Jennie Smith

A short, brisk walk can reduce the urge to drink alcohol among heavy drinkers, a group of researchers has found.

The results of the study mirror findings from research showing that moderate exercise can reduce signals of food and cigarette cravings. However, this was the first study to report that a single session of moderate exercise can significantly reduce attentional bias toward alcohol-related images as well as self-reported cravings (Ment. Health Phys. Act. 2013 Sept. 20 [doi: 10.1016/j.mhpa.2013.09.004]). A previous study in diagnosed alcoholics found that alcohol cravings were reduced during a brief period of exercise but not after it (Addict. 2004;99:1542-7).

©iStock/thinkstockphotos.com

Attentional bias, the tendency to focus on emotionally dominant stimuli, is an important measure used in studies of cravings, as it relies not on self-reporting but on visual attention paid to images presented by investigators. In the current study, led by Adrian H. Taylor, Ph.D., of the University of Exeter, in Devon, England, investigators measured two types of attentional bias – initial and maintained – related to alcohol imagery. The latter was found to be significantly reduced in the group that had exercised, compared with the controls. Self-reported cravings also were shown to be reduced.

For their research, Dr. Taylor and his colleagues recruited 20 healthy volunteers (mean age, 20.8 years; 11 women) who were not alcoholics seeking treatment but who self-reported drinking heavily. The women reported drinking 14 units of alcohol or more per week, and the men reported drinking 21 units or more per week.

Subjects were randomly assigned either to 15 minutes of sitting without access to reading materials or other stimuli or to 15 minutes of moderate walking on a treadmill. Before and after the period of sitting or walking, participants completed a task that matched neutral and alcohol images randomly presented for either 200 ms to measure initial attentional bias (IAB) or 1 second to measure maintained attentional bias (MAB). A standardized Alcohol Urge Questionnaire also was administered before, and three times after, the period of sitting or walking to collect information on self-reported cravings.

The study’s results showed that MAB was significantly reduced after exercise, compared with the control condition (P = .058).

The mechanisms mediating the effect of exercise on alcohol urges during exercise are unclear, Dr. Taylor and his colleagues said. Drinking alcohol regulates moods and reduces negative feelings. Perhaps exercise also enhances "affect and mood in a way that reduces drinking urges and salience of alcohol as a source of pleasure and reward." Animal research has suggested that numerous neurobiological mechanisms are implicated in drug use and might be modifiable by exercise, "including dopamine, glutamate, norepinephrine, opioids, PKA [protein kinase A], extracellular signal-related kinase, and brain-derived neurotropic factor," they wrote.

However, the investigators also acknowledged that they could not exclude the possibility that the effect seen in the intervention group was tied to distraction rather than physical activity. Future studies, they said, should include a third arm of subjects who would be allowed to watch television or participate in other distracting activity prior to being tested. Another limitation cited by the investigators was the fact that participants were not clinically diagnosed as alcoholics but self-reported as heavy drinkers.

Further research is needed to determine whether short bursts of exercise could help reduce alcohol cravings in people prone to them, the authors wrote. However, they said, the findings had some immediate implications for practice: "A short, brisk walk may be an attractive self-help strategy to manage cravings and provide immediate relief for those experiencing alcohol urges."

The authors received no external funding, and neither Dr. Taylor nor his coauthors had conflicts of interest.

A short, brisk walk can reduce the urge to drink alcohol among heavy drinkers, a group of researchers has found.

The results of the study mirror findings from research showing that moderate exercise can reduce signals of food and cigarette cravings. However, this was the first study to report that a single session of moderate exercise can significantly reduce attentional bias toward alcohol-related images as well as self-reported cravings (Ment. Health Phys. Act. 2013 Sept. 20 [doi: 10.1016/j.mhpa.2013.09.004]). A previous study in diagnosed alcoholics found that alcohol cravings were reduced during a brief period of exercise but not after it (Addict. 2004;99:1542-7).

©iStock/thinkstockphotos.com

Attentional bias, the tendency to focus on emotionally dominant stimuli, is an important measure used in studies of cravings, as it relies not on self-reporting but on visual attention paid to images presented by investigators. In the current study, led by Adrian H. Taylor, Ph.D., of the University of Exeter, in Devon, England, investigators measured two types of attentional bias – initial and maintained – related to alcohol imagery. The latter was found to be significantly reduced in the group that had exercised, compared with the controls. Self-reported cravings also were shown to be reduced.

For their research, Dr. Taylor and his colleagues recruited 20 healthy volunteers (mean age, 20.8 years; 11 women) who were not alcoholics seeking treatment but who self-reported drinking heavily. The women reported drinking 14 units of alcohol or more per week, and the men reported drinking 21 units or more per week.

Subjects were randomly assigned either to 15 minutes of sitting without access to reading materials or other stimuli or to 15 minutes of moderate walking on a treadmill. Before and after the period of sitting or walking, participants completed a task that matched neutral and alcohol images randomly presented for either 200 ms to measure initial attentional bias (IAB) or 1 second to measure maintained attentional bias (MAB). A standardized Alcohol Urge Questionnaire also was administered before, and three times after, the period of sitting or walking to collect information on self-reported cravings.

The study’s results showed that MAB was significantly reduced after exercise, compared with the control condition (P = .058).

The mechanisms mediating the effect of exercise on alcohol urges during exercise are unclear, Dr. Taylor and his colleagues said. Drinking alcohol regulates moods and reduces negative feelings. Perhaps exercise also enhances "affect and mood in a way that reduces drinking urges and salience of alcohol as a source of pleasure and reward." Animal research has suggested that numerous neurobiological mechanisms are implicated in drug use and might be modifiable by exercise, "including dopamine, glutamate, norepinephrine, opioids, PKA [protein kinase A], extracellular signal-related kinase, and brain-derived neurotropic factor," they wrote.

However, the investigators also acknowledged that they could not exclude the possibility that the effect seen in the intervention group was tied to distraction rather than physical activity. Future studies, they said, should include a third arm of subjects who would be allowed to watch television or participate in other distracting activity prior to being tested. Another limitation cited by the investigators was the fact that participants were not clinically diagnosed as alcoholics but self-reported as heavy drinkers.

Further research is needed to determine whether short bursts of exercise could help reduce alcohol cravings in people prone to them, the authors wrote. However, they said, the findings had some immediate implications for practice: "A short, brisk walk may be an attractive self-help strategy to manage cravings and provide immediate relief for those experiencing alcohol urges."

The authors received no external funding, and neither Dr. Taylor nor his coauthors had conflicts of interest.

A short, brisk walk can reduce the urge to drink alcohol among heavy drinkers, a group of researchers has found.

The results of the study mirror findings from research showing that moderate exercise can reduce signals of food and cigarette cravings. However, this was the first study to report that a single session of moderate exercise can significantly reduce attentional bias toward alcohol-related images as well as self-reported cravings (Ment. Health Phys. Act. 2013 Sept. 20 [doi: 10.1016/j.mhpa.2013.09.004]). A previous study in diagnosed alcoholics found that alcohol cravings were reduced during a brief period of exercise but not after it (Addict. 2004;99:1542-7).

©iStock/thinkstockphotos.com

Attentional bias, the tendency to focus on emotionally dominant stimuli, is an important measure used in studies of cravings, as it relies not on self-reporting but on visual attention paid to images presented by investigators. In the current study, led by Adrian H. Taylor, Ph.D., of the University of Exeter, in Devon, England, investigators measured two types of attentional bias – initial and maintained – related to alcohol imagery. The latter was found to be significantly reduced in the group that had exercised, compared with the controls. Self-reported cravings also were shown to be reduced.

For their research, Dr. Taylor and his colleagues recruited 20 healthy volunteers (mean age, 20.8 years; 11 women) who were not alcoholics seeking treatment but who self-reported drinking heavily. The women reported drinking 14 units of alcohol or more per week, and the men reported drinking 21 units or more per week.

Subjects were randomly assigned either to 15 minutes of sitting without access to reading materials or other stimuli or to 15 minutes of moderate walking on a treadmill. Before and after the period of sitting or walking, participants completed a task that matched neutral and alcohol images randomly presented for either 200 ms to measure initial attentional bias (IAB) or 1 second to measure maintained attentional bias (MAB). A standardized Alcohol Urge Questionnaire also was administered before, and three times after, the period of sitting or walking to collect information on self-reported cravings.

The study’s results showed that MAB was significantly reduced after exercise, compared with the control condition (P = .058).

The mechanisms mediating the effect of exercise on alcohol urges during exercise are unclear, Dr. Taylor and his colleagues said. Drinking alcohol regulates moods and reduces negative feelings. Perhaps exercise also enhances "affect and mood in a way that reduces drinking urges and salience of alcohol as a source of pleasure and reward." Animal research has suggested that numerous neurobiological mechanisms are implicated in drug use and might be modifiable by exercise, "including dopamine, glutamate, norepinephrine, opioids, PKA [protein kinase A], extracellular signal-related kinase, and brain-derived neurotropic factor," they wrote.

However, the investigators also acknowledged that they could not exclude the possibility that the effect seen in the intervention group was tied to distraction rather than physical activity. Future studies, they said, should include a third arm of subjects who would be allowed to watch television or participate in other distracting activity prior to being tested. Another limitation cited by the investigators was the fact that participants were not clinically diagnosed as alcoholics but self-reported as heavy drinkers.

Further research is needed to determine whether short bursts of exercise could help reduce alcohol cravings in people prone to them, the authors wrote. However, they said, the findings had some immediate implications for practice: "A short, brisk walk may be an attractive self-help strategy to manage cravings and provide immediate relief for those experiencing alcohol urges."

The authors received no external funding, and neither Dr. Taylor nor his coauthors had conflicts of interest.

Nearly half of heroin users who are hospitalized for medical or surgical treatment perceive themselves to be in good, very good, or excellent health, "underlining a disconnect between addiction and perceived health status," according to a study of 112 patients.

The apparent disparity between self-reported health and disease burden suggests that "perceptions of health status may not actually reflect physical health but a different construct altogether," Lidia Z. Meshesa and her colleagues wrote.

The investigators enrolled 112 non–treatment-seeking hospitalized heroin users in the study. The average age of the participants was 40 years, and 72% were male, reported Ms. Meshesa, of the Clinical Research and Education (CARE) Unit at Boston Medical Center, and her coauthors (Addict. Behav. 2013;38:2884-7). None was currently in treatment for substance abuse. All the participants completed a standard questionnaire on health-related quality of life and were asked detailed questions about their drug use and mental and physical health histories.

The investigators found that each day of heroin use in the previous month was associated with 8% lower odds of reporting health as good or better (odds ratio, 0.92; 95% confidence interval, 0.87-0.97; P less than .05). While about 47% of subjects self-reported their health status as good, very good, or excellent, some 68% also reported having been diagnosed with one or more chronic diseases, including diabetes, viral hepatitis, cardiovascular disease, HIV, or cancer. The main causes of hospitalization were cellulitis, drug overdose or withdrawal, pneumonia, endocarditis or sepsis, and HIV disease.

For this cohort, perceptions of good health could be associated more with absence of withdrawal symptoms than presence of disease, the investigators suggested. Of the 21 subjects reporting an accidental overdose within the previous 6 months, 62% also rated their health as good or better. Such subjects "may have a sense of immortality or lack of vulnerability after having survived a near-death experience," the investigators wrote in their analysis. "Therefore, it may be seen that using heroin frequently is a way of alleviating health problems."

Although the study found the number of days of heroin use in the previous month to be correlated with self-rated health status, use of other substances such as cocaine, marijuana, cigarettes, and alcohol did not show significant correlations to perceptions of overall health. Some 63% of the cohort had reported using cocaine in the previous month.

"Our study adds to this body of literature demonstrating that there is a graded effect between number of days using heroin and health status. However, this study also suggests that patients with opiate addiction may not recognize other risky drug use behaviors as being important to their health," the investigators wrote.

Because perceptions of poor health have been shown in other studies to affect users’ likelihood of seeking treatment (J. Subst. Abuse Treat. 2006;31:143-50; Addict. Behav. 2006;31:1904-18), the finding of good self-reported health status in nearly half of a cohort of hospitalized heroin users "suggests that a perception of good health may be a barrier to engaging in substance use treatment. Providers may need to help patients reframe addictions and risky behaviors as important components of overall health," Ms. Meshesha and her colleagues wrote.

The investigators described as limitations of their study the use of a single question to define self-perceived health status and the fact that all subjects were hospitalized when interviewed, limiting the generalizability of findings. Finally, "neurocognitive deficits due to drug use may contribute to impaired self-awareness," they wrote.

The study was funded by a grant from the National Institute on Drug Abuse. None of its authors declared conflicts of interest.

Nearly half of heroin users who are hospitalized for medical or surgical treatment perceive themselves to be in good, very good, or excellent health, "underlining a disconnect between addiction and perceived health status," according to a study of 112 patients.

The apparent disparity between self-reported health and disease burden suggests that "perceptions of health status may not actually reflect physical health but a different construct altogether," Lidia Z. Meshesa and her colleagues wrote.

The investigators enrolled 112 non–treatment-seeking hospitalized heroin users in the study. The average age of the participants was 40 years, and 72% were male, reported Ms. Meshesa, of the Clinical Research and Education (CARE) Unit at Boston Medical Center, and her coauthors (Addict. Behav. 2013;38:2884-7). None was currently in treatment for substance abuse. All the participants completed a standard questionnaire on health-related quality of life and were asked detailed questions about their drug use and mental and physical health histories.

The investigators found that each day of heroin use in the previous month was associated with 8% lower odds of reporting health as good or better (odds ratio, 0.92; 95% confidence interval, 0.87-0.97; P less than .05). While about 47% of subjects self-reported their health status as good, very good, or excellent, some 68% also reported having been diagnosed with one or more chronic diseases, including diabetes, viral hepatitis, cardiovascular disease, HIV, or cancer. The main causes of hospitalization were cellulitis, drug overdose or withdrawal, pneumonia, endocarditis or sepsis, and HIV disease.

For this cohort, perceptions of good health could be associated more with absence of withdrawal symptoms than presence of disease, the investigators suggested. Of the 21 subjects reporting an accidental overdose within the previous 6 months, 62% also rated their health as good or better. Such subjects "may have a sense of immortality or lack of vulnerability after having survived a near-death experience," the investigators wrote in their analysis. "Therefore, it may be seen that using heroin frequently is a way of alleviating health problems."

Although the study found the number of days of heroin use in the previous month to be correlated with self-rated health status, use of other substances such as cocaine, marijuana, cigarettes, and alcohol did not show significant correlations to perceptions of overall health. Some 63% of the cohort had reported using cocaine in the previous month.

"Our study adds to this body of literature demonstrating that there is a graded effect between number of days using heroin and health status. However, this study also suggests that patients with opiate addiction may not recognize other risky drug use behaviors as being important to their health," the investigators wrote.

Because perceptions of poor health have been shown in other studies to affect users’ likelihood of seeking treatment (J. Subst. Abuse Treat. 2006;31:143-50; Addict. Behav. 2006;31:1904-18), the finding of good self-reported health status in nearly half of a cohort of hospitalized heroin users "suggests that a perception of good health may be a barrier to engaging in substance use treatment. Providers may need to help patients reframe addictions and risky behaviors as important components of overall health," Ms. Meshesha and her colleagues wrote.

The investigators described as limitations of their study the use of a single question to define self-perceived health status and the fact that all subjects were hospitalized when interviewed, limiting the generalizability of findings. Finally, "neurocognitive deficits due to drug use may contribute to impaired self-awareness," they wrote.

The study was funded by a grant from the National Institute on Drug Abuse. None of its authors declared conflicts of interest.

Nearly half of heroin users who are hospitalized for medical or surgical treatment perceive themselves to be in good, very good, or excellent health, "underlining a disconnect between addiction and perceived health status," according to a study of 112 patients.

The apparent disparity between self-reported health and disease burden suggests that "perceptions of health status may not actually reflect physical health but a different construct altogether," Lidia Z. Meshesa and her colleagues wrote.

The investigators enrolled 112 non–treatment-seeking hospitalized heroin users in the study. The average age of the participants was 40 years, and 72% were male, reported Ms. Meshesa, of the Clinical Research and Education (CARE) Unit at Boston Medical Center, and her coauthors (Addict. Behav. 2013;38:2884-7). None was currently in treatment for substance abuse. All the participants completed a standard questionnaire on health-related quality of life and were asked detailed questions about their drug use and mental and physical health histories.

The investigators found that each day of heroin use in the previous month was associated with 8% lower odds of reporting health as good or better (odds ratio, 0.92; 95% confidence interval, 0.87-0.97; P less than .05). While about 47% of subjects self-reported their health status as good, very good, or excellent, some 68% also reported having been diagnosed with one or more chronic diseases, including diabetes, viral hepatitis, cardiovascular disease, HIV, or cancer. The main causes of hospitalization were cellulitis, drug overdose or withdrawal, pneumonia, endocarditis or sepsis, and HIV disease.

For this cohort, perceptions of good health could be associated more with absence of withdrawal symptoms than presence of disease, the investigators suggested. Of the 21 subjects reporting an accidental overdose within the previous 6 months, 62% also rated their health as good or better. Such subjects "may have a sense of immortality or lack of vulnerability after having survived a near-death experience," the investigators wrote in their analysis. "Therefore, it may be seen that using heroin frequently is a way of alleviating health problems."

Although the study found the number of days of heroin use in the previous month to be correlated with self-rated health status, use of other substances such as cocaine, marijuana, cigarettes, and alcohol did not show significant correlations to perceptions of overall health. Some 63% of the cohort had reported using cocaine in the previous month.

"Our study adds to this body of literature demonstrating that there is a graded effect between number of days using heroin and health status. However, this study also suggests that patients with opiate addiction may not recognize other risky drug use behaviors as being important to their health," the investigators wrote.

Because perceptions of poor health have been shown in other studies to affect users’ likelihood of seeking treatment (J. Subst. Abuse Treat. 2006;31:143-50; Addict. Behav. 2006;31:1904-18), the finding of good self-reported health status in nearly half of a cohort of hospitalized heroin users "suggests that a perception of good health may be a barrier to engaging in substance use treatment. Providers may need to help patients reframe addictions and risky behaviors as important components of overall health," Ms. Meshesha and her colleagues wrote.

The investigators described as limitations of their study the use of a single question to define self-perceived health status and the fact that all subjects were hospitalized when interviewed, limiting the generalizability of findings. Finally, "neurocognitive deficits due to drug use may contribute to impaired self-awareness," they wrote.

The study was funded by a grant from the National Institute on Drug Abuse. None of its authors declared conflicts of interest.

Brivaracetam was found to be a safe and tolerable add-on treatment for uncontrolled epilepsy in adults, in a phase III, randomized, double-blind placebo-controlled trial.

This confirms findings from previous phase II trials of the investigational antiepileptic drug.

The current industry-sponsored study found similar rates of adverse events in the placebo and treatment groups. Efficacy endpoints were secondary in this trial; however, most of these did not reach statistical significance (Epilepsia 2013 Oct. 3 [doi:10.1111/epi.12391]).

Dr. Patrick Kwan, chair of neurology at the University of Melbourne, and his colleagues, recruited 480 adults with focal epilepsy (n = 431) subjects) or generalized epilepsy (n = 49) who were already taking one to three antiepileptic drugs, and randomized them (3:1) to brivaracetam or placebo. A total of 74 outpatient centers in 15 countries enrolled the patients between October 2007 and December 2008.

Doses of brivaracetam could begin at 20 mg/day, with titration up to 150 mg/day during an initial 8-week dose-finding period, after which fixed-dose treatment was continued for another 8 weeks. More than 70% of patients in the treatment group ended up on a dose of 100 mg or higher.

The 16-week study was completed by 90% of patients in the treatment group and 92% in the placebo group. Similar percentages of patients in the treatment (66%) and placebo groups (65%) reported adverse events, most frequently headache, somnolence, and dizziness, mostly in the dose-finding period. Patients with generalized seizures, a group for which treatment options are more limited, tolerated brivaracetam as well as did patients with focal seizures.

In patients with focal seizures, the baseline-adjusted percent reduction in seizure frequency per week in the brivaracetam group (n = 323) over the placebo group (n = 108) was 7.3% (P = .125) during the treatment period. The median percent reduction in baseline-adjusted seizure frequency per week was 26.9% for brivaracetam, compared with 18.9% for placebo (P = .070).

In the smaller group of patients with generalized seizures, seizure days per week decreased from 1.42 at baseline to 0.63 during the treatment period in the brivaracetam group and from 1.47 at baseline to 1.26 during the treatment period in placebo-treated patients.

One efficacy endpoint that did meet statistical significance was the 50% or higher responder rate in patients with focal seizures, which was 30.3% for the treatment group, compared with 16.7% for the placebo group (P = .006).

Dr. Kwan and his colleagues wrote in their analysis that both the 50% or higher responder rate and median percent reduction from baseline in the treatment group were comparable with findings from a study that evaluated brivaracetam at 50 mg/day and 150 mg/day (Epilepsia 2013;54:89-97), but lower than those reported in another study that investigated dosing up to 50 mg/day (Neurology 2010;75:519-25). The optimal dose "remains to be defined," they wrote.

Brivaracetam is an analogue of the antiepileptic drug levetiracetam, and was shown in preclinical studies to be a far more powerful inhibitor of seizures than levetiracetam. However, Dr. Kwan and his colleagues wrote, "the expected corresponding efficacy benefit was not observed in this study." Another phase III trial is currently in progress to determine the most efficacious dose of brivaracetam.

The investigators acknowledged the flexible dosing design as a limitation of their study, "which may hinder conclusions regarding efficacy." They also noted that the numbers of patients with generalized epilepsy included were small, meaning that any results from that group should be considered exploratory and approached with caution.

The study was funded by UCB Pharma, the manufacturer of brivaracetam. Dr. Kwan disclosed financial relationships with UCB and GlaxoSmithKline and having served on scientific advisory boards for Eisai. Dr. Kwan’s coauthors disclosed consulting, honoraria, or advisory relationships with UCB and many other companies marketing antiepileptic drugs. Two coauthors are employees of UCB.

Brivaracetam was found to be a safe and tolerable add-on treatment for uncontrolled epilepsy in adults, in a phase III, randomized, double-blind placebo-controlled trial.

This confirms findings from previous phase II trials of the investigational antiepileptic drug.

The current industry-sponsored study found similar rates of adverse events in the placebo and treatment groups. Efficacy endpoints were secondary in this trial; however, most of these did not reach statistical significance (Epilepsia 2013 Oct. 3 [doi:10.1111/epi.12391]).

Dr. Patrick Kwan, chair of neurology at the University of Melbourne, and his colleagues, recruited 480 adults with focal epilepsy (n = 431) subjects) or generalized epilepsy (n = 49) who were already taking one to three antiepileptic drugs, and randomized them (3:1) to brivaracetam or placebo. A total of 74 outpatient centers in 15 countries enrolled the patients between October 2007 and December 2008.

Doses of brivaracetam could begin at 20 mg/day, with titration up to 150 mg/day during an initial 8-week dose-finding period, after which fixed-dose treatment was continued for another 8 weeks. More than 70% of patients in the treatment group ended up on a dose of 100 mg or higher.

The 16-week study was completed by 90% of patients in the treatment group and 92% in the placebo group. Similar percentages of patients in the treatment (66%) and placebo groups (65%) reported adverse events, most frequently headache, somnolence, and dizziness, mostly in the dose-finding period. Patients with generalized seizures, a group for which treatment options are more limited, tolerated brivaracetam as well as did patients with focal seizures.

In patients with focal seizures, the baseline-adjusted percent reduction in seizure frequency per week in the brivaracetam group (n = 323) over the placebo group (n = 108) was 7.3% (P = .125) during the treatment period. The median percent reduction in baseline-adjusted seizure frequency per week was 26.9% for brivaracetam, compared with 18.9% for placebo (P = .070).

In the smaller group of patients with generalized seizures, seizure days per week decreased from 1.42 at baseline to 0.63 during the treatment period in the brivaracetam group and from 1.47 at baseline to 1.26 during the treatment period in placebo-treated patients.

One efficacy endpoint that did meet statistical significance was the 50% or higher responder rate in patients with focal seizures, which was 30.3% for the treatment group, compared with 16.7% for the placebo group (P = .006).

Dr. Kwan and his colleagues wrote in their analysis that both the 50% or higher responder rate and median percent reduction from baseline in the treatment group were comparable with findings from a study that evaluated brivaracetam at 50 mg/day and 150 mg/day (Epilepsia 2013;54:89-97), but lower than those reported in another study that investigated dosing up to 50 mg/day (Neurology 2010;75:519-25). The optimal dose "remains to be defined," they wrote.

Brivaracetam is an analogue of the antiepileptic drug levetiracetam, and was shown in preclinical studies to be a far more powerful inhibitor of seizures than levetiracetam. However, Dr. Kwan and his colleagues wrote, "the expected corresponding efficacy benefit was not observed in this study." Another phase III trial is currently in progress to determine the most efficacious dose of brivaracetam.

The investigators acknowledged the flexible dosing design as a limitation of their study, "which may hinder conclusions regarding efficacy." They also noted that the numbers of patients with generalized epilepsy included were small, meaning that any results from that group should be considered exploratory and approached with caution.

The study was funded by UCB Pharma, the manufacturer of brivaracetam. Dr. Kwan disclosed financial relationships with UCB and GlaxoSmithKline and having served on scientific advisory boards for Eisai. Dr. Kwan’s coauthors disclosed consulting, honoraria, or advisory relationships with UCB and many other companies marketing antiepileptic drugs. Two coauthors are employees of UCB.

Brivaracetam was found to be a safe and tolerable add-on treatment for uncontrolled epilepsy in adults, in a phase III, randomized, double-blind placebo-controlled trial.

This confirms findings from previous phase II trials of the investigational antiepileptic drug.

The current industry-sponsored study found similar rates of adverse events in the placebo and treatment groups. Efficacy endpoints were secondary in this trial; however, most of these did not reach statistical significance (Epilepsia 2013 Oct. 3 [doi:10.1111/epi.12391]).

Dr. Patrick Kwan, chair of neurology at the University of Melbourne, and his colleagues, recruited 480 adults with focal epilepsy (n = 431) subjects) or generalized epilepsy (n = 49) who were already taking one to three antiepileptic drugs, and randomized them (3:1) to brivaracetam or placebo. A total of 74 outpatient centers in 15 countries enrolled the patients between October 2007 and December 2008.

Doses of brivaracetam could begin at 20 mg/day, with titration up to 150 mg/day during an initial 8-week dose-finding period, after which fixed-dose treatment was continued for another 8 weeks. More than 70% of patients in the treatment group ended up on a dose of 100 mg or higher.

The 16-week study was completed by 90% of patients in the treatment group and 92% in the placebo group. Similar percentages of patients in the treatment (66%) and placebo groups (65%) reported adverse events, most frequently headache, somnolence, and dizziness, mostly in the dose-finding period. Patients with generalized seizures, a group for which treatment options are more limited, tolerated brivaracetam as well as did patients with focal seizures.

In patients with focal seizures, the baseline-adjusted percent reduction in seizure frequency per week in the brivaracetam group (n = 323) over the placebo group (n = 108) was 7.3% (P = .125) during the treatment period. The median percent reduction in baseline-adjusted seizure frequency per week was 26.9% for brivaracetam, compared with 18.9% for placebo (P = .070).

In the smaller group of patients with generalized seizures, seizure days per week decreased from 1.42 at baseline to 0.63 during the treatment period in the brivaracetam group and from 1.47 at baseline to 1.26 during the treatment period in placebo-treated patients.

One efficacy endpoint that did meet statistical significance was the 50% or higher responder rate in patients with focal seizures, which was 30.3% for the treatment group, compared with 16.7% for the placebo group (P = .006).

Dr. Kwan and his colleagues wrote in their analysis that both the 50% or higher responder rate and median percent reduction from baseline in the treatment group were comparable with findings from a study that evaluated brivaracetam at 50 mg/day and 150 mg/day (Epilepsia 2013;54:89-97), but lower than those reported in another study that investigated dosing up to 50 mg/day (Neurology 2010;75:519-25). The optimal dose "remains to be defined," they wrote.

Brivaracetam is an analogue of the antiepileptic drug levetiracetam, and was shown in preclinical studies to be a far more powerful inhibitor of seizures than levetiracetam. However, Dr. Kwan and his colleagues wrote, "the expected corresponding efficacy benefit was not observed in this study." Another phase III trial is currently in progress to determine the most efficacious dose of brivaracetam.

The investigators acknowledged the flexible dosing design as a limitation of their study, "which may hinder conclusions regarding efficacy." They also noted that the numbers of patients with generalized epilepsy included were small, meaning that any results from that group should be considered exploratory and approached with caution.

The study was funded by UCB Pharma, the manufacturer of brivaracetam. Dr. Kwan disclosed financial relationships with UCB and GlaxoSmithKline and having served on scientific advisory boards for Eisai. Dr. Kwan’s coauthors disclosed consulting, honoraria, or advisory relationships with UCB and many other companies marketing antiepileptic drugs. Two coauthors are employees of UCB.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

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For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

The U.S. Preventive Services Task Force has determined, for the second time in 10 years, that there is not enough quality evidence to recommend – or not recommend – regular blood pressure screening as part of standard pediatric care.

The task force, chaired by Dr. Virginia A. Moyer, argues that the evidence to support routine screening for primary hypertension remains insufficient in a paper published online Oct. 7 in Pediatrics (2013;132:1-8 [doi:10.1542/peds.2013-2864]). The task force’s position on pediatric screening is little changed from 2003 when it issued recommendations on screening for both children and adults (Am. Fam. Physician 2003;68:2019-22).

©kzenon/iStockphoto.com

For its newest recommendation, however, the task force authors looked solely at the issue of screening in asymptomatic children and adolescents without a risk factor for hypertension, such as high body mass index.

It evaluated studies on diagnostic accuracy, the relationship of childhood primary hypertension with adult hypertension and cardiovascular disease, the effectiveness of treatment, and the harms related to screening or treatment. But the task force determined that it had not found enough quality evidence to weigh in.

One of the rationales for regular blood pressure screening in asymptomatic children 3 years and older – a practice that has been recommended for more than 35 years (Pediatrics 1977;59(suppl.):797-820)and is currently advocated by the American Academy of Pediatrics, the American Heart Association, and the National Heart, Lung, and Blood Institute – is to identify children at increased risk for adult hypertension and cardiovascular disease.

However, predictive values of childhood hypertension for adult hypertension "are at best modest," wrote the authors. A recent, related study also conducted by the task force found no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults (Pediatrics 2013;131:490-525).

Some practitioners have criticized the USPSTF’s focus on primary hypertension and adult outcomes, saying that pediatricians have other reasons to screen children routinely for hypertension, including identifying asymptomatic secondary hypertension. Indeed, for some pediatricians, reducing adult cardiovascular events is not seen as the primary goal of screening. Dr. Bonita Falkner, then incoming chair of the International Pediatric Hypertension Association, clearly outlined this position in a letter to the editor published in Pediatrics in March 2013 in response to a review conducted for the USPSTF.

The task force emphasized that "clinical decisions involve more considerations than evidence alone," and noted that screening between the ages of 3 and 17 years is recommended by the AAP and other organizations.

Dr. Sarah de Ferranti, the director of the preventive cardiology clinic at Boston Children’s Hospital and a member of the AAP committee on nutrition, said in an interview that she, like the task force authors, would like to see more evidence on the relationship between childhood and adult hypertension, and that she would not dismiss the important question of risk or harms related to screening.

But she also said she had no intention of abandoning routine screening as part of her practice, and would counsel other pediatricians not to do so, either. "There are definitely patients identified as having other medical problems by blood pressure – such as kidney problems and endocrine problems. There are cases where the blood pressure is the identifying cause," she said.

"We still identify children with primary and secondary hypertension, and that is important in terms of outcomes," Dr. de Ferranti continued. Observational and longitudinal studies, she pointed out, have found evidence linking pediatric hypertension with adult arterial stiffness, subclinical atherosclerosis, and carotid intima-media thickness, and even with cardiovascular damage that occurs before adulthood.

Moreover, Dr. de Ferranti said, there are logistical barriers to obtaining the type of evidence the USPSTF seeks in its recommendations, such as a randomized controlled trial to determine whether blood pressure reduction improves adult outcomes. "Few parents would be interested in having their child take a placebo or dummy pill for 30 years to find out the answers to these questions," she said.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.

Recent research has suggested that tumor necrosis factor inhibitors can significantly reduce diabetes risk in people with rheumatoid arthritis.

Dr. Siri Lillegraven of Diakonhjemmet Hospital in Oslo presented results from the CORRONA (Consortium of Rheumatology Researchers of North America) study, which Dr. Lillegraven, its lead author, called "the first large study to find the same association" at the annual European Congress of Rheumatology. The study used CORRONA registry data from 22,943 patients and about 22,000 RA treatment regimens with a mean duration between 1.5 and 2.4 years.

Dr. Lillegraven and her colleagues found an adjusted hazard ratio for type 2 diabetes of 0.35 for TNF inhibitors (95% confidence interval, 0.13-0.91), compared with a reference group of non-methotrexate, non-hydroxychloroquine, nonbiologic disease-modifying antirheumatic drugs such as cyclosporine, sulfasalazine, and leflunomide. The DMARDs hydroxychloroquine and methotrexate were separately compared with this reference group.

"It was a statistically significant finding, and the model was adjusted for differences between patients who received TNF inhibitors and the patients who received the comparator drugs," Dr. Lillegraven said in an interview.

One of Dr. Lillegraven’s coauthors on the study, Dr. Daniel Solomon of Brigham and Women’s Hospital in Boston earlier reported a lower risk of type 2 diabetes for individuals taking TNF inhibitors or hydroxychloroquine, compared with nonbiologic DMARDs (JAMA 2011;305:2525-31).

In that study, which enrolled about 14,000 patients and evaluated about 22,000 treatment episodes, the multivariate adjusted hazard ratio for diabetes was 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, compared with other nonbiologic DMARDs. The effect was even greater for hydroxychloroquine, compared with other nonbiologics (hazard ratio, 0.54; 95% CI, 0.36-0.80).

Dr. Lillegraven and her colleagues saw a similar effect size for hydroxychloroquine, compared with the nonbiologic DMARDs, but this did not reach statistical significance.

As both studies were observational in design, Dr. Lillegraven noted, the results do not carry the weight of randomized, controlled trial findings. "We would have loved to have a clinical trial that confirmed the findings," she said, adding that designing such a trial would be difficult. "The outcome is relatively rare, and you will not likely get enough diabetes outcomes to be able to conclude whether an exposure had an effect." In Dr. Lillegraven and her colleagues’ study, for example, only 84 incident cases of diabetes occurred.

Last year, investigators reported that TNF inhibitors were associated with a halving of diabetes risk, compared with RA patients who had never used them (HR, 0.49; 95% CI 0.24-0.99), in a cohort of 1,587 RA patients without diabetes at enrollment who were followed for 3-4 years (Arthritis Care Res. 2012;64:215-21), and several studies have suggested a relationship between the biologic pathways that TNF inhibitors affect and diabetes.

Dr. Lillegraven also analyzed the impact of body-mass index (BMI) and steroid dosage on diabetes incidence in these patients. Those with a BMI of more than 30 kg/m² had a statistically significant sixfold increased rate of incident diabetes, compared with patients with a BMI of less than 25 kg/m². Patients with a BMI of 25-30 kg/m² had a significant, nearly twofold increased rate. Patients who received a steroid dose of at least 7.5 mg/day had a statistically significant, twofold increased diabetes incidence, compared with patients who did not receive any steroid treatment.

Dr. Lillegraven said that her study’s findings, added to the earlier findings, support "a potential for tailoring treatment in high-risk individuals." But it is still too early to draw any definite conclusions regarding how this should be carried out in the clinic, she cautioned.

Dr. Lillegraven declared no conflicts of interest relevant to her study. Dr. Solomon declared unpaid consultancies for Pfizer and Novartis. Three other coauthors reported financial relationships with pharmaceutical firms and CORRONA, a database registry for rheumatologic diseases; one is an employee of CORRONA.