Patrice Wendling

CHICAGO — Percutaneous hepatic perfusion with melphalan improved local disease control, but not overall survival when compared with best available care in patients with ocular or cutaneous melanoma that had metastasized to the liver.

Chemoembolization is the standard of care in patients with hepatic metastases from ocular melanoma, a group that made up about 88% of the trial population. Systemic chemotherapy or immunotherapies do not appear to alter the natural history of the disease, which has a one-year survival of about 10%.

“Increased drug delivery achieved through novel regional therapeutic approaches may increase efficacy for a given agent (versus systemic administration) by overcoming a low therapeutic index,” said Dr. James Pingpank, Jr. who presented the late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.

Forty-four patients were randomized to hepatic perfusion and 49 to best available care by the treating physician. More than half, 55%, of the control arm, crossed over to receive hepatic perfusion after hepatic progression.

High-dose melphalan at 3.0 mg/kg was infused into the hepatic artery via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double-balloon catheter and hemofiltration cartridges. Patients underwent 4 to 6 procedures at 28- to 35-day intervals.

The device and drug combination is under consideration by the Food and Drug Administration.

When compared with best available care, percutaneous hepatic perfusion increased median hepatic progression-free survival from 49 days to 245 days (hazard ratio 0.30, logrank P less than .0001), and overall progression-free survival from 46 days to 186 days (HR. 0.40, logrank P less than .0001).

No patients progressed while on hepatic perfusion with melphalan, and there were no differences in progression-free survival of ocular vs. cutaneous melanoma, said Dr. Pingpank of the University of Pittsburgh Hillman Cancer Center in Pittsburgh.

Median overall survival was similar at 301 days for best available care and 298 days for hepatic perfusion (HR 0.92, logrank P = .77). This was likely due to the high crossover rate, he said. When overall survival was examined in the control arm alone, it reached 398 days in patients who crossed over vs. 124 days for those who did not (logrank P = .0117).

Invited discussant Dr. Dirk Schadendorf, director of dermatology at University Hospital Essen in Essen, Germany, took issue with the high crossover rate and said a previous German trial (Br. J. Cancer 2002;87:840-5 also failed to show a significant survival advantage for intraarterial or IV fotemustine plus interferon-alpha and interleukin 2 in metastatic ocular melanoma.

“The clinical benefit besides local control is open and has not been answered by this trial,” he said. “The crossover in my view is a clear sign of bias and is not proving this treatment is of any benefit to the patient.”

Dr. Schadendorf said that additional relevant information is missing, such as the number of patients with liver-only metastases compared with other sites of metastasis, thus making it difficult to determine whether there is any potential patient imbalance between arms.

The most common therapy of the primary tumor was radiation in 52% of the experimental arm and 49% of the control arm, roughly 85% of patients had an ECOG performance status of 0, and their mean age was 55 years.

Expansion of the single-institution study to multiple centers proved safe and effective, Dr. Pingpank said. The most common grade 3/4 treatment-related toxicities in 40 evaluable patients receiving 116 perfusion treatments were thrombocytopenia (74%), neutropenia (61%), and anemia (47%). Three treatment-related deaths occurred, two due to neutropenic sepsis and one to hepatic failure.

Study sponsor Delcath Systems, Inc. provided melphalan and double-balloon catheters for the trial. The researchers disclosed serving on the scientific advisory board for and receiving research support from Delcath. Dr. Schadendorf disclosed honoraria or an advisory/consultancy role with AZD, Bristol-Myers Squibb, Plexxikon, Roche, Schering-Plough, and Bayer Schering Pharma.

CHICAGO — Percutaneous hepatic perfusion with melphalan improved local disease control, but not overall survival when compared with best available care in patients with ocular or cutaneous melanoma that had metastasized to the liver.

Chemoembolization is the standard of care in patients with hepatic metastases from ocular melanoma, a group that made up about 88% of the trial population. Systemic chemotherapy or immunotherapies do not appear to alter the natural history of the disease, which has a one-year survival of about 10%.

“Increased drug delivery achieved through novel regional therapeutic approaches may increase efficacy for a given agent (versus systemic administration) by overcoming a low therapeutic index,” said Dr. James Pingpank, Jr. who presented the late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.

Forty-four patients were randomized to hepatic perfusion and 49 to best available care by the treating physician. More than half, 55%, of the control arm, crossed over to receive hepatic perfusion after hepatic progression.

High-dose melphalan at 3.0 mg/kg was infused into the hepatic artery via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double-balloon catheter and hemofiltration cartridges. Patients underwent 4 to 6 procedures at 28- to 35-day intervals.

The device and drug combination is under consideration by the Food and Drug Administration.

When compared with best available care, percutaneous hepatic perfusion increased median hepatic progression-free survival from 49 days to 245 days (hazard ratio 0.30, logrank P less than .0001), and overall progression-free survival from 46 days to 186 days (HR. 0.40, logrank P less than .0001).

No patients progressed while on hepatic perfusion with melphalan, and there were no differences in progression-free survival of ocular vs. cutaneous melanoma, said Dr. Pingpank of the University of Pittsburgh Hillman Cancer Center in Pittsburgh.

Median overall survival was similar at 301 days for best available care and 298 days for hepatic perfusion (HR 0.92, logrank P = .77). This was likely due to the high crossover rate, he said. When overall survival was examined in the control arm alone, it reached 398 days in patients who crossed over vs. 124 days for those who did not (logrank P = .0117).

Invited discussant Dr. Dirk Schadendorf, director of dermatology at University Hospital Essen in Essen, Germany, took issue with the high crossover rate and said a previous German trial (Br. J. Cancer 2002;87:840-5 also failed to show a significant survival advantage for intraarterial or IV fotemustine plus interferon-alpha and interleukin 2 in metastatic ocular melanoma.

“The clinical benefit besides local control is open and has not been answered by this trial,” he said. “The crossover in my view is a clear sign of bias and is not proving this treatment is of any benefit to the patient.”

Dr. Schadendorf said that additional relevant information is missing, such as the number of patients with liver-only metastases compared with other sites of metastasis, thus making it difficult to determine whether there is any potential patient imbalance between arms.

The most common therapy of the primary tumor was radiation in 52% of the experimental arm and 49% of the control arm, roughly 85% of patients had an ECOG performance status of 0, and their mean age was 55 years.

Expansion of the single-institution study to multiple centers proved safe and effective, Dr. Pingpank said. The most common grade 3/4 treatment-related toxicities in 40 evaluable patients receiving 116 perfusion treatments were thrombocytopenia (74%), neutropenia (61%), and anemia (47%). Three treatment-related deaths occurred, two due to neutropenic sepsis and one to hepatic failure.

Study sponsor Delcath Systems, Inc. provided melphalan and double-balloon catheters for the trial. The researchers disclosed serving on the scientific advisory board for and receiving research support from Delcath. Dr. Schadendorf disclosed honoraria or an advisory/consultancy role with AZD, Bristol-Myers Squibb, Plexxikon, Roche, Schering-Plough, and Bayer Schering Pharma.

CHICAGO — Percutaneous hepatic perfusion with melphalan improved local disease control, but not overall survival when compared with best available care in patients with ocular or cutaneous melanoma that had metastasized to the liver.

Chemoembolization is the standard of care in patients with hepatic metastases from ocular melanoma, a group that made up about 88% of the trial population. Systemic chemotherapy or immunotherapies do not appear to alter the natural history of the disease, which has a one-year survival of about 10%.

“Increased drug delivery achieved through novel regional therapeutic approaches may increase efficacy for a given agent (versus systemic administration) by overcoming a low therapeutic index,” said Dr. James Pingpank, Jr. who presented the late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.

Forty-four patients were randomized to hepatic perfusion and 49 to best available care by the treating physician. More than half, 55%, of the control arm, crossed over to receive hepatic perfusion after hepatic progression.

High-dose melphalan at 3.0 mg/kg was infused into the hepatic artery via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double-balloon catheter and hemofiltration cartridges. Patients underwent 4 to 6 procedures at 28- to 35-day intervals.

The device and drug combination is under consideration by the Food and Drug Administration.

When compared with best available care, percutaneous hepatic perfusion increased median hepatic progression-free survival from 49 days to 245 days (hazard ratio 0.30, logrank P less than .0001), and overall progression-free survival from 46 days to 186 days (HR. 0.40, logrank P less than .0001).

No patients progressed while on hepatic perfusion with melphalan, and there were no differences in progression-free survival of ocular vs. cutaneous melanoma, said Dr. Pingpank of the University of Pittsburgh Hillman Cancer Center in Pittsburgh.

Median overall survival was similar at 301 days for best available care and 298 days for hepatic perfusion (HR 0.92, logrank P = .77). This was likely due to the high crossover rate, he said. When overall survival was examined in the control arm alone, it reached 398 days in patients who crossed over vs. 124 days for those who did not (logrank P = .0117).

Invited discussant Dr. Dirk Schadendorf, director of dermatology at University Hospital Essen in Essen, Germany, took issue with the high crossover rate and said a previous German trial (Br. J. Cancer 2002;87:840-5 also failed to show a significant survival advantage for intraarterial or IV fotemustine plus interferon-alpha and interleukin 2 in metastatic ocular melanoma.

“The clinical benefit besides local control is open and has not been answered by this trial,” he said. “The crossover in my view is a clear sign of bias and is not proving this treatment is of any benefit to the patient.”

Dr. Schadendorf said that additional relevant information is missing, such as the number of patients with liver-only metastases compared with other sites of metastasis, thus making it difficult to determine whether there is any potential patient imbalance between arms.

The most common therapy of the primary tumor was radiation in 52% of the experimental arm and 49% of the control arm, roughly 85% of patients had an ECOG performance status of 0, and their mean age was 55 years.

Expansion of the single-institution study to multiple centers proved safe and effective, Dr. Pingpank said. The most common grade 3/4 treatment-related toxicities in 40 evaluable patients receiving 116 perfusion treatments were thrombocytopenia (74%), neutropenia (61%), and anemia (47%). Three treatment-related deaths occurred, two due to neutropenic sepsis and one to hepatic failure.

Study sponsor Delcath Systems, Inc. provided melphalan and double-balloon catheters for the trial. The researchers disclosed serving on the scientific advisory board for and receiving research support from Delcath. Dr. Schadendorf disclosed honoraria or an advisory/consultancy role with AZD, Bristol-Myers Squibb, Plexxikon, Roche, Schering-Plough, and Bayer Schering Pharma.

Major Finding: Six hours after administration, 50% of children treated with ibuprofen alone were febrile versus all but one child treated with combined or alternating doses of ibuprofen and acetaminophen.

Data Source: Randomized trial in 60 febrile children.

Disclosures: The research was supported by grants from the George L. Laverty Foundation, the National Institutes of Health, and the Penn State General Clinical Research Center. Dr. Paul disclosed serving as a consultant for Novartis, Procter & Gamble, and the Consumer Healthcare Products Association. Dr. Sekhar reported no conflicts.

VANCOUVER, B.C. — Combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone in a randomized trial involving 60 febrile children.

Although combining and alternating doses of these agents is common, there are limited data to support this practice with standard U.S. doses.

In 2001 the American Academy of Pediatrics stated that “alternating doses every 6 hours might be used so that one drug or the other is administered every 3 hours,” but urged clinicians to “exercise discretion when considering this therapy” (Pediatrics 2001;108:1020–4). The current study evenly randomized children, aged 6 months to 7 years (mean, 3.4 years), with temporal artery temperatures of at least 38° C (mean, 38.7°) to ibuprofen alone, ibuprofen combined with acetaminophen, or ibuprofen followed by acetaminophen 3 hours later. Ibuprofen was dosed at 10 mg/kg and acetaminophen at 15 mg/kg.

At baseline, there was no significant difference in the children's temperatures, but at hour 4 there was a statistically significant increase in the ibuprofen-alone group that was maintained at hours 5 and 6, Dr. Deepa Sekhar reported on behalf of principal investigator Dr. Ian M. Paul and their colleagues at Pennsylvania State University in Hershey.

At hour 6, 50% of the ibuprofen-alone children were febrile (mean, 38.5° C), whereas in both of the combined groups, all of the children were afebrile, except one in the ibuprofen plus acetaminophen group.

The findings at hours 4, 5, and 6 for the combined arm are highly relevant to parents who give medications to their children prior to day care, school, or sleep, Dr. Sekhar said at the meeting.

“Right or wrong, fever phobia is widespread among parents and caregivers alike,” she commented.

One attendee questioned whether using two medications reinforces this phobia. Dr. Sekhar agreed, but said that many parents she sees are already using two and that now she can tell them these regimens work and are safe.

The regimen of ibuprofen followed by acetaminophen 3 hours later was chosen because health care providers tend to prefer ibuprofen first for higher fevers, Dr. Paul said in an interview.

A previous survey of 161 pediatric providers found that 50% advise parents to alternate acetaminophen and ibuprofen for febrile illnesses, and that 57% use ibuprofen for temperatures of 102° F or higher (Pediatrics 2000;105:1009–12).

Another attendee questioned whether fever should be fought as it is, observing that several infectious disease colleagues favor fever and feel it is associated with a number of immunologic changes that could be beneficial for fighting infection.

Again Dr. Chakar agreed, and to a round of laughter added, “But school nurses are powerful people.”

Dr. Paul told this news organization: “Day cares and schools are more concerned with a number on the thermometer rather than what should or shouldn't be fought or even the activity/functioning of the child. They have firm rules as to who gets sent home and who doesn't based on this number. This has a trickle-down effect to parents and health care providers.”

Major Finding: Six hours after administration, 50% of children treated with ibuprofen alone were febrile versus all but one child treated with combined or alternating doses of ibuprofen and acetaminophen.

Data Source: Randomized trial in 60 febrile children.

Disclosures: The research was supported by grants from the George L. Laverty Foundation, the National Institutes of Health, and the Penn State General Clinical Research Center. Dr. Paul disclosed serving as a consultant for Novartis, Procter & Gamble, and the Consumer Healthcare Products Association. Dr. Sekhar reported no conflicts.

VANCOUVER, B.C. — Combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone in a randomized trial involving 60 febrile children.

Although combining and alternating doses of these agents is common, there are limited data to support this practice with standard U.S. doses.

In 2001 the American Academy of Pediatrics stated that “alternating doses every 6 hours might be used so that one drug or the other is administered every 3 hours,” but urged clinicians to “exercise discretion when considering this therapy” (Pediatrics 2001;108:1020–4). The current study evenly randomized children, aged 6 months to 7 years (mean, 3.4 years), with temporal artery temperatures of at least 38° C (mean, 38.7°) to ibuprofen alone, ibuprofen combined with acetaminophen, or ibuprofen followed by acetaminophen 3 hours later. Ibuprofen was dosed at 10 mg/kg and acetaminophen at 15 mg/kg.

At baseline, there was no significant difference in the children's temperatures, but at hour 4 there was a statistically significant increase in the ibuprofen-alone group that was maintained at hours 5 and 6, Dr. Deepa Sekhar reported on behalf of principal investigator Dr. Ian M. Paul and their colleagues at Pennsylvania State University in Hershey.

At hour 6, 50% of the ibuprofen-alone children were febrile (mean, 38.5° C), whereas in both of the combined groups, all of the children were afebrile, except one in the ibuprofen plus acetaminophen group.

The findings at hours 4, 5, and 6 for the combined arm are highly relevant to parents who give medications to their children prior to day care, school, or sleep, Dr. Sekhar said at the meeting.

“Right or wrong, fever phobia is widespread among parents and caregivers alike,” she commented.

One attendee questioned whether using two medications reinforces this phobia. Dr. Sekhar agreed, but said that many parents she sees are already using two and that now she can tell them these regimens work and are safe.

The regimen of ibuprofen followed by acetaminophen 3 hours later was chosen because health care providers tend to prefer ibuprofen first for higher fevers, Dr. Paul said in an interview.

A previous survey of 161 pediatric providers found that 50% advise parents to alternate acetaminophen and ibuprofen for febrile illnesses, and that 57% use ibuprofen for temperatures of 102° F or higher (Pediatrics 2000;105:1009–12).

Another attendee questioned whether fever should be fought as it is, observing that several infectious disease colleagues favor fever and feel it is associated with a number of immunologic changes that could be beneficial for fighting infection.

Again Dr. Chakar agreed, and to a round of laughter added, “But school nurses are powerful people.”

Dr. Paul told this news organization: “Day cares and schools are more concerned with a number on the thermometer rather than what should or shouldn't be fought or even the activity/functioning of the child. They have firm rules as to who gets sent home and who doesn't based on this number. This has a trickle-down effect to parents and health care providers.”

Major Finding: Six hours after administration, 50% of children treated with ibuprofen alone were febrile versus all but one child treated with combined or alternating doses of ibuprofen and acetaminophen.

Data Source: Randomized trial in 60 febrile children.

Disclosures: The research was supported by grants from the George L. Laverty Foundation, the National Institutes of Health, and the Penn State General Clinical Research Center. Dr. Paul disclosed serving as a consultant for Novartis, Procter & Gamble, and the Consumer Healthcare Products Association. Dr. Sekhar reported no conflicts.

VANCOUVER, B.C. — Combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone in a randomized trial involving 60 febrile children.

Although combining and alternating doses of these agents is common, there are limited data to support this practice with standard U.S. doses.

In 2001 the American Academy of Pediatrics stated that “alternating doses every 6 hours might be used so that one drug or the other is administered every 3 hours,” but urged clinicians to “exercise discretion when considering this therapy” (Pediatrics 2001;108:1020–4). The current study evenly randomized children, aged 6 months to 7 years (mean, 3.4 years), with temporal artery temperatures of at least 38° C (mean, 38.7°) to ibuprofen alone, ibuprofen combined with acetaminophen, or ibuprofen followed by acetaminophen 3 hours later. Ibuprofen was dosed at 10 mg/kg and acetaminophen at 15 mg/kg.

At baseline, there was no significant difference in the children's temperatures, but at hour 4 there was a statistically significant increase in the ibuprofen-alone group that was maintained at hours 5 and 6, Dr. Deepa Sekhar reported on behalf of principal investigator Dr. Ian M. Paul and their colleagues at Pennsylvania State University in Hershey.

At hour 6, 50% of the ibuprofen-alone children were febrile (mean, 38.5° C), whereas in both of the combined groups, all of the children were afebrile, except one in the ibuprofen plus acetaminophen group.

The findings at hours 4, 5, and 6 for the combined arm are highly relevant to parents who give medications to their children prior to day care, school, or sleep, Dr. Sekhar said at the meeting.

“Right or wrong, fever phobia is widespread among parents and caregivers alike,” she commented.

One attendee questioned whether using two medications reinforces this phobia. Dr. Sekhar agreed, but said that many parents she sees are already using two and that now she can tell them these regimens work and are safe.

The regimen of ibuprofen followed by acetaminophen 3 hours later was chosen because health care providers tend to prefer ibuprofen first for higher fevers, Dr. Paul said in an interview.

A previous survey of 161 pediatric providers found that 50% advise parents to alternate acetaminophen and ibuprofen for febrile illnesses, and that 57% use ibuprofen for temperatures of 102° F or higher (Pediatrics 2000;105:1009–12).

Another attendee questioned whether fever should be fought as it is, observing that several infectious disease colleagues favor fever and feel it is associated with a number of immunologic changes that could be beneficial for fighting infection.

Again Dr. Chakar agreed, and to a round of laughter added, “But school nurses are powerful people.”

Dr. Paul told this news organization: “Day cares and schools are more concerned with a number on the thermometer rather than what should or shouldn't be fought or even the activity/functioning of the child. They have firm rules as to who gets sent home and who doesn't based on this number. This has a trickle-down effect to parents and health care providers.”

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent; 10% reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and was due for all three vaccines but a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated, Dr. Ford reported.

If the unaccompanied minor was 12 years old, 50% would not get influenza or Tdap, and 70% would not get the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%–70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

“We still have to think hard about how to get all teens vaccinated, but I think that this study really highlights the fact that there are a lot of missed opportunities among these older teens,” she said in an interview.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals have a great deal of variety and flexibility regarding the process of documenting consent, Dr. Ford said.

Federal law requires that all health care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

The American Academy of Pediatrics believes that physicians have an ethical and legal obligation in most cases to obtain parental permission to undertake recommended medical interventions, and that in many circumstances they should also solicit patient assent when developmentally appropriate (Pediatrics 1995;95:314–7). The AAP also notes that physicians should seek informed consent directly from patients in cases involving emancipated or mature minors with adequate decision-making capacity, or when otherwise permitted by law.

During a discussion of the study, it was noted that most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, Dr. Ford said.

Disclosures: Dr. Ford reported that she had no disclosures.

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent; 10% reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and was due for all three vaccines but a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated, Dr. Ford reported.

If the unaccompanied minor was 12 years old, 50% would not get influenza or Tdap, and 70% would not get the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%–70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

“We still have to think hard about how to get all teens vaccinated, but I think that this study really highlights the fact that there are a lot of missed opportunities among these older teens,” she said in an interview.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals have a great deal of variety and flexibility regarding the process of documenting consent, Dr. Ford said.

Federal law requires that all health care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

The American Academy of Pediatrics believes that physicians have an ethical and legal obligation in most cases to obtain parental permission to undertake recommended medical interventions, and that in many circumstances they should also solicit patient assent when developmentally appropriate (Pediatrics 1995;95:314–7). The AAP also notes that physicians should seek informed consent directly from patients in cases involving emancipated or mature minors with adequate decision-making capacity, or when otherwise permitted by law.

During a discussion of the study, it was noted that most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, Dr. Ford said.

Disclosures: Dr. Ford reported that she had no disclosures.

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent; 10% reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and was due for all three vaccines but a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated, Dr. Ford reported.

If the unaccompanied minor was 12 years old, 50% would not get influenza or Tdap, and 70% would not get the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%–70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

“We still have to think hard about how to get all teens vaccinated, but I think that this study really highlights the fact that there are a lot of missed opportunities among these older teens,” she said in an interview.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals have a great deal of variety and flexibility regarding the process of documenting consent, Dr. Ford said.

Federal law requires that all health care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

The American Academy of Pediatrics believes that physicians have an ethical and legal obligation in most cases to obtain parental permission to undertake recommended medical interventions, and that in many circumstances they should also solicit patient assent when developmentally appropriate (Pediatrics 1995;95:314–7). The AAP also notes that physicians should seek informed consent directly from patients in cases involving emancipated or mature minors with adequate decision-making capacity, or when otherwise permitted by law.

During a discussion of the study, it was noted that most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, Dr. Ford said.

Disclosures: Dr. Ford reported that she had no disclosures.

CHICAGO — Thyroid-stimulating hormone receptor messenger RNA is a clinically useful blood test in the pre- and postoperative management of thyroid cancer, based on results from a prospective validation study in 1,095 consecutive patients.

If detectable preoperatively, when fine-needle aspiration suggests follicular neoplasm, thyroid-stimulating hormone receptor (TSHR) messenger RNA (mRNA) accurately predicts thyroid cancer and guides the extent of surgery, reported Dr. Mira Milas, principal investigator.

“It has a practical role to predict thyroid cancers where other modalities may fall short,” she said. In addition, high levels on the first postoperative day alert physicians to persistent disease, while its presence during long-term surveillance aids in identifying recurrence.

“We are encouraged by this performance and the fact that it is a convenient blood test to perform,” said Dr. Milas, director of the thyroid center at the Cleveland Clinic. “Our next steps are to search for multicenter trials and [Food and Drug Administration] approval for some of these indications.”

No new blood tests for differentiated thyroid cancer have been introduced into routine clinical practice since thyroglobulin. Thyroglobulin is used for cancer follow-up, but not initial diagnosis.

The TSHR mRNA assay was developed 9 years ago at the clinic's pathology department by study collaborator Manjula Gupta, Ph.D.

TSHR mRNA acts as a surrogate marker for circulating thyroid cancer cells, and in initial studies distinguished benign from malignant thyroid diseases.

A recent report suggests that TSHR mRNA is detectable even in thyroid microcarcinomas, and may characterize those with potentially more aggressive histology (Surgery 2009;146:1081–9).

The aim of the current analysis was to validate the clinical use of the marker 1 year after its introduction at the Cleveland Clinic, where the test is now used daily in all patients scheduled for thyroid surgery and those undergoing consultation for thyroid disease in the office.

From October 2008 through September 2009, TSHR mRNA was measured by quantitative real-time polymerase chain reaction from blood drawn in 403 patients undergoing thyroid surgery, postoperatively in 541 patients, and in 151 patients monitored for benign goiters.

Preoperative Use

Preoperative TSHR mRNA greater than 1 ng/mcg as a sole predictor of cancer had a positive predictive value (PPV) of 81% and specificity of 83% in 374 patients with surgically confirmed pathology, Dr. Milas said. Sensitivity was modest at 61%, as was negative predictive value at 64%. However, its PPV was 100% in patients with papillary thyroid cancers greater than 1 cm.

She observed that TSHR mRNA is particularly useful in detecting cancer in patients with follicular neoplasms on fine-needle aspiration. In 54 such patients, TSHR mRNA alone had a PPV of 96%, a specificity of 96%, and accuracy of 85%. The sensitivity of diagnosing cancer improved from 76% to 97% when the blood test was combined with ultrasound. Ultrasound features such as irregular margins, hypervascularity, indistinct borders, and microcalcification are suggestive of cancer in follicular neoplasms, but none are independently diagnostic. The highest risk of a false positive occurs with Hashimoto's disease, Dr. Milas acknowledged.

Postoperative Use

Use of the blood test in 69 paired samples with thyroid cancer revealed that elevated TSHR mRNA levels became undetectable in all patients on postoperative day 1, except in seven who had persistent or recurrent cancer within the year and unfavorable histologic features.

In contrast, all 40 patients with benign disease had undetectable TSHR mRNA levels on day 1 after thyroidectomy. “This suggests the potential use of TSHR mRNA as an early marker of adequate surgical clearance of disease or future recurrence,” Dr. Milas said in an interview.

Long-Term Surveillance

TSHR mRNA also showed merit during long-term follow-up of thyroid cancer, notably in two particularly challenging scenarios: when thyroglobulin antibodies were present, and when patients had residual thyroid tissue from original surgery and detectable thyroglobulin levels between 0.2 and 49 ng/mL that are difficult to interpret, she said.

At a median follow-up of about 2 years in 60 patients with elevated thyroglobulin antibodies, detectable TSHR mRNA was the only blood test to confirm cancer in four patients. Negative TSHR mRNA reassured absence of disease in 54 of the 56 remaining patients whose imaging was also negative.

All 59 patients with residual thyroid tissue because of partial thyroidectomy for cancer had undetectable TSHR mRNA levels and no radiologic evidence of cancer recurrence at follow-up, she said.

“This assay has come of age,” remarked Dr. Collin Weber, the invited discussant and chief of endocrine surgery at Emory University Hospital in Atlanta.

He questioned whether total thyroidectomy is performed at the Cleveland Clinic on all indeterminate lesions when the assay is positive and whether its accuracy is good enough to recommend observation of TSHR mRNA-negative follicular neoplasms greater than 2.5 cm in size.

Dr. Milas responded that total thyroidectomy would be advised based on abnormal TSHR mRNA levels because a positive predictive value of 96% is reassuring and has held up in daily practice since the analysis was closed.

She said the assay is not accurate enough, however, to recommend observation in sonographically suspicious, 2.5-cm or greater tumors with undetectable TSHR mRNA levels, but “is possibly and cautiously” enough when combined with an informed discussion with the patient when smaller lesions lack concerning ultrasound features and in patients with medical comorbidities who face increased risk during a diagnostic thyroidectomy.

Disclosures: Dr. Milas and Dr. Weber stated they had no relevant disclosures.

TSHR mRNA had a positive predictive value of 100% in patients with papillary thyroid cancers greater than 1 cm.

Source DR. MILAS

CHICAGO — Thyroid-stimulating hormone receptor messenger RNA is a clinically useful blood test in the pre- and postoperative management of thyroid cancer, based on results from a prospective validation study in 1,095 consecutive patients.

If detectable preoperatively, when fine-needle aspiration suggests follicular neoplasm, thyroid-stimulating hormone receptor (TSHR) messenger RNA (mRNA) accurately predicts thyroid cancer and guides the extent of surgery, reported Dr. Mira Milas, principal investigator.

“It has a practical role to predict thyroid cancers where other modalities may fall short,” she said. In addition, high levels on the first postoperative day alert physicians to persistent disease, while its presence during long-term surveillance aids in identifying recurrence.

“We are encouraged by this performance and the fact that it is a convenient blood test to perform,” said Dr. Milas, director of the thyroid center at the Cleveland Clinic. “Our next steps are to search for multicenter trials and [Food and Drug Administration] approval for some of these indications.”

No new blood tests for differentiated thyroid cancer have been introduced into routine clinical practice since thyroglobulin. Thyroglobulin is used for cancer follow-up, but not initial diagnosis.

The TSHR mRNA assay was developed 9 years ago at the clinic's pathology department by study collaborator Manjula Gupta, Ph.D.

TSHR mRNA acts as a surrogate marker for circulating thyroid cancer cells, and in initial studies distinguished benign from malignant thyroid diseases.

A recent report suggests that TSHR mRNA is detectable even in thyroid microcarcinomas, and may characterize those with potentially more aggressive histology (Surgery 2009;146:1081–9).

The aim of the current analysis was to validate the clinical use of the marker 1 year after its introduction at the Cleveland Clinic, where the test is now used daily in all patients scheduled for thyroid surgery and those undergoing consultation for thyroid disease in the office.

From October 2008 through September 2009, TSHR mRNA was measured by quantitative real-time polymerase chain reaction from blood drawn in 403 patients undergoing thyroid surgery, postoperatively in 541 patients, and in 151 patients monitored for benign goiters.

Preoperative Use

Preoperative TSHR mRNA greater than 1 ng/mcg as a sole predictor of cancer had a positive predictive value (PPV) of 81% and specificity of 83% in 374 patients with surgically confirmed pathology, Dr. Milas said. Sensitivity was modest at 61%, as was negative predictive value at 64%. However, its PPV was 100% in patients with papillary thyroid cancers greater than 1 cm.

She observed that TSHR mRNA is particularly useful in detecting cancer in patients with follicular neoplasms on fine-needle aspiration. In 54 such patients, TSHR mRNA alone had a PPV of 96%, a specificity of 96%, and accuracy of 85%. The sensitivity of diagnosing cancer improved from 76% to 97% when the blood test was combined with ultrasound. Ultrasound features such as irregular margins, hypervascularity, indistinct borders, and microcalcification are suggestive of cancer in follicular neoplasms, but none are independently diagnostic. The highest risk of a false positive occurs with Hashimoto's disease, Dr. Milas acknowledged.

Postoperative Use

Use of the blood test in 69 paired samples with thyroid cancer revealed that elevated TSHR mRNA levels became undetectable in all patients on postoperative day 1, except in seven who had persistent or recurrent cancer within the year and unfavorable histologic features.

In contrast, all 40 patients with benign disease had undetectable TSHR mRNA levels on day 1 after thyroidectomy. “This suggests the potential use of TSHR mRNA as an early marker of adequate surgical clearance of disease or future recurrence,” Dr. Milas said in an interview.

Long-Term Surveillance

TSHR mRNA also showed merit during long-term follow-up of thyroid cancer, notably in two particularly challenging scenarios: when thyroglobulin antibodies were present, and when patients had residual thyroid tissue from original surgery and detectable thyroglobulin levels between 0.2 and 49 ng/mL that are difficult to interpret, she said.

At a median follow-up of about 2 years in 60 patients with elevated thyroglobulin antibodies, detectable TSHR mRNA was the only blood test to confirm cancer in four patients. Negative TSHR mRNA reassured absence of disease in 54 of the 56 remaining patients whose imaging was also negative.

All 59 patients with residual thyroid tissue because of partial thyroidectomy for cancer had undetectable TSHR mRNA levels and no radiologic evidence of cancer recurrence at follow-up, she said.

“This assay has come of age,” remarked Dr. Collin Weber, the invited discussant and chief of endocrine surgery at Emory University Hospital in Atlanta.

He questioned whether total thyroidectomy is performed at the Cleveland Clinic on all indeterminate lesions when the assay is positive and whether its accuracy is good enough to recommend observation of TSHR mRNA-negative follicular neoplasms greater than 2.5 cm in size.

Dr. Milas responded that total thyroidectomy would be advised based on abnormal TSHR mRNA levels because a positive predictive value of 96% is reassuring and has held up in daily practice since the analysis was closed.

She said the assay is not accurate enough, however, to recommend observation in sonographically suspicious, 2.5-cm or greater tumors with undetectable TSHR mRNA levels, but “is possibly and cautiously” enough when combined with an informed discussion with the patient when smaller lesions lack concerning ultrasound features and in patients with medical comorbidities who face increased risk during a diagnostic thyroidectomy.

Disclosures: Dr. Milas and Dr. Weber stated they had no relevant disclosures.

TSHR mRNA had a positive predictive value of 100% in patients with papillary thyroid cancers greater than 1 cm.

Source DR. MILAS

CHICAGO — Thyroid-stimulating hormone receptor messenger RNA is a clinically useful blood test in the pre- and postoperative management of thyroid cancer, based on results from a prospective validation study in 1,095 consecutive patients.

If detectable preoperatively, when fine-needle aspiration suggests follicular neoplasm, thyroid-stimulating hormone receptor (TSHR) messenger RNA (mRNA) accurately predicts thyroid cancer and guides the extent of surgery, reported Dr. Mira Milas, principal investigator.

“It has a practical role to predict thyroid cancers where other modalities may fall short,” she said. In addition, high levels on the first postoperative day alert physicians to persistent disease, while its presence during long-term surveillance aids in identifying recurrence.

“We are encouraged by this performance and the fact that it is a convenient blood test to perform,” said Dr. Milas, director of the thyroid center at the Cleveland Clinic. “Our next steps are to search for multicenter trials and [Food and Drug Administration] approval for some of these indications.”

No new blood tests for differentiated thyroid cancer have been introduced into routine clinical practice since thyroglobulin. Thyroglobulin is used for cancer follow-up, but not initial diagnosis.

The TSHR mRNA assay was developed 9 years ago at the clinic's pathology department by study collaborator Manjula Gupta, Ph.D.

TSHR mRNA acts as a surrogate marker for circulating thyroid cancer cells, and in initial studies distinguished benign from malignant thyroid diseases.

A recent report suggests that TSHR mRNA is detectable even in thyroid microcarcinomas, and may characterize those with potentially more aggressive histology (Surgery 2009;146:1081–9).

The aim of the current analysis was to validate the clinical use of the marker 1 year after its introduction at the Cleveland Clinic, where the test is now used daily in all patients scheduled for thyroid surgery and those undergoing consultation for thyroid disease in the office.

From October 2008 through September 2009, TSHR mRNA was measured by quantitative real-time polymerase chain reaction from blood drawn in 403 patients undergoing thyroid surgery, postoperatively in 541 patients, and in 151 patients monitored for benign goiters.

Preoperative Use

Preoperative TSHR mRNA greater than 1 ng/mcg as a sole predictor of cancer had a positive predictive value (PPV) of 81% and specificity of 83% in 374 patients with surgically confirmed pathology, Dr. Milas said. Sensitivity was modest at 61%, as was negative predictive value at 64%. However, its PPV was 100% in patients with papillary thyroid cancers greater than 1 cm.

She observed that TSHR mRNA is particularly useful in detecting cancer in patients with follicular neoplasms on fine-needle aspiration. In 54 such patients, TSHR mRNA alone had a PPV of 96%, a specificity of 96%, and accuracy of 85%. The sensitivity of diagnosing cancer improved from 76% to 97% when the blood test was combined with ultrasound. Ultrasound features such as irregular margins, hypervascularity, indistinct borders, and microcalcification are suggestive of cancer in follicular neoplasms, but none are independently diagnostic. The highest risk of a false positive occurs with Hashimoto's disease, Dr. Milas acknowledged.

Postoperative Use

Use of the blood test in 69 paired samples with thyroid cancer revealed that elevated TSHR mRNA levels became undetectable in all patients on postoperative day 1, except in seven who had persistent or recurrent cancer within the year and unfavorable histologic features.

In contrast, all 40 patients with benign disease had undetectable TSHR mRNA levels on day 1 after thyroidectomy. “This suggests the potential use of TSHR mRNA as an early marker of adequate surgical clearance of disease or future recurrence,” Dr. Milas said in an interview.

Long-Term Surveillance

TSHR mRNA also showed merit during long-term follow-up of thyroid cancer, notably in two particularly challenging scenarios: when thyroglobulin antibodies were present, and when patients had residual thyroid tissue from original surgery and detectable thyroglobulin levels between 0.2 and 49 ng/mL that are difficult to interpret, she said.

At a median follow-up of about 2 years in 60 patients with elevated thyroglobulin antibodies, detectable TSHR mRNA was the only blood test to confirm cancer in four patients. Negative TSHR mRNA reassured absence of disease in 54 of the 56 remaining patients whose imaging was also negative.

All 59 patients with residual thyroid tissue because of partial thyroidectomy for cancer had undetectable TSHR mRNA levels and no radiologic evidence of cancer recurrence at follow-up, she said.

“This assay has come of age,” remarked Dr. Collin Weber, the invited discussant and chief of endocrine surgery at Emory University Hospital in Atlanta.

He questioned whether total thyroidectomy is performed at the Cleveland Clinic on all indeterminate lesions when the assay is positive and whether its accuracy is good enough to recommend observation of TSHR mRNA-negative follicular neoplasms greater than 2.5 cm in size.

Dr. Milas responded that total thyroidectomy would be advised based on abnormal TSHR mRNA levels because a positive predictive value of 96% is reassuring and has held up in daily practice since the analysis was closed.

She said the assay is not accurate enough, however, to recommend observation in sonographically suspicious, 2.5-cm or greater tumors with undetectable TSHR mRNA levels, but “is possibly and cautiously” enough when combined with an informed discussion with the patient when smaller lesions lack concerning ultrasound features and in patients with medical comorbidities who face increased risk during a diagnostic thyroidectomy.

Disclosures: Dr. Milas and Dr. Weber stated they had no relevant disclosures.

TSHR mRNA had a positive predictive value of 100% in patients with papillary thyroid cancers greater than 1 cm.

Source DR. MILAS

Major Finding: The average length of stay for RSV fell 12.9% after the introduction of palivizumab, versus a decrease of 3.4% for other causes of infant hospitalization.

Data Source: Retrospective cross-section comparison of two time periods.

Disclosures: Dr. Racine reported no conflicts or external study support.

VANCOUVER, B.C. — The introduction of palivizumab as a preventative treatment for respiratory syncytial virus appears to be associated with a shorter length of hospital stay for the disease, one California study showed.

Hospital charges for respiratory syncytial virus (RSV) also increased at a slower pace than for other causes of infant hospitalization, according to a retrospective analysis of California discharges among 3,443,918 infants less than 1 year of age.

The data provide real-world evidence about the impact of palivizumab (Synagis) in the community since its approval in 1998 based on one company-sponsored study, said Dr. Andrew Racine, chief of the general pediatrics section at Albert Einstein College of Medicine in New York City<

“This is important for the following reason: The U.S. sales of palivizumab have gone from about &dollar;225 million dollars in 1998 to over &dollar;1.5 billion dollars in 2007,” he said. “We're using a lot of this; we might as well know if it's effective.”

Palivizumab costs about &dollar;900 a dose, with most at-risk children receiving five doses as prophylaxis. There is no treatment for RSV.

Dr. Racine cautioned that the data are from a single state and were not stratified by risk categories for RSV. In addition, the findings were based on an intent-to-treat analysis and thus may not reflect whether patients actually received the medication. There are plans to link the birth certificate to the hospitalization and to identify gestational age and congenital illnesses.

The researchers used data from the California Patient Discharge Database and individual level hospitalization records to compare length of stay and hospitalization costs among infants less than 1 year of age during two time periods—before (1995-1997) and after (2005-2007) palivizumab.

The mean length of stay for RSV hospitalizations fell 12.9% from 3.95 days before palivizumab to 3.43 days after the drug. This compares with a decrease of 3.4% for non-RSV hospitalizations, which went from 3.2 days to 3.09. The difference was statistically significant at a P value less than .001, Dr. Racine said at the meeting.

Median hospital charges in constant 2007 dollars for an RSV diagnosis increased 20.1% from &dollar;16,060 to &dollar;19,390 after palivizumab, while non-RSV charges rose 58.6% from &dollar;11,901 to &dollar;18,857 over the two periods. Again the difference was significant at a P value equal to .001.

Session moderator Dr. Esther Chung, a pediatrician with Thomas Jefferson University Hospitals in Philadelphia, suggested that factors besides length of stay could be driving down RSV hospitalization costs.

Dr. Racine said that lower use of albuterol, corticosteroids, and imaging studies also may have occurred during the second time period, but that these data were not examined and that his own “heartbreaking” experience suggests that these practices continue.

“There are a lot of things we are still doing to these children with this condition that are completely unnecessary and costly,” he said.

A study led by Dr. Caroline B. Hall, whose earlier work led to the approval of palivizumab, reported that only 3% of 355 outpatients with confirmed RSV infection received an RSV diagnosis, with 20% of these children diagnosed with bronchiolitis. Dr. Hall and her associates estimated that RSV infection results in 1 of 334 hospitalizations among children under the age of 5 years (N. Engl. J. Med. 2009;360:588-98).

Major Finding: The average length of stay for RSV fell 12.9% after the introduction of palivizumab, versus a decrease of 3.4% for other causes of infant hospitalization.

Data Source: Retrospective cross-section comparison of two time periods.

Disclosures: Dr. Racine reported no conflicts or external study support.

VANCOUVER, B.C. — The introduction of palivizumab as a preventative treatment for respiratory syncytial virus appears to be associated with a shorter length of hospital stay for the disease, one California study showed.

Hospital charges for respiratory syncytial virus (RSV) also increased at a slower pace than for other causes of infant hospitalization, according to a retrospective analysis of California discharges among 3,443,918 infants less than 1 year of age.

The data provide real-world evidence about the impact of palivizumab (Synagis) in the community since its approval in 1998 based on one company-sponsored study, said Dr. Andrew Racine, chief of the general pediatrics section at Albert Einstein College of Medicine in New York City<

“This is important for the following reason: The U.S. sales of palivizumab have gone from about &dollar;225 million dollars in 1998 to over &dollar;1.5 billion dollars in 2007,” he said. “We're using a lot of this; we might as well know if it's effective.”

Palivizumab costs about &dollar;900 a dose, with most at-risk children receiving five doses as prophylaxis. There is no treatment for RSV.

Dr. Racine cautioned that the data are from a single state and were not stratified by risk categories for RSV. In addition, the findings were based on an intent-to-treat analysis and thus may not reflect whether patients actually received the medication. There are plans to link the birth certificate to the hospitalization and to identify gestational age and congenital illnesses.

The researchers used data from the California Patient Discharge Database and individual level hospitalization records to compare length of stay and hospitalization costs among infants less than 1 year of age during two time periods—before (1995-1997) and after (2005-2007) palivizumab.

The mean length of stay for RSV hospitalizations fell 12.9% from 3.95 days before palivizumab to 3.43 days after the drug. This compares with a decrease of 3.4% for non-RSV hospitalizations, which went from 3.2 days to 3.09. The difference was statistically significant at a P value less than .001, Dr. Racine said at the meeting.

Median hospital charges in constant 2007 dollars for an RSV diagnosis increased 20.1% from &dollar;16,060 to &dollar;19,390 after palivizumab, while non-RSV charges rose 58.6% from &dollar;11,901 to &dollar;18,857 over the two periods. Again the difference was significant at a P value equal to .001.

Session moderator Dr. Esther Chung, a pediatrician with Thomas Jefferson University Hospitals in Philadelphia, suggested that factors besides length of stay could be driving down RSV hospitalization costs.

Dr. Racine said that lower use of albuterol, corticosteroids, and imaging studies also may have occurred during the second time period, but that these data were not examined and that his own “heartbreaking” experience suggests that these practices continue.

“There are a lot of things we are still doing to these children with this condition that are completely unnecessary and costly,” he said.

A study led by Dr. Caroline B. Hall, whose earlier work led to the approval of palivizumab, reported that only 3% of 355 outpatients with confirmed RSV infection received an RSV diagnosis, with 20% of these children diagnosed with bronchiolitis. Dr. Hall and her associates estimated that RSV infection results in 1 of 334 hospitalizations among children under the age of 5 years (N. Engl. J. Med. 2009;360:588-98).

Major Finding: The average length of stay for RSV fell 12.9% after the introduction of palivizumab, versus a decrease of 3.4% for other causes of infant hospitalization.

Data Source: Retrospective cross-section comparison of two time periods.

Disclosures: Dr. Racine reported no conflicts or external study support.

VANCOUVER, B.C. — The introduction of palivizumab as a preventative treatment for respiratory syncytial virus appears to be associated with a shorter length of hospital stay for the disease, one California study showed.

Hospital charges for respiratory syncytial virus (RSV) also increased at a slower pace than for other causes of infant hospitalization, according to a retrospective analysis of California discharges among 3,443,918 infants less than 1 year of age.

The data provide real-world evidence about the impact of palivizumab (Synagis) in the community since its approval in 1998 based on one company-sponsored study, said Dr. Andrew Racine, chief of the general pediatrics section at Albert Einstein College of Medicine in New York City<

“This is important for the following reason: The U.S. sales of palivizumab have gone from about &dollar;225 million dollars in 1998 to over &dollar;1.5 billion dollars in 2007,” he said. “We're using a lot of this; we might as well know if it's effective.”

Palivizumab costs about &dollar;900 a dose, with most at-risk children receiving five doses as prophylaxis. There is no treatment for RSV.

Dr. Racine cautioned that the data are from a single state and were not stratified by risk categories for RSV. In addition, the findings were based on an intent-to-treat analysis and thus may not reflect whether patients actually received the medication. There are plans to link the birth certificate to the hospitalization and to identify gestational age and congenital illnesses.

The researchers used data from the California Patient Discharge Database and individual level hospitalization records to compare length of stay and hospitalization costs among infants less than 1 year of age during two time periods—before (1995-1997) and after (2005-2007) palivizumab.

The mean length of stay for RSV hospitalizations fell 12.9% from 3.95 days before palivizumab to 3.43 days after the drug. This compares with a decrease of 3.4% for non-RSV hospitalizations, which went from 3.2 days to 3.09. The difference was statistically significant at a P value less than .001, Dr. Racine said at the meeting.

Median hospital charges in constant 2007 dollars for an RSV diagnosis increased 20.1% from &dollar;16,060 to &dollar;19,390 after palivizumab, while non-RSV charges rose 58.6% from &dollar;11,901 to &dollar;18,857 over the two periods. Again the difference was significant at a P value equal to .001.

Session moderator Dr. Esther Chung, a pediatrician with Thomas Jefferson University Hospitals in Philadelphia, suggested that factors besides length of stay could be driving down RSV hospitalization costs.

Dr. Racine said that lower use of albuterol, corticosteroids, and imaging studies also may have occurred during the second time period, but that these data were not examined and that his own “heartbreaking” experience suggests that these practices continue.

“There are a lot of things we are still doing to these children with this condition that are completely unnecessary and costly,” he said.

A study led by Dr. Caroline B. Hall, whose earlier work led to the approval of palivizumab, reported that only 3% of 355 outpatients with confirmed RSV infection received an RSV diagnosis, with 20% of these children diagnosed with bronchiolitis. Dr. Hall and her associates estimated that RSV infection results in 1 of 334 hospitalizations among children under the age of 5 years (N. Engl. J. Med. 2009;360:588-98).

Major Finding: Overall, 75% of patients randomized to Lactobacillus GG returned to normal stool, vs. 70% of those receiving placebo.

Data Source: Double-blind randomized trial of Lactobacillus GG in 129 children with acute infectious diarrhea.

Disclosures: Amerifit Brands Inc. provided the study product and placebo, and a small patient incentive. Dr. Nixon disclosed no conflicts of interest.

VANCOUVER, B.C. — Contrary to prior studies, Lactobacillus GG did not significantly affect the overall duration or severity of acute infectious diarrhea, in a double-blind, randomized trial of 129 children presenting in the pediatric emergency department.

Children with longer diarrheal illness however, appeared to respond better to outpatient use of Lactobacillus GG (LGG), Dr. Abigail Nixon, a pediatric fellow in training at the Jacobi Medical Center, New York, said at the annual meeting of the Pediatric Academic Societies.

Probiotics have been shown to decrease the duration of infectious diarrhea, although there are no U.S. studies of the use of probiotics to treat infectious diarrhea in the outpatient setting.

The study involved 129 children, aged 6 months to 6 years (mean 25.5 months), presenting to the emergency department (ED) with acute diarrhea, defined as more than two loose stools in the preceding 24 hours (mean 5.3 episodes). Patients were randomized to 10 capsules of dissolvable powder containing LGG or placebo containing inulin, a polysaccharide. Parents administered the powder twice daily for 5 days and recorded in a home diary the number of stools. A blinded researcher called the caregiver daily for 5 days, and recorded the number of stools and the date and time of the first normal stool.

The percentage of children returning to normal stool during the study period was similar among patients randomized to LGG and those receiving placebo, at 75% and 70%, respectively, Dr. Nixon said. There also was no significant difference in the median time to normal stool—60 hours with LGG vs. 74 hours with placebo—or in the number of diarrheal stools during the study—5.0 with LGG vs. 6.5 with placebo.

The lack of a significant benefit from LGG may be caused by the fact that children treated and discharged from the ED are in general not as ill as those who are admitted, Dr. Nixon explained, and therefore it's more difficult to document an effect of the probiotic.

“I think there's a population of children who probably have very mild disease who don't benefit from probiotics because they don't need it; they would have gotten better on their own,” she said in an interview. “I think that's why as a group as a whole, we didn't see a meaningful difference.” Still, the results support a trend for a benefit of probiotics, she added.

Among patients presenting with more than 2 days of diarrhea, a post hoc subgroup analysis revealed that a significantly higher percentage of the LGG patients returned to normal stool than did placebo-treated patients, 79% vs. 58%.

In addition, LGG patients returned to normal stool almost 24 hours earlier than did their counterparts treated with placebo (51 hours vs. 74 hours), and had half the number of diarrheal stools (3.5 vs. 7). Both differences were statistically significant.

After the researchers adjusted for age, children with more than 2 days of diarrhea treated with LGG were twice as likely to return to normal stool as were children in the placebo group.

“LGG may have a restorative effect on the intestinal flora and therefore would preferentially benefit patients presenting with prolonged diarrhea,” said Dr. Nixon, who recommends probiotics, either as tablets or fortified yogurt, to her patients in the ED.

She noted that a reduction in the time to resolution of diarrhea might have important public health implications in terms of missed work, lost revenue, and school absenteeism. Diarrhea accounts for about 1.5 million pediatric outpatient visits and more than 200,000 hospitalizations annually in the United States, Dr. Nixon said at the meeting.

Dr. Nixon's study was awarded this year's American Pediatric Association Ludwig-Seidel Award for the best research project in pediatric emergency medicine led by a fellow.

'LGG may have a restorative effect on the intestinal flora' and so, might benefit kids with diarrhea for more than 2 days.

Source DR. NIXON

Major Finding: Overall, 75% of patients randomized to Lactobacillus GG returned to normal stool, vs. 70% of those receiving placebo.

Data Source: Double-blind randomized trial of Lactobacillus GG in 129 children with acute infectious diarrhea.

Disclosures: Amerifit Brands Inc. provided the study product and placebo, and a small patient incentive. Dr. Nixon disclosed no conflicts of interest.

VANCOUVER, B.C. — Contrary to prior studies, Lactobacillus GG did not significantly affect the overall duration or severity of acute infectious diarrhea, in a double-blind, randomized trial of 129 children presenting in the pediatric emergency department.

Children with longer diarrheal illness however, appeared to respond better to outpatient use of Lactobacillus GG (LGG), Dr. Abigail Nixon, a pediatric fellow in training at the Jacobi Medical Center, New York, said at the annual meeting of the Pediatric Academic Societies.

Probiotics have been shown to decrease the duration of infectious diarrhea, although there are no U.S. studies of the use of probiotics to treat infectious diarrhea in the outpatient setting.

The study involved 129 children, aged 6 months to 6 years (mean 25.5 months), presenting to the emergency department (ED) with acute diarrhea, defined as more than two loose stools in the preceding 24 hours (mean 5.3 episodes). Patients were randomized to 10 capsules of dissolvable powder containing LGG or placebo containing inulin, a polysaccharide. Parents administered the powder twice daily for 5 days and recorded in a home diary the number of stools. A blinded researcher called the caregiver daily for 5 days, and recorded the number of stools and the date and time of the first normal stool.

The percentage of children returning to normal stool during the study period was similar among patients randomized to LGG and those receiving placebo, at 75% and 70%, respectively, Dr. Nixon said. There also was no significant difference in the median time to normal stool—60 hours with LGG vs. 74 hours with placebo—or in the number of diarrheal stools during the study—5.0 with LGG vs. 6.5 with placebo.

The lack of a significant benefit from LGG may be caused by the fact that children treated and discharged from the ED are in general not as ill as those who are admitted, Dr. Nixon explained, and therefore it's more difficult to document an effect of the probiotic.

“I think there's a population of children who probably have very mild disease who don't benefit from probiotics because they don't need it; they would have gotten better on their own,” she said in an interview. “I think that's why as a group as a whole, we didn't see a meaningful difference.” Still, the results support a trend for a benefit of probiotics, she added.

Among patients presenting with more than 2 days of diarrhea, a post hoc subgroup analysis revealed that a significantly higher percentage of the LGG patients returned to normal stool than did placebo-treated patients, 79% vs. 58%.

In addition, LGG patients returned to normal stool almost 24 hours earlier than did their counterparts treated with placebo (51 hours vs. 74 hours), and had half the number of diarrheal stools (3.5 vs. 7). Both differences were statistically significant.

After the researchers adjusted for age, children with more than 2 days of diarrhea treated with LGG were twice as likely to return to normal stool as were children in the placebo group.

“LGG may have a restorative effect on the intestinal flora and therefore would preferentially benefit patients presenting with prolonged diarrhea,” said Dr. Nixon, who recommends probiotics, either as tablets or fortified yogurt, to her patients in the ED.

She noted that a reduction in the time to resolution of diarrhea might have important public health implications in terms of missed work, lost revenue, and school absenteeism. Diarrhea accounts for about 1.5 million pediatric outpatient visits and more than 200,000 hospitalizations annually in the United States, Dr. Nixon said at the meeting.

Dr. Nixon's study was awarded this year's American Pediatric Association Ludwig-Seidel Award for the best research project in pediatric emergency medicine led by a fellow.

'LGG may have a restorative effect on the intestinal flora' and so, might benefit kids with diarrhea for more than 2 days.

Source DR. NIXON

Major Finding: Overall, 75% of patients randomized to Lactobacillus GG returned to normal stool, vs. 70% of those receiving placebo.

Data Source: Double-blind randomized trial of Lactobacillus GG in 129 children with acute infectious diarrhea.

Disclosures: Amerifit Brands Inc. provided the study product and placebo, and a small patient incentive. Dr. Nixon disclosed no conflicts of interest.

VANCOUVER, B.C. — Contrary to prior studies, Lactobacillus GG did not significantly affect the overall duration or severity of acute infectious diarrhea, in a double-blind, randomized trial of 129 children presenting in the pediatric emergency department.

Children with longer diarrheal illness however, appeared to respond better to outpatient use of Lactobacillus GG (LGG), Dr. Abigail Nixon, a pediatric fellow in training at the Jacobi Medical Center, New York, said at the annual meeting of the Pediatric Academic Societies.

Probiotics have been shown to decrease the duration of infectious diarrhea, although there are no U.S. studies of the use of probiotics to treat infectious diarrhea in the outpatient setting.

The study involved 129 children, aged 6 months to 6 years (mean 25.5 months), presenting to the emergency department (ED) with acute diarrhea, defined as more than two loose stools in the preceding 24 hours (mean 5.3 episodes). Patients were randomized to 10 capsules of dissolvable powder containing LGG or placebo containing inulin, a polysaccharide. Parents administered the powder twice daily for 5 days and recorded in a home diary the number of stools. A blinded researcher called the caregiver daily for 5 days, and recorded the number of stools and the date and time of the first normal stool.

The percentage of children returning to normal stool during the study period was similar among patients randomized to LGG and those receiving placebo, at 75% and 70%, respectively, Dr. Nixon said. There also was no significant difference in the median time to normal stool—60 hours with LGG vs. 74 hours with placebo—or in the number of diarrheal stools during the study—5.0 with LGG vs. 6.5 with placebo.

The lack of a significant benefit from LGG may be caused by the fact that children treated and discharged from the ED are in general not as ill as those who are admitted, Dr. Nixon explained, and therefore it's more difficult to document an effect of the probiotic.

“I think there's a population of children who probably have very mild disease who don't benefit from probiotics because they don't need it; they would have gotten better on their own,” she said in an interview. “I think that's why as a group as a whole, we didn't see a meaningful difference.” Still, the results support a trend for a benefit of probiotics, she added.

Among patients presenting with more than 2 days of diarrhea, a post hoc subgroup analysis revealed that a significantly higher percentage of the LGG patients returned to normal stool than did placebo-treated patients, 79% vs. 58%.

In addition, LGG patients returned to normal stool almost 24 hours earlier than did their counterparts treated with placebo (51 hours vs. 74 hours), and had half the number of diarrheal stools (3.5 vs. 7). Both differences were statistically significant.

After the researchers adjusted for age, children with more than 2 days of diarrhea treated with LGG were twice as likely to return to normal stool as were children in the placebo group.

“LGG may have a restorative effect on the intestinal flora and therefore would preferentially benefit patients presenting with prolonged diarrhea,” said Dr. Nixon, who recommends probiotics, either as tablets or fortified yogurt, to her patients in the ED.

She noted that a reduction in the time to resolution of diarrhea might have important public health implications in terms of missed work, lost revenue, and school absenteeism. Diarrhea accounts for about 1.5 million pediatric outpatient visits and more than 200,000 hospitalizations annually in the United States, Dr. Nixon said at the meeting.

Dr. Nixon's study was awarded this year's American Pediatric Association Ludwig-Seidel Award for the best research project in pediatric emergency medicine led by a fellow.

'LGG may have a restorative effect on the intestinal flora' and so, might benefit kids with diarrhea for more than 2 days.

Source DR. NIXON

Major Finding: At 6 months after starting a sleep intervention plan, families reported a 74% improvement in their children's sleep. A control group reported a 53% improvement.

Data Source: Randomized trial of 108 families nested within a population survey of 1,519 parents of children entering 22 public schools in Melbourne.

Disclosures: Mr. Quach reported receiving a scholarship from the Australian National Health Medical Research Council.

VANCOUVER, B.C. — A brief, behavioral sleep intervention improved child and parent outcomes in the short term in a randomized trial involving 108 families.

At 3 and 6 months, children in the intervention group displayed less bedtime resistance and bedtime delay, as well less daytime tiredness, based on parent reports.

The children were selected for the study based on a survey of parents of 1,519 children entering 22 public schools in Melbourne. The survey indicated 28% of children had mild sleep problems and 11% had moderate to severe sleep problems. From this population, 108 families of children with moderate to severe sleep problems were recruited in the first 6 months of school and randomized to one to two consultations with a health professional or no sleep advice. The children's mean age was 5.6 years.

The intervention included an initial 45-minute private consultation with parents at the school, a 20-minute telephone call 10 days later, and a 30-minute private consultation at the school, if needed, said principal investigator Jon L. Quach, a doctoral student in the pediatrics department at the University of Melbourne.

The content included a discussion of normal sleep requirements and good sleep practices such as maintaining a routine bedtime and minimizing exposure to media, as well as use of flexible, yet standardized behavioral sleep management strategies.

At 3 months, intervention families reported a nonsignificant improvement in their child's sleep of 67%, compared with a 57% improvement in the control group, he said.

At 6 months, the improvement increased to 74% in the intervention group vs. 53% in the control group, which was statistically significant.

At both time points, there was less bedtime resistance and bedtime delay in the intervention group, as well less daytime tiredness, Mr. Quach said.

At 3 months, intervention children had better psychosocial health-related quality of life scores, specifically social functioning, and emotional functioning. The intervention had no impact on attention-deficit/hyperactivity disorder symptoms, he said.

At 6 months, only social functioning was improved in the intervention group.

At 3 months, parents in the intervention group reported fewer depression symptoms.

The findings demonstrate that a brief, behavioral intervention has significant benefits in the short to medium term, and that it is possible to deliver such an intervention in the school environment, Mr. Quach said. Twelve-month outcomes and teacher assessments will be conducted in the future.

Sleep problems are associated with poorer child behavior, health-related quality of life, and learning, which are all important to a successful transition to school. Identifying and treating sleep problems during the first year of schooling may help to optimize this transition.

Mr. Quach emphasized that improvements in child sleep are best achieved when sleep management plans are tailored to each family. He advised presenting a menu of flexible, yet standardized, behavioral sleep strategies and encouraging parents to choose strategies that can be readily incorporated into their family setting.

Major Finding: At 6 months after starting a sleep intervention plan, families reported a 74% improvement in their children's sleep. A control group reported a 53% improvement.

Data Source: Randomized trial of 108 families nested within a population survey of 1,519 parents of children entering 22 public schools in Melbourne.

Disclosures: Mr. Quach reported receiving a scholarship from the Australian National Health Medical Research Council.

VANCOUVER, B.C. — A brief, behavioral sleep intervention improved child and parent outcomes in the short term in a randomized trial involving 108 families.

At 3 and 6 months, children in the intervention group displayed less bedtime resistance and bedtime delay, as well less daytime tiredness, based on parent reports.

The children were selected for the study based on a survey of parents of 1,519 children entering 22 public schools in Melbourne. The survey indicated 28% of children had mild sleep problems and 11% had moderate to severe sleep problems. From this population, 108 families of children with moderate to severe sleep problems were recruited in the first 6 months of school and randomized to one to two consultations with a health professional or no sleep advice. The children's mean age was 5.6 years.

The intervention included an initial 45-minute private consultation with parents at the school, a 20-minute telephone call 10 days later, and a 30-minute private consultation at the school, if needed, said principal investigator Jon L. Quach, a doctoral student in the pediatrics department at the University of Melbourne.

The content included a discussion of normal sleep requirements and good sleep practices such as maintaining a routine bedtime and minimizing exposure to media, as well as use of flexible, yet standardized behavioral sleep management strategies.

At 3 months, intervention families reported a nonsignificant improvement in their child's sleep of 67%, compared with a 57% improvement in the control group, he said.

At 6 months, the improvement increased to 74% in the intervention group vs. 53% in the control group, which was statistically significant.

At both time points, there was less bedtime resistance and bedtime delay in the intervention group, as well less daytime tiredness, Mr. Quach said.

At 3 months, intervention children had better psychosocial health-related quality of life scores, specifically social functioning, and emotional functioning. The intervention had no impact on attention-deficit/hyperactivity disorder symptoms, he said.

At 6 months, only social functioning was improved in the intervention group.

At 3 months, parents in the intervention group reported fewer depression symptoms.

The findings demonstrate that a brief, behavioral intervention has significant benefits in the short to medium term, and that it is possible to deliver such an intervention in the school environment, Mr. Quach said. Twelve-month outcomes and teacher assessments will be conducted in the future.

Sleep problems are associated with poorer child behavior, health-related quality of life, and learning, which are all important to a successful transition to school. Identifying and treating sleep problems during the first year of schooling may help to optimize this transition.

Mr. Quach emphasized that improvements in child sleep are best achieved when sleep management plans are tailored to each family. He advised presenting a menu of flexible, yet standardized, behavioral sleep strategies and encouraging parents to choose strategies that can be readily incorporated into their family setting.

Major Finding: At 6 months after starting a sleep intervention plan, families reported a 74% improvement in their children's sleep. A control group reported a 53% improvement.

Data Source: Randomized trial of 108 families nested within a population survey of 1,519 parents of children entering 22 public schools in Melbourne.

Disclosures: Mr. Quach reported receiving a scholarship from the Australian National Health Medical Research Council.

VANCOUVER, B.C. — A brief, behavioral sleep intervention improved child and parent outcomes in the short term in a randomized trial involving 108 families.

At 3 and 6 months, children in the intervention group displayed less bedtime resistance and bedtime delay, as well less daytime tiredness, based on parent reports.

The children were selected for the study based on a survey of parents of 1,519 children entering 22 public schools in Melbourne. The survey indicated 28% of children had mild sleep problems and 11% had moderate to severe sleep problems. From this population, 108 families of children with moderate to severe sleep problems were recruited in the first 6 months of school and randomized to one to two consultations with a health professional or no sleep advice. The children's mean age was 5.6 years.

The intervention included an initial 45-minute private consultation with parents at the school, a 20-minute telephone call 10 days later, and a 30-minute private consultation at the school, if needed, said principal investigator Jon L. Quach, a doctoral student in the pediatrics department at the University of Melbourne.

The content included a discussion of normal sleep requirements and good sleep practices such as maintaining a routine bedtime and minimizing exposure to media, as well as use of flexible, yet standardized behavioral sleep management strategies.

At 3 months, intervention families reported a nonsignificant improvement in their child's sleep of 67%, compared with a 57% improvement in the control group, he said.

At 6 months, the improvement increased to 74% in the intervention group vs. 53% in the control group, which was statistically significant.

At both time points, there was less bedtime resistance and bedtime delay in the intervention group, as well less daytime tiredness, Mr. Quach said.

At 3 months, intervention children had better psychosocial health-related quality of life scores, specifically social functioning, and emotional functioning. The intervention had no impact on attention-deficit/hyperactivity disorder symptoms, he said.

At 6 months, only social functioning was improved in the intervention group.

At 3 months, parents in the intervention group reported fewer depression symptoms.

The findings demonstrate that a brief, behavioral intervention has significant benefits in the short to medium term, and that it is possible to deliver such an intervention in the school environment, Mr. Quach said. Twelve-month outcomes and teacher assessments will be conducted in the future.

Sleep problems are associated with poorer child behavior, health-related quality of life, and learning, which are all important to a successful transition to school. Identifying and treating sleep problems during the first year of schooling may help to optimize this transition.

Mr. Quach emphasized that improvements in child sleep are best achieved when sleep management plans are tailored to each family. He advised presenting a menu of flexible, yet standardized, behavioral sleep strategies and encouraging parents to choose strategies that can be readily incorporated into their family setting.

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent. Ten percent reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and were due for all three vaccines and “all the stars were lined up for them to get the vaccines,” except that a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated.

If the unaccompanied minor were 12 years old, 50% would not get influenza or Tdap, and 70% would not the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if they were unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%-70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals and medical sites have a great deal of variety and flexibility regarding the process of documenting consent.

Federal law requires that all heath care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

Most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, said Dr. Ford, who reported having no conflicts.

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent. Ten percent reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and were due for all three vaccines and “all the stars were lined up for them to get the vaccines,” except that a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated.

If the unaccompanied minor were 12 years old, 50% would not get influenza or Tdap, and 70% would not the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if they were unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%-70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals and medical sites have a great deal of variety and flexibility regarding the process of documenting consent.

Federal law requires that all heath care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

Most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, said Dr. Ford, who reported having no conflicts.

VANCOUVER, B.C. — The inability of older adolescents to provide consent for vaccinations creates a barrier to vaccine delivery, new research suggests.

In a survey of 280 medical providers from 43 states, 95% said that 17-year-olds “sometimes” or “often” present without a parent. Ten percent reported that this is true for 12-year-olds.

The providers were then asked how likely it was that an unaccompanied minor adolescent in their state would be vaccinated for influenza; combined tetanus, diphtheria, and pertussis (Tdap); and human papillomavirus (HPV) if the vaccines were available for free, the patient was medically eligible, and the parent was not available to consent.

Responses varied by vaccine type, patient age, and clinical setting, said Dr. Carol Ford of the University of North Carolina, Chapel Hill.

If a 17-year-old presented alone for routine care in a private primary care clinic and were due for all three vaccines and “all the stars were lined up for them to get the vaccines,” except that a parent could not be reached, 30% would not get any of the vaccines. If the same patient presented alone to a private clinic for confidential services, 40% would not get vaccinated.

If the unaccompanied minor were 12 years old, 50% would not get influenza or Tdap, and 70% would not the HPV vaccine, according to the survey.

In a public primary care setting, approximately half of 17-year-olds presenting for routine care and 65% of 12-year-olds would not get any vaccines if they were unaccompanied by a parent, she noted.

Between 30% and 50% of health care provider respondents said that an adolescent presenting to a public clinic for confidential services would not get the HPV vaccine and 60%-70% would not get Tdap or influenza vaccines, with variation by age, Dr. Ford said.

Interventions to increase adolescent vaccinations include strategies such as anticipatory consent for vaccinations at the time of school physical examinations; advance consent for additional doses, as with the three-dose HPV vaccine; and calling parents on cell phones.

Providers must work within the context of legal, ethical, and professional guidelines regarding minor consent, but hospitals and medical sites have a great deal of variety and flexibility regarding the process of documenting consent.

Federal law requires that all heath care providers give vaccine information statements to parents or patients before administering each dose of the vaccines listed in the 2010 vaccine schedule.

Most states require patient assent, not consent. Survey respondents would support efforts to allow minors to consent for vaccination at a mean of 14.26 years for Tdap, 14.08 years for influenza, and 13.81 for HPV, said Dr. Ford, who reported having no conflicts.

Major Finding: There were 125 blood draws per month for bilirubin before and 117 after implementation of a routine screening protocol. An average of 6.8 infants per month underwent predischarge phototherapy before and 4.6 after routine screening was adopted. When readmission phototherapy was included, 9.5 infants received treatment before and 8 infants after routine screening was implemented.

Data Source: Retrospective analysis of 2,055 term infants.

Disclosures: The study was funded by the Clinical Practice Innovation program at the Mayo Clinic. The authors disclosed no conflicts of interest.

VANCOUVER, B.C. — Universal neonatal screening for hyperbilirubinemia can be implemented without increasing blood draws or phototherapy usage, according to a retrospective analysis involving 2,055 newborns.

The number of blood draws for bilirubin was similar at 125 per month before implementation of a routine transcutaneous bilirubin screening protocol vs. 117 per month after implementation.

The average number of infants who underwent phototherapy during initial hospitalization was 6.8 before vs. 4.6 after implementation. The decrease approached statistical significance, with a P value of .053, reported Dr. Andrea Wickremasinghe of the Mayo Clinic in Rochester, Minn.

Overall monthly phototherapy usage was also similar when readmission phototherapy was included, at 9.5 infants before and 8 infants after adoption of the protocol, the researchers found.

Several professional organizations have endorsed such screening, including the Canadian Paediatric Society and the American Academy of Pediatrics, which recommends that all infants undergo systematic assessment for hyperbilirubinemia before discharge. Last year, however, the U.S. Preventive Services Task Force concluded that there is insufficient evidence to determine if universal screening can prevent chronic bilirubin encephalopathy (kernicterus).

Jaundice occurs in two-thirds of newborns in the first week of life and typically resolves without sequelae, but in rare cases it leads to acute or chronic bilirubin encephalopathy.

Hyperbilirubinemia is increasingly being missed because more newborns are discharged from hospitals within 2 days of birth. Bilirubin levels peak at 3–5 days after birth, when hyperbilirubinemia usually becomes clinically evident, Dr. Wickremasinghe said. Problems with breastfeeding and late follow-up care also increase the risk for missed cases.

Transcutaneous bilirubin (TcB) testing is gaining in popularity as a predischarge screening method, and is thought to reasonably approximate total serum bilirubin (TSB) levels without the pain of a puncture or need to wait for lab results, she said. In one study, selective TcB screening did not change the number of blood draws for bilirubin, but did decrease readmissions for jaundice within 7 days of discharge (Clin. Chem. 2005;51:540–4).

Last year, a study conducted by two of Dr. Wickremasinghe's coauthors suggested that TcB testing systematically overestimates serum bilirubin levels and that 1 mg/dL should be subtracted from TcB levels.

The current analysis looked at electronic medical records from August 2008 through January 2009 and February 2009 through August 2009—before and after implementation of TcB screening.

During the first study period, serum bilirubin was obtained based on clinical judgment from 906 infants and plotted on an hour-specific nomogram (www.bilitool.org

During the second period, TcB measurements were obtained shortly before discharge using the BiliChek device (Philips) on the forehead in 1,149 infants. The values were adjusted by 1 mg/dL and plotted on the same serum bilirubin nomogram. A serum bilirubin level was obtained if patients were thought to be high risk, defined by a bilirubin value in the 95th percentile for their age on the nomogram, or high-intermediate risk, defined by a value in the 75th or higher percentile for age, Dr. Wickremasinghe said.

The average monthly nursery census was similar in each group, at 151 infants during the first period and 161 infants during the second.

Dr. Wickremasinghe acknowledged that the study limitations were that it was retrospective, that TcB values were plotted on a TSB nomogram, and that it may be difficult to generalize the results to other ethnicities because the population was predominantly white. The effect of TcB screening on costs was not determined, but may be analyzed in the future.

During a discussion of the findings, Dr. M. Jeffrey Maisels, chair of pediatrics at Beaumont Hospitals in Royal Oak, Mich., applauded the authors for adjusting TcB values in the analysis, noting that such values have been as much as 2–3 mg higher than those obtained with other methods in some studies. He said that although it may never be known if predischarge bilirubin screening can prevent an infant from developing kernicterus, screening does seem to reduce the number of infants readmitted with very high bilirubin levels.

This view is supported by a recent prospective study reporting a dramatic decline in severe hyperbilirubinemia among more than 1 million infants born between May 2004 and December 2008. The incidence of infants with total bilirubin levels of 25.0–29.9 mg/dL declined from 43/100,000 before implementation of universal predischarge bilirubin screening to 27/100,000 after implementation, while the incidence of infants with total bilirubin levels of at least 30 mg/dL dropped from 9/100,000 to 3/100,000. The change was associated with a small but statistically significant increase in use of phototherapy (Pediatrics 2010;125:e1143–8).

Hyperbilirubinemia is being missed because more newborns are discharged within 2 days of birth.

Source DR. WICKREMASINGHE

Major Finding: There were 125 blood draws per month for bilirubin before and 117 after implementation of a routine screening protocol. An average of 6.8 infants per month underwent predischarge phototherapy before and 4.6 after routine screening was adopted. When readmission phototherapy was included, 9.5 infants received treatment before and 8 infants after routine screening was implemented.

Data Source: Retrospective analysis of 2,055 term infants.

Disclosures: The study was funded by the Clinical Practice Innovation program at the Mayo Clinic. The authors disclosed no conflicts of interest.

VANCOUVER, B.C. — Universal neonatal screening for hyperbilirubinemia can be implemented without increasing blood draws or phototherapy usage, according to a retrospective analysis involving 2,055 newborns.

The number of blood draws for bilirubin was similar at 125 per month before implementation of a routine transcutaneous bilirubin screening protocol vs. 117 per month after implementation.

The average number of infants who underwent phototherapy during initial hospitalization was 6.8 before vs. 4.6 after implementation. The decrease approached statistical significance, with a P value of .053, reported Dr. Andrea Wickremasinghe of the Mayo Clinic in Rochester, Minn.

Overall monthly phototherapy usage was also similar when readmission phototherapy was included, at 9.5 infants before and 8 infants after adoption of the protocol, the researchers found.

Several professional organizations have endorsed such screening, including the Canadian Paediatric Society and the American Academy of Pediatrics, which recommends that all infants undergo systematic assessment for hyperbilirubinemia before discharge. Last year, however, the U.S. Preventive Services Task Force concluded that there is insufficient evidence to determine if universal screening can prevent chronic bilirubin encephalopathy (kernicterus).

Jaundice occurs in two-thirds of newborns in the first week of life and typically resolves without sequelae, but in rare cases it leads to acute or chronic bilirubin encephalopathy.

Hyperbilirubinemia is increasingly being missed because more newborns are discharged from hospitals within 2 days of birth. Bilirubin levels peak at 3–5 days after birth, when hyperbilirubinemia usually becomes clinically evident, Dr. Wickremasinghe said. Problems with breastfeeding and late follow-up care also increase the risk for missed cases.

Transcutaneous bilirubin (TcB) testing is gaining in popularity as a predischarge screening method, and is thought to reasonably approximate total serum bilirubin (TSB) levels without the pain of a puncture or need to wait for lab results, she said. In one study, selective TcB screening did not change the number of blood draws for bilirubin, but did decrease readmissions for jaundice within 7 days of discharge (Clin. Chem. 2005;51:540–4).

Last year, a study conducted by two of Dr. Wickremasinghe's coauthors suggested that TcB testing systematically overestimates serum bilirubin levels and that 1 mg/dL should be subtracted from TcB levels.

The current analysis looked at electronic medical records from August 2008 through January 2009 and February 2009 through August 2009—before and after implementation of TcB screening.

During the first study period, serum bilirubin was obtained based on clinical judgment from 906 infants and plotted on an hour-specific nomogram (www.bilitool.org

During the second period, TcB measurements were obtained shortly before discharge using the BiliChek device (Philips) on the forehead in 1,149 infants. The values were adjusted by 1 mg/dL and plotted on the same serum bilirubin nomogram. A serum bilirubin level was obtained if patients were thought to be high risk, defined by a bilirubin value in the 95th percentile for their age on the nomogram, or high-intermediate risk, defined by a value in the 75th or higher percentile for age, Dr. Wickremasinghe said.

The average monthly nursery census was similar in each group, at 151 infants during the first period and 161 infants during the second.

Dr. Wickremasinghe acknowledged that the study limitations were that it was retrospective, that TcB values were plotted on a TSB nomogram, and that it may be difficult to generalize the results to other ethnicities because the population was predominantly white. The effect of TcB screening on costs was not determined, but may be analyzed in the future.

During a discussion of the findings, Dr. M. Jeffrey Maisels, chair of pediatrics at Beaumont Hospitals in Royal Oak, Mich., applauded the authors for adjusting TcB values in the analysis, noting that such values have been as much as 2–3 mg higher than those obtained with other methods in some studies. He said that although it may never be known if predischarge bilirubin screening can prevent an infant from developing kernicterus, screening does seem to reduce the number of infants readmitted with very high bilirubin levels.

This view is supported by a recent prospective study reporting a dramatic decline in severe hyperbilirubinemia among more than 1 million infants born between May 2004 and December 2008. The incidence of infants with total bilirubin levels of 25.0–29.9 mg/dL declined from 43/100,000 before implementation of universal predischarge bilirubin screening to 27/100,000 after implementation, while the incidence of infants with total bilirubin levels of at least 30 mg/dL dropped from 9/100,000 to 3/100,000. The change was associated with a small but statistically significant increase in use of phototherapy (Pediatrics 2010;125:e1143–8).

Hyperbilirubinemia is being missed because more newborns are discharged within 2 days of birth.

Source DR. WICKREMASINGHE

Major Finding: There were 125 blood draws per month for bilirubin before and 117 after implementation of a routine screening protocol. An average of 6.8 infants per month underwent predischarge phototherapy before and 4.6 after routine screening was adopted. When readmission phototherapy was included, 9.5 infants received treatment before and 8 infants after routine screening was implemented.

Data Source: Retrospective analysis of 2,055 term infants.

Disclosures: The study was funded by the Clinical Practice Innovation program at the Mayo Clinic. The authors disclosed no conflicts of interest.

VANCOUVER, B.C. — Universal neonatal screening for hyperbilirubinemia can be implemented without increasing blood draws or phototherapy usage, according to a retrospective analysis involving 2,055 newborns.

The number of blood draws for bilirubin was similar at 125 per month before implementation of a routine transcutaneous bilirubin screening protocol vs. 117 per month after implementation.

The average number of infants who underwent phototherapy during initial hospitalization was 6.8 before vs. 4.6 after implementation. The decrease approached statistical significance, with a P value of .053, reported Dr. Andrea Wickremasinghe of the Mayo Clinic in Rochester, Minn.

Overall monthly phototherapy usage was also similar when readmission phototherapy was included, at 9.5 infants before and 8 infants after adoption of the protocol, the researchers found.

Several professional organizations have endorsed such screening, including the Canadian Paediatric Society and the American Academy of Pediatrics, which recommends that all infants undergo systematic assessment for hyperbilirubinemia before discharge. Last year, however, the U.S. Preventive Services Task Force concluded that there is insufficient evidence to determine if universal screening can prevent chronic bilirubin encephalopathy (kernicterus).

Jaundice occurs in two-thirds of newborns in the first week of life and typically resolves without sequelae, but in rare cases it leads to acute or chronic bilirubin encephalopathy.

Hyperbilirubinemia is increasingly being missed because more newborns are discharged from hospitals within 2 days of birth. Bilirubin levels peak at 3–5 days after birth, when hyperbilirubinemia usually becomes clinically evident, Dr. Wickremasinghe said. Problems with breastfeeding and late follow-up care also increase the risk for missed cases.

Transcutaneous bilirubin (TcB) testing is gaining in popularity as a predischarge screening method, and is thought to reasonably approximate total serum bilirubin (TSB) levels without the pain of a puncture or need to wait for lab results, she said. In one study, selective TcB screening did not change the number of blood draws for bilirubin, but did decrease readmissions for jaundice within 7 days of discharge (Clin. Chem. 2005;51:540–4).

Last year, a study conducted by two of Dr. Wickremasinghe's coauthors suggested that TcB testing systematically overestimates serum bilirubin levels and that 1 mg/dL should be subtracted from TcB levels.

The current analysis looked at electronic medical records from August 2008 through January 2009 and February 2009 through August 2009—before and after implementation of TcB screening.

During the first study period, serum bilirubin was obtained based on clinical judgment from 906 infants and plotted on an hour-specific nomogram (www.bilitool.org

During the second period, TcB measurements were obtained shortly before discharge using the BiliChek device (Philips) on the forehead in 1,149 infants. The values were adjusted by 1 mg/dL and plotted on the same serum bilirubin nomogram. A serum bilirubin level was obtained if patients were thought to be high risk, defined by a bilirubin value in the 95th percentile for their age on the nomogram, or high-intermediate risk, defined by a value in the 75th or higher percentile for age, Dr. Wickremasinghe said.

The average monthly nursery census was similar in each group, at 151 infants during the first period and 161 infants during the second.

Dr. Wickremasinghe acknowledged that the study limitations were that it was retrospective, that TcB values were plotted on a TSB nomogram, and that it may be difficult to generalize the results to other ethnicities because the population was predominantly white. The effect of TcB screening on costs was not determined, but may be analyzed in the future.

During a discussion of the findings, Dr. M. Jeffrey Maisels, chair of pediatrics at Beaumont Hospitals in Royal Oak, Mich., applauded the authors for adjusting TcB values in the analysis, noting that such values have been as much as 2–3 mg higher than those obtained with other methods in some studies. He said that although it may never be known if predischarge bilirubin screening can prevent an infant from developing kernicterus, screening does seem to reduce the number of infants readmitted with very high bilirubin levels.

This view is supported by a recent prospective study reporting a dramatic decline in severe hyperbilirubinemia among more than 1 million infants born between May 2004 and December 2008. The incidence of infants with total bilirubin levels of 25.0–29.9 mg/dL declined from 43/100,000 before implementation of universal predischarge bilirubin screening to 27/100,000 after implementation, while the incidence of infants with total bilirubin levels of at least 30 mg/dL dropped from 9/100,000 to 3/100,000. The change was associated with a small but statistically significant increase in use of phototherapy (Pediatrics 2010;125:e1143–8).

Hyperbilirubinemia is being missed because more newborns are discharged within 2 days of birth.

Source DR. WICKREMASINGHE

FT. LAUDERDALE, FLA. — What do atypical antipsychotics, an analeptic, and targeted magnets have in common? They all might play a role in the treatment of anorexia nervosa.

“When you have a disorder that is so treatment resistant, it's like metastatic breast cancer; you have to think outside the box for new interventions,” Dr. Allan S. Kaplan said at a workshop on eating disorders at the meeting.

Current statistics indicate that 20% of patients diagnosed with anorexia are resistant to any intervention, and remain chronically ill and disabled. The needs of these patients have been largely neglected by the field, even though their numbers continue to grow as a result of the mortality gradually decreasing from 22% in older studies to about 8%-10% today, said Dr. Kaplan, the Loretta Anne Rogers Chair in Eating Disorders and professor of psychiatry at the University of Toronto.

In his experience, many of these patients are now in their 40s and 50s, and have been ill for 20-30 years. Most suffer from significant medical complications, including renal failure, cardiac arrhythmias, and osteoporosis with resulting hip fractures that have left them wheelchair-bound.

“They are unbelievably disabled,” he said. “They are more disabled on quality-of-life measurements than a comparative group of schizophrenics in the hospital. It's a sobering experience to spend time with these patients.”

One novel approach that might be useful is use of repetitive transcranial magnetic stimulation (rTMS), which has been shown to be effective in some patients with depression, schizophrenia, and obsessive-compulsive disorder. Current magnets stimulate superficial cortical areas of the brain, but Dr. Kaplan suggests that a better target might be the insula—a cerebral cortex structure located deep within the lateral fissure that plays a role in interoceptive awareness and motor control. His group recently completed an unpublished meta-analysis of neuroimaging studies in anorexia that provides evidence for overactivity in the insula.

The team members have subsequently contracted with an Israeli biotechnology firm to construct a patented magnet for rTMS that will specifically target the insula. They also plan to launch an open-label pilot trial of rTMS for anorexia shortly.

The approach is not without controversy, Dr. Kaplan acknowledged. Although the seizure rate with rTMS is very low in patients with depression, patients with anorexia are at an increased risk for seizures at a rate of about 10% in general.

“It's a bit of a shot in the dark, but when you have no other effective treatment, you have to do that,” he said.

Atypical antipsychotics have come under increased scrutiny for anorexia, but with limited success in the few small studies and case reports to date. A recent meta-analysis of 43 publications concluded that there is not enough evidence in anorexia to confirm that these medications increase weight (Eur. Eat. Disord. Rev. 2010;18:10-21).

Olanzapine is an atypical antipsychotic that has been the most reported drug in the literature for treating anorexia and has been the subject of three small randomized, controlled trials. Researchers in Ottawa showed that 10 weeks of olanzapine plus intensive day treatment resulted in faster weight gain and a greater decrease in obsessive symptoms compared with placebo in 34 patients with anorexia, but the amount of weight gain was the same overall (Am. J. Psychiatry 2008;165:1281-8).

Dr. Evelyn Attia from New York State Psychiatric Institute/Columbia University and Dr. Kaplan reported in a separate unpublished trial supported by a developmental grant from the National Institute of Mental Health in 2005 that patients gained a mean of almost 2 kg after 8 weeks of up to 10 mg olanzapine. Patients credited this weight gain not to an increase in hunger, but to being less anxious and consumed by thoughts of weight and shape. Importantly, there was absolutely no change in lipids, glucose, or insulin sensitivity, suggesting something might be different about the way the anorexic brain handles these drugs, Dr. Kaplan said. The problem with olanzapine, however, is compliance, said Dr. Kaplan, noting that patients with eating disorders are well-informed of its side effect of stimulating weight gain. Aripiprazole has been found to be less likely to cause significant weight gain in schizophrenia patients and was more acceptable in another small unpublished trial reported by Dr. Kaplan and his associates in 2005. Unfortunately, it had little impact on weight or measures of anxiety or depression in the eight patients in which it was tried, he said.

Positive results on both weight gain and cognition have been seen with ziprasidone and quetiapine, but their use has been limited by concerns about QT interval prolongation, which is already an issue for anorexics. Because of this concern, olanzapine was selected instead of ziprasidone as the study drug for a large multicenter anorexia trial that is planned, he said.

The rationale for using atypical antipsychotics in anorexia lies not just in their potential side effect of weight gain, but also in their ability to ameliorate the core disturbances in cognition, affect regulation, and motor activity seen in patients with anorexia nervosa, Dr. Kaplan explained.

“Anorexia is often underestimated as being a disturbance of motor activity,” he said. “Our patients are hyperactive in the face of increasing emaciation, which you don't see in any other condition.”

Finally, workshop attendee Dr. Charles Price reported an acute response in a single patient with anorexia given modafinil and followed for 6 months. In a counterintuitive finding, the drug did not have the weight loss aspects observed with other stimulants.

“Basically, it cured her anorexia; now it is an 'N' of one,” said Dr. Price, who is in private practice in Reno, Nev.

“It's still worth writing up as a case report,” Dr. Kaplan said to the agreement of the audience.

Disclosures: Dr. Kaplan reported having no conflicts of interest. Dr. Attia reported having received research support from Pfizer and Eli Lilly.

'Anorexia is often underestimated as being a disturbance of motor activity.'

Source DR. KAPLAN

FT. LAUDERDALE, FLA. — What do atypical antipsychotics, an analeptic, and targeted magnets have in common? They all might play a role in the treatment of anorexia nervosa.

“When you have a disorder that is so treatment resistant, it's like metastatic breast cancer; you have to think outside the box for new interventions,” Dr. Allan S. Kaplan said at a workshop on eating disorders at the meeting.

Current statistics indicate that 20% of patients diagnosed with anorexia are resistant to any intervention, and remain chronically ill and disabled. The needs of these patients have been largely neglected by the field, even though their numbers continue to grow as a result of the mortality gradually decreasing from 22% in older studies to about 8%-10% today, said Dr. Kaplan, the Loretta Anne Rogers Chair in Eating Disorders and professor of psychiatry at the University of Toronto.

In his experience, many of these patients are now in their 40s and 50s, and have been ill for 20-30 years. Most suffer from significant medical complications, including renal failure, cardiac arrhythmias, and osteoporosis with resulting hip fractures that have left them wheelchair-bound.

“They are unbelievably disabled,” he said. “They are more disabled on quality-of-life measurements than a comparative group of schizophrenics in the hospital. It's a sobering experience to spend time with these patients.”

One novel approach that might be useful is use of repetitive transcranial magnetic stimulation (rTMS), which has been shown to be effective in some patients with depression, schizophrenia, and obsessive-compulsive disorder. Current magnets stimulate superficial cortical areas of the brain, but Dr. Kaplan suggests that a better target might be the insula—a cerebral cortex structure located deep within the lateral fissure that plays a role in interoceptive awareness and motor control. His group recently completed an unpublished meta-analysis of neuroimaging studies in anorexia that provides evidence for overactivity in the insula.

The team members have subsequently contracted with an Israeli biotechnology firm to construct a patented magnet for rTMS that will specifically target the insula. They also plan to launch an open-label pilot trial of rTMS for anorexia shortly.

The approach is not without controversy, Dr. Kaplan acknowledged. Although the seizure rate with rTMS is very low in patients with depression, patients with anorexia are at an increased risk for seizures at a rate of about 10% in general.

“It's a bit of a shot in the dark, but when you have no other effective treatment, you have to do that,” he said.

Atypical antipsychotics have come under increased scrutiny for anorexia, but with limited success in the few small studies and case reports to date. A recent meta-analysis of 43 publications concluded that there is not enough evidence in anorexia to confirm that these medications increase weight (Eur. Eat. Disord. Rev. 2010;18:10-21).

Olanzapine is an atypical antipsychotic that has been the most reported drug in the literature for treating anorexia and has been the subject of three small randomized, controlled trials. Researchers in Ottawa showed that 10 weeks of olanzapine plus intensive day treatment resulted in faster weight gain and a greater decrease in obsessive symptoms compared with placebo in 34 patients with anorexia, but the amount of weight gain was the same overall (Am. J. Psychiatry 2008;165:1281-8).

Dr. Evelyn Attia from New York State Psychiatric Institute/Columbia University and Dr. Kaplan reported in a separate unpublished trial supported by a developmental grant from the National Institute of Mental Health in 2005 that patients gained a mean of almost 2 kg after 8 weeks of up to 10 mg olanzapine. Patients credited this weight gain not to an increase in hunger, but to being less anxious and consumed by thoughts of weight and shape. Importantly, there was absolutely no change in lipids, glucose, or insulin sensitivity, suggesting something might be different about the way the anorexic brain handles these drugs, Dr. Kaplan said. The problem with olanzapine, however, is compliance, said Dr. Kaplan, noting that patients with eating disorders are well-informed of its side effect of stimulating weight gain. Aripiprazole has been found to be less likely to cause significant weight gain in schizophrenia patients and was more acceptable in another small unpublished trial reported by Dr. Kaplan and his associates in 2005. Unfortunately, it had little impact on weight or measures of anxiety or depression in the eight patients in which it was tried, he said.

Positive results on both weight gain and cognition have been seen with ziprasidone and quetiapine, but their use has been limited by concerns about QT interval prolongation, which is already an issue for anorexics. Because of this concern, olanzapine was selected instead of ziprasidone as the study drug for a large multicenter anorexia trial that is planned, he said.

The rationale for using atypical antipsychotics in anorexia lies not just in their potential side effect of weight gain, but also in their ability to ameliorate the core disturbances in cognition, affect regulation, and motor activity seen in patients with anorexia nervosa, Dr. Kaplan explained.

“Anorexia is often underestimated as being a disturbance of motor activity,” he said. “Our patients are hyperactive in the face of increasing emaciation, which you don't see in any other condition.”

Finally, workshop attendee Dr. Charles Price reported an acute response in a single patient with anorexia given modafinil and followed for 6 months. In a counterintuitive finding, the drug did not have the weight loss aspects observed with other stimulants.

“Basically, it cured her anorexia; now it is an 'N' of one,” said Dr. Price, who is in private practice in Reno, Nev.

“It's still worth writing up as a case report,” Dr. Kaplan said to the agreement of the audience.

Disclosures: Dr. Kaplan reported having no conflicts of interest. Dr. Attia reported having received research support from Pfizer and Eli Lilly.

'Anorexia is often underestimated as being a disturbance of motor activity.'

Source DR. KAPLAN

FT. LAUDERDALE, FLA. — What do atypical antipsychotics, an analeptic, and targeted magnets have in common? They all might play a role in the treatment of anorexia nervosa.

“When you have a disorder that is so treatment resistant, it's like metastatic breast cancer; you have to think outside the box for new interventions,” Dr. Allan S. Kaplan said at a workshop on eating disorders at the meeting.

Current statistics indicate that 20% of patients diagnosed with anorexia are resistant to any intervention, and remain chronically ill and disabled. The needs of these patients have been largely neglected by the field, even though their numbers continue to grow as a result of the mortality gradually decreasing from 22% in older studies to about 8%-10% today, said Dr. Kaplan, the Loretta Anne Rogers Chair in Eating Disorders and professor of psychiatry at the University of Toronto.

In his experience, many of these patients are now in their 40s and 50s, and have been ill for 20-30 years. Most suffer from significant medical complications, including renal failure, cardiac arrhythmias, and osteoporosis with resulting hip fractures that have left them wheelchair-bound.

“They are unbelievably disabled,” he said. “They are more disabled on quality-of-life measurements than a comparative group of schizophrenics in the hospital. It's a sobering experience to spend time with these patients.”

One novel approach that might be useful is use of repetitive transcranial magnetic stimulation (rTMS), which has been shown to be effective in some patients with depression, schizophrenia, and obsessive-compulsive disorder. Current magnets stimulate superficial cortical areas of the brain, but Dr. Kaplan suggests that a better target might be the insula—a cerebral cortex structure located deep within the lateral fissure that plays a role in interoceptive awareness and motor control. His group recently completed an unpublished meta-analysis of neuroimaging studies in anorexia that provides evidence for overactivity in the insula.

The team members have subsequently contracted with an Israeli biotechnology firm to construct a patented magnet for rTMS that will specifically target the insula. They also plan to launch an open-label pilot trial of rTMS for anorexia shortly.

The approach is not without controversy, Dr. Kaplan acknowledged. Although the seizure rate with rTMS is very low in patients with depression, patients with anorexia are at an increased risk for seizures at a rate of about 10% in general.

“It's a bit of a shot in the dark, but when you have no other effective treatment, you have to do that,” he said.

Atypical antipsychotics have come under increased scrutiny for anorexia, but with limited success in the few small studies and case reports to date. A recent meta-analysis of 43 publications concluded that there is not enough evidence in anorexia to confirm that these medications increase weight (Eur. Eat. Disord. Rev. 2010;18:10-21).

Olanzapine is an atypical antipsychotic that has been the most reported drug in the literature for treating anorexia and has been the subject of three small randomized, controlled trials. Researchers in Ottawa showed that 10 weeks of olanzapine plus intensive day treatment resulted in faster weight gain and a greater decrease in obsessive symptoms compared with placebo in 34 patients with anorexia, but the amount of weight gain was the same overall (Am. J. Psychiatry 2008;165:1281-8).

Dr. Evelyn Attia from New York State Psychiatric Institute/Columbia University and Dr. Kaplan reported in a separate unpublished trial supported by a developmental grant from the National Institute of Mental Health in 2005 that patients gained a mean of almost 2 kg after 8 weeks of up to 10 mg olanzapine. Patients credited this weight gain not to an increase in hunger, but to being less anxious and consumed by thoughts of weight and shape. Importantly, there was absolutely no change in lipids, glucose, or insulin sensitivity, suggesting something might be different about the way the anorexic brain handles these drugs, Dr. Kaplan said. The problem with olanzapine, however, is compliance, said Dr. Kaplan, noting that patients with eating disorders are well-informed of its side effect of stimulating weight gain. Aripiprazole has been found to be less likely to cause significant weight gain in schizophrenia patients and was more acceptable in another small unpublished trial reported by Dr. Kaplan and his associates in 2005. Unfortunately, it had little impact on weight or measures of anxiety or depression in the eight patients in which it was tried, he said.

Positive results on both weight gain and cognition have been seen with ziprasidone and quetiapine, but their use has been limited by concerns about QT interval prolongation, which is already an issue for anorexics. Because of this concern, olanzapine was selected instead of ziprasidone as the study drug for a large multicenter anorexia trial that is planned, he said.

The rationale for using atypical antipsychotics in anorexia lies not just in their potential side effect of weight gain, but also in their ability to ameliorate the core disturbances in cognition, affect regulation, and motor activity seen in patients with anorexia nervosa, Dr. Kaplan explained.

“Anorexia is often underestimated as being a disturbance of motor activity,” he said. “Our patients are hyperactive in the face of increasing emaciation, which you don't see in any other condition.”

Finally, workshop attendee Dr. Charles Price reported an acute response in a single patient with anorexia given modafinil and followed for 6 months. In a counterintuitive finding, the drug did not have the weight loss aspects observed with other stimulants.

“Basically, it cured her anorexia; now it is an 'N' of one,” said Dr. Price, who is in private practice in Reno, Nev.

“It's still worth writing up as a case report,” Dr. Kaplan said to the agreement of the audience.

Disclosures: Dr. Kaplan reported having no conflicts of interest. Dr. Attia reported having received research support from Pfizer and Eli Lilly.

'Anorexia is often underestimated as being a disturbance of motor activity.'

Source DR. KAPLAN