NEWS WATCH

CLINICAL INSIGHTS

Highlights from the 14th Annual Meeting of the North American Menopause Society

Can this insulin-sensitizing agent inhibit postmenopausal heart disease?

That's the implication of this preliminary Australian study presented at last month's North American Menopause Society's (NAMS) annual meeting in Miami Beach. Over 12 weeks, a small group of postmenopausal women with type 2 diabetes were randomized to either 4 mg of rosiglitazone or placebo daily. At the end of the 12 weeks, 50 µg of transdermal estradiol and 100 mg of micronized progesterone were added to the rosiglitazone regimen for an additional 12 weeks, with control patients again receiving placebo.

At the end of the first 12 weeks, rosiglitazone significantly improved triglycerides, systolic and diastolic blood pressure, blood flow in the brachial artery, and systemic arterial compliance, a measure of blood vessel elasticity. Unfortunately, adding HT to the mix wasn't very helpful: It reduced brachial artery blood flow and did nothing to any of the other vascular parameters.

Honisett S, Stojanovska L, Sudhir K, et al. The effects of rosiglitazone and HRT on vascular function in postmenopausal women with type 2 diabetes mellitus. (Abstract S-4)

Comparing the bone-sparing effects of bisphosphonates and HT

Stopping estrogen therapy quickly eliminates the hormone's beneficial effect on bone mineral density (BMD) in postmenopausal women, according to this NAMS presentation. But the same can't be said for alendronate, according to two placebo-controlled clinical trials.

In both trials—one among healthy women with an intact uterus, the other in osteoporotic patients without one—alendronate and HT (either estrogen/progestogen or estrogen alone) both increased BMD. But after withholding HT, lumbar spine BMD declined by almost 7.7% over 2 years among those in the prevention trial, compared to only 2.4% among those who stopped the bisphosphonate. In the treatment study, discontinuing HT caused a 4.5% drop in BMD after 1 year, while women who stopped alendronate had virtually no change in bone density. These results are consistent with a recently published international trial that found alendronate maintains or increases spinal and hip BMD in women who discontinue HT.

Simon J, Lombardi A, Santora A, et al. Consistent alendronate skeletal benefits in postmenopausal women with natural or surgical menopause. (Abstract S-2)

Ascott-Evans BH, Guanadens 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.

Soy isoflavones may improve postmenopausal memory

In healthy postmenopausal women, 40 g a day of isoflavone-rich soy powder may improve mental functioning. Participants in the Soy Health Effects Study were put on either a soy product containing 86 mg of isoflavones or one that did not contain these phytoestrogens. While both groups saw improvements in test scores that measured cognitive functioning over 2 years, the percent change was somewhat greater among women on isoflavones. Immediate verbal memory, for instance, improved by 27.2% in the isoflavone group versus 16.5% in the placebo group; similar differences were seen in tests that measure delayed verbal memory (39.9% vs. 29.2%).

Kritz-Silverstein D, von Muhlen D, Barrett-Connor E, et al. Soy and cognitive function in postmenopausal women. (Abstract S-10)

NAMS releases new HT guidelines

Based on the recommendations of a blue ribbon panel of clinicians and researchers, the latest NAMS guidelines on hormone therapy cover some familiar ground but also offer several valuable insights and nuances. Like most other expert groups, the panel reaffirmed that estrogen therapy (ET) and estrogen/progestogen therapy (EPT) are still indicated for the treatment of moderate-to-severe menopausal symptoms and should be offered at the lowest possible dose for the shortest amount of time. They urge clinicians to consider lower-than-standard doses of ET and EPT for vasomotor and vulvovaginal symptoms—daily doses of 0.3 mg conjugated estrogens tablets, 0.25–0.5 mg micronized 17ß-estradiol tablets, a 0.025 mg 17ß-estradiol patch or the equivalent—because research has shown that their effects are nearly equivalent to the standard doses.

It also generally recommends a local ET/EPT product when hormones are being considered solely for moderate-to-severe vulvar and vaginal atrophy.

With the WHI and HERS findings in hand, NAMS states emphatically that EPT should not be used to prevent heart disease. But the data on ET are less clearcut.

They also point out that both studies should be applied cautiously to women younger than 50 because WHI and HERS studied much older women. The entire list of NAMS recommendations is available at www.menopause.org/positionstatement.pdf .

Another reason to cut back on animal fat

In addition to reducing intake of saturated fats for cardiovascular health, women should reduce their consumption of dietary fat from animal sources to reduce their exposure to dioxins and dioxin-like compounds (DLCs), according to a report from the Institute of Medicine.

DLCs occur as widespread, low-level contaminants in animal feed and the human food supply. They accumulate in the fatty tissue of animals. Consumption of food products from such animals, such as meat and whole milk, is the primary pathway of contamination in humans. In humans, dioxins are metabolized slowly and accumulate in body fat over a lifetime. They have been linked to cancer and other health problems and can be passed through the placenta or through breast milk.

While levels of DLCs have dropped in recent years, the pollutants are still found in the environment. Since testing food for DLCs is not cost-effective at present and since a safe level of dioxin intake has yet to be determined, the government recommends healthier eating as the best precaution with no more than 10% of a person's daily diet coming from animal fat.

Dioxins and Dioxin-like Compounds in the Food Supply: Strategies to Decrease Exposure. The National Academies Institute of Medicine. July 1, 2003.

Using ultrasound to help pinpoint osteoporosis

Quantitative ultrasound is more reliable than asking women about risk factors for osteoporosis when it comes to identifying patients who should receive dual energy x-ray absorptiometry (DXA), according to a recent comparative study.

Researchers assessed 200 women between the ages of 60 and 69 attending a primary-care clinic in England over a 4-month period. They found that only 19% of the women with risk factors for osteoporosis actually had the condition, and that one third of the women with osteoporosis were missed by this method. Ultrasound scanning with a cutoff point of T=-1.7 doubled the specificity of risk factor inquiry while providing roughly the same sensitivity. Combining the two methods increased identification of women with osteoporosis to 90% and slightly increased prediction of women without the condition.

The researchers concluded that since good clinical practice requires an overall assessment, and since ultrasound scanning is simple, quick, nonionizing, portable, and inexpensive, primary-care practitioners should consider combining the methods to optimize their selection of women who should be followed up with DXA.

Hodson J, Marsh J. Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal osteoporosis: comparative study in primary care. BMJ. 2003; 326:1250-1251.

Are infants born on weekends more likely to die?

While decades-old studies indicate increased neonatal mortality for infants born on weekends as compared to weekdays, a recent study of more than 1.5 million births demonstrates that the minor increase in weekend neonatal mortality is a result of adverse birthweight distribution and not of compromised weekend perinatal care.

The study involved more than 1.6 million live births (weight >500 g) in California between 1995 and 1997. Observed neonatal mortality rates averaged 2.80 deaths per 1,000 live weekday births and 3.12 deaths per 1,000 live weekend births. Although there was a 17.5% decrease in all births on weekends, the decrease was least pronounced among smaller infants, resulting in a higher weekend concentration of very low-birthweight (<1,500 g) births and, consequently, higher mortality. Once researchers adjusted for birthweight and for congenital abnormalities, the increased likelihood of death for infants born on weekends was not statistically significant.

The study also found a decrease in the proportion of cesarean deliveries from 22% on weekdays to 16% on weekends, suggesting that the national Healthy People 2010 goals of a primary cesarean delivery rate of 15% and a repeat rate of 63% may be possible to achieve without compromising neonatal mortality.

Gould JB, Qin C, Marks AR, Chavez G. Neonatal mortality in weekend vs. weekday births. JAMA. 2003;289:2958-2962.

Monochorionic always = monozygotic...or does it?

A case report of monochorionic, dizygotic twins in The New England Journal of Medicine disproves the long-held notion that monochorionic twin placentas are monozygotic. More importantly, the unusual gestation suggests that assisted reproductive technology (ART) may influence normal development in unexpected ways.

Researchers from the University of Washington reported on a 48-year-old woman who conceived twins by in vitro fertilization (IVF) without intracytoplasmic sperm injection and with the help of donor oocytes. Three blastocysts were placed in the patient's uterus and ultrasound (U/S) at 12 weeks' gestation showed a viable twin pregnancy. The findings—thin intertwin membrane, T-shaped insertion of the membrane, and absence of the lambda sign—all suggested a monochorionic, diamniotic gestation. U/S at 20 weeks' gestation also suggested monochorionicity but suggested sex discordance.

A healthy boy and girl with no evidence of sexual ambiguity were delivered at 37 weeks' gestation. Pathologic examination of the placenta showed that it was monochorionic and diamniotic. Zygosity and cytogenetic studies of peripheral blood were done at 1 week and 3 months of age. The initial zygosity studies showed a 99.9% probability that the twins came from a single zygote, whereas on zygosity tests of skin (done at 5 months), they differed at 16 of 26 markers, suggesting dizygosity. The girl was 46,XY[96]/46,XX[4] at 3 months and 46,XY[91]/ 46,XX[9] at 5 months and the boy was 46,XY[46]/46,XX[4] and 46,XY[92]/46,XX[8] at the same time periods. Physical examination and ultrasound studies at 5 months were normal.

Three scenarios, the authors speculate, could lead to a dizygous, monochorionic gestation: (1) fusion of the chorions early in pregnancy, with subsequent degeneration of the fused chorion within the dividing membrane; (2) fusion of trophoblasts from two embryos before implantation, creating genetically distinct, nonchimeric inner cell masses in a chimeric trophoblast "shell"; and (3) double fertilization of the meiotic products of a single oocyte with two sperm, leading to "sesquizygotic" twins that each have distinct paternal and identical maternal genomes. The mechanism in this case is unknown, but the authors comment that the event may have been promoted by ART because IVF is associated with an increase in embryo splitting and monozygotic twinning and blastocyst culture may further amplify this risk.

Souter VL, Kapur RP, Nyholt DR, et al. A report of dizygous monochorionic twins. N Engl J Med. 2003;349:154-158.

Adjunctive ultrasonography improves breast cancer detection

Adding ultrasonography to clinical breast examination (CBE) and mammography (MAM) significantly increases the diagnostic yield for breast cancer, according to a recent study.

Researchers from the Netherlands examined almost 4,000 breasts in just over 2,000 patients during a 10-month period. The prevalence of breast cancer was 6.3%. Breast ultrasonography detected eight additional malignancies missed by CBE and MAM alone and correctly downgraded 332 cases from positive to negative. On the other hand, the procedure yielded 46 false-positive results and one false-negative. The three procedures in combination had an overall sensitivity of 96.9% and a specificity of 94.8%.

The authors of the study caution that ultrasonography should be restricted to patients most likely to benefit in order to contain costs and other consequences of unnecessary examinations. According to their results, ultrasonography is most beneficial for patients referred for palpable lumps, in which ultrasonography downgraded 133 positive results from CBE plus MAM and detected three new malignancies, and women with abnormal screening MAM results, of which ultrasonography correctly downgraded 29 positive MAM results to a negative diagnosis and detected no new malignancies.

Flobbe K, Bosch AM, Kessels AG, et al. The additional diagnostic value of ultrasonography in the diagnosis of breast cancer. Arch Intern Med. 2003;163:1194-1199.

Women may ovulate more than once a month

It's possible that many women ovulate two or even three times a menstrual cycle, according to Canadian researchers. Not only may the finding rewrite the textbooks, it would also explain why the "rhythm" method is unreliable, why hormonal contraceptives sometimes fail even when used correctly, and why it is possible to have fraternal twins with different conception dates. The finding that women can potentially yield many more oocytes per month also offers new hope for assisted reproduction.

In a prospective, longitudinal study, researchers from the University of Saskatchewan performed daily ultrasound scans on 63 women with normal menstrual cycles. Some were nulliparous, while others had up to three children. The researchers found that contrary to long-held belief, 68% of the women exhibited two waves of follicle development per menstrual cycle and 32% exhibited three waves. Waves were characterized by an increase and subsequent decrease in number, as well as size, of follicles. Current technology allows for viewing of follicles, but not of actual eggs, so while the findings are suggestive, they are not conclusive.

Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003;80:116-122.

Alcohol consumption may lower risk of type 2 diabetes

A glass or two of wine or beer a day may lower the risk of type 2 diabetes mellitus in premenopausal women, according to a prospective study of 109,690 participants between the ages of 25 and 42 in the Nurses' Health Study II.

Researchers found a significant inverse relationship between alcohol intake and risk of diabetes up to 29.9 g/d. Women consuming 0.1 to 4.9 g/d alcohol reduced their risk by about 25%, while those consuming 5.0 to 29.9 g/d reduced their risk by about 50%. Adjustment for variables such as cigarette smoking, use of oral contraceptives, history of high blood pressure and/or cholesterol, or infertility, use of an antihypertensive drug, physical activity, and family history of diabetes did not significantly alter the relationship.

The relationship was slightly stronger in inactive, as opposed to active, women and was more apparent in beer and wine drinkers.

Wannamethee SG, Camargo CA Jr, Manson JE, et al. Alcohol drinking patterns and risk of type 2 diabetes mellitus among younger women. Arch Intern Med. 2003;163:1329-1336.

Outcomes for people with open spina bifida vary widely

The long-term outcome for adults with open spina bifida ranges from virtually normal to severely disabled, with approximately half dying by about age 35 and 37% of survivors requiring daily care, according to a community-based, prospective study of an unselected cohort in England.

Of 54 survivors in the study, 46 had a cerebrospinal fluid shunt, 39 had an IQ less than or equal to 80, 16 could walk 50 meters or more with or without aids, 11 were fully continent, 30 had had pressure sores, and 30 were overweight. Twenty-two lived independently in the community, although seven of those were confined to wheelchairs. Twelve lived in situations in which help was available if needed, and 20, who were severely disabled, needed daily care, either from a parent, partner, or social services. Thirteen were employed and nine had had children, none of whom had visible spina bifida.

The authors of the study hope that the information will help guide parents, as well as those counseling them, to make informed decisions concerning termination of pregnancy and treatment at birth.

Hunt GM, Oakeshott P. Outcome in people with open spina bifida at age 35: prospective community based cohort study. BMJ. 2003;326:1365-1366.

Early puberty a strong risk factor for breast cancer

Early exposure to pubertal hormones, rather than excessive cumulative hormone exposure over time, is a strong risk factor for an earlier diagnosis of breast cancer, according to a recent case-control study of 1,900 pairs of twins in whom one or both developed the disease.

The researchers found that within disease-discordant monozygotic pairs of twins, relative age at puberty was unrelated to the risk of breast cancer. But in disease-concordant pairs, the first twin to enter puberty, especially if she did so before the age of 12 years, was more than five times as likely to receive a diagnosis of breast cancer first. In fact, earlier puberty ranked among the strongest predictors of breast cancer; age at first full-term pregnancy, parity, and age at menopause were all unrelated to the sequence of breast cancer diagnoses.

The authors of the study note that as the age at puberty continues to decline, a larger group of women may be at increased risk.

Hamilton AS, Mack TM. Puberty and genetic susceptibility to breast cancer in a case-control study in twins. N Engl J Med. 2003;348:2313-2322.

Clear amniotic fluid: unreliable sign of fetal wellness

Most infants with a poor outcome do not pass meconium during labor, according to a prospective cohort study.

The authors of the study, which involved over 8,000 low-risk laboring women, calculated that meconium was passed in 5.2% of labors, but was not detected until delivery in more than half (51.5%) of these. While the presence of meconium was associated with moderate or severe acidosis, low Apgar score at 5 minutes, and neonatal seizures, meconium was not a very sensitive marker for these problems. The study also found that meconium is more likely to be passed with longer labors, oxytocin usage, epidural analgesia, and in nulliparous women.

The take-home message: Don't be lulled into complacency by clear amniotic fluid.

Greenwood C, Lalchandani S, MacQuillan K, et al. Meconium passed in labor: how reassuring is clear amniotic fluid? Obstet Gynecol. 2003;102:89-93.

PROFESSIONAL UPDATE

Do you give patients what they ask for?

More and more patients are making direct requests of their physicians for certain clinical services. And those who make such requests for diagnostic tests, specialty referrals, or new prescription medication are more likely to get what they ask for, according to a study in the Archives of Internal Medicine (7/28/03).

Specifically, the study's researchers found that almost one in four patients directly requested at least one diagnostic test, a new prescription, or referral to a specialist. Moreover, patients were more likely to receive a referral to a specialist or a new prescription when they requested it. Still, 13% of patients made at least one request for services that was "overtly denied, passively skipped, or incompletely fulfilled."

So how do doctors feel about all this "patient participation"? The researchers found that physicians rated encounters with patients who requested diagnostic tests as more demanding than visits in which no such requests were made, but there was no increase in stress by physicians who cared for patients who requested referrals or new prescriptions.

The researcher's findings were based on tape-recorded encounters between 559 patients who had a new problem or significant health concern and 45 physicians practicing internal medicine, family medicine, and cardiology in two health systems in Sacramento, Calif.

Hospital-physician relationships: Beware the legal entanglements

With the recent federal grand jury indictments of Tenant HealthSystems Hospitals and Alvarado Hospital Medical Center, both subsidiaries of Tenet Healthcare Corp., physicians and hospitals need to pay extra attention to referral arrangements to ensure compliance with federal Stark II laws.

The Stark laws prohibit Medicare payment to a provider if patients are referred by physicians who have a financial relationship with the provider. Exceptions to the law exist, however, and physicians and hospitals need to ensure that any hospital-physician agreements comply with these exceptions to avoid criminal charges.

For example, according to MD Practice Alert (7/30/03), under the bona fide employment exception, any remuneration provided under an agreement must be commercially reasonable even if no referrals are made. That means that any hospital-physician agreement would have to meet (1) the fair market value standard, which ensures that the transaction is consistent with general market value, and (2) the commercially reasonable standard, which ensures that the arrangement is "a sensible, prudent business agreement from the perspective of the particular parties involved," said Thomas Becker, a physician compensation expert and senior consultant with Clark Consulting.

While the fair market value of a deal can be determined by using comparable transactions such as salary survey data, determining whether an arrangement is commercially reasonable is a subjective art. Looking at the facts, such as whether there are business reasons for adding doctors or increasing compensation, would need to be explored to determine if the agreement satisfies Stark II.

Many states fail to live up to newborn testing recommendations

When it comes to adequate screening of newborns for metabolic disorders, few states are making the grade, according to the March of Dimes. Only nine states screen for the nine disorders recommended by the national nonprofit health organization, and 18 states plus Puerto Rico offer five or fewer tests.

In 2000, the March of Dimes recommended that every newborn in the United States be screened at a minimum for the following treatable disorders: phenylketonuria (PKU), congenital hypothyroidism, congenital adrenal hyperplasia (CAH), biotinidase deficiency, maple syrup urine disease, galactosemia, homocystinuria, sickle cell anemia, and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

The nine states that offer tests for all nine of the recommended disorders are Illinois, Indiana, Maine, Massachusetts, Mississippi, New York, Oregon, Rhode Island, and Wisconsin. The 18 states that offer five or fewer tests are Alabama, Arkansas, California, Florida, Kansas, Kentucky, Louisiana, Missouri, Montana, New Hampshire, Oklahoma, South Dakota, Tennessee, Texas, Utah, Washington, West Virginia, and Wyoming.

The March of Dimes and the American Academy of Pediatrics also advise a hearing test for newborns—and all states and the District of Columbia have complied. However, 11 states—Alaska, California, Iowa, Louisiana, Maryland, New Hampshire, North Dakota, Ohio, Pennsylvania, South Dakota, and Washington—do not ensure that at least 90% of newborns born in the state are actually tested.

FTC settles antitrust charges against physicians

The Federal Trade Commission recently settled antitrust charges against the Washington University Physician Network in St. Louis. The FTC charged that the not-for-profit, 1,500-member physicians' network collectively negotiated contracts between its members and third-party payers, raising the cost of medical care in the city's market, according to Modern Physician (07/15/03).

In the proposed settlement, the medical group is prohibited from negotiating with payers on behalf of those doctors in the group's PPO network. These doctors must now negotiate contracts with payers individually. In addition, the medical group cannot share information about contract terms among its members. Each violation of the settlement's terms could result in an $11,000 civil penalty for the group.

A pay-for-performance program uses report cards to rate MDs

Starting in September 2004, the National Committee for Quality Assurance will issue "report cards" grading the clinical performance of certain medical groups participating in a performance-based rewards program. Financial bonuses will be awarded based on the report cards, as well as patient satisfaction surveys and efforts to utilize clinical information technology.

The rewards program, called Pay for Performance, is an effort by the Integrated Healthcare Association, a healthcare policy group, to promote quality with financial incentives. Six insurers—Aetna, Blue Cross of California, Blue Shield of California, Cigna, Health Net, and PacifiCare—have agreed to pay bonuses to physicians who meet performance goals during a 3-year period that started in January.

The report cards, which will make up 50% of each medical group's performance score, will focus on each group's efforts in preventive care for administering mammograms, Pap smears, and childhood immunizations, and in chronic disease management of patients with asthma, diabetes, and coronary artery disease. Patient satisfaction surveys will account for 40% of the score, and the integration and physician access to information technology will account for 10%.

Most wanted doctors: Don't count yourself out

Demand for physicians is no longer centered on three or four specialties, according to Merritt, Hawkins & Associates, an Irving, Tex.-based recruiting firm. Although the demand for radiologists, orthopedists, cardiologists, and anesthesiologists remained strong over the past year, Merritt's recruiting assignments focused on other areas, such as pediatric subspecialties, as well. While the need for primary-care physicians is less acute than for specialists, ob/gyns, family practitioners, and internists still rank among the firm's top 10 searches.

What potential employers are willing to pay (2002-03)

Female physicians should practice what they preach

While nearly all women MDs say they exercise, fewer than half exercise enough to meet the American College of Sports Medicine's recommendation. And as you might expect, the exercise habits of female physicians influence their counseling of patients on the subject, according to a recent study in the Journal of the American Medical Women's Association (Summer 2003). The study's researchers found that while 96% of the female physicians surveyed got some form of exercise, just 49% reported exercising a minimum of 30 minutes at least three times per week as recommended by ACSM.

Moreover, the researchers found that those female physicians who comply with the ACSM recommendations were more likely to discuss exercise with their patients at every visit, to be confident in their ability to counsel patients about exercise, and to have extensive training in the subject. In addition, wrote the researchers, "Having a high priority to exercise more was associated with greater odds of frequent exercise counseling."

 

Clinical Insights/Professional Update. Contemporary Ob/Gyn Oct. 1, 2003;48:15-29.