Oral combination chemotherapy in conjunction with filgrastim (G-CSF) in the treatment of AIDS-related non-Hodgkin's lymphoma: evaluation of the role of G-CSF; quality-of-life analysis and long-term follow-up.

In 1993 we reported the efficacy and toxicity profile of an oral combination regimen administered to 18 patients with AIDS-related lymphoma (NHL-1 study). We observed a 61% response rate; 39% one-year survival rate; nearly two-thirds of patients developed > or = grade 3 leukopenia; and 28% of cycles were associated with febrile neutropenia. These results prompted us to shorten the duration of therapy and to add G-CSF to ameliorate the myelosuppression. Twenty patients with biopsy-proven AIDS-related lymphoma were treated with three 6-week cycles of oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, cycles no. 1 and 3; etoposide 200 mg/m2 days 1-3; cyclophosphamide and procarbazine both 100 mg/m2 days 22-31; and G-CSF 5 microg/kg subcutaneously days 5-21 and days 33-42 (NHL-2 study). The following analyses were undertaken: (1) evaluation of toxicity and efficacy parameters for patients in the current (NHL-2) study; (2) analysis of the clinical role of G-CSF by (historical) comparison with the NHL-1 study of the same regimen without G-CSF; (3) quality-of-life assessments using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments for all 38 patients (NHL-1+2); and (4) long-term follow-up for all 38 patients. In the current study the overall objective response using ECOG criteria was 70% (95% CI, 50-90%) with 6 CRs (30%) and 8 PRs (40%). The median survival duration was 7.3 months (range: 0.5-51+ months). One patient developed CNS relapse. There were no significant differences with respect to demographics or prognostic factors between the patient populations of the NHL-1 study and the current study (P > 0.2 for each factor). Myelosuppression was the major toxicity in both studies. In the current study versus the NHL-1 study, although the lower incidences of grade 3/4 myelosuppression (51% vs. 64%) and febrile neutropenia (17% vs. 28%) on a per cycle basis were not statistically significant, fewer patients (40% vs. 60%) were affected. However, the severity of myelotoxicity was lessened with the addition of G-CSF, measured in terms of the discontinuation of therapy, myelotoxic deaths, and freedom from grade 3/4 myelotoxicity ( P < 0.02). The number of hospitalizations for febrile neutropenia (7 in the NHL-2 study vs. 13 in the NHL-1 study) was also significantly different (P < 0.05). Quality-of-life analysis confirmed no significant functional or psychological deterioration during therapy except for patients experiencing febrile neutropenia, whose functional capacity deteriorated (P < 0.04). The 1-year, 18-month, and 2-year survival rates for the combined studies (38 patients) were 32%, 21%, and 13%, respectively. At time of death 49% of patients were free from progression of their lymphoma. Administration of the oral regimen has resulted in 13% of patients surviving two years, and half of patients surviving free from progression of their lymphoma. This regimen is efficacious and considerate of patient quality-of-life issues. The addition of G-CSF to the regimen decreases the frequency of hospitalization for febrile neutropenia.

Practice effects, test-retest stability, and dual baseline assessments with the California Verbal Learning Test in an HIV sample.

Repeated neuropsychological assessments have been recently employed to investigate the natural course and effects of interventions in individuals with human immunodeficiency virus (HIV) infection. Important considerations when interpreting serial assessments are the roles of practice effects and test-retest reliability on follow-up performance. Although several statistical and methodological controls have been proposed for minimizing practice effects, they have not been empirically tested in HIV samples. Three groups (HIV+/symptomatic, HIV+/asymptomatic, HIV- "at risk" controls) were administered the California Verbal Learning Test (CVLT) twice with a brief test-retest interval. Significant practice effects were observed on six of the CVLT measures. Test-retest stability coefficients were reported. A third and fourth administration of the CVLT was conducted to observe the impact of the dual baseline assessment approach on test performance. Trend analyses indicated that the dual baseline approach is a viable method for minimizing practice effects. The dual baseline approach also lead to improvement in a number of the stability coefficients. Limitations and future directions are discussed.

Serial neuropsychological assessment with the National Institute of Mental Health (NIMH) AIDS Abbreviated Neuropsychological Battery.

The effect of repeated administration of the (NIMH) AIDS Abbreviated Neuropsychological Battery was evaluated in a group of "at risk" individuals who served as control subjects in a larger research project. Subjects' performance across five assessment points was evaluated by repeated measures analysis. Statistically significant trends were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task, and the State scale of the State-Trait Anxiety Inventory. No discernable trends were detected on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised, total time or errors on the Visual Search Task, the Hamilton Depression Rating Scale, or the Trait scale of the State-Trait Anxiety Inventory. The implications of these findings in both clinical and research settings are discussed.

Longitudinal analysis of olfactory deficits in HIV infection.

The presence and degree of odor identification deficits in 55 HIV-infected (30 asymptomatic, 25 symptomatic) and 29 HIV-negative at-risk control volunteers were examined longitudinally using the University of Pennsylvania Smell Identification Test (UPSIT). Factors other than HIV infection that could account for olfactory loss (i.e., sinusitis or upper respiratory infection) were also considered by obtaining MRI scans of the nasal passages and information from an olfaction questionnaire. No differences were found among groups at the first administration of the UPSIT, with significant differences among groups emerging at the 1-year and 2-year follow-ups. The symptomatic group showed a significant decline in odor identification scores across time, while means for the asymptomatic and control groups remained stable. The presence of sinusitis or an upper respiratory infection appeared to have no effect on odor identification. The implications for these findings in relationship to cognitive decline in neurodegenerative diseases are discussed.

Practice effects with the NIMH AIDS abbreviated neuropsychological battery.

The degree of practice effects with the Brief NIMH Neuropsychological Battery for HIV Infection and AIDS is reported using a 7-10 day test-retest interval. The patient groups were asymptomatic and symptomatic of HIV while the control group was made up of "at risk" volunteers. Statistically significant practice effects were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task and the Visual Search Test among the infected individuals. The controls subjects demonstrated statistically significant practice effects on all of the neuropsychological tests. The implications of these findings in prospective studies are discussed.

Effects of repeated neuropsychological assessments.

The effects of repeated administrations of neuropsychological instruments were evaluated in a group of chronic cigarette smokers who served as control subjects in a larger research project. Subjects performance on 13 neuropsychological variables across four assessments was evaluated using trend analyses. Statistically significant results were obtained on the Logical and Figurai Memory Subtests of the Wechsler Memory Scale (Form I-Russell's Revision) Part B of the Trail Making Test and the Grooved Pegboard Test (preferred hand). Of the remaining seven variables the Speech Sounds Perception Test, the Seashore Rhythm Test and Simple Auditory Reaction Time were highly consistent across all four assessments. The implications of these findings in clinical practice and research settings are addressed.

Computational Formulas for Multivariate Strength of Association from Approximate F and χ(2) Tests.

There are numerous occasions, in conducting a priori, prospective power analyses for example, in which a measure of multivariate strength of association is desired but cannot be recovered from published research reports. Measures of multivariate strength of association, defined as a function of the eigenvalues of Q(-1) EQH or (QE + QH)(-1)QH, may be computed in conjunction with any of four multivariate test statistics. A large majority of research publications that perform multivariate analyses do not report a measure of strength of association, nor do they report sufficient information to compute multivariate measures of strength of association. Most manuscripts, however, do typically report F-test or χ(2) approximations with associated degrees of freedom. In this article we develop computational formulas for recovering measures of strength of association from approximate F and χ(2) tests associated with four multivariate test statistics.

Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature.

Twenty-two cases of PCL were reviewed, in which 9 patients had AIDS and 13 did not. A review of the literature identified 247 cases of AIDS-related PCL. Differences between patients with AIDS and immunocompetent PCL were noted in our series. AIDS-related PCL when compared to non-AIDS PCL in our series has the following notable clinical features: 1) significantly younger age at presentation, median age 34 versus 59 years; 2) significantly higher incidence of B symptoms, 44% versus 8%; 3) worse median performance status at presentation, 3 versus 1; and, 4) shorter median survival, 3 versus 10 months. Differences in performance status and survival, however, were not significant. AIDS-related PCL is further characterized by frequent (44%) ring-enhancing mass lesions on head CT scan, a finding that makes it clinically difficult to distinguish from toxoplasmosis. Median survival appears to be improved in the absence of opportunistic infection at time of diagnosis of PCL, 6 versus 2 months. The therapeutic approach to patients with PCL, with and without AIDS, is variable. Combined modality therapy may improve the survival in patients with non-AIDS PCL. Therapy for patients with AIDS-related PCL is tailored to the status of the individual and it is, therefore, difficult to make comparisons to non-AIDS PCL patients. AIDS patients are often too ill to tolerate aggressive surgery or systemic treatment and in this instance, radiotherapy alone may be an acceptable alternative. Nonetheless, overall survival for patients with AIDS-related and non-AIDS PCL remains poor.

An assertiveness scale for adolescents.

This study developed a situation-specific instrument that measures assertiveness of adolescents. The Assertiveness Scale for Adolescents (ASA), which contains 33 items, was constructed using a multiple-choice format with three response alternatives. Based on data from 682 elementary and secondary school students, adequate reliability and validity of the ASA were obtained when tested against several variables about which predictions could be made. Potential use of the instrument in clinical diagnosis and research was discussed.

Endorsement of Ellis' Irrational Beliefs as a function of age.

Administered to a total of 788 children from grade 5 (N = 133), 7 (N = 193), 9 (N = 151), 11 (N = 158), and 13 (N = 153) a modification of Ellis' 11 irrational beliefs questionnaire reformulated for use with younger children. Results showed a linear decrease of percent item endorsement from younger to older children on 8 of 11 irrational ideas. Analysis of variance on the mean number of irrational ideas endorsed showed significant differences between children. Results indicated that endorsing irrational beliefs is a function of age and provided construct validity for the instrument presented here. Research and counseling uses of the scale are discussed.

Complex factorial structure of Ellis' Irrational Beliefs.

Previous research with a newly developed children's scale for measuring Ellis' constructs with regard to irrational beliefs showed that while the scale clearly reflected theoretically predicted developmental trends, the internal consistency reliability of the overall 11-item scale was relatively low (.56). This low internal consistency suggested that the 11 items were in fact heterogeneous and were not measuring a single, univocal, construct. An exploratory factor analysis was performed on the responses of 788 fifth-through thirteenth-grade students. Results of the Alpha factor and analysis clearly indicate that the scale is multifaceted, i.e., comprised of four orthogonal, interpretable factors. Estimates of internal consistency reliabilities for the separate factors, when corrected for length, revealed that each of the new factors was more reliable than the full scale score in this sample. Potential revisions of the scale, as well as cautions for its use in clinical applications on its present form are discussed.