John R. Bell

STOWE, VT. — Although Clostridium difficile-associated diarrhea is now more severe and more drug resistant than before, because of the evolution of a recently identified and more robust strain, a variety of new agents are in the pipeline.

And in some patients, several current treatments can effectively eliminate the organism, according to Dr. Samuel Pegram, who spoke at an emergency medicine update sponsored by the University of Vermont.

C. difficile, first identified in 1935, has evolved from a fairly benign bacterium to a multidrug-resistant pathogen that is responsible for an increasing portion of pediatric and adult cases of severe diarrhea, known as C. difficile-associated diarrhea or disease (CDAD), said Dr. Pegram, professor of medicine at Wake Forest University, Winston-Salem, N.C.

Currently, the pathogen is present in up to 30% of patients who have antibody-associated diarrhea, he said, and up to 65% of patients with antibody-associated colitis test positive for the bacterium. He cited a recent study that found that among children presenting to an emergency department with diarrhea, 47% had a bacterial pathogen, and nearly 7% were infected with C. difficile (Clin. Infect. Dis. 2006;43:807–13).

Moreover, a new strain is responsible for greater symptom severity and is resistant to many traditional therapies. This strain is known by various names, including BI, NAP1, ribotype 027, and toxinotype II, depending on what type of analysis is used to identify it in a particular laboratory. This new variant produces 16 times the amount of toxin A as prior strains and 23 times the amount of toxin B as toxinotype 0 strains, said Dr. Pegram, who is also the director of the Infectious Diseases Specialty Clinic at the university. In addition, the new subtype shows resistance to fluoroquinolones, including ciprofloxacin.

Several new treatments are in the developmental pipeline, however. They include tolevamer, a nonantibiotic toxin-binding polymer expected go on the market this year, and the antibiotic ramoplanin (Oscient Pharmaceuticals), which is in phase III trials, as is the novel macrocycle OPT-80 (Optimer Pharmaceuticals). An antibiotic called Rifalazil (ActivBiotics Inc.) is in phase II development, along with a monoclonal antibody to toxin A and B (Medarex Inc.). In addition, a toxoid vaccine is in phase I development (Acambis).

Yet the mainstream therapies for infection are still viable in many patients, though they have various abilities to overcome recurrence and come with a wide range of treatment costs, Dr. Pegram noted.

The least expensive treatment, at $18 for a 10-day course, is generic metronidazole 500 mg orally three times daily, he said, although a brand formulation also exists (Flagyl, Pfizer Inc.), costing $147 for the same treatment duration. Vancomycin (Vancocin, Viropharma Inc.), for which no generic exists, costs $611 for 10 days. Dr. Pegram estimated recurrence rates to be 20%–25% with metronidazole or vancomycin. Toxin-binding resins currently available include cholestyramine and colestipol.

Other weapons in the physician's arsenal are the oral antibiotic rifaximin (Xifaxan, Salix Pharmaceuticals), approved for E. coli-associated traveler's diarrhea in patients at least 12 years old, and nitazoxanide (Alinia, Romark Laboratories), approved for treatment of diarrhea caused by Giardia lamblia orCryptosporidium parvum.

Probiotic agents including yogurt, yeast, and oral lactobacillus may also be effective, he noted. Brands of lactobacillus include Lactinex (Becton Dickinson) and Culturelle (Kirkman). Yeast products include Saccharomyces boulardii and Florastor (Biocodex Inc.), which he said can be given in a dosage of two 250-mg capsules daily for 4–6 weeks.

In addition to pharmacologic and probiotic therapy, there remains the option of fecal transplantation to replenish the decimated gut flora, Dr. Pegram said. This can be done by collecting 30–50 g of fresh stool from a healthy donor and delivering it in a saline vehicle via either an enema or a nasogastric tube. Despite the perhaps unsettling nature of this treatment, “it certainly has worked,” Dr. Pegram said, although it carries a risk of transmitting other pathogens to the recipient. Thus, this option “is less desirable,” he said.

Intravenous immunoglobulin is also an option, he said. “Half the people sitting in this audience will have detectable antitoxin to toxins A and B,” said Dr. Pegram. Thus “pooled intravenous immune globulin might work. You give it as a one-time dose—a large dose and very expensive—400 mg/kg. And it's actually proven to be a very valuable asset when adding on therapy to the very sick patient.”

He noted that research is underway to develop a “hyper-immune globulin” by using plasmapheresis to cull these antibodies from persons with high antibody levels.

Dr. Pegram also noted that the Centers for Disease Control and Prevention has outlined steps that health care providers can take to prevent the spread of C. difficile. Perhaps most surprising is the admonition to use soap and water instead of alcohol-based sanitizers—which, he pointed out, can kill other hardy bacteria, such as methicillin-resistant Staphylococcus aureus, but not C. difficile.

A polymerase chain reaction test for detection of C. difficile toxin will likely be introduced this year, Dr. Pegram said.

STOWE, VT. — Although Clostridium difficile-associated diarrhea is now more severe and more drug resistant than before, because of the evolution of a recently identified and more robust strain, a variety of new agents are in the pipeline.

And in some patients, several current treatments can effectively eliminate the organism, according to Dr. Samuel Pegram, who spoke at an emergency medicine update sponsored by the University of Vermont.

C. difficile, first identified in 1935, has evolved from a fairly benign bacterium to a multidrug-resistant pathogen that is responsible for an increasing portion of pediatric and adult cases of severe diarrhea, known as C. difficile-associated diarrhea or disease (CDAD), said Dr. Pegram, professor of medicine at Wake Forest University, Winston-Salem, N.C.

Currently, the pathogen is present in up to 30% of patients who have antibody-associated diarrhea, he said, and up to 65% of patients with antibody-associated colitis test positive for the bacterium. He cited a recent study that found that among children presenting to an emergency department with diarrhea, 47% had a bacterial pathogen, and nearly 7% were infected with C. difficile (Clin. Infect. Dis. 2006;43:807–13).

Moreover, a new strain is responsible for greater symptom severity and is resistant to many traditional therapies. This strain is known by various names, including BI, NAP1, ribotype 027, and toxinotype II, depending on what type of analysis is used to identify it in a particular laboratory. This new variant produces 16 times the amount of toxin A as prior strains and 23 times the amount of toxin B as toxinotype 0 strains, said Dr. Pegram, who is also the director of the Infectious Diseases Specialty Clinic at the university. In addition, the new subtype shows resistance to fluoroquinolones, including ciprofloxacin.

Several new treatments are in the developmental pipeline, however. They include tolevamer, a nonantibiotic toxin-binding polymer expected go on the market this year, and the antibiotic ramoplanin (Oscient Pharmaceuticals), which is in phase III trials, as is the novel macrocycle OPT-80 (Optimer Pharmaceuticals). An antibiotic called Rifalazil (ActivBiotics Inc.) is in phase II development, along with a monoclonal antibody to toxin A and B (Medarex Inc.). In addition, a toxoid vaccine is in phase I development (Acambis).

Yet the mainstream therapies for infection are still viable in many patients, though they have various abilities to overcome recurrence and come with a wide range of treatment costs, Dr. Pegram noted.

The least expensive treatment, at $18 for a 10-day course, is generic metronidazole 500 mg orally three times daily, he said, although a brand formulation also exists (Flagyl, Pfizer Inc.), costing $147 for the same treatment duration. Vancomycin (Vancocin, Viropharma Inc.), for which no generic exists, costs $611 for 10 days. Dr. Pegram estimated recurrence rates to be 20%–25% with metronidazole or vancomycin. Toxin-binding resins currently available include cholestyramine and colestipol.

Other weapons in the physician's arsenal are the oral antibiotic rifaximin (Xifaxan, Salix Pharmaceuticals), approved for E. coli-associated traveler's diarrhea in patients at least 12 years old, and nitazoxanide (Alinia, Romark Laboratories), approved for treatment of diarrhea caused by Giardia lamblia orCryptosporidium parvum.

Probiotic agents including yogurt, yeast, and oral lactobacillus may also be effective, he noted. Brands of lactobacillus include Lactinex (Becton Dickinson) and Culturelle (Kirkman). Yeast products include Saccharomyces boulardii and Florastor (Biocodex Inc.), which he said can be given in a dosage of two 250-mg capsules daily for 4–6 weeks.

In addition to pharmacologic and probiotic therapy, there remains the option of fecal transplantation to replenish the decimated gut flora, Dr. Pegram said. This can be done by collecting 30–50 g of fresh stool from a healthy donor and delivering it in a saline vehicle via either an enema or a nasogastric tube. Despite the perhaps unsettling nature of this treatment, “it certainly has worked,” Dr. Pegram said, although it carries a risk of transmitting other pathogens to the recipient. Thus, this option “is less desirable,” he said.

Intravenous immunoglobulin is also an option, he said. “Half the people sitting in this audience will have detectable antitoxin to toxins A and B,” said Dr. Pegram. Thus “pooled intravenous immune globulin might work. You give it as a one-time dose—a large dose and very expensive—400 mg/kg. And it's actually proven to be a very valuable asset when adding on therapy to the very sick patient.”

He noted that research is underway to develop a “hyper-immune globulin” by using plasmapheresis to cull these antibodies from persons with high antibody levels.

Dr. Pegram also noted that the Centers for Disease Control and Prevention has outlined steps that health care providers can take to prevent the spread of C. difficile. Perhaps most surprising is the admonition to use soap and water instead of alcohol-based sanitizers—which, he pointed out, can kill other hardy bacteria, such as methicillin-resistant Staphylococcus aureus, but not C. difficile.

A polymerase chain reaction test for detection of C. difficile toxin will likely be introduced this year, Dr. Pegram said.

STOWE, VT. — Although Clostridium difficile-associated diarrhea is now more severe and more drug resistant than before, because of the evolution of a recently identified and more robust strain, a variety of new agents are in the pipeline.

And in some patients, several current treatments can effectively eliminate the organism, according to Dr. Samuel Pegram, who spoke at an emergency medicine update sponsored by the University of Vermont.

C. difficile, first identified in 1935, has evolved from a fairly benign bacterium to a multidrug-resistant pathogen that is responsible for an increasing portion of pediatric and adult cases of severe diarrhea, known as C. difficile-associated diarrhea or disease (CDAD), said Dr. Pegram, professor of medicine at Wake Forest University, Winston-Salem, N.C.

Currently, the pathogen is present in up to 30% of patients who have antibody-associated diarrhea, he said, and up to 65% of patients with antibody-associated colitis test positive for the bacterium. He cited a recent study that found that among children presenting to an emergency department with diarrhea, 47% had a bacterial pathogen, and nearly 7% were infected with C. difficile (Clin. Infect. Dis. 2006;43:807–13).

Moreover, a new strain is responsible for greater symptom severity and is resistant to many traditional therapies. This strain is known by various names, including BI, NAP1, ribotype 027, and toxinotype II, depending on what type of analysis is used to identify it in a particular laboratory. This new variant produces 16 times the amount of toxin A as prior strains and 23 times the amount of toxin B as toxinotype 0 strains, said Dr. Pegram, who is also the director of the Infectious Diseases Specialty Clinic at the university. In addition, the new subtype shows resistance to fluoroquinolones, including ciprofloxacin.

Several new treatments are in the developmental pipeline, however. They include tolevamer, a nonantibiotic toxin-binding polymer expected go on the market this year, and the antibiotic ramoplanin (Oscient Pharmaceuticals), which is in phase III trials, as is the novel macrocycle OPT-80 (Optimer Pharmaceuticals). An antibiotic called Rifalazil (ActivBiotics Inc.) is in phase II development, along with a monoclonal antibody to toxin A and B (Medarex Inc.). In addition, a toxoid vaccine is in phase I development (Acambis).

Yet the mainstream therapies for infection are still viable in many patients, though they have various abilities to overcome recurrence and come with a wide range of treatment costs, Dr. Pegram noted.

The least expensive treatment, at $18 for a 10-day course, is generic metronidazole 500 mg orally three times daily, he said, although a brand formulation also exists (Flagyl, Pfizer Inc.), costing $147 for the same treatment duration. Vancomycin (Vancocin, Viropharma Inc.), for which no generic exists, costs $611 for 10 days. Dr. Pegram estimated recurrence rates to be 20%–25% with metronidazole or vancomycin. Toxin-binding resins currently available include cholestyramine and colestipol.

Other weapons in the physician's arsenal are the oral antibiotic rifaximin (Xifaxan, Salix Pharmaceuticals), approved for E. coli-associated traveler's diarrhea in patients at least 12 years old, and nitazoxanide (Alinia, Romark Laboratories), approved for treatment of diarrhea caused by Giardia lamblia orCryptosporidium parvum.

Probiotic agents including yogurt, yeast, and oral lactobacillus may also be effective, he noted. Brands of lactobacillus include Lactinex (Becton Dickinson) and Culturelle (Kirkman). Yeast products include Saccharomyces boulardii and Florastor (Biocodex Inc.), which he said can be given in a dosage of two 250-mg capsules daily for 4–6 weeks.

In addition to pharmacologic and probiotic therapy, there remains the option of fecal transplantation to replenish the decimated gut flora, Dr. Pegram said. This can be done by collecting 30–50 g of fresh stool from a healthy donor and delivering it in a saline vehicle via either an enema or a nasogastric tube. Despite the perhaps unsettling nature of this treatment, “it certainly has worked,” Dr. Pegram said, although it carries a risk of transmitting other pathogens to the recipient. Thus, this option “is less desirable,” he said.

Intravenous immunoglobulin is also an option, he said. “Half the people sitting in this audience will have detectable antitoxin to toxins A and B,” said Dr. Pegram. Thus “pooled intravenous immune globulin might work. You give it as a one-time dose—a large dose and very expensive—400 mg/kg. And it's actually proven to be a very valuable asset when adding on therapy to the very sick patient.”

He noted that research is underway to develop a “hyper-immune globulin” by using plasmapheresis to cull these antibodies from persons with high antibody levels.

Dr. Pegram also noted that the Centers for Disease Control and Prevention has outlined steps that health care providers can take to prevent the spread of C. difficile. Perhaps most surprising is the admonition to use soap and water instead of alcohol-based sanitizers—which, he pointed out, can kill other hardy bacteria, such as methicillin-resistant Staphylococcus aureus, but not C. difficile.

A polymerase chain reaction test for detection of C. difficile toxin will likely be introduced this year, Dr. Pegram said.

LAS VEGAS — Solutions to several challenging treatment scenarios in patients undergoing biologic therapy for rheumatologic or dermatologic conditions were considered by a panel of experts at seminar sponsored by Skin Disease Education Foundation.

The head of the panel, Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, presented one scenario in which a patient being treated with a biologic is about to travel abroad to a developing country for a brief visit and needs to get the recommended vaccinations. Among the questions he asked the panel: Should the patient get the vaccinations? If so, should he discontinue the biologic?

Discontinuing the biologic to get the vaccinations was deemed an option by the panel, but with caveats. “It depends on the agent,” said Dr. Robert Kalb of the State University of New York at Buffalo. “If the person's on etanercept, and it's a short visit, [discontinuation is] certainly a very reasonable option. [If] the person's on efalizumab, I'd be a little bit more leery. The half-life of infliximab is such that, depending on the timing of the infusion, you might be able to get away with it.” He noted that he advises continuing the biologic during vaccinations that use killed vaccine and thus there is no reason to stop therapy for influenza or pneumonia vaccinations.

Dr. Bruce Strober of New York University, New York, said that stopping the biologic makes it more likely the vaccine will be at its peak efficacy. “I think there are some tangential studies that show if you give some types of vaccines in the midst of biologic therapy, some immunologic readouts are reduced, but the clinical relevance of that hasn't been established.” He noted that live vaccines are contraindicated with biologics. As to the length of time for biologic discontinuation in the setting of live vaccine use, “you would like the biologic to be more or less inactive in the patient, so four to five half-lives,” he said.

This estimate was shared by panelist Dr. Francisco Kerdel of Cedars Medical Center in Miami, who also raised the question of whether biologic treatment brings an increased risk of contracting disease, especially in regions with a greater number and variety of nefarious microbes. “When you talk about the granulomatous diseases being activated by the use of anti-[tumor necrosis factor], most of the time it applies to patients reactivating what they already have,” he said.

Dr. Strober suggested that physicians ask patients taking biologics about their future travel plans and vaccinations.

Flare-up of the disease itself is one of the foremost risks of stopping a biologic, especially efalizumab, Dr. Leonardi noted. Disease rebound is less of a risk, however, with TNF-α antagonists.

Another challenging scenario that Dr. Leonardi presented involved an elderly patient with psoriatic arthritis and heart failure (HF) who is unwilling to accept conventional treatment and insists on biologic therapy.

“I think you need to define the severity of HF,” Dr. Strober said, adding that studies of etanercept and infliximab showed that only patients with very severe heart failure experienced problems on infliximab, and only on the highest dose of 10 mg/kg. He advised consulting with a cardiologist to determine if tumor necrosis factor inhibitors are an option. Even so, he suggested trying efalizumab or alefacept first.

The panel also discussed the issue of weight and body mass index with biologic therapy. Morbidly obese patients don't respond as well to etanercept, Dr. Kalb noted, but the biologics with weight-based dosing, efalizumab and infliximab, have demonstrated similar responses in patients with and without high body mass index. Part of the difficulty in treating heavier patients may lie in weight-based dosing.

The final scenario presented involved a patient on a biologic who is about to undergo elective surgery for chronic cholecystitis refractory to antibiotics. Dr. Leonardi advised stopping the biologic and restarting it after surgery, except in the case of etanercept. Biologics might pose some effect on postsurgical wound healing and infection risk, but little is known about such interactions, Dr. Kerdel said.

It is important, however, to tell the surgeon what biologic the patient is taking, Dr. Leonardi said. “The surgeon may have no idea what these medicines are,” he said.

Dr. Kalb noted that many patients with Crohn's disease need surgery and that many continue taking infliximab.

Dr. Kerdel noted that if the cholecystitis patient is taking efalizumab, “I would continue [treatment], because I think the risk of having a rebound phenomenon … would be greater than the risk of infections that we know of.”

Dr. Leonardi is a consultant for Amgen, Abbott, Genentech, and Centocor. Dr. Kerdel is a consultant for Abbott, Amgen, and Centocor.

Dr. Kalb has been a consultant for the latter three firms, as well as for Genentech. Dr. Strober has received funding from, advised, or been a speaker for Genentech, Amgen/Wyeth, Centocor, Abbott, and Astellas.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

LAS VEGAS — Solutions to several challenging treatment scenarios in patients undergoing biologic therapy for rheumatologic or dermatologic conditions were considered by a panel of experts at seminar sponsored by Skin Disease Education Foundation.

The head of the panel, Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, presented one scenario in which a patient being treated with a biologic is about to travel abroad to a developing country for a brief visit and needs to get the recommended vaccinations. Among the questions he asked the panel: Should the patient get the vaccinations? If so, should he discontinue the biologic?

Discontinuing the biologic to get the vaccinations was deemed an option by the panel, but with caveats. “It depends on the agent,” said Dr. Robert Kalb of the State University of New York at Buffalo. “If the person's on etanercept, and it's a short visit, [discontinuation is] certainly a very reasonable option. [If] the person's on efalizumab, I'd be a little bit more leery. The half-life of infliximab is such that, depending on the timing of the infusion, you might be able to get away with it.” He noted that he advises continuing the biologic during vaccinations that use killed vaccine and thus there is no reason to stop therapy for influenza or pneumonia vaccinations.

Dr. Bruce Strober of New York University, New York, said that stopping the biologic makes it more likely the vaccine will be at its peak efficacy. “I think there are some tangential studies that show if you give some types of vaccines in the midst of biologic therapy, some immunologic readouts are reduced, but the clinical relevance of that hasn't been established.” He noted that live vaccines are contraindicated with biologics. As to the length of time for biologic discontinuation in the setting of live vaccine use, “you would like the biologic to be more or less inactive in the patient, so four to five half-lives,” he said.

This estimate was shared by panelist Dr. Francisco Kerdel of Cedars Medical Center in Miami, who also raised the question of whether biologic treatment brings an increased risk of contracting disease, especially in regions with a greater number and variety of nefarious microbes. “When you talk about the granulomatous diseases being activated by the use of anti-[tumor necrosis factor], most of the time it applies to patients reactivating what they already have,” he said.

Dr. Strober suggested that physicians ask patients taking biologics about their future travel plans and vaccinations.

Flare-up of the disease itself is one of the foremost risks of stopping a biologic, especially efalizumab, Dr. Leonardi noted. Disease rebound is less of a risk, however, with TNF-α antagonists.

Another challenging scenario that Dr. Leonardi presented involved an elderly patient with psoriatic arthritis and heart failure (HF) who is unwilling to accept conventional treatment and insists on biologic therapy.

“I think you need to define the severity of HF,” Dr. Strober said, adding that studies of etanercept and infliximab showed that only patients with very severe heart failure experienced problems on infliximab, and only on the highest dose of 10 mg/kg. He advised consulting with a cardiologist to determine if tumor necrosis factor inhibitors are an option. Even so, he suggested trying efalizumab or alefacept first.

The panel also discussed the issue of weight and body mass index with biologic therapy. Morbidly obese patients don't respond as well to etanercept, Dr. Kalb noted, but the biologics with weight-based dosing, efalizumab and infliximab, have demonstrated similar responses in patients with and without high body mass index. Part of the difficulty in treating heavier patients may lie in weight-based dosing.

The final scenario presented involved a patient on a biologic who is about to undergo elective surgery for chronic cholecystitis refractory to antibiotics. Dr. Leonardi advised stopping the biologic and restarting it after surgery, except in the case of etanercept. Biologics might pose some effect on postsurgical wound healing and infection risk, but little is known about such interactions, Dr. Kerdel said.

It is important, however, to tell the surgeon what biologic the patient is taking, Dr. Leonardi said. “The surgeon may have no idea what these medicines are,” he said.

Dr. Kalb noted that many patients with Crohn's disease need surgery and that many continue taking infliximab.

Dr. Kerdel noted that if the cholecystitis patient is taking efalizumab, “I would continue [treatment], because I think the risk of having a rebound phenomenon … would be greater than the risk of infections that we know of.”

Dr. Leonardi is a consultant for Amgen, Abbott, Genentech, and Centocor. Dr. Kerdel is a consultant for Abbott, Amgen, and Centocor.

Dr. Kalb has been a consultant for the latter three firms, as well as for Genentech. Dr. Strober has received funding from, advised, or been a speaker for Genentech, Amgen/Wyeth, Centocor, Abbott, and Astellas.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

LAS VEGAS — Solutions to several challenging treatment scenarios in patients undergoing biologic therapy for rheumatologic or dermatologic conditions were considered by a panel of experts at seminar sponsored by Skin Disease Education Foundation.

The head of the panel, Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, presented one scenario in which a patient being treated with a biologic is about to travel abroad to a developing country for a brief visit and needs to get the recommended vaccinations. Among the questions he asked the panel: Should the patient get the vaccinations? If so, should he discontinue the biologic?

Discontinuing the biologic to get the vaccinations was deemed an option by the panel, but with caveats. “It depends on the agent,” said Dr. Robert Kalb of the State University of New York at Buffalo. “If the person's on etanercept, and it's a short visit, [discontinuation is] certainly a very reasonable option. [If] the person's on efalizumab, I'd be a little bit more leery. The half-life of infliximab is such that, depending on the timing of the infusion, you might be able to get away with it.” He noted that he advises continuing the biologic during vaccinations that use killed vaccine and thus there is no reason to stop therapy for influenza or pneumonia vaccinations.

Dr. Bruce Strober of New York University, New York, said that stopping the biologic makes it more likely the vaccine will be at its peak efficacy. “I think there are some tangential studies that show if you give some types of vaccines in the midst of biologic therapy, some immunologic readouts are reduced, but the clinical relevance of that hasn't been established.” He noted that live vaccines are contraindicated with biologics. As to the length of time for biologic discontinuation in the setting of live vaccine use, “you would like the biologic to be more or less inactive in the patient, so four to five half-lives,” he said.

This estimate was shared by panelist Dr. Francisco Kerdel of Cedars Medical Center in Miami, who also raised the question of whether biologic treatment brings an increased risk of contracting disease, especially in regions with a greater number and variety of nefarious microbes. “When you talk about the granulomatous diseases being activated by the use of anti-[tumor necrosis factor], most of the time it applies to patients reactivating what they already have,” he said.

Dr. Strober suggested that physicians ask patients taking biologics about their future travel plans and vaccinations.

Flare-up of the disease itself is one of the foremost risks of stopping a biologic, especially efalizumab, Dr. Leonardi noted. Disease rebound is less of a risk, however, with TNF-α antagonists.

Another challenging scenario that Dr. Leonardi presented involved an elderly patient with psoriatic arthritis and heart failure (HF) who is unwilling to accept conventional treatment and insists on biologic therapy.

“I think you need to define the severity of HF,” Dr. Strober said, adding that studies of etanercept and infliximab showed that only patients with very severe heart failure experienced problems on infliximab, and only on the highest dose of 10 mg/kg. He advised consulting with a cardiologist to determine if tumor necrosis factor inhibitors are an option. Even so, he suggested trying efalizumab or alefacept first.

The panel also discussed the issue of weight and body mass index with biologic therapy. Morbidly obese patients don't respond as well to etanercept, Dr. Kalb noted, but the biologics with weight-based dosing, efalizumab and infliximab, have demonstrated similar responses in patients with and without high body mass index. Part of the difficulty in treating heavier patients may lie in weight-based dosing.

The final scenario presented involved a patient on a biologic who is about to undergo elective surgery for chronic cholecystitis refractory to antibiotics. Dr. Leonardi advised stopping the biologic and restarting it after surgery, except in the case of etanercept. Biologics might pose some effect on postsurgical wound healing and infection risk, but little is known about such interactions, Dr. Kerdel said.

It is important, however, to tell the surgeon what biologic the patient is taking, Dr. Leonardi said. “The surgeon may have no idea what these medicines are,” he said.

Dr. Kalb noted that many patients with Crohn's disease need surgery and that many continue taking infliximab.

Dr. Kerdel noted that if the cholecystitis patient is taking efalizumab, “I would continue [treatment], because I think the risk of having a rebound phenomenon … would be greater than the risk of infections that we know of.”

Dr. Leonardi is a consultant for Amgen, Abbott, Genentech, and Centocor. Dr. Kerdel is a consultant for Abbott, Amgen, and Centocor.

Dr. Kalb has been a consultant for the latter three firms, as well as for Genentech. Dr. Strober has received funding from, advised, or been a speaker for Genentech, Amgen/Wyeth, Centocor, Abbott, and Astellas.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

AUSTIN, TEX. – Patients with schizophrenia who are trying to quit smoking may display altered results on various psychiatric tests, according to preliminary findings presented at the annual meeting of the Society for Research on Nicotine and Tobacco.

Kristi Sacco, Psy.D., of Yale University, New Haven, Conn., and her colleagues noted that patients with schizophrenia have well-documented cognitive deficits, including sensory-motor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response. It also has been documented that such persons have high rates of smoking, Dr. Sacco said.

Her group examined the correlation between PPI and results on the Wisconsin Card Sorting Test (WCST) in 12 smokers with schizophrenia, 7 nonsmokers with schizophrenia, 13 nonpsychiatric control smokers, and 12 nonpsychiatric control nonsmokers.

At 3 years' follow-up, they found a significant association in smokers with schizophrenia between PPI and the “categories completed” WCST measure. However, no such correlation was found between these outcomes in the other three groups.

Thus, it should come as no surprise to see patients with schizophrenia who quit smoking display attentional and processing difficulties, Dr. Sacco said in an interview. That is especially the case if patients “go cold-turkey with their quitting,” she said.

AUSTIN, TEX. – Patients with schizophrenia who are trying to quit smoking may display altered results on various psychiatric tests, according to preliminary findings presented at the annual meeting of the Society for Research on Nicotine and Tobacco.

Kristi Sacco, Psy.D., of Yale University, New Haven, Conn., and her colleagues noted that patients with schizophrenia have well-documented cognitive deficits, including sensory-motor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response. It also has been documented that such persons have high rates of smoking, Dr. Sacco said.

Her group examined the correlation between PPI and results on the Wisconsin Card Sorting Test (WCST) in 12 smokers with schizophrenia, 7 nonsmokers with schizophrenia, 13 nonpsychiatric control smokers, and 12 nonpsychiatric control nonsmokers.

At 3 years' follow-up, they found a significant association in smokers with schizophrenia between PPI and the “categories completed” WCST measure. However, no such correlation was found between these outcomes in the other three groups.

Thus, it should come as no surprise to see patients with schizophrenia who quit smoking display attentional and processing difficulties, Dr. Sacco said in an interview. That is especially the case if patients “go cold-turkey with their quitting,” she said.

AUSTIN, TEX. – Patients with schizophrenia who are trying to quit smoking may display altered results on various psychiatric tests, according to preliminary findings presented at the annual meeting of the Society for Research on Nicotine and Tobacco.

Kristi Sacco, Psy.D., of Yale University, New Haven, Conn., and her colleagues noted that patients with schizophrenia have well-documented cognitive deficits, including sensory-motor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response. It also has been documented that such persons have high rates of smoking, Dr. Sacco said.

Her group examined the correlation between PPI and results on the Wisconsin Card Sorting Test (WCST) in 12 smokers with schizophrenia, 7 nonsmokers with schizophrenia, 13 nonpsychiatric control smokers, and 12 nonpsychiatric control nonsmokers.

At 3 years' follow-up, they found a significant association in smokers with schizophrenia between PPI and the “categories completed” WCST measure. However, no such correlation was found between these outcomes in the other three groups.

Thus, it should come as no surprise to see patients with schizophrenia who quit smoking display attentional and processing difficulties, Dr. Sacco said in an interview. That is especially the case if patients “go cold-turkey with their quitting,” she said.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

A Congressional push for fast-track approval of generic biologics likely won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations—both regular and NPH—have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are instead regulated by the Food, Drug, and Cosmetic Act of 1938, which allows the accelerated approval of new drugs based on prior evidence. In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but instead a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics—a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “the other important thing to understand is, this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus, the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “Good science requires proof of safety. From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle that came from a bunch of yeast and bacteria.”

The savings to state Medicaid budgets that fast-track approvals of nonanalogue human rDNA insulins could produce would depend on how much of these traditional insulins a given state purchases in lieu of the more advanced analogues.

A Congressional push for fast-track approval of generic biologics likely won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations—both regular and NPH—have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are instead regulated by the Food, Drug, and Cosmetic Act of 1938, which allows the accelerated approval of new drugs based on prior evidence. In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but instead a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics—a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “the other important thing to understand is, this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus, the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “Good science requires proof of safety. From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle that came from a bunch of yeast and bacteria.”

The savings to state Medicaid budgets that fast-track approvals of nonanalogue human rDNA insulins could produce would depend on how much of these traditional insulins a given state purchases in lieu of the more advanced analogues.

A Congressional push for fast-track approval of generic biologics likely won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations—both regular and NPH—have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are instead regulated by the Food, Drug, and Cosmetic Act of 1938, which allows the accelerated approval of new drugs based on prior evidence. In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but instead a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics—a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “the other important thing to understand is, this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus, the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “Good science requires proof of safety. From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle that came from a bunch of yeast and bacteria.”

The savings to state Medicaid budgets that fast-track approvals of nonanalogue human rDNA insulins could produce would depend on how much of these traditional insulins a given state purchases in lieu of the more advanced analogues.

BALTIMORE – When deciding which drug to prescribe a patient with restless legs syndrome, the frequency and painfulness of symptoms are crucial to making the correct choice, Dr. Christopher J. Earley said at a neurology meeting sponsored by Johns Hopkins University.

“For [75%]-80%, depending on the population that you deal with, pain is not what they experience,” said Dr. Earley, a neurologist at Johns Hopkins. A far greater portion instead describe their RLS as uncomfortable, he said. But for those with painful RLS, that pain must be treated. “So I tend to use the antiseizure medications [e.g., gabapentin, lamotrigine, pregabalin] or the opiates as my first line of treatment, as opposed to the dopamine [DA] agents, when I'm dealing with painful symptoms,” he said. “If it's partially responsive… then I will consider the dopamine agonists. If I really get desperate … I might consider sedation.”

For painless nightly RLS, he advises a DA agonist as first-line therapy, opiates as a second-line choice, and sedatives as third-line treatment. Frequent painless RLS (2–3 nights per week) warrants a sedative first, followed by opiates and, if those fail, levodopa. For occasional RLS (less than twice per week), he advises either a half or whole tablet of carbidopa 25 mg/levodopa 100 mg (available as Sinemet and Parcopa brands) as needed for first-line therapy. “This is going to be effective in 99.9% of patients, barring side effects like nausea,” he said. He recommends a DA agonist and a sedative as second- and third-line treatment, respectively. Drugs that can aggravate restless legs syndrome include neuroleptics and antiemetics, as well as SSRIs and tricyclic antidepressants (except for bupropion and trazodone) and antihistamines.

A disadvantage of the DA agonists is that they take 2 hours to reach peak dose effect (3 hours if taken with a meal or after symptom onset), compared with 30–60 minutes for opiates. Thus dopamine agonists are most useful for situations such as airplane flights, he said, but less practical for nighttime RLS. Dr. Earley favors levodopa for occasional nonpainful restless legs syndrome.

“If you have any doubts about whether this is RLS or not RLS, you can use the levodopa”-carbidopa combination (carbidopa 25 mg/levodopa 100 mg) of 1/2–11/2 tablets for 3 days. “If they get no real benefits from that, this is not RLS–at least not the RLS that I know.”

The DA agonists do have other disadvantages besides their delayed effect, Dr. Earley noted. They can cause compulsive behaviors–though this has been observed more in patients with Parkinson's disease than with restless legs syndrome. They also can cause hypersomnia. “It's almost like narcolepsy,” he said. “They're sitting there talking to someone, and they literally fall asleep in the middle of the conversation.”

Moreover, DA agonists risk the phenomenon of augmentation, whereby an increase in dosage leads to an increase in symptoms, so that a patient is treated effectively for a time period in which RLS occurs (e.g., bedtime), but then the RLS begins to occur either before or after the treated period. “Augmentation is the single biggest reason why you have to stop this drug,” Dr. Earley warned. He consulted on the case of a woman whose RLS progressed over the course of 2 years from initially requiring one dose of Sinemet nightly “to taking Sinemet every hour on the hour, and she was only getting 2 or 3 hours of sleep.” He urged physicians to “never, ever, ever go beyond the recommended dose. In fact, I never achieve the recommended dose.”

He advised that when patients taking a DA agonist for sleep complain of RLS symptoms before or after bedtime, the physician should not prescribe additional drug. As long as the patient can sleep without RLS awakening them or interfering with their falling asleep, RLS symptoms at other times of the day are not worth medicating. They are free to walk around in the evenings and the primary lifestyle problem of RLS interference with sleep is still under control, Dr. Earley said.

Notably, opiates do not pose augmentation risk, he said. With opiates, “you're going to get about 85% of them up walking away relatively happy.” Options in this drug category are codeine, propoxyphene, controlled-release oxycodone, methadone, and the fentanyl patch. Dr. Earley observed that methadone is by far the least expensive, at approximately $0.05 per dose. Dr. Earley cautioned that opiates have relatively short half-lives–approximately 4 hours for codeine derivatives and roughly 6 hours for the synthetic opiate propoxyphene.

Iron deficiency has been implicated as a possible cause of restless legs syndrome, he noted. “I check ferritins in everybody,” he said. Deficiency is defined as less than 18 ng/mL or iron saturation less than 16%. He recommends ferrous sulfate 325 mg plus 200 mg vitamin C or orange juice, to be given on an empty stomach in the absence of calcium or milk.

BALTIMORE – When deciding which drug to prescribe a patient with restless legs syndrome, the frequency and painfulness of symptoms are crucial to making the correct choice, Dr. Christopher J. Earley said at a neurology meeting sponsored by Johns Hopkins University.

“For [75%]-80%, depending on the population that you deal with, pain is not what they experience,” said Dr. Earley, a neurologist at Johns Hopkins. A far greater portion instead describe their RLS as uncomfortable, he said. But for those with painful RLS, that pain must be treated. “So I tend to use the antiseizure medications [e.g., gabapentin, lamotrigine, pregabalin] or the opiates as my first line of treatment, as opposed to the dopamine [DA] agents, when I'm dealing with painful symptoms,” he said. “If it's partially responsive… then I will consider the dopamine agonists. If I really get desperate … I might consider sedation.”

For painless nightly RLS, he advises a DA agonist as first-line therapy, opiates as a second-line choice, and sedatives as third-line treatment. Frequent painless RLS (2–3 nights per week) warrants a sedative first, followed by opiates and, if those fail, levodopa. For occasional RLS (less than twice per week), he advises either a half or whole tablet of carbidopa 25 mg/levodopa 100 mg (available as Sinemet and Parcopa brands) as needed for first-line therapy. “This is going to be effective in 99.9% of patients, barring side effects like nausea,” he said. He recommends a DA agonist and a sedative as second- and third-line treatment, respectively. Drugs that can aggravate restless legs syndrome include neuroleptics and antiemetics, as well as SSRIs and tricyclic antidepressants (except for bupropion and trazodone) and antihistamines.

A disadvantage of the DA agonists is that they take 2 hours to reach peak dose effect (3 hours if taken with a meal or after symptom onset), compared with 30–60 minutes for opiates. Thus dopamine agonists are most useful for situations such as airplane flights, he said, but less practical for nighttime RLS. Dr. Earley favors levodopa for occasional nonpainful restless legs syndrome.

“If you have any doubts about whether this is RLS or not RLS, you can use the levodopa”-carbidopa combination (carbidopa 25 mg/levodopa 100 mg) of 1/2–11/2 tablets for 3 days. “If they get no real benefits from that, this is not RLS–at least not the RLS that I know.”

The DA agonists do have other disadvantages besides their delayed effect, Dr. Earley noted. They can cause compulsive behaviors–though this has been observed more in patients with Parkinson's disease than with restless legs syndrome. They also can cause hypersomnia. “It's almost like narcolepsy,” he said. “They're sitting there talking to someone, and they literally fall asleep in the middle of the conversation.”

Moreover, DA agonists risk the phenomenon of augmentation, whereby an increase in dosage leads to an increase in symptoms, so that a patient is treated effectively for a time period in which RLS occurs (e.g., bedtime), but then the RLS begins to occur either before or after the treated period. “Augmentation is the single biggest reason why you have to stop this drug,” Dr. Earley warned. He consulted on the case of a woman whose RLS progressed over the course of 2 years from initially requiring one dose of Sinemet nightly “to taking Sinemet every hour on the hour, and she was only getting 2 or 3 hours of sleep.” He urged physicians to “never, ever, ever go beyond the recommended dose. In fact, I never achieve the recommended dose.”

He advised that when patients taking a DA agonist for sleep complain of RLS symptoms before or after bedtime, the physician should not prescribe additional drug. As long as the patient can sleep without RLS awakening them or interfering with their falling asleep, RLS symptoms at other times of the day are not worth medicating. They are free to walk around in the evenings and the primary lifestyle problem of RLS interference with sleep is still under control, Dr. Earley said.

Notably, opiates do not pose augmentation risk, he said. With opiates, “you're going to get about 85% of them up walking away relatively happy.” Options in this drug category are codeine, propoxyphene, controlled-release oxycodone, methadone, and the fentanyl patch. Dr. Earley observed that methadone is by far the least expensive, at approximately $0.05 per dose. Dr. Earley cautioned that opiates have relatively short half-lives–approximately 4 hours for codeine derivatives and roughly 6 hours for the synthetic opiate propoxyphene.

Iron deficiency has been implicated as a possible cause of restless legs syndrome, he noted. “I check ferritins in everybody,” he said. Deficiency is defined as less than 18 ng/mL or iron saturation less than 16%. He recommends ferrous sulfate 325 mg plus 200 mg vitamin C or orange juice, to be given on an empty stomach in the absence of calcium or milk.

BALTIMORE – When deciding which drug to prescribe a patient with restless legs syndrome, the frequency and painfulness of symptoms are crucial to making the correct choice, Dr. Christopher J. Earley said at a neurology meeting sponsored by Johns Hopkins University.

“For [75%]-80%, depending on the population that you deal with, pain is not what they experience,” said Dr. Earley, a neurologist at Johns Hopkins. A far greater portion instead describe their RLS as uncomfortable, he said. But for those with painful RLS, that pain must be treated. “So I tend to use the antiseizure medications [e.g., gabapentin, lamotrigine, pregabalin] or the opiates as my first line of treatment, as opposed to the dopamine [DA] agents, when I'm dealing with painful symptoms,” he said. “If it's partially responsive… then I will consider the dopamine agonists. If I really get desperate … I might consider sedation.”

For painless nightly RLS, he advises a DA agonist as first-line therapy, opiates as a second-line choice, and sedatives as third-line treatment. Frequent painless RLS (2–3 nights per week) warrants a sedative first, followed by opiates and, if those fail, levodopa. For occasional RLS (less than twice per week), he advises either a half or whole tablet of carbidopa 25 mg/levodopa 100 mg (available as Sinemet and Parcopa brands) as needed for first-line therapy. “This is going to be effective in 99.9% of patients, barring side effects like nausea,” he said. He recommends a DA agonist and a sedative as second- and third-line treatment, respectively. Drugs that can aggravate restless legs syndrome include neuroleptics and antiemetics, as well as SSRIs and tricyclic antidepressants (except for bupropion and trazodone) and antihistamines.

A disadvantage of the DA agonists is that they take 2 hours to reach peak dose effect (3 hours if taken with a meal or after symptom onset), compared with 30–60 minutes for opiates. Thus dopamine agonists are most useful for situations such as airplane flights, he said, but less practical for nighttime RLS. Dr. Earley favors levodopa for occasional nonpainful restless legs syndrome.

“If you have any doubts about whether this is RLS or not RLS, you can use the levodopa”-carbidopa combination (carbidopa 25 mg/levodopa 100 mg) of 1/2–11/2 tablets for 3 days. “If they get no real benefits from that, this is not RLS–at least not the RLS that I know.”

The DA agonists do have other disadvantages besides their delayed effect, Dr. Earley noted. They can cause compulsive behaviors–though this has been observed more in patients with Parkinson's disease than with restless legs syndrome. They also can cause hypersomnia. “It's almost like narcolepsy,” he said. “They're sitting there talking to someone, and they literally fall asleep in the middle of the conversation.”

Moreover, DA agonists risk the phenomenon of augmentation, whereby an increase in dosage leads to an increase in symptoms, so that a patient is treated effectively for a time period in which RLS occurs (e.g., bedtime), but then the RLS begins to occur either before or after the treated period. “Augmentation is the single biggest reason why you have to stop this drug,” Dr. Earley warned. He consulted on the case of a woman whose RLS progressed over the course of 2 years from initially requiring one dose of Sinemet nightly “to taking Sinemet every hour on the hour, and she was only getting 2 or 3 hours of sleep.” He urged physicians to “never, ever, ever go beyond the recommended dose. In fact, I never achieve the recommended dose.”

He advised that when patients taking a DA agonist for sleep complain of RLS symptoms before or after bedtime, the physician should not prescribe additional drug. As long as the patient can sleep without RLS awakening them or interfering with their falling asleep, RLS symptoms at other times of the day are not worth medicating. They are free to walk around in the evenings and the primary lifestyle problem of RLS interference with sleep is still under control, Dr. Earley said.

Notably, opiates do not pose augmentation risk, he said. With opiates, “you're going to get about 85% of them up walking away relatively happy.” Options in this drug category are codeine, propoxyphene, controlled-release oxycodone, methadone, and the fentanyl patch. Dr. Earley observed that methadone is by far the least expensive, at approximately $0.05 per dose. Dr. Earley cautioned that opiates have relatively short half-lives–approximately 4 hours for codeine derivatives and roughly 6 hours for the synthetic opiate propoxyphene.

Iron deficiency has been implicated as a possible cause of restless legs syndrome, he noted. “I check ferritins in everybody,” he said. Deficiency is defined as less than 18 ng/mL or iron saturation less than 16%. He recommends ferrous sulfate 325 mg plus 200 mg vitamin C or orange juice, to be given on an empty stomach in the absence of calcium or milk.

A Congressional push for fast-track approval of generic biologics probably won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations--both regular and NPH--have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are regulated by the Food, Drug, and Cosmetic Act of 1938, which allows accelerated approval of new drugs based on prior evidence.

In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics--a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle.”

A Congressional push for fast-track approval of generic biologics probably won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations--both regular and NPH--have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are regulated by the Food, Drug, and Cosmetic Act of 1938, which allows accelerated approval of new drugs based on prior evidence.

In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics--a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle.”

A Congressional push for fast-track approval of generic biologics probably won't have any effect on insulin costs for most patients with diabetes, mainly because the types of insulins most patients use now are still on patent, according to an expert.

Patents for several insulin formulations--both regular and NPH--have expired in this decade: Humulin (Eli Lilly & Co.) in 2001 and Novo-Nordisk's Novolin in 2005. However, the Food and Drug Administration has not issued its in-progress guidelines for approval of several new follow-on biologics, each of which is claimed by its manufacturer to contain the identical active ingredient as the approved product and therefore, they argue, should not need additional testing.

Debate remains as to whether existing regulations would or should allow for approval of such products. Applications for new biologics are regulated by the 1944 Public Health Service Act. However, small-molecule drug products are regulated by the Food, Drug, and Cosmetic Act of 1938, which allows accelerated approval of new drugs based on prior evidence.

In 2006, the FDA approved a follow-on of the recombinant human growth hormone Omnitrope, manufactured by Sandoz, but the agency said it considered that product to be not a generic but a “follow-on protein product,” because it had made no determination of therapeutic equivalence.

According to the FDA, other proteins that have received fast-track approval in this manner include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) nasal spray. A member of his staff confirmed that Rep. Henry Waxman (D-Calif.) will reintroduce a bill submitted last session, H.R. 6257, that would effectively force the FDA to fast-track approvals of follow-on generic biologics--a bill that some believe will lead to the production of generic insulins and thus lower costs for state governments and insurers. The date of reintroduction has not been determined, the staff member said.

A Senate version of the same bill, S. 4016, was sponsored by Sen. Hillary Clinton (D-N.Y.), with Sen. Charles Schumer (D-N.Y.), Sen. Patrick Leahy (D-Vt.), and Sen. Debbie Stabenow (D-Mich.) as cosponsors. In each house of Congress, the bill was referred to committee but expired in December, when the 109th Congress ended, as do all pending bills not passed before the end of a session.

Dr. Bill Law Jr., an endocrinologist in private practice in Knoxville, Tenn., said in an interview that confusion in the lay media about the difference between nonanalogue human insulins and analogue human insulins is behind these legislative efforts and public support for them.

“It's only after the 20-year patent law has expired [on a human analogue insulin] that it would be eligible for a generic company to come in and make one,” he noted. And as to the nonanalogue varieties, “unless the companies can sell one for less than $16 a vial, it's not going to change the cost” to the patient, he said. This confusion has given rise to false hopes for a drastic reduction in insulin costs for most patients, according to Dr. Law.

Regarding approval of follow-on biologics, “this is not like creating a pill,” wherein only the active ingredient is important, he added. “Everything else that's in that pill was specifically added by the manufacturer of that pill, whereas the insulin we're talking about is a biologic system,” and thus cellular byproducts can't be as easily modulated. “It's totally different from making a pill, where you have complete control over what goes in that pill.”

Thus the safety of a generic biologic cannot be established as easily as that of a drug, Dr. Law said. “From my standpoint as a doctor treating patients, it's not enough just to show that in that bottle there's a certain amount of insulin. I want to know what else is in that bottle.”

A pediatric dosing chart for the influenza drug oseltamivir (Tamiflu) sent by Roche Laboratories Inc. to health care providers last November contained an error and should have indicated a standard dosage of once daily—rather than twice daily—for 10 days, according to a letter from the company.

The erroneous chart, titled “Standard Dosage of the Tamiflu Oral Suspension for Prophylaxis of Influenza in Pediatric Patients,” had accompanied a Nov. 13 letter announcing that reports of self-injury and delirium in patients taking Tamiflu had been added to the precautions section of the product's package insert.

The company urges medical professionals to discard the incorrect chart.

The letter from Roche noted that none of the Tamiflu on the market contains package inserts with the incorrect dosage chart. Complete prescribing information is available online at www.rocheusa.com/products/tamiflu/pi.pdf

A pediatric dosing chart for the influenza drug oseltamivir (Tamiflu) sent by Roche Laboratories Inc. to health care providers last November contained an error and should have indicated a standard dosage of once daily—rather than twice daily—for 10 days, according to a letter from the company.

The erroneous chart, titled “Standard Dosage of the Tamiflu Oral Suspension for Prophylaxis of Influenza in Pediatric Patients,” had accompanied a Nov. 13 letter announcing that reports of self-injury and delirium in patients taking Tamiflu had been added to the precautions section of the product's package insert.

The company urges medical professionals to discard the incorrect chart.

The letter from Roche noted that none of the Tamiflu on the market contains package inserts with the incorrect dosage chart. Complete prescribing information is available online at www.rocheusa.com/products/tamiflu/pi.pdf

A pediatric dosing chart for the influenza drug oseltamivir (Tamiflu) sent by Roche Laboratories Inc. to health care providers last November contained an error and should have indicated a standard dosage of once daily—rather than twice daily—for 10 days, according to a letter from the company.

The erroneous chart, titled “Standard Dosage of the Tamiflu Oral Suspension for Prophylaxis of Influenza in Pediatric Patients,” had accompanied a Nov. 13 letter announcing that reports of self-injury and delirium in patients taking Tamiflu had been added to the precautions section of the product's package insert.

The company urges medical professionals to discard the incorrect chart.

The letter from Roche noted that none of the Tamiflu on the market contains package inserts with the incorrect dosage chart. Complete prescribing information is available online at www.rocheusa.com/products/tamiflu/pi.pdf

NASHVILLE, TENN. — Postmenopausal women with a history of gastrointestinal side effects on bisphosphonate therapy had a decline in GI symptoms after 6 months of either oral or intravenous ibandronate, although the decline was more pronounced with the intravenous drug, according to interim results presented at the annual meeting of the North American Menopause Society.

Dr. Mark Martens of the University of Oklahoma, Tulsa, reported 6-month data from the ongoing 12-month PRIOR study, which is assessing the tolerability of ibandronate (Boniva) in women with a history of daily or weekly bisphosphonate treatment for osteoporosis or osteopenia.

This trial is not randomized; the patients initially requested either 150-mg ibandronate orally once a month or quarterly intravenous 3-mg ibandronate, and they have the option of switching to the other arm if they experience side effects but may do so only once. The study initially enrolled 546 patients. Patients are assessed every 3 months.

Among 146 patients initially in the oral group, 11 (7.5%) switched to intravenous treatment, and 15 (3.8%) of 396 patients in the intravenous group chose to switch to the oral arm, Dr. Martens said.

Serious adverse events were reported by 4% of all patients—4% of the oral group and 3% of those on the intravenous treatment.

Dr. Martens reported that the total change from baseline in GI tolerance scores was 130 at month 1 for the oral group and 377 at month 1 for the intravenous group.

The primary diagnosis was osteoporosis for 85 patients in the oral group (58%) and 281 patients in the intravenous group (71%). Osteopenia was the primary diagnosis for 61 patients (42%) in the oral group and 115 patients (29%) in the intravenous group.

Dr. Martens disclosed that he has received financial support from GlaxoSmithKline, Procter and Gamble, Merck & Co., and Eli Lilly.

NASHVILLE, TENN. — Postmenopausal women with a history of gastrointestinal side effects on bisphosphonate therapy had a decline in GI symptoms after 6 months of either oral or intravenous ibandronate, although the decline was more pronounced with the intravenous drug, according to interim results presented at the annual meeting of the North American Menopause Society.

Dr. Mark Martens of the University of Oklahoma, Tulsa, reported 6-month data from the ongoing 12-month PRIOR study, which is assessing the tolerability of ibandronate (Boniva) in women with a history of daily or weekly bisphosphonate treatment for osteoporosis or osteopenia.

This trial is not randomized; the patients initially requested either 150-mg ibandronate orally once a month or quarterly intravenous 3-mg ibandronate, and they have the option of switching to the other arm if they experience side effects but may do so only once. The study initially enrolled 546 patients. Patients are assessed every 3 months.

Among 146 patients initially in the oral group, 11 (7.5%) switched to intravenous treatment, and 15 (3.8%) of 396 patients in the intravenous group chose to switch to the oral arm, Dr. Martens said.

Serious adverse events were reported by 4% of all patients—4% of the oral group and 3% of those on the intravenous treatment.

Dr. Martens reported that the total change from baseline in GI tolerance scores was 130 at month 1 for the oral group and 377 at month 1 for the intravenous group.

The primary diagnosis was osteoporosis for 85 patients in the oral group (58%) and 281 patients in the intravenous group (71%). Osteopenia was the primary diagnosis for 61 patients (42%) in the oral group and 115 patients (29%) in the intravenous group.

Dr. Martens disclosed that he has received financial support from GlaxoSmithKline, Procter and Gamble, Merck & Co., and Eli Lilly.

NASHVILLE, TENN. — Postmenopausal women with a history of gastrointestinal side effects on bisphosphonate therapy had a decline in GI symptoms after 6 months of either oral or intravenous ibandronate, although the decline was more pronounced with the intravenous drug, according to interim results presented at the annual meeting of the North American Menopause Society.

Dr. Mark Martens of the University of Oklahoma, Tulsa, reported 6-month data from the ongoing 12-month PRIOR study, which is assessing the tolerability of ibandronate (Boniva) in women with a history of daily or weekly bisphosphonate treatment for osteoporosis or osteopenia.

This trial is not randomized; the patients initially requested either 150-mg ibandronate orally once a month or quarterly intravenous 3-mg ibandronate, and they have the option of switching to the other arm if they experience side effects but may do so only once. The study initially enrolled 546 patients. Patients are assessed every 3 months.

Among 146 patients initially in the oral group, 11 (7.5%) switched to intravenous treatment, and 15 (3.8%) of 396 patients in the intravenous group chose to switch to the oral arm, Dr. Martens said.

Serious adverse events were reported by 4% of all patients—4% of the oral group and 3% of those on the intravenous treatment.

Dr. Martens reported that the total change from baseline in GI tolerance scores was 130 at month 1 for the oral group and 377 at month 1 for the intravenous group.

The primary diagnosis was osteoporosis for 85 patients in the oral group (58%) and 281 patients in the intravenous group (71%). Osteopenia was the primary diagnosis for 61 patients (42%) in the oral group and 115 patients (29%) in the intravenous group.

Dr. Martens disclosed that he has received financial support from GlaxoSmithKline, Procter and Gamble, Merck & Co., and Eli Lilly.

NASHVILLE, TENN. — Cervical polyps in postmenopausal women might pose lower risk of malignancy, dysplasia, and atypia than those found in premenopausal women, according to a study presented at the annual meeting of the North American Menopause Society.

Dr. Peter F. Schnatz of the University of Connecticut, Farmington, and his colleagues searched a pathology database for cases of endocervical polyp excision recorded over a 5-year period. A total of 1,993 polyps were found. Mean patient age was 48 years (range 16–95 years), and most came from private ob.gyn. practices.

For women younger than 50 years, the investigators found an incidence for malignancy, dysplasia, and atypia of 0.18%, 0.70%, and 2.1%, respectively. For women at least 50 years old, the incidence rates were 0.12%, 0.24%, and 1.2%. Although the differences between the two age groups for each individual prevalence did not reach statistical significance, the overall difference in the prevalence of any of the three abnormalities (3% for younger women vs. 1.5% in the older group) did reach significance (P = .03). There were two malignancies reported, with one in each age group.

Dr. Schnatz said that the findings of low prevalence of abnormalities for cervical polyps should reassure patients. Moreover, “routine removal is reasonable, given the high likelihood of symptoms, the small possibility of malignancy or transformation to malignancy, and the potential marker for uterine or extrauterine disease, as well as the ease of removal,” he said.

He noted that polyps are the most common benign neoplastic growth in the cervix; are found in roughly 5% of women, most commonly in multiparous women older than 20 years; and are rare before menarche.

NASHVILLE, TENN. — Cervical polyps in postmenopausal women might pose lower risk of malignancy, dysplasia, and atypia than those found in premenopausal women, according to a study presented at the annual meeting of the North American Menopause Society.

Dr. Peter F. Schnatz of the University of Connecticut, Farmington, and his colleagues searched a pathology database for cases of endocervical polyp excision recorded over a 5-year period. A total of 1,993 polyps were found. Mean patient age was 48 years (range 16–95 years), and most came from private ob.gyn. practices.

For women younger than 50 years, the investigators found an incidence for malignancy, dysplasia, and atypia of 0.18%, 0.70%, and 2.1%, respectively. For women at least 50 years old, the incidence rates were 0.12%, 0.24%, and 1.2%. Although the differences between the two age groups for each individual prevalence did not reach statistical significance, the overall difference in the prevalence of any of the three abnormalities (3% for younger women vs. 1.5% in the older group) did reach significance (P = .03). There were two malignancies reported, with one in each age group.

Dr. Schnatz said that the findings of low prevalence of abnormalities for cervical polyps should reassure patients. Moreover, “routine removal is reasonable, given the high likelihood of symptoms, the small possibility of malignancy or transformation to malignancy, and the potential marker for uterine or extrauterine disease, as well as the ease of removal,” he said.

He noted that polyps are the most common benign neoplastic growth in the cervix; are found in roughly 5% of women, most commonly in multiparous women older than 20 years; and are rare before menarche.

NASHVILLE, TENN. — Cervical polyps in postmenopausal women might pose lower risk of malignancy, dysplasia, and atypia than those found in premenopausal women, according to a study presented at the annual meeting of the North American Menopause Society.

Dr. Peter F. Schnatz of the University of Connecticut, Farmington, and his colleagues searched a pathology database for cases of endocervical polyp excision recorded over a 5-year period. A total of 1,993 polyps were found. Mean patient age was 48 years (range 16–95 years), and most came from private ob.gyn. practices.

For women younger than 50 years, the investigators found an incidence for malignancy, dysplasia, and atypia of 0.18%, 0.70%, and 2.1%, respectively. For women at least 50 years old, the incidence rates were 0.12%, 0.24%, and 1.2%. Although the differences between the two age groups for each individual prevalence did not reach statistical significance, the overall difference in the prevalence of any of the three abnormalities (3% for younger women vs. 1.5% in the older group) did reach significance (P = .03). There were two malignancies reported, with one in each age group.

Dr. Schnatz said that the findings of low prevalence of abnormalities for cervical polyps should reassure patients. Moreover, “routine removal is reasonable, given the high likelihood of symptoms, the small possibility of malignancy or transformation to malignancy, and the potential marker for uterine or extrauterine disease, as well as the ease of removal,” he said.

He noted that polyps are the most common benign neoplastic growth in the cervix; are found in roughly 5% of women, most commonly in multiparous women older than 20 years; and are rare before menarche.