Diana Mahoney

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for treating aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients with either condition in a multicenter, open-label trial.

Nearly 65% of the patients were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to 400 mg IV moxifloxacin once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection; 48 received 1.5–3.0 g IV ampicillin/sulbactam twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess responded to treatment. In the ampicillin/sulbactam group, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections.

“There is limited information on optimal antibacterial therapeutic regimens for aspiration pneumonia and lung abscess patients. This study, which provides the biggest number of these patients published so far, indicates that moxifloxacin's activity against anaerobic bacteria is important and useful in treating these severe conditions,” he said.

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for treating aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients with either condition in a multicenter, open-label trial.

Nearly 65% of the patients were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to 400 mg IV moxifloxacin once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection; 48 received 1.5–3.0 g IV ampicillin/sulbactam twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess responded to treatment. In the ampicillin/sulbactam group, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections.

“There is limited information on optimal antibacterial therapeutic regimens for aspiration pneumonia and lung abscess patients. This study, which provides the biggest number of these patients published so far, indicates that moxifloxacin's activity against anaerobic bacteria is important and useful in treating these severe conditions,” he said.

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for treating aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients with either condition in a multicenter, open-label trial.

Nearly 65% of the patients were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to 400 mg IV moxifloxacin once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection; 48 received 1.5–3.0 g IV ampicillin/sulbactam twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess responded to treatment. In the ampicillin/sulbactam group, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections.

“There is limited information on optimal antibacterial therapeutic regimens for aspiration pneumonia and lung abscess patients. This study, which provides the biggest number of these patients published so far, indicates that moxifloxacin's activity against anaerobic bacteria is important and useful in treating these severe conditions,” he said.

MONTREAL — Short-course therapy with oral gemifloxacin is effective for the treatment of mild to moderate community-acquired pneumonia, including that caused by multidrug resistant Streptococcus pneumoniae, a study has shown.

The findings add to a growing body of evidence suggesting that the optimal duration of antimicrobial therapy may be shorter than current practice prescribes, Thomas M. File Jr., M.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

Proponents of short-course antimicrobial therapy for community-acquired pneumonia believe that shorter duration therapy might enhance compliance, reduce development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, cut treatment costs, and improve patient satisfaction with therapy, he said.

To compare the efficacy of 5-day gemifloxacin treatment with the standard 7-day course, Dr. File, professor of internal medicine at Northeastern Ohio Universities, Rootstown, and his colleagues enrolled 510 patients with mild to moderate CAP in a multicenter, double-blind study. Of the 468 patients who completed the entire treatment protocol, 242 were randomized to receive 320 mg of oral gemifloxacin (Factive) for 5 days, while 226 were given the same dose of the drug for the standard 7 days.

Measures of clinical response at the end of treatment showed a 96% response rate for both the 5-day and 7-day groups. At follow-up (2–3 weeks after treatment), the clinical response rate was 95% for the 5-day group and 92% for the 7-day group, Dr. File reported.

The bacteriological response rates were 94% and 96% for the 5-day and 7-day groups, respectively, at the end of treatment, and were 91% for both groups at follow-up. The radiological response rates, measured only at follow-up, were 98% for the 5-day patients and 95% for those taking the drug for 7 days. None of the differences was statistically significant, he said.

The 5-day dose of gemifloxacin eradicated S. pneumoniae—including five multidrug-resistant strains—in all 26 individuals in which the pathogen was identified. In the 7-day patients, the drug eradicated 87% of the S. pneumoniae, including four of six multidrug-resistant strains.

In terms of safety, the drug was well tolerated in both groups. “Withdrawal due to adverse events was only 1.2% for the 5-day group and 2.0% for the 7-day group,” Dr. File noted. The most common adverse event reported was a laboratory finding of elevated liver enzymes, but a subsequent analysis showed no association between the increase in these laboratory findings and treatment with gemifloxacin, nor did patients display hepatotoxic effects. The rates of drug-related rash were also low in both treatment groups.

Gemifloxacin is the most potent agent among the fluoroquinolones for the treatment of respiratory tract infections, “and more and more we are seeing the benefits of using a short course of the most potent antimicrobial drug in a class for treating infections such as community-acquired pneumonia,” he said.

MONTREAL — Short-course therapy with oral gemifloxacin is effective for the treatment of mild to moderate community-acquired pneumonia, including that caused by multidrug resistant Streptococcus pneumoniae, a study has shown.

The findings add to a growing body of evidence suggesting that the optimal duration of antimicrobial therapy may be shorter than current practice prescribes, Thomas M. File Jr., M.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

Proponents of short-course antimicrobial therapy for community-acquired pneumonia believe that shorter duration therapy might enhance compliance, reduce development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, cut treatment costs, and improve patient satisfaction with therapy, he said.

To compare the efficacy of 5-day gemifloxacin treatment with the standard 7-day course, Dr. File, professor of internal medicine at Northeastern Ohio Universities, Rootstown, and his colleagues enrolled 510 patients with mild to moderate CAP in a multicenter, double-blind study. Of the 468 patients who completed the entire treatment protocol, 242 were randomized to receive 320 mg of oral gemifloxacin (Factive) for 5 days, while 226 were given the same dose of the drug for the standard 7 days.

Measures of clinical response at the end of treatment showed a 96% response rate for both the 5-day and 7-day groups. At follow-up (2–3 weeks after treatment), the clinical response rate was 95% for the 5-day group and 92% for the 7-day group, Dr. File reported.

The bacteriological response rates were 94% and 96% for the 5-day and 7-day groups, respectively, at the end of treatment, and were 91% for both groups at follow-up. The radiological response rates, measured only at follow-up, were 98% for the 5-day patients and 95% for those taking the drug for 7 days. None of the differences was statistically significant, he said.

The 5-day dose of gemifloxacin eradicated S. pneumoniae—including five multidrug-resistant strains—in all 26 individuals in which the pathogen was identified. In the 7-day patients, the drug eradicated 87% of the S. pneumoniae, including four of six multidrug-resistant strains.

In terms of safety, the drug was well tolerated in both groups. “Withdrawal due to adverse events was only 1.2% for the 5-day group and 2.0% for the 7-day group,” Dr. File noted. The most common adverse event reported was a laboratory finding of elevated liver enzymes, but a subsequent analysis showed no association between the increase in these laboratory findings and treatment with gemifloxacin, nor did patients display hepatotoxic effects. The rates of drug-related rash were also low in both treatment groups.

Gemifloxacin is the most potent agent among the fluoroquinolones for the treatment of respiratory tract infections, “and more and more we are seeing the benefits of using a short course of the most potent antimicrobial drug in a class for treating infections such as community-acquired pneumonia,” he said.

MONTREAL — Short-course therapy with oral gemifloxacin is effective for the treatment of mild to moderate community-acquired pneumonia, including that caused by multidrug resistant Streptococcus pneumoniae, a study has shown.

The findings add to a growing body of evidence suggesting that the optimal duration of antimicrobial therapy may be shorter than current practice prescribes, Thomas M. File Jr., M.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

Proponents of short-course antimicrobial therapy for community-acquired pneumonia believe that shorter duration therapy might enhance compliance, reduce development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, cut treatment costs, and improve patient satisfaction with therapy, he said.

To compare the efficacy of 5-day gemifloxacin treatment with the standard 7-day course, Dr. File, professor of internal medicine at Northeastern Ohio Universities, Rootstown, and his colleagues enrolled 510 patients with mild to moderate CAP in a multicenter, double-blind study. Of the 468 patients who completed the entire treatment protocol, 242 were randomized to receive 320 mg of oral gemifloxacin (Factive) for 5 days, while 226 were given the same dose of the drug for the standard 7 days.

Measures of clinical response at the end of treatment showed a 96% response rate for both the 5-day and 7-day groups. At follow-up (2–3 weeks after treatment), the clinical response rate was 95% for the 5-day group and 92% for the 7-day group, Dr. File reported.

The bacteriological response rates were 94% and 96% for the 5-day and 7-day groups, respectively, at the end of treatment, and were 91% for both groups at follow-up. The radiological response rates, measured only at follow-up, were 98% for the 5-day patients and 95% for those taking the drug for 7 days. None of the differences was statistically significant, he said.

The 5-day dose of gemifloxacin eradicated S. pneumoniae—including five multidrug-resistant strains—in all 26 individuals in which the pathogen was identified. In the 7-day patients, the drug eradicated 87% of the S. pneumoniae, including four of six multidrug-resistant strains.

In terms of safety, the drug was well tolerated in both groups. “Withdrawal due to adverse events was only 1.2% for the 5-day group and 2.0% for the 7-day group,” Dr. File noted. The most common adverse event reported was a laboratory finding of elevated liver enzymes, but a subsequent analysis showed no association between the increase in these laboratory findings and treatment with gemifloxacin, nor did patients display hepatotoxic effects. The rates of drug-related rash were also low in both treatment groups.

Gemifloxacin is the most potent agent among the fluoroquinolones for the treatment of respiratory tract infections, “and more and more we are seeing the benefits of using a short course of the most potent antimicrobial drug in a class for treating infections such as community-acquired pneumonia,” he said.

MONTREAL — Monotherapy with oral gemifloxacin for hospitalized patients with community-acquired pneumonia is a more cost-effective option than treatment with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide, a study has shown.

Gemifloxacin (Factive) is a synthetic fluoroquinolone antimicrobial agent with potent activity against most gram-negative and gram-positive organisms, such as Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae, and Moraxella catarrhalis. It is the most active of the pneumococcal quinolones.

A retrospective cost-benefit analysis of the two treatment regimens, which were compared in a randomized, open-label, multicenter investigation, showed that the mean cost per expected success—defined as an infection successfully treated—was $6,316 for the gemifloxacin therapy and $7,310 for the ceftriaxone regimen, Sujata M. Bhavnani, Pharm.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

A total of 341 adults hospitalized with a clinical and radiologic diagnosis of CAP were enrolled in the multicenter study led by Hartmut Lode, M.D., of the Free University of Berlin. Of these patients, 169 were randomized to 320 mg oral gemifloxacin once daily for 7–14 days, while 172 received 2 g intravenous ceftriaxone for 1–7 days, followed by 500 mg oral cefuroxime twice daily for 1–13 days for a total of no more than 14 days. About 39% of the ceftriaxone patients received concomitant macrolide therapy.

The two regimens had similar efficacy, with response rates of 92.2% and 93.4%, respectively, for gemifloxacin and the ceftriaxone regimen. Both treatments were generally well tolerated, with similar types and frequencies of adverse events (Clin. Ther. 2002;24:1915–36).

To evaluate cost efficacy, Dr. Bhavnani, of the Institute for Clinical Pharmacodynamics at the Ordway Research Institute in Albany, N.Y., and colleagues analyzed the costs associated with antibiotic acquisition, antibiotic preparation, dispensing, and administration, as well as the treatment of antibiotic-related adverse events and clinical failures and hospital charges for both therapies.

Median length of stay was 8.0 days for the gemifloxacin group and 9.0 days for the ceftriaxone patients. For gemifloxacin and ceftriaxone, respectively, the mean costs of antibiotic acquisition were $201 and $501, while the combined costs for antibiotic preparation, dispensing, and administration and treatment of adverse events and clinical failures were $223 and $589. The mean hospital per diem costs were $5,823 and $6,828, respectively, Dr. Bhavnani said.

The findings confirm an important role for fluoroquinolones in therapy for CAP, “which could translate into real clinical and economic benefits,” Dr. Bhavnani noted at the conference, which was sponsored by the International Society of Chemotherapy.

MONTREAL — Monotherapy with oral gemifloxacin for hospitalized patients with community-acquired pneumonia is a more cost-effective option than treatment with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide, a study has shown.

Gemifloxacin (Factive) is a synthetic fluoroquinolone antimicrobial agent with potent activity against most gram-negative and gram-positive organisms, such as Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae, and Moraxella catarrhalis. It is the most active of the pneumococcal quinolones.

A retrospective cost-benefit analysis of the two treatment regimens, which were compared in a randomized, open-label, multicenter investigation, showed that the mean cost per expected success—defined as an infection successfully treated—was $6,316 for the gemifloxacin therapy and $7,310 for the ceftriaxone regimen, Sujata M. Bhavnani, Pharm.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

A total of 341 adults hospitalized with a clinical and radiologic diagnosis of CAP were enrolled in the multicenter study led by Hartmut Lode, M.D., of the Free University of Berlin. Of these patients, 169 were randomized to 320 mg oral gemifloxacin once daily for 7–14 days, while 172 received 2 g intravenous ceftriaxone for 1–7 days, followed by 500 mg oral cefuroxime twice daily for 1–13 days for a total of no more than 14 days. About 39% of the ceftriaxone patients received concomitant macrolide therapy.

The two regimens had similar efficacy, with response rates of 92.2% and 93.4%, respectively, for gemifloxacin and the ceftriaxone regimen. Both treatments were generally well tolerated, with similar types and frequencies of adverse events (Clin. Ther. 2002;24:1915–36).

To evaluate cost efficacy, Dr. Bhavnani, of the Institute for Clinical Pharmacodynamics at the Ordway Research Institute in Albany, N.Y., and colleagues analyzed the costs associated with antibiotic acquisition, antibiotic preparation, dispensing, and administration, as well as the treatment of antibiotic-related adverse events and clinical failures and hospital charges for both therapies.

Median length of stay was 8.0 days for the gemifloxacin group and 9.0 days for the ceftriaxone patients. For gemifloxacin and ceftriaxone, respectively, the mean costs of antibiotic acquisition were $201 and $501, while the combined costs for antibiotic preparation, dispensing, and administration and treatment of adverse events and clinical failures were $223 and $589. The mean hospital per diem costs were $5,823 and $6,828, respectively, Dr. Bhavnani said.

The findings confirm an important role for fluoroquinolones in therapy for CAP, “which could translate into real clinical and economic benefits,” Dr. Bhavnani noted at the conference, which was sponsored by the International Society of Chemotherapy.

MONTREAL — Monotherapy with oral gemifloxacin for hospitalized patients with community-acquired pneumonia is a more cost-effective option than treatment with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide, a study has shown.

Gemifloxacin (Factive) is a synthetic fluoroquinolone antimicrobial agent with potent activity against most gram-negative and gram-positive organisms, such as Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae, and Moraxella catarrhalis. It is the most active of the pneumococcal quinolones.

A retrospective cost-benefit analysis of the two treatment regimens, which were compared in a randomized, open-label, multicenter investigation, showed that the mean cost per expected success—defined as an infection successfully treated—was $6,316 for the gemifloxacin therapy and $7,310 for the ceftriaxone regimen, Sujata M. Bhavnani, Pharm.D., reported in a poster presentation at an international conference on community-acquired pneumonia (CAP).

A total of 341 adults hospitalized with a clinical and radiologic diagnosis of CAP were enrolled in the multicenter study led by Hartmut Lode, M.D., of the Free University of Berlin. Of these patients, 169 were randomized to 320 mg oral gemifloxacin once daily for 7–14 days, while 172 received 2 g intravenous ceftriaxone for 1–7 days, followed by 500 mg oral cefuroxime twice daily for 1–13 days for a total of no more than 14 days. About 39% of the ceftriaxone patients received concomitant macrolide therapy.

The two regimens had similar efficacy, with response rates of 92.2% and 93.4%, respectively, for gemifloxacin and the ceftriaxone regimen. Both treatments were generally well tolerated, with similar types and frequencies of adverse events (Clin. Ther. 2002;24:1915–36).

To evaluate cost efficacy, Dr. Bhavnani, of the Institute for Clinical Pharmacodynamics at the Ordway Research Institute in Albany, N.Y., and colleagues analyzed the costs associated with antibiotic acquisition, antibiotic preparation, dispensing, and administration, as well as the treatment of antibiotic-related adverse events and clinical failures and hospital charges for both therapies.

Median length of stay was 8.0 days for the gemifloxacin group and 9.0 days for the ceftriaxone patients. For gemifloxacin and ceftriaxone, respectively, the mean costs of antibiotic acquisition were $201 and $501, while the combined costs for antibiotic preparation, dispensing, and administration and treatment of adverse events and clinical failures were $223 and $589. The mean hospital per diem costs were $5,823 and $6,828, respectively, Dr. Bhavnani said.

The findings confirm an important role for fluoroquinolones in therapy for CAP, “which could translate into real clinical and economic benefits,” Dr. Bhavnani noted at the conference, which was sponsored by the International Society of Chemotherapy.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects has been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers to 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjustment for maternal age, ethnicity, gestational age and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects has been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers to 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjustment for maternal age, ethnicity, gestational age and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects has been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers to 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjustment for maternal age, ethnicity, gestational age and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

LOS ANGELES — Children taking sodium valproate for epilepsy may not be as vulnerable as adults to the significant weight gain associated with the medication, said Cia M. Sharpe, M.D.

In an effort to uncover possible clinical predictors of weight gain associated with valproate in the treatment of epilepsy, Dr. Sharpe and colleagues at the University of California, San Diego, conducted a chart review of 109 patients aged 2–20 years with valproate-treated epilepsy.

The investigators assessed body mass index (BMI) changes in the treated population by computing z slopes representing mean changes in BMI percentile for age at each available visit for each patient.

Using univariate analysis, they looked at the relationship between the z slopes and predictors of weight gain, including pretreatment BMI percentile for age, average valproate dose, average serum valproate level, standard or extended release formulation, age at onset of epilepsy, duration of valproate treatment, seizure disorder type, concurrent use of other medication, gender, and ethnicity—none of which proved to be useful predictors, Dr. Sharpe reported in a moderated poster session at the annual meeting of the Child Neurology Society.

Over the 2-year period, “there were no significant correlations between potential predictors of [weight gain] and z slope,” Dr. Sharpe said. Additionally, “the mean z slopes were less than expected, at -.006 per year, and only 25 of the 109 patients had sufficient BMI changes to increase their z score by 0.5 or more.”

While seemingly significant gains in weight have been reported with valproate therapy in children, “the increases may prove to be normal growth when change in BMI percentile for age is calculated,” Dr. Sharpe concluded.

LOS ANGELES — Children taking sodium valproate for epilepsy may not be as vulnerable as adults to the significant weight gain associated with the medication, said Cia M. Sharpe, M.D.

In an effort to uncover possible clinical predictors of weight gain associated with valproate in the treatment of epilepsy, Dr. Sharpe and colleagues at the University of California, San Diego, conducted a chart review of 109 patients aged 2–20 years with valproate-treated epilepsy.

The investigators assessed body mass index (BMI) changes in the treated population by computing z slopes representing mean changes in BMI percentile for age at each available visit for each patient.

Using univariate analysis, they looked at the relationship between the z slopes and predictors of weight gain, including pretreatment BMI percentile for age, average valproate dose, average serum valproate level, standard or extended release formulation, age at onset of epilepsy, duration of valproate treatment, seizure disorder type, concurrent use of other medication, gender, and ethnicity—none of which proved to be useful predictors, Dr. Sharpe reported in a moderated poster session at the annual meeting of the Child Neurology Society.

Over the 2-year period, “there were no significant correlations between potential predictors of [weight gain] and z slope,” Dr. Sharpe said. Additionally, “the mean z slopes were less than expected, at -.006 per year, and only 25 of the 109 patients had sufficient BMI changes to increase their z score by 0.5 or more.”

While seemingly significant gains in weight have been reported with valproate therapy in children, “the increases may prove to be normal growth when change in BMI percentile for age is calculated,” Dr. Sharpe concluded.

LOS ANGELES — Children taking sodium valproate for epilepsy may not be as vulnerable as adults to the significant weight gain associated with the medication, said Cia M. Sharpe, M.D.

In an effort to uncover possible clinical predictors of weight gain associated with valproate in the treatment of epilepsy, Dr. Sharpe and colleagues at the University of California, San Diego, conducted a chart review of 109 patients aged 2–20 years with valproate-treated epilepsy.

The investigators assessed body mass index (BMI) changes in the treated population by computing z slopes representing mean changes in BMI percentile for age at each available visit for each patient.

Using univariate analysis, they looked at the relationship between the z slopes and predictors of weight gain, including pretreatment BMI percentile for age, average valproate dose, average serum valproate level, standard or extended release formulation, age at onset of epilepsy, duration of valproate treatment, seizure disorder type, concurrent use of other medication, gender, and ethnicity—none of which proved to be useful predictors, Dr. Sharpe reported in a moderated poster session at the annual meeting of the Child Neurology Society.

Over the 2-year period, “there were no significant correlations between potential predictors of [weight gain] and z slope,” Dr. Sharpe said. Additionally, “the mean z slopes were less than expected, at -.006 per year, and only 25 of the 109 patients had sufficient BMI changes to increase their z score by 0.5 or more.”

While seemingly significant gains in weight have been reported with valproate therapy in children, “the increases may prove to be normal growth when change in BMI percentile for age is calculated,” Dr. Sharpe concluded.

LOS ANGELES — Adjunctive therapy with lamotrigine significantly reduced the number of primary generalized tonic-clonic seizures in children and adolescents in whom such seizures are inadequately controlled with other antiepileptic drugs alone, judging from findings reported by Edwin Trevathan, M.D.

The investigators, with funding by GlaxoSmithKline, conducted a subanalysis of a larger double-blind, placebo-controlled study looking at the safety and efficacy of lamotrigine (Lamictal) as an adjunctive therapy in both adults and children with primary generalized tonic-clonic (PGTC) seizures, Dr. Trevathan said at the annual meeting of the Child Neurology Society.

The approved pediatric indications of lamotrigine are management of simple or complex partial seizures or Lennox-Gastaut syndrome, a devastating childhood epileptic encephalopathy. The drug is not approved for use in children under 2 years of age.

In the larger study, 117 children, adolescents, and adults with EEG-confirmed PGTC seizures who were taking one or two concurrent antiepileptic drugs who also experienced three or more PGTC seizures during an 8-week baseline phase were randomized to adjunctive treatment with lamotrigine (58) or placebo (59). In the majority of patients, epilepsy ideology was classified as idiopathic. Patients with evidence of partial seizures were excluded from the study.

Data were collected at baseline, during the 7–12-week dose-escalation phase, and during the 12-week maintenance phase, when the dosage of the study drug and concurrent antiepileptics was held constant.

The results showed that lamotrigine reduced PGTC seizures significantly relative to baseline during both the dose-escalation and maintenance phases individually and during the entire combined treatment period, said Dr. Trevathan, director of pediatric and developmental neurology at Washington University, St. Louis.

In the posthoc subgroup analysis looking at only the results for adolescents and children—21 of whom were randomized to lamotrigine and 24 who got placebo—lamotrigine reduced the number of PGTC seizures from baseline by 77% during the entire treatment period compared with 40% for placebo. “Although the analysis was not powered to evaluate this subset of patients, the reduction is statistically significant,” Dr. Trevathan noted.

In the dose-escalation and maintenance phases, lamotrigine therapy was associated with a seizure frequency reduction from baseline in children of 72% and 83%, respectively, compared with 30% and 42% in the placebo group.

There were no reports of drug-induced serious rashes—rare cases of toxic epidermal necrolysis or Stevens-Johnson syndrome have been reported with lamotrigine treatment—in either treatment group. The most common adverse events reported during treatment were headache (10% with lamotrigine vs. 25% with placebo), nasopharyngitis (14% for lamotrigine vs. 4% for placebo), and convulsion (10% for lamotrigine vs. 13% for placebo). One patient from each treatment group dropped out of the study because of an adverse event.

“The magnitude of the effect that lamotrigine had on seizures in the subgroup analysis was approximately the same as was seen in the overall trial—basically a median percent reduction that was about twofold higher than placebo,” Dr. Trevathan said. Because PGTC seizures are associated with a range of potentially injurious physiologic and behavioral changes before, during, and after they occur and can have life-threatening complications, “effective control of these seizures is especially critical in the vulnerable child and adolescent populations,” said Dr. Trevathan. “We hope the results of this analysis will encourage more clinical trials of children and adolescents who suffer from these seizures.”

LOS ANGELES — Adjunctive therapy with lamotrigine significantly reduced the number of primary generalized tonic-clonic seizures in children and adolescents in whom such seizures are inadequately controlled with other antiepileptic drugs alone, judging from findings reported by Edwin Trevathan, M.D.

The investigators, with funding by GlaxoSmithKline, conducted a subanalysis of a larger double-blind, placebo-controlled study looking at the safety and efficacy of lamotrigine (Lamictal) as an adjunctive therapy in both adults and children with primary generalized tonic-clonic (PGTC) seizures, Dr. Trevathan said at the annual meeting of the Child Neurology Society.

The approved pediatric indications of lamotrigine are management of simple or complex partial seizures or Lennox-Gastaut syndrome, a devastating childhood epileptic encephalopathy. The drug is not approved for use in children under 2 years of age.

In the larger study, 117 children, adolescents, and adults with EEG-confirmed PGTC seizures who were taking one or two concurrent antiepileptic drugs who also experienced three or more PGTC seizures during an 8-week baseline phase were randomized to adjunctive treatment with lamotrigine (58) or placebo (59). In the majority of patients, epilepsy ideology was classified as idiopathic. Patients with evidence of partial seizures were excluded from the study.

Data were collected at baseline, during the 7–12-week dose-escalation phase, and during the 12-week maintenance phase, when the dosage of the study drug and concurrent antiepileptics was held constant.

The results showed that lamotrigine reduced PGTC seizures significantly relative to baseline during both the dose-escalation and maintenance phases individually and during the entire combined treatment period, said Dr. Trevathan, director of pediatric and developmental neurology at Washington University, St. Louis.

In the posthoc subgroup analysis looking at only the results for adolescents and children—21 of whom were randomized to lamotrigine and 24 who got placebo—lamotrigine reduced the number of PGTC seizures from baseline by 77% during the entire treatment period compared with 40% for placebo. “Although the analysis was not powered to evaluate this subset of patients, the reduction is statistically significant,” Dr. Trevathan noted.

In the dose-escalation and maintenance phases, lamotrigine therapy was associated with a seizure frequency reduction from baseline in children of 72% and 83%, respectively, compared with 30% and 42% in the placebo group.

There were no reports of drug-induced serious rashes—rare cases of toxic epidermal necrolysis or Stevens-Johnson syndrome have been reported with lamotrigine treatment—in either treatment group. The most common adverse events reported during treatment were headache (10% with lamotrigine vs. 25% with placebo), nasopharyngitis (14% for lamotrigine vs. 4% for placebo), and convulsion (10% for lamotrigine vs. 13% for placebo). One patient from each treatment group dropped out of the study because of an adverse event.

“The magnitude of the effect that lamotrigine had on seizures in the subgroup analysis was approximately the same as was seen in the overall trial—basically a median percent reduction that was about twofold higher than placebo,” Dr. Trevathan said. Because PGTC seizures are associated with a range of potentially injurious physiologic and behavioral changes before, during, and after they occur and can have life-threatening complications, “effective control of these seizures is especially critical in the vulnerable child and adolescent populations,” said Dr. Trevathan. “We hope the results of this analysis will encourage more clinical trials of children and adolescents who suffer from these seizures.”

LOS ANGELES — Adjunctive therapy with lamotrigine significantly reduced the number of primary generalized tonic-clonic seizures in children and adolescents in whom such seizures are inadequately controlled with other antiepileptic drugs alone, judging from findings reported by Edwin Trevathan, M.D.

The investigators, with funding by GlaxoSmithKline, conducted a subanalysis of a larger double-blind, placebo-controlled study looking at the safety and efficacy of lamotrigine (Lamictal) as an adjunctive therapy in both adults and children with primary generalized tonic-clonic (PGTC) seizures, Dr. Trevathan said at the annual meeting of the Child Neurology Society.

The approved pediatric indications of lamotrigine are management of simple or complex partial seizures or Lennox-Gastaut syndrome, a devastating childhood epileptic encephalopathy. The drug is not approved for use in children under 2 years of age.

In the larger study, 117 children, adolescents, and adults with EEG-confirmed PGTC seizures who were taking one or two concurrent antiepileptic drugs who also experienced three or more PGTC seizures during an 8-week baseline phase were randomized to adjunctive treatment with lamotrigine (58) or placebo (59). In the majority of patients, epilepsy ideology was classified as idiopathic. Patients with evidence of partial seizures were excluded from the study.

Data were collected at baseline, during the 7–12-week dose-escalation phase, and during the 12-week maintenance phase, when the dosage of the study drug and concurrent antiepileptics was held constant.

The results showed that lamotrigine reduced PGTC seizures significantly relative to baseline during both the dose-escalation and maintenance phases individually and during the entire combined treatment period, said Dr. Trevathan, director of pediatric and developmental neurology at Washington University, St. Louis.

In the posthoc subgroup analysis looking at only the results for adolescents and children—21 of whom were randomized to lamotrigine and 24 who got placebo—lamotrigine reduced the number of PGTC seizures from baseline by 77% during the entire treatment period compared with 40% for placebo. “Although the analysis was not powered to evaluate this subset of patients, the reduction is statistically significant,” Dr. Trevathan noted.

In the dose-escalation and maintenance phases, lamotrigine therapy was associated with a seizure frequency reduction from baseline in children of 72% and 83%, respectively, compared with 30% and 42% in the placebo group.

There were no reports of drug-induced serious rashes—rare cases of toxic epidermal necrolysis or Stevens-Johnson syndrome have been reported with lamotrigine treatment—in either treatment group. The most common adverse events reported during treatment were headache (10% with lamotrigine vs. 25% with placebo), nasopharyngitis (14% for lamotrigine vs. 4% for placebo), and convulsion (10% for lamotrigine vs. 13% for placebo). One patient from each treatment group dropped out of the study because of an adverse event.

“The magnitude of the effect that lamotrigine had on seizures in the subgroup analysis was approximately the same as was seen in the overall trial—basically a median percent reduction that was about twofold higher than placebo,” Dr. Trevathan said. Because PGTC seizures are associated with a range of potentially injurious physiologic and behavioral changes before, during, and after they occur and can have life-threatening complications, “effective control of these seizures is especially critical in the vulnerable child and adolescent populations,” said Dr. Trevathan. “We hope the results of this analysis will encourage more clinical trials of children and adolescents who suffer from these seizures.”

CAMBRIDGE, MASS. — Much of the “action” in the immunization arena is shifting to adolescents, according to Colin Marchant, M.D.

“Adolescent immunizations are a quickly evolving area, as youth in this age group are increasingly being recognized as important reservoirs for certain infectious diseases,” Dr. Marchant said at a pediatric infectious disease meeting sponsored by Boston University School of Medicine, PEDIATRIC NEWS, and FAMILY PRACTICE NEWS.

Until recently, the universal immunization recommendation for the 11− to 12-year preadolescent visit was for a diphtheria-tetanus (DT) booster. Earlier this year, the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) added the acellular pertussis and the conjugate meningococcal disease vaccines to its list of recommended immunizations for adolescents.

And it is likely that another vaccine—one of the two human papillomavirus vaccines currently wending their way through safety and efficacy trials—will be added to the adolescent immunization roster as soon the Food and Drug Administration approves them for use, said Dr. Marchant of Boston University.

It is expected that these vaccines will significantly reduce the infection rates of the respective diseases not only among adolescents, but also among infants and immunocompromised individuals in close contact with the adolescents, Dr. Marchant noted.

Acellular Pertussis Vaccine

With respect to pertussis, “adolescent immunization, and in fact adult immunization, is our unfinished business,” said Dr. Marchant, referring to the rise in recent years of pertussis infections.

In 2004, the highest number of U.S. pertussis cases was among individuals 10–18 years of age, with roughly 6,500 cases reported, according to data from the Centers for Disease Control and Prevention. Looking at infection rates across different age groups, “the numbers have remained steady for children ages 1–10, but they increase substantially starting at age 11 and peak around age 15, then start to fall back down,” he said.

“It's no surprise that kids in the adolescent age range have high rates of infection. They have lower antibody levels because their last pertussis immunization was before their 7th birthday.

“By age 11 or so, the vaccine-related antibody levels will have gone down, leaving these kids vulnerable to infection,” said Dr. Marchant.

Because these children are in such close contact with other children, in school and on sports teams, it's likely that once they're exposed to pertussis, they're going to get sick, because the infection is so highly contagious, with an airborne spread and from contact with nasal secretions, he said.

The observed rise in antibody levels after age 15 can be attributed to immunity developed through infection.

“We've known all along that immunity to pertussis wanes, but it wasn't until the late ′80s that we started going around looking for and counting cases of pertussis,” Dr. Marchant stated. With the 1987 introduction of the single-serum blood test to determine pertussis antibody levels, “we began to document cases, and as always, the closer you look, the more you find.”

In 2001, a pertussis outbreak in a youth football team in Arkansas led to 77 documented cases of the disease, forcing a school closure.

Around the same time, 500 cases (median age 13) were documented in a community in Arizona.

In 2003–2004, an outbreak traced to a high school weight room in Wisconsin led to 300 documented cases, primarily among adolescents, but also including some among infants, “who presumably were infected by adolescents or adults and who required hospitalization,” said Dr. Marchant.

These and other outbreaks have led to an increased public awareness of the spread of pertussis infection and have also led to stepped-up efforts to protect adolescents and adults from infection and to minimize the risk of disease transmission to infants, who experience significantly more morbidity and mortality as a result of infection.

In June of this year, with data from large, multicenter trials showing the two tetanus, diphtheria, acellular pertussis vaccines that were recently approved (GlaxoSmithKline's Boostrix and Sanofi Pasteur's Adacel) for use in adolescent and adult populations, ACIP recommended that all adolescents get the pertussis-inclusive vaccine instead of the TD-only booster at the 11− to 12-year visit.

In October of this year, the committee further recommended that adults also receive the pertussis vaccine the next time they are due for a booster, said Dr. Marchant.

Conjugate Meningococcal Vaccine

Life-threatening meningococcal disease affects 1,400–2,800 individuals in the United States each year. While the incidence is highest in children younger than 2 years, adolescents and young adults also are at high risk.

According to CDC data, approximately half of all of meningococcal infections occur in individuals between 15 and 24 years. “Studies have shown the case fatality rate to be especially high in this age group, but they have also shown the percent preventable to be very high,” said Dr. Marchant.

The majority of adolescents and young adults with meningococcal disease are infected with the meningococcal serogroup C, for which vaccine protection is available.

In contrast, infants are generally infected by meningococcal serogroup B, for which there is no vaccine.

Although a polysaccharide meningococcal vaccine (Menomune) has been licensed in the United States since 1978, it was not until the development and FDA licensure of the new quadrivalent conjugate meningococcal vaccine (Menactra) last year that ACIP included it on its list of recommended vaccines for the preadolescent visit.

The conjugate vaccine, approved for use in 11− to 55-year-olds, offers protection against serogroups A, C, Y, and W-135, and it offers improved duration of protection, induction of immunologic memory, booster responses, and reduction in nasopharyngeal bacterial carriage, compared with the polysaccharide vaccine, said Dr. Marchant.

The conjugate vaccine also is recommended for other people at increased risk for meningococcal disease, including college freshmen living in dormitories; microbiologists who are routinely exposed to meningococcal bacteria; U.S. military recruits; individuals traveling to or living in a part of the world where meningococcal disease is common; people who have a damaged spleen or whose spleen has been removed; those with an immune system disorder; and persons who might have been exposed to meningitis during an outbreak.

“We expect the universal immunization recommendation for preadolescents to have a big impact on infection rates,” said Dr. Marchant, noting that universal immunization with the polysaccharide vaccine in the U.S. military significantly reduced meningococcal infections since the immunization policy went into effect, in the early 1970s.

Similarly, a country-wide immunization program with a serogroup C conjugate vaccine in Great Britain (where most of the meningococcal infections among adolescents and young adults have been linked to serogroup C infection) resulted in a significant drop in disease incidence, “suggesting that a conjugate vaccine can control disease,” he said.

An unexpected roadblock to such success with the new conjugate vaccine may be noncompliance with the immunization recommendation resulting from reports of an association with Guillain Barré Syndrome (GBS).

“The immunizations began in the spring of last year, and it came out in September—after 2.8 million doses of the vaccine had been distributed—that there were 6 cases of Guillain Barré that occurred 2–6 weeks post vaccine,” said Dr. Marchant. “While this is more cases than we would like to see, there is not enough evidence to say that this is a cause-and-effect relationship.”

Not only have there not been any further cases reported since that time, there was previous personal or family history of GBS in some of the patients who developed it, further clouding the association, he noted.

“We know that most Guillain Barré is caused by certain infectious agents, but some of these infections are subclinical so we can't get a nice handle on the cause of the cases that occurred.”

Vaccine recommendations are not being altered by these preliminary reports of GBS, Dr. Marchant stressed. “The fact is, GBS has been reported after every vaccine given some time, somewhere, so these few reports are not enough to sway us from stressing the need for protection from meningococcal disease, which has a much higher attack rate and a much higher mortality rate than Guillain Barré Syndrome,” said Dr. Marchant. With respect to the potential for GBS, “we're just going to have to wait and see if it's out there.”

For families who refuse inoculation for their children because of the GBS reports, “it's okay to then recommend the polysaccharide vaccine, with the caveat that it doesn't last as long and may not offer the same protection,” he said.

Human Papillomavirus Vaccine

Although neither of the two human papillomavirus (HPV) vaccines under development—one from GlaxoSmithKline and one from Merck & Co.—have yet to be licensed, infectious disease experts have already begun advocating for their inclusion, upon FDA approval, in the preadolescent immunization lineup.

One of the two vaccines (GlaxoSmithKline's) targets HPV types 16 and 18, which together are responsible for 70% of all cervical cancers. The other vaccine, from Merck, covers these as well as HPV types 6 and 11, which are responsible for approximately 90% of all anogenital warts. “The interesting thing is that types 6 and 11 also cause some abnormal Pap smears, so a vaccine to fight these virus types should also decrease the number of positive Pap smears and procedures that follow,” said Dr. Marchant.

To date, the safety and efficacy of both products in clinical trials looks good compared to placebo, “and the year 2006 has been bandied about as possibilities for licensure,” Dr. Marchant noted. “The most likely scenario will be that these will be added into the 11− to 12-year visit, although there may be some opposition to this from those on the far right.”

Whether the recommendation, if it comes about, will include males as well as females, is still being considered. “Obviously, males don't get cervical cancer, but they can spread HPV to females, and they can also be affected by genital warts,” said Dr. Marchant. “However, it's difficult to show a benefit to immunizing males, in terms of transmission reduction.”

CAMBRIDGE, MASS. — Much of the “action” in the immunization arena is shifting to adolescents, according to Colin Marchant, M.D.

“Adolescent immunizations are a quickly evolving area, as youth in this age group are increasingly being recognized as important reservoirs for certain infectious diseases,” Dr. Marchant said at a pediatric infectious disease meeting sponsored by Boston University School of Medicine, PEDIATRIC NEWS, and FAMILY PRACTICE NEWS.

Until recently, the universal immunization recommendation for the 11− to 12-year preadolescent visit was for a diphtheria-tetanus (DT) booster. Earlier this year, the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) added the acellular pertussis and the conjugate meningococcal disease vaccines to its list of recommended immunizations for adolescents.

And it is likely that another vaccine—one of the two human papillomavirus vaccines currently wending their way through safety and efficacy trials—will be added to the adolescent immunization roster as soon the Food and Drug Administration approves them for use, said Dr. Marchant of Boston University.

It is expected that these vaccines will significantly reduce the infection rates of the respective diseases not only among adolescents, but also among infants and immunocompromised individuals in close contact with the adolescents, Dr. Marchant noted.

Acellular Pertussis Vaccine

With respect to pertussis, “adolescent immunization, and in fact adult immunization, is our unfinished business,” said Dr. Marchant, referring to the rise in recent years of pertussis infections.

In 2004, the highest number of U.S. pertussis cases was among individuals 10–18 years of age, with roughly 6,500 cases reported, according to data from the Centers for Disease Control and Prevention. Looking at infection rates across different age groups, “the numbers have remained steady for children ages 1–10, but they increase substantially starting at age 11 and peak around age 15, then start to fall back down,” he said.

“It's no surprise that kids in the adolescent age range have high rates of infection. They have lower antibody levels because their last pertussis immunization was before their 7th birthday.

“By age 11 or so, the vaccine-related antibody levels will have gone down, leaving these kids vulnerable to infection,” said Dr. Marchant.

Because these children are in such close contact with other children, in school and on sports teams, it's likely that once they're exposed to pertussis, they're going to get sick, because the infection is so highly contagious, with an airborne spread and from contact with nasal secretions, he said.

The observed rise in antibody levels after age 15 can be attributed to immunity developed through infection.

“We've known all along that immunity to pertussis wanes, but it wasn't until the late ′80s that we started going around looking for and counting cases of pertussis,” Dr. Marchant stated. With the 1987 introduction of the single-serum blood test to determine pertussis antibody levels, “we began to document cases, and as always, the closer you look, the more you find.”

In 2001, a pertussis outbreak in a youth football team in Arkansas led to 77 documented cases of the disease, forcing a school closure.

Around the same time, 500 cases (median age 13) were documented in a community in Arizona.

In 2003–2004, an outbreak traced to a high school weight room in Wisconsin led to 300 documented cases, primarily among adolescents, but also including some among infants, “who presumably were infected by adolescents or adults and who required hospitalization,” said Dr. Marchant.

These and other outbreaks have led to an increased public awareness of the spread of pertussis infection and have also led to stepped-up efforts to protect adolescents and adults from infection and to minimize the risk of disease transmission to infants, who experience significantly more morbidity and mortality as a result of infection.

In June of this year, with data from large, multicenter trials showing the two tetanus, diphtheria, acellular pertussis vaccines that were recently approved (GlaxoSmithKline's Boostrix and Sanofi Pasteur's Adacel) for use in adolescent and adult populations, ACIP recommended that all adolescents get the pertussis-inclusive vaccine instead of the TD-only booster at the 11− to 12-year visit.

In October of this year, the committee further recommended that adults also receive the pertussis vaccine the next time they are due for a booster, said Dr. Marchant.

Conjugate Meningococcal Vaccine

Life-threatening meningococcal disease affects 1,400–2,800 individuals in the United States each year. While the incidence is highest in children younger than 2 years, adolescents and young adults also are at high risk.

According to CDC data, approximately half of all of meningococcal infections occur in individuals between 15 and 24 years. “Studies have shown the case fatality rate to be especially high in this age group, but they have also shown the percent preventable to be very high,” said Dr. Marchant.

The majority of adolescents and young adults with meningococcal disease are infected with the meningococcal serogroup C, for which vaccine protection is available.

In contrast, infants are generally infected by meningococcal serogroup B, for which there is no vaccine.

Although a polysaccharide meningococcal vaccine (Menomune) has been licensed in the United States since 1978, it was not until the development and FDA licensure of the new quadrivalent conjugate meningococcal vaccine (Menactra) last year that ACIP included it on its list of recommended vaccines for the preadolescent visit.

The conjugate vaccine, approved for use in 11− to 55-year-olds, offers protection against serogroups A, C, Y, and W-135, and it offers improved duration of protection, induction of immunologic memory, booster responses, and reduction in nasopharyngeal bacterial carriage, compared with the polysaccharide vaccine, said Dr. Marchant.

The conjugate vaccine also is recommended for other people at increased risk for meningococcal disease, including college freshmen living in dormitories; microbiologists who are routinely exposed to meningococcal bacteria; U.S. military recruits; individuals traveling to or living in a part of the world where meningococcal disease is common; people who have a damaged spleen or whose spleen has been removed; those with an immune system disorder; and persons who might have been exposed to meningitis during an outbreak.

“We expect the universal immunization recommendation for preadolescents to have a big impact on infection rates,” said Dr. Marchant, noting that universal immunization with the polysaccharide vaccine in the U.S. military significantly reduced meningococcal infections since the immunization policy went into effect, in the early 1970s.

Similarly, a country-wide immunization program with a serogroup C conjugate vaccine in Great Britain (where most of the meningococcal infections among adolescents and young adults have been linked to serogroup C infection) resulted in a significant drop in disease incidence, “suggesting that a conjugate vaccine can control disease,” he said.

An unexpected roadblock to such success with the new conjugate vaccine may be noncompliance with the immunization recommendation resulting from reports of an association with Guillain Barré Syndrome (GBS).

“The immunizations began in the spring of last year, and it came out in September—after 2.8 million doses of the vaccine had been distributed—that there were 6 cases of Guillain Barré that occurred 2–6 weeks post vaccine,” said Dr. Marchant. “While this is more cases than we would like to see, there is not enough evidence to say that this is a cause-and-effect relationship.”

Not only have there not been any further cases reported since that time, there was previous personal or family history of GBS in some of the patients who developed it, further clouding the association, he noted.

“We know that most Guillain Barré is caused by certain infectious agents, but some of these infections are subclinical so we can't get a nice handle on the cause of the cases that occurred.”

Vaccine recommendations are not being altered by these preliminary reports of GBS, Dr. Marchant stressed. “The fact is, GBS has been reported after every vaccine given some time, somewhere, so these few reports are not enough to sway us from stressing the need for protection from meningococcal disease, which has a much higher attack rate and a much higher mortality rate than Guillain Barré Syndrome,” said Dr. Marchant. With respect to the potential for GBS, “we're just going to have to wait and see if it's out there.”

For families who refuse inoculation for their children because of the GBS reports, “it's okay to then recommend the polysaccharide vaccine, with the caveat that it doesn't last as long and may not offer the same protection,” he said.

Human Papillomavirus Vaccine

Although neither of the two human papillomavirus (HPV) vaccines under development—one from GlaxoSmithKline and one from Merck & Co.—have yet to be licensed, infectious disease experts have already begun advocating for their inclusion, upon FDA approval, in the preadolescent immunization lineup.

One of the two vaccines (GlaxoSmithKline's) targets HPV types 16 and 18, which together are responsible for 70% of all cervical cancers. The other vaccine, from Merck, covers these as well as HPV types 6 and 11, which are responsible for approximately 90% of all anogenital warts. “The interesting thing is that types 6 and 11 also cause some abnormal Pap smears, so a vaccine to fight these virus types should also decrease the number of positive Pap smears and procedures that follow,” said Dr. Marchant.

To date, the safety and efficacy of both products in clinical trials looks good compared to placebo, “and the year 2006 has been bandied about as possibilities for licensure,” Dr. Marchant noted. “The most likely scenario will be that these will be added into the 11− to 12-year visit, although there may be some opposition to this from those on the far right.”

Whether the recommendation, if it comes about, will include males as well as females, is still being considered. “Obviously, males don't get cervical cancer, but they can spread HPV to females, and they can also be affected by genital warts,” said Dr. Marchant. “However, it's difficult to show a benefit to immunizing males, in terms of transmission reduction.”

CAMBRIDGE, MASS. — Much of the “action” in the immunization arena is shifting to adolescents, according to Colin Marchant, M.D.

“Adolescent immunizations are a quickly evolving area, as youth in this age group are increasingly being recognized as important reservoirs for certain infectious diseases,” Dr. Marchant said at a pediatric infectious disease meeting sponsored by Boston University School of Medicine, PEDIATRIC NEWS, and FAMILY PRACTICE NEWS.

Until recently, the universal immunization recommendation for the 11− to 12-year preadolescent visit was for a diphtheria-tetanus (DT) booster. Earlier this year, the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) added the acellular pertussis and the conjugate meningococcal disease vaccines to its list of recommended immunizations for adolescents.

And it is likely that another vaccine—one of the two human papillomavirus vaccines currently wending their way through safety and efficacy trials—will be added to the adolescent immunization roster as soon the Food and Drug Administration approves them for use, said Dr. Marchant of Boston University.

It is expected that these vaccines will significantly reduce the infection rates of the respective diseases not only among adolescents, but also among infants and immunocompromised individuals in close contact with the adolescents, Dr. Marchant noted.

Acellular Pertussis Vaccine

With respect to pertussis, “adolescent immunization, and in fact adult immunization, is our unfinished business,” said Dr. Marchant, referring to the rise in recent years of pertussis infections.

In 2004, the highest number of U.S. pertussis cases was among individuals 10–18 years of age, with roughly 6,500 cases reported, according to data from the Centers for Disease Control and Prevention. Looking at infection rates across different age groups, “the numbers have remained steady for children ages 1–10, but they increase substantially starting at age 11 and peak around age 15, then start to fall back down,” he said.

“It's no surprise that kids in the adolescent age range have high rates of infection. They have lower antibody levels because their last pertussis immunization was before their 7th birthday.

“By age 11 or so, the vaccine-related antibody levels will have gone down, leaving these kids vulnerable to infection,” said Dr. Marchant.

Because these children are in such close contact with other children, in school and on sports teams, it's likely that once they're exposed to pertussis, they're going to get sick, because the infection is so highly contagious, with an airborne spread and from contact with nasal secretions, he said.

The observed rise in antibody levels after age 15 can be attributed to immunity developed through infection.

“We've known all along that immunity to pertussis wanes, but it wasn't until the late ′80s that we started going around looking for and counting cases of pertussis,” Dr. Marchant stated. With the 1987 introduction of the single-serum blood test to determine pertussis antibody levels, “we began to document cases, and as always, the closer you look, the more you find.”

In 2001, a pertussis outbreak in a youth football team in Arkansas led to 77 documented cases of the disease, forcing a school closure.

Around the same time, 500 cases (median age 13) were documented in a community in Arizona.

In 2003–2004, an outbreak traced to a high school weight room in Wisconsin led to 300 documented cases, primarily among adolescents, but also including some among infants, “who presumably were infected by adolescents or adults and who required hospitalization,” said Dr. Marchant.

These and other outbreaks have led to an increased public awareness of the spread of pertussis infection and have also led to stepped-up efforts to protect adolescents and adults from infection and to minimize the risk of disease transmission to infants, who experience significantly more morbidity and mortality as a result of infection.

In June of this year, with data from large, multicenter trials showing the two tetanus, diphtheria, acellular pertussis vaccines that were recently approved (GlaxoSmithKline's Boostrix and Sanofi Pasteur's Adacel) for use in adolescent and adult populations, ACIP recommended that all adolescents get the pertussis-inclusive vaccine instead of the TD-only booster at the 11− to 12-year visit.

In October of this year, the committee further recommended that adults also receive the pertussis vaccine the next time they are due for a booster, said Dr. Marchant.

Conjugate Meningococcal Vaccine

Life-threatening meningococcal disease affects 1,400–2,800 individuals in the United States each year. While the incidence is highest in children younger than 2 years, adolescents and young adults also are at high risk.

According to CDC data, approximately half of all of meningococcal infections occur in individuals between 15 and 24 years. “Studies have shown the case fatality rate to be especially high in this age group, but they have also shown the percent preventable to be very high,” said Dr. Marchant.

The majority of adolescents and young adults with meningococcal disease are infected with the meningococcal serogroup C, for which vaccine protection is available.

In contrast, infants are generally infected by meningococcal serogroup B, for which there is no vaccine.

Although a polysaccharide meningococcal vaccine (Menomune) has been licensed in the United States since 1978, it was not until the development and FDA licensure of the new quadrivalent conjugate meningococcal vaccine (Menactra) last year that ACIP included it on its list of recommended vaccines for the preadolescent visit.

The conjugate vaccine, approved for use in 11− to 55-year-olds, offers protection against serogroups A, C, Y, and W-135, and it offers improved duration of protection, induction of immunologic memory, booster responses, and reduction in nasopharyngeal bacterial carriage, compared with the polysaccharide vaccine, said Dr. Marchant.

The conjugate vaccine also is recommended for other people at increased risk for meningococcal disease, including college freshmen living in dormitories; microbiologists who are routinely exposed to meningococcal bacteria; U.S. military recruits; individuals traveling to or living in a part of the world where meningococcal disease is common; people who have a damaged spleen or whose spleen has been removed; those with an immune system disorder; and persons who might have been exposed to meningitis during an outbreak.

“We expect the universal immunization recommendation for preadolescents to have a big impact on infection rates,” said Dr. Marchant, noting that universal immunization with the polysaccharide vaccine in the U.S. military significantly reduced meningococcal infections since the immunization policy went into effect, in the early 1970s.

Similarly, a country-wide immunization program with a serogroup C conjugate vaccine in Great Britain (where most of the meningococcal infections among adolescents and young adults have been linked to serogroup C infection) resulted in a significant drop in disease incidence, “suggesting that a conjugate vaccine can control disease,” he said.

An unexpected roadblock to such success with the new conjugate vaccine may be noncompliance with the immunization recommendation resulting from reports of an association with Guillain Barré Syndrome (GBS).

“The immunizations began in the spring of last year, and it came out in September—after 2.8 million doses of the vaccine had been distributed—that there were 6 cases of Guillain Barré that occurred 2–6 weeks post vaccine,” said Dr. Marchant. “While this is more cases than we would like to see, there is not enough evidence to say that this is a cause-and-effect relationship.”

Not only have there not been any further cases reported since that time, there was previous personal or family history of GBS in some of the patients who developed it, further clouding the association, he noted.

“We know that most Guillain Barré is caused by certain infectious agents, but some of these infections are subclinical so we can't get a nice handle on the cause of the cases that occurred.”

Vaccine recommendations are not being altered by these preliminary reports of GBS, Dr. Marchant stressed. “The fact is, GBS has been reported after every vaccine given some time, somewhere, so these few reports are not enough to sway us from stressing the need for protection from meningococcal disease, which has a much higher attack rate and a much higher mortality rate than Guillain Barré Syndrome,” said Dr. Marchant. With respect to the potential for GBS, “we're just going to have to wait and see if it's out there.”

For families who refuse inoculation for their children because of the GBS reports, “it's okay to then recommend the polysaccharide vaccine, with the caveat that it doesn't last as long and may not offer the same protection,” he said.

Human Papillomavirus Vaccine

Although neither of the two human papillomavirus (HPV) vaccines under development—one from GlaxoSmithKline and one from Merck & Co.—have yet to be licensed, infectious disease experts have already begun advocating for their inclusion, upon FDA approval, in the preadolescent immunization lineup.

One of the two vaccines (GlaxoSmithKline's) targets HPV types 16 and 18, which together are responsible for 70% of all cervical cancers. The other vaccine, from Merck, covers these as well as HPV types 6 and 11, which are responsible for approximately 90% of all anogenital warts. “The interesting thing is that types 6 and 11 also cause some abnormal Pap smears, so a vaccine to fight these virus types should also decrease the number of positive Pap smears and procedures that follow,” said Dr. Marchant.

To date, the safety and efficacy of both products in clinical trials looks good compared to placebo, “and the year 2006 has been bandied about as possibilities for licensure,” Dr. Marchant noted. “The most likely scenario will be that these will be added into the 11− to 12-year visit, although there may be some opposition to this from those on the far right.”

Whether the recommendation, if it comes about, will include males as well as females, is still being considered. “Obviously, males don't get cervical cancer, but they can spread HPV to females, and they can also be affected by genital warts,” said Dr. Marchant. “However, it's difficult to show a benefit to immunizing males, in terms of transmission reduction.”

ATLANTA — Patients with attention-deficit hyperactivity disorder who engage in drug diversion or misuse are easy to identify, Timothy Wilens, M.D., said at the annual meeting of the American Psychiatric Association.

To gauge the extent and nature of stimulant misuse and diversion, Dr. Wilens and his colleagues at Massachusetts General Hospital in Boston administered a self-report questionnaire on medication use to young adult patients (average age 20.8 years) receiving stimulant drugs for their condition.

Of the 98 patients, 55 had concomitant conduct disorder and/or substance abuse problems. Approximately 11% of the patients surveyed reported selling their medication, and 22% acknowledged deliberate misuse—either by taking more than their prescribed dose or by adding a later dose—primarily to enhance performance or to “get high,” Dr. Wilens said.

All of the patients who sold their drugs had either a conduct or substance abuse disorder, as did all but 5% of those who misused their medication.

Among those who diverted medications, 83% had a substance abuse history, and 30% had comorbid conduct disorder. Among those who misused their medications, 75% had a substance abuse history, and 59% had comorbid conduct disorder.

Those patients taking intermediate-acting formulations of stimulants were more likely to engage in drug diversion or misuse.

No diversion or misuse occurred with extended-release formulations.

“There are a few take-home messages from these findings,” Dr. Wilens noted.

“First is that the majority of ADHD drugs are used appropriately. Diversion and misuse does occur, but not that often,” he said.

In addition, the young people most likely to misuse or divert their medication are easily identifiable in practice because of the concomitant problems.

Particular attention should be paid—looking out for warning signs such as early or too frequent refills—to this subset of patients to make sure medication is being used as directed, Dr. Wilens said.

One option for reducing the risk of misuse or diversion of medications is to start patients with a history of substance abuse or conduct disorder on nonstimulant medications.

If the nonstimulants don't work, “consider extended-release formulations of stimulant drugs, because diversion and misuse occur primarily with shorter-acting formulations,” Dr. Wilens said. “The extended-release drugs are less popular because they don't produce the same high.”

Clinicians should also be talking to all ADHD patients about misuse and diversion, the importance of keeping the medication in a safe place, and being careful who knows about it. “In particular, patients who live in a college dormitory or who share living arrangements should be advised to keep their medication in a secure place, such as a locked cabinet, to prevent it from being taken and diverted,” he said.

ATLANTA — Patients with attention-deficit hyperactivity disorder who engage in drug diversion or misuse are easy to identify, Timothy Wilens, M.D., said at the annual meeting of the American Psychiatric Association.

To gauge the extent and nature of stimulant misuse and diversion, Dr. Wilens and his colleagues at Massachusetts General Hospital in Boston administered a self-report questionnaire on medication use to young adult patients (average age 20.8 years) receiving stimulant drugs for their condition.

Of the 98 patients, 55 had concomitant conduct disorder and/or substance abuse problems. Approximately 11% of the patients surveyed reported selling their medication, and 22% acknowledged deliberate misuse—either by taking more than their prescribed dose or by adding a later dose—primarily to enhance performance or to “get high,” Dr. Wilens said.

All of the patients who sold their drugs had either a conduct or substance abuse disorder, as did all but 5% of those who misused their medication.

Among those who diverted medications, 83% had a substance abuse history, and 30% had comorbid conduct disorder. Among those who misused their medications, 75% had a substance abuse history, and 59% had comorbid conduct disorder.

Those patients taking intermediate-acting formulations of stimulants were more likely to engage in drug diversion or misuse.

No diversion or misuse occurred with extended-release formulations.

“There are a few take-home messages from these findings,” Dr. Wilens noted.

“First is that the majority of ADHD drugs are used appropriately. Diversion and misuse does occur, but not that often,” he said.

In addition, the young people most likely to misuse or divert their medication are easily identifiable in practice because of the concomitant problems.

Particular attention should be paid—looking out for warning signs such as early or too frequent refills—to this subset of patients to make sure medication is being used as directed, Dr. Wilens said.

One option for reducing the risk of misuse or diversion of medications is to start patients with a history of substance abuse or conduct disorder on nonstimulant medications.

If the nonstimulants don't work, “consider extended-release formulations of stimulant drugs, because diversion and misuse occur primarily with shorter-acting formulations,” Dr. Wilens said. “The extended-release drugs are less popular because they don't produce the same high.”

Clinicians should also be talking to all ADHD patients about misuse and diversion, the importance of keeping the medication in a safe place, and being careful who knows about it. “In particular, patients who live in a college dormitory or who share living arrangements should be advised to keep their medication in a secure place, such as a locked cabinet, to prevent it from being taken and diverted,” he said.

ATLANTA — Patients with attention-deficit hyperactivity disorder who engage in drug diversion or misuse are easy to identify, Timothy Wilens, M.D., said at the annual meeting of the American Psychiatric Association.

To gauge the extent and nature of stimulant misuse and diversion, Dr. Wilens and his colleagues at Massachusetts General Hospital in Boston administered a self-report questionnaire on medication use to young adult patients (average age 20.8 years) receiving stimulant drugs for their condition.

Of the 98 patients, 55 had concomitant conduct disorder and/or substance abuse problems. Approximately 11% of the patients surveyed reported selling their medication, and 22% acknowledged deliberate misuse—either by taking more than their prescribed dose or by adding a later dose—primarily to enhance performance or to “get high,” Dr. Wilens said.

All of the patients who sold their drugs had either a conduct or substance abuse disorder, as did all but 5% of those who misused their medication.

Among those who diverted medications, 83% had a substance abuse history, and 30% had comorbid conduct disorder. Among those who misused their medications, 75% had a substance abuse history, and 59% had comorbid conduct disorder.

Those patients taking intermediate-acting formulations of stimulants were more likely to engage in drug diversion or misuse.

No diversion or misuse occurred with extended-release formulations.

“There are a few take-home messages from these findings,” Dr. Wilens noted.

“First is that the majority of ADHD drugs are used appropriately. Diversion and misuse does occur, but not that often,” he said.

In addition, the young people most likely to misuse or divert their medication are easily identifiable in practice because of the concomitant problems.

Particular attention should be paid—looking out for warning signs such as early or too frequent refills—to this subset of patients to make sure medication is being used as directed, Dr. Wilens said.

One option for reducing the risk of misuse or diversion of medications is to start patients with a history of substance abuse or conduct disorder on nonstimulant medications.

If the nonstimulants don't work, “consider extended-release formulations of stimulant drugs, because diversion and misuse occur primarily with shorter-acting formulations,” Dr. Wilens said. “The extended-release drugs are less popular because they don't produce the same high.”

Clinicians should also be talking to all ADHD patients about misuse and diversion, the importance of keeping the medication in a safe place, and being careful who knows about it. “In particular, patients who live in a college dormitory or who share living arrangements should be advised to keep their medication in a secure place, such as a locked cabinet, to prevent it from being taken and diverted,” he said.

ATLANTA — Combining stimulant medication and cognitive therapy is a promising approach for treating adult patients with attention-deficit hyperactivity disorder, reported Anthony L. Rostain, M.D.

In an open-label study involving 45 consecutive adults with ADHD in a university-based clinic, combination therapy was associated with a statistically significant improvement in both ADHD symptoms and overall functioning, Dr. Rostain said in a presentation at the annual meeting of the American Psychiatric Association.

The treatment also appeared to reduce symptoms of comorbid anxiety and depression, which occur frequently in adults with ADHD, he said.

Patients were recruited to the study based on the results of telephone screening assessments.

Approximately 78% of the participants were male and 72% had comorbid mental disorders. Average patient age was 31 years.

At baseline and at the end of treatment, all study participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders and other rating scales to assess symptom prevalence and severity.

The combination treatment used in the study comprised an extended-release formulation of mixed amphetamine salts given at titrated doses based on patient response, and 16 sessions of cognitive therapy focused on patient goals and desired outcomes.

Specifically, the behavioral component was built around the cognitive model of ADHD, “which looks at the compensatory strategies for coping with the maladaptive schemas and beliefs in adults with the condition,” said Dr. Rostain of the University of Pennsylvania, Philadelphia.

These maladaptive schemas include self-mistrust and overwhelming feelings of failure and incompetence, accompanied by unproductive negative thoughts, such as “I am inadequate,” and “I can't rely on myself,” said Dr. Rostain.

Some of the compensatory strategies that adults adopt to deal with these negative processes include procrastination, overcritical judgment, and “pseudoefficiency,” whereby the individuals occupy themselves with busy work as a way to keep themselves from failing at real work, he noted.

Because these destructive thought processes and strategies impair personal, interpersonal, and professional efficacy and are thought to be the root of many of the struggles that adults with ADHD experience, cognitive therapeutic approaches, including the nonmanualized therapy used in the study, focus on eliminating unproductive thought and behavior patterns and developing productive coping patterns, said Dr. Rostain.

A comparison of pre- and posttreatment scores of clinical outcome measures, using a paired samples t-test, analyzed significant effect sizes for improvement in ADHD symptoms, depression, anxiety, hopelessness, and overall functioning.

Because of the small sample size of the combination therapy group, no conclusions can be drawn on the relative contribution of cognitive therapy with stimulant medication to patient improvement. However, “the findings let us know that we are in the ballpark,” by providing further evidence that this combination of therapies can address the problem of ADHD in adults, said Dr. Rostain.

J. Russell Ramsay, Ph.D., also of the University of Pennsylvania, was coinvestigator with Dr. Rostain in this study.

ATLANTA — Combining stimulant medication and cognitive therapy is a promising approach for treating adult patients with attention-deficit hyperactivity disorder, reported Anthony L. Rostain, M.D.

In an open-label study involving 45 consecutive adults with ADHD in a university-based clinic, combination therapy was associated with a statistically significant improvement in both ADHD symptoms and overall functioning, Dr. Rostain said in a presentation at the annual meeting of the American Psychiatric Association.

The treatment also appeared to reduce symptoms of comorbid anxiety and depression, which occur frequently in adults with ADHD, he said.

Patients were recruited to the study based on the results of telephone screening assessments.

Approximately 78% of the participants were male and 72% had comorbid mental disorders. Average patient age was 31 years.

At baseline and at the end of treatment, all study participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders and other rating scales to assess symptom prevalence and severity.

The combination treatment used in the study comprised an extended-release formulation of mixed amphetamine salts given at titrated doses based on patient response, and 16 sessions of cognitive therapy focused on patient goals and desired outcomes.

Specifically, the behavioral component was built around the cognitive model of ADHD, “which looks at the compensatory strategies for coping with the maladaptive schemas and beliefs in adults with the condition,” said Dr. Rostain of the University of Pennsylvania, Philadelphia.

These maladaptive schemas include self-mistrust and overwhelming feelings of failure and incompetence, accompanied by unproductive negative thoughts, such as “I am inadequate,” and “I can't rely on myself,” said Dr. Rostain.

Some of the compensatory strategies that adults adopt to deal with these negative processes include procrastination, overcritical judgment, and “pseudoefficiency,” whereby the individuals occupy themselves with busy work as a way to keep themselves from failing at real work, he noted.

Because these destructive thought processes and strategies impair personal, interpersonal, and professional efficacy and are thought to be the root of many of the struggles that adults with ADHD experience, cognitive therapeutic approaches, including the nonmanualized therapy used in the study, focus on eliminating unproductive thought and behavior patterns and developing productive coping patterns, said Dr. Rostain.

A comparison of pre- and posttreatment scores of clinical outcome measures, using a paired samples t-test, analyzed significant effect sizes for improvement in ADHD symptoms, depression, anxiety, hopelessness, and overall functioning.

Because of the small sample size of the combination therapy group, no conclusions can be drawn on the relative contribution of cognitive therapy with stimulant medication to patient improvement. However, “the findings let us know that we are in the ballpark,” by providing further evidence that this combination of therapies can address the problem of ADHD in adults, said Dr. Rostain.

J. Russell Ramsay, Ph.D., also of the University of Pennsylvania, was coinvestigator with Dr. Rostain in this study.

ATLANTA — Combining stimulant medication and cognitive therapy is a promising approach for treating adult patients with attention-deficit hyperactivity disorder, reported Anthony L. Rostain, M.D.

In an open-label study involving 45 consecutive adults with ADHD in a university-based clinic, combination therapy was associated with a statistically significant improvement in both ADHD symptoms and overall functioning, Dr. Rostain said in a presentation at the annual meeting of the American Psychiatric Association.

The treatment also appeared to reduce symptoms of comorbid anxiety and depression, which occur frequently in adults with ADHD, he said.

Patients were recruited to the study based on the results of telephone screening assessments.

Approximately 78% of the participants were male and 72% had comorbid mental disorders. Average patient age was 31 years.

At baseline and at the end of treatment, all study participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders and other rating scales to assess symptom prevalence and severity.

The combination treatment used in the study comprised an extended-release formulation of mixed amphetamine salts given at titrated doses based on patient response, and 16 sessions of cognitive therapy focused on patient goals and desired outcomes.

Specifically, the behavioral component was built around the cognitive model of ADHD, “which looks at the compensatory strategies for coping with the maladaptive schemas and beliefs in adults with the condition,” said Dr. Rostain of the University of Pennsylvania, Philadelphia.

These maladaptive schemas include self-mistrust and overwhelming feelings of failure and incompetence, accompanied by unproductive negative thoughts, such as “I am inadequate,” and “I can't rely on myself,” said Dr. Rostain.

Some of the compensatory strategies that adults adopt to deal with these negative processes include procrastination, overcritical judgment, and “pseudoefficiency,” whereby the individuals occupy themselves with busy work as a way to keep themselves from failing at real work, he noted.

Because these destructive thought processes and strategies impair personal, interpersonal, and professional efficacy and are thought to be the root of many of the struggles that adults with ADHD experience, cognitive therapeutic approaches, including the nonmanualized therapy used in the study, focus on eliminating unproductive thought and behavior patterns and developing productive coping patterns, said Dr. Rostain.

A comparison of pre- and posttreatment scores of clinical outcome measures, using a paired samples t-test, analyzed significant effect sizes for improvement in ADHD symptoms, depression, anxiety, hopelessness, and overall functioning.

Because of the small sample size of the combination therapy group, no conclusions can be drawn on the relative contribution of cognitive therapy with stimulant medication to patient improvement. However, “the findings let us know that we are in the ballpark,” by providing further evidence that this combination of therapies can address the problem of ADHD in adults, said Dr. Rostain.

J. Russell Ramsay, Ph.D., also of the University of Pennsylvania, was coinvestigator with Dr. Rostain in this study.