Bruce Jancin

VIENNA — Ceftaroline, an investigational fifth-generation cephalosporin in late-stage development, is likely to become a major drug in the treatment of infections caused by Staphylococcus aureus and Streptococcus pneumoniae, including the strains resistant to current widely prescribed antimicrobials.

Ceftaroline exhibited impressive in vitro activity in standardized antimicrobial susceptibility testing involving 8,842 isolates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus(MSSA) from 56 U.S. and European medical centers during 2008–2009, Dr. Helio S. Sader reported at the meeting.

In a separate laboratory study presented at the congress, Dr. Michael R. Jacobs reported that ceftaroline showed more in vitro activity against the prevailing U.S. pediatric and adult serotypes of S. pneumoniae than any of the other 13 agents tested.

The investigational drug's performance was particularly strong against the isolates from pediatric patients, which tend to be among the most resistant to currently available antimicrobials. Indeed, the often multidrug-resistant serotype 19A accounted for 32.6% of all S. pneumoniae isolates from pediatric patients, compared with 15% in adults.

Ceftaroline had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL against serotype 19A, compared with 65.6 mcg/mL for ceftriaxone. The MIC90s for 12 other currently marketed antimicrobials ranged from 13.8 to 100 mcg/mL, noted Dr. Jacobs, professor of clinical microbiology at Case Western Reserve University, Cleveland.

The study included 891 S. pneumoniae isolates that were obtained from patients in 22 U.S. cities in 2008. The isolates came from infections at all body sites, and one-third were from pediatric patients. Pediatric isolates were significantly less susceptible to amoxicillin, penicillin, and ceftriaxone than were adult isolates. Serotypes covered in the seven-valent pneumococcal conjugate vaccine were uncommon in both adults and children.

Ceftaroline is now under Food and Drug Administration review for two potential indications: community-acquired pneumonia and complicated skin and skin structure infections.

In the S. aureus study, ceftaroline was 16-fold more active than was ceftriaxone against MSSA strains. It also showed strong potency against MRSA strains, with MIC90s of 1–2 mg/L, making it at least 64-fold more potent than ceftriaxone, according to Dr. Sader of JMI Laboratories, North Liberty, Iowa.

He drew particular attention to the investigational agent's outstanding performance against MRSA isolates with SCCmec type IV, which is found in the U.S. pandemic community-associated MRSA clone USA300, as well as in several problematic clones circulating in Europe. Ceftaroline's MIC90 of 1 mg/L against these isolates was the most favorable of the 10 drugs tested.

Ceftaroline is being developed by Forest Laboratories, which supported both studies.

VIENNA — Ceftaroline, an investigational fifth-generation cephalosporin in late-stage development, is likely to become a major drug in the treatment of infections caused by Staphylococcus aureus and Streptococcus pneumoniae, including the strains resistant to current widely prescribed antimicrobials.

Ceftaroline exhibited impressive in vitro activity in standardized antimicrobial susceptibility testing involving 8,842 isolates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus(MSSA) from 56 U.S. and European medical centers during 2008–2009, Dr. Helio S. Sader reported at the meeting.

In a separate laboratory study presented at the congress, Dr. Michael R. Jacobs reported that ceftaroline showed more in vitro activity against the prevailing U.S. pediatric and adult serotypes of S. pneumoniae than any of the other 13 agents tested.

The investigational drug's performance was particularly strong against the isolates from pediatric patients, which tend to be among the most resistant to currently available antimicrobials. Indeed, the often multidrug-resistant serotype 19A accounted for 32.6% of all S. pneumoniae isolates from pediatric patients, compared with 15% in adults.

Ceftaroline had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL against serotype 19A, compared with 65.6 mcg/mL for ceftriaxone. The MIC90s for 12 other currently marketed antimicrobials ranged from 13.8 to 100 mcg/mL, noted Dr. Jacobs, professor of clinical microbiology at Case Western Reserve University, Cleveland.

The study included 891 S. pneumoniae isolates that were obtained from patients in 22 U.S. cities in 2008. The isolates came from infections at all body sites, and one-third were from pediatric patients. Pediatric isolates were significantly less susceptible to amoxicillin, penicillin, and ceftriaxone than were adult isolates. Serotypes covered in the seven-valent pneumococcal conjugate vaccine were uncommon in both adults and children.

Ceftaroline is now under Food and Drug Administration review for two potential indications: community-acquired pneumonia and complicated skin and skin structure infections.

In the S. aureus study, ceftaroline was 16-fold more active than was ceftriaxone against MSSA strains. It also showed strong potency against MRSA strains, with MIC90s of 1–2 mg/L, making it at least 64-fold more potent than ceftriaxone, according to Dr. Sader of JMI Laboratories, North Liberty, Iowa.

He drew particular attention to the investigational agent's outstanding performance against MRSA isolates with SCCmec type IV, which is found in the U.S. pandemic community-associated MRSA clone USA300, as well as in several problematic clones circulating in Europe. Ceftaroline's MIC90 of 1 mg/L against these isolates was the most favorable of the 10 drugs tested.

Ceftaroline is being developed by Forest Laboratories, which supported both studies.

VIENNA — Ceftaroline, an investigational fifth-generation cephalosporin in late-stage development, is likely to become a major drug in the treatment of infections caused by Staphylococcus aureus and Streptococcus pneumoniae, including the strains resistant to current widely prescribed antimicrobials.

Ceftaroline exhibited impressive in vitro activity in standardized antimicrobial susceptibility testing involving 8,842 isolates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus(MSSA) from 56 U.S. and European medical centers during 2008–2009, Dr. Helio S. Sader reported at the meeting.

In a separate laboratory study presented at the congress, Dr. Michael R. Jacobs reported that ceftaroline showed more in vitro activity against the prevailing U.S. pediatric and adult serotypes of S. pneumoniae than any of the other 13 agents tested.

The investigational drug's performance was particularly strong against the isolates from pediatric patients, which tend to be among the most resistant to currently available antimicrobials. Indeed, the often multidrug-resistant serotype 19A accounted for 32.6% of all S. pneumoniae isolates from pediatric patients, compared with 15% in adults.

Ceftaroline had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL against serotype 19A, compared with 65.6 mcg/mL for ceftriaxone. The MIC90s for 12 other currently marketed antimicrobials ranged from 13.8 to 100 mcg/mL, noted Dr. Jacobs, professor of clinical microbiology at Case Western Reserve University, Cleveland.

The study included 891 S. pneumoniae isolates that were obtained from patients in 22 U.S. cities in 2008. The isolates came from infections at all body sites, and one-third were from pediatric patients. Pediatric isolates were significantly less susceptible to amoxicillin, penicillin, and ceftriaxone than were adult isolates. Serotypes covered in the seven-valent pneumococcal conjugate vaccine were uncommon in both adults and children.

Ceftaroline is now under Food and Drug Administration review for two potential indications: community-acquired pneumonia and complicated skin and skin structure infections.

In the S. aureus study, ceftaroline was 16-fold more active than was ceftriaxone against MSSA strains. It also showed strong potency against MRSA strains, with MIC90s of 1–2 mg/L, making it at least 64-fold more potent than ceftriaxone, according to Dr. Sader of JMI Laboratories, North Liberty, Iowa.

He drew particular attention to the investigational agent's outstanding performance against MRSA isolates with SCCmec type IV, which is found in the U.S. pandemic community-associated MRSA clone USA300, as well as in several problematic clones circulating in Europe. Ceftaroline's MIC90 of 1 mg/L against these isolates was the most favorable of the 10 drugs tested.

Ceftaroline is being developed by Forest Laboratories, which supported both studies.

MADRID — All-cause mortality is substantially lower in patients with basal cell carcinoma than in those with squamous cell carcinoma, according to a large Danish national registry study.

“In general, patients with basal cell carcinoma are in fact healthier than their counterparts with squamous cell carcinoma or age-matched controls,” Dr. Gregor B.E. Jemec observed at the congress, which was sponsored by the Skin Cancer Foundation.

He cited a study in which investigators at Aarhus (Denmark) University Hospital analyzed causes of death among patients with nonmelanoma skin cancer who were entered into the comprehensive Danish Cancer Registry in 1978–2001. The study population included all 82,837 Danes with basal cell carcinoma (BCC) and the 13,453 with squamous cell carcinoma (SCC) during the study years.

The all-cause mortality rate was 3% lower in the BCC cohort than the standardized rate in the general Danish population, whereas overall mortality in the SCC group was 30% greater than in the general population.

The increased all-cause mortality for patients with SCC was mainly due to excess deaths from chronic obstructive pulmonary disease, cardiovascular disease, cancer, and infectious diseases.

In contrast, patients with BCC had below-average mortality from COPD, diabetes, and cardiovascular disease (Br. J. Dermatol. 2008;159:419–25).

The investigators speculated that the observed mortality benefit among patients with BCC might result in part from the salutary effects of increased serum vitamin D levels on a variety of chronic diseases. BCC is a marker for increased sun exposure, which boosts serum vitamin D levels, which in turn has been linked in a growing number of epidemiologic studies to reduced risks of cardiovascular disease and other major causes of death. However, the Danish registry didn't include data on vitamin D levels, so this is supposition.

Mortality from nonmelanoma skin cancer itself is quite limited. Investigators at the Danish Cancer Registry, using national data for 1984, estimated lethality rates to be 4.3% for SCC and 0.12% for BCC (Br. J. Dermatol. 1991;125:580–2), noted Dr. Jemec of the University of Copenhagen.

Nearly 74,000 deaths in the United States from 1969 to 2000 were attributed to nonmelanoma skin cancer, according to an analysis by investigators at Brown University in Providence, R.I.

Almost 29,000 of these deaths were caused by nonmelanoma skin cancers that arose on genital skin, with a nearly 3:1 ratio of deaths attributed to vulvar and penile-scrotal cancers (J. Invest. Dermatol. 2007;127:2323–7).

Dr. Jemec reported having no conflicts of interest.

MADRID — All-cause mortality is substantially lower in patients with basal cell carcinoma than in those with squamous cell carcinoma, according to a large Danish national registry study.

“In general, patients with basal cell carcinoma are in fact healthier than their counterparts with squamous cell carcinoma or age-matched controls,” Dr. Gregor B.E. Jemec observed at the congress, which was sponsored by the Skin Cancer Foundation.

He cited a study in which investigators at Aarhus (Denmark) University Hospital analyzed causes of death among patients with nonmelanoma skin cancer who were entered into the comprehensive Danish Cancer Registry in 1978–2001. The study population included all 82,837 Danes with basal cell carcinoma (BCC) and the 13,453 with squamous cell carcinoma (SCC) during the study years.

The all-cause mortality rate was 3% lower in the BCC cohort than the standardized rate in the general Danish population, whereas overall mortality in the SCC group was 30% greater than in the general population.

The increased all-cause mortality for patients with SCC was mainly due to excess deaths from chronic obstructive pulmonary disease, cardiovascular disease, cancer, and infectious diseases.

In contrast, patients with BCC had below-average mortality from COPD, diabetes, and cardiovascular disease (Br. J. Dermatol. 2008;159:419–25).

The investigators speculated that the observed mortality benefit among patients with BCC might result in part from the salutary effects of increased serum vitamin D levels on a variety of chronic diseases. BCC is a marker for increased sun exposure, which boosts serum vitamin D levels, which in turn has been linked in a growing number of epidemiologic studies to reduced risks of cardiovascular disease and other major causes of death. However, the Danish registry didn't include data on vitamin D levels, so this is supposition.

Mortality from nonmelanoma skin cancer itself is quite limited. Investigators at the Danish Cancer Registry, using national data for 1984, estimated lethality rates to be 4.3% for SCC and 0.12% for BCC (Br. J. Dermatol. 1991;125:580–2), noted Dr. Jemec of the University of Copenhagen.

Nearly 74,000 deaths in the United States from 1969 to 2000 were attributed to nonmelanoma skin cancer, according to an analysis by investigators at Brown University in Providence, R.I.

Almost 29,000 of these deaths were caused by nonmelanoma skin cancers that arose on genital skin, with a nearly 3:1 ratio of deaths attributed to vulvar and penile-scrotal cancers (J. Invest. Dermatol. 2007;127:2323–7).

Dr. Jemec reported having no conflicts of interest.

MADRID — All-cause mortality is substantially lower in patients with basal cell carcinoma than in those with squamous cell carcinoma, according to a large Danish national registry study.

“In general, patients with basal cell carcinoma are in fact healthier than their counterparts with squamous cell carcinoma or age-matched controls,” Dr. Gregor B.E. Jemec observed at the congress, which was sponsored by the Skin Cancer Foundation.

He cited a study in which investigators at Aarhus (Denmark) University Hospital analyzed causes of death among patients with nonmelanoma skin cancer who were entered into the comprehensive Danish Cancer Registry in 1978–2001. The study population included all 82,837 Danes with basal cell carcinoma (BCC) and the 13,453 with squamous cell carcinoma (SCC) during the study years.

The all-cause mortality rate was 3% lower in the BCC cohort than the standardized rate in the general Danish population, whereas overall mortality in the SCC group was 30% greater than in the general population.

The increased all-cause mortality for patients with SCC was mainly due to excess deaths from chronic obstructive pulmonary disease, cardiovascular disease, cancer, and infectious diseases.

In contrast, patients with BCC had below-average mortality from COPD, diabetes, and cardiovascular disease (Br. J. Dermatol. 2008;159:419–25).

The investigators speculated that the observed mortality benefit among patients with BCC might result in part from the salutary effects of increased serum vitamin D levels on a variety of chronic diseases. BCC is a marker for increased sun exposure, which boosts serum vitamin D levels, which in turn has been linked in a growing number of epidemiologic studies to reduced risks of cardiovascular disease and other major causes of death. However, the Danish registry didn't include data on vitamin D levels, so this is supposition.

Mortality from nonmelanoma skin cancer itself is quite limited. Investigators at the Danish Cancer Registry, using national data for 1984, estimated lethality rates to be 4.3% for SCC and 0.12% for BCC (Br. J. Dermatol. 1991;125:580–2), noted Dr. Jemec of the University of Copenhagen.

Nearly 74,000 deaths in the United States from 1969 to 2000 were attributed to nonmelanoma skin cancer, according to an analysis by investigators at Brown University in Providence, R.I.

Almost 29,000 of these deaths were caused by nonmelanoma skin cancers that arose on genital skin, with a nearly 3:1 ratio of deaths attributed to vulvar and penile-scrotal cancers (J. Invest. Dermatol. 2007;127:2323–7).

Dr. Jemec reported having no conflicts of interest.

STOCKHOLM — New-generation, highly sensitive troponin T assays provide added value in the form of improved early risk stratification of normotensive patients who have acute pulmonary embolism, according to the results of a prospective head-to-head study.

“I think the most important finding of this study is that with this new high sensitivity troponin T assay, we could safely identify those patients who have a low 30-day risk of adverse events, with a sensitivity of 100% and also a negative predictive value of 100%,” Dr. Mareike Lankeit said at the congress.

In contrast, the conventional troponin T assay had a negative predictive value of only 50%. It would have missed half of the patients who experienced an adverse event (defined as death, endotracheal intubation, need for catecholamines, or cardiopulmonary resuscitation).

Moreover, of the three biomarkers that were studied, including N-terminal prohormone brain natriuretic peptide, only baseline highly sensitive troponin T (hsTnT) was a significant predictor of mortality risk during long-term prospective follow-up of nearly 3 years, added Dr. Lankeit of Georg-August University Göttingen (Germany).

Recent guidelines emphasize the need for early risk stratification of patients with acute pulmonary embolism. Consensus exists that patients who present with refractory hypotension or shock are at very high risk of early mortality and should undergo urgent recanalization.

Strategies for non–high-risk patients (that is, those who are normotensive on admission) remain controversial.

Dr. Lankeit's hypothesis was that the use of more-sensitive laboratory biomarkers in the emergency department would result in improved prognostic assessment of these normotensive patients with acute pulmonary embolism.

Patients who were identified in this way as low risk might be possible candidates for home treatment.

She presented a prospective study of 156 consecutive normotensive patients with confirmed acute pulmonary embolism in which she compared the prognostic value of baseline hsTnT, conventional TnT, and NT-proBNP testing.

An hsTnT cutoff value of 14 pg/mL, which 64% of patients met or exceeded, had a 100% prognostic sensitivity and negative predictive value for 30-day adverse outcomes. The NT-proBNP assay performed equally well, but the conventional TnT assay, using the cutoff value of 0.03 ng/mL, would have misclassified 50% of patients with an adverse early outcome as being at low risk.

Dr. Lankeit and her associates found that an elevated baseline hsTnT alone was associated with a twofold increased risk of adverse 30-day outcomes.

An elevated NT-proBNP was associated with a 2.3-fold risk. But when an hsTnT of at least 14 pg/mL was associated with evidence of right ventricular dysfunction on echocardiography, the 30-day adverse outcome risk was increased to 11.9-fold.

The prognostic power of echocardiographic evidence of right ventricular dysfunction plus an NT-proBNP of at least 1,000 pg/mL was even more impressive, with an associated 17.8-fold increased risk of an adverse 30-day outcome.

In contrast, the conventional TnT assay didn't provide additive prognostic information when it was combined with evidence of right ventricular dysfunction.

During a median follow-up of close to 3 years, 14.4% of patients died. The only baseline variables that were significantly associated with increased long-term mortality risk were an elevated hsTnT, malignancy, and heart failure. Thus, a baseline hsTnT of 14 pg/mL or greater identifies a subgroup of patients with acute pulmonary embolism who warrant closer long-term follow-up, according to Dr. Lankeit.

She said that in her hospital, where hsTnT is now part of the routine diagnostic laboratory panel that is administered in the emergency department to patients presenting with acute pulmonary embolism, the hsTnT results come back within 30 minutes.

Several of Dr. Lankeit's coinvestigators have received research funding and honoraria for lectures from Roche Diagnostics, which markets the hsTnT assay. Dr. Lankeit declared that she has no financial conflicts.

'We could safely identify those patients who have a low 30-day risk of adverse events.'

Source DR. LANKEIT

STOCKHOLM — New-generation, highly sensitive troponin T assays provide added value in the form of improved early risk stratification of normotensive patients who have acute pulmonary embolism, according to the results of a prospective head-to-head study.

“I think the most important finding of this study is that with this new high sensitivity troponin T assay, we could safely identify those patients who have a low 30-day risk of adverse events, with a sensitivity of 100% and also a negative predictive value of 100%,” Dr. Mareike Lankeit said at the congress.

In contrast, the conventional troponin T assay had a negative predictive value of only 50%. It would have missed half of the patients who experienced an adverse event (defined as death, endotracheal intubation, need for catecholamines, or cardiopulmonary resuscitation).

Moreover, of the three biomarkers that were studied, including N-terminal prohormone brain natriuretic peptide, only baseline highly sensitive troponin T (hsTnT) was a significant predictor of mortality risk during long-term prospective follow-up of nearly 3 years, added Dr. Lankeit of Georg-August University Göttingen (Germany).

Recent guidelines emphasize the need for early risk stratification of patients with acute pulmonary embolism. Consensus exists that patients who present with refractory hypotension or shock are at very high risk of early mortality and should undergo urgent recanalization.

Strategies for non–high-risk patients (that is, those who are normotensive on admission) remain controversial.

Dr. Lankeit's hypothesis was that the use of more-sensitive laboratory biomarkers in the emergency department would result in improved prognostic assessment of these normotensive patients with acute pulmonary embolism.

Patients who were identified in this way as low risk might be possible candidates for home treatment.

She presented a prospective study of 156 consecutive normotensive patients with confirmed acute pulmonary embolism in which she compared the prognostic value of baseline hsTnT, conventional TnT, and NT-proBNP testing.

An hsTnT cutoff value of 14 pg/mL, which 64% of patients met or exceeded, had a 100% prognostic sensitivity and negative predictive value for 30-day adverse outcomes. The NT-proBNP assay performed equally well, but the conventional TnT assay, using the cutoff value of 0.03 ng/mL, would have misclassified 50% of patients with an adverse early outcome as being at low risk.

Dr. Lankeit and her associates found that an elevated baseline hsTnT alone was associated with a twofold increased risk of adverse 30-day outcomes.

An elevated NT-proBNP was associated with a 2.3-fold risk. But when an hsTnT of at least 14 pg/mL was associated with evidence of right ventricular dysfunction on echocardiography, the 30-day adverse outcome risk was increased to 11.9-fold.

The prognostic power of echocardiographic evidence of right ventricular dysfunction plus an NT-proBNP of at least 1,000 pg/mL was even more impressive, with an associated 17.8-fold increased risk of an adverse 30-day outcome.

In contrast, the conventional TnT assay didn't provide additive prognostic information when it was combined with evidence of right ventricular dysfunction.

During a median follow-up of close to 3 years, 14.4% of patients died. The only baseline variables that were significantly associated with increased long-term mortality risk were an elevated hsTnT, malignancy, and heart failure. Thus, a baseline hsTnT of 14 pg/mL or greater identifies a subgroup of patients with acute pulmonary embolism who warrant closer long-term follow-up, according to Dr. Lankeit.

She said that in her hospital, where hsTnT is now part of the routine diagnostic laboratory panel that is administered in the emergency department to patients presenting with acute pulmonary embolism, the hsTnT results come back within 30 minutes.

Several of Dr. Lankeit's coinvestigators have received research funding and honoraria for lectures from Roche Diagnostics, which markets the hsTnT assay. Dr. Lankeit declared that she has no financial conflicts.

'We could safely identify those patients who have a low 30-day risk of adverse events.'

Source DR. LANKEIT

STOCKHOLM — New-generation, highly sensitive troponin T assays provide added value in the form of improved early risk stratification of normotensive patients who have acute pulmonary embolism, according to the results of a prospective head-to-head study.

“I think the most important finding of this study is that with this new high sensitivity troponin T assay, we could safely identify those patients who have a low 30-day risk of adverse events, with a sensitivity of 100% and also a negative predictive value of 100%,” Dr. Mareike Lankeit said at the congress.

In contrast, the conventional troponin T assay had a negative predictive value of only 50%. It would have missed half of the patients who experienced an adverse event (defined as death, endotracheal intubation, need for catecholamines, or cardiopulmonary resuscitation).

Moreover, of the three biomarkers that were studied, including N-terminal prohormone brain natriuretic peptide, only baseline highly sensitive troponin T (hsTnT) was a significant predictor of mortality risk during long-term prospective follow-up of nearly 3 years, added Dr. Lankeit of Georg-August University Göttingen (Germany).

Recent guidelines emphasize the need for early risk stratification of patients with acute pulmonary embolism. Consensus exists that patients who present with refractory hypotension or shock are at very high risk of early mortality and should undergo urgent recanalization.

Strategies for non–high-risk patients (that is, those who are normotensive on admission) remain controversial.

Dr. Lankeit's hypothesis was that the use of more-sensitive laboratory biomarkers in the emergency department would result in improved prognostic assessment of these normotensive patients with acute pulmonary embolism.

Patients who were identified in this way as low risk might be possible candidates for home treatment.

She presented a prospective study of 156 consecutive normotensive patients with confirmed acute pulmonary embolism in which she compared the prognostic value of baseline hsTnT, conventional TnT, and NT-proBNP testing.

An hsTnT cutoff value of 14 pg/mL, which 64% of patients met or exceeded, had a 100% prognostic sensitivity and negative predictive value for 30-day adverse outcomes. The NT-proBNP assay performed equally well, but the conventional TnT assay, using the cutoff value of 0.03 ng/mL, would have misclassified 50% of patients with an adverse early outcome as being at low risk.

Dr. Lankeit and her associates found that an elevated baseline hsTnT alone was associated with a twofold increased risk of adverse 30-day outcomes.

An elevated NT-proBNP was associated with a 2.3-fold risk. But when an hsTnT of at least 14 pg/mL was associated with evidence of right ventricular dysfunction on echocardiography, the 30-day adverse outcome risk was increased to 11.9-fold.

The prognostic power of echocardiographic evidence of right ventricular dysfunction plus an NT-proBNP of at least 1,000 pg/mL was even more impressive, with an associated 17.8-fold increased risk of an adverse 30-day outcome.

In contrast, the conventional TnT assay didn't provide additive prognostic information when it was combined with evidence of right ventricular dysfunction.

During a median follow-up of close to 3 years, 14.4% of patients died. The only baseline variables that were significantly associated with increased long-term mortality risk were an elevated hsTnT, malignancy, and heart failure. Thus, a baseline hsTnT of 14 pg/mL or greater identifies a subgroup of patients with acute pulmonary embolism who warrant closer long-term follow-up, according to Dr. Lankeit.

She said that in her hospital, where hsTnT is now part of the routine diagnostic laboratory panel that is administered in the emergency department to patients presenting with acute pulmonary embolism, the hsTnT results come back within 30 minutes.

Several of Dr. Lankeit's coinvestigators have received research funding and honoraria for lectures from Roche Diagnostics, which markets the hsTnT assay. Dr. Lankeit declared that she has no financial conflicts.

'We could safely identify those patients who have a low 30-day risk of adverse events.'

Source DR. LANKEIT

SAN ANTONIO — Children with obstructive sleep apnea get worse grades in school than do their classmates without sleep-disordered breathing, a study shows.

These 10- to 16-year-olds with even mild obstructive sleep apnea (OSA) were also independently rated both by parents and by teachers as more likely to have attention and learning problems, Dean W. Beebe, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

“There was an impressive impact of sleep-disordered breathing on academic grades. That leaves the subjects with moderate to severe sleep apnea at a serious disadvantage,” said Dr. Beebe of Cincinnati Children's Hospital Medical Center.

The study included 163 overweight youths aged 10–16 years, who were recruited from sleep or weight management clinics. Investigators rated 42 of them as having moderate to severe OSA based on an apnea-hypopnea index in excess of 5 events/hr. Another 58 had mild OSA, defined by an apnea-hypopnea index of 1–5 events/hr. Twenty-six participants were classified as snorers, while 37 were free of sleep-disordered breathing (SDB).

Subjects without SDB maintained a collective B average at school. Snorers trended toward lower grades, although the difference was not significant. But participants with OSA, whether mild or more severe, averaged half a grade point lower than did those without SDB. The difference—a B–/C+ average rather than a solid B—could have implications down the road in terms of college and career opportunities, Dr. Beebe noted.

Thirty percent of students with moderate to severe OSA had a C average or less, compared with just 15% of those without SDB. And while 15% of subjects with no SDB had an A average academically, that was the case for only a single student with moderate to severe OSA.

On the validated Behavior Assessment System for Children (BASC), teachers rated the students with mild or more severe OSA as having significantly more attention and learning problems than those without SDB. Teachers also rated the non-SDB youths significantly higher in terms of the BASC adaptive functioning domains of leadership, social skills, and study skills.

Parents of students with SDB rated them on the BASC as having more attention, anxiety, depression, aggression, and hyperactivity problems.

Given the worsening obesity epidemic and the fact that obesity is a major risk factor for SDB in middle childhood, the evidence that SDB has adverse academic, behavioral, and cognitive consequences suggests a major public health concern, according to Dr. Beebe.

He said the next stage of his research will be to see whether the academic and learning deficits associated with SDB in middle childhood and adolescence are remediable when the respiratory condition is treated.

The study was funded by the American Sleep Medicine Foundation and the National Institutes of Health. Dr. Beebe reported having no financial conflicts.

SAN ANTONIO — Children with obstructive sleep apnea get worse grades in school than do their classmates without sleep-disordered breathing, a study shows.

These 10- to 16-year-olds with even mild obstructive sleep apnea (OSA) were also independently rated both by parents and by teachers as more likely to have attention and learning problems, Dean W. Beebe, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

“There was an impressive impact of sleep-disordered breathing on academic grades. That leaves the subjects with moderate to severe sleep apnea at a serious disadvantage,” said Dr. Beebe of Cincinnati Children's Hospital Medical Center.

The study included 163 overweight youths aged 10–16 years, who were recruited from sleep or weight management clinics. Investigators rated 42 of them as having moderate to severe OSA based on an apnea-hypopnea index in excess of 5 events/hr. Another 58 had mild OSA, defined by an apnea-hypopnea index of 1–5 events/hr. Twenty-six participants were classified as snorers, while 37 were free of sleep-disordered breathing (SDB).

Subjects without SDB maintained a collective B average at school. Snorers trended toward lower grades, although the difference was not significant. But participants with OSA, whether mild or more severe, averaged half a grade point lower than did those without SDB. The difference—a B–/C+ average rather than a solid B—could have implications down the road in terms of college and career opportunities, Dr. Beebe noted.

Thirty percent of students with moderate to severe OSA had a C average or less, compared with just 15% of those without SDB. And while 15% of subjects with no SDB had an A average academically, that was the case for only a single student with moderate to severe OSA.

On the validated Behavior Assessment System for Children (BASC), teachers rated the students with mild or more severe OSA as having significantly more attention and learning problems than those without SDB. Teachers also rated the non-SDB youths significantly higher in terms of the BASC adaptive functioning domains of leadership, social skills, and study skills.

Parents of students with SDB rated them on the BASC as having more attention, anxiety, depression, aggression, and hyperactivity problems.

Given the worsening obesity epidemic and the fact that obesity is a major risk factor for SDB in middle childhood, the evidence that SDB has adverse academic, behavioral, and cognitive consequences suggests a major public health concern, according to Dr. Beebe.

He said the next stage of his research will be to see whether the academic and learning deficits associated with SDB in middle childhood and adolescence are remediable when the respiratory condition is treated.

The study was funded by the American Sleep Medicine Foundation and the National Institutes of Health. Dr. Beebe reported having no financial conflicts.

SAN ANTONIO — Children with obstructive sleep apnea get worse grades in school than do their classmates without sleep-disordered breathing, a study shows.

These 10- to 16-year-olds with even mild obstructive sleep apnea (OSA) were also independently rated both by parents and by teachers as more likely to have attention and learning problems, Dean W. Beebe, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

“There was an impressive impact of sleep-disordered breathing on academic grades. That leaves the subjects with moderate to severe sleep apnea at a serious disadvantage,” said Dr. Beebe of Cincinnati Children's Hospital Medical Center.

The study included 163 overweight youths aged 10–16 years, who were recruited from sleep or weight management clinics. Investigators rated 42 of them as having moderate to severe OSA based on an apnea-hypopnea index in excess of 5 events/hr. Another 58 had mild OSA, defined by an apnea-hypopnea index of 1–5 events/hr. Twenty-six participants were classified as snorers, while 37 were free of sleep-disordered breathing (SDB).

Subjects without SDB maintained a collective B average at school. Snorers trended toward lower grades, although the difference was not significant. But participants with OSA, whether mild or more severe, averaged half a grade point lower than did those without SDB. The difference—a B–/C+ average rather than a solid B—could have implications down the road in terms of college and career opportunities, Dr. Beebe noted.

Thirty percent of students with moderate to severe OSA had a C average or less, compared with just 15% of those without SDB. And while 15% of subjects with no SDB had an A average academically, that was the case for only a single student with moderate to severe OSA.

On the validated Behavior Assessment System for Children (BASC), teachers rated the students with mild or more severe OSA as having significantly more attention and learning problems than those without SDB. Teachers also rated the non-SDB youths significantly higher in terms of the BASC adaptive functioning domains of leadership, social skills, and study skills.

Parents of students with SDB rated them on the BASC as having more attention, anxiety, depression, aggression, and hyperactivity problems.

Given the worsening obesity epidemic and the fact that obesity is a major risk factor for SDB in middle childhood, the evidence that SDB has adverse academic, behavioral, and cognitive consequences suggests a major public health concern, according to Dr. Beebe.

He said the next stage of his research will be to see whether the academic and learning deficits associated with SDB in middle childhood and adolescence are remediable when the respiratory condition is treated.

The study was funded by the American Sleep Medicine Foundation and the National Institutes of Health. Dr. Beebe reported having no financial conflicts.

VAIL, COLO. — Tick paralysis is often misdiagnosed — with potentially dire consequences — as one of the other diseases that cause an acute ascending paralysis with preserved mental status.

The arthropod-inflicted paralysis is most often confused with Guillain-Barré syndrome. Other causes of an acute ascending paralysis with preserved mental status include spinal cord tumors and acute poliomyelitis.

Botulism, in contrast, causes a descending paralysis with preserved mental status, Dr. Sean O'Leary said at the conference which was sponsored by the Children's Hospital, Denver.

Conducting a thorough search for an embedded tick is essential in a patient with an acute ascending paralysis with preserved sensorium, particularly when there is a history consistent with potential tick exposure. Treatment of tick paralysis is simple: remove the tick. Clinical improvement will follow within hours.

In unrecognized and untreated cases of tick paralysis, however, the fatality rate is about 10%, with death typically occurring just 18–30 hours after symptom onset, according to Dr. O'Leary of the Children's Hospital and the University of Colorado, both in Denver.

Tick paralysis is more common in children than adults. The highest-risk group is young girls with long hair that can readily hide an engorged tick that's had a blood meal.

At 3 days after attachment, the tick (usually a female) begins secreting the neurotoxin that causes the paralysis. Symptoms appear 4–7 days after attachment. The peak time for tick paralysis is tick mating season: April through June.

The clinical scenario typically begins with loss of appetite and voice, followed by gait instability, ascending flaccid paralysis, excessive salivation, eye irritation, pupillary asymmetry, and vomiting. Death is usually from respiratory failure.

For more than half a century, there have been postmortem reports of ticks being found embedded in the skin of people who died suddenly of unexplained paralytic illnesses.

About 8% of the 870 named tick species have been associated with intoxication syndromes. The species that cause the most cases of human, dog, and livestock paralysis in North America are Dermacentor andersoni and D. variabilis, both of which are vectors for the rickettsial disease Rocky Mountain spotted fever. In the United States, tick paralysis occurs most often in the Pacific Northwest and Rocky Mountain states.

The tick toxin's pathogenic mechanism isn't fully understood. Australian investigators have reported that the toxin inhibits acetylcholine release at the neuromuscular synapse, but tick paralysis there is caused by Ixodes species, and it's not clear that the same mechanism is at work in the paralysis caused by Dermacentor species, Dr. O'Leary said.

Dr. O'Leary declared having no relevant financial relationships.

The peak time for tick paralysis is tick mating season: April through June.

Source DR. O'LEARY

Do's and Don'ts of Proper Tick Removal

The proper way to remove a tick is to grab it with blunt forceps as close to the skin as possible and pull it straight out with steady pressure, according to Dr. O'Leary.

Don't apply a hot nail or blown-out match to the critter's backside. Don't use tweezers or sharp forceps. Avoid using a twisting or corkscrew motion in removing the tick. Don't crush or squeeze the tick's body, as that can cause the tick to release more of the infectious organism or toxin.

Don't handle the tick barehanded. “There have been documented cases of disease transmission” in people who did that, said Dr. O'Leary.

And although in bygone days it was a popular practice to apply gasoline, lidocaine, petroleum jelly, or other substances to the embedded tick to encourage it to back out, the current thinking is, don't do it.

“There are horror stories about the use of those things,” he said.

VAIL, COLO. — Tick paralysis is often misdiagnosed — with potentially dire consequences — as one of the other diseases that cause an acute ascending paralysis with preserved mental status.

The arthropod-inflicted paralysis is most often confused with Guillain-Barré syndrome. Other causes of an acute ascending paralysis with preserved mental status include spinal cord tumors and acute poliomyelitis.

Botulism, in contrast, causes a descending paralysis with preserved mental status, Dr. Sean O'Leary said at the conference which was sponsored by the Children's Hospital, Denver.

Conducting a thorough search for an embedded tick is essential in a patient with an acute ascending paralysis with preserved sensorium, particularly when there is a history consistent with potential tick exposure. Treatment of tick paralysis is simple: remove the tick. Clinical improvement will follow within hours.

In unrecognized and untreated cases of tick paralysis, however, the fatality rate is about 10%, with death typically occurring just 18–30 hours after symptom onset, according to Dr. O'Leary of the Children's Hospital and the University of Colorado, both in Denver.

Tick paralysis is more common in children than adults. The highest-risk group is young girls with long hair that can readily hide an engorged tick that's had a blood meal.

At 3 days after attachment, the tick (usually a female) begins secreting the neurotoxin that causes the paralysis. Symptoms appear 4–7 days after attachment. The peak time for tick paralysis is tick mating season: April through June.

The clinical scenario typically begins with loss of appetite and voice, followed by gait instability, ascending flaccid paralysis, excessive salivation, eye irritation, pupillary asymmetry, and vomiting. Death is usually from respiratory failure.

For more than half a century, there have been postmortem reports of ticks being found embedded in the skin of people who died suddenly of unexplained paralytic illnesses.

About 8% of the 870 named tick species have been associated with intoxication syndromes. The species that cause the most cases of human, dog, and livestock paralysis in North America are Dermacentor andersoni and D. variabilis, both of which are vectors for the rickettsial disease Rocky Mountain spotted fever. In the United States, tick paralysis occurs most often in the Pacific Northwest and Rocky Mountain states.

The tick toxin's pathogenic mechanism isn't fully understood. Australian investigators have reported that the toxin inhibits acetylcholine release at the neuromuscular synapse, but tick paralysis there is caused by Ixodes species, and it's not clear that the same mechanism is at work in the paralysis caused by Dermacentor species, Dr. O'Leary said.

Dr. O'Leary declared having no relevant financial relationships.

The peak time for tick paralysis is tick mating season: April through June.

Source DR. O'LEARY

Do's and Don'ts of Proper Tick Removal

The proper way to remove a tick is to grab it with blunt forceps as close to the skin as possible and pull it straight out with steady pressure, according to Dr. O'Leary.

Don't apply a hot nail or blown-out match to the critter's backside. Don't use tweezers or sharp forceps. Avoid using a twisting or corkscrew motion in removing the tick. Don't crush or squeeze the tick's body, as that can cause the tick to release more of the infectious organism or toxin.

Don't handle the tick barehanded. “There have been documented cases of disease transmission” in people who did that, said Dr. O'Leary.

And although in bygone days it was a popular practice to apply gasoline, lidocaine, petroleum jelly, or other substances to the embedded tick to encourage it to back out, the current thinking is, don't do it.

“There are horror stories about the use of those things,” he said.

VAIL, COLO. — Tick paralysis is often misdiagnosed — with potentially dire consequences — as one of the other diseases that cause an acute ascending paralysis with preserved mental status.

The arthropod-inflicted paralysis is most often confused with Guillain-Barré syndrome. Other causes of an acute ascending paralysis with preserved mental status include spinal cord tumors and acute poliomyelitis.

Botulism, in contrast, causes a descending paralysis with preserved mental status, Dr. Sean O'Leary said at the conference which was sponsored by the Children's Hospital, Denver.

Conducting a thorough search for an embedded tick is essential in a patient with an acute ascending paralysis with preserved sensorium, particularly when there is a history consistent with potential tick exposure. Treatment of tick paralysis is simple: remove the tick. Clinical improvement will follow within hours.

In unrecognized and untreated cases of tick paralysis, however, the fatality rate is about 10%, with death typically occurring just 18–30 hours after symptom onset, according to Dr. O'Leary of the Children's Hospital and the University of Colorado, both in Denver.

Tick paralysis is more common in children than adults. The highest-risk group is young girls with long hair that can readily hide an engorged tick that's had a blood meal.

At 3 days after attachment, the tick (usually a female) begins secreting the neurotoxin that causes the paralysis. Symptoms appear 4–7 days after attachment. The peak time for tick paralysis is tick mating season: April through June.

The clinical scenario typically begins with loss of appetite and voice, followed by gait instability, ascending flaccid paralysis, excessive salivation, eye irritation, pupillary asymmetry, and vomiting. Death is usually from respiratory failure.

For more than half a century, there have been postmortem reports of ticks being found embedded in the skin of people who died suddenly of unexplained paralytic illnesses.

About 8% of the 870 named tick species have been associated with intoxication syndromes. The species that cause the most cases of human, dog, and livestock paralysis in North America are Dermacentor andersoni and D. variabilis, both of which are vectors for the rickettsial disease Rocky Mountain spotted fever. In the United States, tick paralysis occurs most often in the Pacific Northwest and Rocky Mountain states.

The tick toxin's pathogenic mechanism isn't fully understood. Australian investigators have reported that the toxin inhibits acetylcholine release at the neuromuscular synapse, but tick paralysis there is caused by Ixodes species, and it's not clear that the same mechanism is at work in the paralysis caused by Dermacentor species, Dr. O'Leary said.

Dr. O'Leary declared having no relevant financial relationships.

The peak time for tick paralysis is tick mating season: April through June.

Source DR. O'LEARY

Do's and Don'ts of Proper Tick Removal

The proper way to remove a tick is to grab it with blunt forceps as close to the skin as possible and pull it straight out with steady pressure, according to Dr. O'Leary.

Don't apply a hot nail or blown-out match to the critter's backside. Don't use tweezers or sharp forceps. Avoid using a twisting or corkscrew motion in removing the tick. Don't crush or squeeze the tick's body, as that can cause the tick to release more of the infectious organism or toxin.

Don't handle the tick barehanded. “There have been documented cases of disease transmission” in people who did that, said Dr. O'Leary.

And although in bygone days it was a popular practice to apply gasoline, lidocaine, petroleum jelly, or other substances to the embedded tick to encourage it to back out, the current thinking is, don't do it.

“There are horror stories about the use of those things,” he said.

VAIL, COLO. — A patient arrives at the clinic with a recognized tick bite. To use prophylaxis for Lyme disease or not?

“This is actually a fairly common call to our infectious diseases division in the summertime: 'I had a child come into the office. We've got the tick. What do we do?'” Dr. Sean O'Leary said at the annual conference on pediatric infectious diseases sponsored by the Children's Hospital, Denver.

The answer he and his pediatric infectious disease colleagues at the hospital almost always provide is a strong “no” to antimicrobial prophylaxis. That's consistent with detailed Infectious Diseases Society of America guidelines on the topic, Dr. O'Leary noted.

The risk/benefit numbers argue against prophylaxis under most circumstances, he continued. Assuming a 1.4% attack rate of Lyme disease following a tick bite in an endemic area, the number needed to treat in order to prevent 1 infection is 83 patients — a hefty NNT. With the use of amoxicillin for prophylaxis, for every 10 cases of early Lyme disease prevented, it's to be expected that 1 patient would develop a severe, life-threatening drug reaction and 10 would experience a drug-induced rash. And, in a study involving prophylaxis with doxycycline, 30% of patients had adverse events.

The Infectious Disease Society of America guidelines specify the limited circumstances in which prophylaxis is “moderately” favored. The tick must be reliably identified as an adult or nymphal Ixodes scapularis, commonly known as the deer tick, that's been attached to the skin for more than 36 hours based upon the extent of engorgement with blood.

The local rate of infection of this tick species with Borrelia burgdorferi has to exceed 20%, as is generally true in areas of New England, the Mid-Atlantic states, and the upper Midwest. And prophylaxis can be started less than 72 hours after removal of the tick.

When all those conditions are met, the IDSA guidelines state that it's reasonable to offer a single dose of doxycycline in patients without a contraindication to the drug. The dose for Lyme prevention is 200 mg in adults and 4 mg/kg up to a maximum of 200 mg in children above 8 years of age.

As for prophylaxis against other tick-borne pathogens, Dr. O'Leary said that fewer than 1 in 1,000 Dermacentor ticks carry Rickettsia rickettsii, the cause of Rocky Mountain spotted fever. And while there are very few studies on other tick-borne diseases, the risk is considered “very, very low,” he noted.

“In general, the risk of prophylaxis far outweighs any potential benefit,” Dr. O'Leary stressed.

Dr. O'Leary disclosed having no relevant financial conflicts.

Vitals

Source Elsevier Global Medical News

The IDSA guidelines specify the limited circumstances in which prophylaxis is 'moderately' favored.

Source Courtesy Scott Bauer/USDA

VAIL, COLO. — A patient arrives at the clinic with a recognized tick bite. To use prophylaxis for Lyme disease or not?

“This is actually a fairly common call to our infectious diseases division in the summertime: 'I had a child come into the office. We've got the tick. What do we do?'” Dr. Sean O'Leary said at the annual conference on pediatric infectious diseases sponsored by the Children's Hospital, Denver.

The answer he and his pediatric infectious disease colleagues at the hospital almost always provide is a strong “no” to antimicrobial prophylaxis. That's consistent with detailed Infectious Diseases Society of America guidelines on the topic, Dr. O'Leary noted.

The risk/benefit numbers argue against prophylaxis under most circumstances, he continued. Assuming a 1.4% attack rate of Lyme disease following a tick bite in an endemic area, the number needed to treat in order to prevent 1 infection is 83 patients — a hefty NNT. With the use of amoxicillin for prophylaxis, for every 10 cases of early Lyme disease prevented, it's to be expected that 1 patient would develop a severe, life-threatening drug reaction and 10 would experience a drug-induced rash. And, in a study involving prophylaxis with doxycycline, 30% of patients had adverse events.

The Infectious Disease Society of America guidelines specify the limited circumstances in which prophylaxis is “moderately” favored. The tick must be reliably identified as an adult or nymphal Ixodes scapularis, commonly known as the deer tick, that's been attached to the skin for more than 36 hours based upon the extent of engorgement with blood.

The local rate of infection of this tick species with Borrelia burgdorferi has to exceed 20%, as is generally true in areas of New England, the Mid-Atlantic states, and the upper Midwest. And prophylaxis can be started less than 72 hours after removal of the tick.

When all those conditions are met, the IDSA guidelines state that it's reasonable to offer a single dose of doxycycline in patients without a contraindication to the drug. The dose for Lyme prevention is 200 mg in adults and 4 mg/kg up to a maximum of 200 mg in children above 8 years of age.

As for prophylaxis against other tick-borne pathogens, Dr. O'Leary said that fewer than 1 in 1,000 Dermacentor ticks carry Rickettsia rickettsii, the cause of Rocky Mountain spotted fever. And while there are very few studies on other tick-borne diseases, the risk is considered “very, very low,” he noted.

“In general, the risk of prophylaxis far outweighs any potential benefit,” Dr. O'Leary stressed.

Dr. O'Leary disclosed having no relevant financial conflicts.

Vitals

Source Elsevier Global Medical News

The IDSA guidelines specify the limited circumstances in which prophylaxis is 'moderately' favored.

Source Courtesy Scott Bauer/USDA

VAIL, COLO. — A patient arrives at the clinic with a recognized tick bite. To use prophylaxis for Lyme disease or not?

“This is actually a fairly common call to our infectious diseases division in the summertime: 'I had a child come into the office. We've got the tick. What do we do?'” Dr. Sean O'Leary said at the annual conference on pediatric infectious diseases sponsored by the Children's Hospital, Denver.

The answer he and his pediatric infectious disease colleagues at the hospital almost always provide is a strong “no” to antimicrobial prophylaxis. That's consistent with detailed Infectious Diseases Society of America guidelines on the topic, Dr. O'Leary noted.

The risk/benefit numbers argue against prophylaxis under most circumstances, he continued. Assuming a 1.4% attack rate of Lyme disease following a tick bite in an endemic area, the number needed to treat in order to prevent 1 infection is 83 patients — a hefty NNT. With the use of amoxicillin for prophylaxis, for every 10 cases of early Lyme disease prevented, it's to be expected that 1 patient would develop a severe, life-threatening drug reaction and 10 would experience a drug-induced rash. And, in a study involving prophylaxis with doxycycline, 30% of patients had adverse events.

The Infectious Disease Society of America guidelines specify the limited circumstances in which prophylaxis is “moderately” favored. The tick must be reliably identified as an adult or nymphal Ixodes scapularis, commonly known as the deer tick, that's been attached to the skin for more than 36 hours based upon the extent of engorgement with blood.

The local rate of infection of this tick species with Borrelia burgdorferi has to exceed 20%, as is generally true in areas of New England, the Mid-Atlantic states, and the upper Midwest. And prophylaxis can be started less than 72 hours after removal of the tick.

When all those conditions are met, the IDSA guidelines state that it's reasonable to offer a single dose of doxycycline in patients without a contraindication to the drug. The dose for Lyme prevention is 200 mg in adults and 4 mg/kg up to a maximum of 200 mg in children above 8 years of age.

As for prophylaxis against other tick-borne pathogens, Dr. O'Leary said that fewer than 1 in 1,000 Dermacentor ticks carry Rickettsia rickettsii, the cause of Rocky Mountain spotted fever. And while there are very few studies on other tick-borne diseases, the risk is considered “very, very low,” he noted.

“In general, the risk of prophylaxis far outweighs any potential benefit,” Dr. O'Leary stressed.

Dr. O'Leary disclosed having no relevant financial conflicts.

Vitals

Source Elsevier Global Medical News

The IDSA guidelines specify the limited circumstances in which prophylaxis is 'moderately' favored.

Source Courtesy Scott Bauer/USDA

KEYSTONE, COLO. — Pfizer Inc.'s Exubera earned marketing approval to enormous fanfare in 2006 as the first inhaled insulin. Expectations were high for what was expected to be a blockbuster product. Yet Exubera was pulled from the market the next year, brought down not by safety issues, but because it was a spectacular commercial failure.

The Exubera flameout has not dissuaded other pharmaceutical companies from pursuing development of intranasal, buccal, oral, peritoneal, and even rectal insulins, according to Dr. Jay S. Skyler. He presented an update on many of these novel insulins and new delivery systems at the conference, which was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver:

▸ Inhaled insulin. Afrezza, MannKind Corp.'s investigational inhaled insulin with fumaryl diketopiperazine, reaches peak plasma insulin concentrations in just 10 minutes, far faster than currently available rapid-acting insulins. And the Afrezza inhaler is no bigger than a thumb, in contrast to the bulky and awkward Exubera inhaler.

“Everybody criticizes Afrezza. They say, 'Exubera failed.' Well, it probably failed in the marketplace because of its delivery system and lack of pharmacokinetic advantages compared to existing insulins, whereas with Afrezza you get both the pharmacokinetic advantage and convenience of delivery,” said Dr. Skyler, professor of medicine, pediatrics, and psychology and former director of the division of endocrinology, diabetes, and metabolism at the University of Miami.

Afrezza is now under review by the Food and Drug Administration for possible marketing approval.

▸ Intraperitoneal insulin delivery. In the mid-1990s, Dr. Skyler and coworkers demonstrated that when insulin was delivered intraperitoneally, 51% of it was rapidly absorbed into the portal circulation and went straight to the liver.

The redesigned DiaPort percutaneously implanted peritoneal port system, under development by Roche, can be connected to an external insulin pump, according to two unpublished studies: In a recent 6-month study, patients who were randomized to standard insulin pump therapy with continuous subcutaneous insulin infusion gained an average of 1.5 kg, whereas those assigned to the DiaPort system experienced no change in body weight. And in another trial, episodes of recurrent severe hypoglycemia in patients using the DiaPort system were reduced sevenfold, compared with baseline, even though their hemoglobin A_1c fell by nearly 2%.

“I think the peritoneal approach is one we need to seriously think about as we move into automated systems,” the endocrinologist said.

▸ Oral insulins. These agents' Achilles heel has been poor bioavailability, typically less than 1%. Proposed solutions include using liposomal coatings, absorption promoters, or protease inhibitors, and packaging the oral insulin in hydrogels or microspheres to stabilize it against degradation.

Oral insulins in the developmental pipeline that appear to achieve rapid peak plasma insulin concentrations include Emisphere Technologies' oral insulin (Diabetes Care 2010;33:1288–90) and Biocon's IN-105 oral insulin polymer (J. Diabetes Sci. Technol. 2009;3:568–84).

In contrast, Capsulin, under development by Diabetology Ltd., a U.K. company, has a far less impressive early plasma effect (Diabetes Obes. Metab. 2010;12:82–7).

“This one doesn't look like it's going anywhere as a rapid-acting insulin, but it might actually work as a basal insulin, given orally,” Dr. Skyler said.

Another product with a delayed effect is the oral insulin capsule being developed by Oramed Pharmaceuticals, an Israeli company. This product, known as ORMD 0801, is designed for intestinal absorption. Phase II studies have been completed in patients with type 2 diabetes.

▸ Novel basal insulins. Novo Nordisk A/S's ultralong-acting insulin degludec has a half-life in excess of 24 hours and can be detected in the circulation at least 96 hours post injection. It can be given once daily or three times per week, although Dr. Skyler suspects that many patients would have difficulty sticking to the latter schedule.

Insulin degludec achieves protracted absorption in subcutaneous tissue by utilizing a soluble multihexamer formation rather than the standard single hexamer formation. Insulin degludec will be studied in the pivotal phase III BEGIN and BOOST trials, which together will involve more than 10,000 patients and will be the largest-ever clinical trial program for insulin therapy in diabetes.

Eli Lilly & Co.'s insulin lispro protamine suspension has been studied with favorable results as part of a basal-bolus approach in patients with type 1 diabetes (Diabet. Med. 2010;27:563–9), as well as in insulin-naive patients with type 2 diabetes that is poorly controlled with oral agents (Diabet. Med. 2010;27:181–8). This insulin is already marketed in some parts of the world.

A French company, Flamel Technologies Inc., is developing FT-105, a basal insulin consisting of a vitamin E and glutamic acid polyaminoacid polymer linked to the insulin protein. When administered by subcutaneous injection, FT-105 aggregates into dense microparticles that take a long time to dissolve.

Altea Therapeutics Corp.'s PassPort is a transdermal insulin delivery system. The patient applies a proprietary patch on the skin, presses an attached button to create micropores, then slaps an insulin-containing patch over the site. Studies indicate that the system provides protracted availability of basal insulin with resultant plasma insulin levels that are proportionate to the various insulin concentrations available in the patch reservoir.

Valeritas Inc.'s insulin device V-Go consists of a small, patchlike insulin pump that contains no electronic components. The disposable skin patch lasts 24 hours, during which it provides basal insulin at a steady rate. The patient can push a small button to release a few extra units of insulin at a time, as a premeal bolus. In addition, Sanofi-Aventis has a very long-acting insulin analogue in phase I studies, and Eli Lilly has a new basal insulin in phase I as well.

▸ New rapid-acting prandial insulins. Development of such products would help to control the daunting problem of postprandial hyperglycemia. One possible solution is Becton, Dickinson & Co.'s device for intradermal injection of insulin lispro, which capitalizes on the fact that insulin is consistently absorbed more rapidly intradermally than subcutaneously. The Becton, Dickinson device consists of a skin patch containing an array of tiny intradermal needles, each of which is no longer than the E in the “E Pluribus Unum” on the back of a penny.

Yet another intradermal insulin product in development is Debiotech SA's Jewel micropump, which is mounted to a disposable skin patch. The system, which is considerably smaller than a fingertip, is now under FDA review.

▸ Ultrarapid-acting insulins. Afrezza is one. The DiaPort system for intraperitoneal delivery is another ultrarapid-acting solution. Yet another is Biodel Inc.'s VIAject, which comprises insulin with ethylenediaminetetraacetic acid and citric acid that forms rapidly absorbed monomers upon subcutaneous injection. In a 16-patient crossover study, peak insulin concentrations were achieved in 34 minutes with VIAject, compared with 63 minutes for insulin lispro and 139 minutes for regular human insulin.

Whether that's quick enough to make for a commercial success remains to be seen, Dr. Skyler said. VIAject is now in phase III testing.

Halozyme Therapeutics' insulin-PH20 technology combines currently available mealtime insulins with recombinant human PH20 hyaluronidase, which results in greatly accelerated insulin action.

▸ Buccal insulin. “The buccal route has been argued about for many, many years,” Dr. Skyler observed. One device for buccal administration that has drawn research and commercial attention recently (Diabetes Obes. Metab. 2010;12:91–6) is Generex Biotechnology Corp.'s Oral-lyn insulin spray, an aerosolized aqueous solution of regular human insulin. The device delivers 10 units per puff to the oral cavity at a velocity of 100 mph. Oral-lyn is marketed only in Ecuador, which Dr. Skyler considers a less-than-ringing endorsement.

▸ “Smart” insulins. Insulin with a built-in glucose sensor was first proposed in the 1970s. The concept is to harness an insulin polymer conjugate to a multivalent glucose-binding molecule. Upon contact with blood glucose, the glucose displaces the insulin in the polymer, freeing the insulin to go into the circulation.

“I'd be quite thrilled to see this kind of insulin come to the market, but I'm a bit skeptical,” Dr. Skyler said.

Dr. Skyler disclosed that he has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

KEYSTONE, COLO. — Pfizer Inc.'s Exubera earned marketing approval to enormous fanfare in 2006 as the first inhaled insulin. Expectations were high for what was expected to be a blockbuster product. Yet Exubera was pulled from the market the next year, brought down not by safety issues, but because it was a spectacular commercial failure.

The Exubera flameout has not dissuaded other pharmaceutical companies from pursuing development of intranasal, buccal, oral, peritoneal, and even rectal insulins, according to Dr. Jay S. Skyler. He presented an update on many of these novel insulins and new delivery systems at the conference, which was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver:

▸ Inhaled insulin. Afrezza, MannKind Corp.'s investigational inhaled insulin with fumaryl diketopiperazine, reaches peak plasma insulin concentrations in just 10 minutes, far faster than currently available rapid-acting insulins. And the Afrezza inhaler is no bigger than a thumb, in contrast to the bulky and awkward Exubera inhaler.

“Everybody criticizes Afrezza. They say, 'Exubera failed.' Well, it probably failed in the marketplace because of its delivery system and lack of pharmacokinetic advantages compared to existing insulins, whereas with Afrezza you get both the pharmacokinetic advantage and convenience of delivery,” said Dr. Skyler, professor of medicine, pediatrics, and psychology and former director of the division of endocrinology, diabetes, and metabolism at the University of Miami.

Afrezza is now under review by the Food and Drug Administration for possible marketing approval.

▸ Intraperitoneal insulin delivery. In the mid-1990s, Dr. Skyler and coworkers demonstrated that when insulin was delivered intraperitoneally, 51% of it was rapidly absorbed into the portal circulation and went straight to the liver.

The redesigned DiaPort percutaneously implanted peritoneal port system, under development by Roche, can be connected to an external insulin pump, according to two unpublished studies: In a recent 6-month study, patients who were randomized to standard insulin pump therapy with continuous subcutaneous insulin infusion gained an average of 1.5 kg, whereas those assigned to the DiaPort system experienced no change in body weight. And in another trial, episodes of recurrent severe hypoglycemia in patients using the DiaPort system were reduced sevenfold, compared with baseline, even though their hemoglobin A_1c fell by nearly 2%.

“I think the peritoneal approach is one we need to seriously think about as we move into automated systems,” the endocrinologist said.

▸ Oral insulins. These agents' Achilles heel has been poor bioavailability, typically less than 1%. Proposed solutions include using liposomal coatings, absorption promoters, or protease inhibitors, and packaging the oral insulin in hydrogels or microspheres to stabilize it against degradation.

Oral insulins in the developmental pipeline that appear to achieve rapid peak plasma insulin concentrations include Emisphere Technologies' oral insulin (Diabetes Care 2010;33:1288–90) and Biocon's IN-105 oral insulin polymer (J. Diabetes Sci. Technol. 2009;3:568–84).

In contrast, Capsulin, under development by Diabetology Ltd., a U.K. company, has a far less impressive early plasma effect (Diabetes Obes. Metab. 2010;12:82–7).

“This one doesn't look like it's going anywhere as a rapid-acting insulin, but it might actually work as a basal insulin, given orally,” Dr. Skyler said.

Another product with a delayed effect is the oral insulin capsule being developed by Oramed Pharmaceuticals, an Israeli company. This product, known as ORMD 0801, is designed for intestinal absorption. Phase II studies have been completed in patients with type 2 diabetes.

▸ Novel basal insulins. Novo Nordisk A/S's ultralong-acting insulin degludec has a half-life in excess of 24 hours and can be detected in the circulation at least 96 hours post injection. It can be given once daily or three times per week, although Dr. Skyler suspects that many patients would have difficulty sticking to the latter schedule.

Insulin degludec achieves protracted absorption in subcutaneous tissue by utilizing a soluble multihexamer formation rather than the standard single hexamer formation. Insulin degludec will be studied in the pivotal phase III BEGIN and BOOST trials, which together will involve more than 10,000 patients and will be the largest-ever clinical trial program for insulin therapy in diabetes.

Eli Lilly & Co.'s insulin lispro protamine suspension has been studied with favorable results as part of a basal-bolus approach in patients with type 1 diabetes (Diabet. Med. 2010;27:563–9), as well as in insulin-naive patients with type 2 diabetes that is poorly controlled with oral agents (Diabet. Med. 2010;27:181–8). This insulin is already marketed in some parts of the world.

A French company, Flamel Technologies Inc., is developing FT-105, a basal insulin consisting of a vitamin E and glutamic acid polyaminoacid polymer linked to the insulin protein. When administered by subcutaneous injection, FT-105 aggregates into dense microparticles that take a long time to dissolve.

Altea Therapeutics Corp.'s PassPort is a transdermal insulin delivery system. The patient applies a proprietary patch on the skin, presses an attached button to create micropores, then slaps an insulin-containing patch over the site. Studies indicate that the system provides protracted availability of basal insulin with resultant plasma insulin levels that are proportionate to the various insulin concentrations available in the patch reservoir.

Valeritas Inc.'s insulin device V-Go consists of a small, patchlike insulin pump that contains no electronic components. The disposable skin patch lasts 24 hours, during which it provides basal insulin at a steady rate. The patient can push a small button to release a few extra units of insulin at a time, as a premeal bolus. In addition, Sanofi-Aventis has a very long-acting insulin analogue in phase I studies, and Eli Lilly has a new basal insulin in phase I as well.

▸ New rapid-acting prandial insulins. Development of such products would help to control the daunting problem of postprandial hyperglycemia. One possible solution is Becton, Dickinson & Co.'s device for intradermal injection of insulin lispro, which capitalizes on the fact that insulin is consistently absorbed more rapidly intradermally than subcutaneously. The Becton, Dickinson device consists of a skin patch containing an array of tiny intradermal needles, each of which is no longer than the E in the “E Pluribus Unum” on the back of a penny.

Yet another intradermal insulin product in development is Debiotech SA's Jewel micropump, which is mounted to a disposable skin patch. The system, which is considerably smaller than a fingertip, is now under FDA review.

▸ Ultrarapid-acting insulins. Afrezza is one. The DiaPort system for intraperitoneal delivery is another ultrarapid-acting solution. Yet another is Biodel Inc.'s VIAject, which comprises insulin with ethylenediaminetetraacetic acid and citric acid that forms rapidly absorbed monomers upon subcutaneous injection. In a 16-patient crossover study, peak insulin concentrations were achieved in 34 minutes with VIAject, compared with 63 minutes for insulin lispro and 139 minutes for regular human insulin.

Whether that's quick enough to make for a commercial success remains to be seen, Dr. Skyler said. VIAject is now in phase III testing.

Halozyme Therapeutics' insulin-PH20 technology combines currently available mealtime insulins with recombinant human PH20 hyaluronidase, which results in greatly accelerated insulin action.

▸ Buccal insulin. “The buccal route has been argued about for many, many years,” Dr. Skyler observed. One device for buccal administration that has drawn research and commercial attention recently (Diabetes Obes. Metab. 2010;12:91–6) is Generex Biotechnology Corp.'s Oral-lyn insulin spray, an aerosolized aqueous solution of regular human insulin. The device delivers 10 units per puff to the oral cavity at a velocity of 100 mph. Oral-lyn is marketed only in Ecuador, which Dr. Skyler considers a less-than-ringing endorsement.

▸ “Smart” insulins. Insulin with a built-in glucose sensor was first proposed in the 1970s. The concept is to harness an insulin polymer conjugate to a multivalent glucose-binding molecule. Upon contact with blood glucose, the glucose displaces the insulin in the polymer, freeing the insulin to go into the circulation.

“I'd be quite thrilled to see this kind of insulin come to the market, but I'm a bit skeptical,” Dr. Skyler said.

Dr. Skyler disclosed that he has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

KEYSTONE, COLO. — Pfizer Inc.'s Exubera earned marketing approval to enormous fanfare in 2006 as the first inhaled insulin. Expectations were high for what was expected to be a blockbuster product. Yet Exubera was pulled from the market the next year, brought down not by safety issues, but because it was a spectacular commercial failure.

The Exubera flameout has not dissuaded other pharmaceutical companies from pursuing development of intranasal, buccal, oral, peritoneal, and even rectal insulins, according to Dr. Jay S. Skyler. He presented an update on many of these novel insulins and new delivery systems at the conference, which was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver:

▸ Inhaled insulin. Afrezza, MannKind Corp.'s investigational inhaled insulin with fumaryl diketopiperazine, reaches peak plasma insulin concentrations in just 10 minutes, far faster than currently available rapid-acting insulins. And the Afrezza inhaler is no bigger than a thumb, in contrast to the bulky and awkward Exubera inhaler.

“Everybody criticizes Afrezza. They say, 'Exubera failed.' Well, it probably failed in the marketplace because of its delivery system and lack of pharmacokinetic advantages compared to existing insulins, whereas with Afrezza you get both the pharmacokinetic advantage and convenience of delivery,” said Dr. Skyler, professor of medicine, pediatrics, and psychology and former director of the division of endocrinology, diabetes, and metabolism at the University of Miami.

Afrezza is now under review by the Food and Drug Administration for possible marketing approval.

▸ Intraperitoneal insulin delivery. In the mid-1990s, Dr. Skyler and coworkers demonstrated that when insulin was delivered intraperitoneally, 51% of it was rapidly absorbed into the portal circulation and went straight to the liver.

The redesigned DiaPort percutaneously implanted peritoneal port system, under development by Roche, can be connected to an external insulin pump, according to two unpublished studies: In a recent 6-month study, patients who were randomized to standard insulin pump therapy with continuous subcutaneous insulin infusion gained an average of 1.5 kg, whereas those assigned to the DiaPort system experienced no change in body weight. And in another trial, episodes of recurrent severe hypoglycemia in patients using the DiaPort system were reduced sevenfold, compared with baseline, even though their hemoglobin A_1c fell by nearly 2%.

“I think the peritoneal approach is one we need to seriously think about as we move into automated systems,” the endocrinologist said.

▸ Oral insulins. These agents' Achilles heel has been poor bioavailability, typically less than 1%. Proposed solutions include using liposomal coatings, absorption promoters, or protease inhibitors, and packaging the oral insulin in hydrogels or microspheres to stabilize it against degradation.

Oral insulins in the developmental pipeline that appear to achieve rapid peak plasma insulin concentrations include Emisphere Technologies' oral insulin (Diabetes Care 2010;33:1288–90) and Biocon's IN-105 oral insulin polymer (J. Diabetes Sci. Technol. 2009;3:568–84).

In contrast, Capsulin, under development by Diabetology Ltd., a U.K. company, has a far less impressive early plasma effect (Diabetes Obes. Metab. 2010;12:82–7).

“This one doesn't look like it's going anywhere as a rapid-acting insulin, but it might actually work as a basal insulin, given orally,” Dr. Skyler said.

Another product with a delayed effect is the oral insulin capsule being developed by Oramed Pharmaceuticals, an Israeli company. This product, known as ORMD 0801, is designed for intestinal absorption. Phase II studies have been completed in patients with type 2 diabetes.

▸ Novel basal insulins. Novo Nordisk A/S's ultralong-acting insulin degludec has a half-life in excess of 24 hours and can be detected in the circulation at least 96 hours post injection. It can be given once daily or three times per week, although Dr. Skyler suspects that many patients would have difficulty sticking to the latter schedule.

Insulin degludec achieves protracted absorption in subcutaneous tissue by utilizing a soluble multihexamer formation rather than the standard single hexamer formation. Insulin degludec will be studied in the pivotal phase III BEGIN and BOOST trials, which together will involve more than 10,000 patients and will be the largest-ever clinical trial program for insulin therapy in diabetes.

Eli Lilly & Co.'s insulin lispro protamine suspension has been studied with favorable results as part of a basal-bolus approach in patients with type 1 diabetes (Diabet. Med. 2010;27:563–9), as well as in insulin-naive patients with type 2 diabetes that is poorly controlled with oral agents (Diabet. Med. 2010;27:181–8). This insulin is already marketed in some parts of the world.

A French company, Flamel Technologies Inc., is developing FT-105, a basal insulin consisting of a vitamin E and glutamic acid polyaminoacid polymer linked to the insulin protein. When administered by subcutaneous injection, FT-105 aggregates into dense microparticles that take a long time to dissolve.

Altea Therapeutics Corp.'s PassPort is a transdermal insulin delivery system. The patient applies a proprietary patch on the skin, presses an attached button to create micropores, then slaps an insulin-containing patch over the site. Studies indicate that the system provides protracted availability of basal insulin with resultant plasma insulin levels that are proportionate to the various insulin concentrations available in the patch reservoir.

Valeritas Inc.'s insulin device V-Go consists of a small, patchlike insulin pump that contains no electronic components. The disposable skin patch lasts 24 hours, during which it provides basal insulin at a steady rate. The patient can push a small button to release a few extra units of insulin at a time, as a premeal bolus. In addition, Sanofi-Aventis has a very long-acting insulin analogue in phase I studies, and Eli Lilly has a new basal insulin in phase I as well.

▸ New rapid-acting prandial insulins. Development of such products would help to control the daunting problem of postprandial hyperglycemia. One possible solution is Becton, Dickinson & Co.'s device for intradermal injection of insulin lispro, which capitalizes on the fact that insulin is consistently absorbed more rapidly intradermally than subcutaneously. The Becton, Dickinson device consists of a skin patch containing an array of tiny intradermal needles, each of which is no longer than the E in the “E Pluribus Unum” on the back of a penny.

Yet another intradermal insulin product in development is Debiotech SA's Jewel micropump, which is mounted to a disposable skin patch. The system, which is considerably smaller than a fingertip, is now under FDA review.

▸ Ultrarapid-acting insulins. Afrezza is one. The DiaPort system for intraperitoneal delivery is another ultrarapid-acting solution. Yet another is Biodel Inc.'s VIAject, which comprises insulin with ethylenediaminetetraacetic acid and citric acid that forms rapidly absorbed monomers upon subcutaneous injection. In a 16-patient crossover study, peak insulin concentrations were achieved in 34 minutes with VIAject, compared with 63 minutes for insulin lispro and 139 minutes for regular human insulin.

Whether that's quick enough to make for a commercial success remains to be seen, Dr. Skyler said. VIAject is now in phase III testing.

Halozyme Therapeutics' insulin-PH20 technology combines currently available mealtime insulins with recombinant human PH20 hyaluronidase, which results in greatly accelerated insulin action.

▸ Buccal insulin. “The buccal route has been argued about for many, many years,” Dr. Skyler observed. One device for buccal administration that has drawn research and commercial attention recently (Diabetes Obes. Metab. 2010;12:91–6) is Generex Biotechnology Corp.'s Oral-lyn insulin spray, an aerosolized aqueous solution of regular human insulin. The device delivers 10 units per puff to the oral cavity at a velocity of 100 mph. Oral-lyn is marketed only in Ecuador, which Dr. Skyler considers a less-than-ringing endorsement.

▸ “Smart” insulins. Insulin with a built-in glucose sensor was first proposed in the 1970s. The concept is to harness an insulin polymer conjugate to a multivalent glucose-binding molecule. Upon contact with blood glucose, the glucose displaces the insulin in the polymer, freeing the insulin to go into the circulation.

“I'd be quite thrilled to see this kind of insulin come to the market, but I'm a bit skeptical,” Dr. Skyler said.

Dr. Skyler disclosed that he has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

SAN ANTONIO – Many children with attention-deficit/hyperactivity disorder or oppositional defiant disorder no longer meet diagnostic criteria for these psychopathologies 6 months after they undergo adenotonsillectomy for standard indications, a large prospective patient series suggests.

The most striking finding in this study of 140 children aged 3-12 years who underwent adenotonsillectomy involved the 81% reduction in the prevalence of oppositional defiant disorder (ODD) at 6 months post surgery, Dr. James E. Dillon reported.

Baseline rates of ADHD and ODD were high, in accord with earlier studies of children scheduled for adenotonsillectomy: In all, 54 children (39%) met DSM-IV criteria for some form of ADHD, whereas 26 (19%) met criteria for ODD.

At 6 months after adenotonsillectomy, however, only 32 patients (23%) still met criteria for some form of ADHD. The rest no longer did. Particularly impressive was the reduction in ADHD of the combined type: Overall, 30 kids (21%) met the diagnostic criteria for this disorder at baseline, compared with 18 (13%) at follow-up, said Dr. Dillon, a child and adolescent psychiatrist at the University of Michigan, Ann Arbor.

Meanwhile, the prevalence of ODD dropped from 26 children at baseline to just 5 (3.6%) at 6 months post surgery, he said.

Participants were recruited from various otolaryngology practices in Michigan. Before being approached for the study, all of the children were already scheduled for adenotonsillectomy. The subjects' mean age was 7.2 years, 55% were boys, and 78% of the children were white.

The participants included 35 preschoolers. Nineteen preschoolers (54%) had a behavior disorder at baseline, compared with 12 (34%) at follow-up. In all, 9 preschoolers met criteria for ODD at enrollment, compared with just 2 at follow-up, and 19 had any form of ADHD at entry, as did 12 at follow-up.

Disclosures: Dr. Dillon reported no financial conflicts with regard to the study.

SAN ANTONIO – Many children with attention-deficit/hyperactivity disorder or oppositional defiant disorder no longer meet diagnostic criteria for these psychopathologies 6 months after they undergo adenotonsillectomy for standard indications, a large prospective patient series suggests.

The most striking finding in this study of 140 children aged 3-12 years who underwent adenotonsillectomy involved the 81% reduction in the prevalence of oppositional defiant disorder (ODD) at 6 months post surgery, Dr. James E. Dillon reported.

Baseline rates of ADHD and ODD were high, in accord with earlier studies of children scheduled for adenotonsillectomy: In all, 54 children (39%) met DSM-IV criteria for some form of ADHD, whereas 26 (19%) met criteria for ODD.

At 6 months after adenotonsillectomy, however, only 32 patients (23%) still met criteria for some form of ADHD. The rest no longer did. Particularly impressive was the reduction in ADHD of the combined type: Overall, 30 kids (21%) met the diagnostic criteria for this disorder at baseline, compared with 18 (13%) at follow-up, said Dr. Dillon, a child and adolescent psychiatrist at the University of Michigan, Ann Arbor.

Meanwhile, the prevalence of ODD dropped from 26 children at baseline to just 5 (3.6%) at 6 months post surgery, he said.

Participants were recruited from various otolaryngology practices in Michigan. Before being approached for the study, all of the children were already scheduled for adenotonsillectomy. The subjects' mean age was 7.2 years, 55% were boys, and 78% of the children were white.

The participants included 35 preschoolers. Nineteen preschoolers (54%) had a behavior disorder at baseline, compared with 12 (34%) at follow-up. In all, 9 preschoolers met criteria for ODD at enrollment, compared with just 2 at follow-up, and 19 had any form of ADHD at entry, as did 12 at follow-up.

Disclosures: Dr. Dillon reported no financial conflicts with regard to the study.

SAN ANTONIO – Many children with attention-deficit/hyperactivity disorder or oppositional defiant disorder no longer meet diagnostic criteria for these psychopathologies 6 months after they undergo adenotonsillectomy for standard indications, a large prospective patient series suggests.

The most striking finding in this study of 140 children aged 3-12 years who underwent adenotonsillectomy involved the 81% reduction in the prevalence of oppositional defiant disorder (ODD) at 6 months post surgery, Dr. James E. Dillon reported.

Baseline rates of ADHD and ODD were high, in accord with earlier studies of children scheduled for adenotonsillectomy: In all, 54 children (39%) met DSM-IV criteria for some form of ADHD, whereas 26 (19%) met criteria for ODD.

At 6 months after adenotonsillectomy, however, only 32 patients (23%) still met criteria for some form of ADHD. The rest no longer did. Particularly impressive was the reduction in ADHD of the combined type: Overall, 30 kids (21%) met the diagnostic criteria for this disorder at baseline, compared with 18 (13%) at follow-up, said Dr. Dillon, a child and adolescent psychiatrist at the University of Michigan, Ann Arbor.

Meanwhile, the prevalence of ODD dropped from 26 children at baseline to just 5 (3.6%) at 6 months post surgery, he said.

Participants were recruited from various otolaryngology practices in Michigan. Before being approached for the study, all of the children were already scheduled for adenotonsillectomy. The subjects' mean age was 7.2 years, 55% were boys, and 78% of the children were white.

The participants included 35 preschoolers. Nineteen preschoolers (54%) had a behavior disorder at baseline, compared with 12 (34%) at follow-up. In all, 9 preschoolers met criteria for ODD at enrollment, compared with just 2 at follow-up, and 19 had any form of ADHD at entry, as did 12 at follow-up.

Disclosures: Dr. Dillon reported no financial conflicts with regard to the study.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.

STOCKHOLM – A cardiac rehabilitation program built around supervised high-intensity treadmill aerobic interval workouts improves peak oxygen uptake to a greater degree than does standard moderate-intensity cardiac rehab, according to a randomized trial.

Moreover, the advantage favoring aerobic interval training remained significant at follow-up 30 months after patients completed their formal 12-week cardiac rehab program, Dr. Trine T. Moholdt reported at the annual congress of the European Society of Cardiology.

This evidence of a long-term benefit stemming from a 12-week investment in a group exercise program is particularly encouraging.

“One of the biggest challenges in cardiac rehabilitation is how to make patients continue with a healthier lifestyle after ending the rehab program. There are no long-term effects of exercise training; that is, you have to keep on doing it to get the benefit from it,” observed Dr. Moholdt of the Norwegian University of Science and Technology, Trondheim.

The group assigned to the aerobic interval cardiac rehab program reported exercising more regularly and at considerably higher intensity than did the standard rehab group during the 30 months after their structured program ended. That’s the likely explanation for why their peak oxygen uptake (VO2max) at 30 months remained significantly higher than in the control group, although VO2max declined over time in both groups, she said.

Her study comprised 107 MI patients undergoing 12 weeks of cardiac rehab at three Norwegian hospitals. They were randomized to aerobic interval training or conventional cardiac rehab entailing two physical therapist-led group sessions per week, each lasting about 60 minutes and performed at 70%-80% of an individual’s maximum heart rate.

The aerobic interval regimen consisted of a 10-minute warm-up followed by about 40 minutes of uphill treadmill walking or jogging intervals. The workout consisted of four 4-minute-long high-intensity intervals at 85%-95% of a patient’s individually determined maximum heart rate, followed by a 3-minute recovery, then a final cool down. The high-intensity intervals were designed to be just challenging enough so that patients could say only a few words while doing them but would not experience pain in the chest or legs.

Subjects in both study arms were encouraged to do one additional workout per week at home.

Eighteen patients dropped out of the 12-week cardiac rehab program. Among completers, the aerobic interval group showed a mean improvement in VO2max from 31.6 mL/kg per minute at baseline to 36.2 at 12 weeks. This was a significantly greater gain than that seen in the moderate-intensity rehab group, which improved from 32.2 to 34.7 mL/kg per minute.

Follow-up assessments were conducted at 6 and 30 months after completion of the rehab program. VO2max declined over time in both groups. By 30 months VO2max in the aerobic interval training group was back to baseline; however, VO2max in the standard cardiac rehab group had declined to significantly below baseline. Thus, the aerobic interval training group retained a significant relative advantage, although it seems clear that some sort of refresher intervention needs to be developed.

In terms of secondary study end points, flow-mediated dilatation of the brachial artery increased significantly in both groups after the rehab program, with no between-group difference. So did quality of life scores and increases in plasma adiponectin, a hormone with multiple beneficial metabolic effects. However, only the aerobic interval program graduates experienced a significant increase in HDL levels, which rose from 49.9 mg/dL at baseline to 51.5 mg/dL after 12 weeks.

In the 69 subjects who presented at 30 months post rehab, self-reported physical activity varied markedly between the two study groups. Fully 20% of the standard-rehab patients reported being physically inactive, compared with just 4% in the aerobic interval group. Fifteen percent in the standard-rehab group indicated they engaged in high-intensity exercise, compared with 46% of graduates of the aerobic interval-based program – and therein lies the explanation for the significant long-term difference between the two groups in VO2max, according to Dr. Moholdt.

She noted that these results are consistent with an earlier randomized study she and her coworkers conducted in coronary artery bypass graft surgery patients followed for 6 months after completing cardiac rehab emphasizing either aerobic interval training or continuous moderate exercise (Am. Heart J. 2009;158:1031-7).

Audience members at the session devoted to research in cardiac rehab were generally enthusiastic about the Trondheim study findings and found the data convincing. One attendee said that the aerobic interval training program was as much a psychological as a physiological intervention.

“You’ve proved that a different self-reported behavior pattern was created. You’ve shown the patients that they could dare to perform high-level exercise,” he said.

“I do agree,” Dr. Moholdt replied. “Many patients quickly realized, often after the very first session, that it’s not dangerous to become exhausted.”

Dr. Josef Niebauer, session cochair, was the sole vocal skeptic.

“I’m just not buying it. I think these data should not be overinterpreted in the face of quite a high number of dropouts and mainly self-reported data,” said Dr. Niebauer of the University of Salzburg (Austria).

He added that although he believes aerobic interval training has a useful place in cardiac rehab, he believes it is currently in an “overhyped” phase within the field.

Disclosures: Dr. Moholdt’s study was funded by the Norwegian Foundation for Health and Rehabilitation. She declared having no financial conflicts.