Bercedis L. Peterson

PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS. PATIENTS AND METHODS: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m(2)/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P <.001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P =.007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P =.001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P =.03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C. CONCLUSION: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.

BACKGROUND: Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia. METHODS: Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body-surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter every 28 days). Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles. RESULTS: Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens. CONCLUSIONS: When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.

Bercedis Peterson, Frank E. Harrell, Jr, Partial Proportional Odds Models for Ordinal Response Variables, Journal of the Royal Statistical Society. Series C (Applied Statistics), Vol. 39, No. 2 (1990), pp. 205-217

OBJECTIVE: The effects of religious belief and activity on remission of depression were examined in medically ill hospitalized older patients. METHOD: Consecutive patients aged 60 years or over who had been admitted to medical inpatient services at a university medical center were screened for depressive symptoms. Of 111 patients scoring 16 or higher on the Center for Epidemiologic Studies Depression Scale, 94 were diagnosed with depressive disorder (DSM-III major depression or subsyndromal depression) by a psychiatrist using a structured psychiatric interview. After hospital discharge, depressed patients were followed up by telephone at 12-week intervals four times. At each follow-up contact, criterion symptoms were reassessed, and changes in each symptom over the interval since last contact were determined. The median follow-up time for 87 depressed patients was 47 weeks. Religious variables were examined as predictors of time to remission by means of a multivariate Cox model, with controls for demographic, physical health, psychosocial, and treatment factors. RESULTS: During the follow-up period, 47 patients (54.0%) had remissions; the median time to remission was 30 weeks. Intrinsic religiosity was significantly and independently related to time to remission, but church attendance and private religious activities were not. Depressed patients with higher intrinsic religiosity scores had more rapid remissions than patients with lower scores. CONCLUSIONS: In this study, greater intrinsic religiosity independently predicted shorter time to remission. To the authors' knowledge, this is the first report in which religiosity has been examined as a predictor of outcome of depressive disorder.

BACKGROUND: Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control. OBJECTIVE: To compare diabetes control in patients receiving nurse case management and patients receiving usual care. DESIGN: Randomized, controlled trial. SETTING: Primary care clinics in a group-model health maintenance organization (HMO). PATIENTS: 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus. INTERVENTION: The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians. MEASUREMENTS: The primary outcome, hemoglobin A1c (HbA1c) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed. RESULTS: 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events. CONCLUSIONS: A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO.