Citations

This study examined how information obtained from an adolescent screening instrument administered in a medical clinic is affected by the method of data collection and knowledge that a summary report would be given to the provider. The Adolescent Health Review (AHR) was administered to 610 adolescent patients randomly assigned to 1 of 3 conditions to test the effect of mode of administration (paper vs. computer) and disclosure of results to the provider versus only to researchers (using the computer version). The AHR obtained information on mental health, sexual experiences, and use of psychoactive substances. Response patterns varied by mode of administration, with the paper version generally eliciting higher, and arguably more accurate, rates of disclosure. Knowing that the results would be provided to the doctor further attenuated disclosure. Results suggest that the paper version's higher rates of reporting must be weighed against the computer version's benefits of automated scoring and reporting.

AbstractBuilding on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

Purpose Retrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH. Patients and Methods Between 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/I) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years. Results Chromosomal abnormalities detected by FISH at study entry predicted overall survival. Eighteen patients experienced clonal evolution during follow-up. The rate of clonal evolution increased with duration of follow-up with only one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63; 27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of ZAP-70–negative and 42% of ZAP-70–positive patients at 5+ years (P = .008). Conclusion This clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.

OBJECTIVE—The degree to which chronic glycemic exposure (CGE) (fasting plasma glucose [FPG], HbA1c [A1C], duration of diabetes, age at onset of diabetes, or combinations of these) is associated with or predicts the severity of microvessel complications is unsettled. Specifically, we test whether combinations of components correlate and predict complications better than individual components. RESEARCH DESIGN AND METHODS—Correlations and predictions of CGE and complications were assessed in the Rochester Diabetic Neuropathy Study, a population-based, cross-sectional, and longitudinal epidemiologic survey of 504 patients with diabetes followed for up to 20 years. RESULTS—In multivariate analysis, A1C and duration of diabetes (and to a lesser degree age at onset of diabetes but not FPG) were the main significant CGE risk covariates for complications. A derived glycemic exposure index (GEi) correlated with and predicted complications better than did individual components. Composite or staged measures of polyneuropathy provided higher correlations and better predictions than did dichotomous measures of whether polyneuropathy was present or not. Generally, the mean GEi was significantly higher with increasing stages of severity of complications. CONCLUSIONS—A combination of A1C, duration of diabetes, and age at onset of diabetes (a mathematical index, GEi) correlates significantly with complications and predicts later complications better than single components of CGE. Serial measures of A1C improved the correlations and predictions. For polyneuropathy, continuous or staged measurements performed better than dichotomous judgments. Even with intensive assessment of CGE and complications over long times, only about one-third of the variability of the severity of complications is explained, emphasizing the role of other putative risk covariates.

Strict morphologic criteria must be used for patient selection to achieve durable success with endovascular aortic aneurysm repair (EVAR). The goal of this study was to assess morphologic suitability (MS) of abdominal aortic aneurysms (AAAs) for 2 currently approved bifurcated stent grafts and identify reasons for exclusion from EVAR. The authors reviewed the electronic charts of 1,795 consecutive patients who were diagnosed as having AAA between January 1999 and July 2001 at their institution. Three hundred and twenty patients had an AAA with a diameter of =5.0 cm, measured on computed tomography (CT). The records of 301 patients, 254 men, 47 women, with a mean age of 74 years were available for review, and these patients constituted the study cohort. Criteria used for MS included a proximal neck length =15 mm; neck diameter between 18 and 26 mm; neck angulation =60°; common or external iliac artery (CIA or EIA) diameters of 7–16 mm and 8–13 mm, respectively, for AneuRx (Medtronic Ave, Santa Rosa, CA) and Ancure (Guidant Cardiac and Vascular Division, Menlo Park, CA) bifurcated grafts. AAAs were suitable for AneuRx device in 14% of patients (43 of 301; 95% CI = 11–19%) and for Ancure in 5% (16 of 301; 95% CI = 3.1–9%). The main reason for exclusion was an inadequate proximal aortic neck (73%). The neck was too short in 49.5%, too wide in 64% and badly angulated in 12% of the patients. Iliac artery morphology precluded EVAR with AneuRx and Ancure devices in 52% and 80%. Both CIAs were too wide for EVAR in 43% and 77%, respectively. When iliac artery diameter =20 mm was accepted, iliac suitability for AneuRx increased from 49% to 70% and overall suitability increased from 14% to 20%. When more permissive criteria were used for MS (neck length =10 mm, neck diameter =30 mm, CIA =20), 39% of patients became candidates for EVAR. More than three fourths of the patients with an AAA =5.0 cm in size, seen in a tertiary referral center, are morphologically not suitable for EVAR using 2 currently approved bifurcated endografts. The main reasons for exclusion are a short or wide proximal aortic neck. Considerable changes in size of the devices and in proximal attachment techniques have to occur before most AAAs will be suitable for EVAR.

Abstract Purpose: Vinorelbine (Navelbine) is an orally absorbable Vinca with broad antitumor activity. It differs from other Vinca in that it is structurally modified on the catharanthine nucleus and has differential actions on tubulin that render it less neurotoxic than other compounds in this class. We conducted a phase I study of vinorelbine given the activity of Vinca alkaloids in many pediatric tumors. Experimental Design: We evaluated the safety and pharmacokinetics of oral and i.v. vinorelbine administered weekly × 6 in children (age, 2-17 years) with different tumors. Patients with disease involvement in the bone marrow were eligible but were stratified and dose-escalated separately. Oral vinorelbine (week 1) was administered as liquid-filled gelatin capsules at thrice the i.v. dose. Intravenous vinorelbine doses of 24 to 37.5 mg/m2 were administered on weeks 2 to 6. Results: The dose-limiting toxicity in patients without marrow involvement was reversible neutropenia. Common nonhematologic toxicities included ≤ grade 2 nausea/vomiting and increased hepatic transaminases. A higher mean i.v. ClTB was observed (1.75 ± 1.0 L/h/kg) compared with adult reports, with a mean t1/2B of 16.5 ± 9.7 hours. Mean oral bioavailability was 28.5 ± 22.5%. The apparent oral clearance (12.1 ± 13.0 L/h/kg) and volume of distribution (69.4 ± 30.6 L/kg) were substantially higher than in adults given similar oral doses. Conclusions: The maximum tolerated dose in children without bone marrow involvement was 30 mg/m2, similar to that reported in adults, with myelosuppression being the dose-limiting toxicity. Higher plasma clearance resulted in lower area under the plasma concentration-time curves at a given dose compared with that reported in adults.

Abstract Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. Results Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. Conclusions TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.