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March 15, 2001
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A Monoclonal Antibody against HER2 for Metastatic Breast Cancer
In about 25 percent of cases of breast cancer, the tumor cells overexpress a protein called HER2. In this study, the therapeutic efficacy of trastuzumab, a monoclonal antibody against HER2, was tested in women with metastatic, HER2-positive breast cancer. Women were randomly assigned to receive either the usual chemotherapy plus trastuzumab or chemotherapy alone. The combined treatment resulted in a better outcome than did chemotherapy alone. Cardiotoxicity, manifested by heart failure, occurred in 27 percent of the women who received combined treatment that included an anthracycline.
HER2, a receptor for epidermal growth factor, is a unique therapeutic target in breast cancer. Chemotherapy plus a monoclonal antibody directed against the HER2 protein produced encouraging results in a disease with a poor prognosis. However, the cardiotoxicity of the antibody is quite worrisome, especially because anthracyclines, which are often used to treat breast cancer, are also cardiotoxic.
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ABO-Incompatible Heart Transplantation in Infants
The availability of donor hearts for infants with lethal heart diseases is very limited. This study examined whether blood-group compatibility between donors and recipients is required for successful heart transplantation. Ten infants who had severe congenital heart disease or cardiomyopathy received hearts from ABO-incompatible donors. The overall survival was 80 percent. No infant had hyperacute rejection, and there was no morbidity related to the ABO incompatibility between donor and recipient.
The unexpected success of these transplantations may be due in part to the immaturity of the immune system in very young infants. Heart transplantation in ABO-incompatible donor-recipient pairs may shorten the waiting period for grafts and thereby reduce mortality from cardiac disease in these very sick infants.
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La Crosse Encephalitis in Children
This report from West Virginia describes the presentation and clinical course of 127 children with serologically diagnosed La Crosse encephalitis. Nearly half had seizures, including some with status epilepticus, and in 13 percent there were signs of increased intracranial pressure. All the children survived, but some had neurologic deficits at discharge and cognitive deficits at follow-up a year later.
This large series suggests that this mosquito-borne, arboviral infection may be underrecognized. Some of the patients initially received a diagnosis of herpes simplex encephalitis, enteroviral meningitis, or partially treated bacterial meningitis.
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Appendectomy and Protection against Ulcerative Colitis
The cause of ulcerative colitis is not known. Recent reports have suggested that there is a low rate of ulcerative colitis among patients who have had an appendectomy. This study from Sweden further characterizes the relation between appendectomy and the subsequent development of ulcerative colitis. The investigators found that appendectomy for an inflammatory condition, such as appendicitis or lymphadenitis, but not for nonspecific abdominal pain, was associated with a low risk of subsequent ulcerative colitis. This inverse relation was limited to patients who underwent appendectomy before the age of 20 years.
These findings strengthen the evidence for an inverse relation between appendectomy and ulcerative colitis. Although the explanation for the inverse relation remains unclear, this report may help elucidate the pathogenesis of ulcerative colitis.
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Changes in the Cost of Care for HIV Infection
Highly active antiretroviral therapy is effective but expensive. For this analysis, investigators from the HIV Cost and Services Utilization Study used nationally representative data to examine changes in the cost of care since the introduction of such therapy. From 1996 to 1998, the estimated annual total cost per patient declined from $20,300 to $18,300. Increases in the expenditures for drugs were more than offset by reductions in the expenditures for hospital care. The use of highly active antiretroviral therapy was independently associated with a reduction in total expenditures.
The net result of more effective treatment for HIV infection appears to be a reduction in the total use of resources, largely because of the savings from fewer hospitalizations. However, the benefits are not reaching underserved groups, including blacks, women, and patients without private health insurance.
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The Cost Effectiveness of Antiretroviral Therapy for HIV Disease
Using data from several major clinical trials, this study estimates the clinical benefits and cost effectiveness of three-drug antiretroviral therapy for HIV disease. A simulation model was developed that included the CD4 cell count and HIV RNA level as predictors of disease progression. The incremental cost effectiveness of triple-drug therapy, as compared with no therapy, was $23,000 per quality-adjusted year of life gained.
This analysis shows that the treatment of HIV-infected patients with three-drug antiretroviral therapy is a cost-effective use of resources. According to the results of this study, antiretroviral therapy for HIV disease is more cost effective than treatment for hypercholesterolemia and radiation therapy for early-stage breast cancer.
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