Veteran's health care: time for a change?

The Department of Veterans Affairs' mission is "to care for him who are shall have borne the battle for his widow and orphan." The Veterans Health Administration comprises 172 hospitals that are the hub of the health care delivery system. It is the largest provider of graduate medical education, and one of the major research organizations in the United States. The medical care budget exceeds $17 billion annually. Most of the persons cared for are not legally entitled to this health care based on service connected disability. The utilization of acute care hospital beds appears excessive when compared to that obtainable with managed care for Medicare or commercial insurance beneficiaries--the cost per member per month is three times higher. There may also be exploitation of the Veterans Administration hospitals by university medical schools. The Veterans Health Administration is a very expensive way to deliver care to entitled service connected veterans. Therefore, it is suggested that privatization be considered as an alternative vehicle for delivering health care.

The introduction of ambulatory electrocardiographic monitoring for the diagnosis and management of myocardial ischemia.

We report on the introduction of a new technology and a new method for the management of chronic coronary artery disease into a managed care environment. The introduction incurred substantial resistance from subspecialty consultants, primary care physicians, and top management. Strategies were developed to overcome these resistances. Modification of the program as well as the development of incentives occurred. These measures continue to evolve. The program, to date, has achieved approximately 50% penetration. The demonstration of better health outcomes and financial savings will almost certainly temper the resistance encountered from all three groups identified.

Preparation and administration of chemotherapy. Haematological consequences for hospital-based nurses.

This study examined the question of whether previous exposure to cytostatic drugs by oncology nurses was sufficient to lead to haematological phenotypical subclinical abnormalities which had previously been identified in a population of patients who had received chemotherapy as an adjuvant to breast surgery. A comparison of baseline haematological parameters, and the results of a prednisolone stimulation test, was made between nurses regularly coming into contact with such agents and age-adjusted group of nurses who had not been exposed. Although there is a persistent trend toward lower neutrophils, platelets, monocytes and neutrophil reserves in the nurses who handled antineoplastic agents, a statistically significant decrement in these parameters was not identified. Such a finding should help to reassure individuals who have had similar exposure, but does not negate the importance of following published recommended guidelines for the handling and dispensing of antineoplastic agents.

Decision analysis of estrogen and progesterone receptor testing in the management of breast cancer.

Estrogen receptor (ER) and progesterone receptor (PR) assays are used to guide the hormonal treatment of metastatic/recurrent carcinoma of the breast. Sensitivity, specificity, and predictive value were calculated in comparing no receptor testing, ER testing alone, PR testing alone, and ER and PR in parallel. Analyses demonstrate that the indications for utilizing receptor assays are influenced by the valuation of uncertain outcomes and whether hormonal therapy is routinely planned in the absence of receptor test information. The PR assay appears best suited when patient outcome values mandate minimizing the likelihood of a false-positive outcome, with a corresponding increase in the likelihood of a true-negative outcome, even if this results in a reduced chance of a true-positive outcome and an increased chance of a false-negative outcome. Test specificity gives PR an advantage in this case. The ER assay has a comparative advantage when there is little difference in value between true-negative and false-positive outcomes and the primary contribution of testing is to maximize true-positive outcomes, while correspondingly minimizing the false-negative outcomes. This requires high test sensitivity. In either case, parallel testing does not appear to add appreciably to single test performance.

Sister chromatid exchange analysis in nurses handling antineoplastic drugs.

Sister chromatid exchange (SCE) analyses were carried out in hospital nurses to determine whether an increased frequency of SCE may be used as an indicator of occupational exposure to potentially harmful antineoplastic drugs. In our study of 18 oncology nurses who handled these agents for an average of three days per week, we found no increase in mean SCE frequency (9.3 +/- 1.7 SCEs/cell) and no difference in the distribution of individual mean SCE frequencies compared to a group of 18 nurses who did not handle these drugs (9.5 +/- 1.5 SCEs/cell). There was a great deal of individual variation in mean SCE frequency as well as in SCE values in individual cells. No relationship with SCE frequency was found in terms of a subject's age, or the number of days of exposure to the drugs. Since conflicting results have been reported in persons handling antineoplastic drugs, SCE analysis alone is probably not a reliable indicator of exposure to possible mutagenic/carcinogenic effects of these drugs. SCE analysis may be helpful in conjunction with other studies, such as an analysis of urinary mutagens, or in studies of occupational exposure to agents other than antineoplastic drugs which may have a more noticeable effect on SCE frequency.

A trial of razoxane (ICRF-159) in patients with prior therapy for Hodgkin's lymphoma.

Razoxane (ICRF-159) was administered to 11 patients with Stage IV nodular sclerosing Hodgkin's lymphoma. A weekly schedule was employed with a starting dose of 1000 mg/m2 in divided doses. The dose was escalated up to 2000 mg/m2 weekly as tolerated. One objective partial remission was observed. The toxicity of the program was quite tolerable. Further trials of razoxane in this situation are not recommended.

Salvage therapy of aggressive non-Hodgkin's lymphoma with a combination of vinblastine, bleomycin, and cisplatin.

Thirteen patients with aggressive histologic types of non-Hodgkin's lymphoma had failed to respond or relapsed after intensive polychemotherapy of curative intent. They were treated with a combination of vinblastine, bleomycin, and cisplatin. All were Stage III or IV, and eight had systemic symptoms. There were five objective partial remissions, and no complete remissions. The Kaplan-Meier 50% survival estimate is 5 months from initiation of the salvage chemotherapy. Seven of 13 patients had grade II nausea and vomiting, and 7 had nadir platelet counts less than 70,000/mm3. All had significant anemia. There were two episodes of sepsis, and two patients had pulmonary and nephrotoxicity. The program is not effective in this situation, and is quite toxic.

Radiotherapy plus razoxane for advanced limited extent carcinoma of the lung.

Forty-four patients with limited extent American Joint Committee on Cancer Stage II-III non-small cell carcinoma of the lung were randomly assigned to potentially curative radiation therapy plus one of two schedules of razoxane. The weekly schedule was 1 gram per square meter body surface area (BSA) every 8 hours for two doses per week, and the daily schedule was a fixed dose of 250 mg per day. The 50% Kaplan-Meier survival estimate for both groups combined was 9 months. There was no survival difference between the two dose-schedules. Toxicity was formidable with an 82% incidence of esophagitis, and a 20% incidence of grade III-IV esophagitis. Fifty-nine percent of patients developed hematologic toxicity. This was greater with the weekly dose-schedule (P = 0.01). Forty-one percent of patients developed radiographic or symptomatic pneumonitis. One patient developed a fatal myelitis. This program is no more effective than irradiation alone, and has substantial morbidity.

A decision-analysis methodology for consideration of morbidity factors in clinical decision-making.

An explicit and systematic means of incorporation of good medical practice plus individual patient preferences (utilities) for pretreatment and treatment options for a serious but curable neoplastic disease has been investigated. The methodology allows important quality-of-life information to be transmitted to patients, with the goal of providing an improved basis for informed consent. The example of Hodgkin's lymphoma staging and treatment selection is used. Individual patient utilities can be expressed and incorporated into a formal decision analysis for those who face the option of selecting MOPP chemotherapy or of pursuing the staging process in order to obtain a chance of being treated appropriately with irradiation. Equal survival probabilities for the two options are assumed, thus the short- and long-term toxicities (quality of Life) are the determinants of the decision. Patient-derived utilities can be developed for the 15 categories of anticipated toxicity. This, together with probabilistic inputs regarding toxicity severity and duration, will yield expected utilities for each of the decision options. Three physicians were studied and evaluated in the role of a patient. The physicians' toxicity preferences were different and because of this the management option of choice was different for each. This methodology allows explicit patient preferences to be incorporated into medical decisions without the requirement for detailed patient understanding of testing and/or treatment morbidity frequency and severity.

Comparison of treatments for symptomatic Hodgkin's lymphoma employing decision analysis.

A decision analysis methodology has been developed for addressing a comparison of immediate MOPP chemotherapy without staging to staging followed by medically indicated chemotherapy (MOPP) or radiotherapy (XRT). The patients would have symptomatic Hodgkin's lymphoma. Each test and therapy was previously described in terms of 15 toxicity categories. Each was assigned a probability of the occurrence over the five grades of toxicity. Each grade was assigned an expected duration of the toxicity for each test or therapy. Both actual probabilities and judgmental probabilities were used. Utilities for the 15 toxicity categories were solicited. The staging-test-morbidity outcomes only pertained to decision paths which were directed at a chance to receive XRT as the medically dictated therapy. Relative scalar weights were assigned to each grade IV toxicity of zero utility by three physicians. An additive (linear) model was used to compute composite utilities for the paths. There were three different outcomes for these individuals in the initial analysis: 1) MOPP immediately without staging; 2) MOPP immediately or if staging had proceeded to a negative bone marrow then further staging was preferred; and 3) Staging in order to have any change to receive XRT. When a lower toxicity program of presumed equal efficacy was substituted (ChlVPP) the decision changed so that all three participants now would receive ChlVPP instead of staging based on their personal preferences about morbidity outcomes. Decision analysis can contribute to selection between treatments based on differences in an individual's preferences in regard to varying degrees and spectra of toxicity.

Vinblastine, bleomycin, and cis-platin as salvage therapy for MOPP treated patients with Hodgkin's lymphoma.

Seven patients with active Hodgkin's lymphoma who had relapsed 4-39 months following six or more cycles of MOPP were treated with a combination of vinblastine-bleomycin-cis-platin (VBP). Six patients attained a partial response of 1-8 months duration. There were no complete responses. The projected maximum long-term disease-free survivorship with this salvage program is less than 16%. All observed patients had Grade II-III nausea and vomiting, and neutrophil nadir counts less than 700/mm3. Three patients had platelet counts less than or equal to 85,000/mm3. This program does not have significant potential as a salvage therapy for patients with Hodgkin's lymphoma relapsing after MOPP chemotherapy.

Superficial bladder cancer: progression and recurrence.

The tumors in 249 patients presenting initially with stages Ta and T1 bladder cancer were analyzed for tumor progression and recurrence. Only transurethral resection and/or fulguration was used before the first recurrence. Patients who received intravesical chemotherapy after the first tumor recurrence were excluded from an analysis of progression. Progression according to stages Ta and T1, and grades I, II and III was 4, 30, 2, 11 and 45 per cent, respectively. All differences were statistically significant. Progression also correlated with nontumor dysplasia and size. High tumor grade, lamina propria invasion, atypia elsewhere in the bladder, positive urinary cytology, tumor multiplicity and large tumors were associated with shorter intervals free of disease.

A comparison of cisplatin and the combination of cisplatin and cyclophosphamide in advanced urothelial cancer. A National Bladder Cancer Collaborative Group A Study.

A prospective multi-institutional randomized trial compared the use of cisplatin (DDP) alone to the combination of DDP and cyclophosphamide in patients with advanced urothelial cancer. Patients were stratified according to measurable or evaluable tumor and performance status. The dose of DDP was 70 mg/m2 and the initial dose of cyclophosphamide was 750 mg/m2. There were ten objective responders (20%), including five complete responders, among the 50 evaluable patients who received DDP alone, and seven responders (11.9%), three complete, among the 59 receiving the combination therapy. Approximately one third of the patients in each treatment arm were stable at the nine-week evaluation. There was no statistical significance between the response rates in the two treatment arms.

Multimodality therapy of favorable prognosis non-Hodgkin's lymphoma.

Twenty-seven previously untreated patients with favorable prognosis non-Hodgkin's lymphoma were treated with a combination of total body irradiation followed by cyclophosphamide - vincristine - prednisone (CVP). The dose of total body irradiation was planned to be 150 rad followed by 6 cycles of chemotherapy. The complete response rate was 59%; the complete plus partial response rate, 93%. The 50% disease-free survival was 8 months. The actuarial projected 5 year survival was 60% and the disease-free survival at 5 years was 27%. The program was well tolerated by the majority of patients. It is possible for some patients with favorable non-Hodgkin's lymphomas to achieve prolonged periods of disease-free survival when treated with combinations of irradiation plus chemotherapy.

Predicting therapeutic outcome in patients with diffuse histiocytic lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP).

Seventy-five patients with diffuse histiocytic lymphoma (DHL) ranging in age from 33 to 94 years were treated with cyclophosphamide, Adriamycin, vincristine and prednisone (CHOP). Thirty-eight patients (51%) achieved complete remission, but nine of these patients relapsed after remission lasting one to 23 months (median time to relapse, four months). We used multivariate analysis to identify those characteristics that significantly affected treatment outcome. The chances for complete remission were adversely affected by DHL appearing after histologic conversion from another lymphoma (P = 0.006), the presence of systemic symptoms (P = 0.24), and not having the large noncleaved (LNC) histologic subtype (P = 0.40). The chance for relapse from complete remission was increased only by the presence of systemic symptoms (P = 0.042). Overall survival was adversely affected by the presence of bone marrow involvement (P = 0.002), having other than LNC histologic subtype (P = .010), and the presence of systemic symptoms (P = 0.043). It appears that patients whose DHL appears de novo and who also are symptom status A (70% long-term disease-free survival) or have the LNC histologic subtype (67% long-term disease-free survival) have an excellent outlook when treated with CHOP at the doses used in this study. However, patients with B symptoms (16% long-term disease-free survival), histologic conversion to DHL (8% long-term disease-free survival), previous chemotherapy (8% long-term disease-free survival), and bone marrow involvement (8% long-term disease-free survival) respond poorly and for these patients other treatments need to be identified. In addition, patients with B symptoms who achieve complete remission with CHOP are at high risk to relapse (59% relapse rate) and should be considered for "intensification" therapy after complete remission is documented.

Marrow neutrophil reserve after adjuvant chemotherapy for carcinoma of the breast.

The hematologic factors of 16 female patients with breast carcinoma who had received adjuvant chemotherapy with L-phenylalanine-based programs for two years were compared with those for 13 normal female volunteers of similar age. The findings include significant suppression of the mean hemoglobin level, of leukocyte counts, and of circulating neutrophils and lymphocytes in patients 3-27 months after chemotherapy. Marrow neutrophil reserve studies with prednisolone stimulation again demonstrated significant suppression for the patients who had received chemotherapy. The authors conclude that there is a chronic hematologic toxicity associated with this therapy.

Reasons for failure of MOPP to cure Hodgkin's disease: The importance of dose and schedule.

Thirty-six patients with advanced Hodgkin's disease who were treated primarily with MOPP were evaluated to determine the reasons for MOPP failure. Complete remission was achieved in 22 (61%) of the patients, and the predicted 5-year survival rate for all patients is 60%. Reasons for the failure of MOPP to cure patients in this series included: 1) Idiosyncratic drug reactions in 2 patients (6%). MOPP was discontinued after one cycle because of drug-related hepatitis or skin rash; 2) Resistant disease in 8 patients (22%). Primary treatment failure was significantly associated with the presence of B symptoms (p = .005) and age greater than 40 years (p = .02); 3) Death from complicating infection in 5 patients (14%). Four patients died without evidence of Hodgkin's disease while responding to MOPP from pneumocystis pneumonia, viral pneumonia, bacterial pneumonia, or bacterial septicemia. One patient died in complete remission from sudden, overwhelming sepsis; 4) Relapse from complete remission in 4 patients (11%). All patients who relapsed had deviations from the planned dose or timing of MOPP. Remission duration was shorter (p = .06) in patients with documented deviations in MOPP administration than in patients without such changes. It appears that new treatment approaches are needed for patients with B symptoms, and that failure to deliver MOPP on schedule in the planned dose increases the risk of relapse.