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D F Heitjan

Publications and source records attributed to D F Heitjan.

At least 19 recordsLinked to original sources
PubMed2001

Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. METHODS: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. RESULTS: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. CONCLUSIONS: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.

Activities of Daily Living↗
PubMed2001

Predicting analysis times in randomized clinical trials.

Randomized clinical trial designs commonly include one or more planned interim analyses. At these times an external monitoring committee reviews the accumulated data and determines whether it is scientifically and ethically appropriate for the study to continue. With failure-time endpoints, it is common to schedule analyses at the times of occurrence of specified landmark events, such as the 50th event, the 100th event, and so on. Because interim analyses can impose considerable logistical burdens, it is worthwhile predicting their timing as accurately as possible. We describe two model-based methods for making such predictions during the course of a trial. First, we obtain a point prediction by extrapolating the cumulative mortality into the future and selecting the date when the expected number of deaths is equal to the landmark number. Second, we use a Bayesian simulation scheme to generate a predictive distribution of milestone times; prediction intervals are quantiles of this distribution. We illustrate our method with an analysis of data from a trial of immunotherapy in the treatment of chronic granulomatous disease.

Bayes Theorem↗
PubMed2001

Estimating the effect of an intensive surveillance program on stage of breast carcinoma at diagnosis: a propensity score analysis.

BACKGROUND: The authors used propensity score adjustment to investigate the impact of intensive screening on stage of breast carcinoma at diagnosis in women who were at elevated risk for breast carcinoma. METHODS: The authors compared 58 women participating in a surveillance program at the Columbia Presbyterian Medical Center of New York Presbyterian Hospital who developed breast carcinoma with 3022 nonparticipating breast carcinoma patients. A propensity score was constructed for each woman by using important background covariates, and multivariable regression modeling was used to estimate the association of program membership with disease stage after adjusting for the propensity score. RESULTS: Before propensity score adjustment, nine baseline covariates significantly differed between the two groups (number of pregnancies, number of births, age at first delivery, race, how the tumor was discovered, history of prior breast disease, breast carcinoma in mother, breast carcinoma in maternal aunt, and breast carcinoma in sister), and there was a significant difference in stage at diagnosis. After adjustment, no significant differences remained. Program participants were more likely to have lower stage tumors at diagnosis than nonparticipants, but this association did not reach statistical significance (odds ratio, 1.52; 95% confidence interval, 0.94--2.46). CONCLUSIONS: Propensity score methods can remove bias in treatment comparisons in observational studies. An intensive surveillance program at a major cancer center may have had some effect on improving stage at diagnosis, but this effect was not statistically significant.

Breast Neoplasms↗
PubMed2001

Ascertainment and anticipation in family studies.

Many human diseases show anticipation; that is, disease occurs earlier (or with greater severity) in successive generations. In a computer simulation, we assessed the degree of anticipation that one would expect to see in two-generation breast cancer families. Under reasonable assumed distributions for age at cancer onset, number of children, and mortality, we find a consistent earlier mean age at diagnosis in daughters than in mothers, but the same mean age at diagnosis in affected aunts and nieces. We compare these results with published pedigree data for familial breast cancer that show substantial anticipation in affected daughters compared to their mothers. We find that at least some anticipation is expected in human disease families even when the disease is stable and families are ascertained without obvious sampling bias. We further demonstrate that such anticipation is reduced when comparing affected children to the parents' affected siblings.

Adult↗
PubMed2000

Fieller's method and net health benefits.

Statistical and conceptual difficulties complicate the estimation of the incremental cost-effectiveness ratio (ICER). An alternative approach is to measure cost-effectiveness by the incremental net health benefit (INHB), defined as the difference in mean effectiveness of a new treatment compared with a standard, adjusted for cost difference by subtracting the health foregone if purchasing care at the rate of a marginally cost-effective therapy. Because net health benefit (NHB) is dependent on this threshold rate, one can construct confidence intervals for the INHB at various values of the rate. It turns out that the set of rates where new and standard are not significantly different is equal to the Fieller's method confidence set for the ICER. We review the derivation of the Fieller's method confidence set, present numerical examples, and discuss the implications of our result for the calculation and interpretation of NHB analyses.

Bayes Theorem↗
PubMed2000

Mixed-effects models in psychophysiology.

The current methodological policy in Psychophysiology stipulates that repeated-measures designs be analyzed using either multivariate analysis of variance (ANOVA) or repeated-measures ANOVA with the Greenhouse-Geisser or Huynh-Feldt correction. Both techniques lead to appropriate type I error probabilities under general assumptions about the variance-covariance matrix of the data. This report introduces mixed-effects models as an alternative procedure for the analysis of repeated-measures data in Psychophysiology. Mixed-effects models have many advantages over the traditional methods: They handle missing data more effectively and are more efficient, parsimonious, and flexible. We described mixed-effects modeling and illustrated its applicability with a simple example.

Algorithms↗
PubMed1999

Bayesian estimation of cost-effectiveness ratios from clinical trials.

Estimation of the incremental cost-effectiveness ratio (ICER) is difficult for several reasons: treatments that decrease both cost and effectiveness and treatments that increase both cost and effectiveness can yield identical values of the ICER; the ICER is a discontinuous function of the mean difference in effectiveness; and the standard estimate of the ICER is a ratio. To address these difficulties, we have developed a Bayesian methodology that involves computing posterior probabilities for the four quadrants and separate interval estimates of ICER for the quadrants of interest. We compute these quantities by simulating draws from the posterior distribution of the cost and effectiveness parameters and tabulating the appropriate posterior probabilities and quantiles. We demonstrate the method by re-analysing three previously published clinical trials.

Bayes Theorem↗
PubMed1999

The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure.

BACKGROUND: Because left ventricular assist devices have recently been approved by the Food and Drug Administration to support the circulation of patients with end-stage heart failure awaiting cardiac transplantation, these devices are increasingly being considered as a potential alternative to biologic cardiac replacement. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial is a multicenter study supported by the National Heart, Lung, and Blood Institute to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. METHODS: We discuss the rationale for conducting REMATCH, the obstacles to designing this and other randomized surgical trials, the lessons learned in conducting the multicenter pilot study, and the features of the REMATCH study design (objectives, target population, treatments, end points, analysis, and trial organization). CONCLUSIONS: We consider what will be learned from REMATCH, expectations for expanding the use of left ventricular assist devices, and future directions for assessing clinical procedures.

Heart Failure↗
PubMed1999

Volume-outcome relationships in cardiovascular operations: New York State, 1990-1995.

BACKGROUND: It has been known for nearly 20 years that, in cardiovascular operations, a significant inverse relationship exists between clinical outcomes and the volume of procedures performed. Interestingly, this relationship persists 2 decades after it was recognized. OBJECTIVE: The purpose of this study was to examine the relationship between hospital volume and in-hospital deaths in 3 cardiovascular procedures: coronary artery bypass grafting, elective repair of abdominal aortic aneurysms, and repair of congenital cardiac defects. METHODS: The database includes all patients who were hospitalized in New York State during the years 1990 to 1995. Using standard logistic regression techniques, we analyzed the relationship between hospital volume and outcome. RESULTS: No correlation exists between hospital volume and in-hospital deaths in coronary artery bypass grafting. Statewide, 31 hospitals performed 97,137 operations over the 6-year period (overall mortality rate, 2. 75%). By contrast, most of the hospitals statewide (195 of 230 hospitals) performed 9847 elective abdominal aortic aneurysm repairs with an overall mortality rate of 5.5%. In abdominal aortic aneurysm operations, a significant inverse relationship between hospital volume and in-hospital deaths was determined. Sixteen hospitals performed 7199 repairs for congenital cardiac defects. A significant inverse relationship (which was most pronounced for neonates) was found between volume and death. CONCLUSIONS: The importance of these findings lies in the rather striking difference between the volume-outcome relationship found for operations for abdominal aortic aneurysms and congenital cardiac defects and the lack of such a relationship for coronary artery bypass grafting. This observation may be largely explained by the quality improvement program in New York State for bypass operations since 1989. If so, these results have important implications for expanding the scope of quality improvement efforts in New York State.

Adolescent↗
PubMed1999

Causal inference in a clinical trial: a comparative example.

Recently there has been much interest in methods for analyzing clinical trials of treatments that are subject to noncompliance. In this paper I study a small, simple dataset from a clinical trial of immunosuppressive therapy in the treatment of multiple sclerosis. I apply and compare a range of methods: the as-randomized (intention-to-treat) analysis, the as-treated analysis, estimates based on a nonignorable selection model, and Rubin's causal model. The results differ substantially even in this small dataset that exhibits modest noncompliance. For this reason, data analysts should be clear about which parameters are of greatest importance in the analysis of a clinical trial.

Azathioprine↗
PubMed1999

Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.

PURPOSE: To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. METHODS: We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated cancer risks are 56% for breast cancer and 16% for ovarian cancer. We assumed that the sensitivity and specificity of the test were 98% and 99%, respectively, that bilateral prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used Medicare payment data for treatment costs and Surveillance, Epidemiology, and End Results data for cancer survival. RESULTS: Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) for surveillance. The respective cost-effectiveness ratios per life-year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273. CONCLUSION: In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average survival and, depending on costs and screening/treatment strategies, may be cost-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test positive undergo prophylactic surgery. These estimates require confirmation through prospective observational studies and clinical trials.

Adult↗
PubMed1999

Geographic variations in the rates of operative procedures involving the shoulder, including total shoulder replacement, humeral head replacement, and rotator cuff repair.

BACKGROUND: Although geographic variations in the rates of orthopaedic procedures have been well documented, considerable controversy remains regarding the factors that drive these variations, particularly the role of the availability of orthopaedic surgeons. Moreover, little attention has been specifically focused on variations in the rates of commonly performed shoulder procedures. METHODS: The current study documents state-to-state variations in the rates of total shoulder replacement, humeral head replacement, and rotator cuff repair and examines factors that might account for these variations. The regional incidences of these three procedures were analyzed with use of the Health Care Financing Administration Medicare database (MEDPAR, 1992). The rates were age-adjusted, and variations were measured with use of high:low ratios, variation coefficients, and systematic components of variation. Potential causes of variation were analyzed with use of Spearman and partial correlations as well as with Poisson regression. RESULTS: Rates for the three procedures that were studied varied from one state to another by as much as tenfold. Humeral head replacement had the lowest rate of variation according to all three measures. All three procedures were performed less often in states that were more densely populated. With the numbers available for study, no consistent, significant relationship was found between the density of orthopaedists and shoulder surgeons and the rates of any procedure. CONCLUSIONS: The striking variations that were noted for these commonly performed procedures showed that there is a clear need for well designed clinical research to further define the factors that account for the variations and to examine the effectiveness and appropriate indications for the procedures.

Aged↗
PubMed1999

Probabilistic sensitivity analysis in cost-effectiveness. An application from a study of vaccination against pneumococcal bacteremia in the elderly.

OBJECTIVES: We explore the policy implications of probabilistic sensitivity analysis in cost-effectiveness analysis by applying simulation methods to a decision model. METHODS: We present the multiway sensitivity analysis results of a study of the cost-effectiveness of vaccination against pneumococcal bacteremia in the elderly. We then execute a probabilistic sensitivity analysis of the cost-effectiveness ratio by specifying posterior distributions for the uncertain parameters in our decision analysis model. In order to estimate probability intervals, we rank the numerical values of the simulated incremental cost-effectiveness ratios (ICERs) to take into account preferences along the cost-effectiveness plane. RESULTS: The 95% probability intervals for the ICER were generally much narrower than the difference between the best case and worst case results from a multiway sensitivity analysis. Although the multiway sensitivity analysis had indicated that, in the worst case, vaccination in the 85 and older age group was not acceptable from a policy standpoint, probabilistic methods indicated that the cost-effectiveness of vaccination was below $50,000 per quality-adjusted life-year in greater than 92% of the simulations and below $100,000 in greater than 95% of the simulations. CONCLUSIONS: Probabilistic methods can supplement multiway sensitivity analyses to provide a more comprehensive picture of the uncertainty associated with cost-effectiveness ratios and thereby inform policy decisions.

Aged↗
PubMed1998

Rapid reduction in blood flow to the rat ventral prostate gland after castration: preliminary evidence that androgens influence prostate size by regulating blood flow to the prostate gland and prostatic endothelial cell survival.

BACKGROUND: Androgenic steroids regulate the development and size of the mammalian prostate gland. The mechanism(s) for this growth control might involve a direct effect on prostate cell proliferation and survival as well as more complex effects on the tissue environment supporting nourishment and oxygenation. In this study, we evaluated an animal model of androgen action on the prostate, the rat ventral prostate gland, to determine whether acute androgen withdrawal, by means of castration, might alter the primary blood flow to the prostate gland and for the effects of castration on prostatic endothelial cell viability. METHODS: Groups of rats studied included intact control males, males that had been surgically castrated, or males that received a sham-surgical castration. Relative blood flow (RBF) to the rat ventral prostate glands and rat bladders were measured at 18 and 24 hr after castration or sham castration using a fluorescent microsphere infusion technique. Thin sections from fixed and embedded rat ventral prostate glands obtained from unoperated or 12-hr castrated rats were analyzed by the TUNEL immunostaining technique to microscopically identify and quantify apoptotic epithelial, stromal, and endothelial cells. RESULTS: RBF to the rat ventral prostate was reduced by 38%, at 18 hr after castration when compared with intact or sham-operated rats and by 45% at 24 hr after castration (P=0.038 unoperated/0.025 sham operated). In contrast, RBF to the bladder was not significantly different between any of the groups in the 24-hr castrate experiment. TUNEL staining analysis of ventral prostate tissues obtained from 12-hr castrated rats showed only rare TUNEL-positive epithelial cells similar to the control tissue but significantly increased TUNEL labeling for endothelial and other ventral prostate stromal cells. CONCLUSIONS: Castration resulted in a rapid and significant reduction of blood flow to the mature rat ventral prostate gland that was not seen in the bladder. This reduction precedes the appearance of apoptosis in the epithelial cells of the tissue but more coincided with the appearance of TUNEL-positive prostate vascular endothelial and stromal cells, suggesting that androgens support the survival of cells in the vascular and stromal compartment of the rat prostate as well as in the prostatic epithelium. These preliminary data support the concept that androgen action on the prostate might involve primary regulation of prostate blood flow and prostate vascular cell vitality.

Androgens↗
PubMed1998

Changes in biochemical disease-free survival rates as a result of adoption of the consensus conference definition in patients with clinically localized prostate cancer treated with external-beam radiotherapy.

PURPOSE: The optimal definition of biochemical recurrence of prostate cancer after definitive radiotherapy remains elusive. Different institutions have developed their own definitions, and a consensus conference (CC) sponsored by the American Society for Therapeutic Radiology and Oncology has recently proposed another definition. This study compares the definition previously used at our institution with the definition proposed by the CC. METHODS: Two hundred and eight patients were treated for localized prostate cancer with conformal external-beam radiotherapy between 1989-1993 at our institution and followed for at least 24 months. Patients were categorized as failures according to our institutional definition and the CC definition. Our definition (CPMC) required two increases in serum prostate specific antigen (PSA) over at least a 3-month period with a final value of at least 1 ng/ml or a single value resulting in clinical intervention. The CC definition required three consecutive increases in PSA. This was modified to also consider those patients with one or two increases leading to clinical intervention as failures. Differences in the failure rates between the two definitions were evaluated and factors influencing these differences were explored. In an additional analysis, CC was modified such that patients with one or two PSA increases were censored at the time of the PSA prior to the increases (CC-II), rather than at the last PSA (CC). The median follow-up time was 31 months. RESULTS: There were 36 fewer failures according to CC (n = 96) compared with CPMC (n = 132) (p < 0.001). Twenty cases called failures by CPMC subsequently had a decrease in PSA ("false failures"). The other 16 patients have had two increases in PSA, but are awaiting their next follow-up visit to obtain a third PSA ("pending failures"). Analysis of factors predicting "pending failures" showed Gleason score to be the sole predictor of this change in status in multivariate analysis (p = 0.03) with patients with lower-grade tumors being more likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other hand, "false failures," compared to true failures, had a lower mean PSA nadir (1.7 ng/ml vs. 7.0 ng/ml, p < 0.001) and significantly smaller mean increases in PSA (1st increase: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least one of the increases was < or = 0.3 ng/ml compared with 44% (42 of 96) of the true failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared with CC, but did not affect the overall difference between CC and CPMC. A modified definition that defines failure as two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases would result in a "false" failure rate of only 3% (3 of 99) and identify 56% (54 of 96) of the true failures after only two PSA increases. CONCLUSION: The CPMC definition of two PSA increases can falsely identify patients as failures, particularly if the increases in PSA are small (i.e., < or = 0.3 ng/ml). The CC definition requiring three increases in PSA can falsely identify patients as disease-free when the time to failure is long relative to the follow-up time. We propose a that a definition that combines aspects of both definitions (two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases) may be a better definition of biochemical failure.

Consensus Statements as Topic↗
PubMed1998

Biologic classification as an alternative to anatomic staging for clinically localized prostate cancer: a proposal based on patients treated with external beam radiotherapy.

OBJECTIVES: The prognostic significance of clinical stage in patients with prostate cancer who are treated with external beam radiotherapy is unclear. This study evaluates multiple pretreatment factors, including clinical stage, to determine which are the best prognostic factors, and develops a classification system based on these factors. METHODS: All 249 evaluable patients with clinically localized adenocarcinoma of the prostate treated with definitive conformal external beam radiotherapy without androgen deprivation at our institution between 1989 and 1993 were analyzed. Clinical stage, serum PSA level, Gleason score, race, and history of transurethral resection of the prostate (TURP) were evaluated for their ability to predict biochemical disease-free survival (BDFS). Factors predictive of BDFS were then used to construct a classification system. The classification system was then analyzed for its ability to predict BDFS, distant metastases, local recurrence, and clinical disease free survival in univariate and multivariate analyses. Median follow-up was 27 months. RESULTS: Gleason score and PSA predicted BDFS in multivariate analysis (both P <0.0001), whereas clinical stage, race, and history of a TURP did not. These two biologic factors were combined into a four-level classification system. This classification system was analyzed together with Gleason score and PSA and was found to be the only predictor of BDFS on multivariate analysis (P <0.0001). In addition, this classification system was the only predictor of distant metastases in multivariate analysis (P <0.0001). CONCLUSIONS: The classification system derived herein based on the biologic factors of Gleason score and serum PSA levels is the sole predictor of distant metastases and biochemical recurrence for patients treated with definitive conformal external beam radiotherapy for clinically localized prostate cancer. This classification system may be useful when comparing competing therapies and stratifying patients in clinical trials, but requires validation from other institutions and other therapies prior to its widespread use.

Adenocarcinoma↗