Christine Kilgore

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogues,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogues, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15). Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007; 24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators in a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord to maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogues, or oral hypoglycemics could affect “in utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about insulinlike growth factor–I receptor affinity and increased mitogenic potency of some of the insulin analogues. “Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

He reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogues,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogues, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15). Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007; 24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators in a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord to maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogues, or oral hypoglycemics could affect “in utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about insulinlike growth factor–I receptor affinity and increased mitogenic potency of some of the insulin analogues. “Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

He reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogues,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogues, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15). Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007; 24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators in a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord to maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogues, or oral hypoglycemics could affect “in utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about insulinlike growth factor–I receptor affinity and increased mitogenic potency of some of the insulin analogues. “Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

He reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.

WASHINGTON – Recurring, uncomplicated urinary tract infections in female patients may be treated in the future through bacterial interference and other novel approaches, but for now, treatment involves an individualized approach with possible postcoital prophylaxis, chronic low-dose prophylaxis, or self-therapy, said urologist Robert M. Moldwin.

Addressing the case of a 35-year-old, otherwise-healthy woman who has had three culture-documented, symptomatic bacterial cystitis episodes over the last 3 months, Dr. Moldwin said that chronic low-dose prophylaxis may be considered when recurring infections are not related to intercourse.

Chronic prophylaxis should be reserved for frequently recurring infections, he emphasized, and the “goal is to grade down on the dose arbitrarily over a 6- to 12-month span, perhaps going to every other night or every third night, and then hopefully discontinuing this regime altogether,” he said during a panel discussion on UTIs at the meeting.

The two agents that are best supported in the literature for chronic low-dose prophylaxis are nitrofurantoin and methenamine hippurate. Trimethoprim-sulfamethoxazole and early generation cephalosporins “have also been espoused,” said Dr. Moldwin of Hofstra University, Hempstead, N.Y.

“Unfortunately, though,” he said, “recurrent infections are bound to show up at some point when prophylaxis is discontinued.”

Self-therapy can “really pay off” in cases in which infections are recurring less frequently, and it can also be “a great protocol to institute when one takes a patient off of antibiotic prophylaxis,” said Dr. Moldwin, also of the Arthur Smith Institute for Urology in New Hyde Park, N.Y.

In this scenario, the patient is armed with a sterile collection cup, a urinalysis and urine culture prescription, and a prescription for an antibiotic. “At the first sign of infection, the patient is instructed to obtain a midstream urine sample … and start [herself] on an appropriate course of an antibiotic,” he said. “Within 24-48 hours, the patient can bring the specimen to the local laboratory” and can have the results sent to her physician for analysis if symptoms don't resolve, he added.

Cranberry juice has been touted for UTI prevention because it contains various chemicals that may prevent bacterial adherence to the bladder wall. Evidence that was published several years ago concluded that “after many disclaimers, [there] is some evidence to recommend cranberry juice for the prevention of uncomplicated UTIs in women with symptomatic infections,” a randomized clinical trial published this year showed no difference in UTI recurrence between patients who used cranberry juice and those who used placebo (Clin. Infect. Dis. 2011;52:23-30), Dr. Moldwin said.

The trial of 319 college students is “the most recent and probably the best” that has been published to date, he said.

Oral

A Google search shows 45,000-61,000 hits, he said, but a Pub Med search on

Other forms of bacterial interference may prove efficacious, however. The use of vaginal or oral probiotics, for instance, or the introduction of nonpathogenic Escherichia coli “to the vaginal vault, the gut, or even the bladder itself” are among the “novel and viable options that we hope to see more work on in the future,” he said.

Dr. Moldwin disclosed that he is a consultant, adviser, or investigator for Ortho-McNeil Pharmaceuticals, Pfizer, and Pinnacle Pharmaceuticals.

There is some evidence to recommend cranberry juice for prevention of recurring uncomplicated UTIs.

Source ©Tarek El Sombati/iStockphoto.com

WASHINGTON – Recurring, uncomplicated urinary tract infections in female patients may be treated in the future through bacterial interference and other novel approaches, but for now, treatment involves an individualized approach with possible postcoital prophylaxis, chronic low-dose prophylaxis, or self-therapy, said urologist Robert M. Moldwin.

Addressing the case of a 35-year-old, otherwise-healthy woman who has had three culture-documented, symptomatic bacterial cystitis episodes over the last 3 months, Dr. Moldwin said that chronic low-dose prophylaxis may be considered when recurring infections are not related to intercourse.

Chronic prophylaxis should be reserved for frequently recurring infections, he emphasized, and the “goal is to grade down on the dose arbitrarily over a 6- to 12-month span, perhaps going to every other night or every third night, and then hopefully discontinuing this regime altogether,” he said during a panel discussion on UTIs at the meeting.

The two agents that are best supported in the literature for chronic low-dose prophylaxis are nitrofurantoin and methenamine hippurate. Trimethoprim-sulfamethoxazole and early generation cephalosporins “have also been espoused,” said Dr. Moldwin of Hofstra University, Hempstead, N.Y.

“Unfortunately, though,” he said, “recurrent infections are bound to show up at some point when prophylaxis is discontinued.”

Self-therapy can “really pay off” in cases in which infections are recurring less frequently, and it can also be “a great protocol to institute when one takes a patient off of antibiotic prophylaxis,” said Dr. Moldwin, also of the Arthur Smith Institute for Urology in New Hyde Park, N.Y.

In this scenario, the patient is armed with a sterile collection cup, a urinalysis and urine culture prescription, and a prescription for an antibiotic. “At the first sign of infection, the patient is instructed to obtain a midstream urine sample … and start [herself] on an appropriate course of an antibiotic,” he said. “Within 24-48 hours, the patient can bring the specimen to the local laboratory” and can have the results sent to her physician for analysis if symptoms don't resolve, he added.

Cranberry juice has been touted for UTI prevention because it contains various chemicals that may prevent bacterial adherence to the bladder wall. Evidence that was published several years ago concluded that “after many disclaimers, [there] is some evidence to recommend cranberry juice for the prevention of uncomplicated UTIs in women with symptomatic infections,” a randomized clinical trial published this year showed no difference in UTI recurrence between patients who used cranberry juice and those who used placebo (Clin. Infect. Dis. 2011;52:23-30), Dr. Moldwin said.

The trial of 319 college students is “the most recent and probably the best” that has been published to date, he said.

Oral

A Google search shows 45,000-61,000 hits, he said, but a Pub Med search on

Other forms of bacterial interference may prove efficacious, however. The use of vaginal or oral probiotics, for instance, or the introduction of nonpathogenic Escherichia coli “to the vaginal vault, the gut, or even the bladder itself” are among the “novel and viable options that we hope to see more work on in the future,” he said.

Dr. Moldwin disclosed that he is a consultant, adviser, or investigator for Ortho-McNeil Pharmaceuticals, Pfizer, and Pinnacle Pharmaceuticals.

There is some evidence to recommend cranberry juice for prevention of recurring uncomplicated UTIs.

Source ©Tarek El Sombati/iStockphoto.com

WASHINGTON – Recurring, uncomplicated urinary tract infections in female patients may be treated in the future through bacterial interference and other novel approaches, but for now, treatment involves an individualized approach with possible postcoital prophylaxis, chronic low-dose prophylaxis, or self-therapy, said urologist Robert M. Moldwin.

Addressing the case of a 35-year-old, otherwise-healthy woman who has had three culture-documented, symptomatic bacterial cystitis episodes over the last 3 months, Dr. Moldwin said that chronic low-dose prophylaxis may be considered when recurring infections are not related to intercourse.

Chronic prophylaxis should be reserved for frequently recurring infections, he emphasized, and the “goal is to grade down on the dose arbitrarily over a 6- to 12-month span, perhaps going to every other night or every third night, and then hopefully discontinuing this regime altogether,” he said during a panel discussion on UTIs at the meeting.

The two agents that are best supported in the literature for chronic low-dose prophylaxis are nitrofurantoin and methenamine hippurate. Trimethoprim-sulfamethoxazole and early generation cephalosporins “have also been espoused,” said Dr. Moldwin of Hofstra University, Hempstead, N.Y.

“Unfortunately, though,” he said, “recurrent infections are bound to show up at some point when prophylaxis is discontinued.”

Self-therapy can “really pay off” in cases in which infections are recurring less frequently, and it can also be “a great protocol to institute when one takes a patient off of antibiotic prophylaxis,” said Dr. Moldwin, also of the Arthur Smith Institute for Urology in New Hyde Park, N.Y.

In this scenario, the patient is armed with a sterile collection cup, a urinalysis and urine culture prescription, and a prescription for an antibiotic. “At the first sign of infection, the patient is instructed to obtain a midstream urine sample … and start [herself] on an appropriate course of an antibiotic,” he said. “Within 24-48 hours, the patient can bring the specimen to the local laboratory” and can have the results sent to her physician for analysis if symptoms don't resolve, he added.

Cranberry juice has been touted for UTI prevention because it contains various chemicals that may prevent bacterial adherence to the bladder wall. Evidence that was published several years ago concluded that “after many disclaimers, [there] is some evidence to recommend cranberry juice for the prevention of uncomplicated UTIs in women with symptomatic infections,” a randomized clinical trial published this year showed no difference in UTI recurrence between patients who used cranberry juice and those who used placebo (Clin. Infect. Dis. 2011;52:23-30), Dr. Moldwin said.

The trial of 319 college students is “the most recent and probably the best” that has been published to date, he said.

Oral

A Google search shows 45,000-61,000 hits, he said, but a Pub Med search on

Other forms of bacterial interference may prove efficacious, however. The use of vaginal or oral probiotics, for instance, or the introduction of nonpathogenic Escherichia coli “to the vaginal vault, the gut, or even the bladder itself” are among the “novel and viable options that we hope to see more work on in the future,” he said.

Dr. Moldwin disclosed that he is a consultant, adviser, or investigator for Ortho-McNeil Pharmaceuticals, Pfizer, and Pinnacle Pharmaceuticals.

There is some evidence to recommend cranberry juice for prevention of recurring uncomplicated UTIs.

Source ©Tarek El Sombati/iStockphoto.com

WASHINGTON – Research has documented a strong association between the formation of kidney stones and the presence or development of cardiovascular disease, metabolic syndrome, and a number of components of the metabolic syndrome, said Dr. Dean G. Assimos.

"There is increasing evidence" of this link, he noted at the annual meeting of the American Urological Association. "We need to be cognizant of these associations."

Most recently, an analysis of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that individuals who developed kidney stones had a 1.6-fold increased risk of developing subclinical carotid artery atherosclerosis, even after adjustments for major cardiovascular risk factors were made, said Dr. Assimos, professor of urology at Wake Forest University, Winston-Salem, N.C.

The longitudinal cohort study followed 5,115 white and black men and women who were 18-30 years old at the time of recruitment in 1985-1986. Carotid artery intima-media thickness was measured with serial ultrasound periodically throughout the observation period. By 20 years, almost 4% had reported having kidney stones, and kidney stones were associated with a 60% increased risk of carotid atherosclerosis (J. Urol. 2011;185:920-5). Kidney stones were associated with myocardial infarction (MI) in another recent study aimed specifically at assessing "the risk of a kidney stone former developing an MI," Dr. Assimos said. Investigators of this case-controlled study matched almost 4,600 stone formers on age and sex with almost 11,000 control subjects among residents of Olmstead County, Minn.

During a mean follow-up of 9 years, "despite controlling for other medical comorbidities," investigators found that "stone formers had a 31% increased risk of sustaining an MI," he said.

Chronic kidney disease, which itself is a risk factor for MI, was one of the comorbidities adjusted for (J. Am. Soc. Nephrol. 2010;21:1641-4).

Numerous studies published since 2005 have demonstrated positive associations between kidney stone formation and specific components of the metabolic syndrome, as well as with the full constellation of disorders, Dr. Assimos said.

An analysis of National Health and Nutrition Examination Survey III data published in 2008, for instance, showed that individuals with four traits of the metabolic syndrome had two times the risk of having a history of kidney stones (Am. J. Kidney Dis. 2008;51:741-7). The prevalence of self-reported history of kidney stones, moreover, increased as the number of traits or component disorders of the metabolic syndrome increased, from 3% with no disorders to 7.5% with three disorders, and to almost 10% with five disorders. (An individual must have at least three of the five component disorders to qualify as having the metabolic syndrome.)

Similarly, in an Italian study of hospitalized adults, more than 10% of 725 patients with metabolic syndrome had evidence of nephrolithiasis on renal ultrasound (Nephrol. Dial. Transplant 2009;24:900-6). "This is 10 times higher than [rates reported from] renal ultrasound screening studies done in the general population," Dr. Assimos said.

Data from three large cohorts – the Nurses’ Health Study (NHS) I of older women, the NHS II of younger women, and the Health Professionals Follow-Up Study (HPFS) of men aged 40-75 years – have been crucial in elucidating the associations between kidney stones and specific components of the metabolic syndrome.

In one prospective study of the cohorts that looked at the incidence of symptomatic kidney stones, for instance, investigators documented that the relative risk of an obese individual (body mass index, 30 kg/m² or greater) for kidney stone formation, compared with individuals with a BMI of 21-23, was 1.9 in the NHS I cohort, 2.09 in the NHS II cohort, and 1.33 in the HPFS cohort (JAMA 2005;293:455-62).

"There was also a positive correlation in all these cohorts with waist circumference," Dr. Assimos said.

Other analyses of these cohorts have documented positive associations between type 2 diabetes or hypertension, and incident kidney stone formation, as well as associations between a history of kidney stone formation and the diagnosis of diabetes or development of hypertension.

The causative factors underlying the associations between stone formation and cardiovascular disease and the metabolic syndrome include low urinary pH levels. At lower urinary pH levels, "more [of the body’s] uric acid is in its undissociated form and is insoluble in urine," for instance, which increases the risk of uric acid stone formation, Dr. Assimos said.

Studies have demonstrated a negative correlation between BMI and urinary pH, he noted. The reasons are not fully known, but "it is hypothesized that individuals [with higher BMI] do not produce ammonium effectively in the proximal tubule," he said.

Individuals with obesity and low urinary pH also excrete greater amounts of calcium and oxalate, and this increases the risk of calcium oxalate stone formation, he said.

Dr. Assimos’s own research team has identified a possible new pathway for the endogenous synthesis of oxalate. It involves the metabolism of glyoxal, which is stimulated by oxidative stress. The glyoxal metabolism "may explain the increased oxalate excretion in those with obesity as well as diabetes," he said.

The associations between kidney stone formation and cardiovascular risk have hit home for Dr. Assimos, he said at the end of his presentation. At age 39, he developed his first kidney stone. By 3 years later, he developed hypertension. "And 3 years ago. I started having symptoms of gastroesophageal reflux when exercising ... I had a stress test ... and here is my coronary arteriogram," he told the audience. The end result, he said, was successful coronary artery bypass grafting.

Dr. Assimos reported that he is an investigator for the National Institutes of Health and a partner at Piedmont Stone, a facility in Winston-Salem that provides lithotripsy procedures.

WASHINGTON – Research has documented a strong association between the formation of kidney stones and the presence or development of cardiovascular disease, metabolic syndrome, and a number of components of the metabolic syndrome, said Dr. Dean G. Assimos.

"There is increasing evidence" of this link, he noted at the annual meeting of the American Urological Association. "We need to be cognizant of these associations."

Most recently, an analysis of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that individuals who developed kidney stones had a 1.6-fold increased risk of developing subclinical carotid artery atherosclerosis, even after adjustments for major cardiovascular risk factors were made, said Dr. Assimos, professor of urology at Wake Forest University, Winston-Salem, N.C.

The longitudinal cohort study followed 5,115 white and black men and women who were 18-30 years old at the time of recruitment in 1985-1986. Carotid artery intima-media thickness was measured with serial ultrasound periodically throughout the observation period. By 20 years, almost 4% had reported having kidney stones, and kidney stones were associated with a 60% increased risk of carotid atherosclerosis (J. Urol. 2011;185:920-5). Kidney stones were associated with myocardial infarction (MI) in another recent study aimed specifically at assessing "the risk of a kidney stone former developing an MI," Dr. Assimos said. Investigators of this case-controlled study matched almost 4,600 stone formers on age and sex with almost 11,000 control subjects among residents of Olmstead County, Minn.

During a mean follow-up of 9 years, "despite controlling for other medical comorbidities," investigators found that "stone formers had a 31% increased risk of sustaining an MI," he said.

Chronic kidney disease, which itself is a risk factor for MI, was one of the comorbidities adjusted for (J. Am. Soc. Nephrol. 2010;21:1641-4).

Numerous studies published since 2005 have demonstrated positive associations between kidney stone formation and specific components of the metabolic syndrome, as well as with the full constellation of disorders, Dr. Assimos said.

An analysis of National Health and Nutrition Examination Survey III data published in 2008, for instance, showed that individuals with four traits of the metabolic syndrome had two times the risk of having a history of kidney stones (Am. J. Kidney Dis. 2008;51:741-7). The prevalence of self-reported history of kidney stones, moreover, increased as the number of traits or component disorders of the metabolic syndrome increased, from 3% with no disorders to 7.5% with three disorders, and to almost 10% with five disorders. (An individual must have at least three of the five component disorders to qualify as having the metabolic syndrome.)

Similarly, in an Italian study of hospitalized adults, more than 10% of 725 patients with metabolic syndrome had evidence of nephrolithiasis on renal ultrasound (Nephrol. Dial. Transplant 2009;24:900-6). "This is 10 times higher than [rates reported from] renal ultrasound screening studies done in the general population," Dr. Assimos said.

Data from three large cohorts – the Nurses’ Health Study (NHS) I of older women, the NHS II of younger women, and the Health Professionals Follow-Up Study (HPFS) of men aged 40-75 years – have been crucial in elucidating the associations between kidney stones and specific components of the metabolic syndrome.

In one prospective study of the cohorts that looked at the incidence of symptomatic kidney stones, for instance, investigators documented that the relative risk of an obese individual (body mass index, 30 kg/m² or greater) for kidney stone formation, compared with individuals with a BMI of 21-23, was 1.9 in the NHS I cohort, 2.09 in the NHS II cohort, and 1.33 in the HPFS cohort (JAMA 2005;293:455-62).

"There was also a positive correlation in all these cohorts with waist circumference," Dr. Assimos said.

Other analyses of these cohorts have documented positive associations between type 2 diabetes or hypertension, and incident kidney stone formation, as well as associations between a history of kidney stone formation and the diagnosis of diabetes or development of hypertension.

The causative factors underlying the associations between stone formation and cardiovascular disease and the metabolic syndrome include low urinary pH levels. At lower urinary pH levels, "more [of the body’s] uric acid is in its undissociated form and is insoluble in urine," for instance, which increases the risk of uric acid stone formation, Dr. Assimos said.

Studies have demonstrated a negative correlation between BMI and urinary pH, he noted. The reasons are not fully known, but "it is hypothesized that individuals [with higher BMI] do not produce ammonium effectively in the proximal tubule," he said.

Individuals with obesity and low urinary pH also excrete greater amounts of calcium and oxalate, and this increases the risk of calcium oxalate stone formation, he said.

Dr. Assimos’s own research team has identified a possible new pathway for the endogenous synthesis of oxalate. It involves the metabolism of glyoxal, which is stimulated by oxidative stress. The glyoxal metabolism "may explain the increased oxalate excretion in those with obesity as well as diabetes," he said.

The associations between kidney stone formation and cardiovascular risk have hit home for Dr. Assimos, he said at the end of his presentation. At age 39, he developed his first kidney stone. By 3 years later, he developed hypertension. "And 3 years ago. I started having symptoms of gastroesophageal reflux when exercising ... I had a stress test ... and here is my coronary arteriogram," he told the audience. The end result, he said, was successful coronary artery bypass grafting.

Dr. Assimos reported that he is an investigator for the National Institutes of Health and a partner at Piedmont Stone, a facility in Winston-Salem that provides lithotripsy procedures.

WASHINGTON – Research has documented a strong association between the formation of kidney stones and the presence or development of cardiovascular disease, metabolic syndrome, and a number of components of the metabolic syndrome, said Dr. Dean G. Assimos.

"There is increasing evidence" of this link, he noted at the annual meeting of the American Urological Association. "We need to be cognizant of these associations."

Most recently, an analysis of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that individuals who developed kidney stones had a 1.6-fold increased risk of developing subclinical carotid artery atherosclerosis, even after adjustments for major cardiovascular risk factors were made, said Dr. Assimos, professor of urology at Wake Forest University, Winston-Salem, N.C.

The longitudinal cohort study followed 5,115 white and black men and women who were 18-30 years old at the time of recruitment in 1985-1986. Carotid artery intima-media thickness was measured with serial ultrasound periodically throughout the observation period. By 20 years, almost 4% had reported having kidney stones, and kidney stones were associated with a 60% increased risk of carotid atherosclerosis (J. Urol. 2011;185:920-5). Kidney stones were associated with myocardial infarction (MI) in another recent study aimed specifically at assessing "the risk of a kidney stone former developing an MI," Dr. Assimos said. Investigators of this case-controlled study matched almost 4,600 stone formers on age and sex with almost 11,000 control subjects among residents of Olmstead County, Minn.

During a mean follow-up of 9 years, "despite controlling for other medical comorbidities," investigators found that "stone formers had a 31% increased risk of sustaining an MI," he said.

Chronic kidney disease, which itself is a risk factor for MI, was one of the comorbidities adjusted for (J. Am. Soc. Nephrol. 2010;21:1641-4).

Numerous studies published since 2005 have demonstrated positive associations between kidney stone formation and specific components of the metabolic syndrome, as well as with the full constellation of disorders, Dr. Assimos said.

An analysis of National Health and Nutrition Examination Survey III data published in 2008, for instance, showed that individuals with four traits of the metabolic syndrome had two times the risk of having a history of kidney stones (Am. J. Kidney Dis. 2008;51:741-7). The prevalence of self-reported history of kidney stones, moreover, increased as the number of traits or component disorders of the metabolic syndrome increased, from 3% with no disorders to 7.5% with three disorders, and to almost 10% with five disorders. (An individual must have at least three of the five component disorders to qualify as having the metabolic syndrome.)

Similarly, in an Italian study of hospitalized adults, more than 10% of 725 patients with metabolic syndrome had evidence of nephrolithiasis on renal ultrasound (Nephrol. Dial. Transplant 2009;24:900-6). "This is 10 times higher than [rates reported from] renal ultrasound screening studies done in the general population," Dr. Assimos said.

Data from three large cohorts – the Nurses’ Health Study (NHS) I of older women, the NHS II of younger women, and the Health Professionals Follow-Up Study (HPFS) of men aged 40-75 years – have been crucial in elucidating the associations between kidney stones and specific components of the metabolic syndrome.

In one prospective study of the cohorts that looked at the incidence of symptomatic kidney stones, for instance, investigators documented that the relative risk of an obese individual (body mass index, 30 kg/m² or greater) for kidney stone formation, compared with individuals with a BMI of 21-23, was 1.9 in the NHS I cohort, 2.09 in the NHS II cohort, and 1.33 in the HPFS cohort (JAMA 2005;293:455-62).

"There was also a positive correlation in all these cohorts with waist circumference," Dr. Assimos said.

Other analyses of these cohorts have documented positive associations between type 2 diabetes or hypertension, and incident kidney stone formation, as well as associations between a history of kidney stone formation and the diagnosis of diabetes or development of hypertension.

The causative factors underlying the associations between stone formation and cardiovascular disease and the metabolic syndrome include low urinary pH levels. At lower urinary pH levels, "more [of the body’s] uric acid is in its undissociated form and is insoluble in urine," for instance, which increases the risk of uric acid stone formation, Dr. Assimos said.

Studies have demonstrated a negative correlation between BMI and urinary pH, he noted. The reasons are not fully known, but "it is hypothesized that individuals [with higher BMI] do not produce ammonium effectively in the proximal tubule," he said.

Individuals with obesity and low urinary pH also excrete greater amounts of calcium and oxalate, and this increases the risk of calcium oxalate stone formation, he said.

Dr. Assimos’s own research team has identified a possible new pathway for the endogenous synthesis of oxalate. It involves the metabolism of glyoxal, which is stimulated by oxidative stress. The glyoxal metabolism "may explain the increased oxalate excretion in those with obesity as well as diabetes," he said.

The associations between kidney stone formation and cardiovascular risk have hit home for Dr. Assimos, he said at the end of his presentation. At age 39, he developed his first kidney stone. By 3 years later, he developed hypertension. "And 3 years ago. I started having symptoms of gastroesophageal reflux when exercising ... I had a stress test ... and here is my coronary arteriogram," he told the audience. The end result, he said, was successful coronary artery bypass grafting.

Dr. Assimos reported that he is an investigator for the National Institutes of Health and a partner at Piedmont Stone, a facility in Winston-Salem that provides lithotripsy procedures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting. Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well.”

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight. “Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carb diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors). Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting. Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well.”

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight. “Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carb diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors). Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting. Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well.”

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight. “Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carb diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors). Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Short-acting insulin analogues appear to be safe in insulin-requiring pregnancies and have clinical advantages, including increased freedom of meal timing, better matching of insulin dose with meal content, and improved glycemic control with a reduction in the frequency of hypoglyemic events, said Dr. Marshall W. Carpenter.

The analogues lispro (Humalog) and aspart (Novolog) may be advantageous, for instance, for the pregnant woman “with a toddler around who may not know when she is going to sit down to eat,” Dr. Carpenter said at the meeting.

“The benefit is reflected in the [higher, faster] peak insulin values seen with both lispro and aspart compared with human insulin,” said Dr. Carpenter of the department of obstetrics and gynecology at Tufts University, Boston.

Dr. Virginia R. Lupo, who chairs the department of obstetrics and gynecology at the Hennepin County Medical Center in Minneapolis, offered a different take on the utility of short-acting insulin analogues.

Diabetes disproportionately affects women who have annual household incomes below $25,000 and who are more likely to be black, Hispanic, American Indian, or Asian Pacific Islanders than white, she said. For many of these women, a regimen including short-acting insulin analogues is too complex for their lifestyle, eating habits, functional health literacy, and other life circumstances.

“A lot of my patients eat by grazing – there are no distinct meal times,” she said. And because of evening-long food availability and ingestion, these patients “require elevated basal insulin through the evenings.”

“I'm not convinced that insulin analogues are the right way to go,” she said. “I like the idea of NPH twice a day, before breakfast and before supper. It's better to take [insulin] twice a day than not take it five times a day.”

The utility of long-acting insulin analogues in pregnancy, Dr. Carpenter said, is still uncertain considering the lack of substantive real-life clinical experience with these analogues and the safety implications raised in the literature thus far. “And really,” he added in an interview after the meeting, “there's no evidence that glargine (Lantus) offers any benefit over NPH insulin – and NPH insulin is cheaper.”

Questions about the safety of analogues overall stem from the molecular modifications involved in their creation, and specifically the implications of modifying the C-terminal end of the insulin beta chain. Such modifications appear to increase affinity for the insulinlike growth factor–1 (IGF-1) receptor – a receptor that has “a broad array of effects,” from induction of mitogenesis and inhibition of apoptosis, to stimulation of angiogenesis, he said.

Analogues' increased “stimulation of [this receptor] has thus appropriately raised concerns about safety,” he said.

While the current safety profile of the short-acting analogues “suggests no independent effect on retinopathic change or carcinogenesis,” there is reason to be cautious about long-acting analogues until more data are available, he said.

A study published in 2000 comparing the toxicopharmacologic properties of insulin analogues showed that glargine had a six- to eightfold increase in IGF-1 receptor affinity and associated mitogenic potency compared with human insulin, he noted. The two rapidly acting insulin analogues resembled human insulin on all parameters, except for a slightly elevated IGF-1 receptor affinity for lispro (Diabetes 2000;49:999–1005).

A possible association of lispro with proliferative retinopathy was “put on the map” more than a decade ago when Dr. John L. Kitzmiller and his colleagues reported that 3 out of 10 lispro-treated patients with no detected background retinopathy progressed to proliferative retinopathy during pregnancy (Diabetes Care 1999;22:874–5), Dr. Carpenter said.

Studies and commentary since then have shown no adverse impact of insulin analogues on the progression of diabetic retinopathy in pregnant patients, he said. A Finnish study of 69 pregnant women treated with either lispro or conventional human insulin, for instance, showed no significant differences in retinopathy progression (Diabetes Care 2003;26:1193–8).

Experts have also noted that the hemaglobin A_1c levels in women in Dr. Kitzmiller's series were initially high, indicative of poor prepregnancy metabolic control, which raises the question of whether the rapid change to euglycemic control may have been the primary contributor to the advancing retinopathy among these patients rather than a specific lispro effect.

Regardless of insulin choice, rapid tightening of glycemic control is among the predictors of proliferative diabetic retinopathy during pregnancy, along with the duration of diabetes, HbA_1c or plasma glucose at the onset of care, and other factors, he said. “We really ought to have informed consent for the rapid achievement of normal blood sugars from a nonpregnant state to a pregnant state … for patients who are in denial before becoming pregnant, with very poor metabolic control, and who are then enlisted in very careful management to dramatically improve their glycemic control,” Dr. Carpenter said in an interview. “These are the patients we know are at risk of worsening retinopathy.”

Dr. Lupo and Dr. Carpenter said they had no relevant financial disclosures.

WASHINGTON – Short-acting insulin analogues appear to be safe in insulin-requiring pregnancies and have clinical advantages, including increased freedom of meal timing, better matching of insulin dose with meal content, and improved glycemic control with a reduction in the frequency of hypoglyemic events, said Dr. Marshall W. Carpenter.

The analogues lispro (Humalog) and aspart (Novolog) may be advantageous, for instance, for the pregnant woman “with a toddler around who may not know when she is going to sit down to eat,” Dr. Carpenter said at the meeting.

“The benefit is reflected in the [higher, faster] peak insulin values seen with both lispro and aspart compared with human insulin,” said Dr. Carpenter of the department of obstetrics and gynecology at Tufts University, Boston.

Dr. Virginia R. Lupo, who chairs the department of obstetrics and gynecology at the Hennepin County Medical Center in Minneapolis, offered a different take on the utility of short-acting insulin analogues.

Diabetes disproportionately affects women who have annual household incomes below $25,000 and who are more likely to be black, Hispanic, American Indian, or Asian Pacific Islanders than white, she said. For many of these women, a regimen including short-acting insulin analogues is too complex for their lifestyle, eating habits, functional health literacy, and other life circumstances.

“A lot of my patients eat by grazing – there are no distinct meal times,” she said. And because of evening-long food availability and ingestion, these patients “require elevated basal insulin through the evenings.”

“I'm not convinced that insulin analogues are the right way to go,” she said. “I like the idea of NPH twice a day, before breakfast and before supper. It's better to take [insulin] twice a day than not take it five times a day.”

The utility of long-acting insulin analogues in pregnancy, Dr. Carpenter said, is still uncertain considering the lack of substantive real-life clinical experience with these analogues and the safety implications raised in the literature thus far. “And really,” he added in an interview after the meeting, “there's no evidence that glargine (Lantus) offers any benefit over NPH insulin – and NPH insulin is cheaper.”

Questions about the safety of analogues overall stem from the molecular modifications involved in their creation, and specifically the implications of modifying the C-terminal end of the insulin beta chain. Such modifications appear to increase affinity for the insulinlike growth factor–1 (IGF-1) receptor – a receptor that has “a broad array of effects,” from induction of mitogenesis and inhibition of apoptosis, to stimulation of angiogenesis, he said.

Analogues' increased “stimulation of [this receptor] has thus appropriately raised concerns about safety,” he said.

While the current safety profile of the short-acting analogues “suggests no independent effect on retinopathic change or carcinogenesis,” there is reason to be cautious about long-acting analogues until more data are available, he said.

A study published in 2000 comparing the toxicopharmacologic properties of insulin analogues showed that glargine had a six- to eightfold increase in IGF-1 receptor affinity and associated mitogenic potency compared with human insulin, he noted. The two rapidly acting insulin analogues resembled human insulin on all parameters, except for a slightly elevated IGF-1 receptor affinity for lispro (Diabetes 2000;49:999–1005).

A possible association of lispro with proliferative retinopathy was “put on the map” more than a decade ago when Dr. John L. Kitzmiller and his colleagues reported that 3 out of 10 lispro-treated patients with no detected background retinopathy progressed to proliferative retinopathy during pregnancy (Diabetes Care 1999;22:874–5), Dr. Carpenter said.

Studies and commentary since then have shown no adverse impact of insulin analogues on the progression of diabetic retinopathy in pregnant patients, he said. A Finnish study of 69 pregnant women treated with either lispro or conventional human insulin, for instance, showed no significant differences in retinopathy progression (Diabetes Care 2003;26:1193–8).

Experts have also noted that the hemaglobin A_1c levels in women in Dr. Kitzmiller's series were initially high, indicative of poor prepregnancy metabolic control, which raises the question of whether the rapid change to euglycemic control may have been the primary contributor to the advancing retinopathy among these patients rather than a specific lispro effect.

Regardless of insulin choice, rapid tightening of glycemic control is among the predictors of proliferative diabetic retinopathy during pregnancy, along with the duration of diabetes, HbA_1c or plasma glucose at the onset of care, and other factors, he said. “We really ought to have informed consent for the rapid achievement of normal blood sugars from a nonpregnant state to a pregnant state … for patients who are in denial before becoming pregnant, with very poor metabolic control, and who are then enlisted in very careful management to dramatically improve their glycemic control,” Dr. Carpenter said in an interview. “These are the patients we know are at risk of worsening retinopathy.”

Dr. Lupo and Dr. Carpenter said they had no relevant financial disclosures.

WASHINGTON – Short-acting insulin analogues appear to be safe in insulin-requiring pregnancies and have clinical advantages, including increased freedom of meal timing, better matching of insulin dose with meal content, and improved glycemic control with a reduction in the frequency of hypoglyemic events, said Dr. Marshall W. Carpenter.

The analogues lispro (Humalog) and aspart (Novolog) may be advantageous, for instance, for the pregnant woman “with a toddler around who may not know when she is going to sit down to eat,” Dr. Carpenter said at the meeting.

“The benefit is reflected in the [higher, faster] peak insulin values seen with both lispro and aspart compared with human insulin,” said Dr. Carpenter of the department of obstetrics and gynecology at Tufts University, Boston.

Dr. Virginia R. Lupo, who chairs the department of obstetrics and gynecology at the Hennepin County Medical Center in Minneapolis, offered a different take on the utility of short-acting insulin analogues.

Diabetes disproportionately affects women who have annual household incomes below $25,000 and who are more likely to be black, Hispanic, American Indian, or Asian Pacific Islanders than white, she said. For many of these women, a regimen including short-acting insulin analogues is too complex for their lifestyle, eating habits, functional health literacy, and other life circumstances.

“A lot of my patients eat by grazing – there are no distinct meal times,” she said. And because of evening-long food availability and ingestion, these patients “require elevated basal insulin through the evenings.”

“I'm not convinced that insulin analogues are the right way to go,” she said. “I like the idea of NPH twice a day, before breakfast and before supper. It's better to take [insulin] twice a day than not take it five times a day.”

The utility of long-acting insulin analogues in pregnancy, Dr. Carpenter said, is still uncertain considering the lack of substantive real-life clinical experience with these analogues and the safety implications raised in the literature thus far. “And really,” he added in an interview after the meeting, “there's no evidence that glargine (Lantus) offers any benefit over NPH insulin – and NPH insulin is cheaper.”

Questions about the safety of analogues overall stem from the molecular modifications involved in their creation, and specifically the implications of modifying the C-terminal end of the insulin beta chain. Such modifications appear to increase affinity for the insulinlike growth factor–1 (IGF-1) receptor – a receptor that has “a broad array of effects,” from induction of mitogenesis and inhibition of apoptosis, to stimulation of angiogenesis, he said.

Analogues' increased “stimulation of [this receptor] has thus appropriately raised concerns about safety,” he said.

While the current safety profile of the short-acting analogues “suggests no independent effect on retinopathic change or carcinogenesis,” there is reason to be cautious about long-acting analogues until more data are available, he said.

A study published in 2000 comparing the toxicopharmacologic properties of insulin analogues showed that glargine had a six- to eightfold increase in IGF-1 receptor affinity and associated mitogenic potency compared with human insulin, he noted. The two rapidly acting insulin analogues resembled human insulin on all parameters, except for a slightly elevated IGF-1 receptor affinity for lispro (Diabetes 2000;49:999–1005).

A possible association of lispro with proliferative retinopathy was “put on the map” more than a decade ago when Dr. John L. Kitzmiller and his colleagues reported that 3 out of 10 lispro-treated patients with no detected background retinopathy progressed to proliferative retinopathy during pregnancy (Diabetes Care 1999;22:874–5), Dr. Carpenter said.

Studies and commentary since then have shown no adverse impact of insulin analogues on the progression of diabetic retinopathy in pregnant patients, he said. A Finnish study of 69 pregnant women treated with either lispro or conventional human insulin, for instance, showed no significant differences in retinopathy progression (Diabetes Care 2003;26:1193–8).

Experts have also noted that the hemaglobin A_1c levels in women in Dr. Kitzmiller's series were initially high, indicative of poor prepregnancy metabolic control, which raises the question of whether the rapid change to euglycemic control may have been the primary contributor to the advancing retinopathy among these patients rather than a specific lispro effect.

Regardless of insulin choice, rapid tightening of glycemic control is among the predictors of proliferative diabetic retinopathy during pregnancy, along with the duration of diabetes, HbA_1c or plasma glucose at the onset of care, and other factors, he said. “We really ought to have informed consent for the rapid achievement of normal blood sugars from a nonpregnant state to a pregnant state … for patients who are in denial before becoming pregnant, with very poor metabolic control, and who are then enlisted in very careful management to dramatically improve their glycemic control,” Dr. Carpenter said in an interview. “These are the patients we know are at risk of worsening retinopathy.”

Dr. Lupo and Dr. Carpenter said they had no relevant financial disclosures.

WASHINGTON – Trials of vaginal and urinary inserts are worthwhile for managing stress urinary incontinence in women who are young, women with episodic leakage related to certain activities, or in women who – for various reasons – are not yet ready for a surgical repair or are at high risk from any invasive procedure, Dr. Deborah J. Lightner said.

“It's unfortunate, but many women currently manage their incontinence with pads,” said Dr. Lightner during a discussion of office-based management of stress urinary incontinence (SUI) at the meeting.

The mainstay of SUI management is still active pelvic floor muscle training that's taught and done correctly. But when this is unsuccessful, and when no neurologic abnormalities are detected, pessaries and other inserts – in some cases, a simple tampon – deserve consideration, she said. Research has shown that many women buy pads and tampons for the purposes of helping with urinary leakage and that three-quarters of women who use a tampon or other vaginal insert for mild SUI will be dry with that insert. “Many women know about tampons [for this purpose], but if not, you can offer them a very simple management strategy,” she said.

A tampon may be the best option, for instance, for a 24-year-old woman who leaks when playing soccer and only rarely at other times, especially if pelvic floor management training has provided no relief and if she is planning to have children. “This is an incredibly common scenario. [Urinary leakage] is a real barrier to women's participation in high-impact activities and sports,” said Dr. Lightner, a professor of urology at the Mayo Clinic in Rochester, Minn.

Pessaries are widely available and mainly used for prolapse, but there are a variety of “highly effective” incontinence rings and dishes that provide external compression of the bladder neck, Dr. Lightner said.

Early discontinuation of pessaries and other inserts “can be expected in about one-third of patients [who try them], but when [the inserts] are well tolerated, there's very high long-term success,” she said.

Among women who were randomized to use an intravaginal pessary in the Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial, 63% were satisfied at 3 months, 33% had no bothersome SUI, and more than 50% had a greater than 75% reduction in their urinary leakage, she said. Results of the ATLAS trial were reported last year (Obstet. Gynecol. 2010;115:609–17).

Refitting of pessaries is not uncommon, she noted. (In the ATLAS trial, 47% of the patients assigned to the pessary group needing a refitting, and 92% were ultimately properly fitted.) Minor complications can also occur. In one retrospective study of 273 women fitted with a ring pessary, the rate of minor complications (vaginal bleeding, extrusion, severe vaginal discharge, pain, and constipation, in decreasing order) was a surprisingly high 56% (BJOG 2009;116:1715–21).

“Women will decide early on if this is the right option for them,” Dr. Lightner said. “And if it's not, they can move on to other therapies.”

Clinical experience over the past 2 decades with urethral inserts has been “somewhat challenging,” she said. Colonization and symptomatic urinary tract infections can occur with frequent or long-term use. Calcification and erosion also can occur, but “mainly with indwelling inserts, and not with episodic use.”

The reported continence rate with use of the FemSoft urethral insert – the only one currently available in the United States – is 93% at 48 months. Early discontinuation occurs in up to 40% of users, and UTIs occur in about one-third of patients. Still, with this “excellent” continence rate, the urethral insert may have a role for women who wish to postpone or avoid surgery, she said.

Pelvic floor muscle training – the first-line management option for SUI – is often inadequately taught to women, she emphasized. “It can't be effective it's not done correctly, so I'd have that as part of my physical exam … find out, what can she do with her pelvic floor?”

Dr. Lightner reported that she had no disclosures.

WASHINGTON – Trials of vaginal and urinary inserts are worthwhile for managing stress urinary incontinence in women who are young, women with episodic leakage related to certain activities, or in women who – for various reasons – are not yet ready for a surgical repair or are at high risk from any invasive procedure, Dr. Deborah J. Lightner said.

“It's unfortunate, but many women currently manage their incontinence with pads,” said Dr. Lightner during a discussion of office-based management of stress urinary incontinence (SUI) at the meeting.

The mainstay of SUI management is still active pelvic floor muscle training that's taught and done correctly. But when this is unsuccessful, and when no neurologic abnormalities are detected, pessaries and other inserts – in some cases, a simple tampon – deserve consideration, she said. Research has shown that many women buy pads and tampons for the purposes of helping with urinary leakage and that three-quarters of women who use a tampon or other vaginal insert for mild SUI will be dry with that insert. “Many women know about tampons [for this purpose], but if not, you can offer them a very simple management strategy,” she said.

A tampon may be the best option, for instance, for a 24-year-old woman who leaks when playing soccer and only rarely at other times, especially if pelvic floor management training has provided no relief and if she is planning to have children. “This is an incredibly common scenario. [Urinary leakage] is a real barrier to women's participation in high-impact activities and sports,” said Dr. Lightner, a professor of urology at the Mayo Clinic in Rochester, Minn.

Pessaries are widely available and mainly used for prolapse, but there are a variety of “highly effective” incontinence rings and dishes that provide external compression of the bladder neck, Dr. Lightner said.

Early discontinuation of pessaries and other inserts “can be expected in about one-third of patients [who try them], but when [the inserts] are well tolerated, there's very high long-term success,” she said.

Among women who were randomized to use an intravaginal pessary in the Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial, 63% were satisfied at 3 months, 33% had no bothersome SUI, and more than 50% had a greater than 75% reduction in their urinary leakage, she said. Results of the ATLAS trial were reported last year (Obstet. Gynecol. 2010;115:609–17).

Refitting of pessaries is not uncommon, she noted. (In the ATLAS trial, 47% of the patients assigned to the pessary group needing a refitting, and 92% were ultimately properly fitted.) Minor complications can also occur. In one retrospective study of 273 women fitted with a ring pessary, the rate of minor complications (vaginal bleeding, extrusion, severe vaginal discharge, pain, and constipation, in decreasing order) was a surprisingly high 56% (BJOG 2009;116:1715–21).

“Women will decide early on if this is the right option for them,” Dr. Lightner said. “And if it's not, they can move on to other therapies.”

Clinical experience over the past 2 decades with urethral inserts has been “somewhat challenging,” she said. Colonization and symptomatic urinary tract infections can occur with frequent or long-term use. Calcification and erosion also can occur, but “mainly with indwelling inserts, and not with episodic use.”

The reported continence rate with use of the FemSoft urethral insert – the only one currently available in the United States – is 93% at 48 months. Early discontinuation occurs in up to 40% of users, and UTIs occur in about one-third of patients. Still, with this “excellent” continence rate, the urethral insert may have a role for women who wish to postpone or avoid surgery, she said.

Pelvic floor muscle training – the first-line management option for SUI – is often inadequately taught to women, she emphasized. “It can't be effective it's not done correctly, so I'd have that as part of my physical exam … find out, what can she do with her pelvic floor?”

Dr. Lightner reported that she had no disclosures.

WASHINGTON – Trials of vaginal and urinary inserts are worthwhile for managing stress urinary incontinence in women who are young, women with episodic leakage related to certain activities, or in women who – for various reasons – are not yet ready for a surgical repair or are at high risk from any invasive procedure, Dr. Deborah J. Lightner said.

“It's unfortunate, but many women currently manage their incontinence with pads,” said Dr. Lightner during a discussion of office-based management of stress urinary incontinence (SUI) at the meeting.

The mainstay of SUI management is still active pelvic floor muscle training that's taught and done correctly. But when this is unsuccessful, and when no neurologic abnormalities are detected, pessaries and other inserts – in some cases, a simple tampon – deserve consideration, she said. Research has shown that many women buy pads and tampons for the purposes of helping with urinary leakage and that three-quarters of women who use a tampon or other vaginal insert for mild SUI will be dry with that insert. “Many women know about tampons [for this purpose], but if not, you can offer them a very simple management strategy,” she said.

A tampon may be the best option, for instance, for a 24-year-old woman who leaks when playing soccer and only rarely at other times, especially if pelvic floor management training has provided no relief and if she is planning to have children. “This is an incredibly common scenario. [Urinary leakage] is a real barrier to women's participation in high-impact activities and sports,” said Dr. Lightner, a professor of urology at the Mayo Clinic in Rochester, Minn.

Pessaries are widely available and mainly used for prolapse, but there are a variety of “highly effective” incontinence rings and dishes that provide external compression of the bladder neck, Dr. Lightner said.

Early discontinuation of pessaries and other inserts “can be expected in about one-third of patients [who try them], but when [the inserts] are well tolerated, there's very high long-term success,” she said.

Among women who were randomized to use an intravaginal pessary in the Ambulatory Treatments for Leakage Associated With Stress Incontinence (ATLAS) trial, 63% were satisfied at 3 months, 33% had no bothersome SUI, and more than 50% had a greater than 75% reduction in their urinary leakage, she said. Results of the ATLAS trial were reported last year (Obstet. Gynecol. 2010;115:609–17).

Refitting of pessaries is not uncommon, she noted. (In the ATLAS trial, 47% of the patients assigned to the pessary group needing a refitting, and 92% were ultimately properly fitted.) Minor complications can also occur. In one retrospective study of 273 women fitted with a ring pessary, the rate of minor complications (vaginal bleeding, extrusion, severe vaginal discharge, pain, and constipation, in decreasing order) was a surprisingly high 56% (BJOG 2009;116:1715–21).

“Women will decide early on if this is the right option for them,” Dr. Lightner said. “And if it's not, they can move on to other therapies.”

Clinical experience over the past 2 decades with urethral inserts has been “somewhat challenging,” she said. Colonization and symptomatic urinary tract infections can occur with frequent or long-term use. Calcification and erosion also can occur, but “mainly with indwelling inserts, and not with episodic use.”

The reported continence rate with use of the FemSoft urethral insert – the only one currently available in the United States – is 93% at 48 months. Early discontinuation occurs in up to 40% of users, and UTIs occur in about one-third of patients. Still, with this “excellent” continence rate, the urethral insert may have a role for women who wish to postpone or avoid surgery, she said.

Pelvic floor muscle training – the first-line management option for SUI – is often inadequately taught to women, she emphasized. “It can't be effective it's not done correctly, so I'd have that as part of my physical exam … find out, what can she do with her pelvic floor?”

Dr. Lightner reported that she had no disclosures.

WASHINGTON – How should one manage a 35-year-old woman with multiple sclerosis on self-clean intermittent catheterization who complains of pelvic pain and cloudy urine?

Such a patient with “neurogenic bladder” and possible urinary tract infection needs careful diagnosis, catheterization review, and possibly other management considerations, said Dr. Stephen R. Kraus during a panel discussion of recurrent UTIs at the meeting.

Patients with neurogenic bladder commonly have chronic bacteriuria and recurrent UTIs, and thus generally require a combination of bacteriuria and leukocyturia – as well as clinical symptoms or an increase in autonomic dysreflexia – for the initiation of empirical UTI therapy. Such criteria will help avoid unnecessary use of antibiotics.

“Original criteria were based on bacterial colonization counts but were criticized for being highly insensitive,” said Dr. Kraus, professor and vice chairman of the department of urology at the University of Texas, San Antonio.

Assuming the patient has already had a video urodynamic test, Dr. Kraus said, he would obtain a catheterized specimen for urinalysis, culture, and a sensitivity test; treat as needed; and then consider increasing her catheterization frequency. A trial of a hydrophilic catheter could also be considered in the context of recurrent UTIs, he said.

Various catheter modifications – from silver alloy catheters to antibiotic-impregnated catheters – have been used with some success in reducing the risk of UTIs, but “they carry their own problems such as cost, development of resistance, and even, as one study suggested, the possibility of silver toxicity,” Dr. Kraus said.

Two randomized, controlled trials have shown that hydrophilic catheters will reduce the risk of UTIs, compared with regular polyvinyl chloride catheters, he noted. Although the choice of single-use vs. reusable catheters is “always a point of contention,” several studies have “clearly” shown that clean intermittent catheterization (CIC) poses no greater risk of recurrent UTIs than do single-use catheters, he added.

Frequent changing of intermittent catheters can prevent biofilm development, and one study showed that UTI was five times less likely when CIC was performed six times per day rather than three times per day, he noted.

Routine chronic antibiotic prophylaxis should be avoided in patients with neurogenic bladder, he said, but a short course of antibiotics could be useful during the initial CIC period, and is certainly prudent before any invasive genitourinary procedures are performed.

Dr. Kraus said he is intrigued by the concept of a weekly oral cyclic antibiotic (WOCA) program that uses weekly alternating antibiotics as a prophylactic measure. In one 2-year trial of WOCA, investigators “saw dramatic reductions in UTIs (from 9.4 to 1.8 per patient year) … and most importantly, they did not see any change in the number of multidrug-resistant infections.”

As a final management option for the above-described patient, Dr. Kraus said he would consider injections of botulinum toxin (Botox). This approach “has exploded in the market for neurogenic bladder management, and it has been associated with a significant reduction in UTI at 6 months … presumably because the neurogenic bladder management is that much better.”

The term “neurogenic bladder,” Dr. Kraus noted, is one that's “not very precise.” For the purposes of his discussion, he defined it as a condition in which the bladder is affected by a neurologic process and has an impaired ability to store and empty urine.

Dr. Kraus disclosed that he is an investigator for the National Institute of Diabetes and Digestive and Kidney Diseases, a course director for Laborie (which manufactures catheters and other products for urinary and pelvic disorders), and a consultant/adviser for Pfizer.

WASHINGTON – How should one manage a 35-year-old woman with multiple sclerosis on self-clean intermittent catheterization who complains of pelvic pain and cloudy urine?

Such a patient with “neurogenic bladder” and possible urinary tract infection needs careful diagnosis, catheterization review, and possibly other management considerations, said Dr. Stephen R. Kraus during a panel discussion of recurrent UTIs at the meeting.

Patients with neurogenic bladder commonly have chronic bacteriuria and recurrent UTIs, and thus generally require a combination of bacteriuria and leukocyturia – as well as clinical symptoms or an increase in autonomic dysreflexia – for the initiation of empirical UTI therapy. Such criteria will help avoid unnecessary use of antibiotics.

“Original criteria were based on bacterial colonization counts but were criticized for being highly insensitive,” said Dr. Kraus, professor and vice chairman of the department of urology at the University of Texas, San Antonio.

Assuming the patient has already had a video urodynamic test, Dr. Kraus said, he would obtain a catheterized specimen for urinalysis, culture, and a sensitivity test; treat as needed; and then consider increasing her catheterization frequency. A trial of a hydrophilic catheter could also be considered in the context of recurrent UTIs, he said.

Various catheter modifications – from silver alloy catheters to antibiotic-impregnated catheters – have been used with some success in reducing the risk of UTIs, but “they carry their own problems such as cost, development of resistance, and even, as one study suggested, the possibility of silver toxicity,” Dr. Kraus said.

Two randomized, controlled trials have shown that hydrophilic catheters will reduce the risk of UTIs, compared with regular polyvinyl chloride catheters, he noted. Although the choice of single-use vs. reusable catheters is “always a point of contention,” several studies have “clearly” shown that clean intermittent catheterization (CIC) poses no greater risk of recurrent UTIs than do single-use catheters, he added.

Frequent changing of intermittent catheters can prevent biofilm development, and one study showed that UTI was five times less likely when CIC was performed six times per day rather than three times per day, he noted.

Routine chronic antibiotic prophylaxis should be avoided in patients with neurogenic bladder, he said, but a short course of antibiotics could be useful during the initial CIC period, and is certainly prudent before any invasive genitourinary procedures are performed.

Dr. Kraus said he is intrigued by the concept of a weekly oral cyclic antibiotic (WOCA) program that uses weekly alternating antibiotics as a prophylactic measure. In one 2-year trial of WOCA, investigators “saw dramatic reductions in UTIs (from 9.4 to 1.8 per patient year) … and most importantly, they did not see any change in the number of multidrug-resistant infections.”

As a final management option for the above-described patient, Dr. Kraus said he would consider injections of botulinum toxin (Botox). This approach “has exploded in the market for neurogenic bladder management, and it has been associated with a significant reduction in UTI at 6 months … presumably because the neurogenic bladder management is that much better.”

The term “neurogenic bladder,” Dr. Kraus noted, is one that's “not very precise.” For the purposes of his discussion, he defined it as a condition in which the bladder is affected by a neurologic process and has an impaired ability to store and empty urine.

Dr. Kraus disclosed that he is an investigator for the National Institute of Diabetes and Digestive and Kidney Diseases, a course director for Laborie (which manufactures catheters and other products for urinary and pelvic disorders), and a consultant/adviser for Pfizer.

WASHINGTON – How should one manage a 35-year-old woman with multiple sclerosis on self-clean intermittent catheterization who complains of pelvic pain and cloudy urine?

Such a patient with “neurogenic bladder” and possible urinary tract infection needs careful diagnosis, catheterization review, and possibly other management considerations, said Dr. Stephen R. Kraus during a panel discussion of recurrent UTIs at the meeting.

Patients with neurogenic bladder commonly have chronic bacteriuria and recurrent UTIs, and thus generally require a combination of bacteriuria and leukocyturia – as well as clinical symptoms or an increase in autonomic dysreflexia – for the initiation of empirical UTI therapy. Such criteria will help avoid unnecessary use of antibiotics.

“Original criteria were based on bacterial colonization counts but were criticized for being highly insensitive,” said Dr. Kraus, professor and vice chairman of the department of urology at the University of Texas, San Antonio.

Assuming the patient has already had a video urodynamic test, Dr. Kraus said, he would obtain a catheterized specimen for urinalysis, culture, and a sensitivity test; treat as needed; and then consider increasing her catheterization frequency. A trial of a hydrophilic catheter could also be considered in the context of recurrent UTIs, he said.

Various catheter modifications – from silver alloy catheters to antibiotic-impregnated catheters – have been used with some success in reducing the risk of UTIs, but “they carry their own problems such as cost, development of resistance, and even, as one study suggested, the possibility of silver toxicity,” Dr. Kraus said.

Two randomized, controlled trials have shown that hydrophilic catheters will reduce the risk of UTIs, compared with regular polyvinyl chloride catheters, he noted. Although the choice of single-use vs. reusable catheters is “always a point of contention,” several studies have “clearly” shown that clean intermittent catheterization (CIC) poses no greater risk of recurrent UTIs than do single-use catheters, he added.

Frequent changing of intermittent catheters can prevent biofilm development, and one study showed that UTI was five times less likely when CIC was performed six times per day rather than three times per day, he noted.

Routine chronic antibiotic prophylaxis should be avoided in patients with neurogenic bladder, he said, but a short course of antibiotics could be useful during the initial CIC period, and is certainly prudent before any invasive genitourinary procedures are performed.

Dr. Kraus said he is intrigued by the concept of a weekly oral cyclic antibiotic (WOCA) program that uses weekly alternating antibiotics as a prophylactic measure. In one 2-year trial of WOCA, investigators “saw dramatic reductions in UTIs (from 9.4 to 1.8 per patient year) … and most importantly, they did not see any change in the number of multidrug-resistant infections.”

As a final management option for the above-described patient, Dr. Kraus said he would consider injections of botulinum toxin (Botox). This approach “has exploded in the market for neurogenic bladder management, and it has been associated with a significant reduction in UTI at 6 months … presumably because the neurogenic bladder management is that much better.”

The term “neurogenic bladder,” Dr. Kraus noted, is one that's “not very precise.” For the purposes of his discussion, he defined it as a condition in which the bladder is affected by a neurologic process and has an impaired ability to store and empty urine.

Dr. Kraus disclosed that he is an investigator for the National Institute of Diabetes and Digestive and Kidney Diseases, a course director for Laborie (which manufactures catheters and other products for urinary and pelvic disorders), and a consultant/adviser for Pfizer.

WASHINGTON – Rapid molecular diagnosis of urinary tract infection will soon enable individualized, evidence-based selection of antibiotics “right at the point of care,” according to Dr. Joseph C. Liao.

“Currently we rely on urine culture, which takes 2–3 days at a central microbiology laboratory,” he said. “What if in the future [you] could obtain molecular diagnosis in less than 1 hour right there in your office? And what if we could tailor the choice of antibiotics for the patient sitting in your office [rather than start broad-spectrum antibiotics empirically]?”

Personalized, evidence-based selection of antibiotics has become an increasingly important goal – for both individual and public health – as the problem of antibiotic resistance has intensified, said Dr. Liao and other speakers at the meeting.

Over the past several years, Dr. Liao and his colleagues in the urology department at Stanford (Calif.) University have used biosensor technology to develop an assay for rapid pathogen identification, as well as a biosensor-based antimicrobial susceptibility test for urinary tract infection (UTI).

“We've been able to achieve pathogen identification within an hour, and antimicrobial susceptibility testing within 3 hours,” Dr. Liao reported.

The biosensor (a molecular sensing device that generates a measurable signal in the presence of a target analyte) is already part of everyday clinical practice, he noted. The glucose sensor and the i-STAT portable clinical analyzer, for example, are commonly used biosensor-based devices.

The biosensor being utilized in the “next generation” of UTI diagnostic tools is composed of a chip about the size of a microscope slide with 16 individual sensors. “Like computer technology, it can be mass produced at a relatively low cost,” said Dr. Liao, who is also chief urologist at the Veterans Affairs Palo Alto (Calif.) Health Care System.

The overall strategy for pathogen identification involves lysis of the bacteria present in a urine sample, followed by a hybridization process that enables the sensor to detect bacterial 16S rRNA, a kind of “bacterial molecular fingerprint.” This results in a signal output.

“Essentially, we're converting a molecular hybridization event into an electrical signal,” Dr. Liao explained. “And the higher the bacterial concentration, the higher the signal.”

Bacterial 16S rRNA is also a marker of bacterial growth, a property that Dr. Liao's research group has exploited to develop a biosensor-based antimicrobial susceptibility test (AST).

By incubating a urine sample in the presence or absence of commonly used antibiotics, and quantifying the 16S rRNA level, “we can follow the differential growth and derive the AST,” he said.

Dr. Liao and his colleagues recently completed a clinical validation study in which they compared results from their biosensor platform with results from standard microbiological analysis in more than 200 urine samples collected from patients at the Spinal Cord Injury Service at the Veterans Affairs Palo Alto system.

Pathogen detection sensitivity and specificity were 92% and 97%, respectively, and “in corresponding AST, we found an overall agreement of 94%,” said Dr. Liao, whose study was published early this year (J. Urol. 2011;185:148–53).

In the future, Dr. Liao hopes to use biosensor technology to also detect biomarkers that are shown to be indicative of infection in the presence of pathogens, he said.

Such an integrated assay would detect both biomarkers and pathogens, and thus address the host immunity response as well as identify the pathogen.

This could further improve the now-challenging task of differentiating colonization, simple UTI, and early complicated UTI, “and [could] help us better differentiate and stratify the severity of infection,” he said.

Dr. Liao reported that he had no disclosures.

WASHINGTON – Rapid molecular diagnosis of urinary tract infection will soon enable individualized, evidence-based selection of antibiotics “right at the point of care,” according to Dr. Joseph C. Liao.

“Currently we rely on urine culture, which takes 2–3 days at a central microbiology laboratory,” he said. “What if in the future [you] could obtain molecular diagnosis in less than 1 hour right there in your office? And what if we could tailor the choice of antibiotics for the patient sitting in your office [rather than start broad-spectrum antibiotics empirically]?”

Personalized, evidence-based selection of antibiotics has become an increasingly important goal – for both individual and public health – as the problem of antibiotic resistance has intensified, said Dr. Liao and other speakers at the meeting.

Over the past several years, Dr. Liao and his colleagues in the urology department at Stanford (Calif.) University have used biosensor technology to develop an assay for rapid pathogen identification, as well as a biosensor-based antimicrobial susceptibility test for urinary tract infection (UTI).

“We've been able to achieve pathogen identification within an hour, and antimicrobial susceptibility testing within 3 hours,” Dr. Liao reported.

The biosensor (a molecular sensing device that generates a measurable signal in the presence of a target analyte) is already part of everyday clinical practice, he noted. The glucose sensor and the i-STAT portable clinical analyzer, for example, are commonly used biosensor-based devices.

The biosensor being utilized in the “next generation” of UTI diagnostic tools is composed of a chip about the size of a microscope slide with 16 individual sensors. “Like computer technology, it can be mass produced at a relatively low cost,” said Dr. Liao, who is also chief urologist at the Veterans Affairs Palo Alto (Calif.) Health Care System.

The overall strategy for pathogen identification involves lysis of the bacteria present in a urine sample, followed by a hybridization process that enables the sensor to detect bacterial 16S rRNA, a kind of “bacterial molecular fingerprint.” This results in a signal output.

“Essentially, we're converting a molecular hybridization event into an electrical signal,” Dr. Liao explained. “And the higher the bacterial concentration, the higher the signal.”

Bacterial 16S rRNA is also a marker of bacterial growth, a property that Dr. Liao's research group has exploited to develop a biosensor-based antimicrobial susceptibility test (AST).

By incubating a urine sample in the presence or absence of commonly used antibiotics, and quantifying the 16S rRNA level, “we can follow the differential growth and derive the AST,” he said.

Dr. Liao and his colleagues recently completed a clinical validation study in which they compared results from their biosensor platform with results from standard microbiological analysis in more than 200 urine samples collected from patients at the Spinal Cord Injury Service at the Veterans Affairs Palo Alto system.

Pathogen detection sensitivity and specificity were 92% and 97%, respectively, and “in corresponding AST, we found an overall agreement of 94%,” said Dr. Liao, whose study was published early this year (J. Urol. 2011;185:148–53).

In the future, Dr. Liao hopes to use biosensor technology to also detect biomarkers that are shown to be indicative of infection in the presence of pathogens, he said.

Such an integrated assay would detect both biomarkers and pathogens, and thus address the host immunity response as well as identify the pathogen.

This could further improve the now-challenging task of differentiating colonization, simple UTI, and early complicated UTI, “and [could] help us better differentiate and stratify the severity of infection,” he said.

Dr. Liao reported that he had no disclosures.

WASHINGTON – Rapid molecular diagnosis of urinary tract infection will soon enable individualized, evidence-based selection of antibiotics “right at the point of care,” according to Dr. Joseph C. Liao.

“Currently we rely on urine culture, which takes 2–3 days at a central microbiology laboratory,” he said. “What if in the future [you] could obtain molecular diagnosis in less than 1 hour right there in your office? And what if we could tailor the choice of antibiotics for the patient sitting in your office [rather than start broad-spectrum antibiotics empirically]?”

Personalized, evidence-based selection of antibiotics has become an increasingly important goal – for both individual and public health – as the problem of antibiotic resistance has intensified, said Dr. Liao and other speakers at the meeting.

Over the past several years, Dr. Liao and his colleagues in the urology department at Stanford (Calif.) University have used biosensor technology to develop an assay for rapid pathogen identification, as well as a biosensor-based antimicrobial susceptibility test for urinary tract infection (UTI).

“We've been able to achieve pathogen identification within an hour, and antimicrobial susceptibility testing within 3 hours,” Dr. Liao reported.

The biosensor (a molecular sensing device that generates a measurable signal in the presence of a target analyte) is already part of everyday clinical practice, he noted. The glucose sensor and the i-STAT portable clinical analyzer, for example, are commonly used biosensor-based devices.

The biosensor being utilized in the “next generation” of UTI diagnostic tools is composed of a chip about the size of a microscope slide with 16 individual sensors. “Like computer technology, it can be mass produced at a relatively low cost,” said Dr. Liao, who is also chief urologist at the Veterans Affairs Palo Alto (Calif.) Health Care System.

The overall strategy for pathogen identification involves lysis of the bacteria present in a urine sample, followed by a hybridization process that enables the sensor to detect bacterial 16S rRNA, a kind of “bacterial molecular fingerprint.” This results in a signal output.

“Essentially, we're converting a molecular hybridization event into an electrical signal,” Dr. Liao explained. “And the higher the bacterial concentration, the higher the signal.”

Bacterial 16S rRNA is also a marker of bacterial growth, a property that Dr. Liao's research group has exploited to develop a biosensor-based antimicrobial susceptibility test (AST).

By incubating a urine sample in the presence or absence of commonly used antibiotics, and quantifying the 16S rRNA level, “we can follow the differential growth and derive the AST,” he said.

Dr. Liao and his colleagues recently completed a clinical validation study in which they compared results from their biosensor platform with results from standard microbiological analysis in more than 200 urine samples collected from patients at the Spinal Cord Injury Service at the Veterans Affairs Palo Alto system.

Pathogen detection sensitivity and specificity were 92% and 97%, respectively, and “in corresponding AST, we found an overall agreement of 94%,” said Dr. Liao, whose study was published early this year (J. Urol. 2011;185:148–53).

In the future, Dr. Liao hopes to use biosensor technology to also detect biomarkers that are shown to be indicative of infection in the presence of pathogens, he said.

Such an integrated assay would detect both biomarkers and pathogens, and thus address the host immunity response as well as identify the pathogen.

This could further improve the now-challenging task of differentiating colonization, simple UTI, and early complicated UTI, “and [could] help us better differentiate and stratify the severity of infection,” he said.

Dr. Liao reported that he had no disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D.

“The more comprehensive the approach, the more adherence can be improved,” she said at the meeting.

The typical response to treatment failures is changing the drug choice or dosing; that's a mistake, she said. It would be better to assess adherence. “All patients are candidates for adherence facilitation.”

Dr. Rains suggested the following strategies for boosting adherence to headache therapy:

▸ Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. “Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens],” she said.

▸ Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

▸ Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side effects. Differentiating current treatment from past failures is key, Dr. Rains said.

▸ Predict a positive but realistic outcome.

▸ Associate any positive outcome to patient behavior and perseverance.

There is no sure way to assess and track adherence accurately, she acknowledged.

Face-to-face interviewing is the most widely used tool, but it also is the least reliable. “Self-reporting actually overestimates adherence by 30%, compared with more objective monitoring,” she said. Diaries and questionnaires are better, and electronic measures are better still. “Yet, even the most objective measures are not entirely reliable,” she said. “Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of the office visit.”

Mechanical and electronic tools can “remind” patients to take a preset dose and track their use, but these tools do not address a patient's conscious decision to alter a regimen, she warned.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that “nonadherence with headache medication regimens is common,” said Dr. Rains, who reviewed the literature on headache treatment compliance and empiric adherence-enhancing strategies.

“And patients who don't take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache,” said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital in Manchester, N.H.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to “wait to see if it's a migraine or if it's severe,” she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others.

“And remember, repetition increases retention,” she said.

Moreover, “the way we engage is important,” Dr. Rains said. Adherence increases “not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they're doing well.”

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. “At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you've been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan.” Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients' motivation for treatment often shifts over time.

Dr. Rains reported that she had no relevant financial disclosures.

'Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens].'

Source DR. RAINS

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D.

“The more comprehensive the approach, the more adherence can be improved,” she said at the meeting.

The typical response to treatment failures is changing the drug choice or dosing; that's a mistake, she said. It would be better to assess adherence. “All patients are candidates for adherence facilitation.”

Dr. Rains suggested the following strategies for boosting adherence to headache therapy:

▸ Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. “Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens],” she said.

▸ Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

▸ Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side effects. Differentiating current treatment from past failures is key, Dr. Rains said.

▸ Predict a positive but realistic outcome.

▸ Associate any positive outcome to patient behavior and perseverance.

There is no sure way to assess and track adherence accurately, she acknowledged.

Face-to-face interviewing is the most widely used tool, but it also is the least reliable. “Self-reporting actually overestimates adherence by 30%, compared with more objective monitoring,” she said. Diaries and questionnaires are better, and electronic measures are better still. “Yet, even the most objective measures are not entirely reliable,” she said. “Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of the office visit.”

Mechanical and electronic tools can “remind” patients to take a preset dose and track their use, but these tools do not address a patient's conscious decision to alter a regimen, she warned.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that “nonadherence with headache medication regimens is common,” said Dr. Rains, who reviewed the literature on headache treatment compliance and empiric adherence-enhancing strategies.

“And patients who don't take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache,” said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital in Manchester, N.H.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to “wait to see if it's a migraine or if it's severe,” she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others.

“And remember, repetition increases retention,” she said.

Moreover, “the way we engage is important,” Dr. Rains said. Adherence increases “not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they're doing well.”

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. “At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you've been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan.” Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients' motivation for treatment often shifts over time.

Dr. Rains reported that she had no relevant financial disclosures.

'Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens].'

Source DR. RAINS

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D.

“The more comprehensive the approach, the more adherence can be improved,” she said at the meeting.

The typical response to treatment failures is changing the drug choice or dosing; that's a mistake, she said. It would be better to assess adherence. “All patients are candidates for adherence facilitation.”

Dr. Rains suggested the following strategies for boosting adherence to headache therapy:

▸ Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. “Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens],” she said.

▸ Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

▸ Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side effects. Differentiating current treatment from past failures is key, Dr. Rains said.

▸ Predict a positive but realistic outcome.

▸ Associate any positive outcome to patient behavior and perseverance.

There is no sure way to assess and track adherence accurately, she acknowledged.

Face-to-face interviewing is the most widely used tool, but it also is the least reliable. “Self-reporting actually overestimates adherence by 30%, compared with more objective monitoring,” she said. Diaries and questionnaires are better, and electronic measures are better still. “Yet, even the most objective measures are not entirely reliable,” she said. “Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of the office visit.”

Mechanical and electronic tools can “remind” patients to take a preset dose and track their use, but these tools do not address a patient's conscious decision to alter a regimen, she warned.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that “nonadherence with headache medication regimens is common,” said Dr. Rains, who reviewed the literature on headache treatment compliance and empiric adherence-enhancing strategies.

“And patients who don't take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache,” said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital in Manchester, N.H.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to “wait to see if it's a migraine or if it's severe,” she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others.

“And remember, repetition increases retention,” she said.

Moreover, “the way we engage is important,” Dr. Rains said. Adherence increases “not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they're doing well.”

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. “At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you've been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan.” Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients' motivation for treatment often shifts over time.

Dr. Rains reported that she had no relevant financial disclosures.

'Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens].'

Source DR. RAINS