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CLINICAL INSIGHTS

Late-breaking News

Aromatase inhibitors take center stage as Ca chemoprevention

Aromatase inhibitors like anastrozole and letrozole seem to protect breast cancer survivors from recurring malignancies, according to two independent controlled trials. In one large-scale study, investigators gave placebo or letrozole to more than 5,000 women with early-stage breast cancer who had already taken tamoxifen for 5 years. About 2 ¹/₂ years into the trial, only 75 woman in the letrozole group had a recurrence or a new primary tumor in the contralateral breast, compared to 132 in the placebo group. The dramatic results prompted researchers to stop the trial. Adverse effects of the aromatase inhibitors included hot flashes, as well as joint and muscle pain.¹ The risk of osteoporosis may also have been slightly greater in the letrozole group.

Italian researchers obtained similar results using anastrozole, presenting their results only a few weeks ago at the San Antonio Breast Cancer Symposium. In that trial, postmenopausal women who had estrogen receptor-positive breast cancer and had been taking 20 mg of tamoxifen daily for 2 or more years either continued on the drug for a total of 5 years or were switched to 1 mg/day of the aromatase inhibitor for the rest of the 5-year period. Among the 426 women enrolled in the study, 26 either died, had a recurrence, or a new primary tumor while on tamoxifen, versus 10 in the anastrozole group. Put another way, anastrozole cut the risk of cancer recurrence by 64% (hazard ratio: 0.36, 95% CI 0.17– 0.75, P = 0.006) and the risk of dying by 82%. Serious side effects were more common in the tamoxifen group.²

1. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer. N Engl J Med. 2003;349:1793-1802.

2. Boccardo F, Rubagotti F, Amoroso D, et al. Anastrozole appears to be superior to tamoxifen in women already receiving adjuvant tamoxifen treatment. Paper presented Wednesday. December 3, 2003. ( www.abstracts2view.com/bcs03 )

Postmenopausal HT doesn't improve—or impede—cognition

Not only shouldn't postmenopausal women take hormone therapy to prevent heart disease, they shouldn't use it to improve or protect cognitive function, according to a large population-based study.

Researchers included 1,462 postmenopausal women residing in Wisconsin and participating in the 5-year follow-up examination for the Epidemiology of Hearing Loss Study in 1998–2000. Ninety-four of the women were cognitively impaired as defined by low Mini-Mental State Examination scores, with 20% of the 94 receiving a diagnosis of Alzheimer's disease.

After adjusting for age, current HT users were slightly less likely than nonusers to be cognitively impaired, but the finding was not statistically significant. Similarly, neither current, past, nor duration of HT use was associated with cognitive impairment. Age and educational attainment seem to play more important roles in postmenopausal cognitive status.

Mitchell JL, Cruickshanks KJ, Klein BE, et al. Postmenopausal hormone therapy and its association with cognitive impairment. Arch Intern Med. 2003;163:2485-2490.

Less frequent Pap smears appear safe for low-risk women

Reducing the frequency of Papanicolaou smears from annually to once every 3 years in low-risk women places only about three per 100,000 more women between the ages of 30 and 64 at risk of cervical cancer, according to a recently published study.

Researchers from California included over 31,000 racially, ethnically, and geographically diverse women who had three or more consecutive negative annual Pap tests. They calculated that avoidance of one additional case of cervical cancer by screening 100,000 women annually for 3 years rather than once in 3 years after the last negative test would require about 69,665 additional Pap smears and 3,861 colposcopies in women 30 to 44 years of age and about 209,324 additional Pap smears and 11,502 colposcopies in women 45 to 59 years of age.

The researchers encourage practitioners and their patients to consider the small increase in risk associated with less frequent screening in comparison to the costs and stress associated with more frequent screening.

Sawaya GF, McConnell KJ, Kulasingam SL, et al. Risk of cervical cancer associated with extending the interval between cervical cancer screenings. N Engl J Med. 2003;349:1501-1509.

Panic in postmenopausal women closely linked to comorbidity

Almost one out of every five postmenopausal women has had a panic attack in the past 6 months, according to the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the 40-center Women's Health Initiative.

The cross-sectional survey of over 3,300 women between the ages of 50 and 79 found that full-blown panic attacks are highly associated with medical comorbidity. Women with a history of migraine, for example, are six times more likely to report full-blown panic than women without headaches. Women who are depressed are more than five times as likely to report a panic attack. Similarly, emphysema and angina each increased the likelihood of a panic attack about four times, cardiovascular disease nearly tripled the risk, and reported chest pain during ambulatory electrocardiography increased the risk two and one half times.

In addition, the researchers confirmed that such attacks impair function and are associated in a dose-response manner with negative life events during the past year.

Smoller JW, Pollack MH, Wassertheil-Smoller S, et al. Prevalence and correlates of panic attack in postmenopausal women. Arch Intern Med. 2003;163:2141-2050.

HER2: critical player in postsurgical cancer cell proliferation

In an effort to determine whether surgery helps to spread remnant breast cancer cells, particularly cells that overexpress HER2, Italian researchers compared histologic sections of primary breast cancers with specimens of re-excised residual tumors obtained within 48 days of the first surgery.

While the investigators found no overall change in tumor proliferation between initial and repeat surgeries, a subset of specimens that overexpressed HER2 displayed a 10% increase in proliferative cells upon re-excision.

In addition, the researchers found that wound drainage fluid and postsurgical serum samples contain growth factors that stimulate proliferation of HER2-positive breast carcinomas. This finding, they suggest, helps to explain why HER2 expression is associated with a poor prognosis and why invasive diagnostic procedures often lead to increased residual tumor growth with other types of cancer.

Lastly, the investigators determined that treatment of HER2-positive tumor cells with trastuzumab abolished drainage fluid-induced proliferation, suggesting a potential therapeutic role for this and other monoclonal antibodies in pre-, peri-, and postoperative settings.

Tagliabue E, Agresti R, Carcangiu L, et al. Role of HER2 in wound-induced breast carcinoma proliferation. Lancet. 2003;362:527-533.

No advantages associated with fetal endoscopic tracheal occlusion

Among fetuses with congenital diaphragmatic hernia, endoscopic tracheal occlusion to induce lung growth doesn't improve survival or morbidity rates, when compared to standard postnatal care. It also increases the likelihood of premature rupture of membranes and preterm delivery, according to a randomized trial.

Researchers randomized 24 women carrying fetuses between 22 and 27 weeks' gestation that had severe, left-sided congenital diaphragmatic hernia to either fetal tracheal occlusion or post-birth repair. Recruitment was halted at 24 patients because of the unexpectedly high 90-day survival rate with standard care (77%) versus 73% with tracheal occlusion.

Neonatal morbidity rates did not differ between the groups, and premature rupture of membranes and preterm delivery were more common in the intervention group than in those receiving postnatal treatment. Because the severity of hernias at randomization was inversely related to survival in both groups, fetuses with lung-to-head ratios of less than 0.9 remain the greatest challenge.

Harrison MR, Keller RL, Hawgood SB, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med. 2003;349:1916-1924.

Continuous use of OCs relieves more endometriosis pain

Continuous use of a combination (ethinyl estradiol/desogestrel) oral contraceptive significantly reduces the frequency and severity of moderate-to-severe endometriosis-associated dysmenorrhea, according to a 2-year prospective clinical trial.

The study involved 50 women who underwent surgery for endometriosis in the previous year and who continued to suffer from dysmenorrhea despite cyclic use of OCs.

At the end of the study period, patients' pain decreased by more than half on average, and 80% of the women were either satisfied or very satisfied with continuous use of the pill. Amenorrhea, spotting, and breakthrough bleeding were reported by 38%, 36%, and 26%, respectively.

Vercellini P, Frontino G, DeGiorgi O, et al. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril. 2003;80:560-563.

CORRECTION:

In the article "Keys to minimizing liability in obstetrics" [November 2003, page 91], in the section Perform amnioinfusion when indicated, it should have read, "The standard technique is to infuse a 500 mL bolus followed by 100 mL/hr" (not 100 mL/min).

Stopping cabergoline doesn't end remission

Discontinuing cabergoline once prolactin levels have normalized and MRI reveals no evidence of tumor doesn't place patients at undue risk of recurrence, according to a study from Italy involving 200 patients with either nontumoral hyperprolactinemia, microprolactinoma, or macroprolactinoma.

While cabergoline has proved highly effective as treatment for these conditions, experts have considered its most significant drawback to be lifelong administration. So Colao and colleagues studied patients receiving on average 0.5 to 1.0 mg/week of cabergoline for an average of 3 to 4 years. They calculated recurrence rates 2 to 5 years after withdrawal of cabergoline of 24% for patients with nontumoral hyperprolactinemia, 31% for patients with microprolactinomas, and 36% for patients with macroprolactinomas, resulting in remission rates that were higher than those generally reported as spontaneous regression. They also calculated that the risk of recurrent hyperprolactinemia increased by 19% with each millimeter increase in tumor remnant size.

While the results look promising, the researchers cautioned that until data from studies with longer follow-up periods become available, close monitoring of patients for recurrent hyperprolactinemia and/or tumor growth is imperative.

Colao A, Di Sarno A, Cappabianca P, et al. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med. 2003;349:2023-2033.

Hydralazine may not be best choice for hypertension in pregnancy

Hydralazine is associated with poorer maternal and perinatal outcomes than labetalol and nifedipine, is less effective than nifedipine or isradipine, and doesn't differ significantly in performance from labetalol, according to a meta-analysis of randomized, controlled clinical trials.

Researchers from British Columbia reviewed 21 randomized, controlled trials published between 1966 and 2002 and involving 1085 women taking short-acting antihypertensives for severe hypertension in pregnancy. They found that hydralazine was associated with more maternal hypotension, caesarean section delivery, placental abruption, maternal oliguria, adverse effects on fetal heart rate, and low Apgar scores at 1 minute than the alternatives. It was also more poorly tolerated, with a greater incidence of headaches, palpitations, and maternal tachycardia than was associated with other antihypertensives, with the possible exception of nifedipine.

While the heterogeneity of their findings made them insufficiently robust to recommend broad alterations in clinical practice, the authors did suggest nifedipine and parenteral labetalol as reasonable alternatives to hydralazine.

Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327:955-960.

Metformin: No. 1 treatment for polycystic ovaries

Metformin is effective as first-line therapy in PCOS-induced anovulation, according to a recently published review and meta-analysis. The drug may also have the added benefit of improving the metabolic syndrome.

Researchers from Australia reviewed 13 trials that included a population of 543 women with polycystic ovary syndrome. They calculated that metformin is almost four times as effective at inducing ovulation as placebo, and that the combination of metformin and clomiphene is about 4.41 times as effective as clomiphene alone. In addition, metformin reduces fasting insulin concentrations, blood pressure, and low-density lipoprotein cholesterol. However, the drug may cause nausea, vomiting, and other gastrointestinal disturbances, and data regarding long-term safety and use in pregnancy are lacking.

Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327:951-953.

PROFESSIONAL UPDATE

Will we run out of MDs in the not-too-distant future?

Reversing its longstanding position that the nation is facing a physician surplus in upcoming years, the Council on Graduate Medical Education is now endorsing an increase in the number of medical student graduates and corresponding first-year residency slots. This abrupt turnaround comes in response to a study the council commissioned that projects a shortage of physicians within the next two decades, reported Modern Healthcare (10/13/03).

The study, conducted by the Center for Health Workforce Studies at the State University of New York, Albany, projected that the nation will face a shortage of 85,000 to 96,000 physicians by 2020. As a result, the council, an advisory board to Congress, is calling for an increase of medical student graduates from about 24,000 to almost 27,000 by 2015. Over the past two decades, the number of medical students has held steady at around 16,000 per year.

Get disruptive physicians under control to manage legal risks

Physicians who exhibit chronic disruptive behavior are a liability risk in hospitals. We're not talking about physicians who have an irascible personality or who occasionally lash out in frustration, but rather those physicians who habitually and continually cause disruptions by, say, using abusive or threatening language or refusing to believe that they could be wrong.

Disruptive physicians tear down staff morale and stifle communication: For example, staff members who are turned off or intimidated by the disruptive physician's behavior may eventually avoid interacting with him or her. This could result in delays in communicating essential information about a patient's care. If a patient is harmed as a result, the hospital could be held liable.

Because of this risk, "medical staff and leadership have the responsibility of trying to eliminate the behavior," says ACOG Today (Nov/Dec 2003). Observing the right to due process, the American Medical Association recommends that disruptive physicians be treated as if they had a substance abuse impairment and referred to a medical staff wellness committee or the equivalent. Whether the disruptive physician can modify his or her behavior—thereby decreasing the threat to the delivery of safe patient care—will determine if the physician must be removed from the medical staff.

Liability rate survey shows double-digit increases again

Nationwide, malpractice insurance rates for obstetrician/gynecologists, internists, and general surgeons continued the climb upward, reported American Medical News (11/10/03). Just how high has it gone? Citing Medical Liability Monitor's 2003 Rate Survey, the majority of ob/gyns, internists, and general surgeons saw double-digit increases in their insurance rates between 2002 and 2003.

Based on rates reported by insurance companies, the survey found that 58.2% of ob/gyns, internists, and general surgeons saw increases of 10% to 49%, and about 1% of these specialties saw increases of 100% or more. On the bright side, 22.6% of physicians in all three specialties saw their premiums remain the same or decrease.

The report also found that ob/gyns in Pennsylvania saw rates increase by 31.2% from $116,388 in 2002 to $152,730 in 2003; Pennsylvania is one of the states with the highest medical liability rates for this specialty and has been identified by the American Medical Association as a crisis state. Although ob/gyns in South Dakota saw the lowest premium in 2003 at $14,662, it still represented a 10% increase from 2002.

The survey also noted that 2004 doesn't look too promising: 83% of companies polled said that they would implement increases this year.

Investment in electronic medical records is increasing

More and more health-care organizations and groups are allocating funds to implement electronic medical records. According to the 2003 Modern Physician/PricewaterhouseCoopers survey on health-care information technology, more than 41% of responding organizations made some investment in EMRs—up from 31% from a year earlier—and 80% say they plan to invest in this technology by 2005.

Breaking the data down by type of organization, the survey found that adoption of EMRs is more common in hospitals than in independent practice. Nearly two thirds of hospital respondents (61.4%) say their institutions invested in EMRs, while half (50%) of physicians surveyed from medical groups affiliated with nonhospital companies and more than a third (36.7%) of those from independent group practices did so.

But are physicians using the technology? The survey, the results of which were reported in Modern Physician (11/1/03), found that about half of the responding organizations have physicians who use computers for patient records—either in their own practices or in the hospitals where they have privileges. That figure is nearly double the 2001 rate of 27.3%.

An option for religious couples with unused frozen embryos

The head of the Christian Medical Association is calling for couples who do not intend to use embryos created through in vitro fertilization to donate them to other couples.

"Many couples who have used reproductive technology in an effort to have children are faced with the issue of embryos who will not be implanted and brought to birth," said Dr. David Stevens, CMA's executive director, in a press release. "Thankfully, such couples now have the option of allowing another couple to receive their embryo(s) and to provide a loving home for any child that may result."

To that end, the CMA helped plan the development of the National Embryo Donation Center at the Baptist Hospital for Women in Knoxville, Tenn. The nonprofit center handles the medical, legal, and social requirements of embryo donation.

Physicians react: IOM calls for more stringent recertification requirements

Some physicians have expressed concern over an Institute of Medicine report released in April that calls for licensed physicians to face more rigorous recertification requirements, according to Medical Economics (9/5/03). Some rank-and-file physicians are concerned that the new recommendations, if implemented, could translate into a heavier workload and more stress.

The IOM report, "Health Professions Education: A Bridge to Quality," recommends that physicians demonstrate five "core competencies." Namely, physicians and other providers should:

• provide patient-centered care;

• work in interdisciplinary teams to ensure continuous and reliable patient care;

• employ evidence-based practice;

• identify errors and hazards in care and implement safety design principles;

• use information technology to support the provider's practice.

With the IOM calling for state medical and certification boards—and also asking the Agency for Healthcare Research and Quality to require, or encourage, physicians to demonstrate their competence to practice—physicians are questioning the need. Physicians interviewed by Medical Economics, a sister publication of Contemporary Ob/Gyn, questioned how competence, and the core competencies, would be gauged, and whether the addition of new credentialing requirements would further overwhelm beleaguered physicians and add to the cost of health care.

While numerous questions have been raised, Edward M. Hundert, a psychiatrist and head of the IOM committee that made the recommendations, notes that integrating core competencies into oversight processes could take as long as 10 years and will require mechanisms for funding. Still, he is optimistic.

"The report isn't suggesting that we keep all the burdensome CME and recredentialing requirements we have now and add more," he told Medical Economics. "Rather, because medicine changes so rapidly, we need to begin a comprehensive reassessment of the whole process across the health professions."

 

Clinical Insights/Professional Update. Contemporary Ob/Gyn Jan. 1, 2004;49:11-22, 84.