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D Faraggi

Publications and source records attributed to D Faraggi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Large sample Bayesian inference on the parameters of the proportional hazard models.

This paper considers large sample Bayesian analysis of the proportional hazards model when interest is in inference on the parameters and estimation of the log relative risk for specified covariate vectors rather than on prediction of the survival function. We use a normal prior distribution for the parameters and make inferences based on the derived posterior distribution. The suggested approach is much simpler than alternative Bayesian analyses previously suggested for the proportional hazards models. Using simulated data we compare estimates obtained from the Bayesian analysis with those obtained from the full proportional hazards model and the reduced model after backwards elimination. We show that under a wider range of assumptions, the Bayesian analysis provides reduced estimation errors and improved rejection of noise variables. Finally, we illustrate the methodology using data from a large study of prognostic markers in breast cancer.

Bayes Theorem↗
PubMed1997

Dexamethasone, etoposide, ifosfamide, and cisplatin as second-line therapy in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: This study analyzed the long term results of a combination of dexamethasone, etoposide, ifosfamide, and cisplatin (DVIP) used at the study center as standard second-line combination therapy in patients with aggressive non-Hodgkin's lymphoma (NHL) after prior exposure to doxorubicin. METHODS: All drugs were given intravenously for 4 consecutive days. The maximum daily doses of etoposide, ifosfamide, and cisplatin were 75 mg/m2, 1200 mg/m2, and 20 mg/m2, respectively. The dexamethasone dose was 20 mg twice daily. Cycles were repeated every 3 weeks. RESULTS: Fifty-six patients were included in the study. Partial response was noted in 18 patients (32%) and complete response (CR) in 18 patients (32%). Pretreatment factors that predicted CR were CR with prior therapy (CR in 17 of 34 in patients with a recurrence vs. 1 of 21 in patients with primary refractory NHL) and age (CR in 12 of 25 patients age < or = 65 years vs. 6 of 31 patients age > 65 years). Median time to treatment failure (TTF) and median survival were 11.5 months and 30 months, respectively, for patients with a CR and 3.5 months and 8 months, respectively, for all patients. Five patients (9%) remained disease free for > 24 months. By multivariate analysis, age was the only independent prognostic factor for TTF, whereas age, serum lactate dehydrogenase, and number of extranodal sites were independent predictors for survival. Myelosuppression (median granulocyte nadir and median platelet nadir of 350/mm3 and 77,000/mm3, respectively) was the major toxicity. There was one possible drug-related death associated with myelosuppression. CONCLUSIONS: DVIP is a relatively safe salvage combination therapy in patients with aggressive NHL. Response to first-line therapy and age are the most important predictors for prognosis after the administration of DVIP. This regimen is highly active in patients with recurrent NHL, but relatively ineffective in patients with primary refractory NHL.

Adult↗
PubMed1997

Confidence intervals for the generalized ROC criterion.

Receiver operating characteristic (ROC) curves are frequently used to assess the usefulness of diagnostic markers. When several diagnostic markers are available, they can be combined by a best linear combination: that is, when the area under the ROC curve of this combination is maximized among all possible linear combinations. This maximal area is the generalized ROC criterion, which provides a measure of how effective the combination of the markers is. This criterion needs to be estimated from the data, and is usually evaluated against single markers. In the present paper, we provide confidence intervals for the generalized ROC criterion under the assumption of homogeneous covariance matrices, derive an approximation for the heterogeneous covariance matrices case, and evaluate the approximation via a simulation study. Finally, we present an illustrative example.

Biomarkers↗
PubMed1996

A simulation study of cross-validation for selecting an optimal cutpoint in univariate survival analysis.

Continuous measurements are often dichotomized for classification of subjects. This paper evaluates two procedures for determining a best cutpoint for a continuous prognostic factor with right censored outcome data. One procedure selects the cutpoint that minimizes the significance level of a logrank test with comparison of the two groups defined by the cutpoint. This procedure adjusts the significance level for maximal selection. The other procedure uses a cross-validation approach. The latter easily extends to accommodate multiple other prognostic factors. We compare the methods in terms of statistical power and bias in estimation of the true relative risk associated with the prognostic factor. Both procedures produce approximately the correct type I error rate. Use of a maximally selected cutpoint without adjustment of the significance level, however, results in a substantially elevated type I error rate. The cross-validation procedure unbiasedly estimated the relative risk under the null hypothesis while the procedure based on the maximally selected test resulted in an upward bias. When the relative risk for the two groups defined by the covariate and true changepoint was small, the cross-validation procedure provided greater power than the maximally selected test. The cross-validation based estimate of relative risk was unbiased while the procedure based on the maximally selected test produced a biased estimate. As the true relative risk increased, the power of the maximally selected test was about 10 per cent greater than the power obtained using cross-validation. The maximally selected test overestimated the relative risk by about 10 per cent. The cross-validation procedure produced at most 5 per cent underestimation of the true relative risk. Finally, we report the effect of dichotomizing a continuous non-linear relationship between covariate and risk. We compare using a linear proportional hazard model to using models based on optimally selected cutpoints. Our simulation study indicates that we can have a substantial loss of statistical power when we use cutpoint models in cases where there is a continuous relationship between covariate and risk.

Humans↗
PubMed1995

A neural network model for survival data.

Neural networks have received considerable attention recently, mostly by non-statisticians. They are considered by many to be very promising tools for classification and prediction. In this paper we present an approach to modelling censored survival data using the input-output relationship associated with a simple feed-forward neural network as the basis for a non-linear proportional hazards model. This approach can be extended to other models used with censored survival data. The proportional hazards neural network parameters are estimated using the method of maximum likelihood. These maximum likelihood based models can be compared, using readily available techniques such as the likelihood ratio test and the Akaike criterion. The neural network models are illustrated using data on the survival of men with prostatic carcinoma. A method of interpreting the neural network predictions based on the factorial contrasts is presented.

Diethylstilbestrol↗
PubMed1995

Brain stem auditory evoked potentials: effects of ovarian steroids correlated with increased incidence of Bell's palsy in pregnancy.

To investigate the effect of ovarian steroids on the brain stem during changes of estrogen and progesterone blood levels, we recorded brain stem auditory evoked potentials with increased stimulus rates from 26 women treated for sterility by menotropins (Pergonal and Metrodin). These women were divided into three groups according to their estrogen and progesterone blood levels. The brain stem auditory evoked potential results revealed a significant delay of peak III only, with an increased stimulus rate in the group with the highest estrogen level. Estrogen may cause a brain stem synaptic impairment, presumably because of ischemic changes, and thus also may be responsible for a higher incidence of Bell's palsy during pregnancy.

Adult↗
PubMed1995

Full dose CHOP chemotherapy in elderly patients with non-Hodgkin's lymphoma.

Twenty-eight previously untreated elderly patients (median age 73 years, range 65-88) with aggressive non-Hodgkin's lymphoma were treated with full-dose CHOP chemotherapy between 1989 and 1992. The median of the average relative dose intensity (ARDI) was calculated for the initial cycles needed to achieve a maximal response or to determine progression of disease (1-6 cycles, median 4), as well as for the whole treatment course. For patients aged 65-74, both ARDIs were 0.89. A comparable group of 36 elderly patients who received reduced doses of CHOP from the start, served as a historical control. There was an increase of 11% and 29% in the ARDIs of the full-dose CHOP as compared with the reduced CHOP, in the initial cycles and for the whole treatment course respectively. Grade III-IV leukopenia was the main toxicity observed in 57% of the patients, and 7 patients were hospitalized for fever and leukopenia. There was no treatment-related death. It is concluded that CHOP chemotherapy without initial dose reduction is feasible in patients aged 65-74 years, resulting in high actual dose intensity with a reasonable degree of toxicity.

Aged↗
PubMed1995

Dynamic treatment allocation adjusting for prognostic factors for more than two treatments.

Methods of sequential allocation of one of K treatments to patients, while controlling for important prognostic factors, are developed and compared. We focus on methods that are based on optimality theory (Begg and Iglewicz, 1980, Biometrics 36, 81-90; Atkinson, 1982, Biometrika 69, 61-67), the permuted block procedure (Zelen, 1974, Journal of Chronic Diseases 27, 365-375), and the compromise method (Faraggi and Reiser, 1991, Communication in Statistics, Simulation and Computation 20, 243-254). These methods are extended to the K treatments case and are evaluated in terms of efficiency and balance. It is shown that each method achieved the best results in the criterion it was designed to optimize, i.e., within stratum balance for the permuted block allocation and efficiency for the allocations that are based on optimality theory, but did not do well with other criteria. The compromise method, on the other hand, has good overall properties in terms of both balance and efficiency.

Biometry↗
PubMed1995

The menstrual cycle and acute appendicitis.

OBJECTIVE: To examine the influence of the menstrual cycle on the incidence and presentation of acute appendicitis. DESIGN: Retrospective study. SETTING: University hospital, Israel. SUBJECTS: 144 women of child bearing age operated on for suspected acute appendicitis and subdivided according to the menstrual phase during which they presented. MAIN OUTCOME MEASURES: The final diagnoses, clinical presentation, and laboratory data. RESULTS: There were no significant differences in the incidence of acute, gangrenous, or perforated appendicitis in patients operated on during the various phases of the menstrual cycle. During menstruation, however, a normal appendix not accompanied by other disease was found significantly more often (p = 0.04). Clinical presentation, physical findings, and laboratory results did not vary throughout the menstrual cycle except for the "classic shifting pain" which was significantly more common during the luteal phase. CONCLUSIONS: Acute appendicitis occurs randomly during the various phases of the menstrual cycle. The incidence of operations for uninflamed appendixes may be higher during the menstrual phase. Significantly more negative laparotomies are done during the menstrual phase, which suggests the existence of a functional disorder that mimics acute appendicitis.

Acute Disease↗
PubMed1993

Is the vestibular system affected by middle ear effusion?

The association between middle ear effusion (MEE) and vestibular pathology is controversial. To investigate this point, 50 children with MEE scheduled for myringotomy and grommet, and 20 normal hearing children without MEE scheduled for adenotonsillectomy, underwent vestibular investigations by craniocorpography and rotatory chair, preoperatively and postoperatively. Most of the correlations, preoperative vs. postoperative, and study vs. control groups, were nonsignificant. Assuming that serous labyrinthitis is responsible for vestibular involvement in MEE, the lack of significant vestibular pathology in our study could probably be explained by the fact that no children with acute otitis media episodes or otalgia were included.

Audiometry↗
PubMed1992

Does isradipine exert a special early-morning blood pressure-lowering effect?

The blood pressure-lowering effect of isradipine at 1.25-2.5 mg twice daily (taken at 0700 and 1900 h) was assessed in a double-blind study involving 28 men with mild-to-moderate hypertension. After a 4-week placebo period, patients were randomized to receive either isradipine (group I) or placebo (group II) for 8 weeks. At the end of the placebo and active-treatment periods, patients were evaluated by 24-h ambulatory blood pressure monitoring. Data were analyzed according to two time periods: daytime, 1000-2300 h; nighttime and early morning, 2300-1000 h. Intersubject analyses were performed comparing values at the end of placebo with those at the end of active treatment. Intrasubject two-way analysis of variance showed that the time of day or night had no influence on blood pressure changes. Comparison of systolic (SBP) and diastolic (DBP) blood pressures with isradipine indicated that there were significantly greater average decreases in SBP at 0600-0800 h than at 1800-2000 h (p = 0.038), and at 0800-1100 h than at 2000-2300 h (p = 0.045). This was also true for the average decreases in DBP (p = 0.006). In conclusion, isradipine exerts blood pressure control throughout 24 h with a pronounced action during the early morning (0600-0800 h) period.

Adult↗
PubMed1992

Stage I-II low grade non-Hodgkin's lymphoma: prognostic factors and treatment results.

48 patients with stage I-II low-grade non-Hodgkin's lymphoma were treated by radiation and/or chemotherapy between 1970 and 1986. The histologic types were diffuse lymphocytic well differentiated, eleven patients; nodular lymphocytic poorly differentiated, 28 patients; nodular mixed, nine patients. Complete remission was obtained in 45 patients (94%). Overall survival was 83% and 68% at five and ten years, respectively. Five and ten-year relapse-free survival of complete responders was 71% and 57%, respectively. Univariate analysis of potential prognosticators showed the following to significantly increase the survival rate: one or two sites of disease (p less than 0.01), stage I (p less than 0.02), age less than 65 years (p less than 0.02), complete excision of tumor mass (p less than 0.03), and the use of radiotherapy (p less than 0.02). The extent of radiotherapy field did not affect survival. Multivariate analysis by the stepwise proportional hazards model of Cox showed that the use of radiotherapy was the factor which significantly produced better survival figures (p less than 0.03). It is concluded that two thirds of stage I-II low-grade lymphoma patients are potentially curable; radiotherapy plays a major role in the management.

Adult↗
PubMed1991

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Adult↗
PubMed1991

Phase II study of echinomycin in patients with advanced breast cancer: a report of Cancer and Leukemia Group B protocol 8641.

Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m2 intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.

Adenocarcinoma↗
PubMed1991

Twenty-four-hour blood pressure control with isradipine in mild essential hypertension.

The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine.

Adult↗
PubMed1990

Survival of diffuse large cell lymphoma. A multivariate analysis including dose intensity variables.

Ninety-five newly diagnosed patients with diffuse large cell lymphoma (DLCL) treated by cyclophosphamide (CTX), doxorubicin (ADM), vincristine (VCR), and prednisone (CHOP regimen) chemotherapy were evaluated for survival factors including dose intensity (DI). DI calculations were done for the initial cycles needed to achieve maximal response. The medians of the relative DI for CTX, ADM, and VCR were 0.9, 0.86, and 0.79, respectively. The median of the average relative DI (ARDI) was 0.83 (range, 0.28 to 1.14). The univariate analysis of potential prognostic variables showed that the following significantly decreased the survival rate: age older than 60 years (P = 0.0005), Stage III to IV (P = 0.02), male sex (P = 0.03), and all four DI variables (CTX, ADM, VCR, and ARDI) less than the median (P = 0.01 to 0.0001). A multivariate analysis by the stepwise proportional hazards model of Cox indicated that the factors predicting a poor prognosis were ARDI less than the median (P = 0.0003) and age older than 60 years (P = 0.02). A multivariate survival analysis of those who achieved complete remission showed ARDI less than the median (P = 0.0003), CTX less than the median (P = 0.02), and Stage III to IV (P = 0.02) to be the most negative factors regarding survival. In conclusion, a high DI in the initial cycles of CHOP chemotherapy for DLCL has a significant positive impact on survival.

Adolescent↗
PubMed1990

The efficacy of oral steroids in the treatment of persistent otitis media with effusion.

One hundred thirty-six children with otitis media with effusion of at least 2 months' duration were investigated in a strict, double-blind, randomized prospective study to evaluate the efficacy of oral steroids in the treatment of this disease. The results of our study showed a significant complete and partial recovery from otitis media with effusion in the group treated by a combination of antibiotics (amoxicillin) and oral steroids (prednisone), compared with an amoxicillin-treated group and a placebo-treated group. We believe that this treatment mostly benefits children aged 4 to 10 years without oversized adenoids. The findings of our study imply that a combined course of antibiotics and oral steroids deserves its place as a routine conservative trial before surgery.

Administration, Oral↗