Patrice Wendling

MIAMI BEACH — Several neonatal vesiculopustular disorders can be life threatening, yet difficult to diagnose, Dr. Ronald C. Hansen said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Neonatal herpes simplex is among the most severe perinatal infections. The case-fatality rate is up to 85% in untreated neonates. As many as two-thirds of the survivors will have some, often neurologic, permanent disability. Infection with herpes simplex virus (HSV) is usually transmitted during labor and delivery, but in only about half of cases will there be a well-documented history of maternal exposure, said Dr. Hansen, professor of dermatology and pediatrics at Phoenix Children's Hospital.

Neonatal herpes can be a tough diagnosis because there are three different clinical patterns of infection: It can be mucocutaneous, can involve the central nervous system, or can be disseminated and involve multiple organs.

Skin lesions can be seen in all three patterns. Vesicles may be single or disseminated, lack an erythematous base, or be large, crusted coalescent erosions, not necessarily where the skin touched the cervix.

Biopsy can be helpful for confirming diagnosis, but it is no longer the preferred method. Rapid methods such as polymerase chain reaction assays, direct fluorescent antibody tests, and viral cultures are now available. Antiviral therapy with acyclovir is useful, but prognosis can be poor even if the child looks healthy and its cerebral spinal fluid is negative, he said.

Only 5% of all neonatal HSV cases are caused by in utero transmission, but that possibility should still be considered. Many of the infants don't appear sick despite multiorgan involvement. Infected infants are often premature and typically present with evidence of chronic infection, atrophy, and scars suggestive of epidermolysis bullosa or aplasia cutis congenita.

A high index of suspicion and the above studies for HSV are needed to confirm the diagnosis. If biopsies are performed, one should biopsy the skin because cultures of the nose, throat, rectum, and spinal fluid can be negative, Dr. Hansen said.

Bullous mastocytosis also may present with vesicles in the newborn period, and is readily confused with HSV or epidermolysis bullosa. Bullous mastocytosis is a rare form of mast-cell disease that can be distinguished clinically by its characteristic layering of blood in flat, intact blisters and red, wrinkly skin. A biopsy anywhere on the body would be positive because of the diffuse infiltration of the skin by mast cells, Dr. Hansen said.

Fetal varicella syndrome is another easy-to-miss diagnosis. Characteristic features include cicatricial lesions with a segmental or dermatomal distribution, and atrophic plaques that can resemble pan-sclerotic morphea. Other features can include neurologic and eye abnormalities, gastrointestinal and genitourinary malformations, and hypoplasia of one limb.

The risk of fetal varicella syndrome in children exposed to chickenpox in utero in the first trimester was estimated at 9%, although newer studies put it at only 1%–2%.

One should also consider neonatal varicella, which can be fatal. The disease is said to be more likely and more severe if the mother develops varicella 5 days before or 2 days after delivery.

This infant with intrauterine herpes simplex virus has deep atrophic and ulcerative lesions suggesting epidermolysis bullosa or aplasia cutis congenita. ©Elsevier, Inc./Pediatric Dermatology, 3rd Edition, p. 248, 2003

MIAMI BEACH — Several neonatal vesiculopustular disorders can be life threatening, yet difficult to diagnose, Dr. Ronald C. Hansen said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Neonatal herpes simplex is among the most severe perinatal infections. The case-fatality rate is up to 85% in untreated neonates. As many as two-thirds of the survivors will have some, often neurologic, permanent disability. Infection with herpes simplex virus (HSV) is usually transmitted during labor and delivery, but in only about half of cases will there be a well-documented history of maternal exposure, said Dr. Hansen, professor of dermatology and pediatrics at Phoenix Children's Hospital.

Neonatal herpes can be a tough diagnosis because there are three different clinical patterns of infection: It can be mucocutaneous, can involve the central nervous system, or can be disseminated and involve multiple organs.

Skin lesions can be seen in all three patterns. Vesicles may be single or disseminated, lack an erythematous base, or be large, crusted coalescent erosions, not necessarily where the skin touched the cervix.

Biopsy can be helpful for confirming diagnosis, but it is no longer the preferred method. Rapid methods such as polymerase chain reaction assays, direct fluorescent antibody tests, and viral cultures are now available. Antiviral therapy with acyclovir is useful, but prognosis can be poor even if the child looks healthy and its cerebral spinal fluid is negative, he said.

Only 5% of all neonatal HSV cases are caused by in utero transmission, but that possibility should still be considered. Many of the infants don't appear sick despite multiorgan involvement. Infected infants are often premature and typically present with evidence of chronic infection, atrophy, and scars suggestive of epidermolysis bullosa or aplasia cutis congenita.

A high index of suspicion and the above studies for HSV are needed to confirm the diagnosis. If biopsies are performed, one should biopsy the skin because cultures of the nose, throat, rectum, and spinal fluid can be negative, Dr. Hansen said.

Bullous mastocytosis also may present with vesicles in the newborn period, and is readily confused with HSV or epidermolysis bullosa. Bullous mastocytosis is a rare form of mast-cell disease that can be distinguished clinically by its characteristic layering of blood in flat, intact blisters and red, wrinkly skin. A biopsy anywhere on the body would be positive because of the diffuse infiltration of the skin by mast cells, Dr. Hansen said.

Fetal varicella syndrome is another easy-to-miss diagnosis. Characteristic features include cicatricial lesions with a segmental or dermatomal distribution, and atrophic plaques that can resemble pan-sclerotic morphea. Other features can include neurologic and eye abnormalities, gastrointestinal and genitourinary malformations, and hypoplasia of one limb.

The risk of fetal varicella syndrome in children exposed to chickenpox in utero in the first trimester was estimated at 9%, although newer studies put it at only 1%–2%.

One should also consider neonatal varicella, which can be fatal. The disease is said to be more likely and more severe if the mother develops varicella 5 days before or 2 days after delivery.

This infant with intrauterine herpes simplex virus has deep atrophic and ulcerative lesions suggesting epidermolysis bullosa or aplasia cutis congenita. ©Elsevier, Inc./Pediatric Dermatology, 3rd Edition, p. 248, 2003

MIAMI BEACH — Several neonatal vesiculopustular disorders can be life threatening, yet difficult to diagnose, Dr. Ronald C. Hansen said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Neonatal herpes simplex is among the most severe perinatal infections. The case-fatality rate is up to 85% in untreated neonates. As many as two-thirds of the survivors will have some, often neurologic, permanent disability. Infection with herpes simplex virus (HSV) is usually transmitted during labor and delivery, but in only about half of cases will there be a well-documented history of maternal exposure, said Dr. Hansen, professor of dermatology and pediatrics at Phoenix Children's Hospital.

Neonatal herpes can be a tough diagnosis because there are three different clinical patterns of infection: It can be mucocutaneous, can involve the central nervous system, or can be disseminated and involve multiple organs.

Skin lesions can be seen in all three patterns. Vesicles may be single or disseminated, lack an erythematous base, or be large, crusted coalescent erosions, not necessarily where the skin touched the cervix.

Biopsy can be helpful for confirming diagnosis, but it is no longer the preferred method. Rapid methods such as polymerase chain reaction assays, direct fluorescent antibody tests, and viral cultures are now available. Antiviral therapy with acyclovir is useful, but prognosis can be poor even if the child looks healthy and its cerebral spinal fluid is negative, he said.

Only 5% of all neonatal HSV cases are caused by in utero transmission, but that possibility should still be considered. Many of the infants don't appear sick despite multiorgan involvement. Infected infants are often premature and typically present with evidence of chronic infection, atrophy, and scars suggestive of epidermolysis bullosa or aplasia cutis congenita.

A high index of suspicion and the above studies for HSV are needed to confirm the diagnosis. If biopsies are performed, one should biopsy the skin because cultures of the nose, throat, rectum, and spinal fluid can be negative, Dr. Hansen said.

Bullous mastocytosis also may present with vesicles in the newborn period, and is readily confused with HSV or epidermolysis bullosa. Bullous mastocytosis is a rare form of mast-cell disease that can be distinguished clinically by its characteristic layering of blood in flat, intact blisters and red, wrinkly skin. A biopsy anywhere on the body would be positive because of the diffuse infiltration of the skin by mast cells, Dr. Hansen said.

Fetal varicella syndrome is another easy-to-miss diagnosis. Characteristic features include cicatricial lesions with a segmental or dermatomal distribution, and atrophic plaques that can resemble pan-sclerotic morphea. Other features can include neurologic and eye abnormalities, gastrointestinal and genitourinary malformations, and hypoplasia of one limb.

The risk of fetal varicella syndrome in children exposed to chickenpox in utero in the first trimester was estimated at 9%, although newer studies put it at only 1%–2%.

One should also consider neonatal varicella, which can be fatal. The disease is said to be more likely and more severe if the mother develops varicella 5 days before or 2 days after delivery.

This infant with intrauterine herpes simplex virus has deep atrophic and ulcerative lesions suggesting epidermolysis bullosa or aplasia cutis congenita. ©Elsevier, Inc./Pediatric Dermatology, 3rd Edition, p. 248, 2003

NEW YORK – Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity. But symptoms differ among younger patients with the disorder. “It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said. A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with BD onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85). Compared with the adolescent-onset BD, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with BD onset after age 30. The patients with earlier-onset BD were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%); and had significantly higher rates of ADHD or ODD or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset BD appears to be more chronic and treatment refractory than does adult-onset BD.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identify significant differences by age of onset in functional outcome after a bipolar episode. Among 89 patients with BD onset at 15–29 years, 15% had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with BD onset after age 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said. “Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified.”

NEW YORK – Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity. But symptoms differ among younger patients with the disorder. “It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said. A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with BD onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85). Compared with the adolescent-onset BD, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with BD onset after age 30. The patients with earlier-onset BD were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%); and had significantly higher rates of ADHD or ODD or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset BD appears to be more chronic and treatment refractory than does adult-onset BD.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identify significant differences by age of onset in functional outcome after a bipolar episode. Among 89 patients with BD onset at 15–29 years, 15% had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with BD onset after age 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said. “Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified.”

NEW YORK – Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity. But symptoms differ among younger patients with the disorder. “It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said. A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with BD onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85). Compared with the adolescent-onset BD, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with BD onset after age 30. The patients with earlier-onset BD were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%); and had significantly higher rates of ADHD or ODD or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset BD appears to be more chronic and treatment refractory than does adult-onset BD.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identify significant differences by age of onset in functional outcome after a bipolar episode. Among 89 patients with BD onset at 15–29 years, 15% had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with BD onset after age 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said. “Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified.”

MILWAUKEE — There are a number of drugs in the developmental pipeline that likely will offer benefits to different categories of patients with irritable bowel syndrome, Dr. William D. Chey reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

New drugs would be welcome, given the scarcity of approved agents for irritable bowel syndrome (IBS), particularly since tegaserod maleate (Zelnorm) was withdrawn from the market on March 30 because of a possible increased risk of serious cardiovascular adverse events. But Dr. Chey cautioned that these new drugs won't be a panacea.

“The one thing that's fair to say is that until we get some biomarkers that stratify patients on the basis of pathophysiology, it's unlikely that you're going to see anything better than what I've shown you repeatedly … and that is these statistically significant benefits that are not overwhelmingly impressive,” he said.

Drugs for Constipation-Predominant IBS

Renzapride, a mixed 5-hydroxytryptamine (HT) type 4 receptor agonist and 5-HT type 3 receptor antagonist, is currently in phase III clinical trials in the United States for patients with constipation-predominant IBS. In a small phase II trial, renzapride was shown to improve stool consistency and ease of stool passage (Clin. Gastroenterol. Hepatol. 2004;2:895–904). But the study was underpowered and did not reach a secondary outcome of satisfactory relief, said Dr. Chey, associate professor of medicine and director of the GI Physiology Laboratory, division of gastroenterology, University of Michigan Medical Center, Ann Arbor.

Lubiprostone, a chloride channel activator, has just recently been assessed in two phase III trials. Preliminary data suggest that 8 mcg of lubiprostone b.i.d. provided a greater overall response among patients with IBS with constipation than did placebo (17.9% responders vs. 10.1%), Dr. Chey said.

MD-1100 or linaclotide, a potent guanylate cyclase-C agonist that acts luminally to increase the production of cyclic guanosine monophosphate in human colon cells, is heading into phase II trials for both IBS with constipation and chronic constipation. A recent 7-day, multidose phase I study in 48 healthy volunteers reported significant changes in stool consistency, ease of stool passage, stool frequency, and stool weight with MD-1100 (Gastroenterology 2006;130[suppl. 2]:A26).

Asimadoline, a kappa-opioid agonist, was originally developed to treat peripheral pain such as arthritis, and is now in clinical development for the treatment of IBS and postoperative ileus. Early results show decreased sensitivity to balloon distention in a barostat study.

Drugs for Diarrhea-Predominant IBS

Phase II trials were recently completed in the United States for crofelemer, a derivative obtained from the sap of the South American Croton lechleri tree. Data from a 12-week dose-ranging study in 246 patients with diarrhea-predominant IBS show significant improvement in pain and a trend toward improvement in stool frequency, said Dr. Chey at the meeting, cosponsored by the University of Wisconsin.

R-verapamil, a calcium channel antagonist, is expected to go into phase II clinical study in the United States sometime in 2007. In one small unpublished eastern European study, R-verapamil was shown to be of benefit for patients with IBS and diarrhea, Dr. Chey said.

There is also very elegant and interesting basic science work and supportive preliminary clinical data suggesting that corticotropin-releasing factor antagonists might offer benefits to patients with IBS and diarrhea. Also being studied are α-agonists, including the compound AGN 203818, in later-stage development, and clonidine as well as the benzodiazepine derivatives, tofisopam and dextofisopam, Dr. Chey said.

MILWAUKEE — There are a number of drugs in the developmental pipeline that likely will offer benefits to different categories of patients with irritable bowel syndrome, Dr. William D. Chey reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

New drugs would be welcome, given the scarcity of approved agents for irritable bowel syndrome (IBS), particularly since tegaserod maleate (Zelnorm) was withdrawn from the market on March 30 because of a possible increased risk of serious cardiovascular adverse events. But Dr. Chey cautioned that these new drugs won't be a panacea.

“The one thing that's fair to say is that until we get some biomarkers that stratify patients on the basis of pathophysiology, it's unlikely that you're going to see anything better than what I've shown you repeatedly … and that is these statistically significant benefits that are not overwhelmingly impressive,” he said.

Drugs for Constipation-Predominant IBS

Renzapride, a mixed 5-hydroxytryptamine (HT) type 4 receptor agonist and 5-HT type 3 receptor antagonist, is currently in phase III clinical trials in the United States for patients with constipation-predominant IBS. In a small phase II trial, renzapride was shown to improve stool consistency and ease of stool passage (Clin. Gastroenterol. Hepatol. 2004;2:895–904). But the study was underpowered and did not reach a secondary outcome of satisfactory relief, said Dr. Chey, associate professor of medicine and director of the GI Physiology Laboratory, division of gastroenterology, University of Michigan Medical Center, Ann Arbor.

Lubiprostone, a chloride channel activator, has just recently been assessed in two phase III trials. Preliminary data suggest that 8 mcg of lubiprostone b.i.d. provided a greater overall response among patients with IBS with constipation than did placebo (17.9% responders vs. 10.1%), Dr. Chey said.

MD-1100 or linaclotide, a potent guanylate cyclase-C agonist that acts luminally to increase the production of cyclic guanosine monophosphate in human colon cells, is heading into phase II trials for both IBS with constipation and chronic constipation. A recent 7-day, multidose phase I study in 48 healthy volunteers reported significant changes in stool consistency, ease of stool passage, stool frequency, and stool weight with MD-1100 (Gastroenterology 2006;130[suppl. 2]:A26).

Asimadoline, a kappa-opioid agonist, was originally developed to treat peripheral pain such as arthritis, and is now in clinical development for the treatment of IBS and postoperative ileus. Early results show decreased sensitivity to balloon distention in a barostat study.

Drugs for Diarrhea-Predominant IBS

Phase II trials were recently completed in the United States for crofelemer, a derivative obtained from the sap of the South American Croton lechleri tree. Data from a 12-week dose-ranging study in 246 patients with diarrhea-predominant IBS show significant improvement in pain and a trend toward improvement in stool frequency, said Dr. Chey at the meeting, cosponsored by the University of Wisconsin.

R-verapamil, a calcium channel antagonist, is expected to go into phase II clinical study in the United States sometime in 2007. In one small unpublished eastern European study, R-verapamil was shown to be of benefit for patients with IBS and diarrhea, Dr. Chey said.

There is also very elegant and interesting basic science work and supportive preliminary clinical data suggesting that corticotropin-releasing factor antagonists might offer benefits to patients with IBS and diarrhea. Also being studied are α-agonists, including the compound AGN 203818, in later-stage development, and clonidine as well as the benzodiazepine derivatives, tofisopam and dextofisopam, Dr. Chey said.

MILWAUKEE — There are a number of drugs in the developmental pipeline that likely will offer benefits to different categories of patients with irritable bowel syndrome, Dr. William D. Chey reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

New drugs would be welcome, given the scarcity of approved agents for irritable bowel syndrome (IBS), particularly since tegaserod maleate (Zelnorm) was withdrawn from the market on March 30 because of a possible increased risk of serious cardiovascular adverse events. But Dr. Chey cautioned that these new drugs won't be a panacea.

“The one thing that's fair to say is that until we get some biomarkers that stratify patients on the basis of pathophysiology, it's unlikely that you're going to see anything better than what I've shown you repeatedly … and that is these statistically significant benefits that are not overwhelmingly impressive,” he said.

Drugs for Constipation-Predominant IBS

Renzapride, a mixed 5-hydroxytryptamine (HT) type 4 receptor agonist and 5-HT type 3 receptor antagonist, is currently in phase III clinical trials in the United States for patients with constipation-predominant IBS. In a small phase II trial, renzapride was shown to improve stool consistency and ease of stool passage (Clin. Gastroenterol. Hepatol. 2004;2:895–904). But the study was underpowered and did not reach a secondary outcome of satisfactory relief, said Dr. Chey, associate professor of medicine and director of the GI Physiology Laboratory, division of gastroenterology, University of Michigan Medical Center, Ann Arbor.

Lubiprostone, a chloride channel activator, has just recently been assessed in two phase III trials. Preliminary data suggest that 8 mcg of lubiprostone b.i.d. provided a greater overall response among patients with IBS with constipation than did placebo (17.9% responders vs. 10.1%), Dr. Chey said.

MD-1100 or linaclotide, a potent guanylate cyclase-C agonist that acts luminally to increase the production of cyclic guanosine monophosphate in human colon cells, is heading into phase II trials for both IBS with constipation and chronic constipation. A recent 7-day, multidose phase I study in 48 healthy volunteers reported significant changes in stool consistency, ease of stool passage, stool frequency, and stool weight with MD-1100 (Gastroenterology 2006;130[suppl. 2]:A26).

Asimadoline, a kappa-opioid agonist, was originally developed to treat peripheral pain such as arthritis, and is now in clinical development for the treatment of IBS and postoperative ileus. Early results show decreased sensitivity to balloon distention in a barostat study.

Drugs for Diarrhea-Predominant IBS

Phase II trials were recently completed in the United States for crofelemer, a derivative obtained from the sap of the South American Croton lechleri tree. Data from a 12-week dose-ranging study in 246 patients with diarrhea-predominant IBS show significant improvement in pain and a trend toward improvement in stool frequency, said Dr. Chey at the meeting, cosponsored by the University of Wisconsin.

R-verapamil, a calcium channel antagonist, is expected to go into phase II clinical study in the United States sometime in 2007. In one small unpublished eastern European study, R-verapamil was shown to be of benefit for patients with IBS and diarrhea, Dr. Chey said.

There is also very elegant and interesting basic science work and supportive preliminary clinical data suggesting that corticotropin-releasing factor antagonists might offer benefits to patients with IBS and diarrhea. Also being studied are α-agonists, including the compound AGN 203818, in later-stage development, and clonidine as well as the benzodiazepine derivatives, tofisopam and dextofisopam, Dr. Chey said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 (63%) of 113 cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest-hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 (63%) of 113 cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest-hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 (63%) of 113 cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest-hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.

TORONTO — An investigational combined infant Haemophilus influenzae type b and meningococcal conjugate vaccine provided immunity without significant side effects in a phase II single-blind study of 606 infants.

GlaxoSmithKline is developing a conjugate vaccine, for use beginning at age 2 months, containing Haemophilus influenzae type b (Hib) polysaccharide and Neisseria meningitidis polysaccharides C and Y (MenCY) conjugated to tetanus toxoid.

The investigational vaccine could allow for the inclusion of two meningococcal antigens in the current U.S. infant immunization program without additional injections, and potentially protect against invasive disease in the first year of life, Dr. Jacqueline Miller and colleagues reported in a poster at the annual meeting of the Pediatric Academic Societies.

An infant meningococcal vaccine is currently not available in the United States, even though the highest rate of meningococcal disease is in infants.

“It's the next big bacterial pathogen in infants to target for vaccination,” Dr. Miller, director of clinical research and medical affairs at GlaxoSmithKline in King of Prussia, Penn., said in an interview. “Neisseria meningitidis is a pretty invasive and aggressive organism. Infections result in a large public health response and a lot of anxiety in the community.

“I think the untold story is that the highest incidence is actually [in] the youngest kids. But because babies aren't in school, their infections don't receive much media attention. But it's serious in infants and more difficult to recognize in this population because their symptomatology is similar to other, less serious infections.”

The investigators randomized healthy infants to a three-dose priming series of the Hib-MenCY study vaccine coadministered at 2, 4, and 6 months of age with Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio) and Prevnar (pneumococcal 7-valent conjugate) vaccines; or to ActHIB (Hib conjugate with tetanus toxoid) vaccine coadministered with Pediarix and Prevnar. A third nonrandomized group of 150 3- to 5-year-old children received a single dose of Menomune vaccine, which contains N. meningitidis serogroups A, C, W-135, and Y.

The mean age of the children was 64 days in the study vaccine and Hib control groups, and 50 months in the Menomune control group.

At 1 month after the last dose, a statistically higher proportion of the 287 infants in the study vaccine group had anti-polyribosylribitol phosphate antibody concentrations of at least 1.0 mcg/mL, compared with the 319 infants in the Hib control group (94% vs. 86%), the authors reported.

Overall, 98% of the infants in the Hib-MenCY group had a consolidated serum bactericidal antibody response to N. meningitidis serogroup C, compared with 79% of the older children vaccinated with a single dose of Menomune. The difference in responses was statistically significant. “However, the data should be interpreted cautiously given the difference in age of the two treatment groups,” the authors wrote.

There was no statistical difference in responses to serogroup Y between the Hib-MenCY study vaccine group and the Menomune group. Serogroups C and Y account for about 94% of all U.S. infections due to serogroups A, C, W-135, and Y.

There was no evidence of interference in the immune responses to the coadministered vaccines in those vaccinated with Hib-MenCY, compared with the Hib control group. A large phase III study is underway in 8,800 infants that will evaluate coadministration of Hib-MenCY with other vaccines and determine how long the vaccine coverage lasts, Dr. Miller said.

Reports of any grade 3 solicited or unsolicited local and systemic adverse events were significantly lower in the Hib-MenCY group, compared with the Hib control group. Dr. Miller called this finding surprising, and had no explanation for why it occurred.

TORONTO — An investigational combined infant Haemophilus influenzae type b and meningococcal conjugate vaccine provided immunity without significant side effects in a phase II single-blind study of 606 infants.

GlaxoSmithKline is developing a conjugate vaccine, for use beginning at age 2 months, containing Haemophilus influenzae type b (Hib) polysaccharide and Neisseria meningitidis polysaccharides C and Y (MenCY) conjugated to tetanus toxoid.

The investigational vaccine could allow for the inclusion of two meningococcal antigens in the current U.S. infant immunization program without additional injections, and potentially protect against invasive disease in the first year of life, Dr. Jacqueline Miller and colleagues reported in a poster at the annual meeting of the Pediatric Academic Societies.

An infant meningococcal vaccine is currently not available in the United States, even though the highest rate of meningococcal disease is in infants.

“It's the next big bacterial pathogen in infants to target for vaccination,” Dr. Miller, director of clinical research and medical affairs at GlaxoSmithKline in King of Prussia, Penn., said in an interview. “Neisseria meningitidis is a pretty invasive and aggressive organism. Infections result in a large public health response and a lot of anxiety in the community.

“I think the untold story is that the highest incidence is actually [in] the youngest kids. But because babies aren't in school, their infections don't receive much media attention. But it's serious in infants and more difficult to recognize in this population because their symptomatology is similar to other, less serious infections.”

The investigators randomized healthy infants to a three-dose priming series of the Hib-MenCY study vaccine coadministered at 2, 4, and 6 months of age with Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio) and Prevnar (pneumococcal 7-valent conjugate) vaccines; or to ActHIB (Hib conjugate with tetanus toxoid) vaccine coadministered with Pediarix and Prevnar. A third nonrandomized group of 150 3- to 5-year-old children received a single dose of Menomune vaccine, which contains N. meningitidis serogroups A, C, W-135, and Y.

The mean age of the children was 64 days in the study vaccine and Hib control groups, and 50 months in the Menomune control group.

At 1 month after the last dose, a statistically higher proportion of the 287 infants in the study vaccine group had anti-polyribosylribitol phosphate antibody concentrations of at least 1.0 mcg/mL, compared with the 319 infants in the Hib control group (94% vs. 86%), the authors reported.

Overall, 98% of the infants in the Hib-MenCY group had a consolidated serum bactericidal antibody response to N. meningitidis serogroup C, compared with 79% of the older children vaccinated with a single dose of Menomune. The difference in responses was statistically significant. “However, the data should be interpreted cautiously given the difference in age of the two treatment groups,” the authors wrote.

There was no statistical difference in responses to serogroup Y between the Hib-MenCY study vaccine group and the Menomune group. Serogroups C and Y account for about 94% of all U.S. infections due to serogroups A, C, W-135, and Y.

There was no evidence of interference in the immune responses to the coadministered vaccines in those vaccinated with Hib-MenCY, compared with the Hib control group. A large phase III study is underway in 8,800 infants that will evaluate coadministration of Hib-MenCY with other vaccines and determine how long the vaccine coverage lasts, Dr. Miller said.

Reports of any grade 3 solicited or unsolicited local and systemic adverse events were significantly lower in the Hib-MenCY group, compared with the Hib control group. Dr. Miller called this finding surprising, and had no explanation for why it occurred.

TORONTO — An investigational combined infant Haemophilus influenzae type b and meningococcal conjugate vaccine provided immunity without significant side effects in a phase II single-blind study of 606 infants.

GlaxoSmithKline is developing a conjugate vaccine, for use beginning at age 2 months, containing Haemophilus influenzae type b (Hib) polysaccharide and Neisseria meningitidis polysaccharides C and Y (MenCY) conjugated to tetanus toxoid.

The investigational vaccine could allow for the inclusion of two meningococcal antigens in the current U.S. infant immunization program without additional injections, and potentially protect against invasive disease in the first year of life, Dr. Jacqueline Miller and colleagues reported in a poster at the annual meeting of the Pediatric Academic Societies.

An infant meningococcal vaccine is currently not available in the United States, even though the highest rate of meningococcal disease is in infants.

“It's the next big bacterial pathogen in infants to target for vaccination,” Dr. Miller, director of clinical research and medical affairs at GlaxoSmithKline in King of Prussia, Penn., said in an interview. “Neisseria meningitidis is a pretty invasive and aggressive organism. Infections result in a large public health response and a lot of anxiety in the community.

“I think the untold story is that the highest incidence is actually [in] the youngest kids. But because babies aren't in school, their infections don't receive much media attention. But it's serious in infants and more difficult to recognize in this population because their symptomatology is similar to other, less serious infections.”

The investigators randomized healthy infants to a three-dose priming series of the Hib-MenCY study vaccine coadministered at 2, 4, and 6 months of age with Pediarix (diphtheria, tetanus, pertussis, hepatitis B, and polio) and Prevnar (pneumococcal 7-valent conjugate) vaccines; or to ActHIB (Hib conjugate with tetanus toxoid) vaccine coadministered with Pediarix and Prevnar. A third nonrandomized group of 150 3- to 5-year-old children received a single dose of Menomune vaccine, which contains N. meningitidis serogroups A, C, W-135, and Y.

The mean age of the children was 64 days in the study vaccine and Hib control groups, and 50 months in the Menomune control group.

At 1 month after the last dose, a statistically higher proportion of the 287 infants in the study vaccine group had anti-polyribosylribitol phosphate antibody concentrations of at least 1.0 mcg/mL, compared with the 319 infants in the Hib control group (94% vs. 86%), the authors reported.

Overall, 98% of the infants in the Hib-MenCY group had a consolidated serum bactericidal antibody response to N. meningitidis serogroup C, compared with 79% of the older children vaccinated with a single dose of Menomune. The difference in responses was statistically significant. “However, the data should be interpreted cautiously given the difference in age of the two treatment groups,” the authors wrote.

There was no statistical difference in responses to serogroup Y between the Hib-MenCY study vaccine group and the Menomune group. Serogroups C and Y account for about 94% of all U.S. infections due to serogroups A, C, W-135, and Y.

There was no evidence of interference in the immune responses to the coadministered vaccines in those vaccinated with Hib-MenCY, compared with the Hib control group. A large phase III study is underway in 8,800 infants that will evaluate coadministration of Hib-MenCY with other vaccines and determine how long the vaccine coverage lasts, Dr. Miller said.

Reports of any grade 3 solicited or unsolicited local and systemic adverse events were significantly lower in the Hib-MenCY group, compared with the Hib control group. Dr. Miller called this finding surprising, and had no explanation for why it occurred.

CHICAGO — Telmisartan provides greater reduction in proteinuria than losartan does after 1 year of treatment in patients with hypertension and diabetic nephropathy, Dr. George Bakris said at the annual meeting of the American Society of Hypertension.

This difference can't be attributed to differences in blood pressure control, because blood pressure reductions were comparable in patients taking either angiotension II receptor blocker (ARB), Dr. Bakris, lead investigator of the AMADEO study, said during a press briefing.

After stopping the drugs for 2 months, as per protocol, about twice as many patients on telmisartan were reported to have experienced a slightly greater antiproteinuric effect, compared with those on losartan. This is important to both the Food and Drug Administration and clinicians, because it suggests that telmisartan has done something independent of controlling blood pressure to change the natural history or biology of the disease, said Dr. Bakris.

“The differences between these ARBs in terms of receptor binding, lipophilicity, and duration of action may be responsible for the differences in the effects that you see,” said Dr. Bakris, professor of medicine and director of the hypertension unit at the University of Chicago. “These data suggest that at similar levels of blood pressure control, the longer-acting, higher-binding telmisartan may confer relatively greater protection against the development of ESRD [end-stage renal disease], though that hypothesis must be tested prospectively.”

Dr. Bakris and associates randomized 860 patients with type 2 diabetes mellitus, hypertension (defined as blood pressure greater than 130/80 mm Hg), and overt nephropathy to either telmisartan 40 mg or losartan 50 mg for 2 weeks, and then titrated to 80 mg and 100 mg, respectively. If blood pressure was not controlled, concomitant antihypertensives were allowed, except ARBs, angiotensin-converting enzyme inhibitors, and direct vasodilators.

At admission, the average systolic/diastolic blood pressure was 143/80 mm Hg in both groups; mean urinary protein:creatinine ratio was 1,971 mg/gCr in the telmisartan group vs. 2,010.5 mg/gCr in the losartan group; and the mean serum creatinine was 1.54 mg/dL in the telmisartan group vs. 1.55 mg/dL in the losartan group. In all, 827 patients were available for analysis.

After 1 year of treatment, the mean change in morning spot urinary protein:creatinine—the study's primary end point—was 0.71 for telmisartan and 0.80 for losartan. This translated to a 29% reduction from baseline for telmisartan and a 20% reduction for losartan. Systolic and diastolic BP reductions were not significant between groups (−4.8/−3.2 mm Hg vs. −2.7/–2.9 mm Hg, respectively).

Among secondary end points, telmisartan produced superior reductions in urinary albumin:creatinine and prolonged the time to first cardiovascular event. There were no significant differences between the drugs in urinary sodium:creatinine, glomerular filtration rate, serum aldosterone, or high-sensitivity C-reactive protein. Adverse events were not different between groups.

Dr. Bakris disclosed that he is a consultant and speaker for Boehringer Ingelheim, which sponsored the study, and he has received research support from the firm.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Telmisartan provides greater reduction in proteinuria than losartan does after 1 year of treatment in patients with hypertension and diabetic nephropathy, Dr. George Bakris said at the annual meeting of the American Society of Hypertension.

This difference can't be attributed to differences in blood pressure control, because blood pressure reductions were comparable in patients taking either angiotension II receptor blocker (ARB), Dr. Bakris, lead investigator of the AMADEO study, said during a press briefing.

After stopping the drugs for 2 months, as per protocol, about twice as many patients on telmisartan were reported to have experienced a slightly greater antiproteinuric effect, compared with those on losartan. This is important to both the Food and Drug Administration and clinicians, because it suggests that telmisartan has done something independent of controlling blood pressure to change the natural history or biology of the disease, said Dr. Bakris.

“The differences between these ARBs in terms of receptor binding, lipophilicity, and duration of action may be responsible for the differences in the effects that you see,” said Dr. Bakris, professor of medicine and director of the hypertension unit at the University of Chicago. “These data suggest that at similar levels of blood pressure control, the longer-acting, higher-binding telmisartan may confer relatively greater protection against the development of ESRD [end-stage renal disease], though that hypothesis must be tested prospectively.”

Dr. Bakris and associates randomized 860 patients with type 2 diabetes mellitus, hypertension (defined as blood pressure greater than 130/80 mm Hg), and overt nephropathy to either telmisartan 40 mg or losartan 50 mg for 2 weeks, and then titrated to 80 mg and 100 mg, respectively. If blood pressure was not controlled, concomitant antihypertensives were allowed, except ARBs, angiotensin-converting enzyme inhibitors, and direct vasodilators.

At admission, the average systolic/diastolic blood pressure was 143/80 mm Hg in both groups; mean urinary protein:creatinine ratio was 1,971 mg/gCr in the telmisartan group vs. 2,010.5 mg/gCr in the losartan group; and the mean serum creatinine was 1.54 mg/dL in the telmisartan group vs. 1.55 mg/dL in the losartan group. In all, 827 patients were available for analysis.

After 1 year of treatment, the mean change in morning spot urinary protein:creatinine—the study's primary end point—was 0.71 for telmisartan and 0.80 for losartan. This translated to a 29% reduction from baseline for telmisartan and a 20% reduction for losartan. Systolic and diastolic BP reductions were not significant between groups (−4.8/−3.2 mm Hg vs. −2.7/–2.9 mm Hg, respectively).

Among secondary end points, telmisartan produced superior reductions in urinary albumin:creatinine and prolonged the time to first cardiovascular event. There were no significant differences between the drugs in urinary sodium:creatinine, glomerular filtration rate, serum aldosterone, or high-sensitivity C-reactive protein. Adverse events were not different between groups.

Dr. Bakris disclosed that he is a consultant and speaker for Boehringer Ingelheim, which sponsored the study, and he has received research support from the firm.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Telmisartan provides greater reduction in proteinuria than losartan does after 1 year of treatment in patients with hypertension and diabetic nephropathy, Dr. George Bakris said at the annual meeting of the American Society of Hypertension.

This difference can't be attributed to differences in blood pressure control, because blood pressure reductions were comparable in patients taking either angiotension II receptor blocker (ARB), Dr. Bakris, lead investigator of the AMADEO study, said during a press briefing.

After stopping the drugs for 2 months, as per protocol, about twice as many patients on telmisartan were reported to have experienced a slightly greater antiproteinuric effect, compared with those on losartan. This is important to both the Food and Drug Administration and clinicians, because it suggests that telmisartan has done something independent of controlling blood pressure to change the natural history or biology of the disease, said Dr. Bakris.

“The differences between these ARBs in terms of receptor binding, lipophilicity, and duration of action may be responsible for the differences in the effects that you see,” said Dr. Bakris, professor of medicine and director of the hypertension unit at the University of Chicago. “These data suggest that at similar levels of blood pressure control, the longer-acting, higher-binding telmisartan may confer relatively greater protection against the development of ESRD [end-stage renal disease], though that hypothesis must be tested prospectively.”

Dr. Bakris and associates randomized 860 patients with type 2 diabetes mellitus, hypertension (defined as blood pressure greater than 130/80 mm Hg), and overt nephropathy to either telmisartan 40 mg or losartan 50 mg for 2 weeks, and then titrated to 80 mg and 100 mg, respectively. If blood pressure was not controlled, concomitant antihypertensives were allowed, except ARBs, angiotensin-converting enzyme inhibitors, and direct vasodilators.

At admission, the average systolic/diastolic blood pressure was 143/80 mm Hg in both groups; mean urinary protein:creatinine ratio was 1,971 mg/gCr in the telmisartan group vs. 2,010.5 mg/gCr in the losartan group; and the mean serum creatinine was 1.54 mg/dL in the telmisartan group vs. 1.55 mg/dL in the losartan group. In all, 827 patients were available for analysis.

After 1 year of treatment, the mean change in morning spot urinary protein:creatinine—the study's primary end point—was 0.71 for telmisartan and 0.80 for losartan. This translated to a 29% reduction from baseline for telmisartan and a 20% reduction for losartan. Systolic and diastolic BP reductions were not significant between groups (−4.8/−3.2 mm Hg vs. −2.7/–2.9 mm Hg, respectively).

Among secondary end points, telmisartan produced superior reductions in urinary albumin:creatinine and prolonged the time to first cardiovascular event. There were no significant differences between the drugs in urinary sodium:creatinine, glomerular filtration rate, serum aldosterone, or high-sensitivity C-reactive protein. Adverse events were not different between groups.

Dr. Bakris disclosed that he is a consultant and speaker for Boehringer Ingelheim, which sponsored the study, and he has received research support from the firm.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial.

Dr. Jamerson and his associates reported significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

The investigators randomized 11,463 patients who were aged 55 years or more with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment.

Cardiovascular morbidity and mortality outcomes, which are the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes that the current data will help shift the traditional approach to hypertension management in which providers initiate monotherapy then sequentially use additional medications as needed to achieve target blood pressure goals.

“Too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, only 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials.

The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns. The VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important.

“It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Too many have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are necessary. DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial.

Dr. Jamerson and his associates reported significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

The investigators randomized 11,463 patients who were aged 55 years or more with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment.

Cardiovascular morbidity and mortality outcomes, which are the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes that the current data will help shift the traditional approach to hypertension management in which providers initiate monotherapy then sequentially use additional medications as needed to achieve target blood pressure goals.

“Too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, only 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials.

The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns. The VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important.

“It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Too many have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are necessary. DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial.

Dr. Jamerson and his associates reported significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

The investigators randomized 11,463 patients who were aged 55 years or more with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment.

Cardiovascular morbidity and mortality outcomes, which are the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes that the current data will help shift the traditional approach to hypertension management in which providers initiate monotherapy then sequentially use additional medications as needed to achieve target blood pressure goals.

“Too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, only 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials.

The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns. The VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important.

“It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Too many have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are necessary. DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson thinks this data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy, then add medications as needed to achieve blood pressure goals.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg in Nordic patients, from 142 mm Hg to 129 in the U.S. cohort, and from 145 mm Hg to 133 mm Hg in African Americans.

More work is needed among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH president Dr. Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, disagreed that these results will shift treatment patterns, as the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial already showed that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients, and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine how many hypotensive events are drug related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

The study data support 'broadening the use of combination therapy as an initial therapy.' DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson thinks this data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy, then add medications as needed to achieve blood pressure goals.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg in Nordic patients, from 142 mm Hg to 129 in the U.S. cohort, and from 145 mm Hg to 133 mm Hg in African Americans.

More work is needed among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH president Dr. Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, disagreed that these results will shift treatment patterns, as the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial already showed that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients, and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine how many hypotensive events are drug related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

The study data support 'broadening the use of combination therapy as an initial therapy.' DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in an ongoing large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented interim results from the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson thinks this data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy, then add medications as needed to achieve blood pressure goals.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg in Nordic patients, from 142 mm Hg to 129 in the U.S. cohort, and from 145 mm Hg to 133 mm Hg in African Americans.

More work is needed among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH president Dr. Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, disagreed that these results will shift treatment patterns, as the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial already showed that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients, and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine how many hypotensive events are drug related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

The study data support 'broadening the use of combination therapy as an initial therapy.' DR. JAMERSON

NEW ORLEANS — Nutritional rickets caused by vitamin D deficiency persists, in part because the risk factors may not be fully appreciated, Dr. Arlette Soros and colleagues reported in a poster at the Southern regional meeting of the American Federation for Medical Research.

The authors have encountered nearly a dozen cases in the last decade at Children's Hospital in New Orleans, and have documented four representative cases. The children, aged 3 months to 3 years, shared similar risk factors of limited sun exposure, darker skin pigmentation, and having been breast-fed without any vitamin D supplementation.

Breast milk typically contains a vitamin D concentration of 25 IU or less per liter, which falls far short of the daily recommended minimum intake of 200 IU per day for infants, said Dr. Soros, a pediatrician with the division of endocrinology at Louisiana State University, New Orleans.

“It's wrong to think that a baby will get all the nutrients it needs from breast milk, and not give vitamin D supplementation” she said in an interview. “They may appear healthy, but there is a deficiency going on.”

In addition, synthesis of vitamin D from ultraviolet sunlight is decreased in darker skin pigmentation. Lifestyle and cultural factors may further limit sunlight exposure.

Three of the children were African American and one was Arabic. They presented with tetany, bony deformities such as bowed legs, widening of wrists and ankles, and rachitic rosary.

All of the children had low serum total calcium (range 6.1–7.8 mg/dL) and ionized calcium levels (range 2.2- 4.3 mg/dL); relatively low normal serum phosphorus levels (range 4.3–6.1 mg/dL), and elevated alkaline phosphatase levels (range 391–1,158 U/L).

All had low serum 25-hydroxy vitamin D (range 5.0–21 ng/mL), high parathyroid hormone levels (range 143–454 pg/mL), and relatively high 1,25-dihydroxy vitamin D levels (range 93–195 pg/mL). Renal and liver functions were normal.

One boy had even been put in a soft cast because his pediatrician misdiagnosed the rickets as a sprain. After a single dose of intravenous calcium, ergocalciferol, or calcitriol, all of the children had complete or near-complete resolution of their symptoms. “He was up running the next day,” Dr. Soros said. “This is very preventable.”

In 2003, the American Academy of Pediatrics published new guidelines for vitamin D intake and recommended supplementation of 200 IU for all breast-fed infants. It also has issued directives that infants younger than 6 months should be kept out of direct sunlight.

For the most part, the problem of nutritional rickets has been well identified, although pediatricians are responsible for tolerating lower levels of vitamin D, particularly in African American, Arabic, and Hispanic children, senior author Dr. Alfonso Vargas, professor of pediatrics at Louisiana State, said in an interview.

“The message from the AAP is not collating quickly enough,” he said. “The beauty of this study shows that if a child's vitamin D needs are not addressed, they will be in serious trouble quite quickly.”

The fraying and lack of calcification seen in this x-ray are typical of rickets. Courtesy Dr. Alfonso Vargas/Children's Hospital

NEW ORLEANS — Nutritional rickets caused by vitamin D deficiency persists, in part because the risk factors may not be fully appreciated, Dr. Arlette Soros and colleagues reported in a poster at the Southern regional meeting of the American Federation for Medical Research.

The authors have encountered nearly a dozen cases in the last decade at Children's Hospital in New Orleans, and have documented four representative cases. The children, aged 3 months to 3 years, shared similar risk factors of limited sun exposure, darker skin pigmentation, and having been breast-fed without any vitamin D supplementation.

Breast milk typically contains a vitamin D concentration of 25 IU or less per liter, which falls far short of the daily recommended minimum intake of 200 IU per day for infants, said Dr. Soros, a pediatrician with the division of endocrinology at Louisiana State University, New Orleans.

“It's wrong to think that a baby will get all the nutrients it needs from breast milk, and not give vitamin D supplementation” she said in an interview. “They may appear healthy, but there is a deficiency going on.”

In addition, synthesis of vitamin D from ultraviolet sunlight is decreased in darker skin pigmentation. Lifestyle and cultural factors may further limit sunlight exposure.

Three of the children were African American and one was Arabic. They presented with tetany, bony deformities such as bowed legs, widening of wrists and ankles, and rachitic rosary.

All of the children had low serum total calcium (range 6.1–7.8 mg/dL) and ionized calcium levels (range 2.2- 4.3 mg/dL); relatively low normal serum phosphorus levels (range 4.3–6.1 mg/dL), and elevated alkaline phosphatase levels (range 391–1,158 U/L).

All had low serum 25-hydroxy vitamin D (range 5.0–21 ng/mL), high parathyroid hormone levels (range 143–454 pg/mL), and relatively high 1,25-dihydroxy vitamin D levels (range 93–195 pg/mL). Renal and liver functions were normal.

One boy had even been put in a soft cast because his pediatrician misdiagnosed the rickets as a sprain. After a single dose of intravenous calcium, ergocalciferol, or calcitriol, all of the children had complete or near-complete resolution of their symptoms. “He was up running the next day,” Dr. Soros said. “This is very preventable.”

In 2003, the American Academy of Pediatrics published new guidelines for vitamin D intake and recommended supplementation of 200 IU for all breast-fed infants. It also has issued directives that infants younger than 6 months should be kept out of direct sunlight.

For the most part, the problem of nutritional rickets has been well identified, although pediatricians are responsible for tolerating lower levels of vitamin D, particularly in African American, Arabic, and Hispanic children, senior author Dr. Alfonso Vargas, professor of pediatrics at Louisiana State, said in an interview.

“The message from the AAP is not collating quickly enough,” he said. “The beauty of this study shows that if a child's vitamin D needs are not addressed, they will be in serious trouble quite quickly.”

The fraying and lack of calcification seen in this x-ray are typical of rickets. Courtesy Dr. Alfonso Vargas/Children's Hospital

NEW ORLEANS — Nutritional rickets caused by vitamin D deficiency persists, in part because the risk factors may not be fully appreciated, Dr. Arlette Soros and colleagues reported in a poster at the Southern regional meeting of the American Federation for Medical Research.

The authors have encountered nearly a dozen cases in the last decade at Children's Hospital in New Orleans, and have documented four representative cases. The children, aged 3 months to 3 years, shared similar risk factors of limited sun exposure, darker skin pigmentation, and having been breast-fed without any vitamin D supplementation.

Breast milk typically contains a vitamin D concentration of 25 IU or less per liter, which falls far short of the daily recommended minimum intake of 200 IU per day for infants, said Dr. Soros, a pediatrician with the division of endocrinology at Louisiana State University, New Orleans.

“It's wrong to think that a baby will get all the nutrients it needs from breast milk, and not give vitamin D supplementation” she said in an interview. “They may appear healthy, but there is a deficiency going on.”

In addition, synthesis of vitamin D from ultraviolet sunlight is decreased in darker skin pigmentation. Lifestyle and cultural factors may further limit sunlight exposure.

Three of the children were African American and one was Arabic. They presented with tetany, bony deformities such as bowed legs, widening of wrists and ankles, and rachitic rosary.

All of the children had low serum total calcium (range 6.1–7.8 mg/dL) and ionized calcium levels (range 2.2- 4.3 mg/dL); relatively low normal serum phosphorus levels (range 4.3–6.1 mg/dL), and elevated alkaline phosphatase levels (range 391–1,158 U/L).

All had low serum 25-hydroxy vitamin D (range 5.0–21 ng/mL), high parathyroid hormone levels (range 143–454 pg/mL), and relatively high 1,25-dihydroxy vitamin D levels (range 93–195 pg/mL). Renal and liver functions were normal.

One boy had even been put in a soft cast because his pediatrician misdiagnosed the rickets as a sprain. After a single dose of intravenous calcium, ergocalciferol, or calcitriol, all of the children had complete or near-complete resolution of their symptoms. “He was up running the next day,” Dr. Soros said. “This is very preventable.”

In 2003, the American Academy of Pediatrics published new guidelines for vitamin D intake and recommended supplementation of 200 IU for all breast-fed infants. It also has issued directives that infants younger than 6 months should be kept out of direct sunlight.

For the most part, the problem of nutritional rickets has been well identified, although pediatricians are responsible for tolerating lower levels of vitamin D, particularly in African American, Arabic, and Hispanic children, senior author Dr. Alfonso Vargas, professor of pediatrics at Louisiana State, said in an interview.

“The message from the AAP is not collating quickly enough,” he said. “The beauty of this study shows that if a child's vitamin D needs are not addressed, they will be in serious trouble quite quickly.”

The fraying and lack of calcification seen in this x-ray are typical of rickets. Courtesy Dr. Alfonso Vargas/Children's Hospital

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.