placed on the waiting list between 2001 and 2003. Time-dependent Cox regression models were fitted to determine relative mortality rates for candidates and recipients. Overall, deceased donor transplant recipients had a 79% lower mortality risk than candidates (HR = 0.21; p < 0.001). At Model for End-stage Liver Disease (MELD) 18-20, mortality risk was 38% lower (p < 0.01) among recipients compared to candidates. Survival benefit increased with increasing MELD score; at the maximum score of 40, recipient mortality risk was 96% lower than that for candidates (p < 0.001). In contrast, at lower MELD scores, recipient mortality risk during the first post-transplant year was much higher than for candidates (HR = 3.64 at MELD 6-11, HR = 2.35 at MELD 12-14; both p < 0.001). Liver transplant survival benefit at 1 year is concentrated among patients at higher risk of pre-transplant death. Futile transplants among severely ill patients are not identified under current practice. With 1 year post-transplant follow-up, patients at lower risk of pre-transplant death do not have a demonstrable survival benefit from liver transplant.

Adolescent↗

Timing of first cannulation and vascular access failure in haemodialysis: an analysis of practice patterns at dialysis facilities in the DOPPS.

BACKGROUND: Optimal waiting time before first use of vascular access is not known. METHODS: Two practices-first cannulation time for fistulae and grafts, and blood flow rate-were examined as potential predictors of vascular access failure in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure (defined as time to first failure or first salvage intervention) was modelled using Cox regression. RESULTS: Among 309 haemodialysis facilities, 2730 grafts and 2154 fistulae were studied. For grafts, first cannulation typically occurred within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities. For fistulae, first cannulation occurred <2 months after placement in 36% of US, 79% of European and 98% of Japanese facilities. Overall, the relative risk (RR) of graft failure in Europe was lower compared with the USA (RR = 0.69, P = 0.04). The RR of graft failure (reference group = first cannulation at 2-3 weeks) was 0.84 with first cannulation at <2 weeks (P = 0.11), 0.94 with first cannulation at 3-4 weeks (P = 0.48) and 0.93 with first cannulation at >4 weeks (P = 0.48). The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P = 0.08), 0.91 at 2-3 months (P = 0.43) and 0.87 at >3 months (P = 0.31) (reference group = first cannulation at 1-2 months). Facility median blood flow rate was not a significant predictor of access failure. CONCLUSIONS: Earlier cannulation of a newly placed vascular access at the haemodialysis facility level was not associated with increased risk of vascular access failure. Potential for confounding due to selection bias cannot be excluded, implying the importance of clinical judgement in determining time to first use of vascular access.

Arteriovenous Shunt, Surgical↗

Selection of pediatric candidates under the PELD system.

1. The PELD score accurately predicts the 3 month probability of waiting list death for children with chronic liver disease. 2. Comparing pre and post PELD and MELD implementation, the percent of children receiving deceased donor livers increased and the percent of children dying on the list decreased after PELD/MELD implementation. 3. Excluding children transplanted at status 1, the largest percentage of children are transplanted at a PELD score < 10. 4. Before MELD/PELD 48% of all children receiving deceased donor organs were transplanted at status 1, compared to 41% in the PELD/MELD era. Wide regional variation occurs.

Adult↗

Analytical approaches for transplant research.

It is highly desirable to base decisions designed to improve medical practice or organ allocation policies on the analyses of the most recent data available. Yet there is often a need to balance this desire with the added value of evaluating long-term outcomes (e.g. 5-year mortality rates), which requires the use of data from earlier years. This article explains the methods used by the Scientific Registry of Transplant Recipients in order to achieve these goals simultaneously. The analysis of waiting list and transplant outcomes depends strongly on statistical methods that can combine data from different cohorts of patients that have been followed for different lengths of time. A variety of statistical methods have been designed to address these goals, including the Kaplan-Meier estimator, Cox regression models, and Poisson regression. An in-depth description of the statistical methods used for calculating waiting times associated with the various types of organ transplants is provided. Risk of mortality and graft failure, adjusted analyses, cohort selection, and the many complicating factors surrounding the calculation of follow-up time for various outcomes analyses are also examined.

Cohort Studies↗

Improving liver allocation: MELD and PELD.

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed. Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults. A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.

Adult↗

Predicted lifetimes for adult and pediatric split liver versus adult whole liver transplant recipients.

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted candidates, 907 split and 21,913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post-transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2-year period were calculated. Seventy-six splits (152 recipients) and 24 re-transplants resulted from every 100 livers (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re-transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

Adult↗

Liver transplantation in children with metabolic disorders in the United States.

We studied pediatric liver transplantation for metabolic disease in a large national cohort to determine whether smaller studies suggesting a survival advantage for these recipients could be corroborated. We also hoped to determine whether higher survival rates in recipients with metabolic disease are associated with lack of structural liver disease, and to evaluate these recipients' risk factors for mortality. Data from the Scientific Registry of Transplant Recipients were used to analyze nationwide results (1990-99) of pediatric liver transplantation for patients with biliary atresia and metabolic disease. Adjusted patient survival rates for children with metabolic disease at 1 and 5 years were 94% and 92%, respectively, - significantly higher than for recipients with biliary atresia (90% and 86%) (p = 0.008). Cox regression models identified recipient black race [relative risk (RR) = 5.1] and simultaneous transplantation of other organs (RR = 3.2) as significant risk factors for mortality in the metabolic group. Adjusted survival rates for metabolic patients with structural and nonstructural liver diseases were similar to each other at both 1 and 5 years. Children with metabolic disease had significantly higher adjusted short- and long-term post-transplant survival rates than those with biliary atresia. Structural disease was not a risk factor for worse outcomes.

Adolescent↗

Gender imbalance and outcomes in living donor renal transplantation in the United States.

In living donor kidney transplantation there are disproportionately more female-to-male donations and fewer male-to-female donations. Given the rapid increase in living donor transplantation, we studied gender demographics and outcomes of these transplants. We analyzed living donor kidney transplants in the Scientific Registry of Transplant Recipients (SRTR) database between 1990 and 1999. There were 30 258 living donor transplants [26 510 (87%) biologically related; 2367 (8%) spousal; 1381 (5%) nonspousal unrelated]. Females comprised 68% of spousal and 56% of related and unrelated nonspousal donors (p < 0.0001). The distributions of gender pairings in nonspousal groups (related and unrelated) were significantly imbalanced (p < 0.0001). Opposite-sex pairs demonstrated more female-to-male donations among living related (64%, p < 0.0001), unrelated nonspousal (65%, p < 0.0001), and spousal pairs (68%). The higher incidence of end-stage renal disease among males and the slight predominance of females in the general population did not explain these gender disparities. Male recipients of male donor kidneys demonstrated significantly higher graft survival than other combinations (p < 0.006). Gender disparities in living donor transplantation result from a higher proportion of wife-to-husband donations and disproportionate female-to-male donations among biological relatives and unrelated pairs. There appears to be a graft survival advantage for male recipients of male donor kidneys.

Adult↗

Longitudinal assessment of mortality risk among candidates for liver transplantation.

Liver allocation policy recently was modified to use the Model for End-Stage Liver Disease (MELD) for patients with chronic liver disease to stratify potential recipients according to risk for waitlist death. In this study, a retrospective cohort of 760 adult patients with chronic liver disease placed on the liver transplant waitlist between January 1995 and March 2001 and followed up for up to 74 months was studied to assess the ability of the MELD to predict mortality among waitlisted candidates and evaluate the prognostic importance of changes in MELD score over time. Serial MELD scores predicted waitlist mortality significantly better than baseline MELD scores or medical urgency status. Each unit of the 40-point MELD score was associated with a 22% increased risk for waitlist death (P <.001), whereas medical urgency status was not a significant independent predictor. For any given MELD score, the magnitude and direction of change in MELD score during the previous 30 days (DeltaMELD) was a significant independent mortality predictor. Patients with MELD score increases greater than 5 points over 30 days had a threefold greater waitlist mortality risk than those for whom MELD scores increased more gradually (P <.0001). We conclude that mortality risk on the liver transplant waitlist is predicted more accurately by serial MELD score determinations than by medical urgency status or single MELD measurements. DeltaMELD score over time reflects progression of liver disease and conveys important additional prognostic information that should be considered in the further evolution of national liver allocation policy.

Adult↗

Evaluation of the ESRD managed care demonstration operations.

Individuals with end stage renal disease (ESRD), most of whom are insured by Medicare, are generally prohibited from enrolling in Medicare managed care plans (MCPs). CMS offered ESRD patients the opportunity to participate in an ESRD managed care demonstration mandated by Congress. The demonstration tested whether managed care systems would be of interest to ESRD patients and whether these approaches would be operationally feasible and efficient for treating ESRD patients. This article examines the structure, implementation, and operational outcomes of the three demonstration sites, focusing on: the structure of these managed care programs for ESRD patients, requirements needed to attract and enroll patients, and the challenges of introducing managed care programs in the ESRD arena.

California↗

Patient selection in the ESRD managed care demonstration.

The Centers for Medicare & Medicaid Service's (CMS') end stage renal disease (ESRD) managed care demonstration offered an opportunity to assess patient selection among a chronically ill and inherently costly population. Patient selection refers to the phenomenon whereby those Medicare beneficiaries who choose to enroll or stay in health maintenance organizations (HMOs) are, on average, younger, healthier, and less costly to treat than beneficiaries who remain in the traditional Medicare fee-for-service (FFS) sector. The results presented in this article show that enrollees into the demonstration were generally younger and healthier than a representative group of comparison patients from the same geographic areas.

Adult↗

Quality of life and patient satisfaction: ESRD managed care demonstration.

To study the effects of managed care on dialysis patients, we compared the quality of life and patient satisfaction of patients in a managed care demonstration with three comparison samples: fee-for-service (FFS) patients, managed care patients outside the demonstration, and patients in a separate national study. Managed care patients were less satisfied than FFS patients about access to health care providers, but more satisfied with the financial benefits (copayment coverage, prescription drugs, and nutritional supplements) provided under the demonstration managed care plan (MCP). After 1 year in the demonstration, patients exhibited statistically and clinically significant increases in quality of life scores.

California↗