Cost-effectiveness of screening for hereditary hemochromatosis.

BACKGROUND: Recent studies have estimated the prevalence of hereditary hemochromatosis to be 3 to 8 per 1000. Early detection and treatment can prevent disease manifestations and normalize life expectancy. We used decision analysis techniques to determine whether screening the population at large for hereditary hemochromatosis would be cost-effective. METHODS: We constructed a model to compare the cost and outcome of a strategy of performing screening transferrin saturation tests on cohorts of 30-year old men with that of awaiting symptomatic disease. Baseline estimates of disease prevalence and complication rates were based on the published literature. Costs of treatment were estimated based on prevailing local costs. Sensitivity analyses were then conducted to determine which variables had the most significant impact on the decision to screen. RESULTS: At our baseline estimates, the decision to screen was found to be a dominant strategy and resulted in cost saving. Sensitivity analysis showed that four variables had the most significant impact on the decision to screen: (1) the prevalence of hereditary hemochromatosis, (2) the probability of developing disease manifestations, (3) the cost of the screening test, and (4) the discount rate. Screening was a dominant strategy for asymptomatic men provided that the prevalence of hereditary hemochromatosis was at least 3 per 1000, the probability of developing disease manifestations was greater than 0.4, the test cost was less than $12, and the discount rate was less than 3%. Using more pessimistic estimates, the cost per life year saved was still less than that considered acceptable for many common medical interventions. CONCLUSION: Screening for hereditary hemochromatosis has a favorable cost-effectiveness ratio over a wide range of assumptions. We recommend that practitioners consider including a serum transferrin saturation test in their routine screening for asymptomatic white men.

Septicemia, rash, and pulmonary infiltrates secondary to Corynebacterium group JK infection.

This report describes a leukemic patient undergoing induction therapy in whom a Corynebacterium JK infection developed while he was leukopenic. The clinical triad of perirectal inflammation, skin lesions, and interstitial lung infiltrates, which has not previously been reported, is discussed. Characteristics of the organism and postulated routes of infection as well as treatment are explored.

A randomized phase II study of m-AMSA (NSC 249992) and neocarzinostatin (NSC 157365) in non-small cell bronchogenic carcinoma. An Eastern Cooperative Group Study.

Eighty-nine patients with advanced non-small cell bronchogenic carcinoma were treated with either m-AMSA 120 mg/m2 intravenously every 3 weeks or neocarzinostatin 2.0 mg/m2 intravenously daily X 5 every 4 weeks. There were no responses in 40 evaluable patients who received m-AMSA and three partial responses (7.5%) in 40 patients who received neocarzinostatin. Two patients receiving m-AMSA had drug-related deaths. For m-AMSA the major toxicities were hematologic, while for neocarzinostatin the major toxicities were hematologic, gastrointestinal, and fever. We conclude that m-AMSA is inactive while neocarzinostatin has minimal activity in non-small cell bronchogenic carcinoma.

Leukemia in radiation-treated patients: cytogenetic studies in eight cases.

Abnormal chromosomes have been found in various clinical settings and in cancer patients. Eight patients developed leukemia several years after the diagnosis and treatment of a primary malignant disease. All the patients were being treated with irradiation, and five of them also received chemotherapy, notably, alkylating agents. The type of leukemias and the interval between irradiation and leukemia parallel very well with those reported from the atomic bomb casualties. Chromosomal abnormalities were seen in all the patients. These abnormalities have been reported in irradiated normal persons without developed leukemias. These findings suggest that the development of clinical cancer or leukemia may depend, not only on the presence of abnormal cells, but also on other factors. Perhaps the environment that allowed the original cancer to develop in our patients is capable of allowing the radiation-induced abnormal cells to be expressed as clinical leukemia.

Physician coverage of therapeutic apheresis.

A "snapshot" survey of physician coverage for evaluation and supervision of therapeutic apheresis procedures shows significant variation in current clinical practice between 39 blood center-and 41 non-blood center-based programs. Whereas 56% of blood center-based programs usually require physician's "in person" evaluation of the patient, 86% of non-blood center programs do (P < .005). Similarly, non-blood center-based programs were more likely to have physicians on the premises to supervise first and subsequent procedures and to bill separately for medical coverage. These differences were unrelated to location of the procedure (in hospital, blood bank, outpatient department, or other), the size of the program, or any information provided on adverse reactions.

Definitive treatment of anal-canal carcinoma by means of radiation therapy and chemotherapy.

In the light of the relatively poor response of squamous-cell carcinoma of the anus to surgery, an alternative method of treatment has been sought. During the past five years, in a series of 19 patients, the first four were treated by a combination of preoperative irradiation, 5-fluorouracil (5-FU) and mitomycin C as radiosensitizers plus surgery. As a result of complete responses at the time of surgery of all these patients, 15 additional patients have been treated by definitive radiotherapy combined with 5-FU and mitomycin C, thereby avoiding abdominoperineal resection. Eighteen patients had local control, and the one treatment failure is discussed. The method of treatment is described, and recommendations are made concerning techniques to be used or to be avoided.

Modifications in the classification of primary myelodysplastic syndromes: the addition of a scoring system.

A retrospective series of patients with the primary myelodysplastic syndrome has been reviewed and the survival updated. A scoring system is proposed that has advantages in predicting survival outcome. The importance of either dysmegakaryocytopoiesis or dysgranulocytopoiesis is emphasized because of its prognostic impact on leukaemic progression. Over 50 per cent of the patients die from either acute leukaemia or consequences of defective marrow production of granulocytes and platelets. Although only a few cases were included, the RAEB-T group has a very poor outcome and appears much closer to FAB M2 in biologic behaviour than RAEB. Both the criteria for the FAB subtypes and the scoring system can be applied easily in each case of myelodysplasia. Of the 56 patients only 9 were still alive as of April, 1984. Eight of these were in the RA-S and RA categories (or using the scoring system grouping 7 were group 1). All of the 16 patients who progressed to overt AML died within 4 weeks, and none was treated with chemotherapy. Of the remaining 31 patients, half died as a result of infection and/or haemorrhage and the remainder from apparently unrelated causes (cardiovascular, carcinoma, renal failure). These latter deaths are not surprising in light of the median age of 72 years.

Acute respiratory distress syndrome with pulmonary calcification in two patients with B cell malignancies.

Two patients, one with B cell lymphoma and hypercalcemia and the other with multiple myeloma and hypercalcemia developed acute progressive respiratory insufficiency characteristic of the adult respiratory distress syndrome (ARDS). Both were intubated and placed on mechanical ventilation. Lung compliance deteriorated and became refractory to mechanical inflation. Examination of the lungs at post mortem examination disclosed widespread calcification within alveolar septa and diffuse alveolar damage with hyaline membrane formation consistent with ARDS. Although ARDS has been described with lymphomatous involvement of the lungs, its development in association with metastatic calcification in B cell malignancy has not been previously reported.

Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.