Diana Mahoney

Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, according to Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues.

Previous studies have shown comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IPV vaccines has been linked with inconsistencies in immunologic responses, the authors said (J. Pediatr. 2007;151:43–9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine with that achieved by separate administration of the component vaccines, the researchers enrolled 575 healthy infants from 22 U.S. sites in the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes. The three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups. Despite higher rates of fever observed in the combination group, there were no significant differences in rates at or above 102.2° F [39.0° C], and the fevers were not longlasting or clinically important.

Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, according to Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues.

Previous studies have shown comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IPV vaccines has been linked with inconsistencies in immunologic responses, the authors said (J. Pediatr. 2007;151:43–9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine with that achieved by separate administration of the component vaccines, the researchers enrolled 575 healthy infants from 22 U.S. sites in the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes. The three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups. Despite higher rates of fever observed in the combination group, there were no significant differences in rates at or above 102.2° F [39.0° C], and the fevers were not longlasting or clinically important.

Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, according to Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues.

Previous studies have shown comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IPV vaccines has been linked with inconsistencies in immunologic responses, the authors said (J. Pediatr. 2007;151:43–9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine with that achieved by separate administration of the component vaccines, the researchers enrolled 575 healthy infants from 22 U.S. sites in the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes. The three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups. Despite higher rates of fever observed in the combination group, there were no significant differences in rates at or above 102.2° F [39.0° C], and the fevers were not longlasting or clinically important.

BOSTON — Women on highly active antiretroviral therapy for human immunodeficiency virus whose plasma viral load is below detectable levels may continue to shed the virus intermittently in the genital tract, Dr. Susan Cu-Uvin said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“This finding means we cannot rule out the possibility of continued risk of HIV transmission among women in whom the virus appears to be well controlled,” said Dr. Cu-Uvin of Brown University, Providence, R.I.

The advent of highly active antiretroviral therapy (HAART) has resulted in significant decreases in the replication of HIV in the blood of infected patients, and in so doing it has substantially reduced the associated morbidity and mortality of the disease, Dr. Cu-Uvin said.

“However, several studies have shown evidence of discordance between the RNA shedding of HIV in the blood and in the female genital tract, and when it comes to sexual transmission of HIV, the big player is the amount of genital tract viral load, not the plasma viral load,” she said. “Unfortunately, because the only commercially available tools for assessing HIV viral load are those that look at RNA shedding in plasma, we use plasma viral load as a surrogate for how infectious a given patient is, yet this may not always reflect what is happening in the genital tract.”

Dr. Cu-Uvin and colleagues sought to assess the pattern of HIV genital tract shedding among women already on HAART with sustained below detectable plasma viral loads. Of 55 women with HIV enrolled in an ongoing study of HAART, 49 with below detectable plasma viral load for at least 6 months were included in the analysis. Each of the women underwent serum plasma and genital tract sampling every 4 weeks for 12 weeks. Genital tract secretions were collected from the endocervix, ectocervix, and vagina in 40 of the women, and from the vagina only in 9 women who had previous hysterectomies. The lower limit of viral detection was 80 copies per milliliter for plasma and 3,300 copies per milliliter for the genital tract, Dr. Cu-Uvin noted.

The immune status of all of the patients was “generally good,” with a median CD4 count of 412 cells/mm

Patients were grouped based on their genital tract HIV RNA patterns, Dr. Cu-Uvin explained. Nonshedders were those women with no evidence of detectable genital tract HIV during study visits. Indeterminate shedders had at least one episode of genital tract shedding with no available measurement prior to or following the episode. Women who had genital tract shedding between negative visits were described as intermittent shedders, and those who had at least two consecutive episodes of genital tract shedding were persistent shedders.

Of the 49 patients enrolled, 46 maintained below detectable plasma viral loads during the course of the study. “What was astonishing to us is that more than half of those women had some degree of detectable genital tract shedding,” Dr. Cu-Uvin said. Specifically, 26% of the women with sustained below detectable plasma viral load were indeterminate shedders, 18% were intermittent shedders, and 8% were persistent shedders, “despite being on HAART and having below detectable levels of virus in their plasma,” she said. Among the nine women with total hysterectomy, one demonstrated persistent shedding in the vagina, whereas the others were classified as nonshedders, she said.

Although logistic regression analyses showed the probability of detecting HIV RNA in the genital tract subcompartment was low when plasma viral load was below detectable levels, Dr. Cu-Uvin said, “it worries us that there are some women on antiretroviral therapy who have a very good response in the blood, who, if you look hard enough and at multiple time points, will have evidence of genital tract HIV RNA.”

What this means clinically, she said, is that the potential for sexual transmission of HIV exists even among women whose virus appears to be well controlled. “So, for example, when a woman on HAART comes to me and says she wants to have a baby, there is no way to assure her, even if she has a below detectable plasma viral load, that it's safe to have unprotected sex.”

BOSTON — Women on highly active antiretroviral therapy for human immunodeficiency virus whose plasma viral load is below detectable levels may continue to shed the virus intermittently in the genital tract, Dr. Susan Cu-Uvin said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“This finding means we cannot rule out the possibility of continued risk of HIV transmission among women in whom the virus appears to be well controlled,” said Dr. Cu-Uvin of Brown University, Providence, R.I.

The advent of highly active antiretroviral therapy (HAART) has resulted in significant decreases in the replication of HIV in the blood of infected patients, and in so doing it has substantially reduced the associated morbidity and mortality of the disease, Dr. Cu-Uvin said.

“However, several studies have shown evidence of discordance between the RNA shedding of HIV in the blood and in the female genital tract, and when it comes to sexual transmission of HIV, the big player is the amount of genital tract viral load, not the plasma viral load,” she said. “Unfortunately, because the only commercially available tools for assessing HIV viral load are those that look at RNA shedding in plasma, we use plasma viral load as a surrogate for how infectious a given patient is, yet this may not always reflect what is happening in the genital tract.”

Dr. Cu-Uvin and colleagues sought to assess the pattern of HIV genital tract shedding among women already on HAART with sustained below detectable plasma viral loads. Of 55 women with HIV enrolled in an ongoing study of HAART, 49 with below detectable plasma viral load for at least 6 months were included in the analysis. Each of the women underwent serum plasma and genital tract sampling every 4 weeks for 12 weeks. Genital tract secretions were collected from the endocervix, ectocervix, and vagina in 40 of the women, and from the vagina only in 9 women who had previous hysterectomies. The lower limit of viral detection was 80 copies per milliliter for plasma and 3,300 copies per milliliter for the genital tract, Dr. Cu-Uvin noted.

The immune status of all of the patients was “generally good,” with a median CD4 count of 412 cells/mm

Patients were grouped based on their genital tract HIV RNA patterns, Dr. Cu-Uvin explained. Nonshedders were those women with no evidence of detectable genital tract HIV during study visits. Indeterminate shedders had at least one episode of genital tract shedding with no available measurement prior to or following the episode. Women who had genital tract shedding between negative visits were described as intermittent shedders, and those who had at least two consecutive episodes of genital tract shedding were persistent shedders.

Of the 49 patients enrolled, 46 maintained below detectable plasma viral loads during the course of the study. “What was astonishing to us is that more than half of those women had some degree of detectable genital tract shedding,” Dr. Cu-Uvin said. Specifically, 26% of the women with sustained below detectable plasma viral load were indeterminate shedders, 18% were intermittent shedders, and 8% were persistent shedders, “despite being on HAART and having below detectable levels of virus in their plasma,” she said. Among the nine women with total hysterectomy, one demonstrated persistent shedding in the vagina, whereas the others were classified as nonshedders, she said.

Although logistic regression analyses showed the probability of detecting HIV RNA in the genital tract subcompartment was low when plasma viral load was below detectable levels, Dr. Cu-Uvin said, “it worries us that there are some women on antiretroviral therapy who have a very good response in the blood, who, if you look hard enough and at multiple time points, will have evidence of genital tract HIV RNA.”

What this means clinically, she said, is that the potential for sexual transmission of HIV exists even among women whose virus appears to be well controlled. “So, for example, when a woman on HAART comes to me and says she wants to have a baby, there is no way to assure her, even if she has a below detectable plasma viral load, that it's safe to have unprotected sex.”

BOSTON — Women on highly active antiretroviral therapy for human immunodeficiency virus whose plasma viral load is below detectable levels may continue to shed the virus intermittently in the genital tract, Dr. Susan Cu-Uvin said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“This finding means we cannot rule out the possibility of continued risk of HIV transmission among women in whom the virus appears to be well controlled,” said Dr. Cu-Uvin of Brown University, Providence, R.I.

The advent of highly active antiretroviral therapy (HAART) has resulted in significant decreases in the replication of HIV in the blood of infected patients, and in so doing it has substantially reduced the associated morbidity and mortality of the disease, Dr. Cu-Uvin said.

“However, several studies have shown evidence of discordance between the RNA shedding of HIV in the blood and in the female genital tract, and when it comes to sexual transmission of HIV, the big player is the amount of genital tract viral load, not the plasma viral load,” she said. “Unfortunately, because the only commercially available tools for assessing HIV viral load are those that look at RNA shedding in plasma, we use plasma viral load as a surrogate for how infectious a given patient is, yet this may not always reflect what is happening in the genital tract.”

Dr. Cu-Uvin and colleagues sought to assess the pattern of HIV genital tract shedding among women already on HAART with sustained below detectable plasma viral loads. Of 55 women with HIV enrolled in an ongoing study of HAART, 49 with below detectable plasma viral load for at least 6 months were included in the analysis. Each of the women underwent serum plasma and genital tract sampling every 4 weeks for 12 weeks. Genital tract secretions were collected from the endocervix, ectocervix, and vagina in 40 of the women, and from the vagina only in 9 women who had previous hysterectomies. The lower limit of viral detection was 80 copies per milliliter for plasma and 3,300 copies per milliliter for the genital tract, Dr. Cu-Uvin noted.

The immune status of all of the patients was “generally good,” with a median CD4 count of 412 cells/mm

Patients were grouped based on their genital tract HIV RNA patterns, Dr. Cu-Uvin explained. Nonshedders were those women with no evidence of detectable genital tract HIV during study visits. Indeterminate shedders had at least one episode of genital tract shedding with no available measurement prior to or following the episode. Women who had genital tract shedding between negative visits were described as intermittent shedders, and those who had at least two consecutive episodes of genital tract shedding were persistent shedders.

Of the 49 patients enrolled, 46 maintained below detectable plasma viral loads during the course of the study. “What was astonishing to us is that more than half of those women had some degree of detectable genital tract shedding,” Dr. Cu-Uvin said. Specifically, 26% of the women with sustained below detectable plasma viral load were indeterminate shedders, 18% were intermittent shedders, and 8% were persistent shedders, “despite being on HAART and having below detectable levels of virus in their plasma,” she said. Among the nine women with total hysterectomy, one demonstrated persistent shedding in the vagina, whereas the others were classified as nonshedders, she said.

Although logistic regression analyses showed the probability of detecting HIV RNA in the genital tract subcompartment was low when plasma viral load was below detectable levels, Dr. Cu-Uvin said, “it worries us that there are some women on antiretroviral therapy who have a very good response in the blood, who, if you look hard enough and at multiple time points, will have evidence of genital tract HIV RNA.”

What this means clinically, she said, is that the potential for sexual transmission of HIV exists even among women whose virus appears to be well controlled. “So, for example, when a woman on HAART comes to me and says she wants to have a baby, there is no way to assure her, even if she has a below detectable plasma viral load, that it's safe to have unprotected sex.”

ATLANTA — Vulvar ulcers were associated with a viral illness rather than a sexually transmitted disease in 14 of 46 patients under age 22, based on the findings of a retrospective study.

“Many practitioners are quick to diagnose a genital ulcer as a sexually transmitted disease because STDs are the most common cause; but young women can present with vulvar ulcers that are secondary to a viral infection,” Dr. Rebecca Kyle said in a poster presented at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

“Although such cases may be rare, misdiagnosing this as an STD can be devastating to the patient and her family and can lead to the prescription of unnecessary medications,” she noted.

The findings confirm the need for a thorough physical and history for all young women who present with vulvar or labial ulcers, said Dr. Kyle.

Dr. Kyle and her colleagues at the University of Missouri-Kansas City conducted a retrospective study of all patients aged 12–21 years who presented to Children's Mercy Hospital between 1999 and 2005 with a diagnosis of vulvar ulcer or lesion.

Of the 46 charts identified, “31 were excluded for diagnoses inconsistent with vulvar ulcer or for having positive lab results consistent with a sexually transmitted disease,” said Dr. Kyle.

Of the remaining 15 patients, 14 reported an antecedent history of viral symptoms. “One of the 14 patients with a viral history was eventually diagnosed with Crohn's disease and another patient, who experienced recurrent ulcers, was referred to rheumatology for suspicion of Behçet's disease,” she said.

All of the patients with non-sexually transmitted ulcers were treated symptomatically with complete resolution of the presenting ulcer, said Dr. Kyle.

Additionally, “although they are diagnoses of exclusion, Crohn's disease and Behçet's syndrome must be considered in patients with non-sexually transmitted genital ulcers, particularly when the ulcers are recurrent and occur in conjunction with or following other viral symptoms,” Dr. Kyle stressed.

In particular, she noted, vulvar ulcers that occur in combination with oral ulcers and eye complaints should raise suspicion of Behçet's and those that occur in association with gastrointestinal symptoms potentially point to Crohn's, although genital ulcers as an extraintestinal manifestation of Crohn's can precede intestinal symptoms as well.

ATLANTA — Vulvar ulcers were associated with a viral illness rather than a sexually transmitted disease in 14 of 46 patients under age 22, based on the findings of a retrospective study.

“Many practitioners are quick to diagnose a genital ulcer as a sexually transmitted disease because STDs are the most common cause; but young women can present with vulvar ulcers that are secondary to a viral infection,” Dr. Rebecca Kyle said in a poster presented at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

“Although such cases may be rare, misdiagnosing this as an STD can be devastating to the patient and her family and can lead to the prescription of unnecessary medications,” she noted.

The findings confirm the need for a thorough physical and history for all young women who present with vulvar or labial ulcers, said Dr. Kyle.

Dr. Kyle and her colleagues at the University of Missouri-Kansas City conducted a retrospective study of all patients aged 12–21 years who presented to Children's Mercy Hospital between 1999 and 2005 with a diagnosis of vulvar ulcer or lesion.

Of the 46 charts identified, “31 were excluded for diagnoses inconsistent with vulvar ulcer or for having positive lab results consistent with a sexually transmitted disease,” said Dr. Kyle.

Of the remaining 15 patients, 14 reported an antecedent history of viral symptoms. “One of the 14 patients with a viral history was eventually diagnosed with Crohn's disease and another patient, who experienced recurrent ulcers, was referred to rheumatology for suspicion of Behçet's disease,” she said.

All of the patients with non-sexually transmitted ulcers were treated symptomatically with complete resolution of the presenting ulcer, said Dr. Kyle.

Additionally, “although they are diagnoses of exclusion, Crohn's disease and Behçet's syndrome must be considered in patients with non-sexually transmitted genital ulcers, particularly when the ulcers are recurrent and occur in conjunction with or following other viral symptoms,” Dr. Kyle stressed.

In particular, she noted, vulvar ulcers that occur in combination with oral ulcers and eye complaints should raise suspicion of Behçet's and those that occur in association with gastrointestinal symptoms potentially point to Crohn's, although genital ulcers as an extraintestinal manifestation of Crohn's can precede intestinal symptoms as well.

ATLANTA — Vulvar ulcers were associated with a viral illness rather than a sexually transmitted disease in 14 of 46 patients under age 22, based on the findings of a retrospective study.

“Many practitioners are quick to diagnose a genital ulcer as a sexually transmitted disease because STDs are the most common cause; but young women can present with vulvar ulcers that are secondary to a viral infection,” Dr. Rebecca Kyle said in a poster presented at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

“Although such cases may be rare, misdiagnosing this as an STD can be devastating to the patient and her family and can lead to the prescription of unnecessary medications,” she noted.

The findings confirm the need for a thorough physical and history for all young women who present with vulvar or labial ulcers, said Dr. Kyle.

Dr. Kyle and her colleagues at the University of Missouri-Kansas City conducted a retrospective study of all patients aged 12–21 years who presented to Children's Mercy Hospital between 1999 and 2005 with a diagnosis of vulvar ulcer or lesion.

Of the 46 charts identified, “31 were excluded for diagnoses inconsistent with vulvar ulcer or for having positive lab results consistent with a sexually transmitted disease,” said Dr. Kyle.

Of the remaining 15 patients, 14 reported an antecedent history of viral symptoms. “One of the 14 patients with a viral history was eventually diagnosed with Crohn's disease and another patient, who experienced recurrent ulcers, was referred to rheumatology for suspicion of Behçet's disease,” she said.

All of the patients with non-sexually transmitted ulcers were treated symptomatically with complete resolution of the presenting ulcer, said Dr. Kyle.

Additionally, “although they are diagnoses of exclusion, Crohn's disease and Behçet's syndrome must be considered in patients with non-sexually transmitted genital ulcers, particularly when the ulcers are recurrent and occur in conjunction with or following other viral symptoms,” Dr. Kyle stressed.

In particular, she noted, vulvar ulcers that occur in combination with oral ulcers and eye complaints should raise suspicion of Behçet's and those that occur in association with gastrointestinal symptoms potentially point to Crohn's, although genital ulcers as an extraintestinal manifestation of Crohn's can precede intestinal symptoms as well.

BOSTON— Women with bacterial vaginosis who fail initial treatment with either metronidazole or clindamycin may respond favorably to subsequent treatment with the same medication, results of a small study have shown.

Using data from 119 nonpregnant women with bacterial vaginosis who participated in a randomized controlled trial comparing topical metronidazole with topical clindamycin for the treatment of bacterial vaginosis, Dr. Katherine E. Bunge of the University of Pittsburgh Magee-Womens Research Institute and her colleagues conducted a nested cohort investigation to compare retreatment cure rates in women who failed initial treatment with either of these drugs. For the purposes of this study, bacterial vaginosis was defined clinically as the presence of at least three of the four Amsel's criteria.

Study participants were randomized to receive metronidazole for 5 days or clindamycin for 3 days and were asked to return for follow-up visits at 7–12 days post treatment, 35–45 days post treatment, and 70–90 days post treatment. “At each of the follow-up visits, the women were assessed for clinical cure of bacterial vaginosis, defined as less than two Amsel's criteria,” Dr. Bunge reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Study protocol dictated that women with early treatment failure, defined as clinical evidence of bacterial vaginosis at either the second or third follow-up visit, should be prescribed a second course of the medication to which they were initially randomized.

Of the initial 119 patients enrolled in the larger randomized controlled trial study, 104 had adequate clinical data for inclusion in the subgroup analysis. Of these women, 51 had evidence of failed initial treatment at follow-up visit two or three and 33 were retreated with the same medication they were initially randomized to receive, said Dr. Bunge. “These 33 women make up the cohort in this study,” she said, noting that 19 of the women had been randomized initially to metronidazole treatment and 14 to clindamycin treatment. The mean age of the predominantly nonwhite cohort was 27 years.

Overall, 21 of the 33 women with a single early clinical failure responded successfully to retreatment, “giving a cure rate of 64%,” Dr. Bunge reported. Retreatment resulted in 11 cures in the metronidazole arm and 10 in the clindamycin arm. There was no statistical significance in the difference between the respective cure rates of 58% and 71%, she said.

While the study was not powered to detect differences between women in whom retreatment was and was not successful, said Dr. Bunge, “there were no obvious differences between the two groups in terms of therapy, smoking, age, race, or bacterial vaginosis history.”

Of the 12 women who experienced a second treatment failure, only two received a third course of the same medication to which they were initially randomized and neither had clinical evidence of cure at the subsequent follow-up. The remaining 10 women with two treatment failures were retreated with a different medication, “but only two experienced cure at follow-up,” said Dr. Bunge. “This suggests that women who experience repetitive early treatment failures are unlikely to respond favorably to retreatment.”

The study is limited by its small size, Dr. Bunge noted. “Unfortunately, only 65% of the early treatment failures were retreated with the same medication, as had been our intention.” In addition, she said, “long-term follow-up data were not available.”

Despite the limitations, the findings do lead to the conclusion that for women who experience a single early treatment failure, “retreatment with the same medication is a reasonable approach,” said Dr. Bunge. This is important, she added, because early treatment failure of bacterial vaginosis is common, and there is a lack of data that remotely touch on the best management course.

BOSTON— Women with bacterial vaginosis who fail initial treatment with either metronidazole or clindamycin may respond favorably to subsequent treatment with the same medication, results of a small study have shown.

Using data from 119 nonpregnant women with bacterial vaginosis who participated in a randomized controlled trial comparing topical metronidazole with topical clindamycin for the treatment of bacterial vaginosis, Dr. Katherine E. Bunge of the University of Pittsburgh Magee-Womens Research Institute and her colleagues conducted a nested cohort investigation to compare retreatment cure rates in women who failed initial treatment with either of these drugs. For the purposes of this study, bacterial vaginosis was defined clinically as the presence of at least three of the four Amsel's criteria.

Study participants were randomized to receive metronidazole for 5 days or clindamycin for 3 days and were asked to return for follow-up visits at 7–12 days post treatment, 35–45 days post treatment, and 70–90 days post treatment. “At each of the follow-up visits, the women were assessed for clinical cure of bacterial vaginosis, defined as less than two Amsel's criteria,” Dr. Bunge reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Study protocol dictated that women with early treatment failure, defined as clinical evidence of bacterial vaginosis at either the second or third follow-up visit, should be prescribed a second course of the medication to which they were initially randomized.

Of the initial 119 patients enrolled in the larger randomized controlled trial study, 104 had adequate clinical data for inclusion in the subgroup analysis. Of these women, 51 had evidence of failed initial treatment at follow-up visit two or three and 33 were retreated with the same medication they were initially randomized to receive, said Dr. Bunge. “These 33 women make up the cohort in this study,” she said, noting that 19 of the women had been randomized initially to metronidazole treatment and 14 to clindamycin treatment. The mean age of the predominantly nonwhite cohort was 27 years.

Overall, 21 of the 33 women with a single early clinical failure responded successfully to retreatment, “giving a cure rate of 64%,” Dr. Bunge reported. Retreatment resulted in 11 cures in the metronidazole arm and 10 in the clindamycin arm. There was no statistical significance in the difference between the respective cure rates of 58% and 71%, she said.

While the study was not powered to detect differences between women in whom retreatment was and was not successful, said Dr. Bunge, “there were no obvious differences between the two groups in terms of therapy, smoking, age, race, or bacterial vaginosis history.”

Of the 12 women who experienced a second treatment failure, only two received a third course of the same medication to which they were initially randomized and neither had clinical evidence of cure at the subsequent follow-up. The remaining 10 women with two treatment failures were retreated with a different medication, “but only two experienced cure at follow-up,” said Dr. Bunge. “This suggests that women who experience repetitive early treatment failures are unlikely to respond favorably to retreatment.”

The study is limited by its small size, Dr. Bunge noted. “Unfortunately, only 65% of the early treatment failures were retreated with the same medication, as had been our intention.” In addition, she said, “long-term follow-up data were not available.”

Despite the limitations, the findings do lead to the conclusion that for women who experience a single early treatment failure, “retreatment with the same medication is a reasonable approach,” said Dr. Bunge. This is important, she added, because early treatment failure of bacterial vaginosis is common, and there is a lack of data that remotely touch on the best management course.

BOSTON— Women with bacterial vaginosis who fail initial treatment with either metronidazole or clindamycin may respond favorably to subsequent treatment with the same medication, results of a small study have shown.

Using data from 119 nonpregnant women with bacterial vaginosis who participated in a randomized controlled trial comparing topical metronidazole with topical clindamycin for the treatment of bacterial vaginosis, Dr. Katherine E. Bunge of the University of Pittsburgh Magee-Womens Research Institute and her colleagues conducted a nested cohort investigation to compare retreatment cure rates in women who failed initial treatment with either of these drugs. For the purposes of this study, bacterial vaginosis was defined clinically as the presence of at least three of the four Amsel's criteria.

Study participants were randomized to receive metronidazole for 5 days or clindamycin for 3 days and were asked to return for follow-up visits at 7–12 days post treatment, 35–45 days post treatment, and 70–90 days post treatment. “At each of the follow-up visits, the women were assessed for clinical cure of bacterial vaginosis, defined as less than two Amsel's criteria,” Dr. Bunge reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Study protocol dictated that women with early treatment failure, defined as clinical evidence of bacterial vaginosis at either the second or third follow-up visit, should be prescribed a second course of the medication to which they were initially randomized.

Of the initial 119 patients enrolled in the larger randomized controlled trial study, 104 had adequate clinical data for inclusion in the subgroup analysis. Of these women, 51 had evidence of failed initial treatment at follow-up visit two or three and 33 were retreated with the same medication they were initially randomized to receive, said Dr. Bunge. “These 33 women make up the cohort in this study,” she said, noting that 19 of the women had been randomized initially to metronidazole treatment and 14 to clindamycin treatment. The mean age of the predominantly nonwhite cohort was 27 years.

Overall, 21 of the 33 women with a single early clinical failure responded successfully to retreatment, “giving a cure rate of 64%,” Dr. Bunge reported. Retreatment resulted in 11 cures in the metronidazole arm and 10 in the clindamycin arm. There was no statistical significance in the difference between the respective cure rates of 58% and 71%, she said.

While the study was not powered to detect differences between women in whom retreatment was and was not successful, said Dr. Bunge, “there were no obvious differences between the two groups in terms of therapy, smoking, age, race, or bacterial vaginosis history.”

Of the 12 women who experienced a second treatment failure, only two received a third course of the same medication to which they were initially randomized and neither had clinical evidence of cure at the subsequent follow-up. The remaining 10 women with two treatment failures were retreated with a different medication, “but only two experienced cure at follow-up,” said Dr. Bunge. “This suggests that women who experience repetitive early treatment failures are unlikely to respond favorably to retreatment.”

The study is limited by its small size, Dr. Bunge noted. “Unfortunately, only 65% of the early treatment failures were retreated with the same medication, as had been our intention.” In addition, she said, “long-term follow-up data were not available.”

Despite the limitations, the findings do lead to the conclusion that for women who experience a single early treatment failure, “retreatment with the same medication is a reasonable approach,” said Dr. Bunge. This is important, she added, because early treatment failure of bacterial vaginosis is common, and there is a lack of data that remotely touch on the best management course.

BOSTON — Prenatal smoking exposure is associated with significant increases in irritability in newborn girls but not boys, according to a study presented at a meeting of the Society for Research in Child Development.

The fact that significant differences were not evident in male infants in the large, epidemiologic sample might suggest early links to later sex differences in behavioral outcomes, said Rachel L. Paster, a research assistant in the Centers for Behavioral and Preventive Medicine, Brown University, Providence, R.I.

All of the infants exposed to prenatal smoking exhibited increases in muscle tension, compared with unexposed infants, she said in a poster presentation.

Using data from the New England Cohort of the National Collaborative Perinatal Project (NCPP), Ms. Paster and colleagues examined the effects of smoking during pregnancy on the neurobehavior of male and female newborns in a sample of 991 healthy mother-infant pairs recruited between 1959 and 1962.

As part of the NCPP, smoking was measured prospectively at each prenatal visit and newborn neurobehavior was assessed using the Graham-Rosenblith behavioral examination. For the current investigation, the participants were classified as nonsmokers, moderate smokers (between 1 and 19 cigarettes per day), and heavy smokers (20 or more cigarettes per day).

“We found significant differences between smoking groups for irritability in females, but not in males,” Ms. Paster reported. “Tests revealed significant differences between the heavy smoking group and both the moderate and no smoking groups only for female infants, while significant effects of maternal smoking group on muscle tone emerged for both male and female infants.”

The tests also showed different patterns of effects for males and females with respect to muscle tone. “For females, the heavy smoking group was significantly different from both the moderate and no smoking groups, whereas for males, the moderate smoking group differed significantly from the no smoking and heavy smoking groups,” said Ms. Paster.

Regarding the irritability findings, excessive irritability could indicate an infant withdrawal syndrome, Ms. Paster noted. Additionally, “irritability could potentially affect bonding and attachment with caregivers and may represent an early link to emotional dysregulation,” she said.

BOSTON — Prenatal smoking exposure is associated with significant increases in irritability in newborn girls but not boys, according to a study presented at a meeting of the Society for Research in Child Development.

The fact that significant differences were not evident in male infants in the large, epidemiologic sample might suggest early links to later sex differences in behavioral outcomes, said Rachel L. Paster, a research assistant in the Centers for Behavioral and Preventive Medicine, Brown University, Providence, R.I.

All of the infants exposed to prenatal smoking exhibited increases in muscle tension, compared with unexposed infants, she said in a poster presentation.

Using data from the New England Cohort of the National Collaborative Perinatal Project (NCPP), Ms. Paster and colleagues examined the effects of smoking during pregnancy on the neurobehavior of male and female newborns in a sample of 991 healthy mother-infant pairs recruited between 1959 and 1962.

As part of the NCPP, smoking was measured prospectively at each prenatal visit and newborn neurobehavior was assessed using the Graham-Rosenblith behavioral examination. For the current investigation, the participants were classified as nonsmokers, moderate smokers (between 1 and 19 cigarettes per day), and heavy smokers (20 or more cigarettes per day).

“We found significant differences between smoking groups for irritability in females, but not in males,” Ms. Paster reported. “Tests revealed significant differences between the heavy smoking group and both the moderate and no smoking groups only for female infants, while significant effects of maternal smoking group on muscle tone emerged for both male and female infants.”

The tests also showed different patterns of effects for males and females with respect to muscle tone. “For females, the heavy smoking group was significantly different from both the moderate and no smoking groups, whereas for males, the moderate smoking group differed significantly from the no smoking and heavy smoking groups,” said Ms. Paster.

Regarding the irritability findings, excessive irritability could indicate an infant withdrawal syndrome, Ms. Paster noted. Additionally, “irritability could potentially affect bonding and attachment with caregivers and may represent an early link to emotional dysregulation,” she said.

BOSTON — Prenatal smoking exposure is associated with significant increases in irritability in newborn girls but not boys, according to a study presented at a meeting of the Society for Research in Child Development.

The fact that significant differences were not evident in male infants in the large, epidemiologic sample might suggest early links to later sex differences in behavioral outcomes, said Rachel L. Paster, a research assistant in the Centers for Behavioral and Preventive Medicine, Brown University, Providence, R.I.

All of the infants exposed to prenatal smoking exhibited increases in muscle tension, compared with unexposed infants, she said in a poster presentation.

Using data from the New England Cohort of the National Collaborative Perinatal Project (NCPP), Ms. Paster and colleagues examined the effects of smoking during pregnancy on the neurobehavior of male and female newborns in a sample of 991 healthy mother-infant pairs recruited between 1959 and 1962.

As part of the NCPP, smoking was measured prospectively at each prenatal visit and newborn neurobehavior was assessed using the Graham-Rosenblith behavioral examination. For the current investigation, the participants were classified as nonsmokers, moderate smokers (between 1 and 19 cigarettes per day), and heavy smokers (20 or more cigarettes per day).

“We found significant differences between smoking groups for irritability in females, but not in males,” Ms. Paster reported. “Tests revealed significant differences between the heavy smoking group and both the moderate and no smoking groups only for female infants, while significant effects of maternal smoking group on muscle tone emerged for both male and female infants.”

The tests also showed different patterns of effects for males and females with respect to muscle tone. “For females, the heavy smoking group was significantly different from both the moderate and no smoking groups, whereas for males, the moderate smoking group differed significantly from the no smoking and heavy smoking groups,” said Ms. Paster.

Regarding the irritability findings, excessive irritability could indicate an infant withdrawal syndrome, Ms. Paster noted. Additionally, “irritability could potentially affect bonding and attachment with caregivers and may represent an early link to emotional dysregulation,” she said.

Biologic agents should not be used as first-line therapy for inflammatory bowel disease (IBD), according to the recommendations of a consensus development conference convened by the AGA Institute.

While certain biologic therapies have demonstrated efficacy in some patients with Crohn's disease and ulcerative colitis, especially patients with refractory or fistulizing disease, there is also evidence of serious, potentially fatal side effects, wrote Dr. Paul Rutgeerts and Dr. Steven Hanauer, co-chairs of the consensus conference, as well as the other members of the AGA Institute IBD Biologics Conference panel.

Thus, despite emerging evidence that the early use of biologics may modify the course of IBD, there is insufficient data so far to support their routine use as first-line agents, according to the group's findings, which are reported the July 2007 issue of Gastroenterology.

Biologic therapy can be considered prior to steroid use in some patients with IBD, including those for whom other therapies have failed or in whom steroids are contraindicated, the panel wrote. Additionally, use of biologic agents may be warranted in specific subgroups of patients with IBD, such as those with complex fistulas for whom conventional therapies are relatively ineffective.

The majority of available data regarding the use of biologic agents in IBD relates to anti-tumor necrosis factor (anti-TNF) drugs. In comparing the results of clinical trials of currently available anti-TNF agents approved for Crohn's disease (infliximab and adalimumab) and for ulcerative colitis (infliximab), as well as certolizumab pegol, for which approval is pending for Crohn's disease, the panel determined that the drugs, “when optimally dosed, are similarly effective in their ability to induce response and remission.”

In terms of other biologic agents, the drug etanercept, in doses that are effective in rheumatoid arthritis, “is not effective in Crohn's disease,” while the human monoclonal antibody natalizumab appears to have similar maintenance benefits to those of the anti-TNFs, “although there [are fewer] high-quality data to evaluate pertaining to induction of remission,” the authors wrote.

The degree and duration of therapeutic response to biologic agents can be affected by the development of antibodies to the drugs, which is a common occurrence, the panel stated. High-dose induction accompanied by scheduled maintenance regimens can reduce this immune response, as can immune suppression that has been initiated in advance of the biologic therapy in order to assure adequate immunomodulatory effects, they said.

The use of immune suppression with anti-TNF agents and natalizumab, however, appears to increase the risk of serious infections and neoplasia. For example, natalizumab use with concomitant immune suppression has been associated with progressive multifocal leukoencephalopathy (PML), while infliximab combined with azathioprine has been associated with neoplasia, such as hepatosplenic T-cell lymphomas. “These uncommon but serious risks require additional risk-benefit evaluations for individual patients,” the authors stated.

Despite evidence that biologics modify the course of IBD, there is insufficient data to support their routine use. DR. HANAUER

Biologic agents should not be used as first-line therapy for inflammatory bowel disease (IBD), according to the recommendations of a consensus development conference convened by the AGA Institute.

While certain biologic therapies have demonstrated efficacy in some patients with Crohn's disease and ulcerative colitis, especially patients with refractory or fistulizing disease, there is also evidence of serious, potentially fatal side effects, wrote Dr. Paul Rutgeerts and Dr. Steven Hanauer, co-chairs of the consensus conference, as well as the other members of the AGA Institute IBD Biologics Conference panel.

Thus, despite emerging evidence that the early use of biologics may modify the course of IBD, there is insufficient data so far to support their routine use as first-line agents, according to the group's findings, which are reported the July 2007 issue of Gastroenterology.

Biologic therapy can be considered prior to steroid use in some patients with IBD, including those for whom other therapies have failed or in whom steroids are contraindicated, the panel wrote. Additionally, use of biologic agents may be warranted in specific subgroups of patients with IBD, such as those with complex fistulas for whom conventional therapies are relatively ineffective.

The majority of available data regarding the use of biologic agents in IBD relates to anti-tumor necrosis factor (anti-TNF) drugs. In comparing the results of clinical trials of currently available anti-TNF agents approved for Crohn's disease (infliximab and adalimumab) and for ulcerative colitis (infliximab), as well as certolizumab pegol, for which approval is pending for Crohn's disease, the panel determined that the drugs, “when optimally dosed, are similarly effective in their ability to induce response and remission.”

In terms of other biologic agents, the drug etanercept, in doses that are effective in rheumatoid arthritis, “is not effective in Crohn's disease,” while the human monoclonal antibody natalizumab appears to have similar maintenance benefits to those of the anti-TNFs, “although there [are fewer] high-quality data to evaluate pertaining to induction of remission,” the authors wrote.

The degree and duration of therapeutic response to biologic agents can be affected by the development of antibodies to the drugs, which is a common occurrence, the panel stated. High-dose induction accompanied by scheduled maintenance regimens can reduce this immune response, as can immune suppression that has been initiated in advance of the biologic therapy in order to assure adequate immunomodulatory effects, they said.

The use of immune suppression with anti-TNF agents and natalizumab, however, appears to increase the risk of serious infections and neoplasia. For example, natalizumab use with concomitant immune suppression has been associated with progressive multifocal leukoencephalopathy (PML), while infliximab combined with azathioprine has been associated with neoplasia, such as hepatosplenic T-cell lymphomas. “These uncommon but serious risks require additional risk-benefit evaluations for individual patients,” the authors stated.

Despite evidence that biologics modify the course of IBD, there is insufficient data to support their routine use. DR. HANAUER

Biologic agents should not be used as first-line therapy for inflammatory bowel disease (IBD), according to the recommendations of a consensus development conference convened by the AGA Institute.

While certain biologic therapies have demonstrated efficacy in some patients with Crohn's disease and ulcerative colitis, especially patients with refractory or fistulizing disease, there is also evidence of serious, potentially fatal side effects, wrote Dr. Paul Rutgeerts and Dr. Steven Hanauer, co-chairs of the consensus conference, as well as the other members of the AGA Institute IBD Biologics Conference panel.

Thus, despite emerging evidence that the early use of biologics may modify the course of IBD, there is insufficient data so far to support their routine use as first-line agents, according to the group's findings, which are reported the July 2007 issue of Gastroenterology.

Biologic therapy can be considered prior to steroid use in some patients with IBD, including those for whom other therapies have failed or in whom steroids are contraindicated, the panel wrote. Additionally, use of biologic agents may be warranted in specific subgroups of patients with IBD, such as those with complex fistulas for whom conventional therapies are relatively ineffective.

The majority of available data regarding the use of biologic agents in IBD relates to anti-tumor necrosis factor (anti-TNF) drugs. In comparing the results of clinical trials of currently available anti-TNF agents approved for Crohn's disease (infliximab and adalimumab) and for ulcerative colitis (infliximab), as well as certolizumab pegol, for which approval is pending for Crohn's disease, the panel determined that the drugs, “when optimally dosed, are similarly effective in their ability to induce response and remission.”

In terms of other biologic agents, the drug etanercept, in doses that are effective in rheumatoid arthritis, “is not effective in Crohn's disease,” while the human monoclonal antibody natalizumab appears to have similar maintenance benefits to those of the anti-TNFs, “although there [are fewer] high-quality data to evaluate pertaining to induction of remission,” the authors wrote.

The degree and duration of therapeutic response to biologic agents can be affected by the development of antibodies to the drugs, which is a common occurrence, the panel stated. High-dose induction accompanied by scheduled maintenance regimens can reduce this immune response, as can immune suppression that has been initiated in advance of the biologic therapy in order to assure adequate immunomodulatory effects, they said.

The use of immune suppression with anti-TNF agents and natalizumab, however, appears to increase the risk of serious infections and neoplasia. For example, natalizumab use with concomitant immune suppression has been associated with progressive multifocal leukoencephalopathy (PML), while infliximab combined with azathioprine has been associated with neoplasia, such as hepatosplenic T-cell lymphomas. “These uncommon but serious risks require additional risk-benefit evaluations for individual patients,” the authors stated.

Despite evidence that biologics modify the course of IBD, there is insufficient data to support their routine use. DR. HANAUER

The availability of new agents for the treatment of type 2 diabetes, as well as new indications for existing agents, has broadened the therapeutic landscape for the disease, but without a map, the region can be difficult to navigate. To provide direction, the American College of Endocrinology and the American Association of Clinical Endocrinologists recently revised its “Road Maps for the Prevention and Treatment of Type 2 Diabetes.”

The three road maps—one each for treatment-naive patients, treated patients who had not reached the hemoglobin A_1c (HbA_1c) target, and patients at high risk for progression to diabetes—were introduced in 2005 to provide guidance for meeting existing diabetes treatment guidelines.

“We needed to update [them] because there have been a number of new products introduced, including inhaled insulin, basal insulin analogs, pramlintide, and DPP-4 inhibitors,” said Dr. Paul S. Jellinger, cochairman of the Road Map Task Force. “There are also new indications for some of the drugs already in use. For example, exenatide is now approved for use with [thiazolidinediones] in treatment-naive patients presenting with initial A_1c between 7%–8% who haven't achieved the target A_1c goal of 6.5% or lower with other therapies.”

Although other treatment algorithms have not yet included mention of the newer agents, “we've included recommendations on when and how to use them, based on A_1c-lowering data from FDA- [Food and Drug Administration]approved clinical trials and large randomized trials, as well as expert opinion,” said Dr. Jellinger, who is in private practice in Hollywood, Fla. “We want patients and clinicians to be able to take advantage of the newer-approved therapies without having to wait 10–20 years for more outcome data.”

The road maps also give physicians guidance and specificity all the way through the disease process, said Dr. Jaime A. Davidson, the other task force cochairman. “Rather than taking a treat-to-failure approach by waiting for patients to fail and then giving them a pill, the road maps use a treat-to-target approach from day 1, clearly indicating when to initiate therapy and with what agent. They also specify when to move on. For instance, instead of wasting a year to see if metformin by itself will get a given patient to target, the road maps define what agents to add if target is not met within 3 months.”

In addition, the road maps are geared to the needs of individual patients, continued Dr. Davidson, an endocrinologist at Medical City Dallas Hospital. “Rather than saying, 'We're going to start everyone who comes in with treatment-naive disease on metformin,' the road maps differentiate based on A_1c percentages. If someone comes in with an A_1c between 10%–11% and is symptomatic, they get insulin from day 1.”

That stratification is very important, Dr. Jellinger said. “Patients presenting with an A_1c between 10%–11% certainly require different treatment than those presenting at 7%–8%.” Although an HbA_1c greater than 10% is an indication for insulin in most patients, “other algorithms don't provide clear stratification, and many lump together everyone with an A_1c over 7%,” the glycemic target recommended by the American Diabetes Association.

As in the earlier road maps, the revised versions also advocate an “uncompromising treat-to-target” approach, in which the treatment targets are an HbA_1c value of 6.5% or less, fasting/preprandial glucose levels less than 110 mg/dL, and a 2-hour postprandial glucose level less than 140 mg/dL, as per guidelines from the American Association of Clinical Endocrinologists, said Dr. Jellinger. The goal “is to get patients to target as quickly as possible and to keep them there.”

The road maps help achieve this by targeting, in particular, the treatment of postprandial hyperglycemia in the lower HbA_1c ranges, which also distinguishes the resource from other algorithms. “Studies have shown that the postprandial glucose is higher in the lower A_1c ranges, while fasting hyperglycemia increases in the higher A_1c ranges,” said Dr. Jellinger. “This is why we recommend agents that affect postprandial control, such as the [meglitinide derivatives] and DPP-4 inhibitors, more prominently in treatment-naive patients in the lower A_1c range.”

To best meet and maintain AACE glycemic goals, therapeutic agents should be monitored and adjusted every 2–3 months. “If a treatment is not working as well as it should, change it. The road maps clearly tell you what to do, step by step, to meet and maintain the 6.5% A_1c goal,” said Dr. Jellinger.

In terms of prevention, the road maps stress early identification of high-risk individuals and describe lifestyle modifications and pharmacologic options that have been shown to stave off progression to type 2 diabetes. The document lists four glucose-lowering agents that have, in clinical studies, effectively delayed the onset of type 2 diabetes in high-risk patients, but the agents are not FDA-approved for prediabetes and, as such, AACE does not advocate their off-label use, Dr. Jellinger noted. “The drugs are listed because we recognize that physicians do use them to treat prediabetic individuals, particularly those with impaired glucose tolerance and multiple cardiovascular risk factors.” The AACE is currently developing a consensus conference on the treatment of prediabetes.

The revised road maps are available on the AACE Web site at www.aace.com/meetings/consensus/odimplementation/roadmap.pdf

The availability of new agents for the treatment of type 2 diabetes, as well as new indications for existing agents, has broadened the therapeutic landscape for the disease, but without a map, the region can be difficult to navigate. To provide direction, the American College of Endocrinology and the American Association of Clinical Endocrinologists recently revised its “Road Maps for the Prevention and Treatment of Type 2 Diabetes.”

The three road maps—one each for treatment-naive patients, treated patients who had not reached the hemoglobin A_1c (HbA_1c) target, and patients at high risk for progression to diabetes—were introduced in 2005 to provide guidance for meeting existing diabetes treatment guidelines.

“We needed to update [them] because there have been a number of new products introduced, including inhaled insulin, basal insulin analogs, pramlintide, and DPP-4 inhibitors,” said Dr. Paul S. Jellinger, cochairman of the Road Map Task Force. “There are also new indications for some of the drugs already in use. For example, exenatide is now approved for use with [thiazolidinediones] in treatment-naive patients presenting with initial A_1c between 7%–8% who haven't achieved the target A_1c goal of 6.5% or lower with other therapies.”

Although other treatment algorithms have not yet included mention of the newer agents, “we've included recommendations on when and how to use them, based on A_1c-lowering data from FDA- [Food and Drug Administration]approved clinical trials and large randomized trials, as well as expert opinion,” said Dr. Jellinger, who is in private practice in Hollywood, Fla. “We want patients and clinicians to be able to take advantage of the newer-approved therapies without having to wait 10–20 years for more outcome data.”

The road maps also give physicians guidance and specificity all the way through the disease process, said Dr. Jaime A. Davidson, the other task force cochairman. “Rather than taking a treat-to-failure approach by waiting for patients to fail and then giving them a pill, the road maps use a treat-to-target approach from day 1, clearly indicating when to initiate therapy and with what agent. They also specify when to move on. For instance, instead of wasting a year to see if metformin by itself will get a given patient to target, the road maps define what agents to add if target is not met within 3 months.”

In addition, the road maps are geared to the needs of individual patients, continued Dr. Davidson, an endocrinologist at Medical City Dallas Hospital. “Rather than saying, 'We're going to start everyone who comes in with treatment-naive disease on metformin,' the road maps differentiate based on A_1c percentages. If someone comes in with an A_1c between 10%–11% and is symptomatic, they get insulin from day 1.”

That stratification is very important, Dr. Jellinger said. “Patients presenting with an A_1c between 10%–11% certainly require different treatment than those presenting at 7%–8%.” Although an HbA_1c greater than 10% is an indication for insulin in most patients, “other algorithms don't provide clear stratification, and many lump together everyone with an A_1c over 7%,” the glycemic target recommended by the American Diabetes Association.

As in the earlier road maps, the revised versions also advocate an “uncompromising treat-to-target” approach, in which the treatment targets are an HbA_1c value of 6.5% or less, fasting/preprandial glucose levels less than 110 mg/dL, and a 2-hour postprandial glucose level less than 140 mg/dL, as per guidelines from the American Association of Clinical Endocrinologists, said Dr. Jellinger. The goal “is to get patients to target as quickly as possible and to keep them there.”

The road maps help achieve this by targeting, in particular, the treatment of postprandial hyperglycemia in the lower HbA_1c ranges, which also distinguishes the resource from other algorithms. “Studies have shown that the postprandial glucose is higher in the lower A_1c ranges, while fasting hyperglycemia increases in the higher A_1c ranges,” said Dr. Jellinger. “This is why we recommend agents that affect postprandial control, such as the [meglitinide derivatives] and DPP-4 inhibitors, more prominently in treatment-naive patients in the lower A_1c range.”

To best meet and maintain AACE glycemic goals, therapeutic agents should be monitored and adjusted every 2–3 months. “If a treatment is not working as well as it should, change it. The road maps clearly tell you what to do, step by step, to meet and maintain the 6.5% A_1c goal,” said Dr. Jellinger.

In terms of prevention, the road maps stress early identification of high-risk individuals and describe lifestyle modifications and pharmacologic options that have been shown to stave off progression to type 2 diabetes. The document lists four glucose-lowering agents that have, in clinical studies, effectively delayed the onset of type 2 diabetes in high-risk patients, but the agents are not FDA-approved for prediabetes and, as such, AACE does not advocate their off-label use, Dr. Jellinger noted. “The drugs are listed because we recognize that physicians do use them to treat prediabetic individuals, particularly those with impaired glucose tolerance and multiple cardiovascular risk factors.” The AACE is currently developing a consensus conference on the treatment of prediabetes.

The revised road maps are available on the AACE Web site at www.aace.com/meetings/consensus/odimplementation/roadmap.pdf

The availability of new agents for the treatment of type 2 diabetes, as well as new indications for existing agents, has broadened the therapeutic landscape for the disease, but without a map, the region can be difficult to navigate. To provide direction, the American College of Endocrinology and the American Association of Clinical Endocrinologists recently revised its “Road Maps for the Prevention and Treatment of Type 2 Diabetes.”

The three road maps—one each for treatment-naive patients, treated patients who had not reached the hemoglobin A_1c (HbA_1c) target, and patients at high risk for progression to diabetes—were introduced in 2005 to provide guidance for meeting existing diabetes treatment guidelines.

“We needed to update [them] because there have been a number of new products introduced, including inhaled insulin, basal insulin analogs, pramlintide, and DPP-4 inhibitors,” said Dr. Paul S. Jellinger, cochairman of the Road Map Task Force. “There are also new indications for some of the drugs already in use. For example, exenatide is now approved for use with [thiazolidinediones] in treatment-naive patients presenting with initial A_1c between 7%–8% who haven't achieved the target A_1c goal of 6.5% or lower with other therapies.”

Although other treatment algorithms have not yet included mention of the newer agents, “we've included recommendations on when and how to use them, based on A_1c-lowering data from FDA- [Food and Drug Administration]approved clinical trials and large randomized trials, as well as expert opinion,” said Dr. Jellinger, who is in private practice in Hollywood, Fla. “We want patients and clinicians to be able to take advantage of the newer-approved therapies without having to wait 10–20 years for more outcome data.”

The road maps also give physicians guidance and specificity all the way through the disease process, said Dr. Jaime A. Davidson, the other task force cochairman. “Rather than taking a treat-to-failure approach by waiting for patients to fail and then giving them a pill, the road maps use a treat-to-target approach from day 1, clearly indicating when to initiate therapy and with what agent. They also specify when to move on. For instance, instead of wasting a year to see if metformin by itself will get a given patient to target, the road maps define what agents to add if target is not met within 3 months.”

In addition, the road maps are geared to the needs of individual patients, continued Dr. Davidson, an endocrinologist at Medical City Dallas Hospital. “Rather than saying, 'We're going to start everyone who comes in with treatment-naive disease on metformin,' the road maps differentiate based on A_1c percentages. If someone comes in with an A_1c between 10%–11% and is symptomatic, they get insulin from day 1.”

That stratification is very important, Dr. Jellinger said. “Patients presenting with an A_1c between 10%–11% certainly require different treatment than those presenting at 7%–8%.” Although an HbA_1c greater than 10% is an indication for insulin in most patients, “other algorithms don't provide clear stratification, and many lump together everyone with an A_1c over 7%,” the glycemic target recommended by the American Diabetes Association.

As in the earlier road maps, the revised versions also advocate an “uncompromising treat-to-target” approach, in which the treatment targets are an HbA_1c value of 6.5% or less, fasting/preprandial glucose levels less than 110 mg/dL, and a 2-hour postprandial glucose level less than 140 mg/dL, as per guidelines from the American Association of Clinical Endocrinologists, said Dr. Jellinger. The goal “is to get patients to target as quickly as possible and to keep them there.”

The road maps help achieve this by targeting, in particular, the treatment of postprandial hyperglycemia in the lower HbA_1c ranges, which also distinguishes the resource from other algorithms. “Studies have shown that the postprandial glucose is higher in the lower A_1c ranges, while fasting hyperglycemia increases in the higher A_1c ranges,” said Dr. Jellinger. “This is why we recommend agents that affect postprandial control, such as the [meglitinide derivatives] and DPP-4 inhibitors, more prominently in treatment-naive patients in the lower A_1c range.”

To best meet and maintain AACE glycemic goals, therapeutic agents should be monitored and adjusted every 2–3 months. “If a treatment is not working as well as it should, change it. The road maps clearly tell you what to do, step by step, to meet and maintain the 6.5% A_1c goal,” said Dr. Jellinger.

In terms of prevention, the road maps stress early identification of high-risk individuals and describe lifestyle modifications and pharmacologic options that have been shown to stave off progression to type 2 diabetes. The document lists four glucose-lowering agents that have, in clinical studies, effectively delayed the onset of type 2 diabetes in high-risk patients, but the agents are not FDA-approved for prediabetes and, as such, AACE does not advocate their off-label use, Dr. Jellinger noted. “The drugs are listed because we recognize that physicians do use them to treat prediabetic individuals, particularly those with impaired glucose tolerance and multiple cardiovascular risk factors.” The AACE is currently developing a consensus conference on the treatment of prediabetes.

The revised road maps are available on the AACE Web site at www.aace.com/meetings/consensus/odimplementation/roadmap.pdf

A new assessment index based on six easily accessible variables effectively predicts the risk of nonvertebral fractures in postmenopausal osteoporotic women, a study has shown.

Because of its efficacy and clinical convenience, the new tool can be used to help in the identification and management of high-risk patients, reported lead investigator Dr. Christian Roux of Université de Paris Descartes, and colleagues.

The effect of a given osteoporosis treatment on nonvertebral fracture risk is a potential determinant of treatment choice. As such, the assessment of nonvertebral fracture risk in postmenopausal women with osteoporosis has important management implications, the authors wrote. Because risk assessment in this population can be difficult, in that multiple variables such as type and mechanism of fracture can impact an individual's risk profile, the investigators sought to identify significant predictive factors from which to develop a clinical useful fracture-risk-assessment tool.

Toward this end, they analyzed 3 years of follow-up data from 2,546 postmenopausal osteoporotic women who had been in the placebo groups of three multicenter, randomized controlled trials of the biphosphonate risendronate.

At baseline, the mean age of the study participants was 72 years, the mean femoral T score was −2.5, and 60% and 53% had prevalent vertebral and nonvertebral fractures, respectively.

All of the participants received 1,000 mg of calcium daily and up to 500 IU of vitamin D daily if baseline serum hydroxyvitamin D was less than 16 ng/mL (Ann. Rheum. Dis. 2007;66:931–35).

During the 3-year follow up, 222 nonvertebral fractures were observed in 206 patients. Of 14 variables included in logistic regression analysis of the fracture group, 6 emerged as independent predictors of nonvertebral fracture risk: age, height, prior nonvertebral fracture, number of prevalent vertebral fractures, femoral neck T score, and serum 25-hydroxyvitamin D, the authors reported.

With respect to vitamin D, “In the 48 patients who had a baseline serum hydroxyvitamin D less than 16 ng/mL, the incidence of nonvertebral fractures was 14.58%,” compared with 8.25% among the patients whose baseline measure was 16 ng/mL or higher, the authors wrote.

“Although patients received supplements of calcium and vitamin D, the low baseline level of 25-hydroxyvitamin D was still a significant risk factor for fracture, which may be related to a long-term effect of sarcopenia due to vitamin D deficiency,” they stated.

Based on the odds ratios for fracture associated with each of these variables, the investigators calculated fracture-risk index values for intervals within each variable, adjusting the minimal possible index contribution for each variable to zero (see index value chart).

For example, the risk index value for patients younger than 65 years is 0, while the index value for patients 80 years or older is 0.8.

The area under the receiver operating characteristic (ROC) curve for the final model based on the six predictors was 0.66. To minimize the absolute difference between sensitivity and specificity in the ROC curve, the investigators selected a cut-off value of 0.086 (or 8.6% nonvertebral fracture risk at baseline) for the predicted probability of nonvertebral fracture.

According to the model, patients with an index value of 2.1 or higher belong to a subgroup at high risk for nonvertebral fracture, the authors wrote.

In the 998 women from the original study population with an index value of at least 2.1, “the incidence of nonvertebral fractures was 13.2%, 1.5 times higher than the average of the population,” they noted.

One of the study's primary limitations is the lack of information on falls, which was not available.

This “ignored parameter” can be of crucial importance in explaining the fractures and may be useful in explaining the low value of the ROC curve, according to the researchers.

Still, the study findings suggest that “among osteoporotic women, a proportion of patients with a high risk of nonvertebral fractures can be selected and an index is a convenient tool for this selection in clinical practice,” the authors concluded.

ELSEVIER GLOBAL MEDICAL NEWS

A new assessment index based on six easily accessible variables effectively predicts the risk of nonvertebral fractures in postmenopausal osteoporotic women, a study has shown.

Because of its efficacy and clinical convenience, the new tool can be used to help in the identification and management of high-risk patients, reported lead investigator Dr. Christian Roux of Université de Paris Descartes, and colleagues.

The effect of a given osteoporosis treatment on nonvertebral fracture risk is a potential determinant of treatment choice. As such, the assessment of nonvertebral fracture risk in postmenopausal women with osteoporosis has important management implications, the authors wrote. Because risk assessment in this population can be difficult, in that multiple variables such as type and mechanism of fracture can impact an individual's risk profile, the investigators sought to identify significant predictive factors from which to develop a clinical useful fracture-risk-assessment tool.

Toward this end, they analyzed 3 years of follow-up data from 2,546 postmenopausal osteoporotic women who had been in the placebo groups of three multicenter, randomized controlled trials of the biphosphonate risendronate.

At baseline, the mean age of the study participants was 72 years, the mean femoral T score was −2.5, and 60% and 53% had prevalent vertebral and nonvertebral fractures, respectively.

All of the participants received 1,000 mg of calcium daily and up to 500 IU of vitamin D daily if baseline serum hydroxyvitamin D was less than 16 ng/mL (Ann. Rheum. Dis. 2007;66:931–35).

During the 3-year follow up, 222 nonvertebral fractures were observed in 206 patients. Of 14 variables included in logistic regression analysis of the fracture group, 6 emerged as independent predictors of nonvertebral fracture risk: age, height, prior nonvertebral fracture, number of prevalent vertebral fractures, femoral neck T score, and serum 25-hydroxyvitamin D, the authors reported.

With respect to vitamin D, “In the 48 patients who had a baseline serum hydroxyvitamin D less than 16 ng/mL, the incidence of nonvertebral fractures was 14.58%,” compared with 8.25% among the patients whose baseline measure was 16 ng/mL or higher, the authors wrote.

“Although patients received supplements of calcium and vitamin D, the low baseline level of 25-hydroxyvitamin D was still a significant risk factor for fracture, which may be related to a long-term effect of sarcopenia due to vitamin D deficiency,” they stated.

Based on the odds ratios for fracture associated with each of these variables, the investigators calculated fracture-risk index values for intervals within each variable, adjusting the minimal possible index contribution for each variable to zero (see index value chart).

For example, the risk index value for patients younger than 65 years is 0, while the index value for patients 80 years or older is 0.8.

The area under the receiver operating characteristic (ROC) curve for the final model based on the six predictors was 0.66. To minimize the absolute difference between sensitivity and specificity in the ROC curve, the investigators selected a cut-off value of 0.086 (or 8.6% nonvertebral fracture risk at baseline) for the predicted probability of nonvertebral fracture.

According to the model, patients with an index value of 2.1 or higher belong to a subgroup at high risk for nonvertebral fracture, the authors wrote.

In the 998 women from the original study population with an index value of at least 2.1, “the incidence of nonvertebral fractures was 13.2%, 1.5 times higher than the average of the population,” they noted.

One of the study's primary limitations is the lack of information on falls, which was not available.

This “ignored parameter” can be of crucial importance in explaining the fractures and may be useful in explaining the low value of the ROC curve, according to the researchers.

Still, the study findings suggest that “among osteoporotic women, a proportion of patients with a high risk of nonvertebral fractures can be selected and an index is a convenient tool for this selection in clinical practice,” the authors concluded.

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A new assessment index based on six easily accessible variables effectively predicts the risk of nonvertebral fractures in postmenopausal osteoporotic women, a study has shown.

Because of its efficacy and clinical convenience, the new tool can be used to help in the identification and management of high-risk patients, reported lead investigator Dr. Christian Roux of Université de Paris Descartes, and colleagues.

The effect of a given osteoporosis treatment on nonvertebral fracture risk is a potential determinant of treatment choice. As such, the assessment of nonvertebral fracture risk in postmenopausal women with osteoporosis has important management implications, the authors wrote. Because risk assessment in this population can be difficult, in that multiple variables such as type and mechanism of fracture can impact an individual's risk profile, the investigators sought to identify significant predictive factors from which to develop a clinical useful fracture-risk-assessment tool.

Toward this end, they analyzed 3 years of follow-up data from 2,546 postmenopausal osteoporotic women who had been in the placebo groups of three multicenter, randomized controlled trials of the biphosphonate risendronate.

At baseline, the mean age of the study participants was 72 years, the mean femoral T score was −2.5, and 60% and 53% had prevalent vertebral and nonvertebral fractures, respectively.

All of the participants received 1,000 mg of calcium daily and up to 500 IU of vitamin D daily if baseline serum hydroxyvitamin D was less than 16 ng/mL (Ann. Rheum. Dis. 2007;66:931–35).

During the 3-year follow up, 222 nonvertebral fractures were observed in 206 patients. Of 14 variables included in logistic regression analysis of the fracture group, 6 emerged as independent predictors of nonvertebral fracture risk: age, height, prior nonvertebral fracture, number of prevalent vertebral fractures, femoral neck T score, and serum 25-hydroxyvitamin D, the authors reported.

With respect to vitamin D, “In the 48 patients who had a baseline serum hydroxyvitamin D less than 16 ng/mL, the incidence of nonvertebral fractures was 14.58%,” compared with 8.25% among the patients whose baseline measure was 16 ng/mL or higher, the authors wrote.

“Although patients received supplements of calcium and vitamin D, the low baseline level of 25-hydroxyvitamin D was still a significant risk factor for fracture, which may be related to a long-term effect of sarcopenia due to vitamin D deficiency,” they stated.

Based on the odds ratios for fracture associated with each of these variables, the investigators calculated fracture-risk index values for intervals within each variable, adjusting the minimal possible index contribution for each variable to zero (see index value chart).

For example, the risk index value for patients younger than 65 years is 0, while the index value for patients 80 years or older is 0.8.

The area under the receiver operating characteristic (ROC) curve for the final model based on the six predictors was 0.66. To minimize the absolute difference between sensitivity and specificity in the ROC curve, the investigators selected a cut-off value of 0.086 (or 8.6% nonvertebral fracture risk at baseline) for the predicted probability of nonvertebral fracture.

According to the model, patients with an index value of 2.1 or higher belong to a subgroup at high risk for nonvertebral fracture, the authors wrote.

In the 998 women from the original study population with an index value of at least 2.1, “the incidence of nonvertebral fractures was 13.2%, 1.5 times higher than the average of the population,” they noted.

One of the study's primary limitations is the lack of information on falls, which was not available.

This “ignored parameter” can be of crucial importance in explaining the fractures and may be useful in explaining the low value of the ROC curve, according to the researchers.

Still, the study findings suggest that “among osteoporotic women, a proportion of patients with a high risk of nonvertebral fractures can be selected and an index is a convenient tool for this selection in clinical practice,” the authors concluded.

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Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, a study has shown.

Previous studies have demonstrated comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IBV vaccines has been linked with inconsistencies in immunologic responses, Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues said (J. Pediatr. 2007;151:43-9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine to that achieved via separate administration of all component vaccines, the investigators enrolled a total of 575 healthy infants from 22 U.S. sites into the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes, the investigators reported. Additionally, the three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups.

Although there were significantly higher rates of fever observed in the combination group, compared with both other groups, “there were no significant differences in rates of fever at or above 102.2° F [39.0° C], and the fevers were short in duration,” the authors said. Additionally, while the rates of irritability and some local swelling were higher with the combination vaccine, there were no group differences in the rates of symptoms for which parents sought medical advice, they said.

Immunogenicity of the combination vaccine was at least as good as that achieved with separate vaccines. DR. PICHICHERO

Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, a study has shown.

Previous studies have demonstrated comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IBV vaccines has been linked with inconsistencies in immunologic responses, Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues said (J. Pediatr. 2007;151:43-9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine to that achieved via separate administration of all component vaccines, the investigators enrolled a total of 575 healthy infants from 22 U.S. sites into the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes, the investigators reported. Additionally, the three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups.

Although there were significantly higher rates of fever observed in the combination group, compared with both other groups, “there were no significant differences in rates of fever at or above 102.2° F [39.0° C], and the fevers were short in duration,” the authors said. Additionally, while the rates of irritability and some local swelling were higher with the combination vaccine, there were no group differences in the rates of symptoms for which parents sought medical advice, they said.

Immunogenicity of the combination vaccine was at least as good as that achieved with separate vaccines. DR. PICHICHERO

Coadministering the seven-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine with the pentavalent diphtheria, tetanus, acellular pertussis, hepatitis B, and polio combination vaccine in infants does not compromise the safety and immunogenicity of the latter vaccine, a study has shown.

Previous studies have demonstrated comparable safety and immunogenicity of both the pentavalent vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus vaccines (DTaP-HepB-IPV) and the separate administration of the component vaccines when the H. influenzae type b vaccine (Hib) is administered to both groups. However, the coadministration of the seven-valent pneumococcal conjugate vaccine (PCV-7) with separate DTaP, Hib, HepB, and IBV vaccines has been linked with inconsistencies in immunologic responses, Dr. Michael E. Pichichero of the University of Rochester (N.Y.) and his colleagues said (J. Pediatr. 2007;151:43-9).

To compare the immunogenic impact of coadministration of the PCV-7 and Hib vaccines with the combined DTaP-HepB-IPV vaccine to that achieved via separate administration of all component vaccines, the investigators enrolled a total of 575 healthy infants from 22 U.S. sites into the current study and randomly assigned them to one of three conditions: Combination Vaccine Group (DTap-HepB-IPV plus PCV-7 and Hib), Separate Vaccine Group, or Staggered Vaccine Group (DTap-HepB-IPV plus Hib, with PCV-7 administered 2 weeks later). The vaccines were administered at each of the three primary immunization visits at 2, 4, and 6 months of age.

With respect to diphtheria, tetanus, pertussis, and poliovirus antibody responses, the immunogenicity of the combination vaccine coadministered with Hib and PCV-7 “was at least as good as” that achieved with the separate and staggered vaccine schemes, the investigators reported. Additionally, the three groups achieved similar rates of seroprotection for HepB and Hib, and seropositivity for PCV-7 was high in all groups.

Although there were significantly higher rates of fever observed in the combination group, compared with both other groups, “there were no significant differences in rates of fever at or above 102.2° F [39.0° C], and the fevers were short in duration,” the authors said. Additionally, while the rates of irritability and some local swelling were higher with the combination vaccine, there were no group differences in the rates of symptoms for which parents sought medical advice, they said.

Immunogenicity of the combination vaccine was at least as good as that achieved with separate vaccines. DR. PICHICHERO

Palivizumab prophylaxis against respiratory syncytial virus in premature infants without chronic lung disease significantly reduces the incidence and severity of recurrent wheezing, compared with preterm infants not on the preventive therapy, according to a study by Dr. Eric A.F. Simoes of the University of Colorado, Denver, and his colleagues.

Serious RSV infections in the first year of life among preterm infants are associated with an increased risk for developing recurrent wheezing or asthma, as well as persistent abnormal lung function. Because it has been demonstrated in large clinical trials that treatment with palivizumab–a humanized, anti-RSV monoclonal antibody–significantly reduces hospitalization for severe RSV lower respiratory tract infections (LRTI), the authors sought to determine whether preventive treatment with the drug in preterm infants could have an impact on subsequent recurrent wheezing and lung function.

Toward this end, they conducted a prospective investigation of the respiratory outcomes of a retrospectively selected study population of 421 preterm infants, including 191 who had received palivizumab and 230 who did not. None of the infants in the treated group had a prior history of hospitalization for RSV-induced LRTI, while 76 of the untreated group had been hospitalized previously for this condition. Starting at a mean age of 19 months, the children were observed for 24 months for episodes of recurrent wheezing and physician-diagnosed recurrent wheezing, Dr. Simoes and his colleages reported (J. Pediatr. 2007; 151:34-42).

Recurrent wheezing and physician-diagnosed recurrent wheezing were observed in 13% and 8% of the treated infants, respectively, compared with 26% and 16% of the untreated infants. The significant difference remained so after adjusting for potential confounding variables, including baseline RSV-neutralizing antibody titers, family history of asthma, gestational age at birth, birth weight, the number of adults and siblings in the home, and the presence of a wood-burning stove in the home, the authors reported.

Dr. Simoes and his associates also compared the respiratory outcomes of the treated cohort with those of the 154 infants in the untreated cohort who were not previously hospitalized for RSV LRTI; they observed significant relative reductions in both recurrent wheezing and physician-diagnosed recurrent wheezing episodes. This finding suggests that the protective effect of the prophylaxis is related to the drug's efficacy at preventing RSV-induced LRTIs “not just by preventing hospitalization,” they said.

The results of the study are not generalizable to term infants, as the mechanisms leading to recurrent wheezing differ between preterm and term infants. As such, Dr. Simoes and his associates stressed “our findings do not support widespread use of palivizumab.”

In an accompanying editorial, Dr. H. Cody Meissner of Tufts-New England Medical Center in Boston, noted that the findings, if reproducible, “support the theory that avoidance of early RSV infection can reduce the risk of long-term pulmonary complications [in premature infants without chronic lung disease]” (J. Pediatr. 2007;151:6-7).

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Palivizumab prophylaxis against respiratory syncytial virus in premature infants without chronic lung disease significantly reduces the incidence and severity of recurrent wheezing, compared with preterm infants not on the preventive therapy, according to a study by Dr. Eric A.F. Simoes of the University of Colorado, Denver, and his colleagues.

Serious RSV infections in the first year of life among preterm infants are associated with an increased risk for developing recurrent wheezing or asthma, as well as persistent abnormal lung function. Because it has been demonstrated in large clinical trials that treatment with palivizumab–a humanized, anti-RSV monoclonal antibody–significantly reduces hospitalization for severe RSV lower respiratory tract infections (LRTI), the authors sought to determine whether preventive treatment with the drug in preterm infants could have an impact on subsequent recurrent wheezing and lung function.

Toward this end, they conducted a prospective investigation of the respiratory outcomes of a retrospectively selected study population of 421 preterm infants, including 191 who had received palivizumab and 230 who did not. None of the infants in the treated group had a prior history of hospitalization for RSV-induced LRTI, while 76 of the untreated group had been hospitalized previously for this condition. Starting at a mean age of 19 months, the children were observed for 24 months for episodes of recurrent wheezing and physician-diagnosed recurrent wheezing, Dr. Simoes and his colleages reported (J. Pediatr. 2007; 151:34-42).

Recurrent wheezing and physician-diagnosed recurrent wheezing were observed in 13% and 8% of the treated infants, respectively, compared with 26% and 16% of the untreated infants. The significant difference remained so after adjusting for potential confounding variables, including baseline RSV-neutralizing antibody titers, family history of asthma, gestational age at birth, birth weight, the number of adults and siblings in the home, and the presence of a wood-burning stove in the home, the authors reported.

Dr. Simoes and his associates also compared the respiratory outcomes of the treated cohort with those of the 154 infants in the untreated cohort who were not previously hospitalized for RSV LRTI; they observed significant relative reductions in both recurrent wheezing and physician-diagnosed recurrent wheezing episodes. This finding suggests that the protective effect of the prophylaxis is related to the drug's efficacy at preventing RSV-induced LRTIs “not just by preventing hospitalization,” they said.

The results of the study are not generalizable to term infants, as the mechanisms leading to recurrent wheezing differ between preterm and term infants. As such, Dr. Simoes and his associates stressed “our findings do not support widespread use of palivizumab.”

In an accompanying editorial, Dr. H. Cody Meissner of Tufts-New England Medical Center in Boston, noted that the findings, if reproducible, “support the theory that avoidance of early RSV infection can reduce the risk of long-term pulmonary complications [in premature infants without chronic lung disease]” (J. Pediatr. 2007;151:6-7).

ELSEVIER GLOBAL MEDICAL NEWS

Palivizumab prophylaxis against respiratory syncytial virus in premature infants without chronic lung disease significantly reduces the incidence and severity of recurrent wheezing, compared with preterm infants not on the preventive therapy, according to a study by Dr. Eric A.F. Simoes of the University of Colorado, Denver, and his colleagues.

Serious RSV infections in the first year of life among preterm infants are associated with an increased risk for developing recurrent wheezing or asthma, as well as persistent abnormal lung function. Because it has been demonstrated in large clinical trials that treatment with palivizumab–a humanized, anti-RSV monoclonal antibody–significantly reduces hospitalization for severe RSV lower respiratory tract infections (LRTI), the authors sought to determine whether preventive treatment with the drug in preterm infants could have an impact on subsequent recurrent wheezing and lung function.

Toward this end, they conducted a prospective investigation of the respiratory outcomes of a retrospectively selected study population of 421 preterm infants, including 191 who had received palivizumab and 230 who did not. None of the infants in the treated group had a prior history of hospitalization for RSV-induced LRTI, while 76 of the untreated group had been hospitalized previously for this condition. Starting at a mean age of 19 months, the children were observed for 24 months for episodes of recurrent wheezing and physician-diagnosed recurrent wheezing, Dr. Simoes and his colleages reported (J. Pediatr. 2007; 151:34-42).

Recurrent wheezing and physician-diagnosed recurrent wheezing were observed in 13% and 8% of the treated infants, respectively, compared with 26% and 16% of the untreated infants. The significant difference remained so after adjusting for potential confounding variables, including baseline RSV-neutralizing antibody titers, family history of asthma, gestational age at birth, birth weight, the number of adults and siblings in the home, and the presence of a wood-burning stove in the home, the authors reported.

Dr. Simoes and his associates also compared the respiratory outcomes of the treated cohort with those of the 154 infants in the untreated cohort who were not previously hospitalized for RSV LRTI; they observed significant relative reductions in both recurrent wheezing and physician-diagnosed recurrent wheezing episodes. This finding suggests that the protective effect of the prophylaxis is related to the drug's efficacy at preventing RSV-induced LRTIs “not just by preventing hospitalization,” they said.

The results of the study are not generalizable to term infants, as the mechanisms leading to recurrent wheezing differ between preterm and term infants. As such, Dr. Simoes and his associates stressed “our findings do not support widespread use of palivizumab.”

In an accompanying editorial, Dr. H. Cody Meissner of Tufts-New England Medical Center in Boston, noted that the findings, if reproducible, “support the theory that avoidance of early RSV infection can reduce the risk of long-term pulmonary complications [in premature infants without chronic lung disease]” (J. Pediatr. 2007;151:6-7).

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