NEWS WATCH

CLINICAL INSIGHTS

HRT increases risk of dementia and stroke

Postmenopausal women may need to reexamine their decision to take combination postmenopausal hormone therapy (HRT) once again. New findings indicate that estrogen plus progestin regimens not only do not protect against dementia in the postmenopausal years, but may actually increase the risk of cognitive impairment and of ischemic stroke.

The information on cognition comes from two separate randomized, double-blind, placebo-controlled trials involving over 4,000 women aged 65 and older who participated in the Women's Health Initiative Memory Study. Researchers compared a group of women taking one daily tablet containing 0.625 mg conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) 2.5 mg with women taking a placebo.

In the first study, the incidence of probable dementia in the women taking estrogen plus progestin was twice that of women in the placebo group. The authors of the study calculated that such an increased risk would result in 23 additional cases of dementia for every 10,000 treated women per year. The two groups began to diverge after only 1 year of treatment and continued to diverge through 5 years of follow-up.¹

In the second study, while most of the actively treated women did not experience negative effects on cognition, more women in the estrogen plus progestin group had a substantial and clinically important decline in cognitive function as measured by the Modified Mini-Mental State Examination than women in the placebo group. Researchers concluded that combined estrogen/progestin treatment should not be used to protect cognition in older women.²

With regard to stroke, researchers studied over 16,000 women aged 50 to 79 participating in the Women's Health Initiative. Again, participants received either 0.625 mg/d CEE plus 2.5 mg/d MPA or placebo. The women taking combination HRT had a 31% greater risk of having a stroke than the women taking placebo. The increase was far greater for ischemic than for hemorrhagic stroke and persisted regardless of patient age; prior history of cardiovascular disease; hormone, statin, or aspirin use; hypertension; diabetes; cigarette smoking; and the presence or absence of a number of other risk factors. Increased risk did not appear until after the first year of treatment.³

1. Shumaker SA, Legault C, Thal L, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. JAMA. 2003;289:2651-2662.

2. Rapp SR, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized, controlled trial. JAMA. 2003;289:2663-2672.

3. Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women. JAMA. 2003;289:2673-2684.

Long-term use of OCs increases risk of cervical cancer

Long-term use of all forms of hormonal contraceptives seems to increase a woman's risk of developing cervical cancer, whether or not she is positive for human papillomavirus (HPV), according to a review of 28 studies and over 12,000 women with in situ or invasive cervical cancer.

Compared with never users of hormonal contraceptives, the relative risk of developing cervical cancer was 1.1 for women who used them for less than 5 years, 1.6 for women who used them for 5 to 9 years, and 2.2 for women who used them for 10 or more years. For HPV-positive women, the relative risks compared to never users were 0.9, 1.3, and 2.5, respectively.

Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet. 2003;361:1159-1167.

Stress—not pain—is major barrier to mammography

While women often remark about the pain associated with mammography, physical discomfort does not deter the overwhelming majority of women from getting repeat exams, according to a recent study of 200 women aged 40 or older. In fact, the actual pain experienced and reported by women immediately following mammography is relatively low (an average score of 3 on a 0 to 10 scale).

Three quarters of the women reported the pain associated with the procedure to rank 4 or less, with the highest level of pain associated with compression of the breasts. Ninety-six percent of the women reported the pain to be "less than" or "about as expected," and 94% reported being very likely or somewhat likely to get a mammogram again next year.

But according to 39% of the women, the most discomforting part of the procedure was the stress generated as they waited for the results. With that fact in mind, the researchers recommend clinicians make a greater effort to make patients aware of this waiting period, and if possible find ways to shorten it.

Sharp PC, Michielutte R, Freimanis R, et al. Reported pain following mammography screening. Arch Intern Med. 2003;163:833-836.

Very few frozen embryos available for controversial stem cell research

Approximately 88% of the nearly 400,000 embryos created in US infertility clinics and then frozen are slated for future patient use, according to the first study to investigate the matter, leaving only about 2.8% or about 11,000 embryos available for research, such as that involving stem cells.

The Society for Assisted Reproductive Technology (SART) and RAND, the nation's largest independent health policy research organization, surveyed more than 430 assisted reproductive technology practices in the US. They found that of the 396,526 existing frozen embryos, 349,830 are slated for future patient use. Almost 9,000 are slated for destruction as per patient request. Just over 9,000 are donations awaiting use by other infertile patients. About 750 are being stored for use in quality assurance activities. And almost 14,000 fall into the category of "other," which generally means the embryo is awaiting a disposition decision. That leaves about 11,000 as a potential source of the embryonic stem cells that might be used to grow replacement tissues for people suffering from a variety of diseases.

Hoffman DI, Zellman GL, Fair CC, et al. Cryopreserved embryos in the United States and their availability for research. Fertil Steril. 2003;79:1063-1069.

Perinatal factors implicated in the development of rheumatoid arthritis

High birthweight and low paternal socioeconomic status are associated with a higher incidence of rheumatoid arthritis, according to a Swedish study that is the first to look at a relationship between perinatal factors and adult onset of the disabling disease.

Researchers found that birth-weight of 4,000 g or more increased the odds of later development of rheumatoid arthritis by more than threefold, compared to those born weighing between 3,000 and 3,999 g. Those weighing less than 3,000 g were at almost twice the risk of the mid-range group.

Similarly, babies born to fathers with manual, as opposed to non-manual, careers were almost three times as likely to develop the condition later in life. Early initiation of breastfeeding, however, was found to be protective.

The authors postulate that their findings may be explained by the influence of these factors on the immune system during the perinatal and postnatal periods.

Jacobsson LT, Jacobsson ME, Askling J, et al. Perinatal characteristics and risk of rheumatoid arthritis. BMJ. 2003;326:1068-1069.

Alendronate prevents bone loss in women who quit HRT

Women who quit hormone replacement therapy (HRT) may not have to worry quite so much about osteoporosis any longer. Alendronate, an effective treatment for postmenopausal osteoporosis, maintains or increases spine and hip bone mineral density (BMD) in postmenopausal women who discontinue HRT, according to a randomized, placebo-controlled trial.

Researchers studied 144 postmenopausal women with low BMD. They found that nearly half of those who recently discontinued HRT lost 5% or more of the bone density of their lumbar spine within 12 months of ceasing HRT. Mean loss was 3.2%. Alendronate sodium (10 mg daily) not only prevented this loss, but was also associated with a mean lumbar spine BMD gain of over 2% at 12 months. In addition, greater hip and total body BMD was preserved with alendronate than with placebo. And bone turnover decreased significantly in the alendronate group, but increased in the placebo group.

Alendronate was well tolerated in the study, with rates of adverse events comparable to that in the placebo group. About one sixth of the women in the study reported hot flashes; 5% left the study because of them, presumably to resume HRT.

Ascott-Evans BH, Guanabens N, Kivinen S, et al. Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Arch Intern Med. 2003;163:789-794.

Progestogen doesn't increase or decrease breast cancer risk

Adding a progestogen to estrogen replacement therapy does not affect a postmenopausal woman's risk for breast cancer one way or the other, according to a position statement from the North American Menopause Society (NAMS), the leading nonprofit organization dedicated to promoting the understanding of menopause. But it can make breasts more dense, which can make mammograms more difficult to read. The effect, however, is usually reversed upon cessation of therapy.

Among other conclusions made by NAMS:

• All FDA-approved formulations of progestogens protect the endometrium from the increased risk of cancer associated with unopposed estrogen equally and slightly improve the bone-building benefits of estrogen, as long as dose and duration of treatment are adequate.

• A primary goal of combined hormonal therapy should be to minimize progestogen-induced side effects, including uterine bleeding—a primary reason women stop therapy—mood disturbance, and breast discomfort. Physicians should consider changing the progestogen type, route of administration, or regimen to minimize such effects.

North American Menopause Society. Role of progestogen in hormone therapy for postmenopausal women: position statement of the North American Menopause Society. Menopause. 2003;10:113-132.

Leukoreduction improves secondary but not primary outcomes of premature infants

Universal prestorage leukoreduction of allogeneic red blood cell (RBC) transfusions doesn't reduce mortality or bacteremia in premature, underweight infants, but does reduce a number of other common complications of premature birth, according to a retrospective before-and-after Canadian investigation.

Researchers studied 515 premature infants weighing less than 1,250 g who were admitted to neonatal intensive care units (NICU), received at least one RBC transfusion, and survived at least 48 hours postinfusion. They found that while the process did not significantly reduce NICU mortality, it did reduce the incidence of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and grade 3 or 4 intraventricular hemorrhage. In fact, when all of the secondary outcomes in the study were lumped together, leukoreduction was associated with the prevention of one major secondary complication of premature birth for every 10 premature infants undergoing transfusion with leukoreduced RBCs. The procedure was also associated with an 11-day decrease in NICU stay.

Fergusson D, Hébert PC, Lee SK, et al. Clinical outcomes following institution of universal leukoreduction of blood transfusions for premature infants. JAMA. 2003;289:1950-1956.

PROFESSIONAL UPDATE

New Supreme Court rulings on liability claims and arbitration

The US Supreme Court recently issued two rulings that offer mixed blessings to clinicians, according to Modern Healthcare (4/14/03).

In one of the rulings, the Supreme Court limited damage awards against insurers as punishment for wayward practices. The court held that a $145 million punitive-damages award against a car insurer was unconstitutional, because it grossly exceeded the amount awarded in compensatory damages.

The case involved a jury award to a Utah couple of $2.6 million in compensatory damages and another $145 million to punish State Farm Mutual Automobile Insurance Co. for fraud, bad faith, and emotional distress. The court held in a 6-3 decision that punitive damages should not exceed compensatory damages by more than a single-digit ratio. Although this case involved a car insurer, Modern Healthcare reported, "the court's decision bodes well for health insurers, as well as providers, at a time when malpractice reform legislation is under heated debate."

In the second ruling, the Supreme Court unanimously upheld the use of arbitration to settle disputes between physicians and HMOs. In this case, the court held that arbitration should be used to settle billing disputes between physicians and two HMOs—namely, PacifiCare Health Systems and UnitedHealth Group—as dictated by the doctors' provider contracts.

The doctors involved in the case had argued that the arbitration agreements were not binding, because the agreements excluded the triple-digit damage awards they were seeking under a federal antiracketeering law. According to Modern Healthcare, "the high court ruled it was 'unclear' whether or not the agreements preclude the triple damages allowable under federal law, and said it would be 'premature' for the court to address that question before an arbitrator ruled in the dispute."

Ob/gyns, other high-risk docs sacrifice practices and services

Obstetricians/gynecologists and other high-risk specialists are more likely to make changes to their practices because of liability pressures than their colleagues, according to a survey of 4,846 physicians nationwide. The survey was conducted by the American Medical Association along with 20 national specialty societies and 13 state societies.

The survey found that 64.8% of high-risk specialists—specifically, ob/gyns, emergency physicians, neurosurgeons, general surgeons, and orthopedic surgeons—said they made changes to their practices. In comparison, 56.8% of low-risk specialists and 58.5% of all physicians surveyed reported making changes.

In addition, the survey found that 6.1% of high-risk specialists said they closed their practices versus 4.6% of low-risk specialists. Almost one quarter (24.2%) of high-risk physicians reported that they stopped providing certain services, while less than one fifth (18.1%) of low-risk specialists said they did the same.

Not surprisingly, the survey, the results of which were reported by amednews.com (4/21/03), found that physicians who practice in "crisis states" (those states designated by the AMA as the hardest hit by liability premium increases) were more likely to make changes to their practices because of liability pressures than physicians in noncrisis states—61.4% versus 54%, respectively. About 22% of physicians in crisis states said they stopped providing certain services, while nearly 16% of physicians in noncrisis states reported doing so. And, 5.4% of physicians in crisis states said they had closed their practices versus 4.1% of those in noncrisis states.

Database to allow one-time credentialing

Tired of filling out application after application for credentialing and re-credentialing? If so, the Council for Affordable Quality Healthcare may have the answer. The Washington, D.C.-based nonprofit coalition of health plans and networks has created a Web-based database that allows physicians to submit their credentials in a single application to health-care organizations taking part in the program.

According to American Medical News (5/12/03), the service—known as the Universal Credentialing DataSource—allows physicians to submit one application with their credentialing information to a secure, central database. Updates to the database can be made by Internet or fax, and physicians must verify that the credentialing information is accurate and complete every quarter.

While the service is free to physicians, 23 health plans—including Aetna, Anthem Blue Cross and Blue Shield, CIGNA HealthCare, and Health Net—pay a $3,000 annual fee and $4.50 per plan physician to participate.

As of May, the service has been offered in 14 states and Washington, D.C. Plans are to expand the service nationwide by the end of the year.

Medical students oppose caps on noneconomic damages

Bucking the position of a number of US medical groups, the American Medical Student Association denounced caps on noneconomic damages as the sole solution to addressing skyrocketing insurance costs and medical malpractice reform.

The 40,000-member group established the policy in March at its annual convention, saying caps on such damages were "a 'simplified' approach that hurts patients and will do little to solve the so-called malpractice 'crisis,'" reported Modern Healthcare (4/14/03). Instead, the group advocates a "comprehensive, multifaceted approach" to deal with medical malpractice reform.

"Caps on noneconomic damages will harm only patients who have been deemed worthy of receiving compensation by our legal system. Evidence does not show that caps will eliminate frivolous lawsuits," said Eric Hodgson, MD, AMSA national president, in a press release. "Instead of penalizing our patients, it is time to call into question the insurance companies who are setting the exorbitant premiums—their practices are helping to drive this crisis. Any reform of the medical malpractice system should include insurance reform."

The student group also said that reducing preventable patient injury and providing fair and timely compensation to injured patients should be the most important goals of a medical malpractice system.

House passes patient safety bill; Senate considers it

The US House of Representatives recently passed and referred to the Senate legislation that would allow the voluntary and confidential reporting of medical errors and create a national database to collect and assess the data and recommend ways to avoid future errors. But the bill, which was overwhelmingly approved by the House by a vote of 418-6, has an uncertain future in the Senate.

The Patient Safety and Quality Improvement Act (HR 663) stipulates that the information gathered by the voluntary reporting of medical errors cannot be used as evidence against those who report the errors nor the reporting facilities in civil or administrative proceedings or accreditation actions. Moreover, the bill requires that a national database be created to collect and assess the reported data; the Department of Health and Human Services is charged with analyzing the information reported and disseminating its findings to the medical community.

Aimed at increasing patient safety, the House bill also contains mandates to help healthcare providers reduce medical errors. For instance, the bill requires HHS to offer grants to physicians and other health-care providers for implementing technology such as electronic prescription programs or new or improved computer hardware or software to improve patient safety. The bill would also require the use of bar codes on all FDA-regulated products.

Modern Healthcare (3/17/03) reported that some lawmakers are critical of the bill, citing concerns about its effectiveness in compelling providers to change their practices once trends have been identified, among other things. That viewpoint could derail the bill's passage in the Senate.

At press time, the bill was being considered by the Senate Committee on Health, Education, Labor, and Pensions.

 

Clinical Insights/Professional Update. Contemporary Ob/Gyn Jul. 1, 2003;48:16-22.