NEWSLINE

CLINICAL INSIGHTS

Can aspirin reduce the risk of breast Ca?

Women who take aspirin regularly are about 26% less likely to develop breast cancer than those who don't, according to New York researchers.

The population-based case–control study of almost 3,000 women with and without breast cancer found the association to be strongest among women who take at least one tablet of aspirin per day, among those who take aspirin alone or with other nonsteroidal anti-inflammatory drugs (NSAIDS) (as opposed to other NSAIDS alone), and among current and recent users (within the last 5 years). And they specifically found that aspirin protected most against hormone receptor-positive cancers, reducing the risk by 26% (OR 0.74, 95% CI 0.60–0.93). The findings did not pertain to ibuprofen or acetaminophen.

PLEASE NOTE: If you are using Internet Explorer version 6 or higher, after clicking to enlarge the graphic, click the picture icon that appears in the lower right-hand corner of the graphic.

How might COX-2 inhibitors like aspirin slow down estrogen biosynthesis? In the receptor-positive breast cancer cell at the top of the drawing (1),, various tumor promotors stimulate production of the enzyme cyclooxygenase 2 (COX-2) which in turn is responsible for prostaglandin synthesis (2). Increased PGE₂ production then prompts the formation of aromatase (3) (4), the crucial enzyme that catalyzes the conversion of androgens to estrogens (5). The new research suggests that COX-2 inhibitors block prostaglandin synthesis, slowing down the long chain of events that leads to estrogen production in cancer cells.

While the mechanism of prevention is unclear, experts surmise that inhibition of estrogen biosynthesis plays an important role, as the illustration to the right suggests. While experts generally agree that it is too soon for all women to begin taking aspirin daily solely to prevent breast cancer, clinicians may want to consider this for women at highest risk.

Terry MB, Gammon MD, Zhang FF, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA. 2004;291:2433-2440.

A cluster of early symptoms may help pinpoint ovarian Ca

Contrary to conventional wisdom, ovarian cancer may often be preceded by a cluster of symptoms, according to a recent prospective, case–control study. Researchers have found that women with ovarian masses found at surgery to be malignant tend to report symptoms—albeit broad and sometimes indistinct—of greater severity, greater frequency, and of more recent onset than women with benign masses or other conditions.

Of the women in the study with ovarian cancer, 94% had symptoms—most commonly bloating, increased abdominal size, fatigue, urinary tract symptoms, and pelvic or abdominal pain—in the prior year and 67% had recurring symptoms. Women with malignant masses typically experienced symptoms 20 to 30 times per month. Symptoms such as abdominal or pelvic pain, bloating, constipation, and increased abdominal size, which often point toward irritable bowel syndrome (IBS), were found to be significantly more severe among the women with ovarian cancer than among those found to have IBS.

Researchers also found that such symptoms usually plagued patients with ovarian cancer for about 3 to 6 months prior to a diagnosis, while those with IBS suffered with the symptoms for 1 to 2 years.

The combination of bloating, increased abdominal size, and urinary symptoms was particularly telling, occurring in 43% of the women with cancer and in only 8% of those presenting to primary care clinics.

The authors noted that as cancer patients aged, almost all such symptoms became less frequent and less severe, underscoring the importance of not attributing symptoms associated with ovarian cancer to the aging process.

Goff BA, Mandel LS, Melancon CH, et al. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291:2705-2712 and Daly MB, Ozols RF. Symptoms of ovarian cancer—where to set the bar? JAMA. 2004;291:2755-2756.

Breast milk may prevent atherosclerosis later in life

What a newborn consumes at birth and soon after may permanently shape his or her lipoprotein and cardiovascular profiles, according to the first study to use random assignment of infant diet with prospective follow-up.

The study from England found that at 13 to 16 years of prospective follow-up, adolescents born preterm who received banked breast milk as their sole diet or in addition to their mother's milk had lower C-reactive protein (CRP) concentrations and 14% lower low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol ratios than adolescents who received formula at birth. The researchers also found that greater consumption of human milk in infancy was associated with lower LDL to HDL and apolipoprotein (apo) B to apo A-1 ratios independent of gestational age and potential confounding factors and with reduced CRP concentration later in life.

Because the initial stages of atherosclerosis are strongly related to lipoprotein concentrations in children, breastfeeding in infancy has the potential to protect people from the disease from a young age, to significantly lower cardiovascular mortality, and to do so to a greater extent than dietary interventions in adulthood.

Singhal A, Cole TJ, Fewtrell M, et al. Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study. Lancet. 2004;363:1571-1578.

Using the right stats when discussing a treatment's dangers

The way a physician presents statistics on the risks and benefits of a specific medical intervention can have a profound effect on the decisions patients make concerning treatment.

Study participants presented with only relative risk figures were twice as likely to choose chemotherapy as those presented with absolute risk figures. When subjects were given statistics in four of the most common ways of presenting survival data—relative risk reduction, absolute risk reduction, absolute survival benefit, and number needed to treat—participants reported being confused and less able to make a decision at all.

The researchers concluded that the most effective and least confusing way of presenting data is to use absolute risk reduction and to explain the data using charts or other visual aids that help ensure that all patients make fully informed health-care decisions.

Hede K. When 50 percent is not the same as a coin toss: study examines decisions made based on statistics. J Natl Cancer Inst. 2004;96:737-738 and Chao C, Studts JL, Abell T, et al. Adjuvant chemotherapy for breast cancer: how presentation of recurrence risk influences decision-making. J Clin Oncol. 2003;21:4299-4305.

Providing ECs in advance doesn't lower abortion rate

Having emergency contraception (EC) on hand at home does not reduce the number of abortions, according to a study from the United Kingdom.

Researchers undertook a community intervention study of all women aged 16 to 29 living in Lothian, Scotland. The researchers gave the women five courses of EC free of charge to keep at home.

Of about 85,000 women in this age group, about 17,800 took at least one supply home; over 4,500 gave at least one course to a friend. Not quite half (about 45%) of the women who had a supply used at least one course during the 28-month study. Despite use of EC within 24 hours of unprotected intercourse, about three quarters of the time, abortion rate remained unaffected.

Glasier A, Fairhurst K, Wyke S, et al. Advanced provision of emergency contraception does not reduce abortion rates. Contraception. 2004;69:361-366.

Mammography: tool for detecting cardiovascular disease?

The presence of breast vascular calcifications on routine screening mammography increases the risk of coronary artery disease by 32%, the risk of ischemic stroke by 41%, and threat of risk of heart failure by 52%, according to a cohort study of almost 13,000 women between the ages of 40 and 79. No significant relationships were found with transient ischemic attacks or hemorrhagic stroke.

Breast vascular calcification was present in about 3% of the women studied. The increased risks were tallied after adjustment for age, education level, race, cigarette smoking, alcohol use, body mass index, serum total cholesterol, hypertension, diabetes, parental history of myocardial infarction, parity, and hormone replacement therapy.

The researchers concluded that because mammography is relatively inexpensive and is recommended yearly after age 40 anyway, it may prove to be a useful adjunctive tool in the prediction of cardiovascular disease risk.

Iribarren C, Go AS, Tolstykh I, et al. Breast vascular calcification and risk of coronary heart disease, stroke, and heart failure. J Women's Health. 2004;13:381-389.

Risk factors for postmenopausal UTIs

Having sex more than once per week, a history of urinary tract infection (UTI), treated diabetes mellitus, and incontinence place postmenopausal women at greater risk for a UTI, according to a population-based, case–control study of almost 2,000 healthy, community-dwelling women between the ages of 55 and 75.

Investigators point out that the risk factors for UTI in this population reflect the health status of women as they transition toward old age.

As with younger women, Escherichia coli is the most common infective agent, causing up to 82% of UTIs in this population. Despite the findings of some previous studies, oral estrogen replacement therapy did not reduce the risk of UTI.

Hu KK, Boyko EJ, Scholes D, et al. Risk factors for urinary tract infections in postmenopausal women. Arch Intern Med. 2004;164:989-993.

Does gum-chewing help surgical recovery?

A small randomized study presented at ACOG's annual meeting in Philadelphia suggests it may. And since gum-chewing is inexpensive, it may promote early recovery from postoperative ileus, according to the investigators.

Sixty-four women who underwent abdominal laparotomy participated in the study, done at St. Luke's-Roosevelt Hospital Center, New York, NY. Beginning on the first postop day and continuing until passage of flatus, half the patients chewed gum three times per day and half did not. The gum-chewers passed flatus 11 hours earlier than the non-gum-chewers (44 vs. 55 hours; P<0.03). Times to defecation were comparable in the two groups: 2.5 versus 2.6 days. The gum-chewers had slightly longer postoperative hospital stays: 3.6 versus 3.2 days. Use of gum was not associated with any major complications.

Lee DDK, Runowicz CD, Chambers JT, Langer O. Efficacy of gum chewing in improving the recovery of bowel function after major gynecologic surgery. Obstet Gynecol. 2004;103(suppl):21S.

Pica increases the threat of preterm delivery

An uncommon occurrence, but one that is associated with spontaneous preterm birth (SPTB), pica is harmful to any woman, but presents real danger to a pregnant woman and her baby by blocking iron absorption and causing severe anemia. Adjusting for race, alcohol use, and prior SPTB, women with pica are almost twice as likely to deliver preterm, when compared to those on a normal diet. (OR 1.9, 95% CI 1.1-3.3) For instance, SPTB at less than 37 weeks occurred in 12% of women with pica, versus 6% in those without.

In a study presented at the 2004 ACOG Annual Meeting, Manisha V. Patel, MD, and associates, from the University of Alabama at Birmingham, observed 3,149 pregnant women at 19 to 26 5/7 weeks' gestation, with an overall pica prevalence of 4%.

Pica was more prevalent in black (5%) than in nonblack women (1%, P< 0.0001) and more prevalent in women who drank one or more alcoholic drinks per day as opposed to those who did not. Anemia (hematocrit < 30) was higher in women with pica (15%) than in those without (6%), (P=0.01).

Patel MV, Nuthalapaty FS, Ramsey PS et al. Pica: A neglected risk factor for preterm birth. Obstet Gynecol. 2004; 103 (4, Suppl.): 68S.

Mammography can rupture breast implants

Both silicone gel and saline breast implants may rupture, or existing ruptures may be exacerbated, during compression for screening mammography. In fact, during a 9-year period, at least 33 cases of implants rupturing during mammography were reported to the Food and Drug Administration and at least 17 more were reported in the medical literature, according to agency researchers.

It is unclear whether compression ruptures the implant itself or the scar capsule, converting an intracapsular rupture into an extracapsular one. Regardless, over time as an implant remains in place, pressure resistance and implant strength decrease, which places older implants at greater risk of rupture. Capsular contracture, capsular thickness, and calcification can also increase risk.

Because implants can decrease the amount of breast tissue that is visual on mammography by about 80%, modified positioning techniques, such as the Eklund or pinch technique, are often employed. Such methods, which involve pulling the breast tissue away from the implant and compressing the tissue with up to 45 pounds of force, need to be employed extremely carefully to avoid implant rupture.

Brown SL, Todd JF, Luu HMD. Breast implant adverse events during mammography: reports to the Food and Drug Administration. J Women's Health. 2004;13:371-378.

Cerclage doesn't prevent preterm birth

While it is true that having a shorter cervix is associated with preterm delivery, cervical cerclage with a Shirodkar suture makes no difference in the outcome, according to a randomized, controlled trial of more than 47,000 pregnant women in various countries.

Researchers randomized women with a cervix of 15 mm or less in length to receive either cervical cerclage or expectant management. The proportion of preterm deliveries before 33 weeks' gestation was similar in both groups: 22% in the cerclage group vs. 26% of controls. The procedure also did not reduce perinatal morbidity or mortality.

To MS, Alfirevic Z, Heath VCF, et al. Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial. Lancet. 2004;363:1849-1853.

Can clomiphene therapy be individualized?

A meta-analysis on the relationship between clomiphene dosage and patient response suggests the answer may be yes. The authors caution, however, that prospective studies are necessary to confirm that dosing can be tailored and outcomes improved by monitoring plasma levels of zuclomiphene, an active metabolite of the drug.

Researchers from the University of Sheffield, Sheffield, UK, performed a meta-analysis of 13 published reports on results with clomiphene citrate therapy, which typically is given in 50-mg doses orally on days 2 to 5 of the menstrual cycle. Doses of 100 or 150 mg/day are given to women who do not respond in the first cycle, leading to a 1-month or longer delay in success in these individuals.

The analysis suggests metabolism of the key components of clomiphene citrate—zuclomiphene and enclomiphene—may vary from patient to patient. Women who more rapidly absorb and eliminate zuclomiphene may need higher drug dosages to trigger ovulation. The converse may be true for women who are slow to metabolize the isomer, i.e., those who absorb and eliminate zuclomiphene more slowly may need lower doses.

Monitoring plasma concentrations of zuclomiphene during therapy may help clinicians more quickly identify patients who are likely to respond only to higher-than-normal doses of clomiphene, need lower-than-normal dosages, or are unlikely to respond to clomiphene whatever the dosage. This more individualized approach, the researchers say, could reduce the need for multiple clinic visits, increase the likelihood of singleton pregnancy, and decrease the risk of multiples.

Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL. Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril. 2004;81:1187-1193.

PROFESSIONAL UPDATE

Waiting for an appointment with an ob/gyn

Patients in Boston wait the longest for an appointment with an obstetrician/gynecologist—an average of 45 days—compared to those in 14 other metropolitan areas. In contrast, patients in Miami wait the least amount of time—an average of 10 days, according to a survey conducted by a national physician search and consulting firm.

Posing as new patients, survey researchers from Merritt, Hawkins & Associates tried to make appointments for routine gynecologic exams in doctors' offices in 15 metropolitan areas—Atlanta, Boston, Dallas, Denver, Detroit, Houston, Los Angeles, Miami, Minneapolis, New York, Philadelphia, Portland, San Diego, Seattle, and Washington, D.C.

Among all the cities surveyed, the average time to get an appointment with an ob/gyn was 23.3 days. In 13 of the 15 cities, average wait times were 14 days or more. In eight of the 15 cities, average wait times exceeded 21 days.

According to the Irving, Texas-based firm, physician practices that are booked more than 14 days out are considered busy and may need to consider adding a new associate. In addition, accessibility to physicians becomes a problem—one that may force privately insured patients to seek non-emergent care in hospital emergency rooms.

Clinicians place onus of patient safety on nurses

More than 90% of physicians, administrators, and pharmacists, as well as 96% of nurses, say patient safety rests in the hands of nurses, according to a study in the American Journal of Nursing (6/04). Yet, just 8% of physicians cite nurses as part of the "patient-care decision-making team."

This disparity may put nurses between a rock and a hard place when it comes to dealing with physicians or fulfilling their responsibilities. According to the study's researchers, the survey results may indicate reluctance on the part of nurses to question the clinical judgment of physicians or initiate corrective action in response to an error.

The study was based on the survey responses of nurses, physicians, pharmacists, administrators, and other health-care providers from 29 rural hospitals in nine Western states over a 3-year period.

Audit rates rise for six-figure taxpayers

If you earned $100,000 in 2003, you may have been among the 1% of those in this group to be audited. The audit rate among high-earning taxpayers was higher than that of all taxpayers overall, according to Medical Economics (5/21/04), which cited figures from the Internal Revenue Service. For all taxpayers, the audit rate was 0.7%.

Over the last 2 years, audit rates for high-earning taxpayers have been going up. In 2003, the audit rate for taxpayers earning six-figures or more rose 24%, compared to a 14%-increase for all taxpayers.

Request to soften AMA's gift guidelines rejected

At the request of a group of Washington, D.C. physicians, the American Medical Association's House of Delegates considered, and rejected, a resolution that would revise the kinds of gifts physicians could accept from the pharmaceutical industry. The D.C. doctors stated that the current guidelines are "cumbersome, onerous, and inconsistent, in that it undervalues physicians' time as professionals."

The physicians want AMA delegates to create a "separate parallel policy" that would allow them to accept gifts "under more realistic guidelines," reported the Chicago Tribune (6/10/04). Current AMA policy allows physicians to accept money for educational or research purposes from the pharmaceutical industry, as long as it comes through another organization or foundation.

The House of Delegates rejected the resolution, according to a preliminary report of its actions. It noted that creating a parallel policy would be confusing and that watering down current AMA guidelines could increase the risk of liability for physicians.

The verdict is in on malpractice awards

Childbirth negligence cases had the highest median jury award in 2002 of all medical malpractice cases analyzed by Jury Verdict Research. Data in the annual "Current Award Trends in Personal Injury" showed that the median award for such negligence was $2,252,645. Moreover, plaintiffs won 60% of childbirth negligence cases in 2002, up from 55% in 2001 and 34% in 2000.

Between 1999 and 2002, medical malpractice cases accounted for 52% of jury awards of $1 million or more. Overall, the median award in malpractice cases was $1,010,858 in 2002, up slightly from the $1 million median award reported in 2001 and 2000.

The data also showed that, while physicians won the majority of malpractice cases, plaintiffs still won 42% of the time in 2002, up from 40% in 2001. While the 2-percentage-point increase seems slight, it actually means that plaintiffs won 5% more cases than they did in 2001.

"With the average cost of each loss more than $1 million, 5% is a significant increase," Richard E. Anderson, MD, chair of The Doctors Co., a physician-owned national medical liability insurer, told American Medical News (4/19/04).

President wants electronic records in place within 10 years

President Bush recently called for the implementation of personal electronic medical records (EMRs) that could be accessed and added to by health-care providers with the patient's authorization, reported American Medical News (5/17/04). The goal is to have a secure electronic system to store patients' medical information within 10 years.

During a speech before the American Association of Community Colleges, the president outlined his vision: EMRs—which store a patient's history, prescription information, and other data, such as laboratory test results or x-rays—would be available online for use by a patient's numerous health-care providers.

While physicians and health groups are applauding the President's idea, questions about funding for the project have been expressed. "One thing we don't want to see is an unfunded mandate that forces physicians into somehow having to purchase hardware or software to accomplish this, especially in the current environment where the pressures on physicians are so great," American Medical Association Trustee and gynecologist Joseph M. Heyman told AMNews.

An initial investment of up to $50,000 per physician is needed to implement an EMR system, according to a study by the California Healthcare Foundation. The initial cost can be recouped within a few years, with physicians saving $20,000 per year. In addition, EMRs can help reduce redundant testing, eliminate medical errors, and prevent adverse effects caused by conflicting courses of treatment.

Study looks at errors in primary care

Seemingly trivial errors made in the primary care setting can have serious consequences for patients, including emotional distress, temporary or permanent injury, and even death, according to a recent report based on 15 years of malpractice claims. The researchers of the report reviewed nearly 50,000 malpractice claims made against primary care physicians between 1985 and 2000, and identified 5,921 cases involving medical errors.

Diagnostic mistakes (2,003 errors) were the most common underlying cause of errors, followed by failing to monitor or supervise a patient (972 errors), reported American Medical News (5/3/04). Problems with records was the top contributing factor leading to errors in general (439 errors) and to death (156 errors).

The report's findings are based on data from the Physician Insurers Association of America's Data Sharing Project. Considering the source, experts urge caution in drawing conclusions about primary care errors and patient harm.

"This is a study of malpractice claims, not of injuries or errors. You must not equate the two. Claims capture a very small fraction of incidents, and most importantly, not a random or representative fraction," Lucian Leape, MD, patient safety pioneer and adjunct professor of health policy at the Harvard School of Public Health in Boston, told AMNews.

The report, whose researchers are from the Robert Graham Center in Washington, D.C., was published in the April edition of Quality and Safety in Health Care.

Health illiteracy widespread

Almost half of all US adults (about 90 million people) have difficulty understanding and implementing health information, according to a report from the Institute of Medicine of the National Academies. Such health illiteracy contributes to higher rates of hospitalization and use of emergency services and to billions of dollars being spent unnecessarily.

The problem is more than just an inability to read and is not limited to the uneducated or poor. Health literacy—defined as the degree to which people can obtain, process, and understand basic information and services needed to make appropriate decisions regarding their health—requires writing, listening, speaking, arithmetic, and conceptual skills. According to the report, at some point, most individuals will encounter health information they cannot understand. Contributing factors are the ever-increasing complexity of the healthcare and insurance systems, of medical procedures, and of forms, and the economic pressure on health care workers to spend less time with patients.

Copies of Health Literacy: A Prescription to End Confusion are available from the National Academies Press; tel. (202) 334-3313 or 1-800-624-6242 or on the Internet at http://www.nap.edu.

NEWSLINE: Clinical Insights/Professional Update.

Contemporary Ob/Gyn

Aug. 1, 2004;49:13-24.