Michele G. Sullivan

Deep brain stimulation of the subcallosal cingulate area appears to significantly decrease the symptoms of treatment-resistant depression.

An open-label trial of 21 patients who had failed multiple medical and electroconvulsive treatments found that the electrical implants improved depression scores in up to 62% of patients, Dr. Andres M. Lozano reported in the November issue of the Journal of Neurosurgery (Epub doi: 10.3171/2011.10.JNS102122).

Photo courtesy St. Jude Medical Inc.

A prior study (J. Neurosurg. 2009;111:1209-15), showed similar positive results but was conducted only at a single center. The new study, with data on patients from three different facilities, confirms the procedure’s success, and speaks to its reproducibility in varied hands, said Dr. Lozano of the University of Toronto and his coauthors.

"The results of this multicenter study suggest that the [subcallosal cingulate gyrus] can be reliably targeted for [deep brain stimulation] electrode implantation and that the clinical effects of [the procedure] for [treatment-resistant depression] are robust and reproducible across centers."

Dr. Lozano and his colleagues reported on 21 patients who underwent deep brain stimulation for treatment-resistant depression at the universities of Toronto and British Columbia, and at McGill University in Montreal. All patients had failed repeated medical therapies; 90% had undergone electroconvulsive therapy that proved ineffective. All of the patients had also received psychotherapy. Despite treatment, their depressive symptoms remained serious: (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 47; mean Hamilton Rating Scale for Depression [HRSD-17] score, 28).

The patients were a mean of 47 years old and reported a mean of seven episodes of major depression during their lifetime. The current major depressive episode had lasted a mean of 5 years.

Researchers initially chose the subcallosal cingulate gyrus because it is involved in processing the emotion of acute sadness. It also seems to be overactive in subjects with treatment-resistant depression; this theory is supported by observation that some effective treatments reduce blood flow or metabolic activity in the subcallosal cingulate gyrus (SCG), the authors said.

During surgery, bilateral SCG targets were identified by three-dimensional magnetic resonance imaging. The electrodes were inserted into the targets and fixed to the skull. The surgeon then connected the electrodes to a pulse generator located in the infraclavicular region.

The mean stimulation amplitude after surgery was 4.2 mA, increasing to 4.9 at 6 months, and 5.2 at 12 months.

Patients were considered responders if they experienced at least a 50% reduction in the HRSD-17 score. At 1 month, 57% were classified as responders; at 6 months, 48%, and by 12 months, 29%.

The reductions in depressive symptoms were associated with global improvements in the patients, the authors said. "Patients shifted from being severely ill to being less ill after surgery, and the majority of patients improved with surgery. At 12 months, none of the 20 patients who remained in treatment were worse than at baseline." According to a graph in the paper, the actual number of patients who improved was 15 at 3 months, 13 at 6 months, and 13 at 12 months.

When evaluated with the Clinical Global Impression of Severity (CGI-S) rating scale, 70% were categorized as severely or extremely ill at baseline, while, at 1 year after surgery, 80% experienced clinical improvement and none rated as severely or extremely ill.

One patient committed suicide by drug overdose in the 8th postsurgical week. Another patient attempted suicide between the week 4 and week 5 follow-up visits. "The underlying trigger was thought to be a family matter," the authors noted.

Nine patients reported nausea, vomiting, and diarrhea, although it was unclear whether those adverse events were related to stimulating that region of the brain. One patient experienced a lead extension malfunction immediately after surgery, which required replacing the extension. Another patient experienced superficial skin erosion over a bur site, about 7 weeks after the implant was activated; the incision was revised and this resolved.

Other side effects included headache more than 1 month after surgery (six patients), agitation in reaction to amplitude increase (three), dizziness (three), polyuria (two), and weight gain, buzzing in the ears, and insomnia (one each).

The authors also addressed the apparent decrease in effectiveness by 1 year, saying it could be "somewhat of an artifact of the data analysis." Most patients continued to do well: Depression scores improved by 50% or more in a third of the patients, and 62% experiencing an improvement of at least 40%. But, the investigators said, four of the patients who improved the most dropped to the 40% improvement range by 1 year, "a small change that is likely noise, but which has a large impact when using the 50% cutoff for response in a series with a relatively small number of participants."

A recent report on 20 of the patients concluded that the benefit of DBS was long-lasting (Am. J. Psych. 2011;168:502-10).

"The average response rates 1, 2, and 3 years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. At the last follow-up visit (3-6 years), the average response rate was 64.3%," wrote lead author Dr. Sidney Kennedy of the University of Toronto.

The present study raises some additional questions, said Dr. Lozano and his coauthors. Since the procedure was open label, the analysis cannot account for a placebo effect. Additionally, they said, disease heterogeneity, anatomic variation, and stimulation variants might play a part in which patients respond and which do not.

Nor is the SCG the only possible treatment target, they said. "It is clear that other brain targets may also be useful ... including the nucleus accumbens and the anterior limb of the internal capsule. The specific attributes and potential uses of each of these possible therapeutic targets will require much more investigation."

According to a press statement, St. Jude Medical, the company that created the DBS system in the study, is now conducting a similar study at 20 facilities in the United States and internationally, under a U.S. Food and Drug Administration Investigational Device Exemption.

Dr. Lozano disclosed that he holds intellectual property rights in the field of using DBS for depression and is a consultant for St. Jude Medical Inc. in Minneapolis, which developed the device used in this study.* Other authors indicated relationships with multiple drug companies. Dr. Burchiel reported having no disclosures.

*CLARIFICATION, 11/29/11: Information was added to clarify this sentence.

Deep brain stimulation of the subcallosal cingulate area appears to significantly decrease the symptoms of treatment-resistant depression.

An open-label trial of 21 patients who had failed multiple medical and electroconvulsive treatments found that the electrical implants improved depression scores in up to 62% of patients, Dr. Andres M. Lozano reported in the November issue of the Journal of Neurosurgery (Epub doi: 10.3171/2011.10.JNS102122).

Photo courtesy St. Jude Medical Inc.

A prior study (J. Neurosurg. 2009;111:1209-15), showed similar positive results but was conducted only at a single center. The new study, with data on patients from three different facilities, confirms the procedure’s success, and speaks to its reproducibility in varied hands, said Dr. Lozano of the University of Toronto and his coauthors.

"The results of this multicenter study suggest that the [subcallosal cingulate gyrus] can be reliably targeted for [deep brain stimulation] electrode implantation and that the clinical effects of [the procedure] for [treatment-resistant depression] are robust and reproducible across centers."

Dr. Lozano and his colleagues reported on 21 patients who underwent deep brain stimulation for treatment-resistant depression at the universities of Toronto and British Columbia, and at McGill University in Montreal. All patients had failed repeated medical therapies; 90% had undergone electroconvulsive therapy that proved ineffective. All of the patients had also received psychotherapy. Despite treatment, their depressive symptoms remained serious: (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 47; mean Hamilton Rating Scale for Depression [HRSD-17] score, 28).

The patients were a mean of 47 years old and reported a mean of seven episodes of major depression during their lifetime. The current major depressive episode had lasted a mean of 5 years.

Researchers initially chose the subcallosal cingulate gyrus because it is involved in processing the emotion of acute sadness. It also seems to be overactive in subjects with treatment-resistant depression; this theory is supported by observation that some effective treatments reduce blood flow or metabolic activity in the subcallosal cingulate gyrus (SCG), the authors said.

During surgery, bilateral SCG targets were identified by three-dimensional magnetic resonance imaging. The electrodes were inserted into the targets and fixed to the skull. The surgeon then connected the electrodes to a pulse generator located in the infraclavicular region.

The mean stimulation amplitude after surgery was 4.2 mA, increasing to 4.9 at 6 months, and 5.2 at 12 months.

Patients were considered responders if they experienced at least a 50% reduction in the HRSD-17 score. At 1 month, 57% were classified as responders; at 6 months, 48%, and by 12 months, 29%.

The reductions in depressive symptoms were associated with global improvements in the patients, the authors said. "Patients shifted from being severely ill to being less ill after surgery, and the majority of patients improved with surgery. At 12 months, none of the 20 patients who remained in treatment were worse than at baseline." According to a graph in the paper, the actual number of patients who improved was 15 at 3 months, 13 at 6 months, and 13 at 12 months.

When evaluated with the Clinical Global Impression of Severity (CGI-S) rating scale, 70% were categorized as severely or extremely ill at baseline, while, at 1 year after surgery, 80% experienced clinical improvement and none rated as severely or extremely ill.

One patient committed suicide by drug overdose in the 8th postsurgical week. Another patient attempted suicide between the week 4 and week 5 follow-up visits. "The underlying trigger was thought to be a family matter," the authors noted.

Nine patients reported nausea, vomiting, and diarrhea, although it was unclear whether those adverse events were related to stimulating that region of the brain. One patient experienced a lead extension malfunction immediately after surgery, which required replacing the extension. Another patient experienced superficial skin erosion over a bur site, about 7 weeks after the implant was activated; the incision was revised and this resolved.

Other side effects included headache more than 1 month after surgery (six patients), agitation in reaction to amplitude increase (three), dizziness (three), polyuria (two), and weight gain, buzzing in the ears, and insomnia (one each).

The authors also addressed the apparent decrease in effectiveness by 1 year, saying it could be "somewhat of an artifact of the data analysis." Most patients continued to do well: Depression scores improved by 50% or more in a third of the patients, and 62% experiencing an improvement of at least 40%. But, the investigators said, four of the patients who improved the most dropped to the 40% improvement range by 1 year, "a small change that is likely noise, but which has a large impact when using the 50% cutoff for response in a series with a relatively small number of participants."

A recent report on 20 of the patients concluded that the benefit of DBS was long-lasting (Am. J. Psych. 2011;168:502-10).

"The average response rates 1, 2, and 3 years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. At the last follow-up visit (3-6 years), the average response rate was 64.3%," wrote lead author Dr. Sidney Kennedy of the University of Toronto.

The present study raises some additional questions, said Dr. Lozano and his coauthors. Since the procedure was open label, the analysis cannot account for a placebo effect. Additionally, they said, disease heterogeneity, anatomic variation, and stimulation variants might play a part in which patients respond and which do not.

Nor is the SCG the only possible treatment target, they said. "It is clear that other brain targets may also be useful ... including the nucleus accumbens and the anterior limb of the internal capsule. The specific attributes and potential uses of each of these possible therapeutic targets will require much more investigation."

According to a press statement, St. Jude Medical, the company that created the DBS system in the study, is now conducting a similar study at 20 facilities in the United States and internationally, under a U.S. Food and Drug Administration Investigational Device Exemption.

Dr. Lozano disclosed that he holds intellectual property rights in the field of using DBS for depression and is a consultant for St. Jude Medical Inc. in Minneapolis, which developed the device used in this study.* Other authors indicated relationships with multiple drug companies. Dr. Burchiel reported having no disclosures.

*CLARIFICATION, 11/29/11: Information was added to clarify this sentence.

Deep brain stimulation of the subcallosal cingulate area appears to significantly decrease the symptoms of treatment-resistant depression.

An open-label trial of 21 patients who had failed multiple medical and electroconvulsive treatments found that the electrical implants improved depression scores in up to 62% of patients, Dr. Andres M. Lozano reported in the November issue of the Journal of Neurosurgery (Epub doi: 10.3171/2011.10.JNS102122).

Photo courtesy St. Jude Medical Inc.

A prior study (J. Neurosurg. 2009;111:1209-15), showed similar positive results but was conducted only at a single center. The new study, with data on patients from three different facilities, confirms the procedure’s success, and speaks to its reproducibility in varied hands, said Dr. Lozano of the University of Toronto and his coauthors.

"The results of this multicenter study suggest that the [subcallosal cingulate gyrus] can be reliably targeted for [deep brain stimulation] electrode implantation and that the clinical effects of [the procedure] for [treatment-resistant depression] are robust and reproducible across centers."

Dr. Lozano and his colleagues reported on 21 patients who underwent deep brain stimulation for treatment-resistant depression at the universities of Toronto and British Columbia, and at McGill University in Montreal. All patients had failed repeated medical therapies; 90% had undergone electroconvulsive therapy that proved ineffective. All of the patients had also received psychotherapy. Despite treatment, their depressive symptoms remained serious: (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 47; mean Hamilton Rating Scale for Depression [HRSD-17] score, 28).

The patients were a mean of 47 years old and reported a mean of seven episodes of major depression during their lifetime. The current major depressive episode had lasted a mean of 5 years.

Researchers initially chose the subcallosal cingulate gyrus because it is involved in processing the emotion of acute sadness. It also seems to be overactive in subjects with treatment-resistant depression; this theory is supported by observation that some effective treatments reduce blood flow or metabolic activity in the subcallosal cingulate gyrus (SCG), the authors said.

During surgery, bilateral SCG targets were identified by three-dimensional magnetic resonance imaging. The electrodes were inserted into the targets and fixed to the skull. The surgeon then connected the electrodes to a pulse generator located in the infraclavicular region.

The mean stimulation amplitude after surgery was 4.2 mA, increasing to 4.9 at 6 months, and 5.2 at 12 months.

Patients were considered responders if they experienced at least a 50% reduction in the HRSD-17 score. At 1 month, 57% were classified as responders; at 6 months, 48%, and by 12 months, 29%.

The reductions in depressive symptoms were associated with global improvements in the patients, the authors said. "Patients shifted from being severely ill to being less ill after surgery, and the majority of patients improved with surgery. At 12 months, none of the 20 patients who remained in treatment were worse than at baseline." According to a graph in the paper, the actual number of patients who improved was 15 at 3 months, 13 at 6 months, and 13 at 12 months.

When evaluated with the Clinical Global Impression of Severity (CGI-S) rating scale, 70% were categorized as severely or extremely ill at baseline, while, at 1 year after surgery, 80% experienced clinical improvement and none rated as severely or extremely ill.

One patient committed suicide by drug overdose in the 8th postsurgical week. Another patient attempted suicide between the week 4 and week 5 follow-up visits. "The underlying trigger was thought to be a family matter," the authors noted.

Nine patients reported nausea, vomiting, and diarrhea, although it was unclear whether those adverse events were related to stimulating that region of the brain. One patient experienced a lead extension malfunction immediately after surgery, which required replacing the extension. Another patient experienced superficial skin erosion over a bur site, about 7 weeks after the implant was activated; the incision was revised and this resolved.

Other side effects included headache more than 1 month after surgery (six patients), agitation in reaction to amplitude increase (three), dizziness (three), polyuria (two), and weight gain, buzzing in the ears, and insomnia (one each).

The authors also addressed the apparent decrease in effectiveness by 1 year, saying it could be "somewhat of an artifact of the data analysis." Most patients continued to do well: Depression scores improved by 50% or more in a third of the patients, and 62% experiencing an improvement of at least 40%. But, the investigators said, four of the patients who improved the most dropped to the 40% improvement range by 1 year, "a small change that is likely noise, but which has a large impact when using the 50% cutoff for response in a series with a relatively small number of participants."

A recent report on 20 of the patients concluded that the benefit of DBS was long-lasting (Am. J. Psych. 2011;168:502-10).

"The average response rates 1, 2, and 3 years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. At the last follow-up visit (3-6 years), the average response rate was 64.3%," wrote lead author Dr. Sidney Kennedy of the University of Toronto.

The present study raises some additional questions, said Dr. Lozano and his coauthors. Since the procedure was open label, the analysis cannot account for a placebo effect. Additionally, they said, disease heterogeneity, anatomic variation, and stimulation variants might play a part in which patients respond and which do not.

Nor is the SCG the only possible treatment target, they said. "It is clear that other brain targets may also be useful ... including the nucleus accumbens and the anterior limb of the internal capsule. The specific attributes and potential uses of each of these possible therapeutic targets will require much more investigation."

According to a press statement, St. Jude Medical, the company that created the DBS system in the study, is now conducting a similar study at 20 facilities in the United States and internationally, under a U.S. Food and Drug Administration Investigational Device Exemption.

Dr. Lozano disclosed that he holds intellectual property rights in the field of using DBS for depression and is a consultant for St. Jude Medical Inc. in Minneapolis, which developed the device used in this study.* Other authors indicated relationships with multiple drug companies. Dr. Burchiel reported having no disclosures.

*CLARIFICATION, 11/29/11: Information was added to clarify this sentence.

Infants immunized in the afternoon who mount a temperature soon afterward sleep more over the next 24 hours than do those vaccinated early in the day and those whose temperatures don’t increase, according to a study published online Nov. 28 in Pediatrics.

While prophylactic acetaminophen did increase sleep time slightly, the association became nonsignificant in a multivariate analysis of the randomized controlled trial. The study suggests that suppressing the body’s natural immune response with an antipyretic agent may actually work against sleep, and even the level of immune response, Linda Franck, Ph.D., and her colleagues wrote (Pediatrics 2011 Nov. 28 [doi:10.1542/peds.2011-1712]).

"Temperature increase is considered a marker of immune response and is thought to be related to the release of endogenous pyrogens ... associated with increased T cell activity, enhanced antigen recognition, and immune response," wrote Dr. Franck and her colleagues at the University of California, San Francisco. "Therefore, longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

The investigators examined data from a completed study on sleep disruption in new mothers. The study included a component on prophylactic acetaminophen to reduce infant sleep disturbance after immunization.

For this portion of the study, the researchers had complete data on 70 infants who were randomized into two groups: a control group of standard care and an intervention group in which mothers used predosed acetaminophen 30 minutes before an immunization and every 4 hours afterward, for a total of five doses.

Each infant was fitted with an anklet actigraph that recorded 24 hours of motion data before and after immunization, from which sleep movement was extrapolated. Mothers also used sleep diaries to record infants’ sleep, and digital thermometers to record infants’ axillary temperatures each morning and evening over the 72-hour study period.

"Longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

Mothers’ mean age was 27 years. The group comprised 31% Asian, 26% white, 23% Hispanic, 11% black, and 9% mixed or other race. Most mothers (90%) had finished high school, and 29% had completed college.

The infants’ mean age was almost 9 weeks and the mean birth weight was 3.4 kg. Most (80%) had received all recommended vaccines by the time of enrollment.

Despite the randomization, most infants in the study (80%) got acetaminophen either at the time of immunization or thereafter. However, the researchers noted, infants in the active group were more likely to have gotten the first dose at the time of immunization, and those in the control group were more likely to get it later for symptoms of fever or discomfort.

Those in the intervention group had significantly higher axillary temperatures in the 24 hours after immunization (mean of 0.23 centigrade higher), compared with their temperature prior to immunization. The results of a comparison of all three groups were not statistically significant.

Those in the intervention group also slept significantly longer than did those in the control group (average 69 minutes). "Most of the additional sleep was active, whereas quiet sleep time increased only slightly," Dr. Franck and her colleagues said.

They found a significant correlation between longer sleep and increased axillary temperature. There was also a significant association between additional sleep and the timing of the immunization; infants vaccinated after 1:30 p.m. slept more than did those immunized earlier in the day. Many of the latter slept less than they had in the prior 24 hours.

In a multivariate regression analysis, higher postimmunization axillary temperatures and afternoon immunizations were the only significant predictors of increased sleep over the next 24 hours; these accounted for 32.5% of the variance in postimmunization sleep time.

Although the researchers said the findings proved their hypotheses, they admitted that overall acetaminophen use might have affected the final analysis, noting that "71% in the usual-care group received acetaminophen and 20% received it prophylactically, which made it more difficult to detect group differences."

Only 14 infants in the study did not get the drug. Those 56 who did receive it had smaller increases in postimmunization sleep time regardless of when the drug was given. But because acetaminophen was not a significant factor in the final analysis, increased body temperature could be the main reason for the increased sleep, they said.

"Our findings are consistent [with other studies] and taken together, suggest that antipyretic agents should not be given prophylactically for infant immunization," to allow for natural body temperature increases, Dr. Franck and her colleagues said.

"If further research confirms relationships between the time of day of vaccine administration, increased sleep, and antibody responses, then our findings suggest that afternoon immunizations should be recommended, to facilitate increased infant sleep in the 24 hours after immunization," they said.

The study was supported by the National Institutes of Health. None of the researchers had any relevant financial disclosures.

Infants immunized in the afternoon who mount a temperature soon afterward sleep more over the next 24 hours than do those vaccinated early in the day and those whose temperatures don’t increase, according to a study published online Nov. 28 in Pediatrics.

While prophylactic acetaminophen did increase sleep time slightly, the association became nonsignificant in a multivariate analysis of the randomized controlled trial. The study suggests that suppressing the body’s natural immune response with an antipyretic agent may actually work against sleep, and even the level of immune response, Linda Franck, Ph.D., and her colleagues wrote (Pediatrics 2011 Nov. 28 [doi:10.1542/peds.2011-1712]).

"Temperature increase is considered a marker of immune response and is thought to be related to the release of endogenous pyrogens ... associated with increased T cell activity, enhanced antigen recognition, and immune response," wrote Dr. Franck and her colleagues at the University of California, San Francisco. "Therefore, longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

The investigators examined data from a completed study on sleep disruption in new mothers. The study included a component on prophylactic acetaminophen to reduce infant sleep disturbance after immunization.

For this portion of the study, the researchers had complete data on 70 infants who were randomized into two groups: a control group of standard care and an intervention group in which mothers used predosed acetaminophen 30 minutes before an immunization and every 4 hours afterward, for a total of five doses.

Each infant was fitted with an anklet actigraph that recorded 24 hours of motion data before and after immunization, from which sleep movement was extrapolated. Mothers also used sleep diaries to record infants’ sleep, and digital thermometers to record infants’ axillary temperatures each morning and evening over the 72-hour study period.

"Longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

Mothers’ mean age was 27 years. The group comprised 31% Asian, 26% white, 23% Hispanic, 11% black, and 9% mixed or other race. Most mothers (90%) had finished high school, and 29% had completed college.

The infants’ mean age was almost 9 weeks and the mean birth weight was 3.4 kg. Most (80%) had received all recommended vaccines by the time of enrollment.

Despite the randomization, most infants in the study (80%) got acetaminophen either at the time of immunization or thereafter. However, the researchers noted, infants in the active group were more likely to have gotten the first dose at the time of immunization, and those in the control group were more likely to get it later for symptoms of fever or discomfort.

Those in the intervention group had significantly higher axillary temperatures in the 24 hours after immunization (mean of 0.23 centigrade higher), compared with their temperature prior to immunization. The results of a comparison of all three groups were not statistically significant.

Those in the intervention group also slept significantly longer than did those in the control group (average 69 minutes). "Most of the additional sleep was active, whereas quiet sleep time increased only slightly," Dr. Franck and her colleagues said.

They found a significant correlation between longer sleep and increased axillary temperature. There was also a significant association between additional sleep and the timing of the immunization; infants vaccinated after 1:30 p.m. slept more than did those immunized earlier in the day. Many of the latter slept less than they had in the prior 24 hours.

In a multivariate regression analysis, higher postimmunization axillary temperatures and afternoon immunizations were the only significant predictors of increased sleep over the next 24 hours; these accounted for 32.5% of the variance in postimmunization sleep time.

Although the researchers said the findings proved their hypotheses, they admitted that overall acetaminophen use might have affected the final analysis, noting that "71% in the usual-care group received acetaminophen and 20% received it prophylactically, which made it more difficult to detect group differences."

Only 14 infants in the study did not get the drug. Those 56 who did receive it had smaller increases in postimmunization sleep time regardless of when the drug was given. But because acetaminophen was not a significant factor in the final analysis, increased body temperature could be the main reason for the increased sleep, they said.

"Our findings are consistent [with other studies] and taken together, suggest that antipyretic agents should not be given prophylactically for infant immunization," to allow for natural body temperature increases, Dr. Franck and her colleagues said.

"If further research confirms relationships between the time of day of vaccine administration, increased sleep, and antibody responses, then our findings suggest that afternoon immunizations should be recommended, to facilitate increased infant sleep in the 24 hours after immunization," they said.

The study was supported by the National Institutes of Health. None of the researchers had any relevant financial disclosures.

Infants immunized in the afternoon who mount a temperature soon afterward sleep more over the next 24 hours than do those vaccinated early in the day and those whose temperatures don’t increase, according to a study published online Nov. 28 in Pediatrics.

While prophylactic acetaminophen did increase sleep time slightly, the association became nonsignificant in a multivariate analysis of the randomized controlled trial. The study suggests that suppressing the body’s natural immune response with an antipyretic agent may actually work against sleep, and even the level of immune response, Linda Franck, Ph.D., and her colleagues wrote (Pediatrics 2011 Nov. 28 [doi:10.1542/peds.2011-1712]).

"Temperature increase is considered a marker of immune response and is thought to be related to the release of endogenous pyrogens ... associated with increased T cell activity, enhanced antigen recognition, and immune response," wrote Dr. Franck and her colleagues at the University of California, San Francisco. "Therefore, longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

The investigators examined data from a completed study on sleep disruption in new mothers. The study included a component on prophylactic acetaminophen to reduce infant sleep disturbance after immunization.

For this portion of the study, the researchers had complete data on 70 infants who were randomized into two groups: a control group of standard care and an intervention group in which mothers used predosed acetaminophen 30 minutes before an immunization and every 4 hours afterward, for a total of five doses.

Each infant was fitted with an anklet actigraph that recorded 24 hours of motion data before and after immunization, from which sleep movement was extrapolated. Mothers also used sleep diaries to record infants’ sleep, and digital thermometers to record infants’ axillary temperatures each morning and evening over the 72-hour study period.

"Longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

Mothers’ mean age was 27 years. The group comprised 31% Asian, 26% white, 23% Hispanic, 11% black, and 9% mixed or other race. Most mothers (90%) had finished high school, and 29% had completed college.

The infants’ mean age was almost 9 weeks and the mean birth weight was 3.4 kg. Most (80%) had received all recommended vaccines by the time of enrollment.

Despite the randomization, most infants in the study (80%) got acetaminophen either at the time of immunization or thereafter. However, the researchers noted, infants in the active group were more likely to have gotten the first dose at the time of immunization, and those in the control group were more likely to get it later for symptoms of fever or discomfort.

Those in the intervention group had significantly higher axillary temperatures in the 24 hours after immunization (mean of 0.23 centigrade higher), compared with their temperature prior to immunization. The results of a comparison of all three groups were not statistically significant.

Those in the intervention group also slept significantly longer than did those in the control group (average 69 minutes). "Most of the additional sleep was active, whereas quiet sleep time increased only slightly," Dr. Franck and her colleagues said.

They found a significant correlation between longer sleep and increased axillary temperature. There was also a significant association between additional sleep and the timing of the immunization; infants vaccinated after 1:30 p.m. slept more than did those immunized earlier in the day. Many of the latter slept less than they had in the prior 24 hours.

In a multivariate regression analysis, higher postimmunization axillary temperatures and afternoon immunizations were the only significant predictors of increased sleep over the next 24 hours; these accounted for 32.5% of the variance in postimmunization sleep time.

Although the researchers said the findings proved their hypotheses, they admitted that overall acetaminophen use might have affected the final analysis, noting that "71% in the usual-care group received acetaminophen and 20% received it prophylactically, which made it more difficult to detect group differences."

Only 14 infants in the study did not get the drug. Those 56 who did receive it had smaller increases in postimmunization sleep time regardless of when the drug was given. But because acetaminophen was not a significant factor in the final analysis, increased body temperature could be the main reason for the increased sleep, they said.

"Our findings are consistent [with other studies] and taken together, suggest that antipyretic agents should not be given prophylactically for infant immunization," to allow for natural body temperature increases, Dr. Franck and her colleagues said.

"If further research confirms relationships between the time of day of vaccine administration, increased sleep, and antibody responses, then our findings suggest that afternoon immunizations should be recommended, to facilitate increased infant sleep in the 24 hours after immunization," they said.

The study was supported by the National Institutes of Health. None of the researchers had any relevant financial disclosures.

BOSTON – Obese children with type 2 diabetes and those with hypertension can safely engage in moderate to strenuous physical activity, with a few modifications and some common sense.

Heat-related illness and glucose regulation are the top issues for pediatricians who prescribe exercise for such patients – and these small athletes need supervision by an adult who can monitor them. But almost always, exercise is more beneficial than it is risky, Dr. Claire LeBlanc said at the annual meeting of the American Academy of Pediatrics.

"As long as their conditions are well controlled [and there is no organ damage], we want them to do lifestyle modification and get 60 minutes per day of moderate to vigorous physical activity," said Dr. LeBlanc, a pediatric rheumatologist at the University of Alberta, Edmonton.

But, she added, it’s important to loop in other physicians on the child’s care team. "Include your specialists, like cardiologists, especially if there are issues," and a child is becoming symptomatic.

A few basics are in order for any hypertensive child who begins to exercise, she said. "Obese children have a higher risk of poor heat tolerance and heat illness, so it’s important to consider acclimatization and conditioning." Use caution if children are exercising in a hot or humid environment, and make sure they are well hydrated. Although sodium is a concern with hypertension, these children might actually need a little extra salt if they are exercising strenuously.

Activity recommendations vary with the disease stage:

• Prehypertension. Any competitive sport is okay; the goal is 60 minutes per day of moderate to vigorous exercise. Encourage parents to keep children on a well-balanced diet and monitor blood pressure about twice a year.

• Stage 1 hypertension with no organ damage. Again, there’s no limit on eligibility for competitive sports. But if the child becomes symptomatic during exercise or if the blood pressure is persistently elevated, it’s time to check in with a cardiologist. Dietary modification is also a must.

• Stage 2 hypertension with no organ damage. Unless the blood pressure is stabilized by lifestyle modifications and/or drug therapy, these children shouldn’t engage in high-static sports (A high-static exercise is when there are high levels of isometric muscle contraction, when the muscle fires but there is no movement at a joint. Examples include gymnastics, yoga, rock climbing, and downhill skiing). Sports like boxing, weight lifting, and wrestling can cause acute increases in systolic, diastolic, and mean arterial pressures. A specialist should check out the new athlete after 1 week of exercise if all is going well, but be called immediately if the child becomes symptomatic.

• Hypertension plus cardiovascular disease. Competitive sports might not be out of the question based on the type of heart disease and its severity, but consult with a specialist before advising.

Children with type 2 diabetes can reap huge benefits from exercise, but there are still a few things to keep in mind before setting them loose on the playground or hockey field.

"These children can develop hypoglycemia during exercise, especially if they’re on insulin or oral agents," Dr. LeBlanc said. "To avoid hypoglycemia, be careful about the timing of insulin and exercise," avoiding exercise at the peak of insulin action.

Glucose should be tested before, during, and after exercise. Carbohydrate intake might need adjustment, and emergency glucose needs to be available to treat any emergent hypoglycemia. Adequate hydration is a must.

Hyperglycemia also can be a problem. "There should be no vigorous exercise if the blood glucose is above 250 mg/dL and there is also ketonuria or ketonemia," she said.

As with any diabetes patient, foot care is king. "Make sure there are no blisters or cuts that can become infected and cause problems," Dr. LeBlanc advised. This might mean putting limits on weight-bearing exercise, if the child has early signs of peripheral neuropathy.

"A medic alert bracelet [identifying the child as having diabetes] is always a good thing," she said. "But if the diabetes is under control and there are no serious complications, there are really no restrictions on physical activity."

Dr. LeBlanc said she had no relevant financial disclosures.

BOSTON – Obese children with type 2 diabetes and those with hypertension can safely engage in moderate to strenuous physical activity, with a few modifications and some common sense.

Heat-related illness and glucose regulation are the top issues for pediatricians who prescribe exercise for such patients – and these small athletes need supervision by an adult who can monitor them. But almost always, exercise is more beneficial than it is risky, Dr. Claire LeBlanc said at the annual meeting of the American Academy of Pediatrics.

"As long as their conditions are well controlled [and there is no organ damage], we want them to do lifestyle modification and get 60 minutes per day of moderate to vigorous physical activity," said Dr. LeBlanc, a pediatric rheumatologist at the University of Alberta, Edmonton.

But, she added, it’s important to loop in other physicians on the child’s care team. "Include your specialists, like cardiologists, especially if there are issues," and a child is becoming symptomatic.

A few basics are in order for any hypertensive child who begins to exercise, she said. "Obese children have a higher risk of poor heat tolerance and heat illness, so it’s important to consider acclimatization and conditioning." Use caution if children are exercising in a hot or humid environment, and make sure they are well hydrated. Although sodium is a concern with hypertension, these children might actually need a little extra salt if they are exercising strenuously.

Activity recommendations vary with the disease stage:

• Prehypertension. Any competitive sport is okay; the goal is 60 minutes per day of moderate to vigorous exercise. Encourage parents to keep children on a well-balanced diet and monitor blood pressure about twice a year.

• Stage 1 hypertension with no organ damage. Again, there’s no limit on eligibility for competitive sports. But if the child becomes symptomatic during exercise or if the blood pressure is persistently elevated, it’s time to check in with a cardiologist. Dietary modification is also a must.

• Stage 2 hypertension with no organ damage. Unless the blood pressure is stabilized by lifestyle modifications and/or drug therapy, these children shouldn’t engage in high-static sports (A high-static exercise is when there are high levels of isometric muscle contraction, when the muscle fires but there is no movement at a joint. Examples include gymnastics, yoga, rock climbing, and downhill skiing). Sports like boxing, weight lifting, and wrestling can cause acute increases in systolic, diastolic, and mean arterial pressures. A specialist should check out the new athlete after 1 week of exercise if all is going well, but be called immediately if the child becomes symptomatic.

• Hypertension plus cardiovascular disease. Competitive sports might not be out of the question based on the type of heart disease and its severity, but consult with a specialist before advising.

Children with type 2 diabetes can reap huge benefits from exercise, but there are still a few things to keep in mind before setting them loose on the playground or hockey field.

"These children can develop hypoglycemia during exercise, especially if they’re on insulin or oral agents," Dr. LeBlanc said. "To avoid hypoglycemia, be careful about the timing of insulin and exercise," avoiding exercise at the peak of insulin action.

Glucose should be tested before, during, and after exercise. Carbohydrate intake might need adjustment, and emergency glucose needs to be available to treat any emergent hypoglycemia. Adequate hydration is a must.

Hyperglycemia also can be a problem. "There should be no vigorous exercise if the blood glucose is above 250 mg/dL and there is also ketonuria or ketonemia," she said.

As with any diabetes patient, foot care is king. "Make sure there are no blisters or cuts that can become infected and cause problems," Dr. LeBlanc advised. This might mean putting limits on weight-bearing exercise, if the child has early signs of peripheral neuropathy.

"A medic alert bracelet [identifying the child as having diabetes] is always a good thing," she said. "But if the diabetes is under control and there are no serious complications, there are really no restrictions on physical activity."

Dr. LeBlanc said she had no relevant financial disclosures.

BOSTON – Obese children with type 2 diabetes and those with hypertension can safely engage in moderate to strenuous physical activity, with a few modifications and some common sense.

Heat-related illness and glucose regulation are the top issues for pediatricians who prescribe exercise for such patients – and these small athletes need supervision by an adult who can monitor them. But almost always, exercise is more beneficial than it is risky, Dr. Claire LeBlanc said at the annual meeting of the American Academy of Pediatrics.

"As long as their conditions are well controlled [and there is no organ damage], we want them to do lifestyle modification and get 60 minutes per day of moderate to vigorous physical activity," said Dr. LeBlanc, a pediatric rheumatologist at the University of Alberta, Edmonton.

But, she added, it’s important to loop in other physicians on the child’s care team. "Include your specialists, like cardiologists, especially if there are issues," and a child is becoming symptomatic.

A few basics are in order for any hypertensive child who begins to exercise, she said. "Obese children have a higher risk of poor heat tolerance and heat illness, so it’s important to consider acclimatization and conditioning." Use caution if children are exercising in a hot or humid environment, and make sure they are well hydrated. Although sodium is a concern with hypertension, these children might actually need a little extra salt if they are exercising strenuously.

Activity recommendations vary with the disease stage:

• Prehypertension. Any competitive sport is okay; the goal is 60 minutes per day of moderate to vigorous exercise. Encourage parents to keep children on a well-balanced diet and monitor blood pressure about twice a year.

• Stage 1 hypertension with no organ damage. Again, there’s no limit on eligibility for competitive sports. But if the child becomes symptomatic during exercise or if the blood pressure is persistently elevated, it’s time to check in with a cardiologist. Dietary modification is also a must.

• Stage 2 hypertension with no organ damage. Unless the blood pressure is stabilized by lifestyle modifications and/or drug therapy, these children shouldn’t engage in high-static sports (A high-static exercise is when there are high levels of isometric muscle contraction, when the muscle fires but there is no movement at a joint. Examples include gymnastics, yoga, rock climbing, and downhill skiing). Sports like boxing, weight lifting, and wrestling can cause acute increases in systolic, diastolic, and mean arterial pressures. A specialist should check out the new athlete after 1 week of exercise if all is going well, but be called immediately if the child becomes symptomatic.

• Hypertension plus cardiovascular disease. Competitive sports might not be out of the question based on the type of heart disease and its severity, but consult with a specialist before advising.

Children with type 2 diabetes can reap huge benefits from exercise, but there are still a few things to keep in mind before setting them loose on the playground or hockey field.

"These children can develop hypoglycemia during exercise, especially if they’re on insulin or oral agents," Dr. LeBlanc said. "To avoid hypoglycemia, be careful about the timing of insulin and exercise," avoiding exercise at the peak of insulin action.

Glucose should be tested before, during, and after exercise. Carbohydrate intake might need adjustment, and emergency glucose needs to be available to treat any emergent hypoglycemia. Adequate hydration is a must.

Hyperglycemia also can be a problem. "There should be no vigorous exercise if the blood glucose is above 250 mg/dL and there is also ketonuria or ketonemia," she said.

As with any diabetes patient, foot care is king. "Make sure there are no blisters or cuts that can become infected and cause problems," Dr. LeBlanc advised. This might mean putting limits on weight-bearing exercise, if the child has early signs of peripheral neuropathy.

"A medic alert bracelet [identifying the child as having diabetes] is always a good thing," she said. "But if the diabetes is under control and there are no serious complications, there are really no restrictions on physical activity."

Dr. LeBlanc said she had no relevant financial disclosures.

BOSTON – Because asymptomatic Clostridium difficile colonization is so common among infants, routine testing in cases of diarrhea isn’t warranted, according to Dr. L. Clifford McDonald.

Up to 70% of newborns may be colonized with C. difficile, but that percentage drops rapidly over the first 2 years of life as babies develop a healthy intestinal microbiome.

"In children younger than 2 years, consider other diagnoses first, especially if there hasn’t been any exposure to antibiotics," said Dr. McDonald, senior adviser for science and integrity in the division of health care quality promotion at the Centers for Disease Control and Prevention. "Colonization in this age group doesn’t carry as much weight as it does in other age groups."

The clinical picture begins to change after age 2 when the intestinal flora is well established. "Certainly over 2 years old, C. difficile is not part of the normal microbiota. In this case, you should test and treat as you would in an adult," Dr. McDonald said at the annual meeting of the American Academy of Pediatrics.

Hospital discharge data show about 500,000 health care–acquired C. difficile infections occur each year. This results in about 20,000 excess deaths annually – mostly in older people – and several billion dollars in excess health care costs. Most of the patients are older than 65, but the number of infections is rising in younger people as well.

Antibiotic exposure plays a large part in the changing frequency and toxicity of the infections, Dr. McDonald said. "The bacteria first developed a resistance to fluoroquinolones, and now we are seeing clindamycin-resistant strains," he noted.

One study has examined C. difficile infection outcomes in a national database of children’s hospital discharge records. Children with the infections were 20% more likely to die, 36% more likely to have a colectomy, and four times more likely to have an increased length of stay. They were 11 times more likely to have inflammatory bowel disease and significantly more likely to be on immunosupressant or antibiotic regimens (Arch. Ped. Adolesc. Med. 2011;165:451-7).

"So although these infections are not as common in children as they are in older individuals, you can see there are still some very serious sequelae," he said.

Researchers have identified some risk factors for toxigenic C. difficile strains in young children and infants, including formula feeding and cesarean section. Diseases that require immunosuppression and antibiotics also predispose to the infection, probably because they perturb the normal gut flora. Most transmission occurs in a day care or health care setting, including the hospital.

"We are also seeing new data that infants colonized with C. difficile in the first year of life seem to have higher rates of allergy at up to 5 years old," Dr. McDonald said. "The presence of C. difficile is probably a marker of a perturbation of the child’s intestinal flora and delayed establishment of the normal microbiome," which predisposes to atopy.

Until recently, the treatments of choice have been metronidazole and vancomycin. Although effective for quelling the infection, both have a recurrence rate of 20%-30%. Most recurrences occur soon after treatment, while the microbiota are still off balance, Dr. McDonald said.

A new drug, fidaxomicin, may offer a better solution. Approved by the Food and Drug Administration last May, the drug is not systemically absorbed – a benefit in C. difficile infections. Patients treated with fidaxomicin appear to have a lower recurrence rate – 15% vs. 25% with vancomycin in a phase III trial published earlier this year (N. Engl. J. Med. 2011;364:422-31).

However, Dr. McDonald noted, the drug was not studied in young children.

Dr. McDonald said he had no relevant financial disclosures.

BOSTON – Because asymptomatic Clostridium difficile colonization is so common among infants, routine testing in cases of diarrhea isn’t warranted, according to Dr. L. Clifford McDonald.

Up to 70% of newborns may be colonized with C. difficile, but that percentage drops rapidly over the first 2 years of life as babies develop a healthy intestinal microbiome.

"In children younger than 2 years, consider other diagnoses first, especially if there hasn’t been any exposure to antibiotics," said Dr. McDonald, senior adviser for science and integrity in the division of health care quality promotion at the Centers for Disease Control and Prevention. "Colonization in this age group doesn’t carry as much weight as it does in other age groups."

The clinical picture begins to change after age 2 when the intestinal flora is well established. "Certainly over 2 years old, C. difficile is not part of the normal microbiota. In this case, you should test and treat as you would in an adult," Dr. McDonald said at the annual meeting of the American Academy of Pediatrics.

Hospital discharge data show about 500,000 health care–acquired C. difficile infections occur each year. This results in about 20,000 excess deaths annually – mostly in older people – and several billion dollars in excess health care costs. Most of the patients are older than 65, but the number of infections is rising in younger people as well.

Antibiotic exposure plays a large part in the changing frequency and toxicity of the infections, Dr. McDonald said. "The bacteria first developed a resistance to fluoroquinolones, and now we are seeing clindamycin-resistant strains," he noted.

One study has examined C. difficile infection outcomes in a national database of children’s hospital discharge records. Children with the infections were 20% more likely to die, 36% more likely to have a colectomy, and four times more likely to have an increased length of stay. They were 11 times more likely to have inflammatory bowel disease and significantly more likely to be on immunosupressant or antibiotic regimens (Arch. Ped. Adolesc. Med. 2011;165:451-7).

"So although these infections are not as common in children as they are in older individuals, you can see there are still some very serious sequelae," he said.

Researchers have identified some risk factors for toxigenic C. difficile strains in young children and infants, including formula feeding and cesarean section. Diseases that require immunosuppression and antibiotics also predispose to the infection, probably because they perturb the normal gut flora. Most transmission occurs in a day care or health care setting, including the hospital.

"We are also seeing new data that infants colonized with C. difficile in the first year of life seem to have higher rates of allergy at up to 5 years old," Dr. McDonald said. "The presence of C. difficile is probably a marker of a perturbation of the child’s intestinal flora and delayed establishment of the normal microbiome," which predisposes to atopy.

Until recently, the treatments of choice have been metronidazole and vancomycin. Although effective for quelling the infection, both have a recurrence rate of 20%-30%. Most recurrences occur soon after treatment, while the microbiota are still off balance, Dr. McDonald said.

A new drug, fidaxomicin, may offer a better solution. Approved by the Food and Drug Administration last May, the drug is not systemically absorbed – a benefit in C. difficile infections. Patients treated with fidaxomicin appear to have a lower recurrence rate – 15% vs. 25% with vancomycin in a phase III trial published earlier this year (N. Engl. J. Med. 2011;364:422-31).

However, Dr. McDonald noted, the drug was not studied in young children.

Dr. McDonald said he had no relevant financial disclosures.

BOSTON – Because asymptomatic Clostridium difficile colonization is so common among infants, routine testing in cases of diarrhea isn’t warranted, according to Dr. L. Clifford McDonald.

Up to 70% of newborns may be colonized with C. difficile, but that percentage drops rapidly over the first 2 years of life as babies develop a healthy intestinal microbiome.

"In children younger than 2 years, consider other diagnoses first, especially if there hasn’t been any exposure to antibiotics," said Dr. McDonald, senior adviser for science and integrity in the division of health care quality promotion at the Centers for Disease Control and Prevention. "Colonization in this age group doesn’t carry as much weight as it does in other age groups."

The clinical picture begins to change after age 2 when the intestinal flora is well established. "Certainly over 2 years old, C. difficile is not part of the normal microbiota. In this case, you should test and treat as you would in an adult," Dr. McDonald said at the annual meeting of the American Academy of Pediatrics.

Hospital discharge data show about 500,000 health care–acquired C. difficile infections occur each year. This results in about 20,000 excess deaths annually – mostly in older people – and several billion dollars in excess health care costs. Most of the patients are older than 65, but the number of infections is rising in younger people as well.

Antibiotic exposure plays a large part in the changing frequency and toxicity of the infections, Dr. McDonald said. "The bacteria first developed a resistance to fluoroquinolones, and now we are seeing clindamycin-resistant strains," he noted.

One study has examined C. difficile infection outcomes in a national database of children’s hospital discharge records. Children with the infections were 20% more likely to die, 36% more likely to have a colectomy, and four times more likely to have an increased length of stay. They were 11 times more likely to have inflammatory bowel disease and significantly more likely to be on immunosupressant or antibiotic regimens (Arch. Ped. Adolesc. Med. 2011;165:451-7).

"So although these infections are not as common in children as they are in older individuals, you can see there are still some very serious sequelae," he said.

Researchers have identified some risk factors for toxigenic C. difficile strains in young children and infants, including formula feeding and cesarean section. Diseases that require immunosuppression and antibiotics also predispose to the infection, probably because they perturb the normal gut flora. Most transmission occurs in a day care or health care setting, including the hospital.

"We are also seeing new data that infants colonized with C. difficile in the first year of life seem to have higher rates of allergy at up to 5 years old," Dr. McDonald said. "The presence of C. difficile is probably a marker of a perturbation of the child’s intestinal flora and delayed establishment of the normal microbiome," which predisposes to atopy.

Until recently, the treatments of choice have been metronidazole and vancomycin. Although effective for quelling the infection, both have a recurrence rate of 20%-30%. Most recurrences occur soon after treatment, while the microbiota are still off balance, Dr. McDonald said.

A new drug, fidaxomicin, may offer a better solution. Approved by the Food and Drug Administration last May, the drug is not systemically absorbed – a benefit in C. difficile infections. Patients treated with fidaxomicin appear to have a lower recurrence rate – 15% vs. 25% with vancomycin in a phase III trial published earlier this year (N. Engl. J. Med. 2011;364:422-31).

However, Dr. McDonald noted, the drug was not studied in young children.

Dr. McDonald said he had no relevant financial disclosures.

BOSTON – Writing an exercise prescription for obese children may not be child’s play – but it’s not brain surgery, either.

With a basic physical, some creative thinking, and a few caveats, obese children can safely tolerate 60 minutes of moderate to vigorous exercise every day. The rewards can be not only physical, but also psychosocial, as children build self-confidence and friendships.

But it’s not quite as easy as turning kids loose on the playground, Dr. Blaise A. Nemeth said at theannual meeting of the American Academy of Pediatrics.

Obese children have an increased risk of fractures and knee injuries, so pain complaints should be taken seriously, said Dr. Nemeth of the departments of pediatrics and of orthopedics and rehabilitation at the University of Wisconsin, Madison.

An obese child who presents with knee or hip pain may very well have a slipped capital femoral epiphysis. "Have a low threshold for ordering radiographs for the hips to assess this," he said. "It should be the first consideration in an overweight child," who presents with a limp or hip or knee pain.

Fractures also can be an issue with increased exercise. Since obese children aren’t as agile as nonobese kids, they are more prone to falling while exercising. Poor bone quality caused by diet or sedentary lifestyle means that fractures are more likely in a fall. The overlying adipose tissue also can make fracture diagnosis a bit tougher.

Ironically though, increased exercise is one of the best ways to reduce the fracture risk associated with obesity, he said. Exercise improves bone quality; increases muscle strength and coordination; and promotes weight loss – all of which positively affect fracture risk.

Writing an exercise prescription for these children is a three-step process:

• Obtain a baseline health status. A complete physical will identify any reasons to restrict or modify activity. It also provides a jumping-off point for tracking improvement. When children can see their progress on a chart, it helps motivate them to do more.

• Obtain a baseline fitness status. Exercise testing in a lab or under the eye of a trainer gets everyone on the same page with goal setting. It’s important to set reasonable goals, to maximize motivation by achievement, and to minimize discouragement through failure.

• Maintain follow-up visits. Don’t let go of your patient. Regular visits let you monitor health improvements and identify potential problems, like musculoskeletal issues.

Since most pediatricians’ offices don’t come equipped with a gym, it’s crucial to know your community resources. Help children pair up with a coach or trainer who can focus on strength and conditioning, or sport programs. Community centers will probably offer low-cost activity programs and often have a certified trainer on board. Obesity clinics usually offer exercise programs under medical supervision.

But remember, Dr. Nemeth said, that some community or private fitness facilities have age restrictions. "Usually a doctor’s prescription will provide an exception to this," he said. Some facilities and programs require parental involvement or adult supervision, especially for younger children.

It’s also important to fit the program to the child. "Group activities might be motivating, or they might be intimidating," for an obese child.

When looking for results, he advised, don’t get too hung up on the body mass index. BMI reconciles total body weight with height, but it doesn’t differentiate muscle mass from fat mass. "The body composition may change, but this might not be reflected in the BMI," he said. Other measures, including balance, coordination, stamina, and overall health measures, also can be used to assess progress.

Finally, food will continue to factor into the exercise and weight equation. When children get more active, the time available for food consumption (like sitting in front of the television) decreases. But they may be even hungrier as their metabolism revs up through exercise.

"You need to ensure that they get an adequate caloric intake to cover their energy output during exercise," and prevent a post workout binge. And it almost goes without saying, he added, that "food should never be used as a reward."

Dr. Nemeth said he had no relevant financial disclosures.

BOSTON – Writing an exercise prescription for obese children may not be child’s play – but it’s not brain surgery, either.

With a basic physical, some creative thinking, and a few caveats, obese children can safely tolerate 60 minutes of moderate to vigorous exercise every day. The rewards can be not only physical, but also psychosocial, as children build self-confidence and friendships.

But it’s not quite as easy as turning kids loose on the playground, Dr. Blaise A. Nemeth said at theannual meeting of the American Academy of Pediatrics.

Obese children have an increased risk of fractures and knee injuries, so pain complaints should be taken seriously, said Dr. Nemeth of the departments of pediatrics and of orthopedics and rehabilitation at the University of Wisconsin, Madison.

An obese child who presents with knee or hip pain may very well have a slipped capital femoral epiphysis. "Have a low threshold for ordering radiographs for the hips to assess this," he said. "It should be the first consideration in an overweight child," who presents with a limp or hip or knee pain.

Fractures also can be an issue with increased exercise. Since obese children aren’t as agile as nonobese kids, they are more prone to falling while exercising. Poor bone quality caused by diet or sedentary lifestyle means that fractures are more likely in a fall. The overlying adipose tissue also can make fracture diagnosis a bit tougher.

Ironically though, increased exercise is one of the best ways to reduce the fracture risk associated with obesity, he said. Exercise improves bone quality; increases muscle strength and coordination; and promotes weight loss – all of which positively affect fracture risk.

Writing an exercise prescription for these children is a three-step process:

• Obtain a baseline health status. A complete physical will identify any reasons to restrict or modify activity. It also provides a jumping-off point for tracking improvement. When children can see their progress on a chart, it helps motivate them to do more.

• Obtain a baseline fitness status. Exercise testing in a lab or under the eye of a trainer gets everyone on the same page with goal setting. It’s important to set reasonable goals, to maximize motivation by achievement, and to minimize discouragement through failure.

• Maintain follow-up visits. Don’t let go of your patient. Regular visits let you monitor health improvements and identify potential problems, like musculoskeletal issues.

Since most pediatricians’ offices don’t come equipped with a gym, it’s crucial to know your community resources. Help children pair up with a coach or trainer who can focus on strength and conditioning, or sport programs. Community centers will probably offer low-cost activity programs and often have a certified trainer on board. Obesity clinics usually offer exercise programs under medical supervision.

But remember, Dr. Nemeth said, that some community or private fitness facilities have age restrictions. "Usually a doctor’s prescription will provide an exception to this," he said. Some facilities and programs require parental involvement or adult supervision, especially for younger children.

It’s also important to fit the program to the child. "Group activities might be motivating, or they might be intimidating," for an obese child.

When looking for results, he advised, don’t get too hung up on the body mass index. BMI reconciles total body weight with height, but it doesn’t differentiate muscle mass from fat mass. "The body composition may change, but this might not be reflected in the BMI," he said. Other measures, including balance, coordination, stamina, and overall health measures, also can be used to assess progress.

Finally, food will continue to factor into the exercise and weight equation. When children get more active, the time available for food consumption (like sitting in front of the television) decreases. But they may be even hungrier as their metabolism revs up through exercise.

"You need to ensure that they get an adequate caloric intake to cover their energy output during exercise," and prevent a post workout binge. And it almost goes without saying, he added, that "food should never be used as a reward."

Dr. Nemeth said he had no relevant financial disclosures.

BOSTON – Writing an exercise prescription for obese children may not be child’s play – but it’s not brain surgery, either.

With a basic physical, some creative thinking, and a few caveats, obese children can safely tolerate 60 minutes of moderate to vigorous exercise every day. The rewards can be not only physical, but also psychosocial, as children build self-confidence and friendships.

But it’s not quite as easy as turning kids loose on the playground, Dr. Blaise A. Nemeth said at theannual meeting of the American Academy of Pediatrics.

Obese children have an increased risk of fractures and knee injuries, so pain complaints should be taken seriously, said Dr. Nemeth of the departments of pediatrics and of orthopedics and rehabilitation at the University of Wisconsin, Madison.

An obese child who presents with knee or hip pain may very well have a slipped capital femoral epiphysis. "Have a low threshold for ordering radiographs for the hips to assess this," he said. "It should be the first consideration in an overweight child," who presents with a limp or hip or knee pain.

Fractures also can be an issue with increased exercise. Since obese children aren’t as agile as nonobese kids, they are more prone to falling while exercising. Poor bone quality caused by diet or sedentary lifestyle means that fractures are more likely in a fall. The overlying adipose tissue also can make fracture diagnosis a bit tougher.

Ironically though, increased exercise is one of the best ways to reduce the fracture risk associated with obesity, he said. Exercise improves bone quality; increases muscle strength and coordination; and promotes weight loss – all of which positively affect fracture risk.

Writing an exercise prescription for these children is a three-step process:

• Obtain a baseline health status. A complete physical will identify any reasons to restrict or modify activity. It also provides a jumping-off point for tracking improvement. When children can see their progress on a chart, it helps motivate them to do more.

• Obtain a baseline fitness status. Exercise testing in a lab or under the eye of a trainer gets everyone on the same page with goal setting. It’s important to set reasonable goals, to maximize motivation by achievement, and to minimize discouragement through failure.

• Maintain follow-up visits. Don’t let go of your patient. Regular visits let you monitor health improvements and identify potential problems, like musculoskeletal issues.

Since most pediatricians’ offices don’t come equipped with a gym, it’s crucial to know your community resources. Help children pair up with a coach or trainer who can focus on strength and conditioning, or sport programs. Community centers will probably offer low-cost activity programs and often have a certified trainer on board. Obesity clinics usually offer exercise programs under medical supervision.

But remember, Dr. Nemeth said, that some community or private fitness facilities have age restrictions. "Usually a doctor’s prescription will provide an exception to this," he said. Some facilities and programs require parental involvement or adult supervision, especially for younger children.

It’s also important to fit the program to the child. "Group activities might be motivating, or they might be intimidating," for an obese child.

When looking for results, he advised, don’t get too hung up on the body mass index. BMI reconciles total body weight with height, but it doesn’t differentiate muscle mass from fat mass. "The body composition may change, but this might not be reflected in the BMI," he said. Other measures, including balance, coordination, stamina, and overall health measures, also can be used to assess progress.

Finally, food will continue to factor into the exercise and weight equation. When children get more active, the time available for food consumption (like sitting in front of the television) decreases. But they may be even hungrier as their metabolism revs up through exercise.

"You need to ensure that they get an adequate caloric intake to cover their energy output during exercise," and prevent a post workout binge. And it almost goes without saying, he added, that "food should never be used as a reward."

Dr. Nemeth said he had no relevant financial disclosures.

During the first year after starting a new therapy, patients with autoimmune diseases appear to experience a similar rate of serious infections irrespective of whether the new drug is a biologic or a nonbiologic agent.

Infections requiring hospitalizations were nearly identical, regardless of the initial therapy, in a large retrospective cohort study of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis and spondyloarthropathies.

But within the group of rheumatoid arthritis patients taking biologics, infliximab was associated with significantly more infections than was etanercept or adalimumab (adjusted hazard ratio 1.25). "This observation may have important implications for the interpretation of studies that report on tumor necrosis factor [TNF]–alpha [antagonists as a group, perhaps because the prevalence of infliximab use could have influenced observed associations," wrote Dr. Carlos G. Grijalva of Vanderbilt University, Nashville.

The drug regimens studied included the use of infliximab-based regimens, many of which used methotrexate to inhibit anti-infliximab antibodies. "Disentangling the effect of individual drugs when used concurrently is difficult. Nevertheless, we noted that concurrent methotrexate use was similar for the other TNF-alpha antagonists."

Also, in a strong dose-dependent fashion, glucocorticoid use at baseline significantly increased the infection risk for patients with rheumatoid arthritis or psoriasis and spondyloarthropathy, Dr. Grijalva and his colleagues wrote in a study posted online in JAMA on Nov. 6 (2011 Nov. 6 [doi:10.1001/jama.2011.1692]).

Dr. Grijalva and his coinvestigators based their findings on data extracted from four large U.S. databases – three included Medicaid and Medicare participants and one included pharmaceutical assistance programs for the elderly and disabled – as part of the Safety Assessment of Biologic Therapy (SABER) project.

Outcomes were assessed within the first 365 days of initial therapy with the TNF-alpha antagonists infliximab, adalimumab, or etanercept and with nonbiologic therapies specific to each disorder.

For rheumatoid arthritis, the comparator therapies were leflunomide, sulfasalazine, and hydroxychloroquine after any use of methotrexate in the previous year. For inflammatory bowel disease, the comparators were azathioprine and mercaptopurine. For psoriasis and the spondyloarthropathies, the comparators were methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide.

The cohort consisted of 10,484 matched pairs of rheumatoid arthritis patients, 2,323 with inflammatory bowel disease, and 3,215 with psoriasis or a spondyloarthropathy. Overall, 20% of patients were aged 65 years or older. Over the 1-year follow-up period, 225 patients died; of these, 148 had rheumatoid arthritis, 38 had inflammatory bowel disease, and 39 had psoriasis.

There were 1,172 serious infections requiring hospitalization, and 53% were for pneumonia or skin and soft tissue infections. The death rate was 3.6% for RA patients, 2% for IBD patients, and 7% for those with psoriasis and the spondyloarthropathies.

Among those with RA, the infection rate was 8.16 per 100 person-years for those taking a biologic agent and 7.78 per 100 person-years for those on a nonbiologic agent, a nonsignificant difference.

However, the authors said, there was a significant difference in infections when considering glucocorticoid use. Those who used up to 5 mg/day were 32% more likely to be hospitalized; 5-10 mg/day, 78% more likely; and more than 10 mg/day, three times more likely to have a hospitalization, compared with patients not taking a glucocorticoid.

When the investigators broke the biologics down into individual infection associations, infliximab was associated with a significant increase, compared with the nonbiologics (adjusted HR 1.26). Infliximab was also associated with significantly more hospitalizations than either etanercept or adalimumab (adjusted HR 1.26 and 1.23, respectively).

Among those with IBD, the rate of infection did not differ significantly between those taking nonbiologic and biologic drugs (9.6 per 100 person-years and 10.9 per 100 person-years, respectively). Nor was there a significant association of infection with baseline glucocorticoid use.

Among those with psoriasis or a spondylarthropy, the infection rates were 5.37 per 100 person-years for nonbiologics and 5.4 per 100 person-years for biologics – not significantly different. But again, baseline glucocorticoid use significantly affected these rates. Those taking 5-10 mg/day of glucocorticoids were twice as likely to be hospitalized as those not taking the drug. Those taking more than 10 mg/day were 2.7 times more likely to have a hospitalization.

Compared with prior studies, this analysis found higher rates of infection overall, a finding that might be due to the large numbers of low-income, elderly, and disabled patients – particularly vulnerable groups.

The researchers said the findings are limited by reliance on coded information from claims and limited information on actual use of medications. The study was primarily sponsored by the Food and Drug Administration and the Department of Health and Human Services. Dr. Grijalva did not have any financial disclosures, but eight of the study investigators reported multiple associations with pharmaceutical companies.

During the first year after starting a new therapy, patients with autoimmune diseases appear to experience a similar rate of serious infections irrespective of whether the new drug is a biologic or a nonbiologic agent.

Infections requiring hospitalizations were nearly identical, regardless of the initial therapy, in a large retrospective cohort study of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis and spondyloarthropathies.

But within the group of rheumatoid arthritis patients taking biologics, infliximab was associated with significantly more infections than was etanercept or adalimumab (adjusted hazard ratio 1.25). "This observation may have important implications for the interpretation of studies that report on tumor necrosis factor [TNF]–alpha [antagonists as a group, perhaps because the prevalence of infliximab use could have influenced observed associations," wrote Dr. Carlos G. Grijalva of Vanderbilt University, Nashville.

The drug regimens studied included the use of infliximab-based regimens, many of which used methotrexate to inhibit anti-infliximab antibodies. "Disentangling the effect of individual drugs when used concurrently is difficult. Nevertheless, we noted that concurrent methotrexate use was similar for the other TNF-alpha antagonists."

Also, in a strong dose-dependent fashion, glucocorticoid use at baseline significantly increased the infection risk for patients with rheumatoid arthritis or psoriasis and spondyloarthropathy, Dr. Grijalva and his colleagues wrote in a study posted online in JAMA on Nov. 6 (2011 Nov. 6 [doi:10.1001/jama.2011.1692]).

Dr. Grijalva and his coinvestigators based their findings on data extracted from four large U.S. databases – three included Medicaid and Medicare participants and one included pharmaceutical assistance programs for the elderly and disabled – as part of the Safety Assessment of Biologic Therapy (SABER) project.

Outcomes were assessed within the first 365 days of initial therapy with the TNF-alpha antagonists infliximab, adalimumab, or etanercept and with nonbiologic therapies specific to each disorder.

For rheumatoid arthritis, the comparator therapies were leflunomide, sulfasalazine, and hydroxychloroquine after any use of methotrexate in the previous year. For inflammatory bowel disease, the comparators were azathioprine and mercaptopurine. For psoriasis and the spondyloarthropathies, the comparators were methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide.

The cohort consisted of 10,484 matched pairs of rheumatoid arthritis patients, 2,323 with inflammatory bowel disease, and 3,215 with psoriasis or a spondyloarthropathy. Overall, 20% of patients were aged 65 years or older. Over the 1-year follow-up period, 225 patients died; of these, 148 had rheumatoid arthritis, 38 had inflammatory bowel disease, and 39 had psoriasis.

There were 1,172 serious infections requiring hospitalization, and 53% were for pneumonia or skin and soft tissue infections. The death rate was 3.6% for RA patients, 2% for IBD patients, and 7% for those with psoriasis and the spondyloarthropathies.

Among those with RA, the infection rate was 8.16 per 100 person-years for those taking a biologic agent and 7.78 per 100 person-years for those on a nonbiologic agent, a nonsignificant difference.

However, the authors said, there was a significant difference in infections when considering glucocorticoid use. Those who used up to 5 mg/day were 32% more likely to be hospitalized; 5-10 mg/day, 78% more likely; and more than 10 mg/day, three times more likely to have a hospitalization, compared with patients not taking a glucocorticoid.

When the investigators broke the biologics down into individual infection associations, infliximab was associated with a significant increase, compared with the nonbiologics (adjusted HR 1.26). Infliximab was also associated with significantly more hospitalizations than either etanercept or adalimumab (adjusted HR 1.26 and 1.23, respectively).

Among those with IBD, the rate of infection did not differ significantly between those taking nonbiologic and biologic drugs (9.6 per 100 person-years and 10.9 per 100 person-years, respectively). Nor was there a significant association of infection with baseline glucocorticoid use.

Among those with psoriasis or a spondylarthropy, the infection rates were 5.37 per 100 person-years for nonbiologics and 5.4 per 100 person-years for biologics – not significantly different. But again, baseline glucocorticoid use significantly affected these rates. Those taking 5-10 mg/day of glucocorticoids were twice as likely to be hospitalized as those not taking the drug. Those taking more than 10 mg/day were 2.7 times more likely to have a hospitalization.

Compared with prior studies, this analysis found higher rates of infection overall, a finding that might be due to the large numbers of low-income, elderly, and disabled patients – particularly vulnerable groups.

The researchers said the findings are limited by reliance on coded information from claims and limited information on actual use of medications. The study was primarily sponsored by the Food and Drug Administration and the Department of Health and Human Services. Dr. Grijalva did not have any financial disclosures, but eight of the study investigators reported multiple associations with pharmaceutical companies.

During the first year after starting a new therapy, patients with autoimmune diseases appear to experience a similar rate of serious infections irrespective of whether the new drug is a biologic or a nonbiologic agent.

Infections requiring hospitalizations were nearly identical, regardless of the initial therapy, in a large retrospective cohort study of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis and spondyloarthropathies.

But within the group of rheumatoid arthritis patients taking biologics, infliximab was associated with significantly more infections than was etanercept or adalimumab (adjusted hazard ratio 1.25). "This observation may have important implications for the interpretation of studies that report on tumor necrosis factor [TNF]–alpha [antagonists as a group, perhaps because the prevalence of infliximab use could have influenced observed associations," wrote Dr. Carlos G. Grijalva of Vanderbilt University, Nashville.

The drug regimens studied included the use of infliximab-based regimens, many of which used methotrexate to inhibit anti-infliximab antibodies. "Disentangling the effect of individual drugs when used concurrently is difficult. Nevertheless, we noted that concurrent methotrexate use was similar for the other TNF-alpha antagonists."

Also, in a strong dose-dependent fashion, glucocorticoid use at baseline significantly increased the infection risk for patients with rheumatoid arthritis or psoriasis and spondyloarthropathy, Dr. Grijalva and his colleagues wrote in a study posted online in JAMA on Nov. 6 (2011 Nov. 6 [doi:10.1001/jama.2011.1692]).

Dr. Grijalva and his coinvestigators based their findings on data extracted from four large U.S. databases – three included Medicaid and Medicare participants and one included pharmaceutical assistance programs for the elderly and disabled – as part of the Safety Assessment of Biologic Therapy (SABER) project.

Outcomes were assessed within the first 365 days of initial therapy with the TNF-alpha antagonists infliximab, adalimumab, or etanercept and with nonbiologic therapies specific to each disorder.

For rheumatoid arthritis, the comparator therapies were leflunomide, sulfasalazine, and hydroxychloroquine after any use of methotrexate in the previous year. For inflammatory bowel disease, the comparators were azathioprine and mercaptopurine. For psoriasis and the spondyloarthropathies, the comparators were methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide.

The cohort consisted of 10,484 matched pairs of rheumatoid arthritis patients, 2,323 with inflammatory bowel disease, and 3,215 with psoriasis or a spondyloarthropathy. Overall, 20% of patients were aged 65 years or older. Over the 1-year follow-up period, 225 patients died; of these, 148 had rheumatoid arthritis, 38 had inflammatory bowel disease, and 39 had psoriasis.

There were 1,172 serious infections requiring hospitalization, and 53% were for pneumonia or skin and soft tissue infections. The death rate was 3.6% for RA patients, 2% for IBD patients, and 7% for those with psoriasis and the spondyloarthropathies.

Among those with RA, the infection rate was 8.16 per 100 person-years for those taking a biologic agent and 7.78 per 100 person-years for those on a nonbiologic agent, a nonsignificant difference.

However, the authors said, there was a significant difference in infections when considering glucocorticoid use. Those who used up to 5 mg/day were 32% more likely to be hospitalized; 5-10 mg/day, 78% more likely; and more than 10 mg/day, three times more likely to have a hospitalization, compared with patients not taking a glucocorticoid.

When the investigators broke the biologics down into individual infection associations, infliximab was associated with a significant increase, compared with the nonbiologics (adjusted HR 1.26). Infliximab was also associated with significantly more hospitalizations than either etanercept or adalimumab (adjusted HR 1.26 and 1.23, respectively).

Among those with IBD, the rate of infection did not differ significantly between those taking nonbiologic and biologic drugs (9.6 per 100 person-years and 10.9 per 100 person-years, respectively). Nor was there a significant association of infection with baseline glucocorticoid use.

Among those with psoriasis or a spondylarthropy, the infection rates were 5.37 per 100 person-years for nonbiologics and 5.4 per 100 person-years for biologics – not significantly different. But again, baseline glucocorticoid use significantly affected these rates. Those taking 5-10 mg/day of glucocorticoids were twice as likely to be hospitalized as those not taking the drug. Those taking more than 10 mg/day were 2.7 times more likely to have a hospitalization.

Compared with prior studies, this analysis found higher rates of infection overall, a finding that might be due to the large numbers of low-income, elderly, and disabled patients – particularly vulnerable groups.

The researchers said the findings are limited by reliance on coded information from claims and limited information on actual use of medications. The study was primarily sponsored by the Food and Drug Administration and the Department of Health and Human Services. Dr. Grijalva did not have any financial disclosures, but eight of the study investigators reported multiple associations with pharmaceutical companies.

Major Finding: A high-fat meal increased bacterial endotoxins by 126% in subjects with type 2 diabetes, compared with healthy controls.

Data Source: A prospective food study performed in 54 volunteers.

Disclosures: Dr. Harte reported no financial conflicts.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the meeting.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this “leaky gut” effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium's cell membrane – in the blood.

“Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal,” said Dr. Harte of the University of Warwick (England). “A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals' due to the elevated exposure to endotoxin.”

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides in those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the healthy controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

“A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels,” Dr. Harte said. “The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids.

Major Finding: A high-fat meal increased bacterial endotoxins by 126% in subjects with type 2 diabetes, compared with healthy controls.

Data Source: A prospective food study performed in 54 volunteers.

Disclosures: Dr. Harte reported no financial conflicts.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the meeting.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this “leaky gut” effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium's cell membrane – in the blood.

“Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal,” said Dr. Harte of the University of Warwick (England). “A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals' due to the elevated exposure to endotoxin.”

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides in those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the healthy controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

“A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels,” Dr. Harte said. “The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids.

Major Finding: A high-fat meal increased bacterial endotoxins by 126% in subjects with type 2 diabetes, compared with healthy controls.

Data Source: A prospective food study performed in 54 volunteers.

Disclosures: Dr. Harte reported no financial conflicts.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the meeting.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this “leaky gut” effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium's cell membrane – in the blood.

“Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal,” said Dr. Harte of the University of Warwick (England). “A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals' due to the elevated exposure to endotoxin.”

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides in those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the healthy controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

“A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels,” Dr. Harte said. “The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids.

Major Finding: Reducing HbA_1c, blood pressure, and weight could avert up to 21% of cardiovascular events in patients with type 2 diabetes.

Data Source: A population-based observational study comprising 5,841 patients.

Disclosures: Dr. Heintjes reported having no conflicts of interest. Her employer, PHARMO, however, receives funding from numerous pharmaceutical companies, including Astra Zeneca, which sponsored the current study.

LISBON – Even small changes in hemoglobin A_1c and blood pressure could significantly reduce the risk of heart attack, stroke, and other cardiovascular complications in people who have type 2 diabetes, according to the findings of a population-based observational study of nearly 6,000 patients.

A 0.5% decrease in HbA_1c and a 10–mm Hg decrease in systolic blood pressure could avert 10% of such events over the course of 5 years, Dr. Edith Heintjes said at the annual meeting. Greater changes could reduce cardiovascular events by as much as 21%, said Dr. Heintjes of the PHARMO Institute for Drug Research, Utrecht, the Netherlands.

Although Dr. Heintjes' study on population attributable risk was theoretical, it still adds weight to the emerging theory that small changes can make a big difference to the health of people with type 2 diabetes.

“Even when we examined only modest incremental reductions, which could be achieved in the clinical setting, we found the possibility of significant benefit,” she said.

Those patients who had the greatest risk factors – elevated HbA_1c, high blood pressure, and higher body mass index – stand to gain the most when they improve those factors, she said.

Dr. Heintjes' analysis included 5,841 Dutch patients with a diagnosis of type 2 diabetes for at least 2 years.

The patients were all taking some form of treatment – oral medications, insulin, or both – for at least 6 months to be included in the study.

After examining both baseline data and 5-year outcomes, Dr. Heintjes was able to extrapolate how improvements in the three risk factors might impact the expected number of cardiovascular events.

Patient data were drawn from the PHARMO record linkage system, which includes community pharmaceutical dispensing information, laboratory information, national hospitalization information, and statistics from the Dutch national diabetes monitoring program.

Patients were treated with the aim of achieving the country's national targets: an HbA_1c of below 7%, a systolic blood pressure of 140 mm Hg or lower, and a body mass index of 25 kg/m

At baseline, the patients' average age was 66 years. The average HbA_1c was 7%; systolic blood pressure 149 mm Hg, and body mass index, 29.5 kg/m

Most of the patients (92%) were taking only oral medications. The rest of them were also taking insulin.

Some cardiovascular morbidity was already present in the group, including peripheral artery disease (0.5%), renal impairment (11%), neuropathy (51%), and retinopathy (7%). About half of the group (45%) had a family history of cardiovascular disease.

Dr. Heintjes divided the group according to the number of risk factors each patient exhibited. A quarter (24%) had just one elevated risk factor; 47% had two elevated risk factors, and 26% had elevations in all three risk factors.

A multivariable analysis allowed her to extrapolate that 796 cardiovascular events (heart attack, ischemic heart disease, stroke, and chronic heart failure) would occur if all of the patients were followed for 5 years.

If every patient in this population were able to correct each one of the risk factors to the national recommendations, she said, 687 events would occur – a 14% decrease. Correcting HbA_1c and blood pressure accounted for this change, she said; changing BMI did nothing to increase the benefit.

Theoretically, she said, patients with the most risk factors would reap the greatest benefit. The 24% with one elevated risk factor would experience a 5% reduction in cardiovascular events, while those with all three elevated risk factors, upon correcting them, would see a 21% reduction.

With regard to the group's baseline measurements, correcting to national Dutch standards would mean an average HbA_1c reduction of 0.8%, a 26–mm Hg reduction in systolic blood pressure, and a weight loss of 16 kg (equivalent to a BMI decrease of 5.7 kg/m

However, Dr. Heintjes said, it might not be realistic to expect such changes.

Her second analysis explored the improvements that could arise from smaller changes: a 0.5% reduction in HbA_1c, a 10–mm Hg reduction in systolic blood pressure, and a 10% reduction in total body weight (2.6 kg/m

“With this analysis, we saw in the overall population that 6% of the risk could be averted,” she said. Among those patients in the subpopulation with three risk factors, applying the smaller changes could cut the number of events by 10%.

It's not exactly clear how the results can change clinical practice, Dr. Heintjes acknowledged.“But this does allow us to unders

“But this does allow us to understand how small changes can translate into bigger benefits for people with type 2 diabetes,” she said.

Major Finding: Reducing HbA_1c, blood pressure, and weight could avert up to 21% of cardiovascular events in patients with type 2 diabetes.

Data Source: A population-based observational study comprising 5,841 patients.

Disclosures: Dr. Heintjes reported having no conflicts of interest. Her employer, PHARMO, however, receives funding from numerous pharmaceutical companies, including Astra Zeneca, which sponsored the current study.

LISBON – Even small changes in hemoglobin A_1c and blood pressure could significantly reduce the risk of heart attack, stroke, and other cardiovascular complications in people who have type 2 diabetes, according to the findings of a population-based observational study of nearly 6,000 patients.

A 0.5% decrease in HbA_1c and a 10–mm Hg decrease in systolic blood pressure could avert 10% of such events over the course of 5 years, Dr. Edith Heintjes said at the annual meeting. Greater changes could reduce cardiovascular events by as much as 21%, said Dr. Heintjes of the PHARMO Institute for Drug Research, Utrecht, the Netherlands.

Although Dr. Heintjes' study on population attributable risk was theoretical, it still adds weight to the emerging theory that small changes can make a big difference to the health of people with type 2 diabetes.

“Even when we examined only modest incremental reductions, which could be achieved in the clinical setting, we found the possibility of significant benefit,” she said.

Those patients who had the greatest risk factors – elevated HbA_1c, high blood pressure, and higher body mass index – stand to gain the most when they improve those factors, she said.

Dr. Heintjes' analysis included 5,841 Dutch patients with a diagnosis of type 2 diabetes for at least 2 years.

The patients were all taking some form of treatment – oral medications, insulin, or both – for at least 6 months to be included in the study.

After examining both baseline data and 5-year outcomes, Dr. Heintjes was able to extrapolate how improvements in the three risk factors might impact the expected number of cardiovascular events.

Patient data were drawn from the PHARMO record linkage system, which includes community pharmaceutical dispensing information, laboratory information, national hospitalization information, and statistics from the Dutch national diabetes monitoring program.

Patients were treated with the aim of achieving the country's national targets: an HbA_1c of below 7%, a systolic blood pressure of 140 mm Hg or lower, and a body mass index of 25 kg/m

At baseline, the patients' average age was 66 years. The average HbA_1c was 7%; systolic blood pressure 149 mm Hg, and body mass index, 29.5 kg/m

Most of the patients (92%) were taking only oral medications. The rest of them were also taking insulin.

Some cardiovascular morbidity was already present in the group, including peripheral artery disease (0.5%), renal impairment (11%), neuropathy (51%), and retinopathy (7%). About half of the group (45%) had a family history of cardiovascular disease.

Dr. Heintjes divided the group according to the number of risk factors each patient exhibited. A quarter (24%) had just one elevated risk factor; 47% had two elevated risk factors, and 26% had elevations in all three risk factors.

A multivariable analysis allowed her to extrapolate that 796 cardiovascular events (heart attack, ischemic heart disease, stroke, and chronic heart failure) would occur if all of the patients were followed for 5 years.

If every patient in this population were able to correct each one of the risk factors to the national recommendations, she said, 687 events would occur – a 14% decrease. Correcting HbA_1c and blood pressure accounted for this change, she said; changing BMI did nothing to increase the benefit.

Theoretically, she said, patients with the most risk factors would reap the greatest benefit. The 24% with one elevated risk factor would experience a 5% reduction in cardiovascular events, while those with all three elevated risk factors, upon correcting them, would see a 21% reduction.

With regard to the group's baseline measurements, correcting to national Dutch standards would mean an average HbA_1c reduction of 0.8%, a 26–mm Hg reduction in systolic blood pressure, and a weight loss of 16 kg (equivalent to a BMI decrease of 5.7 kg/m

However, Dr. Heintjes said, it might not be realistic to expect such changes.

Her second analysis explored the improvements that could arise from smaller changes: a 0.5% reduction in HbA_1c, a 10–mm Hg reduction in systolic blood pressure, and a 10% reduction in total body weight (2.6 kg/m

“With this analysis, we saw in the overall population that 6% of the risk could be averted,” she said. Among those patients in the subpopulation with three risk factors, applying the smaller changes could cut the number of events by 10%.

It's not exactly clear how the results can change clinical practice, Dr. Heintjes acknowledged.“But this does allow us to unders

“But this does allow us to understand how small changes can translate into bigger benefits for people with type 2 diabetes,” she said.

Major Finding: Reducing HbA_1c, blood pressure, and weight could avert up to 21% of cardiovascular events in patients with type 2 diabetes.

Data Source: A population-based observational study comprising 5,841 patients.

Disclosures: Dr. Heintjes reported having no conflicts of interest. Her employer, PHARMO, however, receives funding from numerous pharmaceutical companies, including Astra Zeneca, which sponsored the current study.

LISBON – Even small changes in hemoglobin A_1c and blood pressure could significantly reduce the risk of heart attack, stroke, and other cardiovascular complications in people who have type 2 diabetes, according to the findings of a population-based observational study of nearly 6,000 patients.

A 0.5% decrease in HbA_1c and a 10–mm Hg decrease in systolic blood pressure could avert 10% of such events over the course of 5 years, Dr. Edith Heintjes said at the annual meeting. Greater changes could reduce cardiovascular events by as much as 21%, said Dr. Heintjes of the PHARMO Institute for Drug Research, Utrecht, the Netherlands.

Although Dr. Heintjes' study on population attributable risk was theoretical, it still adds weight to the emerging theory that small changes can make a big difference to the health of people with type 2 diabetes.

“Even when we examined only modest incremental reductions, which could be achieved in the clinical setting, we found the possibility of significant benefit,” she said.

Those patients who had the greatest risk factors – elevated HbA_1c, high blood pressure, and higher body mass index – stand to gain the most when they improve those factors, she said.

Dr. Heintjes' analysis included 5,841 Dutch patients with a diagnosis of type 2 diabetes for at least 2 years.

The patients were all taking some form of treatment – oral medications, insulin, or both – for at least 6 months to be included in the study.

After examining both baseline data and 5-year outcomes, Dr. Heintjes was able to extrapolate how improvements in the three risk factors might impact the expected number of cardiovascular events.

Patient data were drawn from the PHARMO record linkage system, which includes community pharmaceutical dispensing information, laboratory information, national hospitalization information, and statistics from the Dutch national diabetes monitoring program.

Patients were treated with the aim of achieving the country's national targets: an HbA_1c of below 7%, a systolic blood pressure of 140 mm Hg or lower, and a body mass index of 25 kg/m

At baseline, the patients' average age was 66 years. The average HbA_1c was 7%; systolic blood pressure 149 mm Hg, and body mass index, 29.5 kg/m

Most of the patients (92%) were taking only oral medications. The rest of them were also taking insulin.

Some cardiovascular morbidity was already present in the group, including peripheral artery disease (0.5%), renal impairment (11%), neuropathy (51%), and retinopathy (7%). About half of the group (45%) had a family history of cardiovascular disease.

Dr. Heintjes divided the group according to the number of risk factors each patient exhibited. A quarter (24%) had just one elevated risk factor; 47% had two elevated risk factors, and 26% had elevations in all three risk factors.

A multivariable analysis allowed her to extrapolate that 796 cardiovascular events (heart attack, ischemic heart disease, stroke, and chronic heart failure) would occur if all of the patients were followed for 5 years.

If every patient in this population were able to correct each one of the risk factors to the national recommendations, she said, 687 events would occur – a 14% decrease. Correcting HbA_1c and blood pressure accounted for this change, she said; changing BMI did nothing to increase the benefit.

Theoretically, she said, patients with the most risk factors would reap the greatest benefit. The 24% with one elevated risk factor would experience a 5% reduction in cardiovascular events, while those with all three elevated risk factors, upon correcting them, would see a 21% reduction.

With regard to the group's baseline measurements, correcting to national Dutch standards would mean an average HbA_1c reduction of 0.8%, a 26–mm Hg reduction in systolic blood pressure, and a weight loss of 16 kg (equivalent to a BMI decrease of 5.7 kg/m

However, Dr. Heintjes said, it might not be realistic to expect such changes.

Her second analysis explored the improvements that could arise from smaller changes: a 0.5% reduction in HbA_1c, a 10–mm Hg reduction in systolic blood pressure, and a 10% reduction in total body weight (2.6 kg/m

“With this analysis, we saw in the overall population that 6% of the risk could be averted,” she said. Among those patients in the subpopulation with three risk factors, applying the smaller changes could cut the number of events by 10%.

It's not exactly clear how the results can change clinical practice, Dr. Heintjes acknowledged.“But this does allow us to unders

“But this does allow us to understand how small changes can translate into bigger benefits for people with type 2 diabetes,” she said.

Major Finding: Up to 65 months after receiving an implanted neuromodulator, 82% of patients with craniofacial pain syndromes still reported significant pain relief.

Data Source: Retrospective study of 99 surgeries performed from 2004 to 2011.

Disclosures: Dr. Mammis had no financial disclosures.

WASHINGTON – Peripheral neuromodulation effectively managed a variety of craniofacial and headache pain syndromes, with 82% of patients reporting significant pain relief up to 65 months after the surgery in a retrospective study.

While percutaneous neuromodulation surgery is by no means a primary therapy for facial pain or headache, “it is something to keep in mind for patients with intractable pain,” Dr. Antonios Mammis said at the meeting.

Dr. Mammis, a resident at the Neurological Institute of New Jersey in Newark, presented a review of 99 patients who underwent occipital or trigeminal branch stimulation for a variety of craniofacial pain syndromes. The study won the group's Ronald Tasker Award for Research in Pain Management. He conducted the study while he was a resident at Long Island Jewish Medical Center, New Hyde Park, N.Y.

The review encompassed procedures done by a single neurosurgeon from 2004 to 2011. During the review, Dr. Mammis reclassified each patient's symptoms according to the International Classification of Headache Disorders, Second Edition. Of the 99 patients, 74 were female. The mean age at surgery was 43 years (range, 11-68 years).

Chiari malformation type 1 was the most common classification (28 patients). This was not a surprise, since the neurosurgeon worked at a Chiari referral center.

Other pain classifications included migraine with or without aura (24), chronic posttraumatic headache attributed to mild head injury (11), occipital neuralgia (8), postcraniotomy headache (7), chronic cluster headache (5), headache secondary to ischemic stroke (5), other terminal branch neuralgias (5), cervicogenic headache (4), hemicrania continua (1), and acromegaly (1).

All patients underwent a 4- to 7-day treatment trial, with a bilateral lead placement performed under local anesthesia with intravenous sedation. The surgeon used surface anatomy and fluoroscopy to determine lead placement. During the trial, patients kept a headache diary noting frequency, duration, and severity.

After the trial period, 79 patients (80%) reported significant pain relief, which was defined as at least a 50% decrease in pain as rated on a visual analog scale. These patients went on to have a permanent neuromodulator implanted. Of these, 56 received only occipital leads, 12 received only trigeminal leads, and 11 had leads implanted on both nerve branches.

Most of the headache syndromes responded equally well to the neurostimulators. At the last follow-up, which ranged from 1 to 65 months, 65 (82%) reported continued use of the stimulator and continued to report significant pain improvement.

At that time, stimulators were still being used in 15 of 18 Chiari malformation patients, 19 of 21 migraine patients, 7 of 7 occipital neuralgia patients, 6 of 7 postcraniotomy patients, 4 of 4 cluster headache patients, 1 of 3 ischemic stroke patients, 1 of 4 terminal branch neuralgia patients, 3 of 3 cervicogenic headache patients, and the one patient with hemicrania continua. The single acromegaly patient received a stimulator, but did not have long-term pain relief.

Complications arose in 10 patients. Four of these were lead migrations that required revision, which is “a problem that is very easily corrected,” Dr. Mammis said. Six patients acquired an infection; three were wound erosions and three were surgical site infections without erosion. “All of these leads were explanted and revised,” he said. There were no infections after revision.

Nearly a quarter of the patients (22%) asked for a cosmetic revision. “This was primarily done because they could see or feel the lead,” Dr. Mammis said. “These were not infected leads, and there were no infections after these revisions.”

Major Finding: Up to 65 months after receiving an implanted neuromodulator, 82% of patients with craniofacial pain syndromes still reported significant pain relief.

Data Source: Retrospective study of 99 surgeries performed from 2004 to 2011.

Disclosures: Dr. Mammis had no financial disclosures.

WASHINGTON – Peripheral neuromodulation effectively managed a variety of craniofacial and headache pain syndromes, with 82% of patients reporting significant pain relief up to 65 months after the surgery in a retrospective study.

While percutaneous neuromodulation surgery is by no means a primary therapy for facial pain or headache, “it is something to keep in mind for patients with intractable pain,” Dr. Antonios Mammis said at the meeting.

Dr. Mammis, a resident at the Neurological Institute of New Jersey in Newark, presented a review of 99 patients who underwent occipital or trigeminal branch stimulation for a variety of craniofacial pain syndromes. The study won the group's Ronald Tasker Award for Research in Pain Management. He conducted the study while he was a resident at Long Island Jewish Medical Center, New Hyde Park, N.Y.

The review encompassed procedures done by a single neurosurgeon from 2004 to 2011. During the review, Dr. Mammis reclassified each patient's symptoms according to the International Classification of Headache Disorders, Second Edition. Of the 99 patients, 74 were female. The mean age at surgery was 43 years (range, 11-68 years).

Chiari malformation type 1 was the most common classification (28 patients). This was not a surprise, since the neurosurgeon worked at a Chiari referral center.

Other pain classifications included migraine with or without aura (24), chronic posttraumatic headache attributed to mild head injury (11), occipital neuralgia (8), postcraniotomy headache (7), chronic cluster headache (5), headache secondary to ischemic stroke (5), other terminal branch neuralgias (5), cervicogenic headache (4), hemicrania continua (1), and acromegaly (1).

All patients underwent a 4- to 7-day treatment trial, with a bilateral lead placement performed under local anesthesia with intravenous sedation. The surgeon used surface anatomy and fluoroscopy to determine lead placement. During the trial, patients kept a headache diary noting frequency, duration, and severity.

After the trial period, 79 patients (80%) reported significant pain relief, which was defined as at least a 50% decrease in pain as rated on a visual analog scale. These patients went on to have a permanent neuromodulator implanted. Of these, 56 received only occipital leads, 12 received only trigeminal leads, and 11 had leads implanted on both nerve branches.

Most of the headache syndromes responded equally well to the neurostimulators. At the last follow-up, which ranged from 1 to 65 months, 65 (82%) reported continued use of the stimulator and continued to report significant pain improvement.

At that time, stimulators were still being used in 15 of 18 Chiari malformation patients, 19 of 21 migraine patients, 7 of 7 occipital neuralgia patients, 6 of 7 postcraniotomy patients, 4 of 4 cluster headache patients, 1 of 3 ischemic stroke patients, 1 of 4 terminal branch neuralgia patients, 3 of 3 cervicogenic headache patients, and the one patient with hemicrania continua. The single acromegaly patient received a stimulator, but did not have long-term pain relief.

Complications arose in 10 patients. Four of these were lead migrations that required revision, which is “a problem that is very easily corrected,” Dr. Mammis said. Six patients acquired an infection; three were wound erosions and three were surgical site infections without erosion. “All of these leads were explanted and revised,” he said. There were no infections after revision.

Nearly a quarter of the patients (22%) asked for a cosmetic revision. “This was primarily done because they could see or feel the lead,” Dr. Mammis said. “These were not infected leads, and there were no infections after these revisions.”

Major Finding: Up to 65 months after receiving an implanted neuromodulator, 82% of patients with craniofacial pain syndromes still reported significant pain relief.

Data Source: Retrospective study of 99 surgeries performed from 2004 to 2011.

Disclosures: Dr. Mammis had no financial disclosures.

WASHINGTON – Peripheral neuromodulation effectively managed a variety of craniofacial and headache pain syndromes, with 82% of patients reporting significant pain relief up to 65 months after the surgery in a retrospective study.

While percutaneous neuromodulation surgery is by no means a primary therapy for facial pain or headache, “it is something to keep in mind for patients with intractable pain,” Dr. Antonios Mammis said at the meeting.

Dr. Mammis, a resident at the Neurological Institute of New Jersey in Newark, presented a review of 99 patients who underwent occipital or trigeminal branch stimulation for a variety of craniofacial pain syndromes. The study won the group's Ronald Tasker Award for Research in Pain Management. He conducted the study while he was a resident at Long Island Jewish Medical Center, New Hyde Park, N.Y.

The review encompassed procedures done by a single neurosurgeon from 2004 to 2011. During the review, Dr. Mammis reclassified each patient's symptoms according to the International Classification of Headache Disorders, Second Edition. Of the 99 patients, 74 were female. The mean age at surgery was 43 years (range, 11-68 years).

Chiari malformation type 1 was the most common classification (28 patients). This was not a surprise, since the neurosurgeon worked at a Chiari referral center.

Other pain classifications included migraine with or without aura (24), chronic posttraumatic headache attributed to mild head injury (11), occipital neuralgia (8), postcraniotomy headache (7), chronic cluster headache (5), headache secondary to ischemic stroke (5), other terminal branch neuralgias (5), cervicogenic headache (4), hemicrania continua (1), and acromegaly (1).

All patients underwent a 4- to 7-day treatment trial, with a bilateral lead placement performed under local anesthesia with intravenous sedation. The surgeon used surface anatomy and fluoroscopy to determine lead placement. During the trial, patients kept a headache diary noting frequency, duration, and severity.

After the trial period, 79 patients (80%) reported significant pain relief, which was defined as at least a 50% decrease in pain as rated on a visual analog scale. These patients went on to have a permanent neuromodulator implanted. Of these, 56 received only occipital leads, 12 received only trigeminal leads, and 11 had leads implanted on both nerve branches.

Most of the headache syndromes responded equally well to the neurostimulators. At the last follow-up, which ranged from 1 to 65 months, 65 (82%) reported continued use of the stimulator and continued to report significant pain improvement.

At that time, stimulators were still being used in 15 of 18 Chiari malformation patients, 19 of 21 migraine patients, 7 of 7 occipital neuralgia patients, 6 of 7 postcraniotomy patients, 4 of 4 cluster headache patients, 1 of 3 ischemic stroke patients, 1 of 4 terminal branch neuralgia patients, 3 of 3 cervicogenic headache patients, and the one patient with hemicrania continua. The single acromegaly patient received a stimulator, but did not have long-term pain relief.

Complications arose in 10 patients. Four of these were lead migrations that required revision, which is “a problem that is very easily corrected,” Dr. Mammis said. Six patients acquired an infection; three were wound erosions and three were surgical site infections without erosion. “All of these leads were explanted and revised,” he said. There were no infections after revision.

Nearly a quarter of the patients (22%) asked for a cosmetic revision. “This was primarily done because they could see or feel the lead,” Dr. Mammis said. “These were not infected leads, and there were no infections after these revisions.”