![[Postgraduate Medicine]](../../../graphics/logonew.gif)
[an error occurred while processing this directive] 
|
||
The medical reference you rely on for trustworthy, current information about diagnosis and treatment is now available online. Harrison's Online offers:
To sign up for your free individual 7-day trial, send an e-mail to: postgrad@mcgraw-hill.com Postgraduate Medicine and Harrison's Online are published by The McGraw-Hill Companies, Inc. |
Harrison's Online Updates
as featured in VOL 118 / NO 3 / SEPTEMBER 2005 / POSTGRADUATE MEDICINE
PGM PICKRisk of breast cancer after a biopsy showing benign disease
Dan L. Longo The widespread use of mammography beginning at age 40 years to look for early stage breast cancer has resulted in a substantial increase in breast biopsies. Among women who begin annual mammography at age 40, over 49% will have a suspicious mammographic lesion after 10 years of testing and 20% will have a biopsy, the vast majority of which will not reveal breast cancer. Instead, these women will be diagnosed with a benign breast lesion, usually fibrocystic disease. Having a previous breast biopsy is a risk factor for the development of breast cancer, but the nature of the risk has been poorly defined. Hartmann and her colleagues (2005) retrospectively examined the risk of developing breast cancer in a cohort of 9087 women who had been followed a median of 15 years with a diagnosis of benign breast disease. The median age was 51 years. Benign breast disease was divided into three categories. The most common abnormality is fibrocystic disease without a proliferative component, which affected 6063 patients. When some ductal proliferation was noted, the condition was called proliferative fibrocystic disease without cellular atypia; this diagnosis was made in 2690 patients. When ductal proliferation and cellular atypia was noted, the condition was called atypical hyperplasia; 336 women had this diagnosis. Over the course of follow-up 707 women with a diagnosis of benign breast disease developed breast cancer; according to SEER data from the National Cancer Institute, 453 cases would have been expected in an age-matched patient population without benign breast disease. This gave an overall relative risk of 1.56. When risk was examined as a function of type of benign breast disease, the relative risk was 1.27 for women with nonproliferative disease, 1.88 for women with proliferative disease without atypia, and 4.24 for women with atypical hyperplasia. Family history was an independent risk factor. Indeed, nearly all the increased risk of breast cancer in women with nonproliferative disease was related to family history; women without a family history of breast cancer who had nonproliferative benign breast disease had no increased risk. The breast cancers that developed had no clear predilection for the breast in which benign disease had previously been detected; 55% of the breast cancers were in the ipsilateral and 45% were in the contralateral breast. The ipsilateral risk was higher in the first 5 years after diagnosis; subsequent breast cancers occurring within 5 years were nearly twice as likely to be in the ipsilateral breast than in the contralateral breast. While the relative risks seem alarming, it is important to relate these relative risks to the absolute risks. According to an accompanying editorial (Elmore and Gigerenzer, 2005), among 100 women in the general population, 5 breast cancers will develop over a 15-year period. For women with nonproliferative benign breast lesions, the relative risk in this study would translate into a single additional case among 100 women in 15 years. By contrast, 19 of 100 women with atypical hyperplasia would be expected to develop breast cancer over 15 years. Thus, the best news in the data is the finding that the majority of women who have benign breast disease are not at increased risk of breast cancer because of the benign breast disease. About two-thirds of women with benign breast disease have nonproliferative fibrocystic disease and are at no increased risk. On the other hand, women with proliferative breast lesions, particularly in the presence of cellular atypia, have a significantly increased risk of breast cancer and should be followed closely. It is not yet clear whether such women would benefit from having MRI scans in place of mammograms. Studies addressing that question are ongoing. If a woman with atypical hyperplasia has other breast cancer risk factors, she and her physician may need to consider chemoprevention with tamoxifen. References Elmore JG, Gigerenzer G: Benign breast disease--the risks of communicating risk. N Engl J Med 353:297, 2005 Hartmann LC, et al: Benign breast disease and the risk of breast cancer. N Engl J Med 353:229, 2005
COGNITIVE IMPAIRMENTLimited value of donepezil for mild cognitive impairment
S. Andrew Josephson Mild cognitive impairment (MCI) is a term used for patients with cognitive dysfunction who do not yet meet criteria for dementia, due usually to lack of functional impairment. The most common type of MCI is "amnestic MCI," where memory is the cognitive domain most prominently affected. It is known that patients with amnestic MCI have a rate of conversion to Alzheimer's disease (AD) of 10 to 15% per year. This figure is nearly 10-fold higher than the rate of conversion to AD in healthy elderly persons, leading many to view amnestic MCI as a transitional state between normal cognitive function and AD. A recently published trial examined two compounds, vitamin E and a cholinesterase inhibitor (donepezil), for their efficacy in MCI patients to prevent conversion to AD. Over 750 subjects were enrolled in multiple centers in the United States and Canada with a diagnosis of amnestic MCI. All subjects received a multivitamin containing a trivial (15 IU) amount of vitamin E. They were then assigned into three groups: (1) 5 to 10 mg daily of donepezil and a placebo, (2) 1000 to 2000 IU daily of vitamin E and placebo, or (3) two placebos. These three groups were stratified to balance Mini Mental Status Examination (MMSE) scores, age, and APOe4 status. The primary end point in this study was the time to development of possible or probable AD according to established clinical criteria. There were no significant differences over the 3-year period of the trial in the conversion of amnestic MCI to AD in either the donepezil or vitamin E groups compared with placebo. A prespecified assessment of outcomes at each 6-month interval throughout the trial showed that donepezil, but not vitamin E, decreased the risk of progression from amnestic MCI to AD in the first 12 months but not thereafter. Adverse events in the vitamin E group were not different than placebo while those patients taking donepezil had statistically higher rates of diarrhea, muscle cramps, insomnia, nausea, abnormal dreams, vomiting, and arthritis. An interesting subgroup in this study were the over 400 patients who carried at least one copy of the APOe4 allele. In this population, treatment with donepezil, but not vitamin E, led to a reduction of conversion to AD by one-third, although the authors caution that the study was not powered to make the distinction between responses to donepezil in patients with or without the APOe4 allele. This treatment effect in this subgroup may warrant further study. The results of this study provide important, much-needed guidance for physicians caring for patients with amnestic MCI. Vitamin E has no benefit in these patients in reducing their risk of progressing to AD. Donepezil may have some benefit in delaying AD for up to 12 months, but this drug leads to no differences in the rate of AD in these patients versus placebo at 3 years. As these two compounds provide little or no benefit for this condition, novel therapeutic agents are needed in patients with amnestic MCI in hopes of reducing their elevated chances of progression to AD. Reference Petersen RC et al: Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 352:2379, 2005
RESPIRATORY DISEASERespiratory syncytial virus infection in elderly, high-risk, and hospitalized adults
Tamar F. Barlam Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in young children, including infants. Its role in respiratory disease in elderly patients is less well understood. Mathematical models of the estimated adult disease burden indicate that about 10,000 deaths each year in persons >65 years of age in the United States may be due to RSV. The development of vaccines and antiviral treatments against RSV may be important, but the epidemiology and health effects of RSV infection in adulthood must first be better defined. Falsey and colleagues (2005) prospectively identified RSV infections during four consecutive winters in three cohorts: healthy, community-dwelling elderly persons; high-risk adults; and persons hospitalized with acute cardiopulmonary disease. The study took place in Rochester, New York, during the winters of 1999 through 2003. High-risk adults included persons >21 years of age who had congestive heart failure or chronic pulmonary disease. Baseline demographic characteristics, medical history, and functional performance were recorded for each participant at enrollment, and blood samples were collected before and after the RSV season. Elderly and high-risk participants in the community notified study personnel if they developed symptoms of a respiratory illness or worsening of baseline cardiopulmonary symptoms. Home visits were conducted, and investigators elicited a history of the illness, conducted a physical examination, and collected nasopharyngeal swabs and blood samples. After 4 to 6 weeks, health status and use of health care services were assessed. The hospitalized cohort underwent a similar evaluation and was followed until discharge. Antibodies to RSV and to influenza A and B viruses were assayed in blood samples. Reverse-transcriptase polymerase chain reaction (RT-PCR) and culture for RSV and influenza virus were performed on nasopharyngeal samples. Outpatient participants included 608 healthy elderly persons and 540 high-risk patients; there were 1388 inpatient participants. The outpatient high-risk group had the greatest exposure to children. The hospitalized group had lower functional scores before hospitalization than did the outpatient cohorts. Overall, 2514 cases were evaluated. Influenza A and B activity varied during the four winters, whereas RSV activity remained relatively stable. RSV infection was diagnosed in 102 outpatients and 142 hospitalized patients. Influenza A was diagnosed in 44 outpatients and 154 inpatients. RSV infection occurred in 3 to 7% of the healthy elderly cohort and in 4 to 10% of the high-risk cohort. Of the RSV infections, 89% were symptomatic. Signs and symptoms of RSV infection were not distinguishable from those of influenza. The rate of use of health care services was higher in the high-risk than in the healthy elderly cohort. Illnesses lasted a mean of 2 weeks. Demographic characteristics of patients and clinical symptoms of infections requiring hospitalization were similar for RSV and influenza, and symptoms were more common among residents of long-term-care facilities. Mortality from RSV was higher if the patient was from a long-term-care facility rather than from the community, but this difference was not found in patients with influenza. Overall, RSV accounted for 10.6% of hospitalizations for pneumonia, 11.4% of those for chronic obstructive lung disease, 5.4% of those for congestive heart failure, and 7.2% of those for asthma. The authors have obtained important information about the epidemiology and health impact of RSV infection in adults--both healthy elderly patients and high-risk adults in the community as well as hospitalized patients with cardiopulmonary disease. The link between RSV infection and hospitalization was confirmed by an increase in antibody titer to RSV in concert with a positive RT-PCR assay for RSV in 61% of inpatient cases. In addition, 83% of patients with a positive RT-PCR for RSV also had a rise in antibody titer, suggesting that transient colonization was unlikely. Almost all RSV disease was symptomatic and led to functional impairment and increased use of health care services. Extrapolating from their results, the authors state that RSV accounts for more than 175,000 hospital admissions each year. In addition, their data predict that 14,000 deaths each year in the United States may be attributable to RSV. RSV is therefore an important illness in adults, and a vaccine for high-risk and elderly patients is needed. In an accompanying editorial, Sethi and Murphy (2005) note that this study has important implications for public health strategy and for the setting of priorities for vaccine and antiviral agent development. However, they do caution that the high-risk cohort may have been colonized to some degree with RSV, and they point out that the lack of a search for bacterial infection is a shortcoming of the study. Still, a vaccine for adults is clearly needed. Although attenuated live-virus vaccine may be appropriate for infants, subunit vaccines are likely to be useful for high-risk older children and adult populations. References Falsey AR et al: Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 352:1749, 2005 Sethi S, Murphy TF: RSV infection--not for kids only (editorial). N Engl J Med 352:1810, 2005
|
|
|
about us | cme | home | issue index | patient notes | pearls | ad services |
Please send technical questions related to the Web site to Ann Harste |
||
![[Harrison's Online]](../../../graphics/harrisons/HPIMdept.gif){kind=small}
![[McGraw-Hill's Access Medicine]](../../../graphics/harrisons/acessmed.gif){kind=small}