Otolaryngology

First-line treatment for adults with obstructive sleep apnea should be continuous positive airway pressure therapy or a mandibular advancement device, according to the American College of Physicians’ clinical practice guideline published online Sept. 24 in Annals of Internal Medicine.

In contrast, no surgical procedures or pharmacologic agents should be considered as first-line treatment, because there is insufficient evidence supporting those approaches, said Dr. Amir Qaseem, director of clinical policy at the ACP, Philadelphia, and his associates on the clinical guidelines committee.

© David Cannings-Bushell/iStockphoto.com

Overweight and obese patients with obstructive sleep apnea (OSA) should be encouraged to lose weight, because that has been shown to improve symptoms and reduce scores on the Apnea-Hypopnea Index. Weight loss also confers many other health benefits, they added, while carrying minimal risk of adverse effects.

Those are the chief recommendations of the clinical practice guideline, which was compiled "to present information on both the benefits and harms of interventions" to all clinicians who treat adults with OSA. The guideline is based on a rigorous review of the evidence regarding OSA published in the literature from 1966 through 2012.

Overall, the evidence concerning hard clinical outcomes for any intervention for OSA was extremely limited.

Continuous positive airway pressure (CPAP) was the most extensively studied intervention for OSA, but the evidence from most studies was considered to be only of moderate quality. Studies assessed only the treatment’s effect on immediate outcomes and did not evaluate longer term outcomes such as cardiovascular illness or mortality. In addition, studies that examined CPAP’s effect on quality of life "were inconsistent and therefore inconclusive."

Nevertheless, the balance of evidence does show that CPAP is more effective than are control conditions or sham CPAP at improving scores on the apnea-hypopnea index, which measures the number of apneic and hypopneic episodes per hour of monitored sleep. CPAP also improved scores on the Epworth Sleepiness Scale, a self-administered questionnaire in which patients rate their likelihood of dozing off during various situations.

CPAP also is effective at improving oxygen saturation and reducing scores on the arousal index, which measures the frequency of arousals per hour of sleep using electroencephalography. However, there were insufficient data to compare the different types of CPAP, such as fixed CPAP, auto-CPAP, flexible bilevel CPAP, or CPAP with humidification.

There also was insufficient evidence to directly compare CPAP against other interventions, Dr. Qaseem and his colleagues said (Ann. Intern. Med. 2013;159:471-83).

The guideline recommends that mandibular or dental advancement devices to position the patient’s jaw while sleeping are a useful alternative for those who prefer this intervention to CPAP or for those who cannot tolerate or adhere to CPAP. Moderate-quality evidence showed that mandibular advancement devices improve scores on the apnea-hypopnea index and the arousal index.

However, that recommendation is considered "weak," because the overall data supporting the use of mandibular advancement devices are of low quality.

The data also were insufficient to recommend the use of any pharmacologic agents as a first-line therapy for OSA, or indeed as any therapy for the condition. Those include mirtazapine, xylometazoline, fluticasone, paroxetine, pantoprazole, steroids, acetazolamide, and protriptyline.

Only seven studies assessed surgical interventions for OSA. They were of varied quality, and their outcomes were inconsistent, so, the evidence is insufficient to support any surgery as first-line treatment. The procedures assessed in the studies included uvulopalatopharyngoplasty (UPPP); laser-assisted uvulopalatoplasty; radiofrequency ablation; and various combinations of pharyngoplasty, tonsillectomy, adenoidectomy, genioglossal advancement septoplasty, ablation of the nasal turbinates, and other nasal surgeries.

However, there was some evidence to suggest that UPPP and tracheostomy reduced mortality in patients with OSA.

The guideline strongly recommends that all OSA patients who are overweight or obese should be encouraged to lose weight. The evidence, albeit of low quality, shows that any intensive weight-loss intervention helps improve OSA symptoms and scores on the apnea-hypopnea index.

Finally, the evidence was insufficient to assess the potential benefits of positional therapy, oropharyngeal exercise, palatal implants, or atrial overdrive pacing for patients who already have dual-chamber pacemakers, Dr. Qaseem and his associates said.

The guideline was supported entirely by the American College of Physicians. The investigators had no relevant conflicts of interest.

First-line treatment for adults with obstructive sleep apnea should be continuous positive airway pressure therapy or a mandibular advancement device, according to the American College of Physicians’ clinical practice guideline published online Sept. 24 in Annals of Internal Medicine.

In contrast, no surgical procedures or pharmacologic agents should be considered as first-line treatment, because there is insufficient evidence supporting those approaches, said Dr. Amir Qaseem, director of clinical policy at the ACP, Philadelphia, and his associates on the clinical guidelines committee.

© David Cannings-Bushell/iStockphoto.com

Overweight and obese patients with obstructive sleep apnea (OSA) should be encouraged to lose weight, because that has been shown to improve symptoms and reduce scores on the Apnea-Hypopnea Index. Weight loss also confers many other health benefits, they added, while carrying minimal risk of adverse effects.

Those are the chief recommendations of the clinical practice guideline, which was compiled "to present information on both the benefits and harms of interventions" to all clinicians who treat adults with OSA. The guideline is based on a rigorous review of the evidence regarding OSA published in the literature from 1966 through 2012.

Overall, the evidence concerning hard clinical outcomes for any intervention for OSA was extremely limited.

Continuous positive airway pressure (CPAP) was the most extensively studied intervention for OSA, but the evidence from most studies was considered to be only of moderate quality. Studies assessed only the treatment’s effect on immediate outcomes and did not evaluate longer term outcomes such as cardiovascular illness or mortality. In addition, studies that examined CPAP’s effect on quality of life "were inconsistent and therefore inconclusive."

Nevertheless, the balance of evidence does show that CPAP is more effective than are control conditions or sham CPAP at improving scores on the apnea-hypopnea index, which measures the number of apneic and hypopneic episodes per hour of monitored sleep. CPAP also improved scores on the Epworth Sleepiness Scale, a self-administered questionnaire in which patients rate their likelihood of dozing off during various situations.

CPAP also is effective at improving oxygen saturation and reducing scores on the arousal index, which measures the frequency of arousals per hour of sleep using electroencephalography. However, there were insufficient data to compare the different types of CPAP, such as fixed CPAP, auto-CPAP, flexible bilevel CPAP, or CPAP with humidification.

There also was insufficient evidence to directly compare CPAP against other interventions, Dr. Qaseem and his colleagues said (Ann. Intern. Med. 2013;159:471-83).

The guideline recommends that mandibular or dental advancement devices to position the patient’s jaw while sleeping are a useful alternative for those who prefer this intervention to CPAP or for those who cannot tolerate or adhere to CPAP. Moderate-quality evidence showed that mandibular advancement devices improve scores on the apnea-hypopnea index and the arousal index.

However, that recommendation is considered "weak," because the overall data supporting the use of mandibular advancement devices are of low quality.

The data also were insufficient to recommend the use of any pharmacologic agents as a first-line therapy for OSA, or indeed as any therapy for the condition. Those include mirtazapine, xylometazoline, fluticasone, paroxetine, pantoprazole, steroids, acetazolamide, and protriptyline.

Only seven studies assessed surgical interventions for OSA. They were of varied quality, and their outcomes were inconsistent, so, the evidence is insufficient to support any surgery as first-line treatment. The procedures assessed in the studies included uvulopalatopharyngoplasty (UPPP); laser-assisted uvulopalatoplasty; radiofrequency ablation; and various combinations of pharyngoplasty, tonsillectomy, adenoidectomy, genioglossal advancement septoplasty, ablation of the nasal turbinates, and other nasal surgeries.

However, there was some evidence to suggest that UPPP and tracheostomy reduced mortality in patients with OSA.

The guideline strongly recommends that all OSA patients who are overweight or obese should be encouraged to lose weight. The evidence, albeit of low quality, shows that any intensive weight-loss intervention helps improve OSA symptoms and scores on the apnea-hypopnea index.

Finally, the evidence was insufficient to assess the potential benefits of positional therapy, oropharyngeal exercise, palatal implants, or atrial overdrive pacing for patients who already have dual-chamber pacemakers, Dr. Qaseem and his associates said.

The guideline was supported entirely by the American College of Physicians. The investigators had no relevant conflicts of interest.

First-line treatment for adults with obstructive sleep apnea should be continuous positive airway pressure therapy or a mandibular advancement device, according to the American College of Physicians’ clinical practice guideline published online Sept. 24 in Annals of Internal Medicine.

In contrast, no surgical procedures or pharmacologic agents should be considered as first-line treatment, because there is insufficient evidence supporting those approaches, said Dr. Amir Qaseem, director of clinical policy at the ACP, Philadelphia, and his associates on the clinical guidelines committee.

© David Cannings-Bushell/iStockphoto.com

Overweight and obese patients with obstructive sleep apnea (OSA) should be encouraged to lose weight, because that has been shown to improve symptoms and reduce scores on the Apnea-Hypopnea Index. Weight loss also confers many other health benefits, they added, while carrying minimal risk of adverse effects.

Those are the chief recommendations of the clinical practice guideline, which was compiled "to present information on both the benefits and harms of interventions" to all clinicians who treat adults with OSA. The guideline is based on a rigorous review of the evidence regarding OSA published in the literature from 1966 through 2012.

Overall, the evidence concerning hard clinical outcomes for any intervention for OSA was extremely limited.

Continuous positive airway pressure (CPAP) was the most extensively studied intervention for OSA, but the evidence from most studies was considered to be only of moderate quality. Studies assessed only the treatment’s effect on immediate outcomes and did not evaluate longer term outcomes such as cardiovascular illness or mortality. In addition, studies that examined CPAP’s effect on quality of life "were inconsistent and therefore inconclusive."

Nevertheless, the balance of evidence does show that CPAP is more effective than are control conditions or sham CPAP at improving scores on the apnea-hypopnea index, which measures the number of apneic and hypopneic episodes per hour of monitored sleep. CPAP also improved scores on the Epworth Sleepiness Scale, a self-administered questionnaire in which patients rate their likelihood of dozing off during various situations.

CPAP also is effective at improving oxygen saturation and reducing scores on the arousal index, which measures the frequency of arousals per hour of sleep using electroencephalography. However, there were insufficient data to compare the different types of CPAP, such as fixed CPAP, auto-CPAP, flexible bilevel CPAP, or CPAP with humidification.

There also was insufficient evidence to directly compare CPAP against other interventions, Dr. Qaseem and his colleagues said (Ann. Intern. Med. 2013;159:471-83).

The guideline recommends that mandibular or dental advancement devices to position the patient’s jaw while sleeping are a useful alternative for those who prefer this intervention to CPAP or for those who cannot tolerate or adhere to CPAP. Moderate-quality evidence showed that mandibular advancement devices improve scores on the apnea-hypopnea index and the arousal index.

However, that recommendation is considered "weak," because the overall data supporting the use of mandibular advancement devices are of low quality.

The data also were insufficient to recommend the use of any pharmacologic agents as a first-line therapy for OSA, or indeed as any therapy for the condition. Those include mirtazapine, xylometazoline, fluticasone, paroxetine, pantoprazole, steroids, acetazolamide, and protriptyline.

Only seven studies assessed surgical interventions for OSA. They were of varied quality, and their outcomes were inconsistent, so, the evidence is insufficient to support any surgery as first-line treatment. The procedures assessed in the studies included uvulopalatopharyngoplasty (UPPP); laser-assisted uvulopalatoplasty; radiofrequency ablation; and various combinations of pharyngoplasty, tonsillectomy, adenoidectomy, genioglossal advancement septoplasty, ablation of the nasal turbinates, and other nasal surgeries.

However, there was some evidence to suggest that UPPP and tracheostomy reduced mortality in patients with OSA.

The guideline strongly recommends that all OSA patients who are overweight or obese should be encouraged to lose weight. The evidence, albeit of low quality, shows that any intensive weight-loss intervention helps improve OSA symptoms and scores on the apnea-hypopnea index.

Finally, the evidence was insufficient to assess the potential benefits of positional therapy, oropharyngeal exercise, palatal implants, or atrial overdrive pacing for patients who already have dual-chamber pacemakers, Dr. Qaseem and his associates said.

The guideline was supported entirely by the American College of Physicians. The investigators had no relevant conflicts of interest.

WASHINGTON – If your patient complains of hoarseness, how do you handle it? Although the causes of hoarseness are often obvious, many patients with hoarseness have vocal folds that appear normal, which can create a diagnostic challenge, said Dr. Seth M. Cohen of Duke University Medical Center in Durham, N.C., and Dr. J. Pieter Noordzij of Boston Medical Center.

Some of the most common causes of hoarseness in patients with normal-looking vocal folds are muscle tension/functional dysphonia, spasmodic dysphonia, vocal fold tremor, Parkinson’s disease, presbylaryngis (vocal fold atrophy), and amyotrophic lateral sclerosis. Dr. Cohen and Dr. Noordzij reviewed these conditions and shared cases at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The Work-Up

When evaluating a patient’s hoarseness, start with a history and physical exam. The history should include the duration of hoarseness, how it started, family history of hoarseness, and the patient’s vocal demands that could contribute to overuse of the voice, Dr. Cohen said. Fluid intake (or lack of) can play a role, as can certain medical conditions such as gastroesophageal reflux disease (GERD) and allergies involving postnasal drip, he said.

The complete evaluation of a hoarse patient should include a full head and neck exam and a full cranial nerve exam, as well as an assessment of general appearance, facial expression, and endolaryngeal findings, Dr. Cohen said.

In addition, clinicians can use a perceptual voice analysis to try to characterize the general voice quality in terms of roughness (raspy), breathiness, strain (voice breaking), pitch (may be lower than normal), articulation, and speed, Dr. Cohen said. Techniques to evaluate patients include asking them to whisper, sing, make sustained vowel sounds (aaah, eee, ooo), and count from 60 to 69 and from 80 to 89.

Although some patients with hoarseness may benefit from surgical procedures, voice therapy is usually the first choice for treatment, he noted.

"Listen to the patient, listen to what they tell you, and listen to what they sound like," Dr. Cohen said.

Muscle Tension/Functional Dysphonia

Patients with muscle tension and functional dysphonia have excessive tension or poor coordination of the muscles in and near the voice box. The hoarseness in these patients often occurs after a cold and may be worse at the end of the day, said Dr. Noordzij.

On physical exam, this patient’s voice may be raspy and lower in pitch than normal. Someone who puts heavy demands on their voice might be susceptible to this condition, Dr. Noordzij said. They perceive their voice as strained and lower pitched, and they feel that are talking at the end of a breath. An endolaryngeal exam may show a gap between the vocal folds and squeezing of the larynx above the vocal folds (called a supraglottic constriction).

Spasmodic Dysphonia

Spasmodic dysphonia (SD) most often occurs in adulthood and can be triggered by a major life stress, Dr. Noordzij said. SD is a neurologic problem, not a functional one, he noted. SD is a movement disorder that involves involuntary, repetitive contractions of the laryngeal muscles. SD may be one of two types: adductor (a spasm that pushes the vocal folds together) or abductor (a spasm that causes the vocal cords to pull apart). Adductor spasmodic dysphonia is the most common form. Vocal characteristics include a strained or strangled voice that breaks on voiced syllables. However, voice breaks do not occur when the patient whispers, sings, or speaks in a falsetto, Dr. Noordzij said.

Vocal Fold Tremor

Vocal tremor is a central nervous system disorder that can be associated with other tremor conditions such as Parkinson’s disease, cerebellar ataxia, and spasmodic dysphonia, Dr. Cohen said.

"The hallmark of the condition is a rhythmic alteration in both the pitch and the loudness," he said. Vocal tremor may be exacerbated by stress or fatigue, and there may be a family history of tremor, he added.

On physical exam, patients with vocal tremor also may have tremor of the hands, head, jaw, voice, pharynx, tongue, or palate. Oscillations of pitch and amplitude are most noticeable during sustained vowels.

Parkinson’s Disease

Patients with Parkinson’s disease can present with voice complaints before they have a Parkinson’s diagnosis, although they also may exhibit Parkinson’s symptoms including hand tremor, rigidity, drooling, or a shuffling gait, Dr. Cohen said.

Hoarseness in these patients is characterized by breathy, flat voice, in a monotone, with breaths at inappropriate times. Patients also may have decreased blinking and a lack of facial expression.

Parkinson’s patients may have a history of not realizing the low volume of their voices, and they may take breaths at inappropriate times, Dr. Cohen noted. An endolaryngeal exam may show evidence of vocal fold bowing and a pooling of secretions, he said.

Presbylaryngis

Presbylaryngis, also known as vocal fold atrophy, is caused by age-related changes in the vocal folds, including ossification of laryngeal cartilage, decreased muscle bulk, decreased mucus production, and thickening or thinning of the epithelium.

"This is one of the hardest problems to treat surgically," Dr. Cohen said. Therefore, voice therapy is the first line treatment, he said.

In general, the pitch of men’s voices rises in cases of presbylaryngis, while the pitch of women’s voices decreases, Dr. Cohen noted. Patients perceive their voices as breathy and weak, with vocal fatigue and decreased ability to project their voices.

Amyotrophic Lateral Sclerosis

Approximately 25% of patients with amyotrophic lateral sclerosis (ALS) present with speech and swallowing problems. ALS is a progressive degeneration of the upper and lower motor neurons. Speech in these patients is typically slow, weak, and hypernasal, said Dr. Cohen. ALS patients may have dysarthria (disturbance of articulation) as well as dysphonia, and involuntary twitches of the tongue, he added.

Neither Dr. Cohen nor Dr. Noordzij had any financial conflicts to disclose.

h.splete@elsevier.com

WASHINGTON – If your patient complains of hoarseness, how do you handle it? Although the causes of hoarseness are often obvious, many patients with hoarseness have vocal folds that appear normal, which can create a diagnostic challenge, said Dr. Seth M. Cohen of Duke University Medical Center in Durham, N.C., and Dr. J. Pieter Noordzij of Boston Medical Center.

Some of the most common causes of hoarseness in patients with normal-looking vocal folds are muscle tension/functional dysphonia, spasmodic dysphonia, vocal fold tremor, Parkinson’s disease, presbylaryngis (vocal fold atrophy), and amyotrophic lateral sclerosis. Dr. Cohen and Dr. Noordzij reviewed these conditions and shared cases at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The Work-Up

When evaluating a patient’s hoarseness, start with a history and physical exam. The history should include the duration of hoarseness, how it started, family history of hoarseness, and the patient’s vocal demands that could contribute to overuse of the voice, Dr. Cohen said. Fluid intake (or lack of) can play a role, as can certain medical conditions such as gastroesophageal reflux disease (GERD) and allergies involving postnasal drip, he said.

The complete evaluation of a hoarse patient should include a full head and neck exam and a full cranial nerve exam, as well as an assessment of general appearance, facial expression, and endolaryngeal findings, Dr. Cohen said.

In addition, clinicians can use a perceptual voice analysis to try to characterize the general voice quality in terms of roughness (raspy), breathiness, strain (voice breaking), pitch (may be lower than normal), articulation, and speed, Dr. Cohen said. Techniques to evaluate patients include asking them to whisper, sing, make sustained vowel sounds (aaah, eee, ooo), and count from 60 to 69 and from 80 to 89.

Although some patients with hoarseness may benefit from surgical procedures, voice therapy is usually the first choice for treatment, he noted.

"Listen to the patient, listen to what they tell you, and listen to what they sound like," Dr. Cohen said.

Muscle Tension/Functional Dysphonia

Patients with muscle tension and functional dysphonia have excessive tension or poor coordination of the muscles in and near the voice box. The hoarseness in these patients often occurs after a cold and may be worse at the end of the day, said Dr. Noordzij.

On physical exam, this patient’s voice may be raspy and lower in pitch than normal. Someone who puts heavy demands on their voice might be susceptible to this condition, Dr. Noordzij said. They perceive their voice as strained and lower pitched, and they feel that are talking at the end of a breath. An endolaryngeal exam may show a gap between the vocal folds and squeezing of the larynx above the vocal folds (called a supraglottic constriction).

Spasmodic Dysphonia

Spasmodic dysphonia (SD) most often occurs in adulthood and can be triggered by a major life stress, Dr. Noordzij said. SD is a neurologic problem, not a functional one, he noted. SD is a movement disorder that involves involuntary, repetitive contractions of the laryngeal muscles. SD may be one of two types: adductor (a spasm that pushes the vocal folds together) or abductor (a spasm that causes the vocal cords to pull apart). Adductor spasmodic dysphonia is the most common form. Vocal characteristics include a strained or strangled voice that breaks on voiced syllables. However, voice breaks do not occur when the patient whispers, sings, or speaks in a falsetto, Dr. Noordzij said.

Vocal Fold Tremor

Vocal tremor is a central nervous system disorder that can be associated with other tremor conditions such as Parkinson’s disease, cerebellar ataxia, and spasmodic dysphonia, Dr. Cohen said.

"The hallmark of the condition is a rhythmic alteration in both the pitch and the loudness," he said. Vocal tremor may be exacerbated by stress or fatigue, and there may be a family history of tremor, he added.

On physical exam, patients with vocal tremor also may have tremor of the hands, head, jaw, voice, pharynx, tongue, or palate. Oscillations of pitch and amplitude are most noticeable during sustained vowels.

Parkinson’s Disease

Patients with Parkinson’s disease can present with voice complaints before they have a Parkinson’s diagnosis, although they also may exhibit Parkinson’s symptoms including hand tremor, rigidity, drooling, or a shuffling gait, Dr. Cohen said.

Hoarseness in these patients is characterized by breathy, flat voice, in a monotone, with breaths at inappropriate times. Patients also may have decreased blinking and a lack of facial expression.

Parkinson’s patients may have a history of not realizing the low volume of their voices, and they may take breaths at inappropriate times, Dr. Cohen noted. An endolaryngeal exam may show evidence of vocal fold bowing and a pooling of secretions, he said.

Presbylaryngis

Presbylaryngis, also known as vocal fold atrophy, is caused by age-related changes in the vocal folds, including ossification of laryngeal cartilage, decreased muscle bulk, decreased mucus production, and thickening or thinning of the epithelium.

"This is one of the hardest problems to treat surgically," Dr. Cohen said. Therefore, voice therapy is the first line treatment, he said.

In general, the pitch of men’s voices rises in cases of presbylaryngis, while the pitch of women’s voices decreases, Dr. Cohen noted. Patients perceive their voices as breathy and weak, with vocal fatigue and decreased ability to project their voices.

Amyotrophic Lateral Sclerosis

Approximately 25% of patients with amyotrophic lateral sclerosis (ALS) present with speech and swallowing problems. ALS is a progressive degeneration of the upper and lower motor neurons. Speech in these patients is typically slow, weak, and hypernasal, said Dr. Cohen. ALS patients may have dysarthria (disturbance of articulation) as well as dysphonia, and involuntary twitches of the tongue, he added.

Neither Dr. Cohen nor Dr. Noordzij had any financial conflicts to disclose.

h.splete@elsevier.com

WASHINGTON – If your patient complains of hoarseness, how do you handle it? Although the causes of hoarseness are often obvious, many patients with hoarseness have vocal folds that appear normal, which can create a diagnostic challenge, said Dr. Seth M. Cohen of Duke University Medical Center in Durham, N.C., and Dr. J. Pieter Noordzij of Boston Medical Center.

Some of the most common causes of hoarseness in patients with normal-looking vocal folds are muscle tension/functional dysphonia, spasmodic dysphonia, vocal fold tremor, Parkinson’s disease, presbylaryngis (vocal fold atrophy), and amyotrophic lateral sclerosis. Dr. Cohen and Dr. Noordzij reviewed these conditions and shared cases at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The Work-Up

When evaluating a patient’s hoarseness, start with a history and physical exam. The history should include the duration of hoarseness, how it started, family history of hoarseness, and the patient’s vocal demands that could contribute to overuse of the voice, Dr. Cohen said. Fluid intake (or lack of) can play a role, as can certain medical conditions such as gastroesophageal reflux disease (GERD) and allergies involving postnasal drip, he said.

The complete evaluation of a hoarse patient should include a full head and neck exam and a full cranial nerve exam, as well as an assessment of general appearance, facial expression, and endolaryngeal findings, Dr. Cohen said.

In addition, clinicians can use a perceptual voice analysis to try to characterize the general voice quality in terms of roughness (raspy), breathiness, strain (voice breaking), pitch (may be lower than normal), articulation, and speed, Dr. Cohen said. Techniques to evaluate patients include asking them to whisper, sing, make sustained vowel sounds (aaah, eee, ooo), and count from 60 to 69 and from 80 to 89.

Although some patients with hoarseness may benefit from surgical procedures, voice therapy is usually the first choice for treatment, he noted.

"Listen to the patient, listen to what they tell you, and listen to what they sound like," Dr. Cohen said.

Muscle Tension/Functional Dysphonia

Patients with muscle tension and functional dysphonia have excessive tension or poor coordination of the muscles in and near the voice box. The hoarseness in these patients often occurs after a cold and may be worse at the end of the day, said Dr. Noordzij.

On physical exam, this patient’s voice may be raspy and lower in pitch than normal. Someone who puts heavy demands on their voice might be susceptible to this condition, Dr. Noordzij said. They perceive their voice as strained and lower pitched, and they feel that are talking at the end of a breath. An endolaryngeal exam may show a gap between the vocal folds and squeezing of the larynx above the vocal folds (called a supraglottic constriction).

Spasmodic Dysphonia

Spasmodic dysphonia (SD) most often occurs in adulthood and can be triggered by a major life stress, Dr. Noordzij said. SD is a neurologic problem, not a functional one, he noted. SD is a movement disorder that involves involuntary, repetitive contractions of the laryngeal muscles. SD may be one of two types: adductor (a spasm that pushes the vocal folds together) or abductor (a spasm that causes the vocal cords to pull apart). Adductor spasmodic dysphonia is the most common form. Vocal characteristics include a strained or strangled voice that breaks on voiced syllables. However, voice breaks do not occur when the patient whispers, sings, or speaks in a falsetto, Dr. Noordzij said.

Vocal Fold Tremor

Vocal tremor is a central nervous system disorder that can be associated with other tremor conditions such as Parkinson’s disease, cerebellar ataxia, and spasmodic dysphonia, Dr. Cohen said.

"The hallmark of the condition is a rhythmic alteration in both the pitch and the loudness," he said. Vocal tremor may be exacerbated by stress or fatigue, and there may be a family history of tremor, he added.

On physical exam, patients with vocal tremor also may have tremor of the hands, head, jaw, voice, pharynx, tongue, or palate. Oscillations of pitch and amplitude are most noticeable during sustained vowels.

Parkinson’s Disease

Patients with Parkinson’s disease can present with voice complaints before they have a Parkinson’s diagnosis, although they also may exhibit Parkinson’s symptoms including hand tremor, rigidity, drooling, or a shuffling gait, Dr. Cohen said.

Hoarseness in these patients is characterized by breathy, flat voice, in a monotone, with breaths at inappropriate times. Patients also may have decreased blinking and a lack of facial expression.

Parkinson’s patients may have a history of not realizing the low volume of their voices, and they may take breaths at inappropriate times, Dr. Cohen noted. An endolaryngeal exam may show evidence of vocal fold bowing and a pooling of secretions, he said.

Presbylaryngis

Presbylaryngis, also known as vocal fold atrophy, is caused by age-related changes in the vocal folds, including ossification of laryngeal cartilage, decreased muscle bulk, decreased mucus production, and thickening or thinning of the epithelium.

"This is one of the hardest problems to treat surgically," Dr. Cohen said. Therefore, voice therapy is the first line treatment, he said.

In general, the pitch of men’s voices rises in cases of presbylaryngis, while the pitch of women’s voices decreases, Dr. Cohen noted. Patients perceive their voices as breathy and weak, with vocal fatigue and decreased ability to project their voices.

Amyotrophic Lateral Sclerosis

Approximately 25% of patients with amyotrophic lateral sclerosis (ALS) present with speech and swallowing problems. ALS is a progressive degeneration of the upper and lower motor neurons. Speech in these patients is typically slow, weak, and hypernasal, said Dr. Cohen. ALS patients may have dysarthria (disturbance of articulation) as well as dysphonia, and involuntary twitches of the tongue, he added.

Neither Dr. Cohen nor Dr. Noordzij had any financial conflicts to disclose.

h.splete@elsevier.com

The risk of postoperative hemorrhage after transoral robotic-assisted surgery was significantly higher in patients taking antithrombotic medication than in those not taking it, based on data from 147 consecutive patients.

"Even with this small sample size, we were able to identify that increased risk was associated with antithrombotic medication use," said Dr. Scott Asher of the University of Alabama at Birmingham.

Transoral robotic-assisted surgery (TORS) is gaining in popularity among head and neck surgeons, but the potential for postop bleeding in patients taking antithrombotic medication remains a problem, Dr. Asher said at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

To assess the postop bleeding complications in TORS patients, Dr. Asher and his colleagues reviewed data from patients seen at a single tertiary academic medical center between March 2007 and September 2011.

Overall, 11 patients (8%) experienced some postop hemorrhage, but 8 of these hemorrhages (72%) occurred in patients taking antithrombotics, Dr. Asher said. Nine patients who hemorrhaged returned to the operating room for further examination and bleeding control, he noted. All postop hemorrhage events were controlled with standard techniques.

The incidence of postop hemorrhage was significantly higher among patients on antithrombotics (17%) compared with those not on antithrombotics (3%). However, no significant difference in the incidence of bleeding occurred between patients undergoing primary surgery and those undergoing salvage surgery (7% vs. 10%). Bleeding occurred an average of 11 days after surgery.

The bleeding events occurred past the time points when most patients would resume their antithrombotic medications, Dr. Asher noted.

"Our recommendation is that patients taking these meds should receive additional preop counseling when considering a TORS procedure," he said.

"A second recommendation is to collaborate preoperatively with the physicians who are prescribing," as well as the anesthesia team, to closely analyze the indications for use of antithrombotics, Dr. Asher added. "If you can safely discontinue them, you can potentially improve your TORS outcomes," he said.

Additional long-term safety and outcomes data are needed for TORS procedures, said Dr. Asher. "We are constantly reflecting on our own experience," he said. "We would encourage other institutions to collect and publish their complications-related data to continue to improve TORS outcomes."

Dr. Asher said he had no relevant financial conflicts.

h.splete@elsevier.com

The risk of postoperative hemorrhage after transoral robotic-assisted surgery was significantly higher in patients taking antithrombotic medication than in those not taking it, based on data from 147 consecutive patients.

"Even with this small sample size, we were able to identify that increased risk was associated with antithrombotic medication use," said Dr. Scott Asher of the University of Alabama at Birmingham.

Transoral robotic-assisted surgery (TORS) is gaining in popularity among head and neck surgeons, but the potential for postop bleeding in patients taking antithrombotic medication remains a problem, Dr. Asher said at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

To assess the postop bleeding complications in TORS patients, Dr. Asher and his colleagues reviewed data from patients seen at a single tertiary academic medical center between March 2007 and September 2011.

Overall, 11 patients (8%) experienced some postop hemorrhage, but 8 of these hemorrhages (72%) occurred in patients taking antithrombotics, Dr. Asher said. Nine patients who hemorrhaged returned to the operating room for further examination and bleeding control, he noted. All postop hemorrhage events were controlled with standard techniques.

The incidence of postop hemorrhage was significantly higher among patients on antithrombotics (17%) compared with those not on antithrombotics (3%). However, no significant difference in the incidence of bleeding occurred between patients undergoing primary surgery and those undergoing salvage surgery (7% vs. 10%). Bleeding occurred an average of 11 days after surgery.

The bleeding events occurred past the time points when most patients would resume their antithrombotic medications, Dr. Asher noted.

"Our recommendation is that patients taking these meds should receive additional preop counseling when considering a TORS procedure," he said.

"A second recommendation is to collaborate preoperatively with the physicians who are prescribing," as well as the anesthesia team, to closely analyze the indications for use of antithrombotics, Dr. Asher added. "If you can safely discontinue them, you can potentially improve your TORS outcomes," he said.

Additional long-term safety and outcomes data are needed for TORS procedures, said Dr. Asher. "We are constantly reflecting on our own experience," he said. "We would encourage other institutions to collect and publish their complications-related data to continue to improve TORS outcomes."

Dr. Asher said he had no relevant financial conflicts.

h.splete@elsevier.com

The risk of postoperative hemorrhage after transoral robotic-assisted surgery was significantly higher in patients taking antithrombotic medication than in those not taking it, based on data from 147 consecutive patients.

"Even with this small sample size, we were able to identify that increased risk was associated with antithrombotic medication use," said Dr. Scott Asher of the University of Alabama at Birmingham.

Transoral robotic-assisted surgery (TORS) is gaining in popularity among head and neck surgeons, but the potential for postop bleeding in patients taking antithrombotic medication remains a problem, Dr. Asher said at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

To assess the postop bleeding complications in TORS patients, Dr. Asher and his colleagues reviewed data from patients seen at a single tertiary academic medical center between March 2007 and September 2011.

Overall, 11 patients (8%) experienced some postop hemorrhage, but 8 of these hemorrhages (72%) occurred in patients taking antithrombotics, Dr. Asher said. Nine patients who hemorrhaged returned to the operating room for further examination and bleeding control, he noted. All postop hemorrhage events were controlled with standard techniques.

The incidence of postop hemorrhage was significantly higher among patients on antithrombotics (17%) compared with those not on antithrombotics (3%). However, no significant difference in the incidence of bleeding occurred between patients undergoing primary surgery and those undergoing salvage surgery (7% vs. 10%). Bleeding occurred an average of 11 days after surgery.

The bleeding events occurred past the time points when most patients would resume their antithrombotic medications, Dr. Asher noted.

"Our recommendation is that patients taking these meds should receive additional preop counseling when considering a TORS procedure," he said.

"A second recommendation is to collaborate preoperatively with the physicians who are prescribing," as well as the anesthesia team, to closely analyze the indications for use of antithrombotics, Dr. Asher added. "If you can safely discontinue them, you can potentially improve your TORS outcomes," he said.

Additional long-term safety and outcomes data are needed for TORS procedures, said Dr. Asher. "We are constantly reflecting on our own experience," he said. "We would encourage other institutions to collect and publish their complications-related data to continue to improve TORS outcomes."

Dr. Asher said he had no relevant financial conflicts.

h.splete@elsevier.com

WASHINGTON – SurgiSIS, a material derived from porcine small intestinal mucosa, can be safely and effectively used for myringoplasty in children, based on data from a prospective, blinded study of 404 patients.

Patients’ tissue is not always available for tympanic membrane repair, and harvesting the graft may increase intraoperative time, said Dr. Riccardo D’Eredita of Vincenza (Italy) Civil Hospital. SurgiSIS (SIS) "promotes early vessel growth, provides scaffolding for remodeling tissues, and is inexpensive and ready to use." He presented the findings at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The material has been used widely in children, and data from previous studies show that SurgiSIS is gradually replaced by host cells, said Dr. D’Eredita. After 30 days, host cells invade SurgiSIS. After 1 year, SurgiSIS is no longer evident, and has been replaced by the patients’ collagen.

In this study, 404 children underwent tympanic membrane repair in 432 ears; 217 were randomized to myringoplasty with SurgiSIS and 215 were randomized to repair using the patients’ own temporalis fascia.

Overall, the group without SurgiSIS had a 97% rate of stable closures and the group with SurgiSIS had a 95% rate. Surgical time was approximately 15 minutes less for SurgiSIS-treated patients, Dr. D’Eredita said.

The researchers assessed the healing of the tympanic membranes over a 10-year period and found comparable reduction of inflammation in the two groups. There were no adverse reactions in the SIS group.

Dr. D’Eredita had no financial conflicts to disclose.

WASHINGTON – SurgiSIS, a material derived from porcine small intestinal mucosa, can be safely and effectively used for myringoplasty in children, based on data from a prospective, blinded study of 404 patients.

Patients’ tissue is not always available for tympanic membrane repair, and harvesting the graft may increase intraoperative time, said Dr. Riccardo D’Eredita of Vincenza (Italy) Civil Hospital. SurgiSIS (SIS) "promotes early vessel growth, provides scaffolding for remodeling tissues, and is inexpensive and ready to use." He presented the findings at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The material has been used widely in children, and data from previous studies show that SurgiSIS is gradually replaced by host cells, said Dr. D’Eredita. After 30 days, host cells invade SurgiSIS. After 1 year, SurgiSIS is no longer evident, and has been replaced by the patients’ collagen.

In this study, 404 children underwent tympanic membrane repair in 432 ears; 217 were randomized to myringoplasty with SurgiSIS and 215 were randomized to repair using the patients’ own temporalis fascia.

Overall, the group without SurgiSIS had a 97% rate of stable closures and the group with SurgiSIS had a 95% rate. Surgical time was approximately 15 minutes less for SurgiSIS-treated patients, Dr. D’Eredita said.

The researchers assessed the healing of the tympanic membranes over a 10-year period and found comparable reduction of inflammation in the two groups. There were no adverse reactions in the SIS group.

Dr. D’Eredita had no financial conflicts to disclose.

WASHINGTON – SurgiSIS, a material derived from porcine small intestinal mucosa, can be safely and effectively used for myringoplasty in children, based on data from a prospective, blinded study of 404 patients.

Patients’ tissue is not always available for tympanic membrane repair, and harvesting the graft may increase intraoperative time, said Dr. Riccardo D’Eredita of Vincenza (Italy) Civil Hospital. SurgiSIS (SIS) "promotes early vessel growth, provides scaffolding for remodeling tissues, and is inexpensive and ready to use." He presented the findings at the annual meeting of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

The material has been used widely in children, and data from previous studies show that SurgiSIS is gradually replaced by host cells, said Dr. D’Eredita. After 30 days, host cells invade SurgiSIS. After 1 year, SurgiSIS is no longer evident, and has been replaced by the patients’ collagen.

In this study, 404 children underwent tympanic membrane repair in 432 ears; 217 were randomized to myringoplasty with SurgiSIS and 215 were randomized to repair using the patients’ own temporalis fascia.

Overall, the group without SurgiSIS had a 97% rate of stable closures and the group with SurgiSIS had a 95% rate. Surgical time was approximately 15 minutes less for SurgiSIS-treated patients, Dr. D’Eredita said.

The researchers assessed the healing of the tympanic membranes over a 10-year period and found comparable reduction of inflammation in the two groups. There were no adverse reactions in the SIS group.

Dr. D’Eredita had no financial conflicts to disclose.

WASHINGTON – Facial nerve dysfunction affected 23% of 43 children who had parotidectomies in a single-center study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

The findings suggest that facial nerve dysfunction after parotidectomy is common enough in children to merit preoperative counseling, said Dr. James A. Owusu of the University of Minnesota, Minneapolis.

Facial nerve dysfunction rates reported in the literature range from 9% to 60% in adults after parotidectomy, but the condition has not been well studied in children.

Dr. Owusu and his colleagues reviewed the charts of 43 patients younger than age 18 years who underwent parotidectomies at a single tertiary care center between 1999 and 2011. Patients who only had parotid biopsies and those without follow-up data were excluded from the study. The average age of the patients was 4 years, and 58% were girls.

Postoperatively, 33 children (77%) had normal nerve function and 10 (23%) had abnormal nerve function. One patient experienced immediate facial nerve paralysis and nine experienced immediate facial nerve paresis. The marginal mandibular branch was affected in seven patients, the frontal branch in one patient, the buccal branch in one, and both marginal mandibular and frontal branches in one.

The most common diagnosis that led to a parotidectomy was atypical mycobacterium infection (37%), followed by branchial cleft abnormality (19%) and lymphangioma (16%). Nearly all (41) of the children underwent superficial parotidectomy; 2 underwent total parotidectomy.

"Age, gender, and pathologic diagnosis were not predictive of postoperative nerve dysfunction," Dr. Owusu said.

In patients with paresis, full nerve recovery occurred within 1 month for 2 patients, within 2 months for 1 patient, within 6 months for 3 patients, and within 10 months for 2 patients. Final nerve status was not available for 1 patient.

The study was limited by its small size and focus on a single center, Dr. Owusu said.

Dr. Owusu had no financial conflicts to disclose.

WASHINGTON – Facial nerve dysfunction affected 23% of 43 children who had parotidectomies in a single-center study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

The findings suggest that facial nerve dysfunction after parotidectomy is common enough in children to merit preoperative counseling, said Dr. James A. Owusu of the University of Minnesota, Minneapolis.

Facial nerve dysfunction rates reported in the literature range from 9% to 60% in adults after parotidectomy, but the condition has not been well studied in children.

Dr. Owusu and his colleagues reviewed the charts of 43 patients younger than age 18 years who underwent parotidectomies at a single tertiary care center between 1999 and 2011. Patients who only had parotid biopsies and those without follow-up data were excluded from the study. The average age of the patients was 4 years, and 58% were girls.

Postoperatively, 33 children (77%) had normal nerve function and 10 (23%) had abnormal nerve function. One patient experienced immediate facial nerve paralysis and nine experienced immediate facial nerve paresis. The marginal mandibular branch was affected in seven patients, the frontal branch in one patient, the buccal branch in one, and both marginal mandibular and frontal branches in one.

The most common diagnosis that led to a parotidectomy was atypical mycobacterium infection (37%), followed by branchial cleft abnormality (19%) and lymphangioma (16%). Nearly all (41) of the children underwent superficial parotidectomy; 2 underwent total parotidectomy.

"Age, gender, and pathologic diagnosis were not predictive of postoperative nerve dysfunction," Dr. Owusu said.

In patients with paresis, full nerve recovery occurred within 1 month for 2 patients, within 2 months for 1 patient, within 6 months for 3 patients, and within 10 months for 2 patients. Final nerve status was not available for 1 patient.

The study was limited by its small size and focus on a single center, Dr. Owusu said.

Dr. Owusu had no financial conflicts to disclose.

WASHINGTON – Facial nerve dysfunction affected 23% of 43 children who had parotidectomies in a single-center study presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

The findings suggest that facial nerve dysfunction after parotidectomy is common enough in children to merit preoperative counseling, said Dr. James A. Owusu of the University of Minnesota, Minneapolis.

Facial nerve dysfunction rates reported in the literature range from 9% to 60% in adults after parotidectomy, but the condition has not been well studied in children.

Dr. Owusu and his colleagues reviewed the charts of 43 patients younger than age 18 years who underwent parotidectomies at a single tertiary care center between 1999 and 2011. Patients who only had parotid biopsies and those without follow-up data were excluded from the study. The average age of the patients was 4 years, and 58% were girls.

Postoperatively, 33 children (77%) had normal nerve function and 10 (23%) had abnormal nerve function. One patient experienced immediate facial nerve paralysis and nine experienced immediate facial nerve paresis. The marginal mandibular branch was affected in seven patients, the frontal branch in one patient, the buccal branch in one, and both marginal mandibular and frontal branches in one.

The most common diagnosis that led to a parotidectomy was atypical mycobacterium infection (37%), followed by branchial cleft abnormality (19%) and lymphangioma (16%). Nearly all (41) of the children underwent superficial parotidectomy; 2 underwent total parotidectomy.

"Age, gender, and pathologic diagnosis were not predictive of postoperative nerve dysfunction," Dr. Owusu said.

In patients with paresis, full nerve recovery occurred within 1 month for 2 patients, within 2 months for 1 patient, within 6 months for 3 patients, and within 10 months for 2 patients. Final nerve status was not available for 1 patient.

The study was limited by its small size and focus on a single center, Dr. Owusu said.

Dr. Owusu had no financial conflicts to disclose.

WASHINGTON – Oropharyngeal squamous cell cancer patients who underwent transoral robotic surgery had an overall 2-year survival rate of 87%, with no significant differences between patients who were positive vs. negative for the human papillomavirus, based on data from 52 patients.

HPV is associated with 45%-70% of cases of oropharyngeal squamous cell carcinoma (OPSCCa), said Dr. Kiran Kakarala, who conducted the study at Ohio State University in Columbus.

Previous studies have shown a significant difference in survival rates for patients with HPV-positive tumors, compared with those with negative tumors, Dr. Kakarala said. However, other studies have suggested that the use of transoral robotic surgery (TORS) for OPSCCa patients could narrow the gap in survival based on HPV status.

Dr. Kakarala and his colleagues reviewed data from 52 patients who underwent TORS with neck dissection and postoperative adjuvant treatment for previously untreated OPSCCa. The patients were part of a prospective single-arm cohort study at a single academic medical center.

HPV status was available for 42 patients; 36 were positive and 6 were negative. Demographic characteristics were not significantly different between the HPV-positive and negative patients. The mean age of the HPV-positive patients was 59 years, and the mean age of the negative patients was 57 years. The tonsil was the primary tumor site in 89% of the positive patients and 83% of the negative patients; the base of the tongue was the primary site in 11% of the positive patients and 17% of the negative patients.

HPV-positive patients had significantly higher N classifications based on the TNM Classification of Malignant Tumors, compared with HPV-negative patients (P = .015), and a significantly higher stage (P = .017). No significant differences were found in the number of HPV-positive vs. negative patients who received postoperative radiation or chemotherapy.

The 2-year survival rate was 87% for all 52 patients, 92% for HPV-positive patients, and 75% for HPV-negative patients. Two-year disease-specific survival rates were 92%, 92%, and 75%, respectively. Two-year disease-free survival rates were 86%, 97%, and 50%, respectively.

"The 2-year overall survival and disease-specific survival were not statistically different between HPV-positive and negative patients treated with TORS followed by radiation with or without chemotherapy as indicated," Dr. Kakarala said.

The study was limited by its small size and retrospective design, but the findings suggest a role for minimally invasive TORS in OPSCCa patients, he said.

"Randomized trials incorporating minimally invasive transoral surgical procedures with radiation therapy and chemotherapy, and comparing survival, quality of life, and cost outcomes between these treatment modalities, are indicated," he added.

The findings were presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

Dr. Kakarala had no financial conflicts to disclose.

WASHINGTON – Oropharyngeal squamous cell cancer patients who underwent transoral robotic surgery had an overall 2-year survival rate of 87%, with no significant differences between patients who were positive vs. negative for the human papillomavirus, based on data from 52 patients.

HPV is associated with 45%-70% of cases of oropharyngeal squamous cell carcinoma (OPSCCa), said Dr. Kiran Kakarala, who conducted the study at Ohio State University in Columbus.

Previous studies have shown a significant difference in survival rates for patients with HPV-positive tumors, compared with those with negative tumors, Dr. Kakarala said. However, other studies have suggested that the use of transoral robotic surgery (TORS) for OPSCCa patients could narrow the gap in survival based on HPV status.

Dr. Kakarala and his colleagues reviewed data from 52 patients who underwent TORS with neck dissection and postoperative adjuvant treatment for previously untreated OPSCCa. The patients were part of a prospective single-arm cohort study at a single academic medical center.

HPV status was available for 42 patients; 36 were positive and 6 were negative. Demographic characteristics were not significantly different between the HPV-positive and negative patients. The mean age of the HPV-positive patients was 59 years, and the mean age of the negative patients was 57 years. The tonsil was the primary tumor site in 89% of the positive patients and 83% of the negative patients; the base of the tongue was the primary site in 11% of the positive patients and 17% of the negative patients.

HPV-positive patients had significantly higher N classifications based on the TNM Classification of Malignant Tumors, compared with HPV-negative patients (P = .015), and a significantly higher stage (P = .017). No significant differences were found in the number of HPV-positive vs. negative patients who received postoperative radiation or chemotherapy.

The 2-year survival rate was 87% for all 52 patients, 92% for HPV-positive patients, and 75% for HPV-negative patients. Two-year disease-specific survival rates were 92%, 92%, and 75%, respectively. Two-year disease-free survival rates were 86%, 97%, and 50%, respectively.

"The 2-year overall survival and disease-specific survival were not statistically different between HPV-positive and negative patients treated with TORS followed by radiation with or without chemotherapy as indicated," Dr. Kakarala said.

The study was limited by its small size and retrospective design, but the findings suggest a role for minimally invasive TORS in OPSCCa patients, he said.

"Randomized trials incorporating minimally invasive transoral surgical procedures with radiation therapy and chemotherapy, and comparing survival, quality of life, and cost outcomes between these treatment modalities, are indicated," he added.

The findings were presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

Dr. Kakarala had no financial conflicts to disclose.

WASHINGTON – Oropharyngeal squamous cell cancer patients who underwent transoral robotic surgery had an overall 2-year survival rate of 87%, with no significant differences between patients who were positive vs. negative for the human papillomavirus, based on data from 52 patients.

HPV is associated with 45%-70% of cases of oropharyngeal squamous cell carcinoma (OPSCCa), said Dr. Kiran Kakarala, who conducted the study at Ohio State University in Columbus.

Previous studies have shown a significant difference in survival rates for patients with HPV-positive tumors, compared with those with negative tumors, Dr. Kakarala said. However, other studies have suggested that the use of transoral robotic surgery (TORS) for OPSCCa patients could narrow the gap in survival based on HPV status.

Dr. Kakarala and his colleagues reviewed data from 52 patients who underwent TORS with neck dissection and postoperative adjuvant treatment for previously untreated OPSCCa. The patients were part of a prospective single-arm cohort study at a single academic medical center.

HPV status was available for 42 patients; 36 were positive and 6 were negative. Demographic characteristics were not significantly different between the HPV-positive and negative patients. The mean age of the HPV-positive patients was 59 years, and the mean age of the negative patients was 57 years. The tonsil was the primary tumor site in 89% of the positive patients and 83% of the negative patients; the base of the tongue was the primary site in 11% of the positive patients and 17% of the negative patients.

HPV-positive patients had significantly higher N classifications based on the TNM Classification of Malignant Tumors, compared with HPV-negative patients (P = .015), and a significantly higher stage (P = .017). No significant differences were found in the number of HPV-positive vs. negative patients who received postoperative radiation or chemotherapy.

The 2-year survival rate was 87% for all 52 patients, 92% for HPV-positive patients, and 75% for HPV-negative patients. Two-year disease-specific survival rates were 92%, 92%, and 75%, respectively. Two-year disease-free survival rates were 86%, 97%, and 50%, respectively.

"The 2-year overall survival and disease-specific survival were not statistically different between HPV-positive and negative patients treated with TORS followed by radiation with or without chemotherapy as indicated," Dr. Kakarala said.

The study was limited by its small size and retrospective design, but the findings suggest a role for minimally invasive TORS in OPSCCa patients, he said.

"Randomized trials incorporating minimally invasive transoral surgical procedures with radiation therapy and chemotherapy, and comparing survival, quality of life, and cost outcomes between these treatment modalities, are indicated," he added.

The findings were presented at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

Dr. Kakarala had no financial conflicts to disclose.

WASHINGTON – Adenotonsillectomy reduced obstructive sleep apnea and bed-wetting in half of 35 children diagnosed with both conditions.

The study was limited by its small size, but the findings suggest that children with severe obstructive sleep apnea and nocturnal enuresis might benefit on both counts with adenotonsillectomy, said Dr. Prasad Thottam of Children’s Hospital of Michigan, Detroit.

The average age of the children studied was 8 years, 60% were male, and their average body mass index was 24 kg/m². Proper bladder function was documented in all of the children, and none had chronic conditions such as cerebral palsy, severe asthma, or morbid obesity. All experienced bed-wetting more than 3 nights per week. Any medications taken for nocturnal enuresis were discontinued for 1 month prior to surgery.

Four children had adenoidectomies, two had tonsillectomies, and 29 had adenotonsillectomies. After an average of 10 weeks post surgery, 51% of the children had reductions in bed-wetting, said Dr. Thottam. The reductions were most notable in children with a higher BMI and worse apnea characteristics on polysomnography.

Girls were five times more likely than were boys to have bed-wetting resolve after surgery. Children with prolonged stage 2 sleep were eight times more likely than were those with a normal duration of stage 2 sleep to have bed-wetting resolve.

In addition, when comparing the sleep architecture of the patients to established normal levels, an apnea-hypopnea index greater than 10 was associated with a higher rate of resolution of bed-wetting compared with the rest of the population.

The findings were presented at the annual meeting of the American Academy for Otolaryngology – Head and Neck Surgery Foundation. Dr. Thottam had no financial conflicts to disclose.

WASHINGTON – Adenotonsillectomy reduced obstructive sleep apnea and bed-wetting in half of 35 children diagnosed with both conditions.

The study was limited by its small size, but the findings suggest that children with severe obstructive sleep apnea and nocturnal enuresis might benefit on both counts with adenotonsillectomy, said Dr. Prasad Thottam of Children’s Hospital of Michigan, Detroit.

The average age of the children studied was 8 years, 60% were male, and their average body mass index was 24 kg/m². Proper bladder function was documented in all of the children, and none had chronic conditions such as cerebral palsy, severe asthma, or morbid obesity. All experienced bed-wetting more than 3 nights per week. Any medications taken for nocturnal enuresis were discontinued for 1 month prior to surgery.

Four children had adenoidectomies, two had tonsillectomies, and 29 had adenotonsillectomies. After an average of 10 weeks post surgery, 51% of the children had reductions in bed-wetting, said Dr. Thottam. The reductions were most notable in children with a higher BMI and worse apnea characteristics on polysomnography.

Girls were five times more likely than were boys to have bed-wetting resolve after surgery. Children with prolonged stage 2 sleep were eight times more likely than were those with a normal duration of stage 2 sleep to have bed-wetting resolve.

In addition, when comparing the sleep architecture of the patients to established normal levels, an apnea-hypopnea index greater than 10 was associated with a higher rate of resolution of bed-wetting compared with the rest of the population.

The findings were presented at the annual meeting of the American Academy for Otolaryngology – Head and Neck Surgery Foundation. Dr. Thottam had no financial conflicts to disclose.

WASHINGTON – Adenotonsillectomy reduced obstructive sleep apnea and bed-wetting in half of 35 children diagnosed with both conditions.

The study was limited by its small size, but the findings suggest that children with severe obstructive sleep apnea and nocturnal enuresis might benefit on both counts with adenotonsillectomy, said Dr. Prasad Thottam of Children’s Hospital of Michigan, Detroit.

The average age of the children studied was 8 years, 60% were male, and their average body mass index was 24 kg/m². Proper bladder function was documented in all of the children, and none had chronic conditions such as cerebral palsy, severe asthma, or morbid obesity. All experienced bed-wetting more than 3 nights per week. Any medications taken for nocturnal enuresis were discontinued for 1 month prior to surgery.

Four children had adenoidectomies, two had tonsillectomies, and 29 had adenotonsillectomies. After an average of 10 weeks post surgery, 51% of the children had reductions in bed-wetting, said Dr. Thottam. The reductions were most notable in children with a higher BMI and worse apnea characteristics on polysomnography.

Girls were five times more likely than were boys to have bed-wetting resolve after surgery. Children with prolonged stage 2 sleep were eight times more likely than were those with a normal duration of stage 2 sleep to have bed-wetting resolve.

In addition, when comparing the sleep architecture of the patients to established normal levels, an apnea-hypopnea index greater than 10 was associated with a higher rate of resolution of bed-wetting compared with the rest of the population.

The findings were presented at the annual meeting of the American Academy for Otolaryngology – Head and Neck Surgery Foundation. Dr. Thottam had no financial conflicts to disclose.

WASHINGTON – Chemokine receptor CCR7 expression is a significant predictor of cervical metastases in patients with squamous cell carcinoma in the oral cavity, based on data from 60 adults.

Metastatic spread of squamous cell carcinoma (SCC) is common, but the mechanisms behind the spread remain unclear, said Dr. Levi G. Ledgerwood of the University of California, Davis. "There has been a great deal of work that has looked at lymphocyte entry into lymphatics," he said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Courtesy Dr. Levi Ledgerwood

Recent research has focused on the chemokine receptor CCR7, a cell-surface molecule that is required for T-cell entry from the bloodstream and peripheral tissues into lymphatics, he noted. Data from previous studies suggest that CCR7 might play a role in various cancers in the metastases of the lymph nodes.

Dr. Ledgerwood and his colleagues reviewed tissue samples from primary tumors in 60 oral SCC patients who underwent surgical resection at a single center between 2006 and 2011. The study included 30 samples from patients with metastases and 30 samples from patients without metastases. There were no significant demographic differences between the groups, although each group had more male than female patients, Dr. Ledgerwood noted. A total of 30 patients were node positive, and 30 were node negative.

Overall, patients with cervical metastases showed significantly higher CCR7 expression than those without cervical metastases (P less than .001). A total of 97% of node-positive patients were positive for CCR7 expression, but only 43% of patients without cervical metastases were positive for CCR7.

Courtesy Dr. Levi Ledgerwood

When the lymph nodes of the samples from metastatic cancer patients were examined, all 30 node-positive patients showed expression of CCR7, Dr. Ledgerwood added.

Although the study was limited by its small size, the results suggest a possible role for CCR7 in T-cell access to lymphatics, said Dr. Ledgerwood.

"This is a preliminary study, but we feel that this receptor could provide a very interesting target for future drug therapies and could also help in predicting the behavior of tumors," he said.

Dr. Ledgerwood had no financial conflicts to disclose.

WASHINGTON – Chemokine receptor CCR7 expression is a significant predictor of cervical metastases in patients with squamous cell carcinoma in the oral cavity, based on data from 60 adults.

Metastatic spread of squamous cell carcinoma (SCC) is common, but the mechanisms behind the spread remain unclear, said Dr. Levi G. Ledgerwood of the University of California, Davis. "There has been a great deal of work that has looked at lymphocyte entry into lymphatics," he said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Courtesy Dr. Levi Ledgerwood

Recent research has focused on the chemokine receptor CCR7, a cell-surface molecule that is required for T-cell entry from the bloodstream and peripheral tissues into lymphatics, he noted. Data from previous studies suggest that CCR7 might play a role in various cancers in the metastases of the lymph nodes.

Dr. Ledgerwood and his colleagues reviewed tissue samples from primary tumors in 60 oral SCC patients who underwent surgical resection at a single center between 2006 and 2011. The study included 30 samples from patients with metastases and 30 samples from patients without metastases. There were no significant demographic differences between the groups, although each group had more male than female patients, Dr. Ledgerwood noted. A total of 30 patients were node positive, and 30 were node negative.

Overall, patients with cervical metastases showed significantly higher CCR7 expression than those without cervical metastases (P less than .001). A total of 97% of node-positive patients were positive for CCR7 expression, but only 43% of patients without cervical metastases were positive for CCR7.

Courtesy Dr. Levi Ledgerwood

When the lymph nodes of the samples from metastatic cancer patients were examined, all 30 node-positive patients showed expression of CCR7, Dr. Ledgerwood added.

Although the study was limited by its small size, the results suggest a possible role for CCR7 in T-cell access to lymphatics, said Dr. Ledgerwood.

"This is a preliminary study, but we feel that this receptor could provide a very interesting target for future drug therapies and could also help in predicting the behavior of tumors," he said.

Dr. Ledgerwood had no financial conflicts to disclose.

WASHINGTON – Chemokine receptor CCR7 expression is a significant predictor of cervical metastases in patients with squamous cell carcinoma in the oral cavity, based on data from 60 adults.

Metastatic spread of squamous cell carcinoma (SCC) is common, but the mechanisms behind the spread remain unclear, said Dr. Levi G. Ledgerwood of the University of California, Davis. "There has been a great deal of work that has looked at lymphocyte entry into lymphatics," he said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Courtesy Dr. Levi Ledgerwood

Recent research has focused on the chemokine receptor CCR7, a cell-surface molecule that is required for T-cell entry from the bloodstream and peripheral tissues into lymphatics, he noted. Data from previous studies suggest that CCR7 might play a role in various cancers in the metastases of the lymph nodes.

Dr. Ledgerwood and his colleagues reviewed tissue samples from primary tumors in 60 oral SCC patients who underwent surgical resection at a single center between 2006 and 2011. The study included 30 samples from patients with metastases and 30 samples from patients without metastases. There were no significant demographic differences between the groups, although each group had more male than female patients, Dr. Ledgerwood noted. A total of 30 patients were node positive, and 30 were node negative.

Overall, patients with cervical metastases showed significantly higher CCR7 expression than those without cervical metastases (P less than .001). A total of 97% of node-positive patients were positive for CCR7 expression, but only 43% of patients without cervical metastases were positive for CCR7.

Courtesy Dr. Levi Ledgerwood

When the lymph nodes of the samples from metastatic cancer patients were examined, all 30 node-positive patients showed expression of CCR7, Dr. Ledgerwood added.

Although the study was limited by its small size, the results suggest a possible role for CCR7 in T-cell access to lymphatics, said Dr. Ledgerwood.

"This is a preliminary study, but we feel that this receptor could provide a very interesting target for future drug therapies and could also help in predicting the behavior of tumors," he said.

Dr. Ledgerwood had no financial conflicts to disclose.

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.