NEWSLINE

CLINICAL INSIGHTS

MRI more sensitive, but less specific than mammography

In women at high risk for breast cancer, magnetic resonance imaging (MRI) detects almost twice as many tumors as mammography, but costs significantly more and puts about three times as many women through the trauma of unnecessary biopsies, according to a prospective, nonrandomized study from the Netherlands.

The trial, partly financed by the Dutch Health Insurance Council, involved more than 1,000 women with a genetic or familial predisposition to breast cancer, 358 of whom had BRCA mutations. The women, who had a cumulative lifetime risk of the disease of 15% or more, were screened every 6 months with a clinical breast examination (CBE) and once yearly by mammography and MRI, with independent readings.

Researchers calculated the sensitivity of CBE, mammography, and MRI to be 17.9%, 33.3%, and 79.5%, respectively and the specificity to be 98.1%, 95%, and 89.8%, respectively. Overall, 32 cancers were found by MRI, 22 of which were not visible on mammography. Thirteen were missed by MRI, eight of which were visible on mammography, including five ductal carcinomas in situ; four were interval cancers. Ten tumors were detected by both MRI and mammography. One tumor was detected by CBE only. While MRI proved more sensitive than mammography at detecting invasive breast cancers, mammography proved more deft than MRI at finding ductal carcinoma in situ.

The author of an accompanying editorial points out that the findings of the study offer new hope for women with BRCA mutations because screening mammography detects less than half of their breast cancers. For these women, Dr. Laura Liberman of Memorial Sloan-Kettering Cancer Center suggests, "the benefit of high sensitivity may outweigh the effects of imperfect specificity." She adds that while MRI may also be valuable in screening women with an increased risk of breast cancer due to nongenetic factors, such as those with prior breast cancer, no data support the use of screening MRI in women at normal risk.

Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med. 2004;351:427-437.

Liberman L. Breast cancer screening with MRI—What are the data for patients at high risk? N Engl J Med. 2004;351:497-500.

Comparing the risks of vacuum and forceps delivery

Although vacuum extraction is more likely to be complicated by postpartum hemorrhage and shoulder dystocia, it is associated with fewer birth injuries, neonatal seizures, and neonates needing assisted ventilation than forceps delivery, according to a population-based study.

Both methods, however, come with similar risks for infant mortality, intracranial hemorrhage, difficulty with feeding, and retinal hemorrhage. Sequential use of both methods is associated with a more frequent need for mechanical ventilation in infants and with more third- and fourth-degree maternal perineal tears.

The use of vacuum extraction relative to forceps increased 27% during the 10-year period from 1990 to 2000, so that in 2000, vacuum extraction accounted for 68% of all operative vaginal deliveries.

Demissie K, Rhoads GG, Smulian JC, et al. Operative vaginal delivery and neonatal and infant adverse outcomes: population based retrospective analysis. BMJ. 2004; 329:24-29.

Can circulating breast tumor cells predict survival?

An assay that counts tumor cells in whole blood has the potential to guide truly individualized treatment of metastatic breast cancer. Researchers have found that counting the number of circulating tumor cells before therapy is initiated and the number at the first follow-up visit more reliably predicted progression-free and overall survival than traditional imaging methods.

The prospective, double-blind study involved 177 women with measurable metastatic breast cancer from 20 US centers. The authors found that women who had five or more circulating tumor cells per 7.5 mL of whole blood prior to treatment had about a 60% shorter median progression-free survival (PFS) time (2.7 vs. 7.0 months, P<0.001) and about a 45% shorter overall survival (10.1 vs. >18 months; P<0.001) than women with fewer than five circulating tumor cells per 7.5 mL of whole blood. Furthermore, the differences persisted at the first follow-up visit after starting therapy: 2.1 versus 7 months PFS (P<0.001), and 8.2 versus more than 18 months overall survival (P<0.001).

An accompanying editorial states that the findings offer an opportunity to predict treatment response as early as 3 to 4 weeks after it's started. The test also has potential application as an adjuvant for women with early breast cancer. A key question moving forward, however, will be whether a change in treatment based on the number of circulating tumor cells translates into better PFS.

Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-791.

Braun S, Marth C. Circulating tumor cells in metastatic breast cancer—toward individualized treatment? N Engl J Med. 2004;351:824-826.

Can interactive computer program replace genetic counselors?

Not yet, but such a program was more effective than traditional one-on-one genetic counseling at educating women at low risk of carrying a BRCA1/2 mutation about genetics and breast cancer. It was less effective, however, at alleviating anxiety and at moving women toward making a decision with which they were satisfied.

The study, performed at six US medical center outpatient clinics offering cancer genetic counseling, involved 211 women with personal or family histories of breast cancer. In general, the computer program was well received by participants; they felt it to be a good use of their time and appreciated the ability to obtain information at their own pace.

In addition to being a better educator, the computer program was effective in reducing low-risk women's perceived risk of getting breast cancer. However, women at high risk of carrying BRCA1/2 mutations felt genetic counselors were better able to provide the information they needed to make an informed and satisfactory decision about testing.

Green MJ, Peterson SK, Baker MW, et al. Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial. JAMA. 2004;292:442-452.

Looking for new ways to reduce preterm births

A new method for detecting intra-amniotic infections (IAI) in pregnant women has the potential to prevent about 175,000 preterm births in the US each year, according to this preliminary report.

With the help of pregnant rhesus monkeys, researchers used proteomic profiling to identify novel peptide biomarkers that are present in amniotic fluid if IAI exists.

The signature the researchers identified was present in all 11 women with a subclinical IAI, in two of 11 women with preterm delivery without an IAI, and in 0 of 11 with preterm labor and term delivery without infection (P<0.001).

While the results were promising, the study involved only 33 women, which means further research is necessary to ascertain whether the proteins are, in fact, universal indicators of IAIs. But the hope is that such findings will lead to the development of a simple test that will detect the presence of these biomarkers, thus permitting pregnant women to receive early treatment.

Gravett MG, Novy MJ, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA. 2004;292:462-469.

The right strategy reduces risky sex among young black girls

Programs focused on ethnic and gender pride, knowledge about HIV infection, communication and condom-use skills, and healthy relationships are more likely to encourage the practice of HIV-preventive behaviors among African-American adolescent girls than interventions focused on exercise, nutrition, and general health, according to a randomized, controlled trial of 522 sexually active African-American 14- to 18-year-old females.

All of the girls in the study participated in four 4-hour group sessions (10-12 participants in each session) on consecutive Saturdays at a family medicine clinic. The researchers sought to build ethnic and gender pride by making teens aware of the achievements of well-known black women, including prominent artists and poets. Compared to the group given general health information, the girls in the intervention group were more likely to use condoms consistently, were more likely to use a condom at last intercourse and to have a higher percentage of condom-protected sex acts, were more likely to apply condoms to their partners, and were more adept at applying them. They also were less likely to have a new vaginal sex partner in the past 30 days and showed a trend toward fewer sexually transmitted diseases and self-reported pregnancies.

DiClemente RJ, Wingood GM, Harrington KF, et al. Efficacy of an HIV prevention intervention for African American adolescent girls: a randomized controlled trial. JAMA. 2004;292:171-179.

Meeting Highlights

American Urogynecologic Society

Oxybutynin vs. tolterodine for OAB

Two anticholinergic agents commonly used to treat overactive bladder (OAB) don't often cause adverse events affecting the CNS, according to a new analysis of data from a large randomized trial of the two agents.

Extended-release formulations of oxybutynin and tolterodine were well-tolerated in patients with OAB according to research presented by Peter K. Sand, MD, at the AUGS meeting in San Diego. Older patients tended to report more CNS effects, but the incidence was still low and did not differ between treatment groups.

"The overall tolerance was excellent in both groups of patients," said Dr. Sand, director of the Evanston Continence Center in Evanston, Ill. "Fewer than 5% of patients discontinued treatment in both groups. Dry mouth was the most common CNS side effect in both groups. Other CNS effects were infrequent. CNS side effects were mostly mild or moderate, and there were no serious adverse events affecting the central nervous system." Efficacy results from the trial tended to favor extended-release oxybutynin, which resulted in a higher rate of total dryness and a lower micturition frequency, he noted.

The patients in the trial were randomized to receive oxybutyinin, 10 mg/day, or tolterodine, 4 mg/day, for 12 weeks. Both therapies significantly reduced voiding frequency, but oxybutynin had a greater effect than tolterodine. Additionally, 23% of oxybutynin patients achieved total dryness compared to 16.8% of tolterodine patients. (Oral Poster 59)

Comparing Ca hydroxyapatite to collagen for urinary incontinence

Calcium hydroxyapatite compares favorably with bovine collagen as treatment for type III urinary incontinence or intrinsic sphincter deficiency, according to an interim analysis of data from an ongoing randomized trial.

At 6 and 12 months, a significantly higher proportion of patients treated with calcium hydroxyapatite had improved at least one Stamey grade, which was the primary outcome stipulated by the FDA. The 1-year change in absorbent pad use also favored the group treated with calcium hydroxyapatite, Peter K. Sand, MD, reported at the AUGS meeting.

"At this point, we can conclude that calcium hydroxyapatite provides durable treatment results and the 6-month and 12-month data are comparable," said Dr. Sand, director of the Evanston Continence Center in Evanston, Ill. "We know from a pilot study that this agent is safe, effective, and durable. We're awaiting final tabulation and analysis, which will be completed [by the end of the year]."

Among the 88 patients followed for at least 6 months, 81% in the calcium hydroxyapatite group had improved by at least one Stamey grade, compared to 62% of patients treated with injectable bovine collagen (P=0.0447). At 12 months the difference was even greater, as 80% of patients had Stamey grade improvement compared to 57% of the collagen group (P=0.0281).

Both groups experienced a decline in use of absorbent pads. At 6 months, the magnitude of decline was similar in the two groups (48%–49%). By 12 months, a nonsignificant advantage had appeared in favor of the patients treated with hydroxyapatite (41% vs. 31%). The hydroxyapatite group also exhibited a trend toward a greater likelihood of improving to Stamey grade 0 (totally dry). (Poster 58)

Are routine cytology and cystoscopy worth the effort?

"Routine use of urinary cytology and cystoscopy should be reconsidered" in the evaluation of women with irritative voiding symptoms, according to one large-scale study presented at this year's AUGS meeting. But while investigators in a second large trial found little correlation between microscopic hematuria and bladder cancer, they concluded that bladder cancer deserves consideration in women with unexplained irritative urinary tract symptoms and that cystoscopy is an essential diagnostic tool in the evaluation of such patients.

"Urinary cytology and cystoscopy are commonly used in the evaluation of women with irritative voiding symptoms and to aid in the detection of urinary tract malignancies," said Eric Sokol, MD, a urogynecology fellow at Brown University in Providence, R.I. "They are standard diagnostic and monitoring tools for superficial bladder cancer. However, they might be low-yield tests in an unscreened population of women with irritative voiding symptoms.

"Traditional teaching has implicitly advocated for cytology and cystoscopy but clinical recommendations are based largely on studies including men or in patients with gross hematuria. Algorithms to define the optimal approach to women with irritative voiding symptoms are lacking."

"We have shown in our population of women with irritative voiding symptoms that high-risk abnormalities on urinary cytologic and cystoscopic testing are rare," said Dr. Sokol. "We believe that urinary cytology and cystoscopy are low-yield tests in the initial evaluation of women with irritative voiding symptoms, and their routine use should be reconsidered."

The second study tried to determine the risk of bladder cancer in women undergoing cystoscopy for evaluation of irritative voiding symptoms. It was also designed to investigate risk factors for cancer, and to evaluate microscopic hematuria's reliability as a screening tool. It involved over 1,500 women presenting with unexplained irritative voiding symptoms. The most common presenting symptom was nocturia (90.2%). Additionally, 23.7% of women had hematuria, including microscopic hematuria in 21.6%. About half the women (47.5%) had a history of urologic surgery, and 10% had a history of previous malignancy.

Overall, 10 cancers were identified in the study. The presence of microscopic hematuria substantially increased the likelihood of cancer (1.7% vs. 0.45%). However, Dr. Goldberg noted, most of the cancers were preceded by normal dipstick urinalysis results. Microscopic hematuria had a sensitivity of 40% and a specificity of 85% for cancer diagnosis.

"The red flag of microscopic hematuria was associated with a higher relative risk of cancer, but the majority of cancers presented without hematuria," said Dr. Goldberg. "Therefore, microscopic hematuria demonstrated poor sensitivity and specificity as a screening tool on the initial visit for evaluation of irritative voiding symptoms. Bladder cancer should be considered for women with unexplained irritative urinary tract symptoms. Cystoscopy continues to represent an essential diagnostic tool." (Abstract 11)

PROFESSIONAL UPDATE

Errors most often linked to communication problems

Miscommunication—rather than incompetence—seems to play a bigger role in propagating diagnostic and treatment errors in primary care settings, according to a study in the Annals of Family Medicine (July/Aug. 2004).

Examining 75 error reports submitted anonymously by 18 family physicians in five states, the study's researchers found a chain of errors in 77% of incidents. A full 80% of the error chains were initiated by some kind of miscommunication, including communication breakdowns among colleagues and with patients (44%), misinformation in the medical record (21%), mishandling of patient requests and messages (18%), inaccessible medical records (12%), and the lack of reminder systems (5%).

The researchers noted that computers or other information technology could help remedy the communication errors that could lead to medical mistakes. They concluded, among other things, that "safety initiatives should focus less on professional interventions to improve clinical judgment and more on management systems to enhance the quality of information transfer."

Senate passes patient safety bill

By unanimous vote, the Senate recently passed a bill that would create a national system of collecting and analyzing data on medical errors. The Patient Safety and Quality Improvement Act is designed to encourage physicians and hospitals to report medical errors to patient safety organizations without fear of reprisals.

The bill authorizes the creation of patient safety organizations that would collect and analyze data on medical errors, and produce reports to help health-care facilities and physicians' practices improve the quality of patient care, according to American Medical News (8/9/04). It also creates a voluntary system of reporting errors and requires that documents submitted to patient safety organizations be kept confidential—an element designed to alleviate fears that the documents could later be used against them. (According to AmNews, the bill does not provide protection from lawsuits for those entities making a voluntary report to a patient safety organization; the usual means of discovering information about an error are still available to injured patients.)

The Senate's bill must now be reconciled with a version of the bill passed by the House of Representatives in March 2003.

New neonate screening guidelines take national spotlight

In the face of a hodgepodge of state legislation on newborn screening, an American College of Medical Genetics report recommended that every state require newborns to be tested for at least 30 genetic diseases. The ACMG made this recommendation, among others, to a special advisory committee to the secretary of the Department of Health and Human Services last month.

Although the 30-disease list includes "relatively rare" conditions, testing is easy—requiring a blood sample from a newborn immediately after birth—and the diseases "typically can be treated or even cured by relatively simple dietary changes," reported The Wall Street Journal (7/30/04).

Even before the report was released, a few states have taken steps to expand the number of tests performed on newborns. For example, California now requires newborns to undergo tests for 41 conditions—up from four. Missouri increased its number of tests on newborns from five to 25, and New York tripled the number of diseases it screens in newborns.

"Caps on malpractice awards won't save doctors"

Faced with an increasing number of million-dollar verdicts in malpractice cases, physicians are urging legislators to cap these awards. But that strategy isn't the answer to their troubles, according to Lewis Laska, an attorney and publisher of Medical Malpractice Verdicts, Settlements & Experts.

"Big verdicts will keep getting bigger until doctors face what's really going wrong in court," wrote Laska in Medical Liability Monitor (7/04).

Laska notes that changes in the way malpractice cases against physicians are presented have contributed to this trend. Rather than playing on jurors' sympathy to win a case, plaintiff's attorneys now build their cases around anger—finding an aspect of the case that will prompt jurors to grant big awards to punish a negligent doctor. Moreover, these attorneys are also working together, forming groups to keep them informed about the latest medical news and standards.

At the same time, Laska said, physicians have not stayed as up-to-date on medical news and standards as trial attorneys. This lack of knowledge and the inability to provide a "science-based answer" in their defense put physicians at a disadvantage in court or in a deposition.

He also believes that "doctors have lost the moral high ground in their effort to limit verdicts." Physicians' perceived arrogance, their diminished public image and news of medical errors have contributed to the increase in large malpractice awards.

More clinicians refuse to supply birth control

An increasing number of physicians, nurses, and pharmacists are refusing to prescribe or dispense pharmaceutical forms of birth control—opting to encourage patients to use natural family planning, according to The San Diego Union-Tribune (8/8/04). While providers had previously cited religious convictions as their motivation for rejecting pharmaceutical forms of contraception, opposition to abortion has now become another reason.

At issue is the debate about when human life begins—whether it is when a sperm penetrates an egg, once a fertilized egg is implanted in the lining of a woman's uterus, or when a baby first draws breath. With these varying interpretations, health-care providers must decide what forms of contraception are ethical.

A number of groups exist to support health-care providers who refuse to supply birth control to patients, including the American Association of Pro-Life Obstetricians and Gynecologists with 2,500 members nationwide. Moreover, one state—South Dakota—has passed a law recognizing the rights of physicians and pharmacists to deny birth control to patients and at least 20 states are considering such legislation. The American Medical Association also upholds a physician's right to refuse to perform any treatment that goes against his or her moral convictions.

Court rules: You can't post unfounded charges against doctor

The N.Y. Court of Appeals ruled that the state health department cannot post charges of misconduct on a public Web site that have been dismissed against a physician. The court noted that making these unsubstantiated charges public "was an abuse of discretion," reported American Medical News (7/26/04).

The case involved a general practice physician in Manhattan who had been charged, among other things, with harassing and abusing a female patient and failing to maintain a medical record for a Cipro prescription. The physician was cleared of all charges except one—failing to maintain a medical record—and received a reprimand. The state then posted the charges and the outcome on a Web site of physician information.

The physician asked to have the information removed, but the state refused, citing its policy to post disciplinary orders. The physician sued, pursuing his case all the way to the N.Y. Court of Appeals.

The physician's attorney warned other N.Y. doctors to check what information the state has posted about them.

'Open-access' patient scheduling is worth considering

In an attempt to reduce lengthy waits for appointments, Jefferson Family Medicine Associates in Philadelphia has implemented a new scheduling philosophy known as open access. The goal is to provide timely appointments to patients—allowing them to see their doctor the next day or the same morning they call the office.

So far, the new scheduling system seems to be working. More than 60% of patients are seen within a day of their call, compared with 15% in the old system. In addition, the number of patients seen has increased—from 61,000 before the switch to 72,000 last year. The practice's revenue has also grown, "in double digits each of the last two years," reported The Philadelphia Inquirer (8/11/04).

Despite anecdotal evidence of the success of open-access scheduling as well as endorsements by the American Academy of Family Physicians and the Department of Veterans Affairs, the scheduling system is not yet commonplace. Switching to this scheduling system is not an easy undertaking: Physicians are often required to work harder for a while to reduce backlog. They must determine the days and times of the year when they are likely to see more patients, and schedule staff accordingly. And a new philosophy to providing care must be adopted—one in which physicians try to solve as many of a patient's concerns in one visit to reduce the likelihood that she will return.

 

NEWSLINE: Clinical Insights/Professional Update. Contemporary Ob/Gyn Oct. 1, 2004;49:12.