Psychotic depression and mortality

OBJECTIVE: Major depressive disorder is associated with elevated mortality rates that increase with the severity of depression. The authors hypothesized that patients with psychotic depression would have higher mortality rates than patients with nonpsychotic depression. METHOD: Survival analytic techniques were used to compare the vital status of 61 patients with psychotic major depression with that of 59 patients with nonpsychotic major depression up to 15 years after hospital admission. Medical status was assessed with the Cumulative Illness Rating Scale. Dexamethasone suppression test (DST) data were available for 101 patients. RESULTS: The mortality rate for subjects with psychotic depression was significantly greater than that for those with nonpsychotic depression, with 41% versus 20%, respectively, dying within 15 years after hospital admission. A proportional hazards model with age and medical status entered as covariates confirmed a significantly higher mortality rate in patients with psychotic depression (hazards ratio=2.31). A positive DST result was associated with psychotic depression but was not related to vital status. CONCLUSIONS: Patients with psychotic depression have a two-fold greater risk of death than do patients with severe, nonpsychotic major depression.     

Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia: in vitro and in vivo studies

BACKGROUND: Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS: Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-gamma (IFN-gamma) expression in CD34(+) cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-gamma blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1-3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS: In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-gamma-expressing CD4(+) cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3(+) MDS cells. Increased numbers of CD34(+) cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L-mediated inhibition and the blockade of IFN-gamma improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-gamma-expressing CD4(+) cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-gammablockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS: Increased frequency of IFN-gamma producing CD4(+) cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-gamma production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients.     

The performance of administrative and self-reported measures for risk adjustment of Veterans Affairs expenditures

OBJECTIVE: To evaluate the performance of different prospective risk adjustment models of outpatient, inpatient, and total expenditures of veterans who regularly use Veterans Affairs (VA) primary care. DATA SOURCES: We utilized administrative, survey and expenditure data on 14,449 VA patients enrolled in a randomized trial that gave providers regular patient health assessments. STUDY DESIGN: This cohort study compared five administrative data-based, two self-report risk adjusters, and base year expenditures in prospective models. DATA EXTRACTION METHODS: VA outpatient care and nonacute inpatient care expenditures were based on unit expenditures and utilization, while VA expenditures for acute inpatient care were calculated from a Medicare-based inpatient cost function. Risk adjusters for this sample were constructed from diagnosis, medication and self-report data collected during a clinical trial. Model performance was compared using adjusted R2 and predictive ratios. PRINCIPAL FINDINGS: In all expenditure models, administrative-based measures performed better than self-reported measures, which performed better than age and gender. The Diagnosis Cost Groups (DCG) model explained total expenditure variation (R2=7.2 percent) better than other models. Prior outpatient expenditures predicted outpatient expenditures best by far (R2=42 percent). Models with multiple measures improved overall prediction, reduced over-prediction of low expenditure quintiles, and reduced under-prediction in the highest quintile of expenditures. CONCLUSIONS: Prediction of VA total expenditures was poor because expenditure variation reflected utilization variation, but not patient severity. Base year expenditures were the best predictor of outpatient expenditures and nearly the best for total expenditures. Models that combined two or more risk adjusters predicted expenditures better than single-measure models, but are more difficult and expensive to apply.     

CDR3 spectratyping identifies clonal expansion within T-cell subpopulations that demonstrate therapeutic antitumor activity

BACKGROUND: Antigen-specific T cells undergoing clonal expansion share common rearrangements of the variable complementary determining region 3 (CDR3) of the T-cell receptor (TCR), which can be identified using polymerase chain reaction-based V beta (VB) spectratyping. The purpose of this study was to determine whether CDR3 spectratyping identifies clonal expansion within tumor-draining lymph node (TDLN) subpopulations with antitumor therapeutic activity. METHODS: Recently sensitized T cells from 4T1 murine mammary carcinoma TDLN were fractionated based on CD62L (L-selectin) surface expression before RNA isolation and culture. L-selectinlow and L-selectinhigh TDLN were analyzed for T-cell receptor usage by immunophenotyping and CDR3 spectratyping, and then culture activated with anti-CD3/IL-2 to assess therapeutic efficacy after adoptive transfer. RESULTS: Adoptive transfer experiments confirmed that mice treated with culture-activated L-selectinlow TDLN cells exhibited delayed subcutaneous tumor growth and prolonged survival as compared to control or L-selectinhigh-treated mice (P < .01). CDR3 spectratyping demonstrated oligoclonal skewing of the CDR3 regions within several VB families including VB3, VB5.2, and VB17 in L-selectinlow but not in L-selectinhigh TDLN. Although fluorescence-activated cell sorter analysis demonstrated the highest percentage of cells expressing VB13 usage in both populations, CDR3 spectratyping did not identify the presence of clonal expansion. CONCLUSIONS: These data suggest that CDR3 spectratyping may be useful in identifying T cells undergoing clonal expansion that demonstrate antitumor therapeutic activity.     

Evolution of clonal cytogenetic abnormalities in aplastic anemia

Prior to the introduction of effective therapies, the high mortality rates of severe aplastic anemia (AA) precluded recognition of late complications of this disease. Once the survival of AA improved, observation of clonal evolution raised questions as to whether the development of secondary myelodysplastic syndrome (MDS) is a part of the extended natural history of the disease or is related to the therapies applied. Clinical features of myelodysplasia and AA can overlap, and typical MDS may evolve as a complication of AA. Common pathophysiologic elements operate in these diseases and are subject to many studies and theories as to what mechanisms in AA may lead to the late evolution of MDS. Similarly, AA has been hypothesized to be a reflection of an over-reactive immune response triggered by the appearance of genetically altered and/or phenotypically abnormal dysplastic clones. Hypocellular variants of myelodysplasia and responsiveness of certain forms of MDS to immunosuppressive regimens serve as the most appealing examples of the intricate and close pathophysiologic relationship of this disease with AA. The diagnosis of clonal evolution in the course of AA can be obvious if secondary cytopenia involves hypercellularity and a high percentage of blasts. In addition, the occurrence of a new karyotypic defect objectively heralds the progression of disease to MDS. However, the diagnostic imprecision of dysplasia recognition in the context of marrow hypocellularity, inability to obtain informative cytogenetics, and a high proportion of MDS cases with normal karyoptype have hampered studies designed to determine the frequency and timing of MDS evolution in AA. In addition, the diagnostic criteria and definitions used are not unified. While some centers recognize that the abnormal karyotype does not preclude the diagnosis of AA; in others, the diagnosis of AA includes the presence of normal karyoptype. Many typical features of dysplastic evolution in AA have been clarified. For example, karyotypes most frequently encountered in MDS secondary to AA involve chromosomes 6, 7 and 8. The evolution rates seem to be in the range of 10 - 15% in 10 years, but there are no predictive clues as to which patients are at greatest risk for this complication. Study of the mechanisms of clonal evolution in AA may help understand the pathophysiology of other forms of MDS and leukemia and also the mechanisms of antileukemic surveillance. Clinically, identification of patients at increased risk for clonal complications may influence the choice of therapies applied.     

VA community-based outpatient clinics: cost performance measures

OBJECTIVE: To examine the direct costs of treating veterans in Community-Based Outpatient Clinics (CBOC) and primary care clinics operated by VA medical centers (VAMCs) between April 1998 and September 1998. RESEARCH DESIGN: In a retrospective observational study of patients in eighteen CBOCs and fourteen VAMCs, direct costs were compared. In addition, the costs of treating patients in new and established CBOCs were also examined. MEASURES: The three types of costs examined include direct cost per primary care visit, direct primary care cost per patient, and total direct cost per patient in ordinary least squares regressions with facility-specific random effects. Indirect costs for overhead and administration were excluded. All cost comparisons controlled for patient characteristics and case-mix differences via the Diagnostic Cost Group methodology. RESULTS: Results indicate that CBOC patients and VAMC patients had similar direct primary care costs on a per visit and per patient basis. Total direct costs for CBOC patients were lower compared with VAMC patients, because of lower specialty and ancillary care costs. Patients in new CBOCs had similar primary, specialty, ancillary and inpatient care costs when compared with patients in established CBOCs. CONCLUSION: Lower total costs for CBOC patients may be a consequence of substituting primary care at CBOCs for expensive specialty and ancillary care at VAMCs. CBOCs may be an alternative approach to providing care to veterans at a lower cost than traditional delivery models based in VA Medical Centers.     

VA community-based outpatient clinics: access and utilization performance measures

OBJECTIVES: The purpose of this study was to compare access and utilization performance measures between Community-Based Outpatient Clinics (CBOC) and primary care clinics at parent VA Medical Centers (VAMC) and between VA-staff CBOCs and contract CBOCs. METHODS: The study design was cross-sectional and retrospective. Performance measures were based on data routinely collected for administrative and research purposes by the VA. The sample included all primary care patients (n = 37,084) treated at the 38 CBOCs opened before 4/1/98 (30 VA-staff and 8 contract) and all primary care patients (n = 318,369) treated at the 32 parent VAMCs. Six months of service use data were used to derive the access and utilization performance measures. Multivariate regression analyses were used to control for observable casemix differences. RESULTS: CBOCs are attracting new high priority patients to the VA health care system. CBOC patients had more primary care encounters and fewer specialty encounters than patients in the primary care clinics of the parent VAMCs. VA-staffed CBOC patients had more primary care encounters and fewer specialty encounters than contract CBOC patients. CONCLUSIONS: CBOCs are helping the VA achieve its goals of attracting new patients and shifting the focus of care from the specialty to the primary care setting.