Miriam E. Tucker

It would take about 5 years to complete a trial to satisfy the Food and Drug Administration's concerns about the cardiovascular safety of the investigational diabetes drug muraglitazar, according to a statement issued by Bristol-Myers Squibb.

The company, which manufactures the dual-acting agent under the trade name Pargluva, has begun discussions with its marketing partner Merck to terminate their collaborative agreement.

At press time, Bristol-Myers Squibb was discussing a range of options with the FDA, including possible termination of muraglitazar's development.

The announcement came just 9 days after the FDA granted an “approval” letter for the combination peroxisome proliferator-activated receptor α and γ activator, in which the agency had also requested more data regarding the drug's safety profile.

Later that same week, an article by Steven E. Nissen, M.D., of the Cleveland Clinic Foundation and his associates outlined increased cardiovascular event rates among muraglitazar-treated patients in phase II and III clinical trials of the drug.

The investigators recommended that the drug not be approved until its safety is documented in a dedicated cardiovascular (CV) events trial (JAMA 2005;294: [Epub doi:10.1001/jama.294.20.joc50147]).

Their analysis was based on data made public on the Food and Drug Administration's Web site on Sept. 8 and discussed in detail at a Sept. 9 meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee. At that time, the panel voted to recommend approval of the drug as monotherapy and in combination with metformin, but not with sulfonylureas (FAMILY PRACTICE NEWS, Oct. 1, 2005, p. 10).

For their analysis, Dr. Nissen, Eric J. Topol, M.D., and Kathy Wolski combined data from five clinical trials, limiting the analysis to diabetic patients given the 2.5-mg and 5-mg doses of muraglitazar for which the companies are seeking licensure.

The primary outcome measure—all-cause mortality, nonfatal MI, or nonfatal stroke—occurred in 1.47% (35) of 2,374 subjects versus 0.67% (9) of 1,351 control patients who received either placebo or 30-mg pioglitazone, for a relative risk (RR) of 2.23.

Substituting CV death for all-cause mortality, the combined end points occurred in 1.14% (27) of 2,374 muraglitazar-treated patients, versus 0.52% (7) of 1,351 controls (RR 2.21). When heart failure and transient ischemic attacks were added to the composite, the incidence rates were 2.11% for muraglitazar and 0.81% for controls (RR 2.62).

Relative risk was consistently higher for individual components of the primary end point in the muraglitazar-treated group versus controls. Rates ranged from 2.14 for fatal or nonfatal MI to 7.43 for adjudicated heart failure. However, the number of events was small and differences for individual components of the primary outcome measure were not statistically significant, the investigators reported.

These and other safety data were analyzed and presented in detail at the Sept. 9 hearing by Julie Golden, M.D., a medical officer in the FDA's Division of Metabolic and Endocrine Drug Products. She, too, had noted that the percentage of CV events in the muraglitazar groups was approximately twice that of comparators. However, when broken down by monotherapy (two studies) and combination therapy (three studies), the imbalance of CV adverse events was seen only in the combination studies, and in fact was mostly driven by one study in which muraglitazar or placebo was added to glyburide (11 vs. 0 events). At least two of these subjects had evidence of other causes for the event.

CV deaths occurred in 9 of 3,226 muraglitazar subjects, 1 of 591 placebo subjects, and none of 823 on pioglitazone, giving an overall death rate 1.5 times higher with muraglitazar than with the comparators. Overall deaths occurred in 19, 1, and 2 patients, respectively; the incidence was 2.5–3 times higher with muraglitazar, Dr. Golden said. However, “the rates in the comparator groups, based on exceedingly small numbers of events, are highly unstable, meaning that even one additional death in either group could impact the result,” she said at the hearing.

Eight of the CV deaths were in subjects taking 2.5 or 5 mg of muraglitazar, and six were subjects from a single study in which 5-mg muraglitazar or 30-mg pioglitazone was added to metformin.

In that study, which had about 580 subjects per treatment arm, there was no marked difference in overall CV events. Moreover, no clear clinical or pathologic pattern could be identified for either deaths or CV events, and the pooled studies did not show a dose-response pattern, she noted.

For its part, Bristol-Myers Squibb had analyzed the data taking into account the duration of drug exposure. For CV events, there were 28.2/1,000 patient-years on muraglitazar, compared with 33.4/1,000 for placebo and 19.7/1,000 with pioglitazone—a nonsignificant difference, Rene Belder, M.D., vice president of global clinical research at Bristol-Myers Squibb, said at the hearing.

Similarly, for the CV deaths, the rates were 3/1,000 patient-years for placebo, compared with 2.6/1,000 with muraglitazar. “By taking into account the difference in patient exposure, the apparent imbalance in cardiovascular death is reversed,” Dr. Belder said.

But that analysis was challenged by James M. Brophy, M.D. in an editorial accompanying the Dr. Nissen's report. He pointed out that the company's analysis included 495 patients who had received subtherapeutic doses of 2.5 mg or less in whom there were no CV events, thereby diluting the risk estimate. When the rates were recalculated to include only those patients receiving the proposed marketed doses of 2.5 or 5 mg, the muraglitazar group shows a 20% increase in events, compared with placebo, and a 67% increase, compared with the combined pioglitazone/placebo control group, said Dr. Brophy, of McGill University, Montreal, who also listed several other flaws in the analysis.

It would take about 5 years to complete a trial to satisfy the Food and Drug Administration's concerns about the cardiovascular safety of the investigational diabetes drug muraglitazar, according to a statement issued by Bristol-Myers Squibb.

The company, which manufactures the dual-acting agent under the trade name Pargluva, has begun discussions with its marketing partner Merck to terminate their collaborative agreement.

At press time, Bristol-Myers Squibb was discussing a range of options with the FDA, including possible termination of muraglitazar's development.

The announcement came just 9 days after the FDA granted an “approval” letter for the combination peroxisome proliferator-activated receptor α and γ activator, in which the agency had also requested more data regarding the drug's safety profile.

Later that same week, an article by Steven E. Nissen, M.D., of the Cleveland Clinic Foundation and his associates outlined increased cardiovascular event rates among muraglitazar-treated patients in phase II and III clinical trials of the drug.

The investigators recommended that the drug not be approved until its safety is documented in a dedicated cardiovascular (CV) events trial (JAMA 2005;294: [Epub doi:10.1001/jama.294.20.joc50147]).

Their analysis was based on data made public on the Food and Drug Administration's Web site on Sept. 8 and discussed in detail at a Sept. 9 meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee. At that time, the panel voted to recommend approval of the drug as monotherapy and in combination with metformin, but not with sulfonylureas (FAMILY PRACTICE NEWS, Oct. 1, 2005, p. 10).

For their analysis, Dr. Nissen, Eric J. Topol, M.D., and Kathy Wolski combined data from five clinical trials, limiting the analysis to diabetic patients given the 2.5-mg and 5-mg doses of muraglitazar for which the companies are seeking licensure.

The primary outcome measure—all-cause mortality, nonfatal MI, or nonfatal stroke—occurred in 1.47% (35) of 2,374 subjects versus 0.67% (9) of 1,351 control patients who received either placebo or 30-mg pioglitazone, for a relative risk (RR) of 2.23.

Substituting CV death for all-cause mortality, the combined end points occurred in 1.14% (27) of 2,374 muraglitazar-treated patients, versus 0.52% (7) of 1,351 controls (RR 2.21). When heart failure and transient ischemic attacks were added to the composite, the incidence rates were 2.11% for muraglitazar and 0.81% for controls (RR 2.62).

Relative risk was consistently higher for individual components of the primary end point in the muraglitazar-treated group versus controls. Rates ranged from 2.14 for fatal or nonfatal MI to 7.43 for adjudicated heart failure. However, the number of events was small and differences for individual components of the primary outcome measure were not statistically significant, the investigators reported.

These and other safety data were analyzed and presented in detail at the Sept. 9 hearing by Julie Golden, M.D., a medical officer in the FDA's Division of Metabolic and Endocrine Drug Products. She, too, had noted that the percentage of CV events in the muraglitazar groups was approximately twice that of comparators. However, when broken down by monotherapy (two studies) and combination therapy (three studies), the imbalance of CV adverse events was seen only in the combination studies, and in fact was mostly driven by one study in which muraglitazar or placebo was added to glyburide (11 vs. 0 events). At least two of these subjects had evidence of other causes for the event.

CV deaths occurred in 9 of 3,226 muraglitazar subjects, 1 of 591 placebo subjects, and none of 823 on pioglitazone, giving an overall death rate 1.5 times higher with muraglitazar than with the comparators. Overall deaths occurred in 19, 1, and 2 patients, respectively; the incidence was 2.5–3 times higher with muraglitazar, Dr. Golden said. However, “the rates in the comparator groups, based on exceedingly small numbers of events, are highly unstable, meaning that even one additional death in either group could impact the result,” she said at the hearing.

Eight of the CV deaths were in subjects taking 2.5 or 5 mg of muraglitazar, and six were subjects from a single study in which 5-mg muraglitazar or 30-mg pioglitazone was added to metformin.

In that study, which had about 580 subjects per treatment arm, there was no marked difference in overall CV events. Moreover, no clear clinical or pathologic pattern could be identified for either deaths or CV events, and the pooled studies did not show a dose-response pattern, she noted.

For its part, Bristol-Myers Squibb had analyzed the data taking into account the duration of drug exposure. For CV events, there were 28.2/1,000 patient-years on muraglitazar, compared with 33.4/1,000 for placebo and 19.7/1,000 with pioglitazone—a nonsignificant difference, Rene Belder, M.D., vice president of global clinical research at Bristol-Myers Squibb, said at the hearing.

Similarly, for the CV deaths, the rates were 3/1,000 patient-years for placebo, compared with 2.6/1,000 with muraglitazar. “By taking into account the difference in patient exposure, the apparent imbalance in cardiovascular death is reversed,” Dr. Belder said.

But that analysis was challenged by James M. Brophy, M.D. in an editorial accompanying the Dr. Nissen's report. He pointed out that the company's analysis included 495 patients who had received subtherapeutic doses of 2.5 mg or less in whom there were no CV events, thereby diluting the risk estimate. When the rates were recalculated to include only those patients receiving the proposed marketed doses of 2.5 or 5 mg, the muraglitazar group shows a 20% increase in events, compared with placebo, and a 67% increase, compared with the combined pioglitazone/placebo control group, said Dr. Brophy, of McGill University, Montreal, who also listed several other flaws in the analysis.

It would take about 5 years to complete a trial to satisfy the Food and Drug Administration's concerns about the cardiovascular safety of the investigational diabetes drug muraglitazar, according to a statement issued by Bristol-Myers Squibb.

The company, which manufactures the dual-acting agent under the trade name Pargluva, has begun discussions with its marketing partner Merck to terminate their collaborative agreement.

At press time, Bristol-Myers Squibb was discussing a range of options with the FDA, including possible termination of muraglitazar's development.

The announcement came just 9 days after the FDA granted an “approval” letter for the combination peroxisome proliferator-activated receptor α and γ activator, in which the agency had also requested more data regarding the drug's safety profile.

Later that same week, an article by Steven E. Nissen, M.D., of the Cleveland Clinic Foundation and his associates outlined increased cardiovascular event rates among muraglitazar-treated patients in phase II and III clinical trials of the drug.

The investigators recommended that the drug not be approved until its safety is documented in a dedicated cardiovascular (CV) events trial (JAMA 2005;294: [Epub doi:10.1001/jama.294.20.joc50147]).

Their analysis was based on data made public on the Food and Drug Administration's Web site on Sept. 8 and discussed in detail at a Sept. 9 meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee. At that time, the panel voted to recommend approval of the drug as monotherapy and in combination with metformin, but not with sulfonylureas (FAMILY PRACTICE NEWS, Oct. 1, 2005, p. 10).

For their analysis, Dr. Nissen, Eric J. Topol, M.D., and Kathy Wolski combined data from five clinical trials, limiting the analysis to diabetic patients given the 2.5-mg and 5-mg doses of muraglitazar for which the companies are seeking licensure.

The primary outcome measure—all-cause mortality, nonfatal MI, or nonfatal stroke—occurred in 1.47% (35) of 2,374 subjects versus 0.67% (9) of 1,351 control patients who received either placebo or 30-mg pioglitazone, for a relative risk (RR) of 2.23.

Substituting CV death for all-cause mortality, the combined end points occurred in 1.14% (27) of 2,374 muraglitazar-treated patients, versus 0.52% (7) of 1,351 controls (RR 2.21). When heart failure and transient ischemic attacks were added to the composite, the incidence rates were 2.11% for muraglitazar and 0.81% for controls (RR 2.62).

Relative risk was consistently higher for individual components of the primary end point in the muraglitazar-treated group versus controls. Rates ranged from 2.14 for fatal or nonfatal MI to 7.43 for adjudicated heart failure. However, the number of events was small and differences for individual components of the primary outcome measure were not statistically significant, the investigators reported.

These and other safety data were analyzed and presented in detail at the Sept. 9 hearing by Julie Golden, M.D., a medical officer in the FDA's Division of Metabolic and Endocrine Drug Products. She, too, had noted that the percentage of CV events in the muraglitazar groups was approximately twice that of comparators. However, when broken down by monotherapy (two studies) and combination therapy (three studies), the imbalance of CV adverse events was seen only in the combination studies, and in fact was mostly driven by one study in which muraglitazar or placebo was added to glyburide (11 vs. 0 events). At least two of these subjects had evidence of other causes for the event.

CV deaths occurred in 9 of 3,226 muraglitazar subjects, 1 of 591 placebo subjects, and none of 823 on pioglitazone, giving an overall death rate 1.5 times higher with muraglitazar than with the comparators. Overall deaths occurred in 19, 1, and 2 patients, respectively; the incidence was 2.5–3 times higher with muraglitazar, Dr. Golden said. However, “the rates in the comparator groups, based on exceedingly small numbers of events, are highly unstable, meaning that even one additional death in either group could impact the result,” she said at the hearing.

Eight of the CV deaths were in subjects taking 2.5 or 5 mg of muraglitazar, and six were subjects from a single study in which 5-mg muraglitazar or 30-mg pioglitazone was added to metformin.

In that study, which had about 580 subjects per treatment arm, there was no marked difference in overall CV events. Moreover, no clear clinical or pathologic pattern could be identified for either deaths or CV events, and the pooled studies did not show a dose-response pattern, she noted.

For its part, Bristol-Myers Squibb had analyzed the data taking into account the duration of drug exposure. For CV events, there were 28.2/1,000 patient-years on muraglitazar, compared with 33.4/1,000 for placebo and 19.7/1,000 with pioglitazone—a nonsignificant difference, Rene Belder, M.D., vice president of global clinical research at Bristol-Myers Squibb, said at the hearing.

Similarly, for the CV deaths, the rates were 3/1,000 patient-years for placebo, compared with 2.6/1,000 with muraglitazar. “By taking into account the difference in patient exposure, the apparent imbalance in cardiovascular death is reversed,” Dr. Belder said.

But that analysis was challenged by James M. Brophy, M.D. in an editorial accompanying the Dr. Nissen's report. He pointed out that the company's analysis included 495 patients who had received subtherapeutic doses of 2.5 mg or less in whom there were no CV events, thereby diluting the risk estimate. When the rates were recalculated to include only those patients receiving the proposed marketed doses of 2.5 or 5 mg, the muraglitazar group shows a 20% increase in events, compared with placebo, and a 67% increase, compared with the combined pioglitazone/placebo control group, said Dr. Brophy, of McGill University, Montreal, who also listed several other flaws in the analysis.

WASHINGTON — Even parents who don't trust vaccines might let you vaccinate their children if they trust you.

That was the conclusion drawn from a survey of parents of 7,810 children aged 19–35 months from the 2001–2002 National Immunization Survey, conducted by Philip J. Smith, Ph.D., and his associates at the Centers for Disease Control and Prevention's National Immunization Program, in Atlanta.

The majority of parents (77%) said they believed vaccines were safe and that their belief was influenced by their child's health care provider (physician, nurse, or other). However, 5.7% of parents reported believing that vaccines were not safe, with 2% saying they were not influenced by their child's health care provider while the other 3.7% reported that they were.

Another 17.2% said that they believed vaccines were safe but their belief was not influenced by a health care provider. This group is of concern, because “One thing we don't want to happen is that these parents' opinions migrate to the other side,” Dr. Smith said at the annual meeting of the American Academy of Pediatrics.

Parents who were not influenced by a health care provider were significantly more likely to say that vaccines were not safe, compared with parents who were influenced by a provider (10.4% vs. 4.6%).

Somewhat surprising, however, were the up-to-date immunization rates among the children of the parents who believe that immunizations are not safe: 71.5% for those who said they were influenced by a health care provider, compared with just 55.8% of those who were not, a highly significant difference. “All this is pointing to the importance of a health care provider talking with the parent,” Dr. Smith said.

Indeed, earlier this year the American Academy of Pediatrics published guidelines on how to respond to parents' refusal of immunization for their children (Pediatrics 2005;115:1428–31).

Among AAP's recommendations are to listen respectfully to what parents have to say and not minimize their concerns. Be honest about the benefits and risks of immunization, correct any misconceptions or misinformation, and refer the parents to trusted sources such as the CDC's National Immunization Program page (www.cdc.gov/nip

WASHINGTON — Even parents who don't trust vaccines might let you vaccinate their children if they trust you.

That was the conclusion drawn from a survey of parents of 7,810 children aged 19–35 months from the 2001–2002 National Immunization Survey, conducted by Philip J. Smith, Ph.D., and his associates at the Centers for Disease Control and Prevention's National Immunization Program, in Atlanta.

The majority of parents (77%) said they believed vaccines were safe and that their belief was influenced by their child's health care provider (physician, nurse, or other). However, 5.7% of parents reported believing that vaccines were not safe, with 2% saying they were not influenced by their child's health care provider while the other 3.7% reported that they were.

Another 17.2% said that they believed vaccines were safe but their belief was not influenced by a health care provider. This group is of concern, because “One thing we don't want to happen is that these parents' opinions migrate to the other side,” Dr. Smith said at the annual meeting of the American Academy of Pediatrics.

Parents who were not influenced by a health care provider were significantly more likely to say that vaccines were not safe, compared with parents who were influenced by a provider (10.4% vs. 4.6%).

Somewhat surprising, however, were the up-to-date immunization rates among the children of the parents who believe that immunizations are not safe: 71.5% for those who said they were influenced by a health care provider, compared with just 55.8% of those who were not, a highly significant difference. “All this is pointing to the importance of a health care provider talking with the parent,” Dr. Smith said.

Indeed, earlier this year the American Academy of Pediatrics published guidelines on how to respond to parents' refusal of immunization for their children (Pediatrics 2005;115:1428–31).

Among AAP's recommendations are to listen respectfully to what parents have to say and not minimize their concerns. Be honest about the benefits and risks of immunization, correct any misconceptions or misinformation, and refer the parents to trusted sources such as the CDC's National Immunization Program page (www.cdc.gov/nip

WASHINGTON — Even parents who don't trust vaccines might let you vaccinate their children if they trust you.

That was the conclusion drawn from a survey of parents of 7,810 children aged 19–35 months from the 2001–2002 National Immunization Survey, conducted by Philip J. Smith, Ph.D., and his associates at the Centers for Disease Control and Prevention's National Immunization Program, in Atlanta.

The majority of parents (77%) said they believed vaccines were safe and that their belief was influenced by their child's health care provider (physician, nurse, or other). However, 5.7% of parents reported believing that vaccines were not safe, with 2% saying they were not influenced by their child's health care provider while the other 3.7% reported that they were.

Another 17.2% said that they believed vaccines were safe but their belief was not influenced by a health care provider. This group is of concern, because “One thing we don't want to happen is that these parents' opinions migrate to the other side,” Dr. Smith said at the annual meeting of the American Academy of Pediatrics.

Parents who were not influenced by a health care provider were significantly more likely to say that vaccines were not safe, compared with parents who were influenced by a provider (10.4% vs. 4.6%).

Somewhat surprising, however, were the up-to-date immunization rates among the children of the parents who believe that immunizations are not safe: 71.5% for those who said they were influenced by a health care provider, compared with just 55.8% of those who were not, a highly significant difference. “All this is pointing to the importance of a health care provider talking with the parent,” Dr. Smith said.

Indeed, earlier this year the American Academy of Pediatrics published guidelines on how to respond to parents' refusal of immunization for their children (Pediatrics 2005;115:1428–31).

Among AAP's recommendations are to listen respectfully to what parents have to say and not minimize their concerns. Be honest about the benefits and risks of immunization, correct any misconceptions or misinformation, and refer the parents to trusted sources such as the CDC's National Immunization Program page (www.cdc.gov/nip

WASHINGTON — Maximizing efforts to vaccinate children at the 18-month well-child visit would dramatically increase the proportion of children who are up to date, Richard A. Schieber, M.D., said at the annual meeting of the American Academy of Pediatrics.

Specifically, if office-based systemic chart reviews and reminder/recall systems, community outreach programs, and individual case management all were focused on bringing children in for immunizations during their 18th month of life, the proportions of those up to date would more than double—from the current 57% up to 87%—for the 4:3:1:3:3:1 series, which includes diphtheria-tetanus-acellular pertussis, poliovirus, measles-mumps-rubella, Haemophilus influenzae type b, hepatitis B, and varicella.

“We're really talking about tailoring an approach to raise consciousness among health care providers,” said Dr. Schieber, senior adviser for influenza at the Centers for Disease Control and Prevention's coordinating center for infectious diseases, Atlanta.

A previous CDC study using data from the 1999 National Immunization Survey found that among children who were not up to date for the 4:3:1:3:3 series (all of those listed above except varicella), 74% needed only one more visit to complete the series, and of those, 62% needed just one more shot.

The authors concluded that if all children who needed one more visit were to receive it, the national coverage for all recommended vaccinations among children aged 19–35 months would be 93%, thus exceeding the 90% Healthy People 2010 goal (Am. J. Prev. Med. 2001;20(suppl.):32–40).

In a follow-up to that study using data from the 2003 National Immunization Survey, a simulated birth cohort of children turning 19 months old was used, comprising 59% white, 14% black, 21% Hispanic, and 6% children of other races.

The simulated dosing rules stated that no multiple administrations of the same antigen would be given.

At prebaseline (the day the child turned 18 months), just 40% were up to date with the 4:3:1:3:3:1 series. If nothing changed after that, 57% would be up to date by the day they turned 19 months.

By 24 months, the proportion would increase to 67%. However, if every child made a visit at age 18 months and received all needed shots (up to four injections) at that time, 87% would be up to date by the day they turned 19 months of age, Dr. Schieber said.

Of the total 43% not up to date by 19 months, 71% needed just one more visit and of those, 44% needed just one more vaccination. Based on U.S. census data, that 71% translates to about 1.2 million children. “That's not a small number of children we'd be affecting by not doing much more than awareness raising among health care providers,” he noted.

The most common vaccinations the children lacked were DTP/DTaP (57%) and varicella (26%). Such a focused program would work for all races, bringing the coverage rates up from 60% to 89% among whites, from 48% to 82% in blacks, and from 56% to 86% among Hispanics. As simulated, all states would achieve at least 80% up-to-date coverage, and 13 states would achieve at least 90%.

Ongoing analysis of the series to include the conjugate pneumococcal vaccine has been hampered by shortages over the last couple of years, but preliminary data suggest that the proportion of children up to date by 19 months would rise from the current 30% to 72% if such a program were implemented. “That's really dramatic,” Dr. Schieber remarked.

Field trials would be needed to back up the real world effectiveness of this approach. None are currently planned, although “we are entering a new budget year, so it is possible that funding for this might become available,” he told FAMILY PRACTICE NEWS.

WASHINGTON — Maximizing efforts to vaccinate children at the 18-month well-child visit would dramatically increase the proportion of children who are up to date, Richard A. Schieber, M.D., said at the annual meeting of the American Academy of Pediatrics.

Specifically, if office-based systemic chart reviews and reminder/recall systems, community outreach programs, and individual case management all were focused on bringing children in for immunizations during their 18th month of life, the proportions of those up to date would more than double—from the current 57% up to 87%—for the 4:3:1:3:3:1 series, which includes diphtheria-tetanus-acellular pertussis, poliovirus, measles-mumps-rubella, Haemophilus influenzae type b, hepatitis B, and varicella.

“We're really talking about tailoring an approach to raise consciousness among health care providers,” said Dr. Schieber, senior adviser for influenza at the Centers for Disease Control and Prevention's coordinating center for infectious diseases, Atlanta.

A previous CDC study using data from the 1999 National Immunization Survey found that among children who were not up to date for the 4:3:1:3:3 series (all of those listed above except varicella), 74% needed only one more visit to complete the series, and of those, 62% needed just one more shot.

The authors concluded that if all children who needed one more visit were to receive it, the national coverage for all recommended vaccinations among children aged 19–35 months would be 93%, thus exceeding the 90% Healthy People 2010 goal (Am. J. Prev. Med. 2001;20(suppl.):32–40).

In a follow-up to that study using data from the 2003 National Immunization Survey, a simulated birth cohort of children turning 19 months old was used, comprising 59% white, 14% black, 21% Hispanic, and 6% children of other races.

The simulated dosing rules stated that no multiple administrations of the same antigen would be given.

At prebaseline (the day the child turned 18 months), just 40% were up to date with the 4:3:1:3:3:1 series. If nothing changed after that, 57% would be up to date by the day they turned 19 months.

By 24 months, the proportion would increase to 67%. However, if every child made a visit at age 18 months and received all needed shots (up to four injections) at that time, 87% would be up to date by the day they turned 19 months of age, Dr. Schieber said.

Of the total 43% not up to date by 19 months, 71% needed just one more visit and of those, 44% needed just one more vaccination. Based on U.S. census data, that 71% translates to about 1.2 million children. “That's not a small number of children we'd be affecting by not doing much more than awareness raising among health care providers,” he noted.

The most common vaccinations the children lacked were DTP/DTaP (57%) and varicella (26%). Such a focused program would work for all races, bringing the coverage rates up from 60% to 89% among whites, from 48% to 82% in blacks, and from 56% to 86% among Hispanics. As simulated, all states would achieve at least 80% up-to-date coverage, and 13 states would achieve at least 90%.

Ongoing analysis of the series to include the conjugate pneumococcal vaccine has been hampered by shortages over the last couple of years, but preliminary data suggest that the proportion of children up to date by 19 months would rise from the current 30% to 72% if such a program were implemented. “That's really dramatic,” Dr. Schieber remarked.

Field trials would be needed to back up the real world effectiveness of this approach. None are currently planned, although “we are entering a new budget year, so it is possible that funding for this might become available,” he told FAMILY PRACTICE NEWS.

WASHINGTON — Maximizing efforts to vaccinate children at the 18-month well-child visit would dramatically increase the proportion of children who are up to date, Richard A. Schieber, M.D., said at the annual meeting of the American Academy of Pediatrics.

Specifically, if office-based systemic chart reviews and reminder/recall systems, community outreach programs, and individual case management all were focused on bringing children in for immunizations during their 18th month of life, the proportions of those up to date would more than double—from the current 57% up to 87%—for the 4:3:1:3:3:1 series, which includes diphtheria-tetanus-acellular pertussis, poliovirus, measles-mumps-rubella, Haemophilus influenzae type b, hepatitis B, and varicella.

“We're really talking about tailoring an approach to raise consciousness among health care providers,” said Dr. Schieber, senior adviser for influenza at the Centers for Disease Control and Prevention's coordinating center for infectious diseases, Atlanta.

A previous CDC study using data from the 1999 National Immunization Survey found that among children who were not up to date for the 4:3:1:3:3 series (all of those listed above except varicella), 74% needed only one more visit to complete the series, and of those, 62% needed just one more shot.

The authors concluded that if all children who needed one more visit were to receive it, the national coverage for all recommended vaccinations among children aged 19–35 months would be 93%, thus exceeding the 90% Healthy People 2010 goal (Am. J. Prev. Med. 2001;20(suppl.):32–40).

In a follow-up to that study using data from the 2003 National Immunization Survey, a simulated birth cohort of children turning 19 months old was used, comprising 59% white, 14% black, 21% Hispanic, and 6% children of other races.

The simulated dosing rules stated that no multiple administrations of the same antigen would be given.

At prebaseline (the day the child turned 18 months), just 40% were up to date with the 4:3:1:3:3:1 series. If nothing changed after that, 57% would be up to date by the day they turned 19 months.

By 24 months, the proportion would increase to 67%. However, if every child made a visit at age 18 months and received all needed shots (up to four injections) at that time, 87% would be up to date by the day they turned 19 months of age, Dr. Schieber said.

Of the total 43% not up to date by 19 months, 71% needed just one more visit and of those, 44% needed just one more vaccination. Based on U.S. census data, that 71% translates to about 1.2 million children. “That's not a small number of children we'd be affecting by not doing much more than awareness raising among health care providers,” he noted.

The most common vaccinations the children lacked were DTP/DTaP (57%) and varicella (26%). Such a focused program would work for all races, bringing the coverage rates up from 60% to 89% among whites, from 48% to 82% in blacks, and from 56% to 86% among Hispanics. As simulated, all states would achieve at least 80% up-to-date coverage, and 13 states would achieve at least 90%.

Ongoing analysis of the series to include the conjugate pneumococcal vaccine has been hampered by shortages over the last couple of years, but preliminary data suggest that the proportion of children up to date by 19 months would rise from the current 30% to 72% if such a program were implemented. “That's really dramatic,” Dr. Schieber remarked.

Field trials would be needed to back up the real world effectiveness of this approach. None are currently planned, although “we are entering a new budget year, so it is possible that funding for this might become available,” he told FAMILY PRACTICE NEWS.

SAN DIEGO — The novel investigational compound sitagliptin significantly lowers glucose levels and is well tolerated in patients with type 2 diabetes, three investigators reported in separate presentations at the annual scientific sessions of the American Diabetes Association.

Sitagliptin, manufactured by Merck & Co., appears to work by inhibiting the enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates the incretin gut hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The two peptides, normally released by the gut after a meal, enhance insulin secretion, while GLP-1 also inhibits glucagon secretion. Inhibition of DPP-IV activity increases the active concentration of these hormones, thereby enhancing their glucose-lowering action.

Unlike some of the new agents that mimic the action of GLP-1, sitagliptin is orally active and in these trials did not appear to be associated with increased gastrointestinal side effects, said Ronald L. Brazg, M.D., of Rainier Clinical Research Center, Renton, Wash.

Russell Scott, M.D., Ph.D., reported data from the largest of three randomized, double-blind, placebo-controlled phase II studies presented at the meeting. In the dose-finding study, 743 patients with type 2 diabetes aged 21–76 years were taken off all other medications and randomized to 5 mg, 12.5 mg, 25 mg, or 50 mg of sitagliptin twice daily; glipizide 5–20 mg twice daily; or placebo. At baseline, the subjects had a mean hemoglobin A1c level of 7.9%, with 21% having an A1c level of 7.0% or lower.

At week 12, there were statistically significant dose-dependent reductions in A1c level, compared with the placebo group, in all sitagliptin dose groups, ranging from a 0.38 percentage point drop with 5 mg twice daily to a 0.77-point drop with 50 mg twice daily. The reduction in the glipizide group—the dose was titrated up every 2 weeks as needed—was 1.0 percentage point. Similarly, 2-hour fasting plasma glucose (FPG) levels fell in a dose-dependent manner, with reductions ranging from 35.0 mg/dL to 54.2 mg/dL in the four sitagliptin groups. Glipizide reduced FPG level by 72.1 mg/dL, reported Dr. Scott, professor of medicine and director of the lipid and diabetes research group at Christchurch Hospital and School of Medicine, New Zealand.

There were no changes in weight with sitagliptin or placebo, compared with a mean 1.1-kg weight gain at week 12 with glipizide. Hypoglycemia occurred in 0%–4% of the sitagliptin groups and 2% of the placebo group, compared with 17% of those taking glipizide. Gastrointestinal adverse events occurred in 8%–17% with sitagliptin, 12% with placebo, and 14% with glipizide.

In a small second study, 28 patients who were already taking 1,500 mg/day or more of metformin were randomized to receive 50 mg of sitagliptin twice daily or placebo. The study was originally designed to have two 4-week crossover periods. However, because the patients who received sitagliptin during the first 4 weeks didn't return to baseline after the end of the second 4 weeks in which they received placebo, Dr. Brazg presented only the results from the first 4 weeks.

Over a 24-hour period, the weighted mean glucose level in the sitagliptin plus metformin group was 125 mg/dL, compared with 158 mg/dL for placebo plus metformin, a mean reduction of 33 mg/dL. The difference in FPG levels—128 vs. 149 mg/dL—also was highly significant, even though those values were not markedly elevated to begin with.

There were no clinically meaningful changes in body weight, in hepatic or muscle enzymes, or in any laboratory parameters, he said.

The third study was presented in a poster by Gary Herman, M.D., of Merck Research Laboratories, Rahway, N.J., and his associates. Here, 552 patients aged 30–74 years with a mean baseline A1c level of 5.8%–10.4% (29% had levels of 7% or less) and mean FPG level of 130 mg/dL or higher were randomized to sitagliptin 25 mg, 50 mg, or 100 mg once daily; sitagliptin 50 mg twice daily; or placebo. Patients who had been taking other oral hypoglycemics underwent a washout period.

At week 12, there were significant mean reductions in A1c level in all treatment groups, compared with the placebo group, ranging from 0.39 percentage points for 25 mg twice daily to 0.56 points for 100 mg once daily.

In an analysis with the last observation carried forward, the differences were greatest in those with the highest A1c levels at baseline, with a reduction of 0.82 percentage points with the 100 mg/day dose for those with baseline A1c values of 8.5% or higher, compared with a 0.37-point drop among those who started out at less than 7%. Similarly, reductions in FPG level, compared with placebo, ranged from 11.0 mg/dL with 25 mg twice daily to 17.2 mg/dL with 100 mg once daily, Dr. Herman and his associates reported.

There were no clinically significant treatment-related trends in clinical or laboratory adverse events or test abnormalities, nor any differences in vital signs or other physical findings. One hypoglycemic event occurred in each sitagliptin group, with none reported in the placebo group.

Phase III trials of sitagliptin are underway, according to a Merck statement.

SAN DIEGO — The novel investigational compound sitagliptin significantly lowers glucose levels and is well tolerated in patients with type 2 diabetes, three investigators reported in separate presentations at the annual scientific sessions of the American Diabetes Association.

Sitagliptin, manufactured by Merck & Co., appears to work by inhibiting the enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates the incretin gut hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The two peptides, normally released by the gut after a meal, enhance insulin secretion, while GLP-1 also inhibits glucagon secretion. Inhibition of DPP-IV activity increases the active concentration of these hormones, thereby enhancing their glucose-lowering action.

Unlike some of the new agents that mimic the action of GLP-1, sitagliptin is orally active and in these trials did not appear to be associated with increased gastrointestinal side effects, said Ronald L. Brazg, M.D., of Rainier Clinical Research Center, Renton, Wash.

Russell Scott, M.D., Ph.D., reported data from the largest of three randomized, double-blind, placebo-controlled phase II studies presented at the meeting. In the dose-finding study, 743 patients with type 2 diabetes aged 21–76 years were taken off all other medications and randomized to 5 mg, 12.5 mg, 25 mg, or 50 mg of sitagliptin twice daily; glipizide 5–20 mg twice daily; or placebo. At baseline, the subjects had a mean hemoglobin A1c level of 7.9%, with 21% having an A1c level of 7.0% or lower.

At week 12, there were statistically significant dose-dependent reductions in A1c level, compared with the placebo group, in all sitagliptin dose groups, ranging from a 0.38 percentage point drop with 5 mg twice daily to a 0.77-point drop with 50 mg twice daily. The reduction in the glipizide group—the dose was titrated up every 2 weeks as needed—was 1.0 percentage point. Similarly, 2-hour fasting plasma glucose (FPG) levels fell in a dose-dependent manner, with reductions ranging from 35.0 mg/dL to 54.2 mg/dL in the four sitagliptin groups. Glipizide reduced FPG level by 72.1 mg/dL, reported Dr. Scott, professor of medicine and director of the lipid and diabetes research group at Christchurch Hospital and School of Medicine, New Zealand.

There were no changes in weight with sitagliptin or placebo, compared with a mean 1.1-kg weight gain at week 12 with glipizide. Hypoglycemia occurred in 0%–4% of the sitagliptin groups and 2% of the placebo group, compared with 17% of those taking glipizide. Gastrointestinal adverse events occurred in 8%–17% with sitagliptin, 12% with placebo, and 14% with glipizide.

In a small second study, 28 patients who were already taking 1,500 mg/day or more of metformin were randomized to receive 50 mg of sitagliptin twice daily or placebo. The study was originally designed to have two 4-week crossover periods. However, because the patients who received sitagliptin during the first 4 weeks didn't return to baseline after the end of the second 4 weeks in which they received placebo, Dr. Brazg presented only the results from the first 4 weeks.

Over a 24-hour period, the weighted mean glucose level in the sitagliptin plus metformin group was 125 mg/dL, compared with 158 mg/dL for placebo plus metformin, a mean reduction of 33 mg/dL. The difference in FPG levels—128 vs. 149 mg/dL—also was highly significant, even though those values were not markedly elevated to begin with.

There were no clinically meaningful changes in body weight, in hepatic or muscle enzymes, or in any laboratory parameters, he said.

The third study was presented in a poster by Gary Herman, M.D., of Merck Research Laboratories, Rahway, N.J., and his associates. Here, 552 patients aged 30–74 years with a mean baseline A1c level of 5.8%–10.4% (29% had levels of 7% or less) and mean FPG level of 130 mg/dL or higher were randomized to sitagliptin 25 mg, 50 mg, or 100 mg once daily; sitagliptin 50 mg twice daily; or placebo. Patients who had been taking other oral hypoglycemics underwent a washout period.

At week 12, there were significant mean reductions in A1c level in all treatment groups, compared with the placebo group, ranging from 0.39 percentage points for 25 mg twice daily to 0.56 points for 100 mg once daily.

In an analysis with the last observation carried forward, the differences were greatest in those with the highest A1c levels at baseline, with a reduction of 0.82 percentage points with the 100 mg/day dose for those with baseline A1c values of 8.5% or higher, compared with a 0.37-point drop among those who started out at less than 7%. Similarly, reductions in FPG level, compared with placebo, ranged from 11.0 mg/dL with 25 mg twice daily to 17.2 mg/dL with 100 mg once daily, Dr. Herman and his associates reported.

There were no clinically significant treatment-related trends in clinical or laboratory adverse events or test abnormalities, nor any differences in vital signs or other physical findings. One hypoglycemic event occurred in each sitagliptin group, with none reported in the placebo group.

Phase III trials of sitagliptin are underway, according to a Merck statement.

SAN DIEGO — The novel investigational compound sitagliptin significantly lowers glucose levels and is well tolerated in patients with type 2 diabetes, three investigators reported in separate presentations at the annual scientific sessions of the American Diabetes Association.

Sitagliptin, manufactured by Merck & Co., appears to work by inhibiting the enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates the incretin gut hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The two peptides, normally released by the gut after a meal, enhance insulin secretion, while GLP-1 also inhibits glucagon secretion. Inhibition of DPP-IV activity increases the active concentration of these hormones, thereby enhancing their glucose-lowering action.

Unlike some of the new agents that mimic the action of GLP-1, sitagliptin is orally active and in these trials did not appear to be associated with increased gastrointestinal side effects, said Ronald L. Brazg, M.D., of Rainier Clinical Research Center, Renton, Wash.

Russell Scott, M.D., Ph.D., reported data from the largest of three randomized, double-blind, placebo-controlled phase II studies presented at the meeting. In the dose-finding study, 743 patients with type 2 diabetes aged 21–76 years were taken off all other medications and randomized to 5 mg, 12.5 mg, 25 mg, or 50 mg of sitagliptin twice daily; glipizide 5–20 mg twice daily; or placebo. At baseline, the subjects had a mean hemoglobin A1c level of 7.9%, with 21% having an A1c level of 7.0% or lower.

At week 12, there were statistically significant dose-dependent reductions in A1c level, compared with the placebo group, in all sitagliptin dose groups, ranging from a 0.38 percentage point drop with 5 mg twice daily to a 0.77-point drop with 50 mg twice daily. The reduction in the glipizide group—the dose was titrated up every 2 weeks as needed—was 1.0 percentage point. Similarly, 2-hour fasting plasma glucose (FPG) levels fell in a dose-dependent manner, with reductions ranging from 35.0 mg/dL to 54.2 mg/dL in the four sitagliptin groups. Glipizide reduced FPG level by 72.1 mg/dL, reported Dr. Scott, professor of medicine and director of the lipid and diabetes research group at Christchurch Hospital and School of Medicine, New Zealand.

There were no changes in weight with sitagliptin or placebo, compared with a mean 1.1-kg weight gain at week 12 with glipizide. Hypoglycemia occurred in 0%–4% of the sitagliptin groups and 2% of the placebo group, compared with 17% of those taking glipizide. Gastrointestinal adverse events occurred in 8%–17% with sitagliptin, 12% with placebo, and 14% with glipizide.

In a small second study, 28 patients who were already taking 1,500 mg/day or more of metformin were randomized to receive 50 mg of sitagliptin twice daily or placebo. The study was originally designed to have two 4-week crossover periods. However, because the patients who received sitagliptin during the first 4 weeks didn't return to baseline after the end of the second 4 weeks in which they received placebo, Dr. Brazg presented only the results from the first 4 weeks.

Over a 24-hour period, the weighted mean glucose level in the sitagliptin plus metformin group was 125 mg/dL, compared with 158 mg/dL for placebo plus metformin, a mean reduction of 33 mg/dL. The difference in FPG levels—128 vs. 149 mg/dL—also was highly significant, even though those values were not markedly elevated to begin with.

There were no clinically meaningful changes in body weight, in hepatic or muscle enzymes, or in any laboratory parameters, he said.

The third study was presented in a poster by Gary Herman, M.D., of Merck Research Laboratories, Rahway, N.J., and his associates. Here, 552 patients aged 30–74 years with a mean baseline A1c level of 5.8%–10.4% (29% had levels of 7% or less) and mean FPG level of 130 mg/dL or higher were randomized to sitagliptin 25 mg, 50 mg, or 100 mg once daily; sitagliptin 50 mg twice daily; or placebo. Patients who had been taking other oral hypoglycemics underwent a washout period.

At week 12, there were significant mean reductions in A1c level in all treatment groups, compared with the placebo group, ranging from 0.39 percentage points for 25 mg twice daily to 0.56 points for 100 mg once daily.

In an analysis with the last observation carried forward, the differences were greatest in those with the highest A1c levels at baseline, with a reduction of 0.82 percentage points with the 100 mg/day dose for those with baseline A1c values of 8.5% or higher, compared with a 0.37-point drop among those who started out at less than 7%. Similarly, reductions in FPG level, compared with placebo, ranged from 11.0 mg/dL with 25 mg twice daily to 17.2 mg/dL with 100 mg once daily, Dr. Herman and his associates reported.

There were no clinically significant treatment-related trends in clinical or laboratory adverse events or test abnormalities, nor any differences in vital signs or other physical findings. One hypoglycemic event occurred in each sitagliptin group, with none reported in the placebo group.

Phase III trials of sitagliptin are underway, according to a Merck statement.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels also reduce these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, data in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL. This was followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by World Health Organization criteria, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

Women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating.

Twenty percent of the women received insulin therapy. Women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar in both groups (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%).

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and these infants were also born at an earlier gestational age.

Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined as a birth weight of 4 kg or greater (10% vs. 21%).

Weight gain was less for women in the intervention group, where fewer were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

In their editorial, Dr. Greene and Dr. Solomon noted that they agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels also reduce these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, data in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL. This was followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by World Health Organization criteria, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

Women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating.

Twenty percent of the women received insulin therapy. Women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar in both groups (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%).

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and these infants were also born at an earlier gestational age.

Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined as a birth weight of 4 kg or greater (10% vs. 21%).

Weight gain was less for women in the intervention group, where fewer were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

In their editorial, Dr. Greene and Dr. Solomon noted that they agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels also reduce these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, data in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL. This was followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by World Health Organization criteria, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

Women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating.

Twenty percent of the women received insulin therapy. Women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar in both groups (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%).

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and these infants were also born at an earlier gestational age.

Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined as a birth weight of 4 kg or greater (10% vs. 21%).

Weight gain was less for women in the intervention group, where fewer were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

In their editorial, Dr. Greene and Dr. Solomon noted that they agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

The American Association of Clinical Endocrinologists and the American College of Endocrinology have weighed in on the growing debate surrounding the term metabolic syndrome by reaffirming their 2003 position statement regarding what they call insulin resistance syndrome.

The new two-page document, “American College of Endocrinology/American Association of Clinical Endocrinologists Reaffirmation of the 2003 ACE Insulin Resistance Syndrome (IRS) Position Statement” (available at www.aace.com

In September, the American Diabetes Association (ADA) and the European Society for the Study of Diabetes (EASD) issued a joint statement calling the term metabolic syndrome into question, citing a lack of data to demonstrate that the term denotes a useful marker for cardiovascular disease beyond its individual components, as well as the concern that patients might misunderstand the implications of the diagnosis (Diabetes Care 2005;28:2289–304).

Then, in mid-October, the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) issued a joint statement affirming the usefulness of the metabolic syndrome term, as originally stated in the 2001 National Cholesterol Education Program Adult Treatment Panel Report III.

The new AHA/NHLBI document, which was in the works before the ADA/EASD statement came out, also clarifies some issues and makes minor modifications to the Adult Treatment Panel III definition of metabolic syndrome (Circulation 2005;112:e285–90).

For their part, the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) still prefer the term insulin resistance syndrome, because in contrast to the poorly defined word metabolic, insulin resistance syndrome “offers a clear statement of the presumed pathogenesis of the syndrome,” according to their earlier document (Endocrine Practice 2003;9:240–52).

Regardless of the term used—metabolic syndrome or insulin resistance syndrome—the ACE/AACE position differs from that of the ADA/EASD, which states that neither entity is well defined enough to qualify as a syndrome.

The ACE/AACE, however, said “the term syndrome (whether metabolic or insulin resistant) is conceptually attractive and clinically useful” and the two terms together provide “a simple construct to characterize the type of patients that clinicians see daily.”

But the two endocrinologist groups do agree with the ADA/EASD statement that such syndromes should be specifically distinguished from type 2 diabetes and cardiovascular disease, because the whole idea is to identify individuals at high risk for these consequences before they occur.

Moreover, the ACE/AACE position emphasizes the importance of recognizing other associated disease consequences beyond cardiovascular disease, such as polycystic ovary syndrome and nonalcoholic fatty liver disease.

The American Association of Clinical Endocrinologists and the American College of Endocrinology have weighed in on the growing debate surrounding the term metabolic syndrome by reaffirming their 2003 position statement regarding what they call insulin resistance syndrome.

The new two-page document, “American College of Endocrinology/American Association of Clinical Endocrinologists Reaffirmation of the 2003 ACE Insulin Resistance Syndrome (IRS) Position Statement” (available at www.aace.com

In September, the American Diabetes Association (ADA) and the European Society for the Study of Diabetes (EASD) issued a joint statement calling the term metabolic syndrome into question, citing a lack of data to demonstrate that the term denotes a useful marker for cardiovascular disease beyond its individual components, as well as the concern that patients might misunderstand the implications of the diagnosis (Diabetes Care 2005;28:2289–304).

Then, in mid-October, the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) issued a joint statement affirming the usefulness of the metabolic syndrome term, as originally stated in the 2001 National Cholesterol Education Program Adult Treatment Panel Report III.

The new AHA/NHLBI document, which was in the works before the ADA/EASD statement came out, also clarifies some issues and makes minor modifications to the Adult Treatment Panel III definition of metabolic syndrome (Circulation 2005;112:e285–90).

For their part, the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) still prefer the term insulin resistance syndrome, because in contrast to the poorly defined word metabolic, insulin resistance syndrome “offers a clear statement of the presumed pathogenesis of the syndrome,” according to their earlier document (Endocrine Practice 2003;9:240–52).

Regardless of the term used—metabolic syndrome or insulin resistance syndrome—the ACE/AACE position differs from that of the ADA/EASD, which states that neither entity is well defined enough to qualify as a syndrome.

The ACE/AACE, however, said “the term syndrome (whether metabolic or insulin resistant) is conceptually attractive and clinically useful” and the two terms together provide “a simple construct to characterize the type of patients that clinicians see daily.”

But the two endocrinologist groups do agree with the ADA/EASD statement that such syndromes should be specifically distinguished from type 2 diabetes and cardiovascular disease, because the whole idea is to identify individuals at high risk for these consequences before they occur.

Moreover, the ACE/AACE position emphasizes the importance of recognizing other associated disease consequences beyond cardiovascular disease, such as polycystic ovary syndrome and nonalcoholic fatty liver disease.

The American Association of Clinical Endocrinologists and the American College of Endocrinology have weighed in on the growing debate surrounding the term metabolic syndrome by reaffirming their 2003 position statement regarding what they call insulin resistance syndrome.

The new two-page document, “American College of Endocrinology/American Association of Clinical Endocrinologists Reaffirmation of the 2003 ACE Insulin Resistance Syndrome (IRS) Position Statement” (available at www.aace.com

In September, the American Diabetes Association (ADA) and the European Society for the Study of Diabetes (EASD) issued a joint statement calling the term metabolic syndrome into question, citing a lack of data to demonstrate that the term denotes a useful marker for cardiovascular disease beyond its individual components, as well as the concern that patients might misunderstand the implications of the diagnosis (Diabetes Care 2005;28:2289–304).

Then, in mid-October, the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) issued a joint statement affirming the usefulness of the metabolic syndrome term, as originally stated in the 2001 National Cholesterol Education Program Adult Treatment Panel Report III.

The new AHA/NHLBI document, which was in the works before the ADA/EASD statement came out, also clarifies some issues and makes minor modifications to the Adult Treatment Panel III definition of metabolic syndrome (Circulation 2005;112:e285–90).

For their part, the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) still prefer the term insulin resistance syndrome, because in contrast to the poorly defined word metabolic, insulin resistance syndrome “offers a clear statement of the presumed pathogenesis of the syndrome,” according to their earlier document (Endocrine Practice 2003;9:240–52).

Regardless of the term used—metabolic syndrome or insulin resistance syndrome—the ACE/AACE position differs from that of the ADA/EASD, which states that neither entity is well defined enough to qualify as a syndrome.

The ACE/AACE, however, said “the term syndrome (whether metabolic or insulin resistant) is conceptually attractive and clinically useful” and the two terms together provide “a simple construct to characterize the type of patients that clinicians see daily.”

But the two endocrinologist groups do agree with the ADA/EASD statement that such syndromes should be specifically distinguished from type 2 diabetes and cardiovascular disease, because the whole idea is to identify individuals at high risk for these consequences before they occur.

Moreover, the ACE/AACE position emphasizes the importance of recognizing other associated disease consequences beyond cardiovascular disease, such as polycystic ovary syndrome and nonalcoholic fatty liver disease.

More than half of all the cases of measles reported among United States residents during 2001–2004 were preventable, according to the Centers for Disease Control and Prevention.

Although endemic measles has been eliminated from the United States, cases continue to be imported from other parts of the world, and infected travelers can transmit the disease to susceptible contacts, the CDC said (MMWR 2005;54:817–20).

Of the 251 measles cases reported to the CDC during 2001–2004, 71% occurred among U.S. residents and 29% among nonresidents. Of the 177 cases among U.S. residents, 100 (56%) were considered preventable, which means that they occurred in persons for whom vaccination against measles is recommended by the Advisory Committee on Immunization Practices, but those individuals had not received one or more doses of measles-containing vaccine.

Among the 177 U.S. residents, 52% (92) were aged 0–19 years and 48% (85) were aged 20 years or older. Nearly one-third (31%) had traveled abroad, while the other 69% were infected in the United States. More than three-fourths (77%) of the total group had not been vaccinated. Of those 136, only 7 cases (5.1%) were considered not preventable, because the individuals were born before 1957 and measles vaccination is not recommended for that age group, the CDC said.

Current recommendations for travelers include vaccination for infants 6–11 months of age and two doses of measles-containing vaccine for travelers aged 12 months and above. Yet the 100 preventable cases in this report included a total of 43 travelers: 17 infants aged 6–15 months, 11 children and adolescents aged 16 months to 19 years, and 15 adults aged 20 and older.

One of these cases was an 11-year-old girl who developed a rash 3 days after returning to the United States from the United Kingdom. She had not been vaccinated because of her parents' religious beliefs. She had close contact with an 11-month-old infant, who subsequently had contact with up to 234 persons at a summer camp 2 days before he also developed a rash. After extensive investigation and control efforts, no further cases were subsequently identified.

Measles cases among persons born before 1957 are rare. However, individuals in this age group who travel internationally might wish to consider vaccination to minimize their risk of measles, the CDC advised. Information on vaccination recommendations for travelers is available at www.cdc.gov/travel

More than half of all the cases of measles reported among United States residents during 2001–2004 were preventable, according to the Centers for Disease Control and Prevention.

Although endemic measles has been eliminated from the United States, cases continue to be imported from other parts of the world, and infected travelers can transmit the disease to susceptible contacts, the CDC said (MMWR 2005;54:817–20).

Of the 251 measles cases reported to the CDC during 2001–2004, 71% occurred among U.S. residents and 29% among nonresidents. Of the 177 cases among U.S. residents, 100 (56%) were considered preventable, which means that they occurred in persons for whom vaccination against measles is recommended by the Advisory Committee on Immunization Practices, but those individuals had not received one or more doses of measles-containing vaccine.

Among the 177 U.S. residents, 52% (92) were aged 0–19 years and 48% (85) were aged 20 years or older. Nearly one-third (31%) had traveled abroad, while the other 69% were infected in the United States. More than three-fourths (77%) of the total group had not been vaccinated. Of those 136, only 7 cases (5.1%) were considered not preventable, because the individuals were born before 1957 and measles vaccination is not recommended for that age group, the CDC said.

Current recommendations for travelers include vaccination for infants 6–11 months of age and two doses of measles-containing vaccine for travelers aged 12 months and above. Yet the 100 preventable cases in this report included a total of 43 travelers: 17 infants aged 6–15 months, 11 children and adolescents aged 16 months to 19 years, and 15 adults aged 20 and older.

One of these cases was an 11-year-old girl who developed a rash 3 days after returning to the United States from the United Kingdom. She had not been vaccinated because of her parents' religious beliefs. She had close contact with an 11-month-old infant, who subsequently had contact with up to 234 persons at a summer camp 2 days before he also developed a rash. After extensive investigation and control efforts, no further cases were subsequently identified.

Measles cases among persons born before 1957 are rare. However, individuals in this age group who travel internationally might wish to consider vaccination to minimize their risk of measles, the CDC advised. Information on vaccination recommendations for travelers is available at www.cdc.gov/travel

More than half of all the cases of measles reported among United States residents during 2001–2004 were preventable, according to the Centers for Disease Control and Prevention.

Although endemic measles has been eliminated from the United States, cases continue to be imported from other parts of the world, and infected travelers can transmit the disease to susceptible contacts, the CDC said (MMWR 2005;54:817–20).

Of the 251 measles cases reported to the CDC during 2001–2004, 71% occurred among U.S. residents and 29% among nonresidents. Of the 177 cases among U.S. residents, 100 (56%) were considered preventable, which means that they occurred in persons for whom vaccination against measles is recommended by the Advisory Committee on Immunization Practices, but those individuals had not received one or more doses of measles-containing vaccine.

Among the 177 U.S. residents, 52% (92) were aged 0–19 years and 48% (85) were aged 20 years or older. Nearly one-third (31%) had traveled abroad, while the other 69% were infected in the United States. More than three-fourths (77%) of the total group had not been vaccinated. Of those 136, only 7 cases (5.1%) were considered not preventable, because the individuals were born before 1957 and measles vaccination is not recommended for that age group, the CDC said.

Current recommendations for travelers include vaccination for infants 6–11 months of age and two doses of measles-containing vaccine for travelers aged 12 months and above. Yet the 100 preventable cases in this report included a total of 43 travelers: 17 infants aged 6–15 months, 11 children and adolescents aged 16 months to 19 years, and 15 adults aged 20 and older.

One of these cases was an 11-year-old girl who developed a rash 3 days after returning to the United States from the United Kingdom. She had not been vaccinated because of her parents' religious beliefs. She had close contact with an 11-month-old infant, who subsequently had contact with up to 234 persons at a summer camp 2 days before he also developed a rash. After extensive investigation and control efforts, no further cases were subsequently identified.

Measles cases among persons born before 1957 are rare. However, individuals in this age group who travel internationally might wish to consider vaccination to minimize their risk of measles, the CDC advised. Information on vaccination recommendations for travelers is available at www.cdc.gov/travel

Emergency department data demonstrate that preschool children are the first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6- to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the different health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children aged 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time of all, with a mean of 50 days. In contrast, adults aged 18 years and older in the ambulatory care and emergency department settings had a mean lead time of just 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, the investigators reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote.

These and other data point to the idea that targeting yearly influenza vaccination to younger children may benefit the entire community. The idea is currently under consideration by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Emergency department data demonstrate that preschool children are the first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6- to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the different health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children aged 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time of all, with a mean of 50 days. In contrast, adults aged 18 years and older in the ambulatory care and emergency department settings had a mean lead time of just 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, the investigators reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote.

These and other data point to the idea that targeting yearly influenza vaccination to younger children may benefit the entire community. The idea is currently under consideration by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Emergency department data demonstrate that preschool children are the first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6- to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the different health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children aged 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time of all, with a mean of 50 days. In contrast, adults aged 18 years and older in the ambulatory care and emergency department settings had a mean lead time of just 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, the investigators reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote.

These and other data point to the idea that targeting yearly influenza vaccination to younger children may benefit the entire community. The idea is currently under consideration by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

WASHINGTON — More than half of North American women receiving treatment for osteoporosis have suboptimal serum vitamin D levels, Anne E. de Papp, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Inadequate vitamin D concentrations can lead to alterations in calcium and phosphate homeostasis, secondary hypoparathyroidism, bone loss, osteoporosis, and an increased risk of fractures.

Yet, data from a cross-sectional study of 1,536 postmenopausal women at 61 North American sites suggest the problem is often overlooked in osteoporosis patients, said Dr. de Papp, of Merck & Co. Inc., West Point, Pa., and her associates.

“We advocate the use of vitamin D supplementation and patient counseling regarding the importance of vitamin D in all women with osteoporosis,” they said in the poster.

The patients had a mean age of 71 years (range, 47–103 years) and a mean body mass index (BMI) of 26.4 kg/m

Vitamin D supplementation at 400 IU/day or more was reported by 59.5%. The rest were taking less. The mean serum level of the active vitamin D metabolite 25-hydroxyvitamin D was 30.4 ng/mL. Most (52%) had levels below 30 ng/mL, the minimum to maintain optimal serum parathyroid hormone levels (Osteoporos Int. 1997;7:439–43), while 36% had 25-hydroxyvitamin D levels below 25 ng/mL, and 18% were below 20 ng/mL. Suboptimal 25-hydroxy vitamin D levels were found in 63% taking less than 400 IU/day of vitamin D, and in 45% of those receiving 400 IU or more per day.

Risk factors include having less than a 12th-grade education, lack of exercise, concomitant medication use, BMI of 30 or higher, nonwhite race, and age over 80 years.

The study was funded by Merck.

WASHINGTON — More than half of North American women receiving treatment for osteoporosis have suboptimal serum vitamin D levels, Anne E. de Papp, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Inadequate vitamin D concentrations can lead to alterations in calcium and phosphate homeostasis, secondary hypoparathyroidism, bone loss, osteoporosis, and an increased risk of fractures.

Yet, data from a cross-sectional study of 1,536 postmenopausal women at 61 North American sites suggest the problem is often overlooked in osteoporosis patients, said Dr. de Papp, of Merck & Co. Inc., West Point, Pa., and her associates.

“We advocate the use of vitamin D supplementation and patient counseling regarding the importance of vitamin D in all women with osteoporosis,” they said in the poster.

The patients had a mean age of 71 years (range, 47–103 years) and a mean body mass index (BMI) of 26.4 kg/m

Vitamin D supplementation at 400 IU/day or more was reported by 59.5%. The rest were taking less. The mean serum level of the active vitamin D metabolite 25-hydroxyvitamin D was 30.4 ng/mL. Most (52%) had levels below 30 ng/mL, the minimum to maintain optimal serum parathyroid hormone levels (Osteoporos Int. 1997;7:439–43), while 36% had 25-hydroxyvitamin D levels below 25 ng/mL, and 18% were below 20 ng/mL. Suboptimal 25-hydroxy vitamin D levels were found in 63% taking less than 400 IU/day of vitamin D, and in 45% of those receiving 400 IU or more per day.

Risk factors include having less than a 12th-grade education, lack of exercise, concomitant medication use, BMI of 30 or higher, nonwhite race, and age over 80 years.

The study was funded by Merck.

WASHINGTON — More than half of North American women receiving treatment for osteoporosis have suboptimal serum vitamin D levels, Anne E. de Papp, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Inadequate vitamin D concentrations can lead to alterations in calcium and phosphate homeostasis, secondary hypoparathyroidism, bone loss, osteoporosis, and an increased risk of fractures.

Yet, data from a cross-sectional study of 1,536 postmenopausal women at 61 North American sites suggest the problem is often overlooked in osteoporosis patients, said Dr. de Papp, of Merck & Co. Inc., West Point, Pa., and her associates.

“We advocate the use of vitamin D supplementation and patient counseling regarding the importance of vitamin D in all women with osteoporosis,” they said in the poster.

The patients had a mean age of 71 years (range, 47–103 years) and a mean body mass index (BMI) of 26.4 kg/m

Vitamin D supplementation at 400 IU/day or more was reported by 59.5%. The rest were taking less. The mean serum level of the active vitamin D metabolite 25-hydroxyvitamin D was 30.4 ng/mL. Most (52%) had levels below 30 ng/mL, the minimum to maintain optimal serum parathyroid hormone levels (Osteoporos Int. 1997;7:439–43), while 36% had 25-hydroxyvitamin D levels below 25 ng/mL, and 18% were below 20 ng/mL. Suboptimal 25-hydroxy vitamin D levels were found in 63% taking less than 400 IU/day of vitamin D, and in 45% of those receiving 400 IU or more per day.

Risk factors include having less than a 12th-grade education, lack of exercise, concomitant medication use, BMI of 30 or higher, nonwhite race, and age over 80 years.

The study was funded by Merck.

Emergency department data demonstrate that preschool children are first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6− to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time, with a mean of 50 days. Adults in the ambulatory care and emergency department settings had a mean lead time of 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, Dr. Brownstein and his associates reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote. These and other data suggest that targeting yearly influenza vaccination to younger children may benefit the entire community.

Emergency department data demonstrate that preschool children are first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6− to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time, with a mean of 50 days. Adults in the ambulatory care and emergency department settings had a mean lead time of 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, Dr. Brownstein and his associates reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote. These and other data suggest that targeting yearly influenza vaccination to younger children may benefit the entire community.

Emergency department data demonstrate that preschool children are first to come down with influenza each year and could play an important role in the infection's spread, according to John S. Brownstein, Ph.D., of Children's Hospital Boston, and his associates.

Data collected from four emergency departments and one ambulatory care setting in Massachusetts during 2000–2004 suggest that children aged 3–4 years are consistently the first to seek care for respiratory illness during each influenza season, and that the temporal pattern of illness in that group strongly predicts mortality due to influenza and pneumonia among people of all ages.

The results bolster arguments in favor of universal vaccination of all preschool-aged children in addition to the 6− to 23-month-olds for whom the vaccine is currently recommended, the investigators said (Am. J. Epidemiol. 2005;162:686–93).

Among patients presenting to the health care settings—including one pediatric emergency department, one adult emergency department, and two that treat both adults and children—children 3–4 years presented earliest in the season, with a mean lead time of 34 days prior to the peak in overall mortality. Children of that age group presenting to pediatric emergency departments had the longest lead time, with a mean of 50 days. Adults in the ambulatory care and emergency department settings had a mean lead time of 12 days.

Prediction of influenza and pneumonia mortality varied by age. Children younger than 3 years were the best predictors, explaining 41% of the deviance, while those aged 3–4 years explained 37%, Dr. Brownstein and his associates reported.

“Although this finding does not necessarily prove that preschool-aged children are driving the yearly influenza epidemics, they intriguingly suggest that preschool-aged children are the initial group infected and may be important in the subsequent spread,” they wrote. These and other data suggest that targeting yearly influenza vaccination to younger children may benefit the entire community.