Jane Salodof MacNeil

ORLANDO, FLA. — Primary care physicians and other clinicians from specialties outside of oncology can expect to find their respective roles spelled out in new guidelines under development for medical management of cancer survivors.

Among the proposals in the works is an individual “end-of-treatment summary” that would be drawn up for each patient when he or she completes treatment. This would describe the therapies delivered and enumerate the long-term responsibilities of oncologists and other physicians in monitoring the patient for late effects.

Patricia A. Ganz, M.D., discussed the guidelines at the annual meeting of the American Society of Clinical Oncology (ASCO). In an interview, she said a template is nearly complete and will be available in November when an Institute of Medicine panel is to issue its report on medical and social issues facing adult cancer survivors.

Dr. Ganz, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, is cochair of a new ASCO Survivorship Task Force, along with the society's incoming president, Sandra J. Horning, M.D.

The task force will hold its first formal meeting this month, outgoing ASCO president David H. Johnson, M.D., said. He also said the society's health services committee is drafting clinical practice guidelines addressing late effects of treatment, secondary malignancies, and psychosocial effects.

The Children's Oncology Group (COG) has already created a Web site, www.survivorshipguidelines.org

“The biggest challenge is transitioning patients from pediatric to adult settings. We hope that the guidelines will smooth the transition somewhat,” said Dr. Bhatia, director of epidemiology and outcomes research in the pediatric division of the City of Hope Comprehensive Cancer Center in Duarte, Calif. She described the guidelines (J. Clin. Oncol. 2004;22:4979–90) and Web site in her discussion of a study that found most childhood cancer survivors had severe health problems by age 45 years.

One challenge Dr. Bhatia cited is that late effects occur many years after these patients are treated in pediatric centers. By then, they usually are cared for in general adult practices where physicians may have limited access to their histories.

She cited a study that found “only 35% of childhood cancer survivors understand that serious health problems could result from past treatment” (JAMA 2002;287:1832–9). Just 72% could report their diagnosis precisely. Although 94% knew they had chemotherapy, fewer could name chemotherapy drugs such as doxorubicin (52%) and daunomycin (30%).

Kevin C. Oeffinger, M.D., principal investigator of the new sudy, estimated that a primary care physician might have three or four pediatric cancer survivors in his or her practice. “Most primary care physicians are not aware of the population, and survivors are not aware of the risk,” said Dr. Oeffinger of the University of Texas Southwestern Medical Center at Dallas.

ORLANDO, FLA. — Primary care physicians and other clinicians from specialties outside of oncology can expect to find their respective roles spelled out in new guidelines under development for medical management of cancer survivors.

Among the proposals in the works is an individual “end-of-treatment summary” that would be drawn up for each patient when he or she completes treatment. This would describe the therapies delivered and enumerate the long-term responsibilities of oncologists and other physicians in monitoring the patient for late effects.

Patricia A. Ganz, M.D., discussed the guidelines at the annual meeting of the American Society of Clinical Oncology (ASCO). In an interview, she said a template is nearly complete and will be available in November when an Institute of Medicine panel is to issue its report on medical and social issues facing adult cancer survivors.

Dr. Ganz, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, is cochair of a new ASCO Survivorship Task Force, along with the society's incoming president, Sandra J. Horning, M.D.

The task force will hold its first formal meeting this month, outgoing ASCO president David H. Johnson, M.D., said. He also said the society's health services committee is drafting clinical practice guidelines addressing late effects of treatment, secondary malignancies, and psychosocial effects.

The Children's Oncology Group (COG) has already created a Web site, www.survivorshipguidelines.org

“The biggest challenge is transitioning patients from pediatric to adult settings. We hope that the guidelines will smooth the transition somewhat,” said Dr. Bhatia, director of epidemiology and outcomes research in the pediatric division of the City of Hope Comprehensive Cancer Center in Duarte, Calif. She described the guidelines (J. Clin. Oncol. 2004;22:4979–90) and Web site in her discussion of a study that found most childhood cancer survivors had severe health problems by age 45 years.

One challenge Dr. Bhatia cited is that late effects occur many years after these patients are treated in pediatric centers. By then, they usually are cared for in general adult practices where physicians may have limited access to their histories.

She cited a study that found “only 35% of childhood cancer survivors understand that serious health problems could result from past treatment” (JAMA 2002;287:1832–9). Just 72% could report their diagnosis precisely. Although 94% knew they had chemotherapy, fewer could name chemotherapy drugs such as doxorubicin (52%) and daunomycin (30%).

Kevin C. Oeffinger, M.D., principal investigator of the new sudy, estimated that a primary care physician might have three or four pediatric cancer survivors in his or her practice. “Most primary care physicians are not aware of the population, and survivors are not aware of the risk,” said Dr. Oeffinger of the University of Texas Southwestern Medical Center at Dallas.

ORLANDO, FLA. — Primary care physicians and other clinicians from specialties outside of oncology can expect to find their respective roles spelled out in new guidelines under development for medical management of cancer survivors.

Among the proposals in the works is an individual “end-of-treatment summary” that would be drawn up for each patient when he or she completes treatment. This would describe the therapies delivered and enumerate the long-term responsibilities of oncologists and other physicians in monitoring the patient for late effects.

Patricia A. Ganz, M.D., discussed the guidelines at the annual meeting of the American Society of Clinical Oncology (ASCO). In an interview, she said a template is nearly complete and will be available in November when an Institute of Medicine panel is to issue its report on medical and social issues facing adult cancer survivors.

Dr. Ganz, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, is cochair of a new ASCO Survivorship Task Force, along with the society's incoming president, Sandra J. Horning, M.D.

The task force will hold its first formal meeting this month, outgoing ASCO president David H. Johnson, M.D., said. He also said the society's health services committee is drafting clinical practice guidelines addressing late effects of treatment, secondary malignancies, and psychosocial effects.

The Children's Oncology Group (COG) has already created a Web site, www.survivorshipguidelines.org

“The biggest challenge is transitioning patients from pediatric to adult settings. We hope that the guidelines will smooth the transition somewhat,” said Dr. Bhatia, director of epidemiology and outcomes research in the pediatric division of the City of Hope Comprehensive Cancer Center in Duarte, Calif. She described the guidelines (J. Clin. Oncol. 2004;22:4979–90) and Web site in her discussion of a study that found most childhood cancer survivors had severe health problems by age 45 years.

One challenge Dr. Bhatia cited is that late effects occur many years after these patients are treated in pediatric centers. By then, they usually are cared for in general adult practices where physicians may have limited access to their histories.

She cited a study that found “only 35% of childhood cancer survivors understand that serious health problems could result from past treatment” (JAMA 2002;287:1832–9). Just 72% could report their diagnosis precisely. Although 94% knew they had chemotherapy, fewer could name chemotherapy drugs such as doxorubicin (52%) and daunomycin (30%).

Kevin C. Oeffinger, M.D., principal investigator of the new sudy, estimated that a primary care physician might have three or four pediatric cancer survivors in his or her practice. “Most primary care physicians are not aware of the population, and survivors are not aware of the risk,” said Dr. Oeffinger of the University of Texas Southwestern Medical Center at Dallas.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teens who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who made up an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study. A subsidiary, Ortho-McNeil Pharmaceutical Inc., manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive. BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial. Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18. Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all were Caucasian.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study. Some mothers declined to allow their minor daughters to participate because the protocol called for birth control, he noted. Another barrier was the girls' concern about possible weight gain from the pill.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls. In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density. The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he said.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teens who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who made up an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study. A subsidiary, Ortho-McNeil Pharmaceutical Inc., manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive. BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial. Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18. Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all were Caucasian.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study. Some mothers declined to allow their minor daughters to participate because the protocol called for birth control, he noted. Another barrier was the girls' concern about possible weight gain from the pill.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls. In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density. The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he said.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teens who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who made up an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study. A subsidiary, Ortho-McNeil Pharmaceutical Inc., manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive. BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial. Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18. Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all were Caucasian.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study. Some mothers declined to allow their minor daughters to participate because the protocol called for birth control, he noted. Another barrier was the girls' concern about possible weight gain from the pill.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls. In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density. The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he said.

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

HOUSTON — Whether to treat genital warts would seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is so widespread that it's “nearly universal.” Moreover, destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” concluded Dr. Lynch, a dermatologist in Sacramento.

Having said all that, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore, he said.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. These are usually smooth but can feel rough if they occur in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy, especially in flat warts, which are the most likely to show dysplasia. More than 90% of vulvar HPV infections are caused by low-risk forms of the virus.

High-risk types such as HPV 16 and HPV 18 occur in 5%–8% of vulvar HPV infections. Although these can lead to malignancy, he characterized the transition as very slow, with ample time for curative therapy.

Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there, as well. The next step, he said, is to choose among the following three therapeutic options:

▸ Home-based medical therapy in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. Dr. Lynch estimated about a third of patients will have complete clearance after 2 months of such treatment.

▸ Office-based medical therapy allows the clinician to monitor compliance. Dr. Lynch characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) will lead to complete clearance in two-thirds of patients, he estimated.

“Unfortunately, there are no criteria to choose one [treatment] over the other. It is disturbing how little we have, except for anecdotal data,” Dr. Lynch said of the three options.

His recommendation: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach.

HOUSTON — Whether to treat genital warts would seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is so widespread that it's “nearly universal.” Moreover, destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” concluded Dr. Lynch, a dermatologist in Sacramento.

Having said all that, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore, he said.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. These are usually smooth but can feel rough if they occur in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy, especially in flat warts, which are the most likely to show dysplasia. More than 90% of vulvar HPV infections are caused by low-risk forms of the virus.

High-risk types such as HPV 16 and HPV 18 occur in 5%–8% of vulvar HPV infections. Although these can lead to malignancy, he characterized the transition as very slow, with ample time for curative therapy.

Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there, as well. The next step, he said, is to choose among the following three therapeutic options:

▸ Home-based medical therapy in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. Dr. Lynch estimated about a third of patients will have complete clearance after 2 months of such treatment.

▸ Office-based medical therapy allows the clinician to monitor compliance. Dr. Lynch characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) will lead to complete clearance in two-thirds of patients, he estimated.

“Unfortunately, there are no criteria to choose one [treatment] over the other. It is disturbing how little we have, except for anecdotal data,” Dr. Lynch said of the three options.

His recommendation: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach.

HOUSTON — Whether to treat genital warts would seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is so widespread that it's “nearly universal.” Moreover, destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” concluded Dr. Lynch, a dermatologist in Sacramento.

Having said all that, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore, he said.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. These are usually smooth but can feel rough if they occur in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy, especially in flat warts, which are the most likely to show dysplasia. More than 90% of vulvar HPV infections are caused by low-risk forms of the virus.

High-risk types such as HPV 16 and HPV 18 occur in 5%–8% of vulvar HPV infections. Although these can lead to malignancy, he characterized the transition as very slow, with ample time for curative therapy.

Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there, as well. The next step, he said, is to choose among the following three therapeutic options:

▸ Home-based medical therapy in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. Dr. Lynch estimated about a third of patients will have complete clearance after 2 months of such treatment.

▸ Office-based medical therapy allows the clinician to monitor compliance. Dr. Lynch characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) will lead to complete clearance in two-thirds of patients, he estimated.

“Unfortunately, there are no criteria to choose one [treatment] over the other. It is disturbing how little we have, except for anecdotal data,” Dr. Lynch said of the three options.

His recommendation: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach.

NEW ORLEANS — A foldable, pseudoaccommodative intraocular lens being tested in Europe shows promise of freeing most users from the need to wear glasses after removal of their cataracts, Thomas Kohnen, M.D., said at the annual meeting of the American Academy of Ophthalmology.

The apodized diffractive lens, known as the AcrySof ReSTOR IOL model MA60D3, was designed to provide a broad functional range, said Dr. Kohnen of Johann Wolfgang Goethe University in Frankfurt, Germany. The lens has 12 diffractive zones, favoring near vision when the pupils contract and distance vision when they expand. “Subtle zone transition provided minimization of visual disturbances and pupil-independent vision,” he said in a presentation of preliminary data.

Eight surgeons are participating in the ongoing open-label trial, which has enrolled 127 patients in France, Germany, Italy, and the United Kingdom. Eligibility requirements included healthy eyes except for bilateral cataracts and 1 D of astigmatism. The trial design does not include a control group.

Dr. Kohnen's presentation focused on 118 patients who had the lens implanted in both eyes. All had been followed for 1 year after the first lens was placed in one eye and 6 months after placement of a second lens in the other eye.

The lens appeared to maintain distance vision while enhancing near vision. Only one patient did not achieve uncorrected distance vision of 20/40 or better with binocular use, and 84% of patients reached 20/25 or better. Uncorrected near vision was at least 20/40 for 98% after 6 months of binocular use, and two-thirds of patients achieved 20/25 without reading glasses.

Visual symptoms fell into the mild to moderate range on a scale of 1–5. The most severe was glare/flare, which registered 1.92. It was followed by halos (1.28), night vision (0.62), blurred near vision (0.47), and blurred far vision (0.4).

Seventy-four percent of 118 patients said they never wore glasses 6 months after the lens was implanted in both their eyes. Distance vision was strong enough for 88% to do without glasses for seeing far objects. Near vision was almost as good, with 84.6% able to give up their reading glasses.

Manufacturer Alcon Inc. of Fort Worth, Tex., is seeking U.S. Food and Drug Administration approval for the ReSTOR IOL, which has been approved in Europe. Dr. Kohnen noted that 100% of patients in the study achieved best-corrected distance vision of 20/40 or better at 6 months after bilateral implantation—exceeding an FDA goal of 92.5%.

Richard Lindstrom, M.D., in private practice in Minneapolis, reviewed the presentation, calling the objective outcomes excellent and the subjective outcomes good. He noted, though, that 10.4% had “significant unwanted vision problems” and two patients had to have the lens removed. Despite concerns about night vision, he concluded that the ReSTOR lens is promising.

NEW ORLEANS — A foldable, pseudoaccommodative intraocular lens being tested in Europe shows promise of freeing most users from the need to wear glasses after removal of their cataracts, Thomas Kohnen, M.D., said at the annual meeting of the American Academy of Ophthalmology.

The apodized diffractive lens, known as the AcrySof ReSTOR IOL model MA60D3, was designed to provide a broad functional range, said Dr. Kohnen of Johann Wolfgang Goethe University in Frankfurt, Germany. The lens has 12 diffractive zones, favoring near vision when the pupils contract and distance vision when they expand. “Subtle zone transition provided minimization of visual disturbances and pupil-independent vision,” he said in a presentation of preliminary data.

Eight surgeons are participating in the ongoing open-label trial, which has enrolled 127 patients in France, Germany, Italy, and the United Kingdom. Eligibility requirements included healthy eyes except for bilateral cataracts and 1 D of astigmatism. The trial design does not include a control group.

Dr. Kohnen's presentation focused on 118 patients who had the lens implanted in both eyes. All had been followed for 1 year after the first lens was placed in one eye and 6 months after placement of a second lens in the other eye.

The lens appeared to maintain distance vision while enhancing near vision. Only one patient did not achieve uncorrected distance vision of 20/40 or better with binocular use, and 84% of patients reached 20/25 or better. Uncorrected near vision was at least 20/40 for 98% after 6 months of binocular use, and two-thirds of patients achieved 20/25 without reading glasses.

Visual symptoms fell into the mild to moderate range on a scale of 1–5. The most severe was glare/flare, which registered 1.92. It was followed by halos (1.28), night vision (0.62), blurred near vision (0.47), and blurred far vision (0.4).

Seventy-four percent of 118 patients said they never wore glasses 6 months after the lens was implanted in both their eyes. Distance vision was strong enough for 88% to do without glasses for seeing far objects. Near vision was almost as good, with 84.6% able to give up their reading glasses.

Manufacturer Alcon Inc. of Fort Worth, Tex., is seeking U.S. Food and Drug Administration approval for the ReSTOR IOL, which has been approved in Europe. Dr. Kohnen noted that 100% of patients in the study achieved best-corrected distance vision of 20/40 or better at 6 months after bilateral implantation—exceeding an FDA goal of 92.5%.

Richard Lindstrom, M.D., in private practice in Minneapolis, reviewed the presentation, calling the objective outcomes excellent and the subjective outcomes good. He noted, though, that 10.4% had “significant unwanted vision problems” and two patients had to have the lens removed. Despite concerns about night vision, he concluded that the ReSTOR lens is promising.

NEW ORLEANS — A foldable, pseudoaccommodative intraocular lens being tested in Europe shows promise of freeing most users from the need to wear glasses after removal of their cataracts, Thomas Kohnen, M.D., said at the annual meeting of the American Academy of Ophthalmology.

The apodized diffractive lens, known as the AcrySof ReSTOR IOL model MA60D3, was designed to provide a broad functional range, said Dr. Kohnen of Johann Wolfgang Goethe University in Frankfurt, Germany. The lens has 12 diffractive zones, favoring near vision when the pupils contract and distance vision when they expand. “Subtle zone transition provided minimization of visual disturbances and pupil-independent vision,” he said in a presentation of preliminary data.

Eight surgeons are participating in the ongoing open-label trial, which has enrolled 127 patients in France, Germany, Italy, and the United Kingdom. Eligibility requirements included healthy eyes except for bilateral cataracts and 1 D of astigmatism. The trial design does not include a control group.

Dr. Kohnen's presentation focused on 118 patients who had the lens implanted in both eyes. All had been followed for 1 year after the first lens was placed in one eye and 6 months after placement of a second lens in the other eye.

The lens appeared to maintain distance vision while enhancing near vision. Only one patient did not achieve uncorrected distance vision of 20/40 or better with binocular use, and 84% of patients reached 20/25 or better. Uncorrected near vision was at least 20/40 for 98% after 6 months of binocular use, and two-thirds of patients achieved 20/25 without reading glasses.

Visual symptoms fell into the mild to moderate range on a scale of 1–5. The most severe was glare/flare, which registered 1.92. It was followed by halos (1.28), night vision (0.62), blurred near vision (0.47), and blurred far vision (0.4).

Seventy-four percent of 118 patients said they never wore glasses 6 months after the lens was implanted in both their eyes. Distance vision was strong enough for 88% to do without glasses for seeing far objects. Near vision was almost as good, with 84.6% able to give up their reading glasses.

Manufacturer Alcon Inc. of Fort Worth, Tex., is seeking U.S. Food and Drug Administration approval for the ReSTOR IOL, which has been approved in Europe. Dr. Kohnen noted that 100% of patients in the study achieved best-corrected distance vision of 20/40 or better at 6 months after bilateral implantation—exceeding an FDA goal of 92.5%.

Richard Lindstrom, M.D., in private practice in Minneapolis, reviewed the presentation, calling the objective outcomes excellent and the subjective outcomes good. He noted, though, that 10.4% had “significant unwanted vision problems” and two patients had to have the lens removed. Despite concerns about night vision, he concluded that the ReSTOR lens is promising.

LOS ANGELES — St. John's wort does not appear to interfere with the antiandrogenic effects of oral contraceptive pills, Robin Fogle, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

She reported that testosterone levels decreased, while a marker of androgen metabolism increased, in 15 healthy women treated with St. John's wort and Loestrin 1/20 (norethindrone/estradiol) during a 4-month study.

Although the changes did not reach statistical significance, the outcomes strongly suggest St. John's wort will not interfere with the oral contraceptives' pill's effectiveness when used as a primary treatment for hirsutism rather than for birth control, said Dr. Fogle, of the University of Southern California, Los Angeles, in an interview.

The study was undertaken because reports have shown the over-the-counter herbal remedy, commonly used for depression and inflammation, induces cytochrome P450 activity. This can interfere with the efficacy of some drugs, including oral contraceptives, Dr. Fogle and her coinvestigators wrote in a poster presented at the meeting.

None of the women in the study had hirsutism. They took Loestrin 1/20 for four consecutive 28-day cycles. During the last two cycles, the protocol added 300 mg of St. John's wort taken three times daily.

Mean testosterone decreased 10.7% (from 44.8 ng/dL to 40.0 ng/dL), and free testosterone dipped 15.8% (from 0.38 ng/dL to 0.32 ng/dL) after the addition of St. John's wort. Conversely, 3α-androstanediol glucuronide, the marker of androgen metabolism, increased 6.5% from 2 ng/mL to 2.13 ng/mL.

“Thus, it appears that St. John's wort enhances androgen metabolism and does not interfere with the antiandrogenic properties of oral contraceptive pills,” the investigators concluded.

LOS ANGELES — St. John's wort does not appear to interfere with the antiandrogenic effects of oral contraceptive pills, Robin Fogle, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

She reported that testosterone levels decreased, while a marker of androgen metabolism increased, in 15 healthy women treated with St. John's wort and Loestrin 1/20 (norethindrone/estradiol) during a 4-month study.

Although the changes did not reach statistical significance, the outcomes strongly suggest St. John's wort will not interfere with the oral contraceptives' pill's effectiveness when used as a primary treatment for hirsutism rather than for birth control, said Dr. Fogle, of the University of Southern California, Los Angeles, in an interview.

The study was undertaken because reports have shown the over-the-counter herbal remedy, commonly used for depression and inflammation, induces cytochrome P450 activity. This can interfere with the efficacy of some drugs, including oral contraceptives, Dr. Fogle and her coinvestigators wrote in a poster presented at the meeting.

None of the women in the study had hirsutism. They took Loestrin 1/20 for four consecutive 28-day cycles. During the last two cycles, the protocol added 300 mg of St. John's wort taken three times daily.

Mean testosterone decreased 10.7% (from 44.8 ng/dL to 40.0 ng/dL), and free testosterone dipped 15.8% (from 0.38 ng/dL to 0.32 ng/dL) after the addition of St. John's wort. Conversely, 3α-androstanediol glucuronide, the marker of androgen metabolism, increased 6.5% from 2 ng/mL to 2.13 ng/mL.

“Thus, it appears that St. John's wort enhances androgen metabolism and does not interfere with the antiandrogenic properties of oral contraceptive pills,” the investigators concluded.

LOS ANGELES — St. John's wort does not appear to interfere with the antiandrogenic effects of oral contraceptive pills, Robin Fogle, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

She reported that testosterone levels decreased, while a marker of androgen metabolism increased, in 15 healthy women treated with St. John's wort and Loestrin 1/20 (norethindrone/estradiol) during a 4-month study.

Although the changes did not reach statistical significance, the outcomes strongly suggest St. John's wort will not interfere with the oral contraceptives' pill's effectiveness when used as a primary treatment for hirsutism rather than for birth control, said Dr. Fogle, of the University of Southern California, Los Angeles, in an interview.

The study was undertaken because reports have shown the over-the-counter herbal remedy, commonly used for depression and inflammation, induces cytochrome P450 activity. This can interfere with the efficacy of some drugs, including oral contraceptives, Dr. Fogle and her coinvestigators wrote in a poster presented at the meeting.

None of the women in the study had hirsutism. They took Loestrin 1/20 for four consecutive 28-day cycles. During the last two cycles, the protocol added 300 mg of St. John's wort taken three times daily.

Mean testosterone decreased 10.7% (from 44.8 ng/dL to 40.0 ng/dL), and free testosterone dipped 15.8% (from 0.38 ng/dL to 0.32 ng/dL) after the addition of St. John's wort. Conversely, 3α-androstanediol glucuronide, the marker of androgen metabolism, increased 6.5% from 2 ng/mL to 2.13 ng/mL.

“Thus, it appears that St. John's wort enhances androgen metabolism and does not interfere with the antiandrogenic properties of oral contraceptive pills,” the investigators concluded.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teenagers who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who comprised an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study.

A subsidiary, Ortho-McNeil Pharmaceutical Inc. manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive.

BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial.

Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18.

Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all participants were white.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study.

Some parents declined to allow their minor daughters to participate because the protocol called for birth control, he noted.

Another barrier to recruitment cited in his talk was the girls' concern about possible weight gain from the pill. “We had to disclose the pills had 0.4 calories per pill,” he said.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls.

In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density.

The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he noted during his presentation.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teenagers who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who comprised an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study.

A subsidiary, Ortho-McNeil Pharmaceutical Inc. manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive.

BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial.

Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18.

Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all participants were white.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study.

Some parents declined to allow their minor daughters to participate because the protocol called for birth control, he noted.

Another barrier to recruitment cited in his talk was the girls' concern about possible weight gain from the pill. “We had to disclose the pills had 0.4 calories per pill,” he said.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls.

In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density.

The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he noted during his presentation.

LOS ANGELES — The oral contraceptive Ortho Tri-Cyclen may help teenaged girls with anorexia nervosa build bone mass as a defense against osteoporosis later in life.

Compared with placebo, it produced significantly greater increases in mean bone mineral density (BMD) of the lumbar spine during a 123-patient, double-blind, randomized trial reported at the annual meeting of the Society for Gynecologic Investigation.

This advantage was significant in 88 teenagers who completed the 13-cycle trial, but did not endure beyond 6 months in 112 girls who comprised an intent-to-treat population. Increases in hip BMD were not significantly different at 6 months or 1 year.

“Treatment of adolescent females with anorexia nervosa may improve lumbar spine but not total hip [BMD] in subjects treated for at least 12 cycles,” investigator Andrew Friedman, M.D., concluded.

Dr. Friedman is senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., which sponsored the study.

A subsidiary, Ortho-McNeil Pharmaceutical Inc. manufactures Ortho Tri-Cyclen.

Although no other oral contraceptives were tested, Dr. Friedman acknowledged that some might offer a similar benefit for this population.

In the intent-to-treat population, average lumbar spine BMD increased 2.4% at 6 months for girls on Ortho Tri-Cyclen, but only 1% for the placebo group.

Among the subjects who completed the trial, average lumbar spine BMD increased 3.1% at 6 months and 4.5% at 1 year for those on the contraceptive.

BMD only increased 1.1% and 2.8%, respectively, in the placebo group.

All subjects received calcium and vitamin D, and both groups gained weight during the trial.

Safety data for the 123 enrollees showed adverse events to be similar for both cohorts, except for worsening of anorexia nervosa. Eleven girls on placebo and 3 on Ortho Tri-Cyclen were hospitalized for relapses.

“To treat the whole patient, [oral contraceptive] is not a substitute for counseling and other types of therapy, but it serves as an important adjunct to improve their [BMD] and maximize their peak bone mass,” Dr. Friedman said in an interview.

The study enrolled postmenarcheal patients up to age 17 years at 91 sites. Their average age was 15 years, and their mean body mass index was below 18.

Dr. Friedman said 10% had primary amenorrhea attributable to anorexia nervosa, and 90% had secondary amenorrhea. Almost all participants were white.

In the interview, he said the girls were advised to use an additional form of contraception if sexually active in case they began to menstruate during the study.

Some parents declined to allow their minor daughters to participate because the protocol called for birth control, he noted.

Another barrier to recruitment cited in his talk was the girls' concern about possible weight gain from the pill. “We had to disclose the pills had 0.4 calories per pill,” he said.

As endogenous estrogen is known to help build bones in puberty, Dr. Friedman said the investigators hypothesized that estrogen in the contraceptive pill would play a similar role in these girls.

In adults, he said there is conflicting data on whether a combination of estrogen and progesterone would build bone density.

The oral contraceptive had not been previously tested in adolescents with anorexia nervosa, according to Dr. Friedman.

“I wouldn't advocate birth control pills for all anorexia nervosa subjects, but it may be appropriate for some subjects, and that is really a clinical decision,” he noted during his presentation.

PHOENIX, ARIZ. — Physicians, get ready. This summer, patients are likely to ask whether they should be spending more time in the sun, Darrell S. Rigel, M.D., warned attendees at a clinical dermatology conference sponsored by Medicis.

He blamed a book, “The UV Advantage” (New York: iBooks, May 2004), which scorns sun avoidance and advocates moderate doses of sunlight for better conversion of vitamin D in the body. Widespread distribution in tanning salons and coverage in the popular press has piqued public interest, according to Dr. Rigel of New York University.

Illustrating his point, he showed videotape of a “Good Morning America” segment in which he debated the author, Michael Holick, M.D.

“There will be a lot of stories this summer about how people should spend more time in the sun,” Dr. Rigel said, urging his audience to have rebuttal data ready to hand.

Dr. Holick, an endocrinologist, is a professor of medicine, physiology, and biophysiology at Boston University. He was asked to resign from the department of dermatology after the book's publication, but he continues to serve as director of the school's vitamin D, skin, and bone research laboratory and of its general clinical research center.

“There's no evidence that you increase your risk of melanoma from sensible sun exposure. In fact, it decreases your risk,” he said in a brief telephone interview following Dr. Rigel's talk.

Here are some of the issues under dispute:

▸ Tanning industry support. Dr. Rigel alleged the tanning industry is the driving force behind the book. “The tanning industry could not claim any health benefits [gained] by going to a tanning salon,” he said, noting that Dr. Holick often speaks at tanning industry functions. “They bankrolled the book. … There is a conflict of interest that is not disclosed.”

Dr. Holick confirmed $150,000 in grants from International Tanning Association but said the money is to be awarded during the next 3 years for research into sunlight and vitamin D. “They did not fund the book. I paid money out of my own pocket, and I haven't made a cent,” he said of its publication.

▸ Vitamin D deficiency. In the book and in a journal article, Dr. Holick warned of “an unrecognized epidemic of Vitamin D deficiency among both children and adults in the United States” (Am. J. Clin. Nutr. 2004;80[suppl. 6]:1678S–88S). Among the potential consequences, he has listed rickets, worsening of bone diseases such as osteoporosis and osteomalacia, and increased risk of cancer, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus.

“Where is this epidemic?” Dr. Rigel asked. “We're not seeing this.”

He questioned whether it is based on a recommendation that blood concentrations of 25-hydroxyvitamin D should be higher than 80 nmol/L. “There is no science to this. It is just an arbitrary argument that levels should be changed,” Dr. Rigel said.

▸ Cancer risk. Dr. Rigel accused the author of ignoring life-threatening consequences of sun exposure. “He says risk of nonmelanoma skin cancer is not really important. He does not talk about melanoma,” Dr. Rigel said.

“Sensible sun exposure decreases your risk of melanoma,” countered Dr. Holick. “Unfortunately, [dermatologists] have very closed minds about this and lump all skin cancers together.”

The author said most melanomas occur in areas of the body with the least sun exposure. He also cited a study that found melanoma patients who have more sun exposure survive longer (J. Natl. Cancer. Inst. 2005;97:195–9)—a conclusion Dr. Rigel dismissed as “advocating getting more sun after diagnosis, so you'll survive better.”

Dr. Rigel said an alternative interpretation could be that people with a history of sun exposure are more concerned about their cancer risk and, therefore, seek treatment earlier. He also cited a commentary that warned the study should be interpreted with caution and questioned whether a more likely explanation involves “a different pathogenesis in melanomas that arise in persons at risk to develop actinic skin damage” (J. Natl. Cancer. Inst. 2005;97:161–3).

▸ Sensible sun exposure. Dr. Holick recommends 5–10 minutes of sun exposure on the face and on the arms and legs or hands and arms two or three times a week, along with increased dietary and supplemental vitamin D.

The average person gets more exposure than that during the normal course of daily life, according to Dr. Rigel. “There's no reason to suggest to your patients they should expose themselves, because they will get enough otherwise,” he said.

He urged physicians to recommend to their patients that sunscreen be part of a total sun-protection program that includes wearing protective clothing and avoiding the midday sun.

Even with sunscreen, incidental levels of UV light appear to lead to normal levels of vitamin D, he said.

PHOENIX, ARIZ. — Physicians, get ready. This summer, patients are likely to ask whether they should be spending more time in the sun, Darrell S. Rigel, M.D., warned attendees at a clinical dermatology conference sponsored by Medicis.

He blamed a book, “The UV Advantage” (New York: iBooks, May 2004), which scorns sun avoidance and advocates moderate doses of sunlight for better conversion of vitamin D in the body. Widespread distribution in tanning salons and coverage in the popular press has piqued public interest, according to Dr. Rigel of New York University.

Illustrating his point, he showed videotape of a “Good Morning America” segment in which he debated the author, Michael Holick, M.D.

“There will be a lot of stories this summer about how people should spend more time in the sun,” Dr. Rigel said, urging his audience to have rebuttal data ready to hand.

Dr. Holick, an endocrinologist, is a professor of medicine, physiology, and biophysiology at Boston University. He was asked to resign from the department of dermatology after the book's publication, but he continues to serve as director of the school's vitamin D, skin, and bone research laboratory and of its general clinical research center.

“There's no evidence that you increase your risk of melanoma from sensible sun exposure. In fact, it decreases your risk,” he said in a brief telephone interview following Dr. Rigel's talk.

Here are some of the issues under dispute:

▸ Tanning industry support. Dr. Rigel alleged the tanning industry is the driving force behind the book. “The tanning industry could not claim any health benefits [gained] by going to a tanning salon,” he said, noting that Dr. Holick often speaks at tanning industry functions. “They bankrolled the book. … There is a conflict of interest that is not disclosed.”

Dr. Holick confirmed $150,000 in grants from International Tanning Association but said the money is to be awarded during the next 3 years for research into sunlight and vitamin D. “They did not fund the book. I paid money out of my own pocket, and I haven't made a cent,” he said of its publication.

▸ Vitamin D deficiency. In the book and in a journal article, Dr. Holick warned of “an unrecognized epidemic of Vitamin D deficiency among both children and adults in the United States” (Am. J. Clin. Nutr. 2004;80[suppl. 6]:1678S–88S). Among the potential consequences, he has listed rickets, worsening of bone diseases such as osteoporosis and osteomalacia, and increased risk of cancer, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus.

“Where is this epidemic?” Dr. Rigel asked. “We're not seeing this.”

He questioned whether it is based on a recommendation that blood concentrations of 25-hydroxyvitamin D should be higher than 80 nmol/L. “There is no science to this. It is just an arbitrary argument that levels should be changed,” Dr. Rigel said.

▸ Cancer risk. Dr. Rigel accused the author of ignoring life-threatening consequences of sun exposure. “He says risk of nonmelanoma skin cancer is not really important. He does not talk about melanoma,” Dr. Rigel said.

“Sensible sun exposure decreases your risk of melanoma,” countered Dr. Holick. “Unfortunately, [dermatologists] have very closed minds about this and lump all skin cancers together.”

The author said most melanomas occur in areas of the body with the least sun exposure. He also cited a study that found melanoma patients who have more sun exposure survive longer (J. Natl. Cancer. Inst. 2005;97:195–9)—a conclusion Dr. Rigel dismissed as “advocating getting more sun after diagnosis, so you'll survive better.”

Dr. Rigel said an alternative interpretation could be that people with a history of sun exposure are more concerned about their cancer risk and, therefore, seek treatment earlier. He also cited a commentary that warned the study should be interpreted with caution and questioned whether a more likely explanation involves “a different pathogenesis in melanomas that arise in persons at risk to develop actinic skin damage” (J. Natl. Cancer. Inst. 2005;97:161–3).

▸ Sensible sun exposure. Dr. Holick recommends 5–10 minutes of sun exposure on the face and on the arms and legs or hands and arms two or three times a week, along with increased dietary and supplemental vitamin D.

The average person gets more exposure than that during the normal course of daily life, according to Dr. Rigel. “There's no reason to suggest to your patients they should expose themselves, because they will get enough otherwise,” he said.

He urged physicians to recommend to their patients that sunscreen be part of a total sun-protection program that includes wearing protective clothing and avoiding the midday sun.

Even with sunscreen, incidental levels of UV light appear to lead to normal levels of vitamin D, he said.

PHOENIX, ARIZ. — Physicians, get ready. This summer, patients are likely to ask whether they should be spending more time in the sun, Darrell S. Rigel, M.D., warned attendees at a clinical dermatology conference sponsored by Medicis.

He blamed a book, “The UV Advantage” (New York: iBooks, May 2004), which scorns sun avoidance and advocates moderate doses of sunlight for better conversion of vitamin D in the body. Widespread distribution in tanning salons and coverage in the popular press has piqued public interest, according to Dr. Rigel of New York University.

Illustrating his point, he showed videotape of a “Good Morning America” segment in which he debated the author, Michael Holick, M.D.

“There will be a lot of stories this summer about how people should spend more time in the sun,” Dr. Rigel said, urging his audience to have rebuttal data ready to hand.

Dr. Holick, an endocrinologist, is a professor of medicine, physiology, and biophysiology at Boston University. He was asked to resign from the department of dermatology after the book's publication, but he continues to serve as director of the school's vitamin D, skin, and bone research laboratory and of its general clinical research center.

“There's no evidence that you increase your risk of melanoma from sensible sun exposure. In fact, it decreases your risk,” he said in a brief telephone interview following Dr. Rigel's talk.

Here are some of the issues under dispute:

▸ Tanning industry support. Dr. Rigel alleged the tanning industry is the driving force behind the book. “The tanning industry could not claim any health benefits [gained] by going to a tanning salon,” he said, noting that Dr. Holick often speaks at tanning industry functions. “They bankrolled the book. … There is a conflict of interest that is not disclosed.”

Dr. Holick confirmed $150,000 in grants from International Tanning Association but said the money is to be awarded during the next 3 years for research into sunlight and vitamin D. “They did not fund the book. I paid money out of my own pocket, and I haven't made a cent,” he said of its publication.

▸ Vitamin D deficiency. In the book and in a journal article, Dr. Holick warned of “an unrecognized epidemic of Vitamin D deficiency among both children and adults in the United States” (Am. J. Clin. Nutr. 2004;80[suppl. 6]:1678S–88S). Among the potential consequences, he has listed rickets, worsening of bone diseases such as osteoporosis and osteomalacia, and increased risk of cancer, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus.

“Where is this epidemic?” Dr. Rigel asked. “We're not seeing this.”

He questioned whether it is based on a recommendation that blood concentrations of 25-hydroxyvitamin D should be higher than 80 nmol/L. “There is no science to this. It is just an arbitrary argument that levels should be changed,” Dr. Rigel said.

▸ Cancer risk. Dr. Rigel accused the author of ignoring life-threatening consequences of sun exposure. “He says risk of nonmelanoma skin cancer is not really important. He does not talk about melanoma,” Dr. Rigel said.

“Sensible sun exposure decreases your risk of melanoma,” countered Dr. Holick. “Unfortunately, [dermatologists] have very closed minds about this and lump all skin cancers together.”

The author said most melanomas occur in areas of the body with the least sun exposure. He also cited a study that found melanoma patients who have more sun exposure survive longer (J. Natl. Cancer. Inst. 2005;97:195–9)—a conclusion Dr. Rigel dismissed as “advocating getting more sun after diagnosis, so you'll survive better.”

Dr. Rigel said an alternative interpretation could be that people with a history of sun exposure are more concerned about their cancer risk and, therefore, seek treatment earlier. He also cited a commentary that warned the study should be interpreted with caution and questioned whether a more likely explanation involves “a different pathogenesis in melanomas that arise in persons at risk to develop actinic skin damage” (J. Natl. Cancer. Inst. 2005;97:161–3).

▸ Sensible sun exposure. Dr. Holick recommends 5–10 minutes of sun exposure on the face and on the arms and legs or hands and arms two or three times a week, along with increased dietary and supplemental vitamin D.

The average person gets more exposure than that during the normal course of daily life, according to Dr. Rigel. “There's no reason to suggest to your patients they should expose themselves, because they will get enough otherwise,” he said.

He urged physicians to recommend to their patients that sunscreen be part of a total sun-protection program that includes wearing protective clothing and avoiding the midday sun.

Even with sunscreen, incidental levels of UV light appear to lead to normal levels of vitamin D, he said.

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study show.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D.

“There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurological disorders; 11 were women.

The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The length of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study show.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D.

“There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurological disorders; 11 were women.

The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The length of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study show.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D.

“There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurological disorders; 11 were women.

The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The length of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.

SCOTTSDALE, ARIZ. – The validity of large, randomized multicenter clinical trials involving treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting. “I really think there is something about phase III trials that impacts the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15–20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers–to get everybody to do the same thing–is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said.

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be standard if it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D. of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem–method.”

SCOTTSDALE, ARIZ. – The validity of large, randomized multicenter clinical trials involving treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting. “I really think there is something about phase III trials that impacts the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15–20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers–to get everybody to do the same thing–is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said.

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be standard if it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D. of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem–method.”

SCOTTSDALE, ARIZ. – The validity of large, randomized multicenter clinical trials involving treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting. “I really think there is something about phase III trials that impacts the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15–20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers–to get everybody to do the same thing–is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said.

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be standard if it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D. of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem–method.”