Christine Kilgore

Dermatologists and their patients taking isotretinoin are entering the second year of the iPLEDGE mandatory risk management program aimed at preventing isotretinoin-related teratogenicity, and the specialty's leaders on the issue are anticipating further improvement in a system they say remains poorly designed.

“It's safe to say that within the first half of 2007, probably in later spring, there should be additional program improvement. … More improvement is coming,” said Dr. Diane Thiboutot, former chair of the American Academy of Dermatology task force on isotretinoin.

What is not clear, however—and won't be for at least another year—is the impact the program is having on the prevention of pregnancies in women taking the teratogenic drug.

Both Dr. Thiboutot, who will continue serving on the task force, and Dr. Susan Walker, who became the director of the Food and Drug Administration's Division of Dermatology and Dental Products last June, said for the first time in February that there is “preliminary” evidence that the program is reducing the number of women who are pregnant at the time they start isotretinoin therapy.

But they offered no details, and Dr. Thiboutot explained that the manufacturers now plan to use data from the first full year of iPLEDGE “as baseline data” for comparison with pregnancy data collected during the entire second year. Before iPLEDGE was implemented, the pregnancy rate in women taking isotretinoin (Accutane) was about 4 per 1,000 women, she said.

“In the interim, some sort of methodology [for evaluating success of the program] will be determined,” said Dr. Thiboutot, professor of dermatology at Pennsyvania State University, Hershey.

The most significant change to come this year, in the meantime, will likely be an elimination of the 23-day lockout period for women of childbearing potential. With such a rule change, women who do not have their prescriptions filled within 7 days could undergo another pregnancy test and office visit and then get a refill without having to wait 23 days.

The FDA eliminated this lockout period last October for males and females of nonchildbearing potential, while promising that a change in this rule for females of childbearing potential would be “rolled out” in 2007 (INTERNAL MEDICINE NEWS, Dec. 1, 2006, p. 11).

A spokesperson for Covance, the Princeton, N.J.-based company that manages iPLEDGE, confirmed that the firm is “working on eliminating [the lockout].”

Dr. Thiboutot said she and other AAD leaders have been pushing for other changes as well—for instance, the incorporation of specific dates rather than time windows in the iPLEDGE online program—based on input from dermatologists who have communicated with the academy as well as a survey of 400 dermatologists taken this summer. The poll showed that 95% were prescribing isotretinoin and that 90% of them were having difficulty with the iPLEDGE program.

Dr. Stephen Stone, who recently assumed the chairmanship of the academy's task force on isotretinoin, said the academy has a “seat at the table” that it did not have as iPLEDGE was being designed and implemented.

“The FDA is definitely listening to us,” said Dr. Stone, immediate past president of the AAD and professor of clinical medicine at Southern Illinois University, Springfield. “My understanding is that iPLEDGE will be improved, at least in its ease of application.”

Even with the elimination of the 23-day lockout period for men and women of nonchildbearing potential, “participation of these patients in the system is still overly complicated,” he said. “There still [needs to be] some liberalization of rules.”

Dermatologists still are debating the program's effects on prescribing. Dr. Noah Scheinfeld, of the dermatology department of Columbia University, New York, estimated last spring that prescribing in his region had dropped by at least 50%. That estimate still holds true, he said.

Dr. Elaine Siegfried, a dermatologist at St. Louis University who chairs the AAD's Environment and Drugs Committee, said, on the other hand, that the number of isotretinoin prescriptions dropped after implementation of iPLEDGE but now appears to be back up to approximately where it was under the voluntary SMART (System to Manage Accutane-Related Teratogenicity) program.

(The total number of prescriptions dispensed in the United States in the year after SMART was implemented had declined 23% from the previous year.)

According to Covance's data, while the number of prescribers and pharmacies activated has remained about the same in the last 6 months, the number of patients activated in the program has risen significantly, from 140,000 patients last June to more than 244,000 in December.

Calls to the AAD office, meanwhile, have continued to decline—a trend that AAD leaders say likely reflects changes made by Covance in the spring (the company added staff to its call center and made changes to its Web site, for instance, resolving some of the program's operational difficulties), as well as time needed to learn the system and delegate responsibility.

The average wait time for getting help from the iPLEDGE call center in December was 2 minutes, according to Covance spokesperson Laurene Isip.

“The program is definitely running light-years better” than it did at the start, said Dr. James Del Rosso, of the department of dermatology at University of Nevada, Reno, and immediate past chairman of the AAD's Environment and Drugs Committee.

Dr. Sharon Gardepe, who has a solo practice in general dermatology in Huntsville, Ala., called her legislators and the AAD soon after implementation about her concerns and experience with iPLEDGE. She also created a handout listing local legislators to give to her patients who complained about the program. “Giving them the list underlined the fact that it wasn't me,” she said.

One year into the program, Dr. Gardepe said her hour-long phone calls to Covance are a thing of the past, but the requirement that prescriptions be picked up within 7 days and the rule that lab tests be conducted no sooner than 1 day before the office visit still result in “a lot of time spent troubleshooting.

“Some people are optimistic that we might be better able to work with [FDA and Covance], but I'm still skeptical” about the extent of future change, she said.

Dr. Siegfried said such skepticism is understandable. “I really am optimistic. I do think that Dr. Walker [at the FDA] wants to build bridges,” she said. “But in the end it's not her call—it's Congress.”

Dr. Siegfried and other AAD leaders urge physicians to remain vigilant and active. Isotretinoin, they caution, will likely be in the limelight this year, since Rep. Bart Stupak (D-Mich.) has announced that he wants to hold a congressional hearing on the FDA's management of the drug.

Dr. Siegfried said that she believes the decision to collect a full year of baseline data and then another year of comparison data before reporting pregnancy rates—rather than releasing iPLEDGE data quarterly, as was first anticipated—reflects the realization that “if the data were made public [along the way], and there's been one pregnancy, it will haunt us and we won't have the drug [at all].”

Dr. Stone said he too is concerned, saying that iPLEDGE “will minimize the number of pregnancies by forcing people to go through the hoops, but I don't think we'll ever eliminate pregnancies.”

The iPLEDGE program 'is definitely running light-years better' than it did at the start. DR. DEL ROSSO

Dermatologists and their patients taking isotretinoin are entering the second year of the iPLEDGE mandatory risk management program aimed at preventing isotretinoin-related teratogenicity, and the specialty's leaders on the issue are anticipating further improvement in a system they say remains poorly designed.

“It's safe to say that within the first half of 2007, probably in later spring, there should be additional program improvement. … More improvement is coming,” said Dr. Diane Thiboutot, former chair of the American Academy of Dermatology task force on isotretinoin.

What is not clear, however—and won't be for at least another year—is the impact the program is having on the prevention of pregnancies in women taking the teratogenic drug.

Both Dr. Thiboutot, who will continue serving on the task force, and Dr. Susan Walker, who became the director of the Food and Drug Administration's Division of Dermatology and Dental Products last June, said for the first time in February that there is “preliminary” evidence that the program is reducing the number of women who are pregnant at the time they start isotretinoin therapy.

But they offered no details, and Dr. Thiboutot explained that the manufacturers now plan to use data from the first full year of iPLEDGE “as baseline data” for comparison with pregnancy data collected during the entire second year. Before iPLEDGE was implemented, the pregnancy rate in women taking isotretinoin (Accutane) was about 4 per 1,000 women, she said.

“In the interim, some sort of methodology [for evaluating success of the program] will be determined,” said Dr. Thiboutot, professor of dermatology at Pennsyvania State University, Hershey.

The most significant change to come this year, in the meantime, will likely be an elimination of the 23-day lockout period for women of childbearing potential. With such a rule change, women who do not have their prescriptions filled within 7 days could undergo another pregnancy test and office visit and then get a refill without having to wait 23 days.

The FDA eliminated this lockout period last October for males and females of nonchildbearing potential, while promising that a change in this rule for females of childbearing potential would be “rolled out” in 2007 (INTERNAL MEDICINE NEWS, Dec. 1, 2006, p. 11).

A spokesperson for Covance, the Princeton, N.J.-based company that manages iPLEDGE, confirmed that the firm is “working on eliminating [the lockout].”

Dr. Thiboutot said she and other AAD leaders have been pushing for other changes as well—for instance, the incorporation of specific dates rather than time windows in the iPLEDGE online program—based on input from dermatologists who have communicated with the academy as well as a survey of 400 dermatologists taken this summer. The poll showed that 95% were prescribing isotretinoin and that 90% of them were having difficulty with the iPLEDGE program.

Dr. Stephen Stone, who recently assumed the chairmanship of the academy's task force on isotretinoin, said the academy has a “seat at the table” that it did not have as iPLEDGE was being designed and implemented.

“The FDA is definitely listening to us,” said Dr. Stone, immediate past president of the AAD and professor of clinical medicine at Southern Illinois University, Springfield. “My understanding is that iPLEDGE will be improved, at least in its ease of application.”

Even with the elimination of the 23-day lockout period for men and women of nonchildbearing potential, “participation of these patients in the system is still overly complicated,” he said. “There still [needs to be] some liberalization of rules.”

Dermatologists still are debating the program's effects on prescribing. Dr. Noah Scheinfeld, of the dermatology department of Columbia University, New York, estimated last spring that prescribing in his region had dropped by at least 50%. That estimate still holds true, he said.

Dr. Elaine Siegfried, a dermatologist at St. Louis University who chairs the AAD's Environment and Drugs Committee, said, on the other hand, that the number of isotretinoin prescriptions dropped after implementation of iPLEDGE but now appears to be back up to approximately where it was under the voluntary SMART (System to Manage Accutane-Related Teratogenicity) program.

(The total number of prescriptions dispensed in the United States in the year after SMART was implemented had declined 23% from the previous year.)

According to Covance's data, while the number of prescribers and pharmacies activated has remained about the same in the last 6 months, the number of patients activated in the program has risen significantly, from 140,000 patients last June to more than 244,000 in December.

Calls to the AAD office, meanwhile, have continued to decline—a trend that AAD leaders say likely reflects changes made by Covance in the spring (the company added staff to its call center and made changes to its Web site, for instance, resolving some of the program's operational difficulties), as well as time needed to learn the system and delegate responsibility.

The average wait time for getting help from the iPLEDGE call center in December was 2 minutes, according to Covance spokesperson Laurene Isip.

“The program is definitely running light-years better” than it did at the start, said Dr. James Del Rosso, of the department of dermatology at University of Nevada, Reno, and immediate past chairman of the AAD's Environment and Drugs Committee.

Dr. Sharon Gardepe, who has a solo practice in general dermatology in Huntsville, Ala., called her legislators and the AAD soon after implementation about her concerns and experience with iPLEDGE. She also created a handout listing local legislators to give to her patients who complained about the program. “Giving them the list underlined the fact that it wasn't me,” she said.

One year into the program, Dr. Gardepe said her hour-long phone calls to Covance are a thing of the past, but the requirement that prescriptions be picked up within 7 days and the rule that lab tests be conducted no sooner than 1 day before the office visit still result in “a lot of time spent troubleshooting.

“Some people are optimistic that we might be better able to work with [FDA and Covance], but I'm still skeptical” about the extent of future change, she said.

Dr. Siegfried said such skepticism is understandable. “I really am optimistic. I do think that Dr. Walker [at the FDA] wants to build bridges,” she said. “But in the end it's not her call—it's Congress.”

Dr. Siegfried and other AAD leaders urge physicians to remain vigilant and active. Isotretinoin, they caution, will likely be in the limelight this year, since Rep. Bart Stupak (D-Mich.) has announced that he wants to hold a congressional hearing on the FDA's management of the drug.

Dr. Siegfried said that she believes the decision to collect a full year of baseline data and then another year of comparison data before reporting pregnancy rates—rather than releasing iPLEDGE data quarterly, as was first anticipated—reflects the realization that “if the data were made public [along the way], and there's been one pregnancy, it will haunt us and we won't have the drug [at all].”

Dr. Stone said he too is concerned, saying that iPLEDGE “will minimize the number of pregnancies by forcing people to go through the hoops, but I don't think we'll ever eliminate pregnancies.”

The iPLEDGE program 'is definitely running light-years better' than it did at the start. DR. DEL ROSSO

Dermatologists and their patients taking isotretinoin are entering the second year of the iPLEDGE mandatory risk management program aimed at preventing isotretinoin-related teratogenicity, and the specialty's leaders on the issue are anticipating further improvement in a system they say remains poorly designed.

“It's safe to say that within the first half of 2007, probably in later spring, there should be additional program improvement. … More improvement is coming,” said Dr. Diane Thiboutot, former chair of the American Academy of Dermatology task force on isotretinoin.

What is not clear, however—and won't be for at least another year—is the impact the program is having on the prevention of pregnancies in women taking the teratogenic drug.

Both Dr. Thiboutot, who will continue serving on the task force, and Dr. Susan Walker, who became the director of the Food and Drug Administration's Division of Dermatology and Dental Products last June, said for the first time in February that there is “preliminary” evidence that the program is reducing the number of women who are pregnant at the time they start isotretinoin therapy.

But they offered no details, and Dr. Thiboutot explained that the manufacturers now plan to use data from the first full year of iPLEDGE “as baseline data” for comparison with pregnancy data collected during the entire second year. Before iPLEDGE was implemented, the pregnancy rate in women taking isotretinoin (Accutane) was about 4 per 1,000 women, she said.

“In the interim, some sort of methodology [for evaluating success of the program] will be determined,” said Dr. Thiboutot, professor of dermatology at Pennsyvania State University, Hershey.

The most significant change to come this year, in the meantime, will likely be an elimination of the 23-day lockout period for women of childbearing potential. With such a rule change, women who do not have their prescriptions filled within 7 days could undergo another pregnancy test and office visit and then get a refill without having to wait 23 days.

The FDA eliminated this lockout period last October for males and females of nonchildbearing potential, while promising that a change in this rule for females of childbearing potential would be “rolled out” in 2007 (INTERNAL MEDICINE NEWS, Dec. 1, 2006, p. 11).

A spokesperson for Covance, the Princeton, N.J.-based company that manages iPLEDGE, confirmed that the firm is “working on eliminating [the lockout].”

Dr. Thiboutot said she and other AAD leaders have been pushing for other changes as well—for instance, the incorporation of specific dates rather than time windows in the iPLEDGE online program—based on input from dermatologists who have communicated with the academy as well as a survey of 400 dermatologists taken this summer. The poll showed that 95% were prescribing isotretinoin and that 90% of them were having difficulty with the iPLEDGE program.

Dr. Stephen Stone, who recently assumed the chairmanship of the academy's task force on isotretinoin, said the academy has a “seat at the table” that it did not have as iPLEDGE was being designed and implemented.

“The FDA is definitely listening to us,” said Dr. Stone, immediate past president of the AAD and professor of clinical medicine at Southern Illinois University, Springfield. “My understanding is that iPLEDGE will be improved, at least in its ease of application.”

Even with the elimination of the 23-day lockout period for men and women of nonchildbearing potential, “participation of these patients in the system is still overly complicated,” he said. “There still [needs to be] some liberalization of rules.”

Dermatologists still are debating the program's effects on prescribing. Dr. Noah Scheinfeld, of the dermatology department of Columbia University, New York, estimated last spring that prescribing in his region had dropped by at least 50%. That estimate still holds true, he said.

Dr. Elaine Siegfried, a dermatologist at St. Louis University who chairs the AAD's Environment and Drugs Committee, said, on the other hand, that the number of isotretinoin prescriptions dropped after implementation of iPLEDGE but now appears to be back up to approximately where it was under the voluntary SMART (System to Manage Accutane-Related Teratogenicity) program.

(The total number of prescriptions dispensed in the United States in the year after SMART was implemented had declined 23% from the previous year.)

According to Covance's data, while the number of prescribers and pharmacies activated has remained about the same in the last 6 months, the number of patients activated in the program has risen significantly, from 140,000 patients last June to more than 244,000 in December.

Calls to the AAD office, meanwhile, have continued to decline—a trend that AAD leaders say likely reflects changes made by Covance in the spring (the company added staff to its call center and made changes to its Web site, for instance, resolving some of the program's operational difficulties), as well as time needed to learn the system and delegate responsibility.

The average wait time for getting help from the iPLEDGE call center in December was 2 minutes, according to Covance spokesperson Laurene Isip.

“The program is definitely running light-years better” than it did at the start, said Dr. James Del Rosso, of the department of dermatology at University of Nevada, Reno, and immediate past chairman of the AAD's Environment and Drugs Committee.

Dr. Sharon Gardepe, who has a solo practice in general dermatology in Huntsville, Ala., called her legislators and the AAD soon after implementation about her concerns and experience with iPLEDGE. She also created a handout listing local legislators to give to her patients who complained about the program. “Giving them the list underlined the fact that it wasn't me,” she said.

One year into the program, Dr. Gardepe said her hour-long phone calls to Covance are a thing of the past, but the requirement that prescriptions be picked up within 7 days and the rule that lab tests be conducted no sooner than 1 day before the office visit still result in “a lot of time spent troubleshooting.

“Some people are optimistic that we might be better able to work with [FDA and Covance], but I'm still skeptical” about the extent of future change, she said.

Dr. Siegfried said such skepticism is understandable. “I really am optimistic. I do think that Dr. Walker [at the FDA] wants to build bridges,” she said. “But in the end it's not her call—it's Congress.”

Dr. Siegfried and other AAD leaders urge physicians to remain vigilant and active. Isotretinoin, they caution, will likely be in the limelight this year, since Rep. Bart Stupak (D-Mich.) has announced that he wants to hold a congressional hearing on the FDA's management of the drug.

Dr. Siegfried said that she believes the decision to collect a full year of baseline data and then another year of comparison data before reporting pregnancy rates—rather than releasing iPLEDGE data quarterly, as was first anticipated—reflects the realization that “if the data were made public [along the way], and there's been one pregnancy, it will haunt us and we won't have the drug [at all].”

Dr. Stone said he too is concerned, saying that iPLEDGE “will minimize the number of pregnancies by forcing people to go through the hoops, but I don't think we'll ever eliminate pregnancies.”

The iPLEDGE program 'is definitely running light-years better' than it did at the start. DR. DEL ROSSO

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel A_1c registry—900,000 A_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of hemoglobin A_1c tests directly to the city's Department of Health and Mental Hygiene.

As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, who is the medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: Surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx.

The medical directors are then responsible for distributing the practice reports—which list patients stratified by A_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician.

This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all hemoglobin A_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10% to 20% of the A_1c results [coming in] are for screening purposes. … We need to be able to wean these out.”

Another unanswered question is how much hemoglobin A_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test hemoglobin A_1c—28 of 38 labs—are now doing so.

Dr. Berger said she anticipates that 100% of laboratories will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden of Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and A_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office A_1c testing, and Dr. Berger said she's actively seeking an answer to that question.

“I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick A_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with hemoglobin A_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith of Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” he said. “Publishing the average A_1c by physician would be interesting. … It's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries.

“My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

Survey: 13% of Adult New Yorkers Are Diabetic

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide.

But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% of adults nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (A_1c less than 7), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel A_1c registry—900,000 A_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of hemoglobin A_1c tests directly to the city's Department of Health and Mental Hygiene.

As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, who is the medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: Surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx.

The medical directors are then responsible for distributing the practice reports—which list patients stratified by A_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician.

This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all hemoglobin A_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10% to 20% of the A_1c results [coming in] are for screening purposes. … We need to be able to wean these out.”

Another unanswered question is how much hemoglobin A_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test hemoglobin A_1c—28 of 38 labs—are now doing so.

Dr. Berger said she anticipates that 100% of laboratories will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden of Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and A_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office A_1c testing, and Dr. Berger said she's actively seeking an answer to that question.

“I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick A_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with hemoglobin A_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith of Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” he said. “Publishing the average A_1c by physician would be interesting. … It's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries.

“My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

Survey: 13% of Adult New Yorkers Are Diabetic

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide.

But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% of adults nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (A_1c less than 7), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel A_1c registry—900,000 A_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of hemoglobin A_1c tests directly to the city's Department of Health and Mental Hygiene.

As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, who is the medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: Surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx.

The medical directors are then responsible for distributing the practice reports—which list patients stratified by A_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician.

This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all hemoglobin A_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10% to 20% of the A_1c results [coming in] are for screening purposes. … We need to be able to wean these out.”

Another unanswered question is how much hemoglobin A_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test hemoglobin A_1c—28 of 38 labs—are now doing so.

Dr. Berger said she anticipates that 100% of laboratories will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden of Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and A_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office A_1c testing, and Dr. Berger said she's actively seeking an answer to that question.

“I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick A_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with hemoglobin A_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith of Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” he said. “Publishing the average A_1c by physician would be interesting. … It's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries.

“My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

Survey: 13% of Adult New Yorkers Are Diabetic

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide.

But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% of adults nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (A_1c less than 7), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel hemoglobin A_1c (Hb A_1c) registry—900,000 HbA_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of HbA_1c tests directly to the city's Department of Health and Mental Hygiene. As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx. The medical directors are then responsible for distributing the practice reports—which list patients stratified by HbA_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician. This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all HbA_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c [levels] to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10%–20% of the A_1c results [coming in] are for screening purposes … We need to be able to wean these out.”

Another unanswered question is how much HbA_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test HbA_1c—28 of 38 labs—are now doing so, and Dr. Berger said she anticipates that 100% will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden, clinical professor of medicine at the Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and HbA_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office HbA_1c testing, and Dr. Berger said she's actively seeking an answer to that question. “I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick HbA_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with HbA_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith, associate professor of medicine at the Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” Dr. Smith said. “Publishing the average A_1c by physician would be interesting … it's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries. “My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

City Health Survey Shows Diabetes Rate High Among Asians

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide. But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (hemoglobin A_1c less than 7%), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (hemoglobin A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel hemoglobin A_1c (Hb A_1c) registry—900,000 HbA_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of HbA_1c tests directly to the city's Department of Health and Mental Hygiene. As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx. The medical directors are then responsible for distributing the practice reports—which list patients stratified by HbA_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician. This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all HbA_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c [levels] to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10%–20% of the A_1c results [coming in] are for screening purposes … We need to be able to wean these out.”

Another unanswered question is how much HbA_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test HbA_1c—28 of 38 labs—are now doing so, and Dr. Berger said she anticipates that 100% will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden, clinical professor of medicine at the Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and HbA_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office HbA_1c testing, and Dr. Berger said she's actively seeking an answer to that question. “I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick HbA_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with HbA_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith, associate professor of medicine at the Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” Dr. Smith said. “Publishing the average A_1c by physician would be interesting … it's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries. “My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

City Health Survey Shows Diabetes Rate High Among Asians

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide. But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (hemoglobin A_1c less than 7%), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (hemoglobin A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

One year into a landmark diabetes monitoring program, hemoglobin A_1c test results are streaming from New York City laboratories into the city's health department and, in a sampling of cases, on to medical directors for distribution to clinicians.

City health officials, in the meantime, are working with a national advisory group of diabetes experts to analyze the data in the city's novel hemoglobin A_1c (Hb A_1c) registry—900,000 HbA_1c test results covering 600,000 individuals, as of last month—and to design subsequent interventions.

The registry, which was launched in January 2006, is being watched by health officials across the country who want to reduce diabetes complications and control what they increasingly view as one of their largest public health crises.

The New York City program mandates that laboratories already reporting communicable diseases must also report results of HbA_1c tests directly to the city's Department of Health and Mental Hygiene. As the program develops, the health department plans to routinely provide information to clinicians on their patients with diabetes and offer services and interventions to patients with poor glycemic control.

“The essence [is] to have it be more than just a surveillance system,” said Dr. Diana Berger, medical director of the city's Diabetes Prevention and Control Program.

“We already have a robust system to establish the prevalence of diabetes,” she said. “We wanted a two-pronged initiative: surveillance plus some sort of intervention.”

For now, in a pilot phase of the program, the city has begun sending quarterly reports to medical directors of seven practices in Manhattan and the South Bronx. The medical directors are then responsible for distributing the practice reports—which list patients stratified by HbA_1c levels—to the 274 clinicians in the practices, Dr. Berger said.

The city plans to expand the pilot project to cover all of the South Bronx (approximately 100 practices) this summer, followed by other high-risk neighborhoods later in the year—a roll-out that officials hope will be helpful for fine-tuning reports and eventually designing interventions.

Interpreting the growing body of registry data, in the meantime, has been a significant undertaking.

Test results come in with the patient's full name, date of birth, and address, as well as the date the test was taken and the name and location of the ordering facility and clinician. This information may be enough for providing profiles to providers, but it's probably not enough to fully understand the epidemic and design optimal interventions, Dr. Berger said.

“The problem is, there's no diagnostic code attached to [the results],” she said. “We don't know whether a patient has diabetes or not [or what type of diabetes it is]. … The database needs a lot of cleaning [and interpretation]—it's a complex process.”

Also complicating the analysis is the fact that the registry, by including all HbA_1c test results, captures tests used for diabetes screening as well as for monitoring, Dr. Berger said.

“There's a current practice of using A_1c [levels] to screen for diabetes,” even though it's not recommended by the American Diabetes Association, she said. “We're estimating that anywhere from 10%–20% of the A_1c results [coming in] are for screening purposes … We need to be able to wean these out.”

Another unanswered question is how much HbA_1c testing is left out of the registry.

As of last month, almost three-fourths of the clinical laboratories required to report all results of blood test HbA_1c—28 of 38 labs—are now doing so, and Dr. Berger said she anticipates that 100% will be reporting test results shortly.

The registry does not, however, include results obtained in office laboratories. Dr. Zachary Bloomgarden, clinical professor of medicine at the Mount Sinai School of Medicine, New York, said his practice is excluded from the program because he does blood draws and HbA_1c testing right in his office lab.

Dr. Bloomgarden said he doesn't “have any real sense” of how many other practices perform in-office HbA_1c testing, and Dr. Berger said she's actively seeking an answer to that question. “I'm in the process of studying that, trying to get a sense of what we're missing,” Dr. Berger said.

Some practices, she said, utilize finger-stick HbA_1c testing to be able to present results immediately to patients, “but just anecdotally, I know that some robust endocrinology practices don't actually trust their figures from the A_1c machines and will also get a [blood] draw.”

Dr. Berger said that she hopes to release the first “surveillance report”—a description, in essence, of all the data in the registry—later this spring, after she and others involved in the program have finished analyzing the data with the help of the advisory group.

The seven practices participating in the pilot project are of varying types, ranging from a large practice linked with an academic medical center to a small community health center and a small private practice.

Patients are stratified by success of glycemic control, with HbA_1c levels less than 7% representing “good control” (the target recommended by the ADA), levels between 7% and 9% reflecting “poorly controlled” diabetes, and levels over 9% representing “very poorly controlled” diabetes.

“It's still very arbitrary,” Dr. Berger said. “We're [providing] a population-based snapshot of the provider's panel. … A provider [can look at the report] and say, 'here are my 15 patients who are doing particularly poorly. Maybe they need to be on insulin, or maybe they need to see a nutritionist.'”

It is too early to know, she and others say, exactly what the practices will do with the reports and what impact the information will have on disease outcomes.

Dr. Donald A. Smith, associate professor of medicine at the Mount Sinai School of Medicine said he's hopeful that the program will spur physicians to “get the patients who are lost and out of control back in” for help.

“It will be interesting to see how the sophistication of the report [evolves],” Dr. Smith said. “Publishing the average A_1c by physician would be interesting … it's incredible how, with stenting and angioplasty, [such physician profiling] has stimulated competitive efforts to improve.”

Dr. Berger said she has received calls from health officials in other municipalities who are seeking advice on starting similar registries. “My advice is, wait to see what our experience is first. … It has great potential, but we need to implement it and evaluate it first.”

ELSEVIER GLOBAL MEDICAL NEWS

City Health Survey Shows Diabetes Rate High Among Asians

Those who are awaiting an official description of data being collected in New York City's hemoglobin A_1c registry have some other striking data to digest while they wait: A new citywide survey modeled after a well-known national survey finds that nearly 13% of the city's adults have diabetes and that about one-third of them—almost 4% of city residents—do not know it.

The first New York City Health and Nutrition Examination Survey (HANES)—and the first community-level HANES survey in the country, health department officials say—used a one-time screening test to estimate diabetes prevalence among approximately 2,000 randomly selected New Yorkers from 144 neighborhoods across all boroughs.

The survey findings confirm past estimates from telephone surveys that about 9% of adults in the city have been diagnosed with diabetes, slightly higher than the 7.3% of adults who have diagnosed diabetes nationwide. But the laboratory results obtained as part of the HANES survey go further, revealing that an additional 3.8% of adults in New York City have undiagnosed diabetes (compared with 3% nationally).

The survey also shows that another 23.5% of adults have prediabetes and that nearly half of all Asian New Yorkers have either diabetes or prediabetes, according to press officials at the New York City Department of Health and Mental Hygiene.

The prevalence of diabetes among Asians, the survey shows, is 16% (nearly 1 in 6). Significantly more Asians—32%–-have prediabetes compared with other ethnic groups. (See chart.)

The higher overall prevalence numbers are “not surprising, [since] we have an extremely ethnically diverse population,” said Dr. Berger.

The high prevalence among Asians specifically, she said, is “somewhat” surprising, though some Asian groups, particularly Southeast Asians, are known to be susceptible to the development of diabetes. “Unfortunately our sample size wasn't large enough to tease out the various Asian groups,” she said.

Among men and women of all ethnicities who have diabetes, the findings show, 52% have well-controlled diabetes (hemoglobin A_1c less than 7%), 32% have moderately poorly controlled blood sugar, and about 16% have very poorly controlled blood sugar (hemoglobin A_1c greater than 9%).

Poor diabetes control appears to be common even among people with access to health care. Of New Yorkers with diagnosed diabetes that is uncontrolled, 94% have some sort of health insurance, including Medicaid.

An “overwhelming” amount of data now suggest that patients with fibromyalgia and a number of overlapping pain syndromes have augmented pain or sensory processing in the central nervous system, resulting in real differences in pain tolerance, judging from the findings of a recent review.

Genetic findings also are accumulating that suggest specific gene mutations may predispose individuals to developing fibromyalgia (FM), according to the authors.

“It is time for us to move past the rhetoric about whether these conditions are real, and take these patients seriously as we endeavor to learn more about the causes and most effective treatments for these disorders,” reported Dr. Daniel J. Clauw, professor of rheumatology at the University of Michigan, Ann Arbor, and director of the U-M Chronic Pain and Fatigue Research Center, and Richard E. Harris, Ph.D., a researcher at the center and the university.

The hyperactivity of pain processing mechanisms that characterizes FM and related conditions–from irritable bowel syndrome to tension headache and temporomandibular syndrome–can occur in association with psychological factors, “but psychological factors are not in any way required for an individual to develop or maintain this augmented central pain state,” they wrote.

Other investigators said in an interview that they hope to see more reviews like it, particularly since many studies of FM are low budget, small and too easily dismissed unless they are viewed together.

Neuroimaging studies, for instance, “are providing a consistent picture” when viewed together of strong neurobiologic underpinnings for FM, said Dr. Nancy Klimas, professor of medicine at the University of Miami. “But if you pull them apart, you can find faults with any one study in it having limited power, or some other limitation.”

“This is what [the authors] are saying–'look at the whole picture, it's impressive,'” said Dr. Klimas. “There's some real science to go behind the pain observation.”

Dr. Klimas said the review reminded her of a grand-rounds lecture she heard several years ago, in which a “prominent” department chair told students and faculty that fibromyalgia “is all in patients' heads.”

“He essentially said, don't let these patients talk to each other, don't let them read anything, don't let them have any support group meetings,” Dr. Klimas said. “I was livid. These patients [with FM] are often treated badly by their physicians. It's bad enough leaving without any hope that something can be done, but it's worse leaving a doctor's office having been made to feel small or patronized.”

Dr. Laurence Bradley, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, agreed that the literature is ripe for strong conclusions. “The [review authors] are correct. A lot of new findings have emerged in the last 5–8 years … regarding gene variance that's associated with FM itself or with [related] disorders.

“And a lot of the neuroimaging work that has been done has demonstrated very convincingly that people with FM have enhanced or abnormal transmission of sensory signals through the CNS,” he said. “Behavioral studies–laboratory pain studies–also show consistent displays of abnormal pain responses in individuals with FM.”

In their review, Dr. Clauw and Dr. Harris described functional imaging studies done with single-photon emission computer tomography (SPECT) and functional magnetic resonance imaging (fMRI) that show differences in neural activation between patients with FM and pain-free controls. The studies indicate that FM patients have abnormalities within their central brain structures, they said.

There is evidence in FM that an “increased gain” in pain processing is driven by defects in both descending inhibitory pathways for pain processing and in spinal excitatory activity, the authors added.

Biochemical studies have supported the notion that the pathology might be a result of high levels of pronociceptive compounds (such as “substance P”), low levels of antinociceptive compounds, or both. Conversely “there is considerable evidence that this increased gain could occur because of a deficiency in one of the major endogenous analgesic pathways, the descending antinociceptive serotonergic-noradrenergic pathway” (Curr. Pain Headache Rep. 2006:10;403–7).

The “ultimate proof” that defective central control mechanisms are playing a role in FM and overlapping pain conditions comes from randomized clinical trials showing that neuroactive compounds that either increase inhibitory activity (such as serotonin-norepinephrine reuptake inhibitors) or decrease facilitatory activity (such as antiepileptics) can be efficacious in treating FM as well as neuropathic pain, said Dr. Clauw and Dr. Harris.

Dr. Bradley said that one of the “missing pieces of information” in the growing knowledge of pain transmission in FM is its original source.

“Where's the starting point?” he asked. “[Many experts] think it originates from abnormalities in the deep muscle tissue, but at this point we have a much better understanding of what goes on at the spinal level than we do of what factors contribute to the initiation of sensory signals.”

What's missing from the review itself, he and others noted, is the “consistent” evidence of altered neuroendocrine function in patients with FM.

Dr. Robert Bennett, who has led studies in this area, said that FM also appears to be a manifestation of an abnormal acute stress response involving abnormalities in levels of cortisol and growth hormone, an imbalance in sympathetic and vagal tone, and other phenomena–a notion that puts FM at least partly in the same camp, for underlying mechanisms, as chronic fatigue syndrome.

“The major things we know now [about FM] relate to the pain system,” said Dr. Bennett, professor of medicine at Oregon Health and Science University, Portland. “The neuroendocrine abnormalities–the manifestations of the acute stress response–have still, I think, been underinvestigated.”

Dr. Klimas, director of the University of Miami's chronic fatigue syndrome research center, said that more than 60% of her patients with the syndrome meet the case definition of FM as well, which reflects at least in part the fact that the FM definition is looser and more inclusive while the chronic fatigue syndrome definition has many exclusionary criteria.

Dr. Bradley added that a number of recent studies have also shown a familial aggregation of pain sensitivity. The studies show that first-degree relatives of patients with FM tend to have the “same sorts of unusual sensitivities to pain and abnormal pain responses,” even though this isn't always manifested as FM.

An “overwhelming” amount of data now suggest that patients with fibromyalgia and a number of overlapping pain syndromes have augmented pain or sensory processing in the central nervous system, resulting in real differences in pain tolerance, judging from the findings of a recent review.

Genetic findings also are accumulating that suggest specific gene mutations may predispose individuals to developing fibromyalgia (FM), according to the authors.

“It is time for us to move past the rhetoric about whether these conditions are real, and take these patients seriously as we endeavor to learn more about the causes and most effective treatments for these disorders,” reported Dr. Daniel J. Clauw, professor of rheumatology at the University of Michigan, Ann Arbor, and director of the U-M Chronic Pain and Fatigue Research Center, and Richard E. Harris, Ph.D., a researcher at the center and the university.

The hyperactivity of pain processing mechanisms that characterizes FM and related conditions–from irritable bowel syndrome to tension headache and temporomandibular syndrome–can occur in association with psychological factors, “but psychological factors are not in any way required for an individual to develop or maintain this augmented central pain state,” they wrote.

Other investigators said in an interview that they hope to see more reviews like it, particularly since many studies of FM are low budget, small and too easily dismissed unless they are viewed together.

Neuroimaging studies, for instance, “are providing a consistent picture” when viewed together of strong neurobiologic underpinnings for FM, said Dr. Nancy Klimas, professor of medicine at the University of Miami. “But if you pull them apart, you can find faults with any one study in it having limited power, or some other limitation.”

“This is what [the authors] are saying–'look at the whole picture, it's impressive,'” said Dr. Klimas. “There's some real science to go behind the pain observation.”

Dr. Klimas said the review reminded her of a grand-rounds lecture she heard several years ago, in which a “prominent” department chair told students and faculty that fibromyalgia “is all in patients' heads.”

“He essentially said, don't let these patients talk to each other, don't let them read anything, don't let them have any support group meetings,” Dr. Klimas said. “I was livid. These patients [with FM] are often treated badly by their physicians. It's bad enough leaving without any hope that something can be done, but it's worse leaving a doctor's office having been made to feel small or patronized.”

Dr. Laurence Bradley, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, agreed that the literature is ripe for strong conclusions. “The [review authors] are correct. A lot of new findings have emerged in the last 5–8 years … regarding gene variance that's associated with FM itself or with [related] disorders.

“And a lot of the neuroimaging work that has been done has demonstrated very convincingly that people with FM have enhanced or abnormal transmission of sensory signals through the CNS,” he said. “Behavioral studies–laboratory pain studies–also show consistent displays of abnormal pain responses in individuals with FM.”

In their review, Dr. Clauw and Dr. Harris described functional imaging studies done with single-photon emission computer tomography (SPECT) and functional magnetic resonance imaging (fMRI) that show differences in neural activation between patients with FM and pain-free controls. The studies indicate that FM patients have abnormalities within their central brain structures, they said.

There is evidence in FM that an “increased gain” in pain processing is driven by defects in both descending inhibitory pathways for pain processing and in spinal excitatory activity, the authors added.

Biochemical studies have supported the notion that the pathology might be a result of high levels of pronociceptive compounds (such as “substance P”), low levels of antinociceptive compounds, or both. Conversely “there is considerable evidence that this increased gain could occur because of a deficiency in one of the major endogenous analgesic pathways, the descending antinociceptive serotonergic-noradrenergic pathway” (Curr. Pain Headache Rep. 2006:10;403–7).

The “ultimate proof” that defective central control mechanisms are playing a role in FM and overlapping pain conditions comes from randomized clinical trials showing that neuroactive compounds that either increase inhibitory activity (such as serotonin-norepinephrine reuptake inhibitors) or decrease facilitatory activity (such as antiepileptics) can be efficacious in treating FM as well as neuropathic pain, said Dr. Clauw and Dr. Harris.

Dr. Bradley said that one of the “missing pieces of information” in the growing knowledge of pain transmission in FM is its original source.

“Where's the starting point?” he asked. “[Many experts] think it originates from abnormalities in the deep muscle tissue, but at this point we have a much better understanding of what goes on at the spinal level than we do of what factors contribute to the initiation of sensory signals.”

What's missing from the review itself, he and others noted, is the “consistent” evidence of altered neuroendocrine function in patients with FM.

Dr. Robert Bennett, who has led studies in this area, said that FM also appears to be a manifestation of an abnormal acute stress response involving abnormalities in levels of cortisol and growth hormone, an imbalance in sympathetic and vagal tone, and other phenomena–a notion that puts FM at least partly in the same camp, for underlying mechanisms, as chronic fatigue syndrome.

“The major things we know now [about FM] relate to the pain system,” said Dr. Bennett, professor of medicine at Oregon Health and Science University, Portland. “The neuroendocrine abnormalities–the manifestations of the acute stress response–have still, I think, been underinvestigated.”

Dr. Klimas, director of the University of Miami's chronic fatigue syndrome research center, said that more than 60% of her patients with the syndrome meet the case definition of FM as well, which reflects at least in part the fact that the FM definition is looser and more inclusive while the chronic fatigue syndrome definition has many exclusionary criteria.

Dr. Bradley added that a number of recent studies have also shown a familial aggregation of pain sensitivity. The studies show that first-degree relatives of patients with FM tend to have the “same sorts of unusual sensitivities to pain and abnormal pain responses,” even though this isn't always manifested as FM.

An “overwhelming” amount of data now suggest that patients with fibromyalgia and a number of overlapping pain syndromes have augmented pain or sensory processing in the central nervous system, resulting in real differences in pain tolerance, judging from the findings of a recent review.

Genetic findings also are accumulating that suggest specific gene mutations may predispose individuals to developing fibromyalgia (FM), according to the authors.

“It is time for us to move past the rhetoric about whether these conditions are real, and take these patients seriously as we endeavor to learn more about the causes and most effective treatments for these disorders,” reported Dr. Daniel J. Clauw, professor of rheumatology at the University of Michigan, Ann Arbor, and director of the U-M Chronic Pain and Fatigue Research Center, and Richard E. Harris, Ph.D., a researcher at the center and the university.

The hyperactivity of pain processing mechanisms that characterizes FM and related conditions–from irritable bowel syndrome to tension headache and temporomandibular syndrome–can occur in association with psychological factors, “but psychological factors are not in any way required for an individual to develop or maintain this augmented central pain state,” they wrote.

Other investigators said in an interview that they hope to see more reviews like it, particularly since many studies of FM are low budget, small and too easily dismissed unless they are viewed together.

Neuroimaging studies, for instance, “are providing a consistent picture” when viewed together of strong neurobiologic underpinnings for FM, said Dr. Nancy Klimas, professor of medicine at the University of Miami. “But if you pull them apart, you can find faults with any one study in it having limited power, or some other limitation.”

“This is what [the authors] are saying–'look at the whole picture, it's impressive,'” said Dr. Klimas. “There's some real science to go behind the pain observation.”

Dr. Klimas said the review reminded her of a grand-rounds lecture she heard several years ago, in which a “prominent” department chair told students and faculty that fibromyalgia “is all in patients' heads.”

“He essentially said, don't let these patients talk to each other, don't let them read anything, don't let them have any support group meetings,” Dr. Klimas said. “I was livid. These patients [with FM] are often treated badly by their physicians. It's bad enough leaving without any hope that something can be done, but it's worse leaving a doctor's office having been made to feel small or patronized.”

Dr. Laurence Bradley, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama, agreed that the literature is ripe for strong conclusions. “The [review authors] are correct. A lot of new findings have emerged in the last 5–8 years … regarding gene variance that's associated with FM itself or with [related] disorders.

“And a lot of the neuroimaging work that has been done has demonstrated very convincingly that people with FM have enhanced or abnormal transmission of sensory signals through the CNS,” he said. “Behavioral studies–laboratory pain studies–also show consistent displays of abnormal pain responses in individuals with FM.”

In their review, Dr. Clauw and Dr. Harris described functional imaging studies done with single-photon emission computer tomography (SPECT) and functional magnetic resonance imaging (fMRI) that show differences in neural activation between patients with FM and pain-free controls. The studies indicate that FM patients have abnormalities within their central brain structures, they said.

There is evidence in FM that an “increased gain” in pain processing is driven by defects in both descending inhibitory pathways for pain processing and in spinal excitatory activity, the authors added.

Biochemical studies have supported the notion that the pathology might be a result of high levels of pronociceptive compounds (such as “substance P”), low levels of antinociceptive compounds, or both. Conversely “there is considerable evidence that this increased gain could occur because of a deficiency in one of the major endogenous analgesic pathways, the descending antinociceptive serotonergic-noradrenergic pathway” (Curr. Pain Headache Rep. 2006:10;403–7).

The “ultimate proof” that defective central control mechanisms are playing a role in FM and overlapping pain conditions comes from randomized clinical trials showing that neuroactive compounds that either increase inhibitory activity (such as serotonin-norepinephrine reuptake inhibitors) or decrease facilitatory activity (such as antiepileptics) can be efficacious in treating FM as well as neuropathic pain, said Dr. Clauw and Dr. Harris.

Dr. Bradley said that one of the “missing pieces of information” in the growing knowledge of pain transmission in FM is its original source.

“Where's the starting point?” he asked. “[Many experts] think it originates from abnormalities in the deep muscle tissue, but at this point we have a much better understanding of what goes on at the spinal level than we do of what factors contribute to the initiation of sensory signals.”

What's missing from the review itself, he and others noted, is the “consistent” evidence of altered neuroendocrine function in patients with FM.

Dr. Robert Bennett, who has led studies in this area, said that FM also appears to be a manifestation of an abnormal acute stress response involving abnormalities in levels of cortisol and growth hormone, an imbalance in sympathetic and vagal tone, and other phenomena–a notion that puts FM at least partly in the same camp, for underlying mechanisms, as chronic fatigue syndrome.

“The major things we know now [about FM] relate to the pain system,” said Dr. Bennett, professor of medicine at Oregon Health and Science University, Portland. “The neuroendocrine abnormalities–the manifestations of the acute stress response–have still, I think, been underinvestigated.”

Dr. Klimas, director of the University of Miami's chronic fatigue syndrome research center, said that more than 60% of her patients with the syndrome meet the case definition of FM as well, which reflects at least in part the fact that the FM definition is looser and more inclusive while the chronic fatigue syndrome definition has many exclusionary criteria.

Dr. Bradley added that a number of recent studies have also shown a familial aggregation of pain sensitivity. The studies show that first-degree relatives of patients with FM tend to have the “same sorts of unusual sensitivities to pain and abnormal pain responses,” even though this isn't always manifested as FM.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

The guidelines detail how children should be evaluated and cared for and clearly state that care for adults is falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001.

The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome.

Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full workup with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007;92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty.

Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature. “There's a new focus on natural, sensitive, and timely puberty induction,” she commented.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

The guidelines detail how children should be evaluated and cared for and clearly state that care for adults is falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001.

The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome.

Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full workup with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007;92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty.

Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature. “There's a new focus on natural, sensitive, and timely puberty induction,” she commented.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

The guidelines detail how children should be evaluated and cared for and clearly state that care for adults is falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001.

The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome.

Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full workup with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007;92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty.

Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature. “There's a new focus on natural, sensitive, and timely puberty induction,” she commented.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with [Turner syndrome] has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology and Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with [Turner syndrome],” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update the old recommendations, first issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of Turner syndrome is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of Turner syndrome patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (Turner syndrome can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose Turner syndrome as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of Turner syndrome, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with Turner syndrome should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

The current consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature, said Dr. Bondy.

“There's a new focus on natural, sensitive, and timely puberty induction,” she said.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than was previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said.

“There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has Turner syndrome] to the woman who's 40 and just got the [Turner syndrome] diagnosis,” commented Dr. Bondy.

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in Turner syndrome, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with [Turner syndrome] has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology and Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with [Turner syndrome],” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update the old recommendations, first issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of Turner syndrome is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of Turner syndrome patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (Turner syndrome can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose Turner syndrome as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of Turner syndrome, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with Turner syndrome should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

The current consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature, said Dr. Bondy.

“There's a new focus on natural, sensitive, and timely puberty induction,” she said.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than was previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said.

“There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has Turner syndrome] to the woman who's 40 and just got the [Turner syndrome] diagnosis,” commented Dr. Bondy.

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in Turner syndrome, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with [Turner syndrome] has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology and Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with [Turner syndrome],” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update the old recommendations, first issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of Turner syndrome is “much broader and often less severe than that described in many textbooks”—a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45,X and 45,X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of Turner syndrome patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (Turner syndrome can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose Turner syndrome as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of Turner syndrome, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with Turner syndrome should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

The current consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature, said Dr. Bondy.

“There's a new focus on natural, sensitive, and timely puberty induction,” she said.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than was previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said.

“There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has Turner syndrome] to the woman who's 40 and just got the [Turner syndrome] diagnosis,” commented Dr. Bondy.

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in Turner syndrome, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

When Dr. Fran Cogen, diabetes program director at Children's National Medical Center in Washington, read last year that patients with neonatal diabetes caused by particular genetic mutations could be successfully switched from insulin therapy to oral sulfonylureas, her mind raced.

“We realized we probably had several children with diabetes who were diagnosed under a year of age,” she said. The news about the mutations and treatment “was very interesting to me.”

She called Dr. Louis Philipson, the endocrinologist at the University of Chicago who—according to the article—had just treated a 6-year-old girl found to have a mutation in the KCNJ11 gene with high-dose sulfonylurea therapy, weaning her off her insulin pump.

After hearing about the treatment firsthand, she called one of the patients at Children's, an 18-year-old male whose diabetes had been diagnosed when he was a young infant. Genetic testing revealed that he too had the KCNJ11 mutation, and the family is now gearing up for treatment and a future that, at least in the short term, may well not involve insulin therapy.

Researchers who have spent the last several years trying to demonstrate that diabetes diagnosed before 6 months of age is almost never autoimmune hope that recent developments and reports in the literature will prompt more endocrinologists to take note of their patients' histories and order genetic tests when appropriate.

Neonatal diabetes, which is estimated to occur in 1 of every 100,000 newborns, is one of several clinical presentations in children for which a diagnosis of monogenic diabetes should be considered, experts say. A variety of genetic causes has been identified, but experts now believe that between 30% and 50% of children diagnosed with diabetes under 6 months of age have one of two mutations that affect the ATP-sensitive potassium channel of the beta cell.

The most common cause of permanent neonatal diabetes mellitus—the type of neonatal diabetes that has required continual insulin treatment from diagnosis onward—is a mutation in the KCNJ11 gene, which encodes a subunit of this channel called Kir6.2.

The mutation makes Kir6.2 less sensitive to the build-up of ATP and the channel thus fails to close in the presence of glucose (and increased intracellular ATP), leading to drastic reductions in insulin secretion.

Another less common cause is associated with mutations in the ABCC8 gene, which encodes the sulfonylurea receptor (SUR1)–another subunit of the beta cell's ATP-sensitive potassium channel.

Research on the mutations—and the notion that sulfonylureas can close this channel through an ATP-independent route—culminated last August when Dr. Andrew Hattersley of Peninsula Medical School in Exeter, England, and colleagues from several countries reported in the New England Journal of Medicine that 44 of 49 (90%) patients with kir6.2 mutations—aged 2 months to 36 years—successfully discontinued insulin after receiving high doses of sulfonylureas.

Glycosylated hemoglobin levels improved in all the patients, from a mean of 8.1% before sulfonylurea treatment to 6.4% at 12 weeks after cessation of insulin.

At 1 year, as the patients continued with much lower doses of sulfonylureas, the improved glycemic control was sustained—without any reports of severe hypoglycemia or any significant change in the frequency of hypoglycemia episodes (N. Engl. J. Med. 2006;355:467–77). As of last month, the patients' responses have been maintained past 2 years, Dr. Hattersley said in an interview.

Investigators of a second study published in the same issue of the journal reported that five out of nine patients with the ABCC8 mutation were also successfully switched from insulin therapy to oral sulfonylurea therapy (N. Engl. J. Med. 2006;355:456–65).

The long-term outlook for these patients, however, is uncertain. “We don't know, will they start having hypoglycemia? Will they start having inappropriate weight gain? Does the effectiveness (of sulfonylureas) wear out?” said Dr. Jay Cohen, medical director of the Endocrine Clinic in Memphis, Tenn.

Formation of a registry to assess long-term safety and efficacy would be helpful, he said, since “it's likely that no one institution will have more than one or two or three kids [with neonatal diabetes].”

Dr. Naomi Neufeld, professor of pediatrics at the University of California, Los Angeles, said she agrees that all children with neonatal diabetes should now be screened for the mutations, but she said she would approach treatment with some words of caution.

“It's intriguing to me to wonder, what happens 10 years from now? Will these children be different from those who burn out their pancreas?” she said.

Dr. Philipson said that while no one knows for sure, he suspects that they will indeed be different. “We know in type 2 diabetes, there's a significant failure of sulfonylureas over time. But these are [often] patients who are obese, insulin resistant, maybe hyperlipidemic, or [who] have other aspects of the metabolic syndrome that could impact negatively on their beta-cell function,” he said in an interview.

“These kids [with neonatal diabetes] are thin. All the children that I've seen and that Dr. Hattersley's seen have normal or below-normal [body mass indexes]. They're highly sensitive to insulin, and the insulin secretion we're looking for is modest,” he said.

In addition to Lilly Jaffe, the little girl he treated last summer, Dr. Philipson and his colleague Dr. Graeme Bell have treated six other children from across the country. He estimates about 20 children have been treated in the United States. “And there are at least several hundred others … who could be reached,” he said.

Tests for the mutations are commercially available through at least one company, Athena Diagnostics, he said.

Dr. Philipson has used glyburide, the sulfonylurea used in most of the patients in Dr. Hattersley's study, in an inpatient protocol that allows rapid switching from insulin. His protocol resembled that followed by investigators in Dr. Hattersley's study, which entailed starting glyburide at a dosage of 0.1 mg/kg twice daily and increasing the dosage by 0.2 mg/kg per day. In an outpatient protocol that some of the investigators chose, glyburide was introduced at 0.1 mg/kg per day and increased by that amount once a week.

In Dr. Hattersley's study, the median dosage of glyburide that was required for insulin independence was 0.45 mg/kg per day.

Lilly Jaffe is now receiving much smaller doses of glyburide twice a day, and “remarkably, her morning blood sugars are still quite reasonable,” said Dr. Philipson.

In Washington, Dr. Cogen said she will be “less worried” about using high doses of glyburide in her 18-year-old patient than she would be in a younger child, though she plans to get the word out to all of her patients with neonatal diabetes. “To be able to take a patient off of insulin is so exciting—it's everybody's dream.”

When Dr. Fran Cogen, diabetes program director at Children's National Medical Center in Washington, read last year that patients with neonatal diabetes caused by particular genetic mutations could be successfully switched from insulin therapy to oral sulfonylureas, her mind raced.

“We realized we probably had several children with diabetes who were diagnosed under a year of age,” she said. The news about the mutations and treatment “was very interesting to me.”

She called Dr. Louis Philipson, the endocrinologist at the University of Chicago who—according to the article—had just treated a 6-year-old girl found to have a mutation in the KCNJ11 gene with high-dose sulfonylurea therapy, weaning her off her insulin pump.

After hearing about the treatment firsthand, she called one of the patients at Children's, an 18-year-old male whose diabetes had been diagnosed when he was a young infant. Genetic testing revealed that he too had the KCNJ11 mutation, and the family is now gearing up for treatment and a future that, at least in the short term, may well not involve insulin therapy.

Researchers who have spent the last several years trying to demonstrate that diabetes diagnosed before 6 months of age is almost never autoimmune hope that recent developments and reports in the literature will prompt more endocrinologists to take note of their patients' histories and order genetic tests when appropriate.

Neonatal diabetes, which is estimated to occur in 1 of every 100,000 newborns, is one of several clinical presentations in children for which a diagnosis of monogenic diabetes should be considered, experts say. A variety of genetic causes has been identified, but experts now believe that between 30% and 50% of children diagnosed with diabetes under 6 months of age have one of two mutations that affect the ATP-sensitive potassium channel of the beta cell.

The most common cause of permanent neonatal diabetes mellitus—the type of neonatal diabetes that has required continual insulin treatment from diagnosis onward—is a mutation in the KCNJ11 gene, which encodes a subunit of this channel called Kir6.2.

The mutation makes Kir6.2 less sensitive to the build-up of ATP and the channel thus fails to close in the presence of glucose (and increased intracellular ATP), leading to drastic reductions in insulin secretion.

Another less common cause is associated with mutations in the ABCC8 gene, which encodes the sulfonylurea receptor (SUR1)–another subunit of the beta cell's ATP-sensitive potassium channel.

Research on the mutations—and the notion that sulfonylureas can close this channel through an ATP-independent route—culminated last August when Dr. Andrew Hattersley of Peninsula Medical School in Exeter, England, and colleagues from several countries reported in the New England Journal of Medicine that 44 of 49 (90%) patients with kir6.2 mutations—aged 2 months to 36 years—successfully discontinued insulin after receiving high doses of sulfonylureas.

Glycosylated hemoglobin levels improved in all the patients, from a mean of 8.1% before sulfonylurea treatment to 6.4% at 12 weeks after cessation of insulin.

At 1 year, as the patients continued with much lower doses of sulfonylureas, the improved glycemic control was sustained—without any reports of severe hypoglycemia or any significant change in the frequency of hypoglycemia episodes (N. Engl. J. Med. 2006;355:467–77). As of last month, the patients' responses have been maintained past 2 years, Dr. Hattersley said in an interview.

Investigators of a second study published in the same issue of the journal reported that five out of nine patients with the ABCC8 mutation were also successfully switched from insulin therapy to oral sulfonylurea therapy (N. Engl. J. Med. 2006;355:456–65).

The long-term outlook for these patients, however, is uncertain. “We don't know, will they start having hypoglycemia? Will they start having inappropriate weight gain? Does the effectiveness (of sulfonylureas) wear out?” said Dr. Jay Cohen, medical director of the Endocrine Clinic in Memphis, Tenn.

Formation of a registry to assess long-term safety and efficacy would be helpful, he said, since “it's likely that no one institution will have more than one or two or three kids [with neonatal diabetes].”

Dr. Naomi Neufeld, professor of pediatrics at the University of California, Los Angeles, said she agrees that all children with neonatal diabetes should now be screened for the mutations, but she said she would approach treatment with some words of caution.

“It's intriguing to me to wonder, what happens 10 years from now? Will these children be different from those who burn out their pancreas?” she said.

Dr. Philipson said that while no one knows for sure, he suspects that they will indeed be different. “We know in type 2 diabetes, there's a significant failure of sulfonylureas over time. But these are [often] patients who are obese, insulin resistant, maybe hyperlipidemic, or [who] have other aspects of the metabolic syndrome that could impact negatively on their beta-cell function,” he said in an interview.

“These kids [with neonatal diabetes] are thin. All the children that I've seen and that Dr. Hattersley's seen have normal or below-normal [body mass indexes]. They're highly sensitive to insulin, and the insulin secretion we're looking for is modest,” he said.

In addition to Lilly Jaffe, the little girl he treated last summer, Dr. Philipson and his colleague Dr. Graeme Bell have treated six other children from across the country. He estimates about 20 children have been treated in the United States. “And there are at least several hundred others … who could be reached,” he said.

Tests for the mutations are commercially available through at least one company, Athena Diagnostics, he said.

Dr. Philipson has used glyburide, the sulfonylurea used in most of the patients in Dr. Hattersley's study, in an inpatient protocol that allows rapid switching from insulin. His protocol resembled that followed by investigators in Dr. Hattersley's study, which entailed starting glyburide at a dosage of 0.1 mg/kg twice daily and increasing the dosage by 0.2 mg/kg per day. In an outpatient protocol that some of the investigators chose, glyburide was introduced at 0.1 mg/kg per day and increased by that amount once a week.

In Dr. Hattersley's study, the median dosage of glyburide that was required for insulin independence was 0.45 mg/kg per day.

Lilly Jaffe is now receiving much smaller doses of glyburide twice a day, and “remarkably, her morning blood sugars are still quite reasonable,” said Dr. Philipson.

In Washington, Dr. Cogen said she will be “less worried” about using high doses of glyburide in her 18-year-old patient than she would be in a younger child, though she plans to get the word out to all of her patients with neonatal diabetes. “To be able to take a patient off of insulin is so exciting—it's everybody's dream.”

When Dr. Fran Cogen, diabetes program director at Children's National Medical Center in Washington, read last year that patients with neonatal diabetes caused by particular genetic mutations could be successfully switched from insulin therapy to oral sulfonylureas, her mind raced.

“We realized we probably had several children with diabetes who were diagnosed under a year of age,” she said. The news about the mutations and treatment “was very interesting to me.”

She called Dr. Louis Philipson, the endocrinologist at the University of Chicago who—according to the article—had just treated a 6-year-old girl found to have a mutation in the KCNJ11 gene with high-dose sulfonylurea therapy, weaning her off her insulin pump.

After hearing about the treatment firsthand, she called one of the patients at Children's, an 18-year-old male whose diabetes had been diagnosed when he was a young infant. Genetic testing revealed that he too had the KCNJ11 mutation, and the family is now gearing up for treatment and a future that, at least in the short term, may well not involve insulin therapy.

Researchers who have spent the last several years trying to demonstrate that diabetes diagnosed before 6 months of age is almost never autoimmune hope that recent developments and reports in the literature will prompt more endocrinologists to take note of their patients' histories and order genetic tests when appropriate.

Neonatal diabetes, which is estimated to occur in 1 of every 100,000 newborns, is one of several clinical presentations in children for which a diagnosis of monogenic diabetes should be considered, experts say. A variety of genetic causes has been identified, but experts now believe that between 30% and 50% of children diagnosed with diabetes under 6 months of age have one of two mutations that affect the ATP-sensitive potassium channel of the beta cell.

The most common cause of permanent neonatal diabetes mellitus—the type of neonatal diabetes that has required continual insulin treatment from diagnosis onward—is a mutation in the KCNJ11 gene, which encodes a subunit of this channel called Kir6.2.

The mutation makes Kir6.2 less sensitive to the build-up of ATP and the channel thus fails to close in the presence of glucose (and increased intracellular ATP), leading to drastic reductions in insulin secretion.

Another less common cause is associated with mutations in the ABCC8 gene, which encodes the sulfonylurea receptor (SUR1)–another subunit of the beta cell's ATP-sensitive potassium channel.

Research on the mutations—and the notion that sulfonylureas can close this channel through an ATP-independent route—culminated last August when Dr. Andrew Hattersley of Peninsula Medical School in Exeter, England, and colleagues from several countries reported in the New England Journal of Medicine that 44 of 49 (90%) patients with kir6.2 mutations—aged 2 months to 36 years—successfully discontinued insulin after receiving high doses of sulfonylureas.

Glycosylated hemoglobin levels improved in all the patients, from a mean of 8.1% before sulfonylurea treatment to 6.4% at 12 weeks after cessation of insulin.

At 1 year, as the patients continued with much lower doses of sulfonylureas, the improved glycemic control was sustained—without any reports of severe hypoglycemia or any significant change in the frequency of hypoglycemia episodes (N. Engl. J. Med. 2006;355:467–77). As of last month, the patients' responses have been maintained past 2 years, Dr. Hattersley said in an interview.

Investigators of a second study published in the same issue of the journal reported that five out of nine patients with the ABCC8 mutation were also successfully switched from insulin therapy to oral sulfonylurea therapy (N. Engl. J. Med. 2006;355:456–65).

The long-term outlook for these patients, however, is uncertain. “We don't know, will they start having hypoglycemia? Will they start having inappropriate weight gain? Does the effectiveness (of sulfonylureas) wear out?” said Dr. Jay Cohen, medical director of the Endocrine Clinic in Memphis, Tenn.

Formation of a registry to assess long-term safety and efficacy would be helpful, he said, since “it's likely that no one institution will have more than one or two or three kids [with neonatal diabetes].”

Dr. Naomi Neufeld, professor of pediatrics at the University of California, Los Angeles, said she agrees that all children with neonatal diabetes should now be screened for the mutations, but she said she would approach treatment with some words of caution.

“It's intriguing to me to wonder, what happens 10 years from now? Will these children be different from those who burn out their pancreas?” she said.

Dr. Philipson said that while no one knows for sure, he suspects that they will indeed be different. “We know in type 2 diabetes, there's a significant failure of sulfonylureas over time. But these are [often] patients who are obese, insulin resistant, maybe hyperlipidemic, or [who] have other aspects of the metabolic syndrome that could impact negatively on their beta-cell function,” he said in an interview.

“These kids [with neonatal diabetes] are thin. All the children that I've seen and that Dr. Hattersley's seen have normal or below-normal [body mass indexes]. They're highly sensitive to insulin, and the insulin secretion we're looking for is modest,” he said.

In addition to Lilly Jaffe, the little girl he treated last summer, Dr. Philipson and his colleague Dr. Graeme Bell have treated six other children from across the country. He estimates about 20 children have been treated in the United States. “And there are at least several hundred others … who could be reached,” he said.

Tests for the mutations are commercially available through at least one company, Athena Diagnostics, he said.

Dr. Philipson has used glyburide, the sulfonylurea used in most of the patients in Dr. Hattersley's study, in an inpatient protocol that allows rapid switching from insulin. His protocol resembled that followed by investigators in Dr. Hattersley's study, which entailed starting glyburide at a dosage of 0.1 mg/kg twice daily and increasing the dosage by 0.2 mg/kg per day. In an outpatient protocol that some of the investigators chose, glyburide was introduced at 0.1 mg/kg per day and increased by that amount once a week.

In Dr. Hattersley's study, the median dosage of glyburide that was required for insulin independence was 0.45 mg/kg per day.

Lilly Jaffe is now receiving much smaller doses of glyburide twice a day, and “remarkably, her morning blood sugars are still quite reasonable,” said Dr. Philipson.

In Washington, Dr. Cogen said she will be “less worried” about using high doses of glyburide in her 18-year-old patient than she would be in a younger child, though she plans to get the word out to all of her patients with neonatal diabetes. “To be able to take a patient off of insulin is so exciting—it's everybody's dream.”

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”–a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45, X and 45, X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”–a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45, X and 45, X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Updated guidelines on evaluating and treating girls and women with Turner syndrome advise against the practice of delaying puberty to increase height and emphasize the importance of early diagnosis, estrogen treatment, and more comprehensive cardiovascular evaluation—including the use of diagnostic MRI—than is typically done today.

Although the guidelines from the international, multidisciplinary Turner Syndrome Consensus Study Group detail how children should be evaluated and cared for—emphasizing, for example, the importance of comprehensive educational evaluation in early childhood—the experts also clearly state that care for adults is more often falling short.

“The care of adults with TS has received less attention than [has] the treatment of children, and many seem to be falling through the cracks with inadequate cardiovascular evaluation and estrogen treatment,” say the new guidelines, published in the Journal of Clinical Endocrinology & Metabolism.

On the other hand, while medical care must be improved and while many questions about care “remain unanswered,” the experts “realize now that we have a lot more well-functioning people with TS,” Dr. Carolyn A. Bondy said in an interview.

Dr. Bondy, chief of the developmental endocrinology branch at the National Institute of Child Health and Human Development in Bethesda, Md., chaired the consensus conference and guideline-writing committee for the consensus group, which met last summer to update recommendations issued in 2001. The guidelines mainly represent “consensus judgments” rather than evidence-based conclusions, the committee noted in its document.

The clinical spectrum of TS is “much broader and often less severe than that described in many textbooks”–a finding that seems at odds with a “high elective abortion rate for incidentally diagnosed 45, X and 45, X/mosaic fetuses,” the guidelines say. This means that the content of prenatal counseling “needs updating” with the input of TS patient and parent groups, the document says.

That's especially true now that the American College of Obstetricians and Gynecologists is recommending that all women, regardless of their age, be offered screening for Down syndrome. Parents who receive a Turner syndrome diagnosis from such screening (TS can be an incidental finding) must be given information about the broad phenotypic spectrum of the syndrome and the high quality of life for many patients, Dr. Brody said.

Recent reports of an often-normal quality of life for those receiving comprehensive medical care should encourage—not mitigate—the efforts of physicians to diagnose TS as early as possible and better appreciate its many consequences, she said.

The diagnosis should be considered in any female with unexplained growth failure or pubertal delay or any constellation of the syndrome's characteristic physical features, the guidelines say.

“Regrettably, late diagnosis of TS, even in adults, is still a problem. No matter what the age of the patient, a full work-up with assessment of congenital malformations should be performed, including all screening tests recommended for younger patients,” the document says.

Adults with TS should then be regularly screened for hypertension, diabetes, dyslipidemia, aortic enlargement, hearing loss, osteoporosis, and thyroid and celiac diseases (J. Clin. Endocrinol. Metab. 2007:92:10–25).

The guidelines offer age-specific suggestions for ovarian hormone replacement and say that “ideally, natural estradiol and progesterone, rather than analogs, should be delivered by transdermal or transmembranous routes so as to mimic age-appropriate physiological patterns as closely as possible.”

Regimens can vary to meet individuals' tolerance and preference, however, and “the most important consideration is that women actually take ovarian hormone replacement,” the authors say.

Without it, the risk of significant osteoporosis is high. “These women can have severe osteoporosis at 25,” said Dr. Bondy. “I have a 30-year-old patient who has lost 2 inches of height and has a hump.”

Estrogen therapy often is required to induce pubertal development (30% or more will undergo some spontaneous pubertal development), but experts used to recommend delaying estrogen therapy until age 15 to optimize height potential.

Today, Dr. Bondy said, the consensus is that such delay undervalues the psychosocial importance of age-appropriate puberty. Recent evidence also suggests that low-dose estrogen does not inhibit growth hormone-enhanced increases in stature.

Recent studies have also suggested a broader spectrum of cardiovascular abnormalities than were previously recognized, and the consensus group agreed to bring “the heart to the forefront,” Dr. Bondy said. “There's a new emphasis [in the guidelines] on the fact that everyone needs cardiovascular screening—from the newborn to the woman who's 20 and just found out she's infertile [and has TS] to the woman who's 40 and just got the [TS] diagnosis.”

And while echocardiography usually is adequate for screening infants and young girls, MRI also must be performed in older girls and adults.

Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concern about the safety of pregnancy in TS, and “preconception assessment must include cardiology evaluation with MRI of the aorta,” the experts say.

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

Treatment with tumor necrosis factor-blocking agents is more effective than methotrexate monotherapy at easing pain and fatigue in patients with psoriatic arthritis and in improving their general health when used in daily clinical practice, according to investigators of an ongoing longitudinal, observational study in Norway.

In a report of 6-month results, investigators said that 526 patients with psoriatic arthritis improved regardless of whether they received methotrexate (MTX) monotherapy or TNF-blocking agents, but “the improvement was larger with TNF-inhibitors.” Assessments were made using numerous measures of disease activity and health-related quality of life (Ann. Rheum. Dis. 2007 Jan. 9 [Epub doi:10.1136/ard.2006. 064808]).

The patients were part of a larger Norwegian registry—the NOR-DMARD Register—in which five Norwegian rheumatology departments consecutively register all their patients with inflammatory arthropathies, said Dr. M.S. Heiberg, of the department of rheumatology in Diakonhjemmet Hospital in Oslo, Norway, and fellow associates.

The patients had a mean age of 48 years and mean disease duration of 7 years. Almost 50% were females; 35% had erosive disease.

Of the 526 patients, 380 received MTX monotherapy and 146 received the TNF-blocking agents infliximab, etanercept, and adalimumab. Of those receiving anti-TNF therapy, 75% of those on infliximab, 60% of those on etanercept, and 79% of those on adalimumab received comcomitant MTX. Patients receiving anti-TNF therapy generally had more active and severe disease.

In assessing the clinical improvement, adjustments were made for age, gender, number of previous disease-modifying antirheumatic drugs, the presence of erosive disease, the treatment center, and the investigator's global assessment, the investigators said.

The adjusted changes at 3 and 6 months were significantly larger in the anti-TNF group for the following assessments: erythrocyte sedimentation rate, Disease Activity Score-28, a shortened version of the health assessment question (M-HAQ), fatigue and global disease activity on a visual analog scale, and four out of eight dimensions on the Short Form-36 health survey (bodily pain, vitality, role physical, and general health).

For instance, SF-36 scores for bodily pain rose by about 18 in the anti-TNF group and by 10 in the MTX group, while scores for general health rose by 7 and 2, respectively. (Scores are computed with a value from 0 to 100, with 100 being the best possible health state.)

Whether concomitant MTX was given in conjunction with anti-TNF therapy made little difference, a subanalysis showed. Improvements in the measures were similar between the subgroups of anti-TNF therapy.

More studies are needed to further establish the role of traditional drugs, they said.

Treatment with tumor necrosis factor-blocking agents is more effective than methotrexate monotherapy at easing pain and fatigue in patients with psoriatic arthritis and in improving their general health when used in daily clinical practice, according to investigators of an ongoing longitudinal, observational study in Norway.

In a report of 6-month results, investigators said that 526 patients with psoriatic arthritis improved regardless of whether they received methotrexate (MTX) monotherapy or TNF-blocking agents, but “the improvement was larger with TNF-inhibitors.” Assessments were made using numerous measures of disease activity and health-related quality of life (Ann. Rheum. Dis. 2007 Jan. 9 [Epub doi:10.1136/ard.2006. 064808]).

The patients were part of a larger Norwegian registry—the NOR-DMARD Register—in which five Norwegian rheumatology departments consecutively register all their patients with inflammatory arthropathies, said Dr. M.S. Heiberg, of the department of rheumatology in Diakonhjemmet Hospital in Oslo, Norway, and fellow associates.

The patients had a mean age of 48 years and mean disease duration of 7 years. Almost 50% were females; 35% had erosive disease.

Of the 526 patients, 380 received MTX monotherapy and 146 received the TNF-blocking agents infliximab, etanercept, and adalimumab. Of those receiving anti-TNF therapy, 75% of those on infliximab, 60% of those on etanercept, and 79% of those on adalimumab received comcomitant MTX. Patients receiving anti-TNF therapy generally had more active and severe disease.

In assessing the clinical improvement, adjustments were made for age, gender, number of previous disease-modifying antirheumatic drugs, the presence of erosive disease, the treatment center, and the investigator's global assessment, the investigators said.

The adjusted changes at 3 and 6 months were significantly larger in the anti-TNF group for the following assessments: erythrocyte sedimentation rate, Disease Activity Score-28, a shortened version of the health assessment question (M-HAQ), fatigue and global disease activity on a visual analog scale, and four out of eight dimensions on the Short Form-36 health survey (bodily pain, vitality, role physical, and general health).

For instance, SF-36 scores for bodily pain rose by about 18 in the anti-TNF group and by 10 in the MTX group, while scores for general health rose by 7 and 2, respectively. (Scores are computed with a value from 0 to 100, with 100 being the best possible health state.)

Whether concomitant MTX was given in conjunction with anti-TNF therapy made little difference, a subanalysis showed. Improvements in the measures were similar between the subgroups of anti-TNF therapy.

More studies are needed to further establish the role of traditional drugs, they said.

Treatment with tumor necrosis factor-blocking agents is more effective than methotrexate monotherapy at easing pain and fatigue in patients with psoriatic arthritis and in improving their general health when used in daily clinical practice, according to investigators of an ongoing longitudinal, observational study in Norway.

In a report of 6-month results, investigators said that 526 patients with psoriatic arthritis improved regardless of whether they received methotrexate (MTX) monotherapy or TNF-blocking agents, but “the improvement was larger with TNF-inhibitors.” Assessments were made using numerous measures of disease activity and health-related quality of life (Ann. Rheum. Dis. 2007 Jan. 9 [Epub doi:10.1136/ard.2006. 064808]).

The patients were part of a larger Norwegian registry—the NOR-DMARD Register—in which five Norwegian rheumatology departments consecutively register all their patients with inflammatory arthropathies, said Dr. M.S. Heiberg, of the department of rheumatology in Diakonhjemmet Hospital in Oslo, Norway, and fellow associates.

The patients had a mean age of 48 years and mean disease duration of 7 years. Almost 50% were females; 35% had erosive disease.

Of the 526 patients, 380 received MTX monotherapy and 146 received the TNF-blocking agents infliximab, etanercept, and adalimumab. Of those receiving anti-TNF therapy, 75% of those on infliximab, 60% of those on etanercept, and 79% of those on adalimumab received comcomitant MTX. Patients receiving anti-TNF therapy generally had more active and severe disease.

In assessing the clinical improvement, adjustments were made for age, gender, number of previous disease-modifying antirheumatic drugs, the presence of erosive disease, the treatment center, and the investigator's global assessment, the investigators said.

The adjusted changes at 3 and 6 months were significantly larger in the anti-TNF group for the following assessments: erythrocyte sedimentation rate, Disease Activity Score-28, a shortened version of the health assessment question (M-HAQ), fatigue and global disease activity on a visual analog scale, and four out of eight dimensions on the Short Form-36 health survey (bodily pain, vitality, role physical, and general health).

For instance, SF-36 scores for bodily pain rose by about 18 in the anti-TNF group and by 10 in the MTX group, while scores for general health rose by 7 and 2, respectively. (Scores are computed with a value from 0 to 100, with 100 being the best possible health state.)

Whether concomitant MTX was given in conjunction with anti-TNF therapy made little difference, a subanalysis showed. Improvements in the measures were similar between the subgroups of anti-TNF therapy.

More studies are needed to further establish the role of traditional drugs, they said.