Biomedical subjects

R Etzioni

Publications and source records attributed to R Etzioni.

30 records · Page 2Linked to original sources

PubMed1995

Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study.

The pharmacokinetics, safety, and efficacy in marrow transplantation of FK506-based immunosuppression for graft-versus-host disease (GVHD) prophylaxis was evaluated in an open label pilot study of 18 patients. Patients more than 12 years of age (median, 35 years; range, 15 to 50 years) with advanced hematologic malignancies receiving HLA-matched sibling marrow grafts were randomized to receive FK506 alone, FK506 and methotrexate (MTX), or FK506 and methyl-prednisolone. Of 17 evaluable patients, all had evidence of sustained marrow engraftment. The median time to an absolute neutrophil count of greater than 500/microL was 15 days for patients receiving FK506 alone or FK506 plus methylprednisolone and 23 days for FK506 plus short MTX. Pharmacokinetic studies did not show any significant difference in clearance of FK506 when administered alone or in combination with methylprednisolone or MTX. The mean bioavailability after oral administration in these same three groups was 0.49 +/- 0.1, 0.27 +/- 0.12, and 0.16 +/- 0.08, respectively (P = .003). The decrease in bioavailability may have resulted from an exacerbation of radiation-induced gastroenteritis by MTX. The most significant adverse effect associated with the administration of FK506 was nephrotoxicity, which occurred in 14 of 18 patients (78%). The mean glomerular filtration rate, determined by clearance of (99MTc)DTPA, decreased to 56% (+/- 18%) of the pretransplant baseline level by week 8 (P = .002). Eight of 18 patients (44%) developed grades II-IV acute GVHD, predominantly of the skin and gastrointestinal tract. The actuarial probability of transplant-related mortality during the first 100 days was 24%. The actuarial probability of 1-year disease-free survival was 39%. In conclusion, although bioavailability of FK506 may be affected in patients receiving MTX, this study suggests that FK506 may have a role in the management of patients after allogeneic marrow transplantation.

Administration, Oral↗

PubMed1995

Community organization to promote breast cancer screening among women ages 50-75.

BACKGROUND: To reduce breast cancer mortality, ways to promote the use of mammography screening among women age 50 and above are needed. Community organization may be a useful approach. METHODS: The Washington State Community Breast Cancer Screening Project involved implementation of promotional activities initiated by physician and lay community boards in two communities. Two comparable communities served as controls for evaluation purposes. Random-digit-dial telephone interviews were used to assess recent use of mammography at baseline and follow-up in independent samples of women ages 50 to 75 from the four communities. The extent of exposure to intervention activities and the relationship between exposure to intervention activities and mammography use were estimated from data collected at follow-up. RESULTS: Exposure to patient reminders from physicians, wallet reminder cards, and newspaper advertisements were consistently related to mammography use. Physician office staff encouragement and a display board were significantly related to mammography use only in Intervention Communities A and B, respectively. Neither exposure to promotional activities nor the change in prevalence of mammography use was significantly higher in the intervention communities than in the comparison communities at follow-up. CONCLUSIONS: Although several activities were useful in promoting mammography use, organization of the community did not enhance efforts undertaken spontaneously by comparable communities.

Aged↗

PubMed1995

Marrow transplantation from unrelated volunteer donors.

Marrow transplants from human leukocyte antigen (HLA)-compatible unrelated volunteer donors have become feasible for more than 30% of patients without a family match and have allowed long-term, disease-free survival in 15-65% of patients with a variety of hematological disorders. However, unrelated donor transplants have a higher incidence of graft failure and graft versus host disease (GVHD) than do HLA-matched sibling transplants. This increase may be due to disparities between donor and recipient for undetected HLA determinants or for non-HLA histocompatibility genes. Because of the large number of HLA loci and their high degree of polymorphism, fully compatible donors will not be found for most patients. Fortunately, a limited degree of HLA mismatch does not necessarily impair long-term survival in patients with hematologic malignancy. Current studies are defining the risk associated with mismatching for each histocompatibility locus and are developing methods for marrow transplantation that can decrease morbidity and improve survival despite genetic disparity between donor and recipient.

Bone Marrow Transplantation↗

PubMed1995

On the catch-up time method for analyzing cancer screening trials.

In randomized cancer screening trials, the ratio of the mortality rate for the screened group to that for the control group is typically not constant as a function of years from randomization. This is due to an initial lag effect, but also to a dilution effect that results from the accrual of comparable cases in both groups after the end of the screening period. In order to combat the potential loss of power when applying conventional analysis tools, specifically the logrank test, Aron and Prorok (International Journal of Epidemiology 15, 36-43), have advocated analyzing the mortality experience using only the subcohort of cases ascertained within a given time period. However, it is not clear how to select an appropriate case ascertainment point, since this will depend on aspects of the natural history of the disease process which are poorly identified. Aron and Prorok suggest choosing the case ascertainment point to be the point at which the cumulative number of cases in the control group first becomes equal to that in the intervention group, that is, the "catch-up time." In this paper, we undertake a thorough evaluation of the bias and power properties of the catch-up time method. We base our study on simulated data resembling the Health Insurance Plan of Greater New York study cohort. We consider several models for postdiagnosis survival under the null hypothesis of no screening effect on mortality, and under the alternative hypothesis of an effect of screening. We show that the catch-up method can yield tests with sizeable bias. In the absence of detailed knowledge about the underlying disease process, we suggest some adaptive tests that maintain nominal size but have more attractive power properties than the standard logrank test.

Adult↗

PubMed1995

A likelihood ratio test for cancer screening trials.

In randomized cancer screening trials, mortality rates for the screened group relative to those of the control group are not likely to be constant as a function of years from randomization due to the inherent lag between initiation of screening and any putative effects of screening on mortality. In this situation, a log rank test for differences in mortality between the randomization groups will not be optimal. Although optimality could potentially be recovered by use of a weighted log rank statistic, the optimal weights are difficult to specify a priori and the potential loss of power by use of poorly specified weights is great. We describe a likelihood ratio test with two degrees of freedom for use in this situation which is based on a fit of a weakly structured full model. Computation of an approximate significance level for this test is described and a large sample justification for this approximation is given. Size and power properties of the proposed statistic are compared to that of several other statistics in a small simulation study and the statistic is applied to data from the HIP Breast Cancer Screening Trial.

Biometry↗

PubMed1994

Monitoring of a pilot toxicity study with two adverse outcomes.

We consider monitoring a pilot toxicity study in which the adverse outcome is bivariate and the goal is to terminate the trial if evidence of excessive toxicity is encountered. We develop a Bayesian monitoring rule, based on the posterior probability that the frequency of either adverse outcome exceeds that observed under standard therapy. This rule is intuitive and ethical, and extends in a straightforward fashion from the univariate to the multivariate case. Since p-values and confidence intervals are standard methods for reporting the results of clinical trials, we also suggest how frequentist inferences may be drawn at the conclusion of a study monitored in this fashion. This work thus represents an integration of Bayesian and frequentist methodology for sequential clinical trials.

Analysis of Variance↗

PubMed1994

Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia.

Graft rejection has been a problem after marrow grafts for patients with aplastic anemia who were conditioned with cyclophosphamide (CY). Rejection lessened when patients were given the marrow donor's peripheral blood buffy-coat cells in addition to the marrow, but this result was achieved at the price of more chronic graft-versus-host disease (GVHD). Results with second transplants suggested that CY alternating with antithymocyte globulin (ATG) was more immunosuppressive than CY alone. Therefore, the current study explored CY and ATG without buffy-coat cell transfusions in 39 patients with aplastic anemia given marrow transplants from HLA-identical family members (siblings in 38 cases, father in 1 case). We hoped both to minimize the risks of graft rejection and of chronic GVHD and to improve survival. Patients were 2 to 52 years of age (median, 24.5); 87% had received previous transfusions, and 41% had therapy with immunosuppressive agents before transplant. They were administered four daily doses of CY (total, 200 mg/kg) alternating with three doses of ATG (total, 90 mg/kg) followed by an HLA-identical marrow graft. Methotrexate and cyclosporine were administered to prevent GVHD. Two patients rejected their grafts (5%), and both were successfully retransplanted. Acute (grade 2 or 3) GVHD occurred in 15% and chronic GVHD in 34% of patients. The actuarial survival rate at 3 years was 92%, which compares favorably to the 72% survival rate in 39 historical patients who were matched with current patients for age and risk factors for rejection and GVHD. CY/ATG is a well-tolerated and effective conditioning program for marrow grafting in aplastic anemia that, when combined with GVHD prevention by methotrexate/cyclosporine, results in excellent survival.

Adult↗

PubMed1994

Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: matching for transplants from related haploidentical donors.

The utility of the MLC assay as a test of HLA-D region matching and predictor of acute graft-versus-host disease (GvHD) was evaluated in 157 patients receiving marrow grafts from HLA-A, B identical related haploidentical donors. All donors and recipients were tested by HLA-DR serology, by Dw phenotyping with homozygous typing cells (HTC) and by standard MLC. Ninety-nine of the donor-recipient pairs were mismatched for a serologically defined HLA-DR antigen while 109 pairs were mismatched for the HLA-DR region by HTC typing. Donor antirecipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from -4% to 100%, with a median of 25%. A comparison of reactivity in MLC with presence or absence of matching by Dw phenotyping, however, showed a significant overlap in the distribution of RRs from HLA-Dw matched versus Dw mismatched pairs, suggesting that the MLC was not a reliable predictor of HLA-Dw matching. Using an optimally-defined cutoff of 3% RR, the MLC was correlated with risk of developing clinically significant grades II-IV acute GvHD (p = 0.03) but not with risk of developing severe grades III-IV GvHD (p = 0.18). In contrast, matching by Dw phenotype was a significant predictor of GvHD, with Dw-compatible transplant recipients less likely to develop either grades II-IV (p = 0.004) or III-IV (p = 0.036) GvHD than Dw-incompatible transplant recipients. Overall, these results underscore the difficulty in using the MLC to measure HLA-D region compatibility and predict the risk of severe graft-versus-host disease among patients receiving related haploidentical marrow grafts. HLA-D (HTC) typing results correlate primarily with DRB compatibility, and with the advent of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing, the precision in donor matching achievable with these methods is far greater than with either HLA-D typing or direct MLC testing.

Adolescent↗

PubMed1993

Small bowel obstruction after nephrectomy for Wilms' tumor. A report of the National Wilms' Tumor Study-3.

OBJECTIVE: This study was undertaken to define the incidence and etiology of small bowel obstruction (SBO) after nephrectomy for Wilms' tumor. SUMMARY BACKGROUND DATA: Intestinal obstruction is one of the most common postoperative complications after nephrectomy for nephroblastoma. However, few reports have evaluated risk factors for SBO. Radiation therapy has been associated with increased intestinal complications in some adult cancer patients, but this has not been reported in children undergoing cancer surgery. METHODS: Postoperative SBO occurred in 131 of 1,910 children (6.9%) enrolled in the Third National Wilms' Tumor Study (NWTS). The etiology of the SBO was bowel adhesions in 104 cases, intussusception in 17, internal hernia in 2, and uncertain in the remaining 8 children. RESULTS: The factors found to be of potential importance in explaining the incidence of SBO were higher local tumor stage, extrarenal intravascular involvement, and en bloc resection of other organs at the time of nephrectomy. The incidence of postoperative SBO was not increased in children who received postoperative radiation therapy. CONCLUSIONS: Although the overall incidence of SBO after nephrectomy for Wilms' tumor is comparable to that after other major abdominal operations in children, it can be responsible for significant morbidity. There were 4 children among the 1,910 patients with infectious complications of SBO, which contributed to their death.

Child, Preschool↗

PubMed1992

Surgical complications after nephrectomy for Wilms' tumor.

We reviewed the charts of 1,910 children enrolled in the Third National Wilms' Tumor Study who underwent primary nephrectomy. Four hundred and ninety-five surgical complications occurred in 379 children (19.8 percent). Patients with inoperable tumors, bilateral renal tumors, peroperative therapy and those who refused treatment were excluded from this review. The most common complication was intestinal obstruction, which occurred in 132 patients (6.9 percent). This was followed by extensive intraoperative hemorrhage (112 patients), defined as blood loss exceeding 50 milliliters per kilogram of body weight. Intraoperative injuries to other visceral organs (including intestine, liver and spleen) occurred in 21 children and extensive vascular injuries were reported in 27 patients. There were nine deaths attributed to surgical complications (0.5 percent), only one of which was intraoperative. Survival of patients with complications was similar to patients without complications when stratified by histologic study and stage. Factors associated with the development of surgical complications included advanced local tumor stage at diagnosis, intravascular tumor extension and resection of other visceral organs at the time of nephrectomy. Complete removal of the tumor is important, but not at the expense of radical removal of adjacent structures, because of gross appearances at operation. They are often not invaded by the tumor, but rather are compressed, distorted or adherent without tumor infiltration. Identification of these groups will aid the surgeon in choosing the appropriate management for these patients at high risk. When initial exploration and precise surgical staging indicate that only a formidable operation will achieve total excision, shrinkage of the tumor with selective use of chemotherapy or radiotherapy, or both, may facilitate removal and decrease surgical morbidity. Preoperative therapy may also be the preferred approach for children with extensive intravascular tumor.

Actuarial Analysis↗

PubMedDate not supplied

Optimizing sampling strategies for estimating quality-adjusted life years.

Accurate estimation of quality of life is critical to cost-effectiveness analysis. Nevertheless, development of sampling algorithms to maximize the accuracy and efficiency of estimated quality of life has received little consideration to date. This paper presents a method to optimize sampling strategies for estimating quality-adjusted life years. In particular, the authors address the questions of when to sample and how many observations to sample at each sampling time, assuming realistically that the sample variance of quality of life is not constant over time. The method is particularly useful for the design problems researchers face when time or research budget constraints limit the number of individuals that can be surveyed to estimate quality of life. The article focuses on cross-sectional sampling. The method proposed requires some knowledge of survival in the population of interest, the approximate variances in utilities at various points along the curve, and the general shape of the quality-adjusted survival curve. Such data are frequently available from disease registries, the literature, or previous studies.

Cost-Benefit Analysis↗

PubMedDate not supplied

Incorporating the time dimension in receiver operating characteristic curves: a case study of prostate cancer.

Early diagnosis of disease has potential to reduce morbidity and mortality. Biomarkers may be useful for detecting disease at early stages before it becomes clinically apparent. Prostate-specific antigen (PSA) is one such marker for prostate cancer. This article is concerned with modeling receiver operating characteristic (ROC) curves associated with biomarkers at various times prior to the time at which the disease is detected clinically, by two methods. The first models the biomarkers statistically using mixed-effects regression models, and uses parameter estimates from these models to estimate the time-specific ROC curves. The second directly models the ROC curves as a function of time prior to diagnosis and may be implemented using software packages with binary regression or generalized linear model routines. The approaches are applied to data from 71 prostate cancer cases and 71 controls who participated in a lung cancer prevention trial. Two biomarkers for prostate cancer were considered: total serum PSA and the ratio of free to total PSA. Not surprisingly, both markers performed better as the interval between PSA measurement and clinical diagnosis decreased. Although the two markers performed similarly eight years prior to diagnosis, it appears that total PSA performed better than the ratio measure at times closer to diagnosis. The area under the ROC curve was consistently greater for total PSA than for the ratio four and two years prior to diagnosis and at the time of diagnosis.

Adult↗