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Prophylactic mastectomy may provide substantial gains in life expectancy for women with cancer-disposing genes

Genetic tests now enable women to be tested for mutations in the BRCA1 and BRCA2 genes that markedly increase their risk of breast and ovarian cancer. The cumulative risk of breast cancer for women with these mutations is estimated to range from 40 to 85 percent compared with 12 percent among the general population of women, and from 5 percent to 60 percent (depending on the population studied) for ovarian cancer, compared with 1.5 percent of women in the general population.

Intensified screening may identify disease at a favorable stage, but it does not prevent cancer. For young women with these gene mutations, prophylactic mastectomy (surgical removal of the breasts) may substantially improve life expectancy, but prophylactic oophorectomy (surgical removal of both ovaries) provides more limited gains in life expectancy. These are the findings of a study supported by the Agency for Health Care Policy and Research (NRSA Training Grant HS00020).

Neither approach completely protects against cancer. Cases of breast cancer after bilateral mastectomy and peritoneal ovarian cancer after bilateral oophorectomy are well documented, notes Deborah Schrag, M.D., of Dana Farber Cancer Institute and Harvard Medical School. Dr. Schrag and her colleagues used decision analysis to compare these surgeries with no prophylactic surgery among women who carry mutations in the BRCA1 or BRCA2 gene. They constructed hypothetical groups of women, defined according to age and risk of cancer, who were evaluated annually for the development of new breast and ovarian tumors, tumor progression, and death. Since the specific risks associated with BRCA1 and BRCA2 mutations among the general population are not yet known, the researchers modeled a range of values for the risks associated with the mutations: level A, 40 percent risk of breast cancer and 5 percent risk of ovarian cancer; level B: 60 percent risk of breast cancer and 20 percent risk of ovarian cancer; and level C: 85 percent risk of breast cancer and 40 percent risk of ovarian cancer.

Dr. Schrag and colleagues calculated that, on average, 30-year-old women who carry BRCA1 or BRCA2 mutations gain from 2.9 to 5.3 years of life expectancy from prophylactic mastectomy and from 0.3 to 1.7 years of life expectancy from prophylactic oophorectomy, depending on their cumulative risk of cancer. Among 30-year-old women, oophorectomy may be delayed 10 years with little loss of life expectancy, but the same is not true for prophylactic mastectomy—delaying mastectomy until age 40 would reduce the years of life expectancy gained from 5.3 to 3.6. The gains in life expectancy for 35-year-old women carrying mutations at risk level B (intermediate risk) who undergo both surgeries are similar to the benefits expected for 35-year-old women who have extraordinarily high cholesterol levels and reduce them to normal.

For details, see "Decision analysis—Effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 and BRCA2 mutations," by Dr. Schrag, Karen M. Kuntz, Sc.D., Judy E. Garber, M.D., M.P.H., and Janice C. Weeks, M.D., in the May 15, 1997 New England Journal of Medicine 336, pp. 1465-1471.

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Women's and Family Health

Removing both ovaries during hysterectomy may increase a woman's risk of heart disease despite estrogen replacement therapy

About one-third of women have a hysterectomy by age 60; in women who have completed their families, removal of both ovaries is often recommended to prevent ovarian cancer. A recent study, supported in part by the Agency for Health Care Policy and Research (HS06726), shows that women who have both ovaries removed during a hysterectomy (bilateral oophorectomy) may end up, in the long-term, with a higher risk for heart disease than women whose ovaries are not removed. Further, this risk is not totally mitigated by estrogen replacement therapy. Women who have hysterectomies without ovary removal have similar or less risk for heart disease than women who do not undergo hysterectomy.

After adjustment for age, body weight, and estrogen use, women 20 or more years past menopause who had both ovaries removed at the time of hysterectomy had significantly higher cholesterol, low-density lipoproteins, postchallenge glucose, and postchallenge insulin than women who had a hysterectomy but retained their ovaries. The latter group had lower cholesterol and postchallenge insulin than women who did not undergo hysterectomy. Among current estrogen users, women whose ovaries had been removed had higher blood pressure. Patterns were similar but not statistically significant for women less than 20 years postmenopause.

These differences were not explained by other factors affecting heart disease risk, such as age, obesity, estrogen use, alcohol consumption, cigarette smoking, or exercise, which were about the same for both groups of women who had hysterectomies, notes Donna Kritz-Silverstein, Ph.D., of the University of California-San Diego. The researchers based their findings on a community-based sample of 1,150 women (505 women who had undergone hysterectomy many years earlier and 645 women who served as controls). Half of the experimental group reported hysterectomy with bilateral oophorectomy, and the other half reported hysterectomy with conservation of one or both ovaries.

See "Hysterectomy, oophorectomy, and heart disease risk factors in older women," by Dr. Kritz-Silverstein, Elizabeth Barrett-Connor, M.D., and Deborah L. Wingard, Ph.D., in the April 1997 issue of the American Journal of Public Health 87(4), pp. 676-680.

Certified nurse-midwives use fewer invasive techniques during labor and delivery for low-risk women than physicians

Midwifery in the United States has never assumed the central role in the management of pregnant women that is the norm in most of Europe. One of the strongest rationales for increasing the role of midwives has been that their obstetrical approach leads to lower intervention rates without any demonstrable differences in outcome, particularly for low-risk patients. A recent study supported by the Agency for Health Care Policy and Research (HS06166) supports this view.

In this study, young urban women with low-risk pregnancies managed by certified nurse-midwives were less likely than similar women managed by obstetricians/ gynecologists (OB/GYNs) and family physicians to be continuously electronically monitored during labor, receive oxytocin to induce or augment labor, be given epidural anesthesia, or undergo episiotomies. Also, the average certified nurse-midwife delivered 83.5 percent of low-risk patients vaginally without use of forceps or vacuum extractors, a significantly higher rate of noninstrumental vaginal delivery than the physicians. Their cesarean section (c-section) rate was 9 percent compared with 14 percent for obstetricians and 15 percent for family physicians. The more active style of intrapartum management used by OB/GYNs was associated with a 12 percent greater use of resources compared with certified nurse-midwives. This was mostly due to costs associated with anesthesia use and longer hospital stays for women having c-sections.

The results achieved by the less intensive approach to obstetrics by nurse-midwives argues for expanding the proportion of deliveries attended by midwives or transferring some of the skill and philosophy that undergird midwifery to physicians who practice obstetrics, asserts Roger A. Rosenblatt, M.D., M.P.H., of the University of Washington School of Medicine.

Dr. Rosenblatt and his colleagues randomly sampled the records of low-risk, predominantly white, privately insured, young patients with uneventful pregnancy and medical histories who were cared for by Washington State OB/GYNs, family physicians, and certified nurse-midwives during 1988 and 1989.

See "Interspecialty differences in the obstetric care of low-risk women," by Dr. Rosenblatt, Sharon A. Dobie, M.C.P., M.D., Gary Hart, Ph.D., and others, in the March 1997 American Journal of Public Health 87, pp. 344-351.

Duration of maternity leave significantly affects maternal health

Mothers with infants are one of the fastest growing segments of the labor force. But the typical 6-week-long maternity leave following childbirth may not be long enough to benefit the health of many women, concludes a study supported in part by the Agency for Health Care Policy and Research (HS06950).

The effect of maternity leave on a woman's health is U-shaped. Initially, less time off is associated with better health, but this relationship reverses itself at later stages of postpartum, when more time off work is associated with better health. In this study, women who took more than 12 weeks leave felt they had more energy and vitality. Those who took more than 15 weeks leave didn't feel as depressed or nervous; and those who took more than 20 weeks leave postpartum felt better able to function in their social roles.

The majority of women studied did not experience these positive effects of leave because they were already back at work. Seventy-five percent of women studied had returned to work by 12 weeks, 85 percent by 15 weeks, and 91 percent by 20 weeks after childbirth. A surprising proportion of women experienced diminished levels of well-being at about 7 months postpartum, showing the delayed effects of short maternity leave that has been found in earlier studies. Potentially infectious symptoms such as colds and flu were experienced by many: about 25 percent of women had one symptom, 18 percent had two, and 37 percent had three or more symptoms. Noninfectious symptoms such as stiff joints, or neck or back pain were also experienced by many: 30 percent of women had one symptom, 19 percent had two, and 20 percent had three or more symptoms.

The cumulative effect of several symptoms across more than one measure of maternal health raises concern for the well-being of employed postpartum women, explains Patricia McGovern, Ph.D., of the University of Minnesota. Dr. McGovern and her colleagues found that, besides longer maternity leave, factors associated with improved health included more sleep, increased social support, increased job satisfaction, less physical exertion on the job, fewer infant symptoms, and less difficulty arranging child care. They used a model of health and workforce participation and a sample of women identified from State vital statistics records to analyze the relationship between maternal postpartum health and time off work after childbirth.

Details are in "Time off work and the postpartum health of employed women," by Dr. McGovern, Bryan Dowd, Ph.D., Dwenda Gjerdingen, M.D., and others, in Medical Care 35(5), pp. 507-521, 1997.

Amoxicillin is often prescribed to prevent middle ear infections in young children, but it is only marginally effective

Middle ear infections occur most often during the first 2 years of life. About 15 percent of children suffer from recurrent infections, that is, three or more episodes every 6 months or four or more episodes in 1 year. The annual costs associated with these episodes is estimated at $3 billion to $4 billion.

The use of antibiotics to treat middle ear infections and to prevent recurrent infections remains high, according to a recent study supported by the Agency for Health Care Policy and Research (HS07816). However, amoxicillin, the antibiotic most commonly prescribed to prevent new ear infections, is no more beneficial as a preventive therapy than placebo, and its use should be discouraged in order to avoid development of antibiotic-resistant pneumonia bacteria, concludes a second AHCPR supported study (HS07283). Both studies, led by Stephen Berman, M.D., of the University of Colorado Health Sciences Center, are summarized here.

Byrnes, P.J., Bondy, J., Glazner, J.E., and Berman, S. (1997, April). "Utilization of services for otitis media by children enrolled in Medicaid." Archives of Pediatric and Adolescent Medicine 151, pp. 407-413.

Medicaid-insured children less than 3 years of age receive an average of more than two antibiotic prescriptions for middle ear infections (otitis media) each year. In fact, this study found that 65 percent of all outpatient visits for these infections result in a filled prescription. Inappropriate use of antibiotics has been cited as an important factor in development of drug-resistant pathogens, evidenced by the increasing prevalence of drug-resistant pneumococcal bacteria. This underscores the importance of reducing inappropriate antibiotic use, note the researchers.

They calculated antibiotic use rates per child and child-year based on Colorado Medicaid data for 1991 and 1992. The rate of antibiotic prescriptions for otitis media was 0.34 per child or 0.48 per child-year. Each child with a middle each infection had an annual average of 1.55 antibiotic courses or 1.82 per child-year. About 22 percent of Medicaid-insured children in the State made at least one outpatient visit with a diagnosis of otitis media, with the peak prevalence (47 percent) occurring between ages 1 and 2 years. Diagnosis of otitis media was more frequent for white (26 percent) and Hispanic (21 percent) children than black (15 percent) and Native American (14 percent) children.

Roark, R., and Berman, S. (1997, April). "Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media." Pediatric Infectious Disease Journal 16, pp. 376-381.

Children with recurrent acute otitis media (AOM), who are given amoxicillin (20 mg/kg), either once or twice a day, or a placebo, all fare about the same, according to this study. Data from other studies are in agreement; they also found only a marginal benefit associated with antibiotic prophylaxis for otitis media. Because of the potential of excessive antibiotic use to promote acquisition of antibiotic-resistant pneumococci and the lack of effectiveness of amoxicillin prophylaxis in this trial, its routine use should be discouraged, suggest the researchers. They recommend treating individual episodes of AOM, rather than using amoxicillin to prevent new episodes. When a child has experienced five or six discrete recurrent episodes of AOM during a 1-year period, it would be reasonable to consider referral for surgical placement of a tube to drain excess fluid from the ear.

The researchers randomized 158 children, 3 months to 6 years of age, with recurrent AOM into the once-a-day, twice-a-day, and placebo groups in a double-blind study (neither parent nor physician knew a child's group assignment) conducted at a hospital-based general pediatric clinic and private pediatric practice in Denver. Of the children remaining free of AOM, 63 percent were in the placebo group, 64 percent were in the once-daily group, and 61 percent were in the twice-daily group. There was no significant difference in new AOM episodes among the three groups, with an overall average of nearly three new episodes during the study period.

Sexually transmitted diseases can directly affect pregnancy outcome

Sexually transmitted diseases (STDs) affect many U.S. women and indirectly affect the health of their newborn babies, according to the Low Birthweight Patient Outcomes Research Team (PORT). The Low Birthweight PORT is supported by the Agency for Health Care Policy and Research (PORT contract 290-92-0055) and led by Robert L. Goldenberg, M.D., of the University of Alabama at Birmingham.

Syphilis and group B Streptococcus infections are proven causes of both stillbirth and neonatal death. Congenital abnormalities have also been associated with STDs, ranging from brain damage and motor disorders to blindness and deafness. In addition, women with STDs are more likely than other women to have preterm births (less than 37 weeks' gestation).

Unlike rubella, cytomegalovirus, and syphilis, which directly affect the fetus during pregnancy, most other STDs generally remain in the cervix and vagina and are transmitted to the infant during labor and delivery. Even transmission of the human immunodeficiency virus (HIV) that causes AIDS has been shown to occur in the last few weeks of pregnancy or during birth.

Syphilis and HIV infections currently are found in 6,000 to 8,000 pregnant women (about 0.15 to 0.2 percent of all pregnant women) each year. Gonorrhea, hepatitis B virus (HBV), and Trichomonas infections are found in 1 to 2 percent (40,000 to 80,000) of all pregnant women each year, and chlamydia is found in about 5 percent (200,000) of pregnant women. Maternal colonization or infection with herpes simplex virus, group B Streptococcus, or bacterial vaginosis is found in about 20 percent (800,000) of pregnant women. Cytomegalovirus colonization or infection is estimated to occur in about one-third (1.3 million) of all pregnant women.

If the mother carries the organism, the estimated proportion of infants who will be infected with the organism after birth range from 0.2 percent for herpes simplex and 3 percent for cytomegalovirus to 25 to 40 percent for syphilis, HBV, and HIV. Gonorrhea is associated with a three-fold increase in the preterm birth rate, and syphilis, chlamydia, and bacterial vaginosis infections with a two-fold increase in preterm births.

If the effect on preterm birth of bacterial vaginosis and other STDs is correct, as many as 100,000 preterm births and 5,000 or more infant deaths, as well as a similar number of major disabilities, may be associated with maternal STDs, according to the researchers.

Details are in "Sexually transmitted diseases and adverse outcomes of pregnancy," by Dr. Goldenberg, William W. Andrews, Ph.D., M.D., Amy C. Yuan, Sc.B., and others, in the March 1997 issue of Clinics in Perinatology 24(1), pp. 23-41.

Physicians are less likely to suspect TB in high-risk women than men

From 1985 to 1992, there was a resurgence of tuberculosis (TB), and during this time, institutional outbreaks of multidrug-resistant TB resulted in mortality rates of 40 to 90 percent. These outbreaks were attributed to physicians' delays in recognizing TB in institutionalized individuals, inadequate respiratory isolation of TB-infected patients, and delays in starting appropriate medications to prevent transmission to other individuals and facility staff.

The incidence of TB increased substantially among women after 1987, owing in part to the increased incidence of HIV/AIDS among women, which elevated their risk of TB infection. However, during the early years of TB's resurgence, physicians tended to suspect TB in male but not female high-risk patients, according to a study supported in part by the Agency for Health Care Policy and Research (NRSA fellowship HS00032, HS06494, and HS07846).

Physicians need to be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent within-hospital transmission of this disease, warns Susan E. Cohn, M.D., M.P.H., of the University of Rochester. She and colleagues retrospectively reviewed the medical records of 2,174 adult patients with AIDS discharged with a diagnosis of Pneumocystis carinii pneumonia (PCP), an HIV-related lung infection, from 96 hospitals in 5 U.S. cities from 1987 to 1990.

Physicians suspected TB (noted it in the chart or ordered a sputum culture) in the first 2 hospital days in 66 percent of these patients in 1987, a rate that increased steadily to 74 percent in 1990. However, the extent to which physicians considered TB among female patients decreased from 76 percent to 71 percent over the 4 years. The odds that TB would be suspected early increased three times more among men than women. In contrast, early consideration of HIV-related PCP remained nearly constant at 93 percent over the 4-year period for both men and women. In known HIV-positive patients, TB was considered early in 62 percent of patients in 1987, increasing to 73 percent in 1990, but remained constant if HIV status was not known on admission. Early consideration of TB did not increase among women known to be HIV positive on admission.

Details are in "Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990," by J. Peter Cegielski, M.D., M.P.H., Matthew B. Goetz, M.D., Jeffrey M. Jacobson, and others, in Infection Control and Hospital Epidemiology 18(4), pp. 237- 243, 1997.

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Critical Care Medicine

Current triage guidelines for admitting patients to critical care units may not be appropriate

Hospital intensive care unit (ICU) beds are scarce and expensive, and decisions about who gets them are often agonizing. Current guidelines recommend that patients with very poor prognosis and little likelihood of benefit should not be admitted to ICUs. However, a new study demonstrates that physicians have great difficulty predicting survival for patients with congestive heart failure (CHF), a leading cause of hospitalization among the elderly, at the time the triage decision has to be made, usually in the emergency department (ED).

In a recent study the 15 patients judged by ED physicians to have the least chance for survival (90 day survival probability of 10 percent or less) had a 33 percent survival rate. This suggests that current triage guidelines may inappropriately exclude a small number of patients from ICUs who actually could benefit from ICU care. As such, these guidelines may be impractical or harmful, according to the authors of the study, which was supported in part by the Agency for Health Care Policy and Research (HS06274).

Wally R. Smith, M.D., of the Medical College of Virginia, and his colleagues studied consecutive adults seen for new or exacerbated congestive heart failure during 1,142 ED visits at a university hospital, a Veterans Affairs medical center, and a community hospital. Physicians caring for these patients scored the probability that each patient would survive for 90 days and for 1 year. The scores were compared with the patient's vital status at those times, based on medical chart review or other data.

Results showed that physicians underestimated survival probability at both 90 days and 1 year, particularly for patients they judged to have the least probability of survival. Furthermore, physicians triage decisions were not strongly related to their predictions of survival. The 405 patients sent home were given statistically significant but numerically only slightly higher average estimates of survival at 90 days and at 1 year than the 491 patients admitted to ward beds or the 240 patients admitted to an ICU. Finally, other studies have shown that there are few patients in ICUs whose likelihood of survival is clearly so small as to make continued intensive care appear futile.

Details are in "Physicians' survival predictions for patients with acute congestive heart failure," by Roy M. Poses, M.D., Dr. Smith, Donna K. McClish, Ph.D., and others, in the May 12, 1997 Archives of Internal Medicine 157, pp. 1001-1007.

Advance directives often are not specific enough to guide end-of-life medical decisions

Advance directives can be used to authorize or refuse life-sustaining medical treatments, such as cardiopulmonary resuscitation (CPR), in the event a patient loses his or her decisionmaking capacity. It has been suggested that advance directives elicit goals of care from patients, such as "treat everything" or "comfort care only," instead of or in addition to specific treatment preferences. Although goals have a valid role in advance directives, they often do not provide enough information for caregivers to judge which treatments the patient would accept or reject in certain medical situations, concludes a study supported in part by the Agency for Health Care Policy and Research (HS06120).

Gary S. Fischer, M.D., of the University of Pittsburgh Medical School, and his colleagues surveyed 716 attending physicians at one Boston hospital to elicit general goals of care along with specific preferences for 11 medical interventions in 6 scenarios: persistent vegetative state, coma with small chance of recovery, severe dementia with terminal illness, severe dementia alone, serious chronic mental or physical illness with acute life-threatening illness, and current state of health with acute life-threatening illness. Care goals were prolong life, treat everything; attempt to cure, but reevaluate often; choose quality of life over longevity; provide comfort care only; and other.

The goal of "treat everything" adequately predicted acceptance of each intervention and "comfort care only" adequately predicted rejection of nearly every intervention. "Attempt cure" adequately predicted acceptance of almost every nonaggressive intervention—such as minor surgery, antibiotics, and blood products—but did not predict acceptance of aggressive interventions such as CPR, tube feeding, renal dialysis, and major surgery. "Quality of life" predicted rejection of aggressive intervention in three scenarios but was not useful in other cases. Finally, physicians confidence in goals as predictors of end-of-life treatment preferences was generally 20 percent or less.

For more details, see "Can goals of care be used to predict intervention preferences in an advance directive?" by Dr. Fischer, Hillel R. Alpert, M.P.M., John D. Stoeckle, M.D., and Linda L. Emanuel, M.D., Ph.D., in the April 14, 1997 issue of the Archives of Internal Medicine 157, pp. 801-807.

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