Michele G. Sullivan

Magnetic resonance imaging is an effective means of diagnosing acute abdominal and pelvic pain in pregnant patients, and it avoids fetal exposure to the radiation of a computerized axial tomography exam, Katherine Birchard, M.D., and her colleagues have reported.

Although there have been no documented cases of MRI causing adverse effects to the fetus, MRI scans should be used in pregnant patients only when the benefits clearly outweigh the risks, the researchers said. “However, we should stress that the single greatest factor in morbidity and mortality of the pregnant patient is delay in diagnosis,” reported Dr. Birchard of the University of North Carolina, and associates (AJR Am. J. Roentgenol. 2005;184:452-8).

The researchers retrospectively analyzed all MRI studies of 29 pregnant patients referred to their facility from 2002 to 2004 for evaluation of acute abdominal or pelvic pain. The patients' mean age was 25 years (18-35 years), and mean gestational age was 23 weeks (10-36 weeks). Most of the patients (22) did not have gadolinium administered.

Every patient underwent fetal sonography before any other imaging. Six also underwent complete abdominal sonographic examination before the MRI, which was the imaging exam used in 23 patients.

MRI identified appendiceal abscess (1 case), appendicitis (2 cases), intraabdominal and rectus muscle abscess (1), pancreatitis (1), and ulcerative colitis (1). MRI also showed Crohn's disease with diffuse peritoneal inflammation (1), intussusception (1), bilateral adrenal hemorrhage (1), pyelonephritis (2), hydronephrosis (1), uterine fibroid degeneration (2), degeneration and torsion of a subserosal uterine fibroid (1), simple ovarian cysts (1), and ovarian torsion (1). The other 12 examinations were normal.

The MRI results were congruent with follow-up medical records in 28 of the 29 patients and accurately described the disease process in all except one patient. This patient was at 18 weeks' gestation and complained of acute right lower quadrant pain. The MRI identified multiple ovarian cysts, but a laparoscopy 1 month later showed a torsed right ovary with multiple cysts. When examined retrospectively, the MRI did not shown this finding.

“We believe this is due to the fact that the ovary was largely cystic, and therefore, edematous tissue was not seen,” the researchers said.

Magnetic resonance imaging is an effective means of diagnosing acute abdominal and pelvic pain in pregnant patients, and it avoids fetal exposure to the radiation of a computerized axial tomography exam, Katherine Birchard, M.D., and her colleagues have reported.

Although there have been no documented cases of MRI causing adverse effects to the fetus, MRI scans should be used in pregnant patients only when the benefits clearly outweigh the risks, the researchers said. “However, we should stress that the single greatest factor in morbidity and mortality of the pregnant patient is delay in diagnosis,” reported Dr. Birchard of the University of North Carolina, and associates (AJR Am. J. Roentgenol. 2005;184:452-8).

The researchers retrospectively analyzed all MRI studies of 29 pregnant patients referred to their facility from 2002 to 2004 for evaluation of acute abdominal or pelvic pain. The patients' mean age was 25 years (18-35 years), and mean gestational age was 23 weeks (10-36 weeks). Most of the patients (22) did not have gadolinium administered.

Every patient underwent fetal sonography before any other imaging. Six also underwent complete abdominal sonographic examination before the MRI, which was the imaging exam used in 23 patients.

MRI identified appendiceal abscess (1 case), appendicitis (2 cases), intraabdominal and rectus muscle abscess (1), pancreatitis (1), and ulcerative colitis (1). MRI also showed Crohn's disease with diffuse peritoneal inflammation (1), intussusception (1), bilateral adrenal hemorrhage (1), pyelonephritis (2), hydronephrosis (1), uterine fibroid degeneration (2), degeneration and torsion of a subserosal uterine fibroid (1), simple ovarian cysts (1), and ovarian torsion (1). The other 12 examinations were normal.

The MRI results were congruent with follow-up medical records in 28 of the 29 patients and accurately described the disease process in all except one patient. This patient was at 18 weeks' gestation and complained of acute right lower quadrant pain. The MRI identified multiple ovarian cysts, but a laparoscopy 1 month later showed a torsed right ovary with multiple cysts. When examined retrospectively, the MRI did not shown this finding.

“We believe this is due to the fact that the ovary was largely cystic, and therefore, edematous tissue was not seen,” the researchers said.

Magnetic resonance imaging is an effective means of diagnosing acute abdominal and pelvic pain in pregnant patients, and it avoids fetal exposure to the radiation of a computerized axial tomography exam, Katherine Birchard, M.D., and her colleagues have reported.

Although there have been no documented cases of MRI causing adverse effects to the fetus, MRI scans should be used in pregnant patients only when the benefits clearly outweigh the risks, the researchers said. “However, we should stress that the single greatest factor in morbidity and mortality of the pregnant patient is delay in diagnosis,” reported Dr. Birchard of the University of North Carolina, and associates (AJR Am. J. Roentgenol. 2005;184:452-8).

The researchers retrospectively analyzed all MRI studies of 29 pregnant patients referred to their facility from 2002 to 2004 for evaluation of acute abdominal or pelvic pain. The patients' mean age was 25 years (18-35 years), and mean gestational age was 23 weeks (10-36 weeks). Most of the patients (22) did not have gadolinium administered.

Every patient underwent fetal sonography before any other imaging. Six also underwent complete abdominal sonographic examination before the MRI, which was the imaging exam used in 23 patients.

MRI identified appendiceal abscess (1 case), appendicitis (2 cases), intraabdominal and rectus muscle abscess (1), pancreatitis (1), and ulcerative colitis (1). MRI also showed Crohn's disease with diffuse peritoneal inflammation (1), intussusception (1), bilateral adrenal hemorrhage (1), pyelonephritis (2), hydronephrosis (1), uterine fibroid degeneration (2), degeneration and torsion of a subserosal uterine fibroid (1), simple ovarian cysts (1), and ovarian torsion (1). The other 12 examinations were normal.

The MRI results were congruent with follow-up medical records in 28 of the 29 patients and accurately described the disease process in all except one patient. This patient was at 18 weeks' gestation and complained of acute right lower quadrant pain. The MRI identified multiple ovarian cysts, but a laparoscopy 1 month later showed a torsed right ovary with multiple cysts. When examined retrospectively, the MRI did not shown this finding.

“We believe this is due to the fact that the ovary was largely cystic, and therefore, edematous tissue was not seen,” the researchers said.

Metoclopramide Eases Adult Migraine

Metoclopramide is an effective migraine treatment for adults; one in four migraine patients will experience significant pain reduction with the drug.

However, other drugs may have more effect on migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England) and his colleagues.

The metaanalysis included five studies of metoclopramide versus placebo (263 adults); three studies of metoclopramide versus other antiemetics (194 patients); two studies of metoclopramide versus nonantiemetics (60 patients): and seven studies of metoclopramide combinations versus other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to make firm conclusions about its relative effectiveness (BMJ 2004;329:1369–73).

Stabbing Triggered Hydrocephalus

Though rare, hydrocephalus should be considered a possible late complication of a spinal stabbing injury in a patient whose condition suddenly deteriorates, reported G. Joseph, M.D., and colleagues.

Five months after a knife attack that involved partial transection of the cervical cord just above the craniovertebral junction, a 19-year-old man developed muscle spasms and dysreflexia episodes, followed by two seizures. Computerized axial tomography showed communicating hydrocephalus resulting in enlargement of all four ventricles, said the investigators, of Southern General Hospital, Glasgow, Scotland (Spinal Cord 2005;43:56–8).

His condition stabilized with placement of a ventriculoperitoneal shunt and gradually improved. Over the next 3 months, the man was partially weaned off ventilator. At 6 years' follow-up, he had recovered complete sensation in all limbs but still required ventilator support at night.

“In our patient … pathogenesis may be related to the high level of the penetrating injury leading to blood from the site of injury entering the basal cisterns and impairing the absorption of the CSF by the arachnoid villi over the hemispheres,” they wrote.

Refractory Epilepsy's Costs for Kids

Controlling seizures often lessens behavioral and neuropsychological problems that are ubiquitous in children with refractory epilepsy, said Marc Boel, M.D., of University Hospitals Gasthuisberg, Leuven, Belgium.

Among 573 such children seen in his clinic, 80% showed behavioral problems, and 15% showed significant mental decline related to their epilepsy.

About half of the entire group had an IQ of below 50 (Eur. J. Pediatr. Neurol. 2005;8:291–7).

Most of the children had either partial epilepsy (29%) or secondary generalized tonic-clonic epilepsy (25%). Approximately 4% had Lennox-Gastaut syndrome.

The most frequent neurobehavioral disorders were pervasive developmental disorder (8%); attention deficit hyperactivity disorder (7.5%); loss of self-esteem (9%), and self-induction of seizures (7%). Psychosis, anxiety disorders, intermittent explosive disorder, and cursive seizures were seen at lower rates.

In 101 of the 220 children who achieved seizure control, behavioral problems disappeared or were minimized.

A Toast for the Aging Brain

A drink a day appears to protect elderly women from cognitive decline, according to new data from the ongoing Nurses' Health Study.

Interviewers gave four cognitive tests to over 11,000 women aged 70–81 years, said Meir Stampfer, M.D., of Brigham and Women's Hospital, Boston, and associates.

They found that moderate drinkers (one drink/day) had a 20% lower risk of cognitive decline than nondrinkers or those who drank two or more drinks/day. Both wine and beer were associated with the protective effect (N. Engl. J. Med. 2005;3:245–53).

Metoclopramide Eases Adult Migraine

Metoclopramide is an effective migraine treatment for adults; one in four migraine patients will experience significant pain reduction with the drug.

However, other drugs may have more effect on migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England) and his colleagues.

The metaanalysis included five studies of metoclopramide versus placebo (263 adults); three studies of metoclopramide versus other antiemetics (194 patients); two studies of metoclopramide versus nonantiemetics (60 patients): and seven studies of metoclopramide combinations versus other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to make firm conclusions about its relative effectiveness (BMJ 2004;329:1369–73).

Stabbing Triggered Hydrocephalus

Though rare, hydrocephalus should be considered a possible late complication of a spinal stabbing injury in a patient whose condition suddenly deteriorates, reported G. Joseph, M.D., and colleagues.

Five months after a knife attack that involved partial transection of the cervical cord just above the craniovertebral junction, a 19-year-old man developed muscle spasms and dysreflexia episodes, followed by two seizures. Computerized axial tomography showed communicating hydrocephalus resulting in enlargement of all four ventricles, said the investigators, of Southern General Hospital, Glasgow, Scotland (Spinal Cord 2005;43:56–8).

His condition stabilized with placement of a ventriculoperitoneal shunt and gradually improved. Over the next 3 months, the man was partially weaned off ventilator. At 6 years' follow-up, he had recovered complete sensation in all limbs but still required ventilator support at night.

“In our patient … pathogenesis may be related to the high level of the penetrating injury leading to blood from the site of injury entering the basal cisterns and impairing the absorption of the CSF by the arachnoid villi over the hemispheres,” they wrote.

Refractory Epilepsy's Costs for Kids

Controlling seizures often lessens behavioral and neuropsychological problems that are ubiquitous in children with refractory epilepsy, said Marc Boel, M.D., of University Hospitals Gasthuisberg, Leuven, Belgium.

Among 573 such children seen in his clinic, 80% showed behavioral problems, and 15% showed significant mental decline related to their epilepsy.

About half of the entire group had an IQ of below 50 (Eur. J. Pediatr. Neurol. 2005;8:291–7).

Most of the children had either partial epilepsy (29%) or secondary generalized tonic-clonic epilepsy (25%). Approximately 4% had Lennox-Gastaut syndrome.

The most frequent neurobehavioral disorders were pervasive developmental disorder (8%); attention deficit hyperactivity disorder (7.5%); loss of self-esteem (9%), and self-induction of seizures (7%). Psychosis, anxiety disorders, intermittent explosive disorder, and cursive seizures were seen at lower rates.

In 101 of the 220 children who achieved seizure control, behavioral problems disappeared or were minimized.

A Toast for the Aging Brain

A drink a day appears to protect elderly women from cognitive decline, according to new data from the ongoing Nurses' Health Study.

Interviewers gave four cognitive tests to over 11,000 women aged 70–81 years, said Meir Stampfer, M.D., of Brigham and Women's Hospital, Boston, and associates.

They found that moderate drinkers (one drink/day) had a 20% lower risk of cognitive decline than nondrinkers or those who drank two or more drinks/day. Both wine and beer were associated with the protective effect (N. Engl. J. Med. 2005;3:245–53).

Metoclopramide Eases Adult Migraine

Metoclopramide is an effective migraine treatment for adults; one in four migraine patients will experience significant pain reduction with the drug.

However, other drugs may have more effect on migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England) and his colleagues.

The metaanalysis included five studies of metoclopramide versus placebo (263 adults); three studies of metoclopramide versus other antiemetics (194 patients); two studies of metoclopramide versus nonantiemetics (60 patients): and seven studies of metoclopramide combinations versus other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to make firm conclusions about its relative effectiveness (BMJ 2004;329:1369–73).

Stabbing Triggered Hydrocephalus

Though rare, hydrocephalus should be considered a possible late complication of a spinal stabbing injury in a patient whose condition suddenly deteriorates, reported G. Joseph, M.D., and colleagues.

Five months after a knife attack that involved partial transection of the cervical cord just above the craniovertebral junction, a 19-year-old man developed muscle spasms and dysreflexia episodes, followed by two seizures. Computerized axial tomography showed communicating hydrocephalus resulting in enlargement of all four ventricles, said the investigators, of Southern General Hospital, Glasgow, Scotland (Spinal Cord 2005;43:56–8).

His condition stabilized with placement of a ventriculoperitoneal shunt and gradually improved. Over the next 3 months, the man was partially weaned off ventilator. At 6 years' follow-up, he had recovered complete sensation in all limbs but still required ventilator support at night.

“In our patient … pathogenesis may be related to the high level of the penetrating injury leading to blood from the site of injury entering the basal cisterns and impairing the absorption of the CSF by the arachnoid villi over the hemispheres,” they wrote.

Refractory Epilepsy's Costs for Kids

Controlling seizures often lessens behavioral and neuropsychological problems that are ubiquitous in children with refractory epilepsy, said Marc Boel, M.D., of University Hospitals Gasthuisberg, Leuven, Belgium.

Among 573 such children seen in his clinic, 80% showed behavioral problems, and 15% showed significant mental decline related to their epilepsy.

About half of the entire group had an IQ of below 50 (Eur. J. Pediatr. Neurol. 2005;8:291–7).

Most of the children had either partial epilepsy (29%) or secondary generalized tonic-clonic epilepsy (25%). Approximately 4% had Lennox-Gastaut syndrome.

The most frequent neurobehavioral disorders were pervasive developmental disorder (8%); attention deficit hyperactivity disorder (7.5%); loss of self-esteem (9%), and self-induction of seizures (7%). Psychosis, anxiety disorders, intermittent explosive disorder, and cursive seizures were seen at lower rates.

In 101 of the 220 children who achieved seizure control, behavioral problems disappeared or were minimized.

A Toast for the Aging Brain

A drink a day appears to protect elderly women from cognitive decline, according to new data from the ongoing Nurses' Health Study.

Interviewers gave four cognitive tests to over 11,000 women aged 70–81 years, said Meir Stampfer, M.D., of Brigham and Women's Hospital, Boston, and associates.

They found that moderate drinkers (one drink/day) had a 20% lower risk of cognitive decline than nondrinkers or those who drank two or more drinks/day. Both wine and beer were associated with the protective effect (N. Engl. J. Med. 2005;3:245–53).

Adolescent women who use the injectable contraceptive depot medroxyprogesterone acetate lose bone mineral density each year they are on the drug but appear to rapidly recover that loss when the drug is withdrawn, results of a prospective study suggest.

“The potential loss of bone density is one consideration of the many that go into a women's choice of contraceptive method,” said Delia Scholes, Ph.D., of the Center for Health Studies, Seattle, and her associates.

Dr. Scholes and her associates prospectively examined BMD in a cohort of 170 females aged 14-18. A total of 80 participants were using DMPA, and 90 were not. The DMPA-exposed teens were significantly more likely to be current smokers, to have been pregnant, have reached earlier menarche, and have a higher body mass index and body fat percentage (Arch. Pediatr. Adolesc. Med. 2005;159:139-44).

During the study, 61 of the DMPA users discontinued the contraceptive, affording the opportunity to observe any subsequent changes in BMD.

The DMPA-exposed subjects were receiving the standard dose of 150 mg every 3 months. About 30% of them had received only 1 injection, 31% had received 2 or 3 injections, 21% had received 4-7 injections, and 18% had received at least 18 injections. In the comparison group, 19% were using oral contraceptives at baseline.

BMD was measured at the hip, spine, and whole body every 6 months for 24-36 months. After adjustment the DMPA users had lost significantly more BMD at the hip (-1.81% vs. -0.19%) and spine (-0.97% vs. 1.32%), compared with nonusers. Both groups gained BMD when the whole body was measured, but the DMPA users gained significantly less than the nonusers (0.73% vs 0.88%). New users lost bone faster than continuous users. After 24 months, new users showed a -6.09% change at the hip, compared with -2.05% in continuous users and -0.92% in nonusers.

Among the 61 subjects who discontinued DMPA during the study, BMD increased. Their annualized adjusted mean change in BMD was 1.34% for hip, 2.86% for spine, and 3.56% for the whole body. There was no significant difference in BMD between nonusers and those who discontinued DMPA 18 months earlier.

The injection is highly effective in preventing pregnancy and may help reduce compliance problems, the researchers said.

In 2004, the Food and Drug Administration issued a black box warning for DMPA stating that prolonged use of the drug could result in significant loss of bone density, that the loss is greater the longer the drug is administered, and that bone density loss may not be completely reversible after discontinuing the drug.

Adolescent women who use the injectable contraceptive depot medroxyprogesterone acetate lose bone mineral density each year they are on the drug but appear to rapidly recover that loss when the drug is withdrawn, results of a prospective study suggest.

“The potential loss of bone density is one consideration of the many that go into a women's choice of contraceptive method,” said Delia Scholes, Ph.D., of the Center for Health Studies, Seattle, and her associates.

Dr. Scholes and her associates prospectively examined BMD in a cohort of 170 females aged 14-18. A total of 80 participants were using DMPA, and 90 were not. The DMPA-exposed teens were significantly more likely to be current smokers, to have been pregnant, have reached earlier menarche, and have a higher body mass index and body fat percentage (Arch. Pediatr. Adolesc. Med. 2005;159:139-44).

During the study, 61 of the DMPA users discontinued the contraceptive, affording the opportunity to observe any subsequent changes in BMD.

The DMPA-exposed subjects were receiving the standard dose of 150 mg every 3 months. About 30% of them had received only 1 injection, 31% had received 2 or 3 injections, 21% had received 4-7 injections, and 18% had received at least 18 injections. In the comparison group, 19% were using oral contraceptives at baseline.

BMD was measured at the hip, spine, and whole body every 6 months for 24-36 months. After adjustment the DMPA users had lost significantly more BMD at the hip (-1.81% vs. -0.19%) and spine (-0.97% vs. 1.32%), compared with nonusers. Both groups gained BMD when the whole body was measured, but the DMPA users gained significantly less than the nonusers (0.73% vs 0.88%). New users lost bone faster than continuous users. After 24 months, new users showed a -6.09% change at the hip, compared with -2.05% in continuous users and -0.92% in nonusers.

Among the 61 subjects who discontinued DMPA during the study, BMD increased. Their annualized adjusted mean change in BMD was 1.34% for hip, 2.86% for spine, and 3.56% for the whole body. There was no significant difference in BMD between nonusers and those who discontinued DMPA 18 months earlier.

The injection is highly effective in preventing pregnancy and may help reduce compliance problems, the researchers said.

In 2004, the Food and Drug Administration issued a black box warning for DMPA stating that prolonged use of the drug could result in significant loss of bone density, that the loss is greater the longer the drug is administered, and that bone density loss may not be completely reversible after discontinuing the drug.

Adolescent women who use the injectable contraceptive depot medroxyprogesterone acetate lose bone mineral density each year they are on the drug but appear to rapidly recover that loss when the drug is withdrawn, results of a prospective study suggest.

“The potential loss of bone density is one consideration of the many that go into a women's choice of contraceptive method,” said Delia Scholes, Ph.D., of the Center for Health Studies, Seattle, and her associates.

Dr. Scholes and her associates prospectively examined BMD in a cohort of 170 females aged 14-18. A total of 80 participants were using DMPA, and 90 were not. The DMPA-exposed teens were significantly more likely to be current smokers, to have been pregnant, have reached earlier menarche, and have a higher body mass index and body fat percentage (Arch. Pediatr. Adolesc. Med. 2005;159:139-44).

During the study, 61 of the DMPA users discontinued the contraceptive, affording the opportunity to observe any subsequent changes in BMD.

The DMPA-exposed subjects were receiving the standard dose of 150 mg every 3 months. About 30% of them had received only 1 injection, 31% had received 2 or 3 injections, 21% had received 4-7 injections, and 18% had received at least 18 injections. In the comparison group, 19% were using oral contraceptives at baseline.

BMD was measured at the hip, spine, and whole body every 6 months for 24-36 months. After adjustment the DMPA users had lost significantly more BMD at the hip (-1.81% vs. -0.19%) and spine (-0.97% vs. 1.32%), compared with nonusers. Both groups gained BMD when the whole body was measured, but the DMPA users gained significantly less than the nonusers (0.73% vs 0.88%). New users lost bone faster than continuous users. After 24 months, new users showed a -6.09% change at the hip, compared with -2.05% in continuous users and -0.92% in nonusers.

Among the 61 subjects who discontinued DMPA during the study, BMD increased. Their annualized adjusted mean change in BMD was 1.34% for hip, 2.86% for spine, and 3.56% for the whole body. There was no significant difference in BMD between nonusers and those who discontinued DMPA 18 months earlier.

The injection is highly effective in preventing pregnancy and may help reduce compliance problems, the researchers said.

In 2004, the Food and Drug Administration issued a black box warning for DMPA stating that prolonged use of the drug could result in significant loss of bone density, that the loss is greater the longer the drug is administered, and that bone density loss may not be completely reversible after discontinuing the drug.

WHITE SULPHUR SPRINGS, W.VA. — Within just 6-12 months of discontinuing hormone therapy, more than 96% of postmenopausal women will show altered vaginal pH, a marker for tissue change and its associated genital atrophy, Murray Freedman, M.D., reported.

Only 10 of 300 women maintained a normal vaginal pH of 4.5 or less after discontinuing HT use, and seven of those women had elevated serum estradiol levels related to obesity-driven estrogen production, said Dr. Freedman, clinical professor of ob.gyn at the Medical College of Georgia, Augusta.

The rest of the women had both elevated vaginal pH and decreased serum estradiol. The most common clinical finding in the study was involution of the vulvar structures and a rapidly occurring introital stenosis, which correlated with frequent complaints of dyspareunia, he noted at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Because the onset of genital atrophy is insidious and its measurement subjective, the number who experienced it was “hard to quantify,” Dr. Freedman told this newspaper. “There is no real measurement for it. But for many of these women, the stenosis became noticeable within 6-12 months.”

His observations led him to conclude that the dyspareunia many postmenopausal women experience has more to do with introital stenosis than vaginal dryness. “The dryness was secondary to the stenosis and the involution of the distal vagina. Once you got past the introitus, the upper vagina was uncompromised.”

His prospective observational study evaluated 300 women who had discontinued HT after publication of the initial Women's Health Initiative results in July 2002. All women underwent a pelvic exam and had their vaginal pH tested within 12 months of therapy discontinuation (most within 6 months). Those with a normal vaginal pH level (4.5 or below) had their serum estradiol level evaluated.

The vast majority of the women (290) had a pH level of more than 4.5. Only 10 maintained a normal vaginal pH. Three of those women had serum estradiol of less than 20 pcg/mL, consistent with postmenopausal status.

The other seven had normal circulating estradiol levels. One of these was a 50-year-old woman with her uterus, fallopian tubes, and ovaries intact, who had been placed on HT for menopausal symptoms. The other six women were older (57-76 years) and either overweight or obese.

In addition to observing introital stenosis, he also noted that the urethral meatus became more prominent in many women, assuming almost a tubular form and expanding to constitute up to two-thirds of the introitus. This is not surprising, he said, because the urethra and trigone are just as heavily endowed with estrogen receptors as are the lower vagina and vulva and just as susceptible to involutional change with estrogen deficiency.

“Embryologically, the vulva, distal vagina, trigone, and urethra are all derived from the urogenital sinus and contain the highest concentration of estrogen receptors. The upper vagina is actually a downgrowth of the müllerian system” and so less susceptible to change associated with estrogen depletion.

Because genital atrophy is so widespread and rapid after menopause in the absence of HT, women should be proactively counseled about how to maintain good genital health, Dr. Freedman said. If the decision is made to discontinue HT, topical estrogen can prevent genital atrophy and, if administered within the first year of estrogen cessation, can even reverse some changes.

Coitus at least once a week helps maintain tissue integrity by dilation and increased genital blood flow. “It's a use-it-or-lose-it phenomenon,” he said. “In the absence of both estrogen and sexual activity, the rapidity of involution is compounded.”

Women without a male partner can be counseled to use topical estrogen and a vibrator or vaginal dilator, and to become orgasmic, periodically. “This will maintain a normal, healthy vagina,” he said.

But most physicians—especially males—never broach the subject of sexuality with their postmenopausal patients. “To those men, I would put this question: 'At what age would you like your genitalia to begin shrinking?'” Dr. Freedman said. “I bet it wouldn't be 51, which is the average age of menopause in this country.”

WHITE SULPHUR SPRINGS, W.VA. — Within just 6-12 months of discontinuing hormone therapy, more than 96% of postmenopausal women will show altered vaginal pH, a marker for tissue change and its associated genital atrophy, Murray Freedman, M.D., reported.

Only 10 of 300 women maintained a normal vaginal pH of 4.5 or less after discontinuing HT use, and seven of those women had elevated serum estradiol levels related to obesity-driven estrogen production, said Dr. Freedman, clinical professor of ob.gyn at the Medical College of Georgia, Augusta.

The rest of the women had both elevated vaginal pH and decreased serum estradiol. The most common clinical finding in the study was involution of the vulvar structures and a rapidly occurring introital stenosis, which correlated with frequent complaints of dyspareunia, he noted at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Because the onset of genital atrophy is insidious and its measurement subjective, the number who experienced it was “hard to quantify,” Dr. Freedman told this newspaper. “There is no real measurement for it. But for many of these women, the stenosis became noticeable within 6-12 months.”

His observations led him to conclude that the dyspareunia many postmenopausal women experience has more to do with introital stenosis than vaginal dryness. “The dryness was secondary to the stenosis and the involution of the distal vagina. Once you got past the introitus, the upper vagina was uncompromised.”

His prospective observational study evaluated 300 women who had discontinued HT after publication of the initial Women's Health Initiative results in July 2002. All women underwent a pelvic exam and had their vaginal pH tested within 12 months of therapy discontinuation (most within 6 months). Those with a normal vaginal pH level (4.5 or below) had their serum estradiol level evaluated.

The vast majority of the women (290) had a pH level of more than 4.5. Only 10 maintained a normal vaginal pH. Three of those women had serum estradiol of less than 20 pcg/mL, consistent with postmenopausal status.

The other seven had normal circulating estradiol levels. One of these was a 50-year-old woman with her uterus, fallopian tubes, and ovaries intact, who had been placed on HT for menopausal symptoms. The other six women were older (57-76 years) and either overweight or obese.

In addition to observing introital stenosis, he also noted that the urethral meatus became more prominent in many women, assuming almost a tubular form and expanding to constitute up to two-thirds of the introitus. This is not surprising, he said, because the urethra and trigone are just as heavily endowed with estrogen receptors as are the lower vagina and vulva and just as susceptible to involutional change with estrogen deficiency.

“Embryologically, the vulva, distal vagina, trigone, and urethra are all derived from the urogenital sinus and contain the highest concentration of estrogen receptors. The upper vagina is actually a downgrowth of the müllerian system” and so less susceptible to change associated with estrogen depletion.

Because genital atrophy is so widespread and rapid after menopause in the absence of HT, women should be proactively counseled about how to maintain good genital health, Dr. Freedman said. If the decision is made to discontinue HT, topical estrogen can prevent genital atrophy and, if administered within the first year of estrogen cessation, can even reverse some changes.

Coitus at least once a week helps maintain tissue integrity by dilation and increased genital blood flow. “It's a use-it-or-lose-it phenomenon,” he said. “In the absence of both estrogen and sexual activity, the rapidity of involution is compounded.”

Women without a male partner can be counseled to use topical estrogen and a vibrator or vaginal dilator, and to become orgasmic, periodically. “This will maintain a normal, healthy vagina,” he said.

But most physicians—especially males—never broach the subject of sexuality with their postmenopausal patients. “To those men, I would put this question: 'At what age would you like your genitalia to begin shrinking?'” Dr. Freedman said. “I bet it wouldn't be 51, which is the average age of menopause in this country.”

WHITE SULPHUR SPRINGS, W.VA. — Within just 6-12 months of discontinuing hormone therapy, more than 96% of postmenopausal women will show altered vaginal pH, a marker for tissue change and its associated genital atrophy, Murray Freedman, M.D., reported.

Only 10 of 300 women maintained a normal vaginal pH of 4.5 or less after discontinuing HT use, and seven of those women had elevated serum estradiol levels related to obesity-driven estrogen production, said Dr. Freedman, clinical professor of ob.gyn at the Medical College of Georgia, Augusta.

The rest of the women had both elevated vaginal pH and decreased serum estradiol. The most common clinical finding in the study was involution of the vulvar structures and a rapidly occurring introital stenosis, which correlated with frequent complaints of dyspareunia, he noted at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Because the onset of genital atrophy is insidious and its measurement subjective, the number who experienced it was “hard to quantify,” Dr. Freedman told this newspaper. “There is no real measurement for it. But for many of these women, the stenosis became noticeable within 6-12 months.”

His observations led him to conclude that the dyspareunia many postmenopausal women experience has more to do with introital stenosis than vaginal dryness. “The dryness was secondary to the stenosis and the involution of the distal vagina. Once you got past the introitus, the upper vagina was uncompromised.”

His prospective observational study evaluated 300 women who had discontinued HT after publication of the initial Women's Health Initiative results in July 2002. All women underwent a pelvic exam and had their vaginal pH tested within 12 months of therapy discontinuation (most within 6 months). Those with a normal vaginal pH level (4.5 or below) had their serum estradiol level evaluated.

The vast majority of the women (290) had a pH level of more than 4.5. Only 10 maintained a normal vaginal pH. Three of those women had serum estradiol of less than 20 pcg/mL, consistent with postmenopausal status.

The other seven had normal circulating estradiol levels. One of these was a 50-year-old woman with her uterus, fallopian tubes, and ovaries intact, who had been placed on HT for menopausal symptoms. The other six women were older (57-76 years) and either overweight or obese.

In addition to observing introital stenosis, he also noted that the urethral meatus became more prominent in many women, assuming almost a tubular form and expanding to constitute up to two-thirds of the introitus. This is not surprising, he said, because the urethra and trigone are just as heavily endowed with estrogen receptors as are the lower vagina and vulva and just as susceptible to involutional change with estrogen deficiency.

“Embryologically, the vulva, distal vagina, trigone, and urethra are all derived from the urogenital sinus and contain the highest concentration of estrogen receptors. The upper vagina is actually a downgrowth of the müllerian system” and so less susceptible to change associated with estrogen depletion.

Because genital atrophy is so widespread and rapid after menopause in the absence of HT, women should be proactively counseled about how to maintain good genital health, Dr. Freedman said. If the decision is made to discontinue HT, topical estrogen can prevent genital atrophy and, if administered within the first year of estrogen cessation, can even reverse some changes.

Coitus at least once a week helps maintain tissue integrity by dilation and increased genital blood flow. “It's a use-it-or-lose-it phenomenon,” he said. “In the absence of both estrogen and sexual activity, the rapidity of involution is compounded.”

Women without a male partner can be counseled to use topical estrogen and a vibrator or vaginal dilator, and to become orgasmic, periodically. “This will maintain a normal, healthy vagina,” he said.

But most physicians—especially males—never broach the subject of sexuality with their postmenopausal patients. “To those men, I would put this question: 'At what age would you like your genitalia to begin shrinking?'” Dr. Freedman said. “I bet it wouldn't be 51, which is the average age of menopause in this country.”

STOCKHOLM — An interactive, online schizophrenia treatment algorithm provides a decision tree complete with graded supporting evidence and special clinical considerations for patients with comorbid or pre-existing conditions, Herbert Meltzer, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

Dr. Meltzer of Vanderbilt University, Nashville, Tenn., is part of a team of international experts who have spent 3 years preparing the algorithm for the International Psychopharmacology Algorithm Project. The algorithm is available at www.ipap.org

“This is meant to be an educational tool that opens the literature to people,” Dr. Meltzer said in an interview. “At each node, you can access extensive material that provides the rationale for each decision and gives more clinical information and key references.”

The algorithm begins with a triage approach to classifying patients by pre-existing condition or comorbid disorder. Clicking on those conditions—including emergent schizophrenia, substance abuse, suicidal and violent tendencies, noncompliance, and pregnancy—will link the user to information critical to the therapeutic decision-making process, Dr. Meltzer said.

The algorithm touches on nonpharmacologic treatments, although the bulk of the evidence deals with medical therapy with a focus on atypical antipsychotics. It stresses the importance of monotherapy for most patients, reserving polypharmacy for those who fail treatment with a single drug or who have very special needs.

Treatment recommendations are graded as to the level of evidence. At each decision node, the user can access links to the supporting literature. The nodes also include information about cost-effectiveness of treatments.

Since the project is meant to have international application, each treatment node also takes into account the variability of both international formularies and practice habits in different countries. And, unlike most treatment algorithms, which remain static after publication, this one will be a “living document” frequentlyupdated with the newest evidence, Dr. Meltzer said. Users will receive automatic notifications of the updates, which are expected to occur quarterly.

Kenneth O. Jobson, M.D., of the Tennessee Psychiatry and Psychopharmacology Clinic founded the International Psychopharmacology Algorithm Project (IPAP) in 1992. The project has been endorsed by the Collegium Internationale Neuro-Psychopharmalogicum. IPAP's goal is to bring together experts in psychiatry, psychopharmacology, and algorithm design to create and enhance algorithms for the systematic treatment of major Axis I psychiatric disorders. The idea for a schizophrenia algorithm was born during an IPAP meeting in China in 2001, when Dr. Jobson suggested the creation of an evidence-based online algorithm with international scope. The development team included specialists from France, Austria, Brazil, Australia, Germany, Canada, China, and Japan, as well as from the United States.

Although the algorithm is longer than most, Dr. Jobson said in an interview, it represents the clinical complexity of schizophrenia. It's also meant to be user-friendly. “We're getting some final comments now from our test group about its usability,” he said. “We're going to incorporate those suggestions into the final product.”

Although it strives for sequential logic and completeness of therapeutic options, the algorithm isn't meant to be used as “cookbook medicine,” Dr. Jobson cautioned.

The project received funding through unrestricted pharmaceutical company grants to The Dean Foundation. AstraZenca, Eli Lilly, Bristol-Myers Squibb, Janssen, Pfizer, and Novartis are also among the sources of funding for the project, Dr. Meltzer noted.

STOCKHOLM — An interactive, online schizophrenia treatment algorithm provides a decision tree complete with graded supporting evidence and special clinical considerations for patients with comorbid or pre-existing conditions, Herbert Meltzer, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

Dr. Meltzer of Vanderbilt University, Nashville, Tenn., is part of a team of international experts who have spent 3 years preparing the algorithm for the International Psychopharmacology Algorithm Project. The algorithm is available at www.ipap.org

“This is meant to be an educational tool that opens the literature to people,” Dr. Meltzer said in an interview. “At each node, you can access extensive material that provides the rationale for each decision and gives more clinical information and key references.”

The algorithm begins with a triage approach to classifying patients by pre-existing condition or comorbid disorder. Clicking on those conditions—including emergent schizophrenia, substance abuse, suicidal and violent tendencies, noncompliance, and pregnancy—will link the user to information critical to the therapeutic decision-making process, Dr. Meltzer said.

The algorithm touches on nonpharmacologic treatments, although the bulk of the evidence deals with medical therapy with a focus on atypical antipsychotics. It stresses the importance of monotherapy for most patients, reserving polypharmacy for those who fail treatment with a single drug or who have very special needs.

Treatment recommendations are graded as to the level of evidence. At each decision node, the user can access links to the supporting literature. The nodes also include information about cost-effectiveness of treatments.

Since the project is meant to have international application, each treatment node also takes into account the variability of both international formularies and practice habits in different countries. And, unlike most treatment algorithms, which remain static after publication, this one will be a “living document” frequentlyupdated with the newest evidence, Dr. Meltzer said. Users will receive automatic notifications of the updates, which are expected to occur quarterly.

Kenneth O. Jobson, M.D., of the Tennessee Psychiatry and Psychopharmacology Clinic founded the International Psychopharmacology Algorithm Project (IPAP) in 1992. The project has been endorsed by the Collegium Internationale Neuro-Psychopharmalogicum. IPAP's goal is to bring together experts in psychiatry, psychopharmacology, and algorithm design to create and enhance algorithms for the systematic treatment of major Axis I psychiatric disorders. The idea for a schizophrenia algorithm was born during an IPAP meeting in China in 2001, when Dr. Jobson suggested the creation of an evidence-based online algorithm with international scope. The development team included specialists from France, Austria, Brazil, Australia, Germany, Canada, China, and Japan, as well as from the United States.

Although the algorithm is longer than most, Dr. Jobson said in an interview, it represents the clinical complexity of schizophrenia. It's also meant to be user-friendly. “We're getting some final comments now from our test group about its usability,” he said. “We're going to incorporate those suggestions into the final product.”

Although it strives for sequential logic and completeness of therapeutic options, the algorithm isn't meant to be used as “cookbook medicine,” Dr. Jobson cautioned.

The project received funding through unrestricted pharmaceutical company grants to The Dean Foundation. AstraZenca, Eli Lilly, Bristol-Myers Squibb, Janssen, Pfizer, and Novartis are also among the sources of funding for the project, Dr. Meltzer noted.

STOCKHOLM — An interactive, online schizophrenia treatment algorithm provides a decision tree complete with graded supporting evidence and special clinical considerations for patients with comorbid or pre-existing conditions, Herbert Meltzer, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

Dr. Meltzer of Vanderbilt University, Nashville, Tenn., is part of a team of international experts who have spent 3 years preparing the algorithm for the International Psychopharmacology Algorithm Project. The algorithm is available at www.ipap.org

“This is meant to be an educational tool that opens the literature to people,” Dr. Meltzer said in an interview. “At each node, you can access extensive material that provides the rationale for each decision and gives more clinical information and key references.”

The algorithm begins with a triage approach to classifying patients by pre-existing condition or comorbid disorder. Clicking on those conditions—including emergent schizophrenia, substance abuse, suicidal and violent tendencies, noncompliance, and pregnancy—will link the user to information critical to the therapeutic decision-making process, Dr. Meltzer said.

The algorithm touches on nonpharmacologic treatments, although the bulk of the evidence deals with medical therapy with a focus on atypical antipsychotics. It stresses the importance of monotherapy for most patients, reserving polypharmacy for those who fail treatment with a single drug or who have very special needs.

Treatment recommendations are graded as to the level of evidence. At each decision node, the user can access links to the supporting literature. The nodes also include information about cost-effectiveness of treatments.

Since the project is meant to have international application, each treatment node also takes into account the variability of both international formularies and practice habits in different countries. And, unlike most treatment algorithms, which remain static after publication, this one will be a “living document” frequentlyupdated with the newest evidence, Dr. Meltzer said. Users will receive automatic notifications of the updates, which are expected to occur quarterly.

Kenneth O. Jobson, M.D., of the Tennessee Psychiatry and Psychopharmacology Clinic founded the International Psychopharmacology Algorithm Project (IPAP) in 1992. The project has been endorsed by the Collegium Internationale Neuro-Psychopharmalogicum. IPAP's goal is to bring together experts in psychiatry, psychopharmacology, and algorithm design to create and enhance algorithms for the systematic treatment of major Axis I psychiatric disorders. The idea for a schizophrenia algorithm was born during an IPAP meeting in China in 2001, when Dr. Jobson suggested the creation of an evidence-based online algorithm with international scope. The development team included specialists from France, Austria, Brazil, Australia, Germany, Canada, China, and Japan, as well as from the United States.

Although the algorithm is longer than most, Dr. Jobson said in an interview, it represents the clinical complexity of schizophrenia. It's also meant to be user-friendly. “We're getting some final comments now from our test group about its usability,” he said. “We're going to incorporate those suggestions into the final product.”

Although it strives for sequential logic and completeness of therapeutic options, the algorithm isn't meant to be used as “cookbook medicine,” Dr. Jobson cautioned.

The project received funding through unrestricted pharmaceutical company grants to The Dean Foundation. AstraZenca, Eli Lilly, Bristol-Myers Squibb, Janssen, Pfizer, and Novartis are also among the sources of funding for the project, Dr. Meltzer noted.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb. The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb. The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb. The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

Being almost compliant with antiretroviral therapy was associated with a sharp increase in the risk that HIV-infected patients would develop resistance to one or more of the drugs, P. Richard Harrigan, Ph.D., reported at an American Medical Association press briefing.

In a prospective cohort study of 1,191 HIV-infected patients, those who picked up 80%-90% of their prescription refills, and those who occasionally had low serum drug levels even if they picked up 95% of their medication, had more than a fourfold increase in the risk of developing drug-resistant mutations, said Dr. Harrigan, director of the British Columbia Center for Excellence in HIV Research Labs, Vancouver, B.C.

He joined other HIV experts in stressing the importance of antiretroviral therapy adherence. Inconsistent drug levels allow viral loads to increase and also put pressure on the virus to adapt. Patients who consistently take all their medication suppress viral reproduction so well that mutations are unlikely, and those with poor adherence don't have enough drugs in their system to stimulate mutations.

“Physicians should get this message to patients: Be fully, completely adherent as much as humanly possible,” he said.

In the study of patients in British Columbia, the median age was 37 years, the median CD4 cell count was 280 cells/μL, and the median viral load was 120,000 copies/mL. All patients began antiretroviral therapy during 1996-1999; 26 drug combinations were used. Viral load, drug levels, and resistance genotyping were assessed at baseline, after 1 month of therapy, and then quarterly (J. Infect. Dis. 2005;191:339-47).

After an average follow-up of 2.5 years, 25% of the cohort had developed resistance to one or more drugs. Among this group, 68.5% were resistant to lamivudine (3TC), 40% to nonnucleoside reverse transcriptase inhibitors, 33% to nucleoside reverse transcriptase inhibitors, and 23% to protease inhibitors.

The highest risk of resistance mutations occurred in those who picked up 80%-90% of their prescription refills. This group was 4.15 times more likely to develop resistance mutations than were those who picked up 0%-20% of their refills.

An 80%-90% refill rate is “pretty reasonable for some diseases, but not for this. It's not like in horseshoes, where close is good enough. Here, close is a bad thing,” Dr. Harrigan said.

Patients with one or two abnormally low drug concentrations in their first two posttherapy plasma samples were 1.45 times more likely to develop mutations than were those with normal drug levels.

But some patients who picked up more than 95% of their medication still weren't taking it consistently, and they, too, were at a high risk of developing resistance mutations. Among this group, those who had two abnormally low drug plasma levels were 4.57 times more likely to develop mutations than were those with normal drug plasma levels.

As long-term survival increases drug resistance is becoming more of a problem, Dr. Harrigan said. In recent studies, up to 50% of the U.S. population being treated for HIV infection had some degree of resistance.

The 25% resistance rate among the study patients reflects free access to antiretroviral drugs, provided by Canada's nationalized health system. Still, even with free access to medication, only 30% of the study group was fully adherent.

The complexities of antiretroviral dosing interfere significantly with adherence, said Kathleen Squires, M.D., of the University of Southern California, Los Angeles. The risk of nonadherence increases as patients move beyond initially prescribed regimens, which usually are the most manageable.

Being almost compliant with antiretroviral therapy was associated with a sharp increase in the risk that HIV-infected patients would develop resistance to one or more of the drugs, P. Richard Harrigan, Ph.D., reported at an American Medical Association press briefing.

In a prospective cohort study of 1,191 HIV-infected patients, those who picked up 80%-90% of their prescription refills, and those who occasionally had low serum drug levels even if they picked up 95% of their medication, had more than a fourfold increase in the risk of developing drug-resistant mutations, said Dr. Harrigan, director of the British Columbia Center for Excellence in HIV Research Labs, Vancouver, B.C.

He joined other HIV experts in stressing the importance of antiretroviral therapy adherence. Inconsistent drug levels allow viral loads to increase and also put pressure on the virus to adapt. Patients who consistently take all their medication suppress viral reproduction so well that mutations are unlikely, and those with poor adherence don't have enough drugs in their system to stimulate mutations.

“Physicians should get this message to patients: Be fully, completely adherent as much as humanly possible,” he said.

In the study of patients in British Columbia, the median age was 37 years, the median CD4 cell count was 280 cells/μL, and the median viral load was 120,000 copies/mL. All patients began antiretroviral therapy during 1996-1999; 26 drug combinations were used. Viral load, drug levels, and resistance genotyping were assessed at baseline, after 1 month of therapy, and then quarterly (J. Infect. Dis. 2005;191:339-47).

After an average follow-up of 2.5 years, 25% of the cohort had developed resistance to one or more drugs. Among this group, 68.5% were resistant to lamivudine (3TC), 40% to nonnucleoside reverse transcriptase inhibitors, 33% to nucleoside reverse transcriptase inhibitors, and 23% to protease inhibitors.

The highest risk of resistance mutations occurred in those who picked up 80%-90% of their prescription refills. This group was 4.15 times more likely to develop resistance mutations than were those who picked up 0%-20% of their refills.

An 80%-90% refill rate is “pretty reasonable for some diseases, but not for this. It's not like in horseshoes, where close is good enough. Here, close is a bad thing,” Dr. Harrigan said.

Patients with one or two abnormally low drug concentrations in their first two posttherapy plasma samples were 1.45 times more likely to develop mutations than were those with normal drug levels.

But some patients who picked up more than 95% of their medication still weren't taking it consistently, and they, too, were at a high risk of developing resistance mutations. Among this group, those who had two abnormally low drug plasma levels were 4.57 times more likely to develop mutations than were those with normal drug plasma levels.

As long-term survival increases drug resistance is becoming more of a problem, Dr. Harrigan said. In recent studies, up to 50% of the U.S. population being treated for HIV infection had some degree of resistance.

The 25% resistance rate among the study patients reflects free access to antiretroviral drugs, provided by Canada's nationalized health system. Still, even with free access to medication, only 30% of the study group was fully adherent.

The complexities of antiretroviral dosing interfere significantly with adherence, said Kathleen Squires, M.D., of the University of Southern California, Los Angeles. The risk of nonadherence increases as patients move beyond initially prescribed regimens, which usually are the most manageable.

Being almost compliant with antiretroviral therapy was associated with a sharp increase in the risk that HIV-infected patients would develop resistance to one or more of the drugs, P. Richard Harrigan, Ph.D., reported at an American Medical Association press briefing.

In a prospective cohort study of 1,191 HIV-infected patients, those who picked up 80%-90% of their prescription refills, and those who occasionally had low serum drug levels even if they picked up 95% of their medication, had more than a fourfold increase in the risk of developing drug-resistant mutations, said Dr. Harrigan, director of the British Columbia Center for Excellence in HIV Research Labs, Vancouver, B.C.

He joined other HIV experts in stressing the importance of antiretroviral therapy adherence. Inconsistent drug levels allow viral loads to increase and also put pressure on the virus to adapt. Patients who consistently take all their medication suppress viral reproduction so well that mutations are unlikely, and those with poor adherence don't have enough drugs in their system to stimulate mutations.

“Physicians should get this message to patients: Be fully, completely adherent as much as humanly possible,” he said.

In the study of patients in British Columbia, the median age was 37 years, the median CD4 cell count was 280 cells/μL, and the median viral load was 120,000 copies/mL. All patients began antiretroviral therapy during 1996-1999; 26 drug combinations were used. Viral load, drug levels, and resistance genotyping were assessed at baseline, after 1 month of therapy, and then quarterly (J. Infect. Dis. 2005;191:339-47).

After an average follow-up of 2.5 years, 25% of the cohort had developed resistance to one or more drugs. Among this group, 68.5% were resistant to lamivudine (3TC), 40% to nonnucleoside reverse transcriptase inhibitors, 33% to nucleoside reverse transcriptase inhibitors, and 23% to protease inhibitors.

The highest risk of resistance mutations occurred in those who picked up 80%-90% of their prescription refills. This group was 4.15 times more likely to develop resistance mutations than were those who picked up 0%-20% of their refills.

An 80%-90% refill rate is “pretty reasonable for some diseases, but not for this. It's not like in horseshoes, where close is good enough. Here, close is a bad thing,” Dr. Harrigan said.

Patients with one or two abnormally low drug concentrations in their first two posttherapy plasma samples were 1.45 times more likely to develop mutations than were those with normal drug levels.

But some patients who picked up more than 95% of their medication still weren't taking it consistently, and they, too, were at a high risk of developing resistance mutations. Among this group, those who had two abnormally low drug plasma levels were 4.57 times more likely to develop mutations than were those with normal drug plasma levels.

As long-term survival increases drug resistance is becoming more of a problem, Dr. Harrigan said. In recent studies, up to 50% of the U.S. population being treated for HIV infection had some degree of resistance.

The 25% resistance rate among the study patients reflects free access to antiretroviral drugs, provided by Canada's nationalized health system. Still, even with free access to medication, only 30% of the study group was fully adherent.

The complexities of antiretroviral dosing interfere significantly with adherence, said Kathleen Squires, M.D., of the University of Southern California, Los Angeles. The risk of nonadherence increases as patients move beyond initially prescribed regimens, which usually are the most manageable.

Metoclopramide is an effective migraine treatment for adults–as few as four patients need to be treated to enable one to achieve significant pain reduction. But other antiemetics may have more effect on pain and migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England), and his colleagues.

Their metaanalysis included five studies of metoclopramide vs. placebo (263 adults); three studies of metoclopramide vs. other antiemetics (194 patients); two studies of metoclopramide vs. non-antiemetics (60 patients); and seven studies of metoclopramide combinations vs. other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea reduction, but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to determine relative effectiveness, the investigators said (BMJ 2004;329:1369–73).

The combination studies suggested that metoclopramide might also be effective as an adjunctive treatment. Several of those studies showed that metoclopramide combinations were similarly, and more, effective for pain relief than were the comparison regimens.

“Given its nonnarcotic and antiemetic properties, metoclopramide should be considered as a primary agent in the treatment of acute migraine in emergency departments,” they said.

Metoclopramide is an effective migraine treatment for adults–as few as four patients need to be treated to enable one to achieve significant pain reduction. But other antiemetics may have more effect on pain and migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England), and his colleagues.

Their metaanalysis included five studies of metoclopramide vs. placebo (263 adults); three studies of metoclopramide vs. other antiemetics (194 patients); two studies of metoclopramide vs. non-antiemetics (60 patients); and seven studies of metoclopramide combinations vs. other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea reduction, but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to determine relative effectiveness, the investigators said (BMJ 2004;329:1369–73).

The combination studies suggested that metoclopramide might also be effective as an adjunctive treatment. Several of those studies showed that metoclopramide combinations were similarly, and more, effective for pain relief than were the comparison regimens.

“Given its nonnarcotic and antiemetic properties, metoclopramide should be considered as a primary agent in the treatment of acute migraine in emergency departments,” they said.

Metoclopramide is an effective migraine treatment for adults–as few as four patients need to be treated to enable one to achieve significant pain reduction. But other antiemetics may have more effect on pain and migraine-related nausea, according to Ian Colman, a postgraduate student at the University of Cambridge (England), and his colleagues.

Their metaanalysis included five studies of metoclopramide vs. placebo (263 adults); three studies of metoclopramide vs. other antiemetics (194 patients); two studies of metoclopramide vs. non-antiemetics (60 patients); and seven studies of metoclopramide combinations vs. other agents (211 patients).

The drug was almost three times as effective as placebo for pain and nausea reduction, but not as effective as other phenothiazine antiemetics (prochlorperazine and chlorpromazine). Metoclopramide compared favorably with ibuprofen and sumatriptan, but there was not enough evidence to determine relative effectiveness, the investigators said (BMJ 2004;329:1369–73).

The combination studies suggested that metoclopramide might also be effective as an adjunctive treatment. Several of those studies showed that metoclopramide combinations were similarly, and more, effective for pain relief than were the comparison regimens.

“Given its nonnarcotic and antiemetic properties, metoclopramide should be considered as a primary agent in the treatment of acute migraine in emergency departments,” they said.

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18-fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery. There were no significant demographic differences between the groups. The mean age of the study participants was 25 years.

Infant birth weight (median about 3,400 g) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%, as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 participants, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.) Conversely, most women with third-degree tears had both sphincters intact.

Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth degree tears. Intact external sphincters were found in 67% of women with third-degree tears and in 41% of those with fourth-degree tears, but this difference was not statistically significant.

There was a very strong correlation between sphincter disruption and development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms.

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) is intact. Courtesy Dr. Catherine M. Nichols

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18-fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery. There were no significant demographic differences between the groups. The mean age of the study participants was 25 years.

Infant birth weight (median about 3,400 g) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%, as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 participants, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.) Conversely, most women with third-degree tears had both sphincters intact.

Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth degree tears. Intact external sphincters were found in 67% of women with third-degree tears and in 41% of those with fourth-degree tears, but this difference was not statistically significant.

There was a very strong correlation between sphincter disruption and development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms.

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) is intact. Courtesy Dr. Catherine M. Nichols

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18-fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery. There were no significant demographic differences between the groups. The mean age of the study participants was 25 years.

Infant birth weight (median about 3,400 g) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%, as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 participants, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.) Conversely, most women with third-degree tears had both sphincters intact.

Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth degree tears. Intact external sphincters were found in 67% of women with third-degree tears and in 41% of those with fourth-degree tears, but this difference was not statistically significant.

There was a very strong correlation between sphincter disruption and development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms.

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) is intact. Courtesy Dr. Catherine M. Nichols

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs