Pulmonary Health Hub

One of the most common conditions that complicate pregnancy is maternal asthma. Evidence continues to mount that adequate control of asthma, including appropriate use of medications, is the best approach to optimizing outcomes. Yet questions persist about the effect of asthma itself, as well as specific medications and the risk for major congenital malformations. As with any exposure during pregnancy, answering these questions is challenging because of the rarity of specific birth defects and the various and increasing number of medications that might be used to treat or prevent asthma symptoms.

Previously in this column ("Beta2-agonists for asthma, December 2011), we reviewed two studies that suggested short-acting beta-agonists used for the treatment of asthma were associated with an increased risk of oral clefts and that long-acting beta-agonists might be associated with an increased risk of cardiac anomalies (Hum. Reprod. 2011;26:3147-54; Birth Defects Res. A. Clin. Mol. Teratol. 2011;91:937-47).

What have we learned since then? Two studies published in 2013 add to the body of knowledge. The first, a database analysis using the United Kingdom’s General Practice Research Database, assessed pregnancy outcomes between 1991 and 2002 in 7,911 women exposed to asthma medications in the first trimester of pregnancy and 15,840 women who were not exposed (Pharmacotherapy 2013;33:363-8). Major anomalies were identified up to 1 year of age. Minor anomalies, chromosomal anomalies, and those associated with prematurity were excluded.

The overall risk for any exposure, compared with no exposure, for any congenital anomaly was 1.1 (95% confidence interval [CI], 1.0-1.3). No significant differences were found by class of asthma medication. Specific categories of defects also were evaluated, including musculoskeletal anomalies, oral clefts, cardiovascular defects, and multiple anomalies. Some estimates were elevated for specific medication classes.

For example, the relative risk (RR) of cleft lip or palate associated with exposure to long-acting beta-agonists was 2.4, but the confidence interval included 1 (0.3-21.8) based on 424 exposed pregnancies. The authors concluded that they found no significant increased risk of congenital anomalies associated with exposure to asthma, asthma medications, or any specific asthma medication classes in the first trimester. Limitations of the study included the inability to verify that exposure took place and insufficient data to adjust for confounding by vitamin supplementation, alcohol use, socioeconomic status, or markers of disease severity (other than number of medications prescribed).

The second study addressed the issue of maternal asthma itself and the risk for congenital anomalies (BJOG 2013;120:812-22). Using a meta-analysis approach, 21 cohort studies published between 1975 and 2012 met the criteria for inclusion. Combining major and minor congenital anomalies, the authors found a slight but statistically significant increased risk for any defect (RR, 1.11; 95% CI, 1.01-1.68), but when the analysis was restricted to major defects alone, the summary estimate was elevated but no longer significant (RR, 1.31; 95% CI, 0.57-3.02). When the specific defect grouping of oral clefts was examined, however, there was a significantly elevated overall relative risk of 1.30 (95% CI, 1.01-1.68). Limitations of this study include differing quality of studies and the appropriateness of combining data to derive a summary estimate.

Although both studies provide reassurance about the overall risk of major defects in the offspring of women with asthma, both suggest that more work needs to be done to follow up on the risk for oral clefts and whether this is linked to underlying disease severity and/or use of specific medications. Furthermore, safety of specific long-acting beta-agonist medications in pregnancy should be further examined.

The take-home message, however, continues to be that the risk for major defects in the offspring of pregnant women with asthma appears to be low, which supports the recommendation to follow guidelines for appropriate treatment of women with asthma both during and outside of pregnancy to control symptoms.

Dr. Chambers is professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said that she had no relevant financial disclosures. 

One of the most common conditions that complicate pregnancy is maternal asthma. Evidence continues to mount that adequate control of asthma, including appropriate use of medications, is the best approach to optimizing outcomes. Yet questions persist about the effect of asthma itself, as well as specific medications and the risk for major congenital malformations. As with any exposure during pregnancy, answering these questions is challenging because of the rarity of specific birth defects and the various and increasing number of medications that might be used to treat or prevent asthma symptoms.

Previously in this column ("Beta2-agonists for asthma, December 2011), we reviewed two studies that suggested short-acting beta-agonists used for the treatment of asthma were associated with an increased risk of oral clefts and that long-acting beta-agonists might be associated with an increased risk of cardiac anomalies (Hum. Reprod. 2011;26:3147-54; Birth Defects Res. A. Clin. Mol. Teratol. 2011;91:937-47).

What have we learned since then? Two studies published in 2013 add to the body of knowledge. The first, a database analysis using the United Kingdom’s General Practice Research Database, assessed pregnancy outcomes between 1991 and 2002 in 7,911 women exposed to asthma medications in the first trimester of pregnancy and 15,840 women who were not exposed (Pharmacotherapy 2013;33:363-8). Major anomalies were identified up to 1 year of age. Minor anomalies, chromosomal anomalies, and those associated with prematurity were excluded.

The overall risk for any exposure, compared with no exposure, for any congenital anomaly was 1.1 (95% confidence interval [CI], 1.0-1.3). No significant differences were found by class of asthma medication. Specific categories of defects also were evaluated, including musculoskeletal anomalies, oral clefts, cardiovascular defects, and multiple anomalies. Some estimates were elevated for specific medication classes.

For example, the relative risk (RR) of cleft lip or palate associated with exposure to long-acting beta-agonists was 2.4, but the confidence interval included 1 (0.3-21.8) based on 424 exposed pregnancies. The authors concluded that they found no significant increased risk of congenital anomalies associated with exposure to asthma, asthma medications, or any specific asthma medication classes in the first trimester. Limitations of the study included the inability to verify that exposure took place and insufficient data to adjust for confounding by vitamin supplementation, alcohol use, socioeconomic status, or markers of disease severity (other than number of medications prescribed).

The second study addressed the issue of maternal asthma itself and the risk for congenital anomalies (BJOG 2013;120:812-22). Using a meta-analysis approach, 21 cohort studies published between 1975 and 2012 met the criteria for inclusion. Combining major and minor congenital anomalies, the authors found a slight but statistically significant increased risk for any defect (RR, 1.11; 95% CI, 1.01-1.68), but when the analysis was restricted to major defects alone, the summary estimate was elevated but no longer significant (RR, 1.31; 95% CI, 0.57-3.02). When the specific defect grouping of oral clefts was examined, however, there was a significantly elevated overall relative risk of 1.30 (95% CI, 1.01-1.68). Limitations of this study include differing quality of studies and the appropriateness of combining data to derive a summary estimate.

Although both studies provide reassurance about the overall risk of major defects in the offspring of women with asthma, both suggest that more work needs to be done to follow up on the risk for oral clefts and whether this is linked to underlying disease severity and/or use of specific medications. Furthermore, safety of specific long-acting beta-agonist medications in pregnancy should be further examined.

The take-home message, however, continues to be that the risk for major defects in the offspring of pregnant women with asthma appears to be low, which supports the recommendation to follow guidelines for appropriate treatment of women with asthma both during and outside of pregnancy to control symptoms.

Dr. Chambers is professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said that she had no relevant financial disclosures. 

One of the most common conditions that complicate pregnancy is maternal asthma. Evidence continues to mount that adequate control of asthma, including appropriate use of medications, is the best approach to optimizing outcomes. Yet questions persist about the effect of asthma itself, as well as specific medications and the risk for major congenital malformations. As with any exposure during pregnancy, answering these questions is challenging because of the rarity of specific birth defects and the various and increasing number of medications that might be used to treat or prevent asthma symptoms.

Previously in this column ("Beta2-agonists for asthma, December 2011), we reviewed two studies that suggested short-acting beta-agonists used for the treatment of asthma were associated with an increased risk of oral clefts and that long-acting beta-agonists might be associated with an increased risk of cardiac anomalies (Hum. Reprod. 2011;26:3147-54; Birth Defects Res. A. Clin. Mol. Teratol. 2011;91:937-47).

What have we learned since then? Two studies published in 2013 add to the body of knowledge. The first, a database analysis using the United Kingdom’s General Practice Research Database, assessed pregnancy outcomes between 1991 and 2002 in 7,911 women exposed to asthma medications in the first trimester of pregnancy and 15,840 women who were not exposed (Pharmacotherapy 2013;33:363-8). Major anomalies were identified up to 1 year of age. Minor anomalies, chromosomal anomalies, and those associated with prematurity were excluded.

The overall risk for any exposure, compared with no exposure, for any congenital anomaly was 1.1 (95% confidence interval [CI], 1.0-1.3). No significant differences were found by class of asthma medication. Specific categories of defects also were evaluated, including musculoskeletal anomalies, oral clefts, cardiovascular defects, and multiple anomalies. Some estimates were elevated for specific medication classes.

For example, the relative risk (RR) of cleft lip or palate associated with exposure to long-acting beta-agonists was 2.4, but the confidence interval included 1 (0.3-21.8) based on 424 exposed pregnancies. The authors concluded that they found no significant increased risk of congenital anomalies associated with exposure to asthma, asthma medications, or any specific asthma medication classes in the first trimester. Limitations of the study included the inability to verify that exposure took place and insufficient data to adjust for confounding by vitamin supplementation, alcohol use, socioeconomic status, or markers of disease severity (other than number of medications prescribed).

The second study addressed the issue of maternal asthma itself and the risk for congenital anomalies (BJOG 2013;120:812-22). Using a meta-analysis approach, 21 cohort studies published between 1975 and 2012 met the criteria for inclusion. Combining major and minor congenital anomalies, the authors found a slight but statistically significant increased risk for any defect (RR, 1.11; 95% CI, 1.01-1.68), but when the analysis was restricted to major defects alone, the summary estimate was elevated but no longer significant (RR, 1.31; 95% CI, 0.57-3.02). When the specific defect grouping of oral clefts was examined, however, there was a significantly elevated overall relative risk of 1.30 (95% CI, 1.01-1.68). Limitations of this study include differing quality of studies and the appropriateness of combining data to derive a summary estimate.

Although both studies provide reassurance about the overall risk of major defects in the offspring of women with asthma, both suggest that more work needs to be done to follow up on the risk for oral clefts and whether this is linked to underlying disease severity and/or use of specific medications. Furthermore, safety of specific long-acting beta-agonist medications in pregnancy should be further examined.

The take-home message, however, continues to be that the risk for major defects in the offspring of pregnant women with asthma appears to be low, which supports the recommendation to follow guidelines for appropriate treatment of women with asthma both during and outside of pregnancy to control symptoms.

Dr. Chambers is professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said that she had no relevant financial disclosures. 

MADRID – Patients with systemic sclerosis should undergo annual screening for pulmonary arterial hypertension using a combination of transthoracic echocardiography and pulmonary function tests, an international expert panel said.

These are the first evidence- and consensus-based recommendations for pulmonary arterial hypertension (PAH) screening in patients with systemic sclerosis, and the panel also called for screening patients with mixed or other connective tissue diseases with scleroderma features. "Our hope is that these recommendations will lead to earlier detection of PAH in connective tissue diseases and improve patient outcomes," Dr. Dinesh Khanna said while presenting the screening recommendations at the annual European Congress of Rheumatology.

About 5%-15% of patients with systemic sclerosis develop PAH, and once PAH occurs, up to 30% of patients will die within 3 years, said Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor.

"Despite having approved drugs available" to treat systemic sclerosis and other scleroderma-spectrum disorder connective tissue diseases, these treatments "have not had a huge impact on survival. The only thing we can offer patients is screening, followed by early diagnosis and treatment," Dr. Khanna said in an interview.

The new recommendations say that patients with a tricuspid regurgitant velocity measured by transthoracic echocardiography greater than 2.8 m/s require assessment for PAH by right heart catheterization. Right heart catheterization is also needed for patients with a tricuspid regurgitant velocity of 2.5-2.8 m/s if they also have signs or symptoms of PAH such as dyspnea, fatigue, chest pain, dizziness, loud pulmonary sound, or peripheral edema. Another echo finding that should trigger right heart catheterization regardless of signs or symptoms or tricuspid regurgitation is right atrial or ventricular enlargement.

The key measures on pulmonary function tests that trigger right heart catheterization is a forced vital capacity (FVC) to diffusion capacity of lungs for carbon monoxide (DLCO) ratio of more than 1.6, or a DLCO of less than 60% if either appears in the setting of PAH signs or symptoms. Alternatively, meeting either of these pulmonary criteria should lead to right heart catheterization regardless of signs and symptoms if the patient’s most recent blood level of N-terminal pro-brain natriuretic peptide (NT-ProBNP) was greater than twice the upper limit of normal.

The panel also said that patients should undergo right heart catheterization regardless of PAH signs and symptoms if they fulfill the screening algorithm developed for the DETECT study (Ann. Rheum. Dis. 2013 May 18 [doi:10.1036/annrheumdis-2013-203301]).

The panel recommended annual transthoracic echo and pulmonary function test screening, or more frequently if a patient shows new signs or symptoms. Measurement of NT-ProBNP should happen at baseline, and then be repeated if new signs or symptoms of PAH appear. They also recommended applying the full DETECT screening algorithm in patients diagnosed with systemic sclerosis or other scleroderma spectrum connective-tissue disease for more than 3 years and a DLCO that is less than 60%. Right heart catheterization is mandatory to definitively diagnose PAH, Dr. Khanna stressed. The panel also said screening is not needed in patients with mixed- or other connective tissue disorders who did not have scleroderma-like features.

In a separate report at the meeting Dr. Khanna and his associates assessed the ability of transthoracic echocardiography and pulmonary function tests to screen patients with PAH. They used data from 69 patients with PAH in two separate reported series that together had 347 patients with systemic sclerosis who underwent assessment for suspected PAH (J. Rheumatol. 2011;38:2172-9 and J. Rheumatol. 2010;37:2290-8).

The new, retrospective analysis showed that combining transthoracic echo and pulmonary-function test screens can have a negative predictive accuracy of 98% for correctly ruling out PAH in patients with systemic sclerosis, reported Dr. Heather Gladue, a rheumatology fellow at the University of Michigan.

The recommendations panel cautioned that its proposals should not substitute for individualized, direct assessment of each patient. The panel also noted that the cost effectiveness of its recommendations had not yet been assessed. In addition to representatives from the University of Michigan, the task force included members from the University of California, Los Angeles; Massachusetts General Hospital, Boston; Stanford (Calif.) University; the University of Zurich; University Hospital in Lille, France; the University of Paris-South; McGill University, Montreal; Johns Hopkins University, Baltimore; and St. Joseph Hospital, Phoenix.

The task force was supported by the Scleroderma Foundation and the Pulmonary Hypertension Association. Dr. Khanna said that he has been a consultant to several drug companies including Actelion, Bayer, Genentech/Roche, Gilead, Merck, and DIGNA. Dr. Gladue said that she had no disclosures.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

MADRID – Patients with systemic sclerosis should undergo annual screening for pulmonary arterial hypertension using a combination of transthoracic echocardiography and pulmonary function tests, an international expert panel said.

These are the first evidence- and consensus-based recommendations for pulmonary arterial hypertension (PAH) screening in patients with systemic sclerosis, and the panel also called for screening patients with mixed or other connective tissue diseases with scleroderma features. "Our hope is that these recommendations will lead to earlier detection of PAH in connective tissue diseases and improve patient outcomes," Dr. Dinesh Khanna said while presenting the screening recommendations at the annual European Congress of Rheumatology.

About 5%-15% of patients with systemic sclerosis develop PAH, and once PAH occurs, up to 30% of patients will die within 3 years, said Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor.

"Despite having approved drugs available" to treat systemic sclerosis and other scleroderma-spectrum disorder connective tissue diseases, these treatments "have not had a huge impact on survival. The only thing we can offer patients is screening, followed by early diagnosis and treatment," Dr. Khanna said in an interview.

The new recommendations say that patients with a tricuspid regurgitant velocity measured by transthoracic echocardiography greater than 2.8 m/s require assessment for PAH by right heart catheterization. Right heart catheterization is also needed for patients with a tricuspid regurgitant velocity of 2.5-2.8 m/s if they also have signs or symptoms of PAH such as dyspnea, fatigue, chest pain, dizziness, loud pulmonary sound, or peripheral edema. Another echo finding that should trigger right heart catheterization regardless of signs or symptoms or tricuspid regurgitation is right atrial or ventricular enlargement.

The key measures on pulmonary function tests that trigger right heart catheterization is a forced vital capacity (FVC) to diffusion capacity of lungs for carbon monoxide (DLCO) ratio of more than 1.6, or a DLCO of less than 60% if either appears in the setting of PAH signs or symptoms. Alternatively, meeting either of these pulmonary criteria should lead to right heart catheterization regardless of signs and symptoms if the patient’s most recent blood level of N-terminal pro-brain natriuretic peptide (NT-ProBNP) was greater than twice the upper limit of normal.

The panel also said that patients should undergo right heart catheterization regardless of PAH signs and symptoms if they fulfill the screening algorithm developed for the DETECT study (Ann. Rheum. Dis. 2013 May 18 [doi:10.1036/annrheumdis-2013-203301]).

The panel recommended annual transthoracic echo and pulmonary function test screening, or more frequently if a patient shows new signs or symptoms. Measurement of NT-ProBNP should happen at baseline, and then be repeated if new signs or symptoms of PAH appear. They also recommended applying the full DETECT screening algorithm in patients diagnosed with systemic sclerosis or other scleroderma spectrum connective-tissue disease for more than 3 years and a DLCO that is less than 60%. Right heart catheterization is mandatory to definitively diagnose PAH, Dr. Khanna stressed. The panel also said screening is not needed in patients with mixed- or other connective tissue disorders who did not have scleroderma-like features.

In a separate report at the meeting Dr. Khanna and his associates assessed the ability of transthoracic echocardiography and pulmonary function tests to screen patients with PAH. They used data from 69 patients with PAH in two separate reported series that together had 347 patients with systemic sclerosis who underwent assessment for suspected PAH (J. Rheumatol. 2011;38:2172-9 and J. Rheumatol. 2010;37:2290-8).

The new, retrospective analysis showed that combining transthoracic echo and pulmonary-function test screens can have a negative predictive accuracy of 98% for correctly ruling out PAH in patients with systemic sclerosis, reported Dr. Heather Gladue, a rheumatology fellow at the University of Michigan.

The recommendations panel cautioned that its proposals should not substitute for individualized, direct assessment of each patient. The panel also noted that the cost effectiveness of its recommendations had not yet been assessed. In addition to representatives from the University of Michigan, the task force included members from the University of California, Los Angeles; Massachusetts General Hospital, Boston; Stanford (Calif.) University; the University of Zurich; University Hospital in Lille, France; the University of Paris-South; McGill University, Montreal; Johns Hopkins University, Baltimore; and St. Joseph Hospital, Phoenix.

The task force was supported by the Scleroderma Foundation and the Pulmonary Hypertension Association. Dr. Khanna said that he has been a consultant to several drug companies including Actelion, Bayer, Genentech/Roche, Gilead, Merck, and DIGNA. Dr. Gladue said that she had no disclosures.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

MADRID – Patients with systemic sclerosis should undergo annual screening for pulmonary arterial hypertension using a combination of transthoracic echocardiography and pulmonary function tests, an international expert panel said.

These are the first evidence- and consensus-based recommendations for pulmonary arterial hypertension (PAH) screening in patients with systemic sclerosis, and the panel also called for screening patients with mixed or other connective tissue diseases with scleroderma features. "Our hope is that these recommendations will lead to earlier detection of PAH in connective tissue diseases and improve patient outcomes," Dr. Dinesh Khanna said while presenting the screening recommendations at the annual European Congress of Rheumatology.

About 5%-15% of patients with systemic sclerosis develop PAH, and once PAH occurs, up to 30% of patients will die within 3 years, said Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor.

"Despite having approved drugs available" to treat systemic sclerosis and other scleroderma-spectrum disorder connective tissue diseases, these treatments "have not had a huge impact on survival. The only thing we can offer patients is screening, followed by early diagnosis and treatment," Dr. Khanna said in an interview.

The new recommendations say that patients with a tricuspid regurgitant velocity measured by transthoracic echocardiography greater than 2.8 m/s require assessment for PAH by right heart catheterization. Right heart catheterization is also needed for patients with a tricuspid regurgitant velocity of 2.5-2.8 m/s if they also have signs or symptoms of PAH such as dyspnea, fatigue, chest pain, dizziness, loud pulmonary sound, or peripheral edema. Another echo finding that should trigger right heart catheterization regardless of signs or symptoms or tricuspid regurgitation is right atrial or ventricular enlargement.

The key measures on pulmonary function tests that trigger right heart catheterization is a forced vital capacity (FVC) to diffusion capacity of lungs for carbon monoxide (DLCO) ratio of more than 1.6, or a DLCO of less than 60% if either appears in the setting of PAH signs or symptoms. Alternatively, meeting either of these pulmonary criteria should lead to right heart catheterization regardless of signs and symptoms if the patient’s most recent blood level of N-terminal pro-brain natriuretic peptide (NT-ProBNP) was greater than twice the upper limit of normal.

The panel also said that patients should undergo right heart catheterization regardless of PAH signs and symptoms if they fulfill the screening algorithm developed for the DETECT study (Ann. Rheum. Dis. 2013 May 18 [doi:10.1036/annrheumdis-2013-203301]).

The panel recommended annual transthoracic echo and pulmonary function test screening, or more frequently if a patient shows new signs or symptoms. Measurement of NT-ProBNP should happen at baseline, and then be repeated if new signs or symptoms of PAH appear. They also recommended applying the full DETECT screening algorithm in patients diagnosed with systemic sclerosis or other scleroderma spectrum connective-tissue disease for more than 3 years and a DLCO that is less than 60%. Right heart catheterization is mandatory to definitively diagnose PAH, Dr. Khanna stressed. The panel also said screening is not needed in patients with mixed- or other connective tissue disorders who did not have scleroderma-like features.

In a separate report at the meeting Dr. Khanna and his associates assessed the ability of transthoracic echocardiography and pulmonary function tests to screen patients with PAH. They used data from 69 patients with PAH in two separate reported series that together had 347 patients with systemic sclerosis who underwent assessment for suspected PAH (J. Rheumatol. 2011;38:2172-9 and J. Rheumatol. 2010;37:2290-8).

The new, retrospective analysis showed that combining transthoracic echo and pulmonary-function test screens can have a negative predictive accuracy of 98% for correctly ruling out PAH in patients with systemic sclerosis, reported Dr. Heather Gladue, a rheumatology fellow at the University of Michigan.

The recommendations panel cautioned that its proposals should not substitute for individualized, direct assessment of each patient. The panel also noted that the cost effectiveness of its recommendations had not yet been assessed. In addition to representatives from the University of Michigan, the task force included members from the University of California, Los Angeles; Massachusetts General Hospital, Boston; Stanford (Calif.) University; the University of Zurich; University Hospital in Lille, France; the University of Paris-South; McGill University, Montreal; Johns Hopkins University, Baltimore; and St. Joseph Hospital, Phoenix.

The task force was supported by the Scleroderma Foundation and the Pulmonary Hypertension Association. Dr. Khanna said that he has been a consultant to several drug companies including Actelion, Bayer, Genentech/Roche, Gilead, Merck, and DIGNA. Dr. Gladue said that she had no disclosures.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

Giving clinicians the option to wait up to 3 days before treating the most common presentation of acute bacterial sinusitis is among the changes to the American Academy of Pediatrics’ updated clinical practice guidelines for treating these infections.

About 5%-10% of upper respiratory tract infections in children develop into acute bacterial sinusitis, according to the new guidelines, published in Pediatrics.

Other changes include a new presentation, and discouraging the use of x-rays to confirm diagnosis. The guidelines published online were written by Dr. Ellen R. Wald, chair of pediatrics at the University of Wisconsin, Madison, and her associates (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1071]). The guidelines incorporated data from an accompanying systematic review of the research published since the last guidelines were issued in 2001.

The added presentation is a worsening course, defined as "worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement." This presentation joins the existing severe onset (a fever of at least 39° C [102.2° F] with at least 3 days of a purulent nasal discharge) and, most common, persistent illness lasting more than 10 days without improvement.

For those with symptoms of nasal discharge, daytime cough, or fever lasting more than 10 days, clinicians may discuss with the parent whether to treat right away or wait a few days. For severe onset and worsening symptoms, clinicians should prescribe antibiotic therapy right away. First-line treatment is amoxicillin with or without clavulanate, followed by a reassessment of initial management if the symptoms worsen or do not improve within 72 hours.

The guidelines do not recommend adjuvant therapies, including intranasal corticosteroids, saline nasal irrigation or lavage, topical or oral decongestants, mucolytics, and topical or oral antihistamines.

Among the four major changes to the guidelines, including the updated evidence, the option for delayed treatment in nonsevere cases and the recommendation not to use imaging are especially relevant for clinical practice, according to Dr. Wald, a pediatric infectious disease specialist.

"When the AAP writes about this, they’re talking about it as joint decision making," Dr. Wald said in an interview. "If the parent really wants treatment at that time, I think the doctor’s going to want to do it. It’s being a little bit more permissive in tolerating the symptoms for a few more days. The clinician is given the option to treat immediately or, with the parents’ consent, they can wait a few days to see if the child gets better spontaneously."

Dr. Wald noted that the decision to treat can involve a trade-off, so these guidelines offer the clinicians more latitude in making the cost-benefit analysis with the parent, taking into account the illness severity, the child’s quality of life, and the parents’ values and concerns.

"The reason we like to treat it is that kids get better faster," Dr. Wald said. "On the one hand, we want the kid to get better faster, but on the other hand, we don’t want to use the antibiotic if we don’t have to because we want to avoid side effects or, from a public health perspective, the increased antibiotic resistance for the population." The most common side effect of antibiotics is diarrhea, she said; fewer patients may experience a rash.

The guideline discouraging imaging stems from findings that imaging offers little clinical benefit. "In the past, a diagnostician would get a set of x-rays to see if the sinuses were cloudy and confirm the diagnosis if they found cloudy sinuses," Dr. Wald said. "However, x-rays are frequently abnormal even in children with uncomplicated colds, so the x-rays are not a help. Therefore, we’re encouraging people to make the diagnosis only on clinical grounds."

However, the guidelines do encourage clinicians to get a "contrast-enhanced CT scan of the paranasal sinuses and/or an MRI with contrast whenever a child is suspected of having orbital or central nervous system complications of acute bacterial sinusitis" because discovered abscesses may require surgical intervention.

The systematic review, conducted by Dr. Michael J. Smith, a pediatric infectious disease specialist at the University of Louisville (Ky.), included evidence from 17 randomized controlled trials in the treatment of sinusitis in children (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1072]. All published since 2001, these trials add to the evidence base from the 21 studies published between 1966 and 1999 that were used in the previous guidelines.

Among the 17 new trials, 4 were randomized, double-blind, placebo-controlled trials of antimicrobial therapy used on a combined 392 children, but they were too heterogenous in criteria and results (2 favored treatment and 2 found no significant difference between treatment and control) to use in conducting a formal meta-analysis. Comparisons were further complicated by the long time span over which they were conducted, the introduction of universal conjugate pneumococcal vaccination, the increase in prevalence of other bacterial infections, and the variance in placebo group clinical improvement, ranging from 14% to 79% across the studies.

Five other trials that compared antimicrobial therapies lacked placebo controls, three dealt with subacute sinusitis rather than acute, and six tested various ancillary treatments. These ancillary treatments included steroids, nasal spray, saline irrigation, and mucolytic agents, but with small study populations and mostly equivocal results.

"Greater severity of illness at the time of presentation seems to be associated with increased likelihood of antimicrobial efficacy," Dr. Smith said.

Dr. Smith identified several clinical questions that require additional research: definitions of acute, subacute, and recurrent acute sinusitis; the epidemiology of sinusitis in the pneumococcal conjugate vaccine era; the effectiveness of antimicrobial prophylaxis; accurate estimates for duration of symptoms; and clinical utility of various imaging types.

The guidelines and systematic review did not identify any external funding used. Dr. Smith has received research funding from Sanofi Pasteur and Novartis. Dr. Nelson is employed by McKesson Health Solutions. Dr. Wald, Dr. Shaikh, and Dr. Rosenfeld have published research related to sinusitis. No other disclosures were reported.

Giving clinicians the option to wait up to 3 days before treating the most common presentation of acute bacterial sinusitis is among the changes to the American Academy of Pediatrics’ updated clinical practice guidelines for treating these infections.

About 5%-10% of upper respiratory tract infections in children develop into acute bacterial sinusitis, according to the new guidelines, published in Pediatrics.

Other changes include a new presentation, and discouraging the use of x-rays to confirm diagnosis. The guidelines published online were written by Dr. Ellen R. Wald, chair of pediatrics at the University of Wisconsin, Madison, and her associates (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1071]). The guidelines incorporated data from an accompanying systematic review of the research published since the last guidelines were issued in 2001.

The added presentation is a worsening course, defined as "worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement." This presentation joins the existing severe onset (a fever of at least 39° C [102.2° F] with at least 3 days of a purulent nasal discharge) and, most common, persistent illness lasting more than 10 days without improvement.

For those with symptoms of nasal discharge, daytime cough, or fever lasting more than 10 days, clinicians may discuss with the parent whether to treat right away or wait a few days. For severe onset and worsening symptoms, clinicians should prescribe antibiotic therapy right away. First-line treatment is amoxicillin with or without clavulanate, followed by a reassessment of initial management if the symptoms worsen or do not improve within 72 hours.

The guidelines do not recommend adjuvant therapies, including intranasal corticosteroids, saline nasal irrigation or lavage, topical or oral decongestants, mucolytics, and topical or oral antihistamines.

Among the four major changes to the guidelines, including the updated evidence, the option for delayed treatment in nonsevere cases and the recommendation not to use imaging are especially relevant for clinical practice, according to Dr. Wald, a pediatric infectious disease specialist.

"When the AAP writes about this, they’re talking about it as joint decision making," Dr. Wald said in an interview. "If the parent really wants treatment at that time, I think the doctor’s going to want to do it. It’s being a little bit more permissive in tolerating the symptoms for a few more days. The clinician is given the option to treat immediately or, with the parents’ consent, they can wait a few days to see if the child gets better spontaneously."

Dr. Wald noted that the decision to treat can involve a trade-off, so these guidelines offer the clinicians more latitude in making the cost-benefit analysis with the parent, taking into account the illness severity, the child’s quality of life, and the parents’ values and concerns.

"The reason we like to treat it is that kids get better faster," Dr. Wald said. "On the one hand, we want the kid to get better faster, but on the other hand, we don’t want to use the antibiotic if we don’t have to because we want to avoid side effects or, from a public health perspective, the increased antibiotic resistance for the population." The most common side effect of antibiotics is diarrhea, she said; fewer patients may experience a rash.

The guideline discouraging imaging stems from findings that imaging offers little clinical benefit. "In the past, a diagnostician would get a set of x-rays to see if the sinuses were cloudy and confirm the diagnosis if they found cloudy sinuses," Dr. Wald said. "However, x-rays are frequently abnormal even in children with uncomplicated colds, so the x-rays are not a help. Therefore, we’re encouraging people to make the diagnosis only on clinical grounds."

However, the guidelines do encourage clinicians to get a "contrast-enhanced CT scan of the paranasal sinuses and/or an MRI with contrast whenever a child is suspected of having orbital or central nervous system complications of acute bacterial sinusitis" because discovered abscesses may require surgical intervention.

The systematic review, conducted by Dr. Michael J. Smith, a pediatric infectious disease specialist at the University of Louisville (Ky.), included evidence from 17 randomized controlled trials in the treatment of sinusitis in children (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1072]. All published since 2001, these trials add to the evidence base from the 21 studies published between 1966 and 1999 that were used in the previous guidelines.

Among the 17 new trials, 4 were randomized, double-blind, placebo-controlled trials of antimicrobial therapy used on a combined 392 children, but they were too heterogenous in criteria and results (2 favored treatment and 2 found no significant difference between treatment and control) to use in conducting a formal meta-analysis. Comparisons were further complicated by the long time span over which they were conducted, the introduction of universal conjugate pneumococcal vaccination, the increase in prevalence of other bacterial infections, and the variance in placebo group clinical improvement, ranging from 14% to 79% across the studies.

Five other trials that compared antimicrobial therapies lacked placebo controls, three dealt with subacute sinusitis rather than acute, and six tested various ancillary treatments. These ancillary treatments included steroids, nasal spray, saline irrigation, and mucolytic agents, but with small study populations and mostly equivocal results.

"Greater severity of illness at the time of presentation seems to be associated with increased likelihood of antimicrobial efficacy," Dr. Smith said.

Dr. Smith identified several clinical questions that require additional research: definitions of acute, subacute, and recurrent acute sinusitis; the epidemiology of sinusitis in the pneumococcal conjugate vaccine era; the effectiveness of antimicrobial prophylaxis; accurate estimates for duration of symptoms; and clinical utility of various imaging types.

The guidelines and systematic review did not identify any external funding used. Dr. Smith has received research funding from Sanofi Pasteur and Novartis. Dr. Nelson is employed by McKesson Health Solutions. Dr. Wald, Dr. Shaikh, and Dr. Rosenfeld have published research related to sinusitis. No other disclosures were reported.

Giving clinicians the option to wait up to 3 days before treating the most common presentation of acute bacterial sinusitis is among the changes to the American Academy of Pediatrics’ updated clinical practice guidelines for treating these infections.

About 5%-10% of upper respiratory tract infections in children develop into acute bacterial sinusitis, according to the new guidelines, published in Pediatrics.

Other changes include a new presentation, and discouraging the use of x-rays to confirm diagnosis. The guidelines published online were written by Dr. Ellen R. Wald, chair of pediatrics at the University of Wisconsin, Madison, and her associates (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1071]). The guidelines incorporated data from an accompanying systematic review of the research published since the last guidelines were issued in 2001.

The added presentation is a worsening course, defined as "worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement." This presentation joins the existing severe onset (a fever of at least 39° C [102.2° F] with at least 3 days of a purulent nasal discharge) and, most common, persistent illness lasting more than 10 days without improvement.

For those with symptoms of nasal discharge, daytime cough, or fever lasting more than 10 days, clinicians may discuss with the parent whether to treat right away or wait a few days. For severe onset and worsening symptoms, clinicians should prescribe antibiotic therapy right away. First-line treatment is amoxicillin with or without clavulanate, followed by a reassessment of initial management if the symptoms worsen or do not improve within 72 hours.

The guidelines do not recommend adjuvant therapies, including intranasal corticosteroids, saline nasal irrigation or lavage, topical or oral decongestants, mucolytics, and topical or oral antihistamines.

Among the four major changes to the guidelines, including the updated evidence, the option for delayed treatment in nonsevere cases and the recommendation not to use imaging are especially relevant for clinical practice, according to Dr. Wald, a pediatric infectious disease specialist.

"When the AAP writes about this, they’re talking about it as joint decision making," Dr. Wald said in an interview. "If the parent really wants treatment at that time, I think the doctor’s going to want to do it. It’s being a little bit more permissive in tolerating the symptoms for a few more days. The clinician is given the option to treat immediately or, with the parents’ consent, they can wait a few days to see if the child gets better spontaneously."

Dr. Wald noted that the decision to treat can involve a trade-off, so these guidelines offer the clinicians more latitude in making the cost-benefit analysis with the parent, taking into account the illness severity, the child’s quality of life, and the parents’ values and concerns.

"The reason we like to treat it is that kids get better faster," Dr. Wald said. "On the one hand, we want the kid to get better faster, but on the other hand, we don’t want to use the antibiotic if we don’t have to because we want to avoid side effects or, from a public health perspective, the increased antibiotic resistance for the population." The most common side effect of antibiotics is diarrhea, she said; fewer patients may experience a rash.

The guideline discouraging imaging stems from findings that imaging offers little clinical benefit. "In the past, a diagnostician would get a set of x-rays to see if the sinuses were cloudy and confirm the diagnosis if they found cloudy sinuses," Dr. Wald said. "However, x-rays are frequently abnormal even in children with uncomplicated colds, so the x-rays are not a help. Therefore, we’re encouraging people to make the diagnosis only on clinical grounds."

However, the guidelines do encourage clinicians to get a "contrast-enhanced CT scan of the paranasal sinuses and/or an MRI with contrast whenever a child is suspected of having orbital or central nervous system complications of acute bacterial sinusitis" because discovered abscesses may require surgical intervention.

The systematic review, conducted by Dr. Michael J. Smith, a pediatric infectious disease specialist at the University of Louisville (Ky.), included evidence from 17 randomized controlled trials in the treatment of sinusitis in children (Pediatrics 2013 June 24 [doi:10.1542/peds.2013-1072]. All published since 2001, these trials add to the evidence base from the 21 studies published between 1966 and 1999 that were used in the previous guidelines.

Among the 17 new trials, 4 were randomized, double-blind, placebo-controlled trials of antimicrobial therapy used on a combined 392 children, but they were too heterogenous in criteria and results (2 favored treatment and 2 found no significant difference between treatment and control) to use in conducting a formal meta-analysis. Comparisons were further complicated by the long time span over which they were conducted, the introduction of universal conjugate pneumococcal vaccination, the increase in prevalence of other bacterial infections, and the variance in placebo group clinical improvement, ranging from 14% to 79% across the studies.

Five other trials that compared antimicrobial therapies lacked placebo controls, three dealt with subacute sinusitis rather than acute, and six tested various ancillary treatments. These ancillary treatments included steroids, nasal spray, saline irrigation, and mucolytic agents, but with small study populations and mostly equivocal results.

"Greater severity of illness at the time of presentation seems to be associated with increased likelihood of antimicrobial efficacy," Dr. Smith said.

Dr. Smith identified several clinical questions that require additional research: definitions of acute, subacute, and recurrent acute sinusitis; the epidemiology of sinusitis in the pneumococcal conjugate vaccine era; the effectiveness of antimicrobial prophylaxis; accurate estimates for duration of symptoms; and clinical utility of various imaging types.

The guidelines and systematic review did not identify any external funding used. Dr. Smith has received research funding from Sanofi Pasteur and Novartis. Dr. Nelson is employed by McKesson Health Solutions. Dr. Wald, Dr. Shaikh, and Dr. Rosenfeld have published research related to sinusitis. No other disclosures were reported.

MADRID – The use of a two-step algorithm significantly increased the rate at which pulmonary arterial hypertension was diagnosed in patients with systemic sclerosis in a prospective, observational, cross-sectional study.

The results of the DETECT study, presented at the annual European Congress of Rheumatology, showed that the two-step algorithm had a sensitivity of 96% for correctly identifying the condition, which was higher than the 71% sensitivity obtained using methods recommended currently by the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. The ESC/ERS recommendations are mainly based on consensus rather than robust evidence, and focus on the use of transthoracic echocardiography.

"DETECT is unique because it shows that if you just do an echocardiogram that you miss 29% of people who subsequently have pulmonary arterial hypertension [PAH], whereas if you apply the DETECT algorithm you miss only 4% of the people," Dr. Dinesh Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor, said in an interview.

Dr. Khanna, who was a coinvestigator in the study, added: "PAH is a leading cause of mortality; it has high prevalence [and] it has a median survival of 2 to 3 years. ... You don’t want to miss these patients." Dr. Khanna presented recommendations for annual screening of PAH in systemic sclerosis patients at another session at the meeting.

Although 4% of patients are still being missed, this is a dramatic improvement over current clinical practice, said DETECT investigator Dr. Christopher Denton, who presented the findings of the international, multicenter trial. The study was also recently published online (Ann. Rheum. Dis. 2013 May 18 [doi: 10.1136/annrheumdis-2013-203301]).

"There is a general feeling that patients need to be screened so that diagnoses can be made and licensed therapies can be initiated," said Dr. Denton of the Royal Free Hospital in London. "The goal of the study was to rationalize a large number of potential variables into a small number that could be developed into a risk score," he added, and "ultimately to ensure that the most appropriate patients are referred for diagnostic right heart catheter studies." Right heart catheterization (RHC) remains the only method for confirming a diagnosis of PAH.

A total of 646 adult patients with established scleroderma (greater than 3 years) and reduced diffusing capacity of the lung for carbon monoxide (DLCO less than 60% of predicted) were screened and 466 enrolled in the study. All of them underwent RHC, and 145 (31%) were found to have PAH. This was defined as a mean pulmonary arterial pressure of 25 mm Hg or higher.

Of the 145 patients with PAH, 87 met World Health Organization (WHO) group 1 criteria for mild PAH, and this was the group of interest, as a diagnosis of PAH "had been robustly excluded" by normal methods, Dr. Denton said. This group of patients was compared with the group that did not have PAH (n = 321).

Patients with WHO group 1 PAH were slightly older than patients who did not have PAH (mean ages, 61 and 56 years). The PAH patients also tended to have a longer disease duration (163 vs. 130 months) and had slightly lower DLCO (43% vs. 48% of predicted).

The DETECT investigators examined 112 variables, including demographic and clinical parameters, serum tests, and electro- and echocardiogram results, that they thought might be able to help differentiate patients with PAH from those without it. After expert analysis and various types of statistical modeling, they ended up with eight items that were used to develop the two-step algorithm.

Step 1 of the algorithm involves testing for lung function, expressed as a ratio of the percentage predicted forced vital capacity and DLCO; the presence of current or past telangiectasia; serum anticentromere antibody positivity; serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP); serum urate levels; and right axis deviation on an electrocardiogram. Step 2 involves measurement of two echocardiographic parameters: right atrium area and tricuspid regurgitation velocity.

"The aim is to make this a computer-based system," Dr. Denton explained. A trial electronic version of the tool is being tested, which involves the aforementioned clinical variables being entered first to determine if an echocardiogram is warranted, and then determining if the results of the echocardiogram warrant further referral for RHC.

The rates of referral for RHC were higher if the two-step algorithm was used, compared with the use of ESC/ERS guideline-recommended methods (62% and 40%). The specificity of the algorithm was 48%, with positive and negative predictive values of 35% and 98%, respectively. The values for guideline-recommended methods were 69%, 40%, and 89%.

The DETECT algorithm has the potential to revise standards of care in patients with systemic sclerosis. Dr. Denton noted that not only was it a sensitive, noninvasive screening tool, but that it also had the potential to reduce the number of missed diagnoses and to potentially identify PAH earlier in mildly symptomatic patients.

"The reason to use a two-step approach is that this potentially will improve the use of echocardiography as well as the more invasive test of right heart catheterization," he commented. "So we hope that this sort of approach will ultimately improve the approach and the standard of care for systemic sclerosis."

DETECT was an academic-led study funded by Actelion. Dr. Denton has received consulting and speaker fees and/or research funding from, or has been a clinical trial investigator for, several companies including Actelion, Boehringer Ingelheim, and CSL Behring. Dr. Khanna disclosed acting as a consultant for several companies including Actelion, Bayer, and Celgene.

MADRID – The use of a two-step algorithm significantly increased the rate at which pulmonary arterial hypertension was diagnosed in patients with systemic sclerosis in a prospective, observational, cross-sectional study.

The results of the DETECT study, presented at the annual European Congress of Rheumatology, showed that the two-step algorithm had a sensitivity of 96% for correctly identifying the condition, which was higher than the 71% sensitivity obtained using methods recommended currently by the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. The ESC/ERS recommendations are mainly based on consensus rather than robust evidence, and focus on the use of transthoracic echocardiography.

"DETECT is unique because it shows that if you just do an echocardiogram that you miss 29% of people who subsequently have pulmonary arterial hypertension [PAH], whereas if you apply the DETECT algorithm you miss only 4% of the people," Dr. Dinesh Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor, said in an interview.

Dr. Khanna, who was a coinvestigator in the study, added: "PAH is a leading cause of mortality; it has high prevalence [and] it has a median survival of 2 to 3 years. ... You don’t want to miss these patients." Dr. Khanna presented recommendations for annual screening of PAH in systemic sclerosis patients at another session at the meeting.

Although 4% of patients are still being missed, this is a dramatic improvement over current clinical practice, said DETECT investigator Dr. Christopher Denton, who presented the findings of the international, multicenter trial. The study was also recently published online (Ann. Rheum. Dis. 2013 May 18 [doi: 10.1136/annrheumdis-2013-203301]).

"There is a general feeling that patients need to be screened so that diagnoses can be made and licensed therapies can be initiated," said Dr. Denton of the Royal Free Hospital in London. "The goal of the study was to rationalize a large number of potential variables into a small number that could be developed into a risk score," he added, and "ultimately to ensure that the most appropriate patients are referred for diagnostic right heart catheter studies." Right heart catheterization (RHC) remains the only method for confirming a diagnosis of PAH.

A total of 646 adult patients with established scleroderma (greater than 3 years) and reduced diffusing capacity of the lung for carbon monoxide (DLCO less than 60% of predicted) were screened and 466 enrolled in the study. All of them underwent RHC, and 145 (31%) were found to have PAH. This was defined as a mean pulmonary arterial pressure of 25 mm Hg or higher.

Of the 145 patients with PAH, 87 met World Health Organization (WHO) group 1 criteria for mild PAH, and this was the group of interest, as a diagnosis of PAH "had been robustly excluded" by normal methods, Dr. Denton said. This group of patients was compared with the group that did not have PAH (n = 321).

Patients with WHO group 1 PAH were slightly older than patients who did not have PAH (mean ages, 61 and 56 years). The PAH patients also tended to have a longer disease duration (163 vs. 130 months) and had slightly lower DLCO (43% vs. 48% of predicted).

The DETECT investigators examined 112 variables, including demographic and clinical parameters, serum tests, and electro- and echocardiogram results, that they thought might be able to help differentiate patients with PAH from those without it. After expert analysis and various types of statistical modeling, they ended up with eight items that were used to develop the two-step algorithm.

Step 1 of the algorithm involves testing for lung function, expressed as a ratio of the percentage predicted forced vital capacity and DLCO; the presence of current or past telangiectasia; serum anticentromere antibody positivity; serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP); serum urate levels; and right axis deviation on an electrocardiogram. Step 2 involves measurement of two echocardiographic parameters: right atrium area and tricuspid regurgitation velocity.

"The aim is to make this a computer-based system," Dr. Denton explained. A trial electronic version of the tool is being tested, which involves the aforementioned clinical variables being entered first to determine if an echocardiogram is warranted, and then determining if the results of the echocardiogram warrant further referral for RHC.

The rates of referral for RHC were higher if the two-step algorithm was used, compared with the use of ESC/ERS guideline-recommended methods (62% and 40%). The specificity of the algorithm was 48%, with positive and negative predictive values of 35% and 98%, respectively. The values for guideline-recommended methods were 69%, 40%, and 89%.

The DETECT algorithm has the potential to revise standards of care in patients with systemic sclerosis. Dr. Denton noted that not only was it a sensitive, noninvasive screening tool, but that it also had the potential to reduce the number of missed diagnoses and to potentially identify PAH earlier in mildly symptomatic patients.

"The reason to use a two-step approach is that this potentially will improve the use of echocardiography as well as the more invasive test of right heart catheterization," he commented. "So we hope that this sort of approach will ultimately improve the approach and the standard of care for systemic sclerosis."

DETECT was an academic-led study funded by Actelion. Dr. Denton has received consulting and speaker fees and/or research funding from, or has been a clinical trial investigator for, several companies including Actelion, Boehringer Ingelheim, and CSL Behring. Dr. Khanna disclosed acting as a consultant for several companies including Actelion, Bayer, and Celgene.

MADRID – The use of a two-step algorithm significantly increased the rate at which pulmonary arterial hypertension was diagnosed in patients with systemic sclerosis in a prospective, observational, cross-sectional study.

The results of the DETECT study, presented at the annual European Congress of Rheumatology, showed that the two-step algorithm had a sensitivity of 96% for correctly identifying the condition, which was higher than the 71% sensitivity obtained using methods recommended currently by the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. The ESC/ERS recommendations are mainly based on consensus rather than robust evidence, and focus on the use of transthoracic echocardiography.

"DETECT is unique because it shows that if you just do an echocardiogram that you miss 29% of people who subsequently have pulmonary arterial hypertension [PAH], whereas if you apply the DETECT algorithm you miss only 4% of the people," Dr. Dinesh Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor, said in an interview.

Dr. Khanna, who was a coinvestigator in the study, added: "PAH is a leading cause of mortality; it has high prevalence [and] it has a median survival of 2 to 3 years. ... You don’t want to miss these patients." Dr. Khanna presented recommendations for annual screening of PAH in systemic sclerosis patients at another session at the meeting.

Although 4% of patients are still being missed, this is a dramatic improvement over current clinical practice, said DETECT investigator Dr. Christopher Denton, who presented the findings of the international, multicenter trial. The study was also recently published online (Ann. Rheum. Dis. 2013 May 18 [doi: 10.1136/annrheumdis-2013-203301]).

"There is a general feeling that patients need to be screened so that diagnoses can be made and licensed therapies can be initiated," said Dr. Denton of the Royal Free Hospital in London. "The goal of the study was to rationalize a large number of potential variables into a small number that could be developed into a risk score," he added, and "ultimately to ensure that the most appropriate patients are referred for diagnostic right heart catheter studies." Right heart catheterization (RHC) remains the only method for confirming a diagnosis of PAH.

A total of 646 adult patients with established scleroderma (greater than 3 years) and reduced diffusing capacity of the lung for carbon monoxide (DLCO less than 60% of predicted) were screened and 466 enrolled in the study. All of them underwent RHC, and 145 (31%) were found to have PAH. This was defined as a mean pulmonary arterial pressure of 25 mm Hg or higher.

Of the 145 patients with PAH, 87 met World Health Organization (WHO) group 1 criteria for mild PAH, and this was the group of interest, as a diagnosis of PAH "had been robustly excluded" by normal methods, Dr. Denton said. This group of patients was compared with the group that did not have PAH (n = 321).

Patients with WHO group 1 PAH were slightly older than patients who did not have PAH (mean ages, 61 and 56 years). The PAH patients also tended to have a longer disease duration (163 vs. 130 months) and had slightly lower DLCO (43% vs. 48% of predicted).

The DETECT investigators examined 112 variables, including demographic and clinical parameters, serum tests, and electro- and echocardiogram results, that they thought might be able to help differentiate patients with PAH from those without it. After expert analysis and various types of statistical modeling, they ended up with eight items that were used to develop the two-step algorithm.

Step 1 of the algorithm involves testing for lung function, expressed as a ratio of the percentage predicted forced vital capacity and DLCO; the presence of current or past telangiectasia; serum anticentromere antibody positivity; serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP); serum urate levels; and right axis deviation on an electrocardiogram. Step 2 involves measurement of two echocardiographic parameters: right atrium area and tricuspid regurgitation velocity.

"The aim is to make this a computer-based system," Dr. Denton explained. A trial electronic version of the tool is being tested, which involves the aforementioned clinical variables being entered first to determine if an echocardiogram is warranted, and then determining if the results of the echocardiogram warrant further referral for RHC.

The rates of referral for RHC were higher if the two-step algorithm was used, compared with the use of ESC/ERS guideline-recommended methods (62% and 40%). The specificity of the algorithm was 48%, with positive and negative predictive values of 35% and 98%, respectively. The values for guideline-recommended methods were 69%, 40%, and 89%.

The DETECT algorithm has the potential to revise standards of care in patients with systemic sclerosis. Dr. Denton noted that not only was it a sensitive, noninvasive screening tool, but that it also had the potential to reduce the number of missed diagnoses and to potentially identify PAH earlier in mildly symptomatic patients.

"The reason to use a two-step approach is that this potentially will improve the use of echocardiography as well as the more invasive test of right heart catheterization," he commented. "So we hope that this sort of approach will ultimately improve the approach and the standard of care for systemic sclerosis."

DETECT was an academic-led study funded by Actelion. Dr. Denton has received consulting and speaker fees and/or research funding from, or has been a clinical trial investigator for, several companies including Actelion, Boehringer Ingelheim, and CSL Behring. Dr. Khanna disclosed acting as a consultant for several companies including Actelion, Bayer, and Celgene.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

CHICAGO – The VeriStrat test is useful in guiding second-line treatment decisions in non–small-cell lung cancer patients with unknown or wild-type epidermal growth factor receptor status, according to results from the prospective phase III PROSE trial.

Patients classified as VeriStrat "good" had the same median overall survival of 10.92 months with chemotherapy and of 10.95 months with erlotinib (Tarceva) (hazard ratio 1.06; P = .714).

VeriStrat "poor" patients, however, derived a significant survival benefit from chemotherapy, with a median survival of 6.38 months vs. 2.98 months with erlotinib (HR 1.72; P = .022).

The interaction between treatment outcome and VeriStrat classification was statistically significant (HR 1.85; P = .031), Dr. Vanessa Gregorc reported at the annual meeting of the American Society of Clinical Oncology.

Erlotinib, an antiepidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is frequently used in patients who harbor an EGFR mutation, but about 90% of non-Asian patients are EGFR wild-type and 35%-45% are never tested for EGFR status.

Patrice Wendling/IMNG Medical Media

VeriStrat is a serum protein test that uses mass spectrometry technique – Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) – and proprietary algorithms to analyze proteins in a patient’s serum, according to the manufacturer, Biodesix.

The VeriStrat test is already known to be of value in identifying good versus poor prognosis in NSCLC patients. Initial retrospective validation studies showed that pretreatment classification with VeriStrat correlated with overall survival after treatment with EGFR-TKIs, but not with chemotherapy. Additional retrospective studies have shown the test to be both predictive and prognostic, explained Dr. Gregorc of the San Raffaele Scientific Institute, Milan.

There have been some doubts about whether the VeriStrat signature was only prognostic, but now "... we know VeriStrat is also predictive," said Dr. Luis Paz-Ares of Virgen Del Rocio University Hospital, Seville, Spain, who was invited to discuss the study.

Possibly more important, in a subanalysis restricted to only EGFR wild-type patients, the hazard ratio was even higher (1.94) and the VeriStrat treatment interaction was significant (P = .024), he added.

PROSE study

PROSE (Randomized Proteomic Stratified Phase III Study of Second Line Erlotinib versus Chemotherapy in Patients with Inoperable Non–Small-Cell Lung Cancer) involved 285 patients at 14 centers across Italy who had stage IIIb or IV inoperable NSCLC treated with one previous line of platinum-based chemotherapy and no EGFR-TKIs. Patients were stratified by ECOG performance status, smoking status, and blinded pretreatment VeriStrat classification, and randomly assigned within 5 working days of their blood draw to receive erlotinib or chemotherapy with pemetrexed or docetaxel at standard doses.

Among the 263 patients evaluable for the primary analysis, 129 received chemotherapy, of which 88 were VeriStrat classified as good and 41 as poor, and 134 received erlotinib, of which 96 were VeriStrat classified as good and 38 as poor.

EGFR mutation status analysis was performed in 190 of the 263 evaluable patients and indicated that 91 of 97 (94%) chemotherapy patients tested and 85 of 93 (91%) erlotinib patients tested were EGFR wild-type.

Median overall survival was 9.0 months with chemotherapy and 7.7 months with erlotinib (HR 1.14; P = .313), Dr. Gregorc reported.

In a survival analysis adjusted for several potential confounding factors, ECOG performance status 2 vs. 0-1 (HR 2.55; P less than .001) and VeriStrat poor vs. good classification (HR 1.89; P = .002) were prognostic for outcome independent of treatment. VeriStrat was predictive of a significant differential treatment benefit between chemotherapy and erlotinib (HR 1.98; P = .022).

During a discussion of the study, Dr. Tony Mok, lead investigator for the pivotal IPASS (Iressa Pan Asian Study), said he agreed that VeriStrat was predictive in patients with EGFR-negative status, but wasn’t sure about this conclusion for patients with unknown mutation status "because the proportion with EGFR-mutation positive likely had higher predictive power than what the VeriStrat can offer."

Dr. Gregorc said the sample sizes aren’t representative of what they’d planned to show, but that additional analyses are supportive of the findings.

"Our suggestion is, if you can, do the analysis with tissue," she said. "If you can’t or the patients have EGFR mutations, this is what you have to drive your clinical decision."

Another attendee described PROSE as an important trial, but said it "feels like the cake is only half baked" without data on progression-free survival and response rates. Dr. Gregorc responded that they didn’t have sufficient time to complete a thorough progression-free survival analysis before the meeting, and that these data will be presented at the European Society for Medical Oncology meeting this fall.

DELTA study

Data presented during the same session from the phase III DELTA (Docetaxel and Erlotinib Lung Cancer Trial) reinforced the role of chemotherapy over erlotinib in the second- and third-line setting of advanced NSCLC patients with EGFR wild-type status.

Among all 301 EGFR-unselected Japanese patients, docetaxel chemotherapy and erlotinib resulted in similar median progression-free (3.2 months vs. 2.0 months; HR 1.22; P = .092) and overall survival (12.2 months vs. 14.8 months; HR 0.90; P = .527).

Among the subset of 199 patients found to be EGFR wild-type, however, median progression-free survival was significantly longer at 2.9 months with chemotherapy vs. 1.3 months with erlotinib (HR 1.45; P = .01). A Cox regression analysis that adjusted for gender, performance status, and histology confirmed this benefit of chemotherapy on progression (HR 1.57; no P value given), said Dr. Yoshio Okana of Kochi (Japan) National Hospital.

Further, EGFR wild-type patients given chemotherapy had significantly better response rates (20% vs. 5.6%; P = .003) and disease control (70.6% vs. 53%; P = .017), although overall survival was similar (10.1 months vs. 9.0 months; HR 0.97; P .907), he said.

PROSE was funded by the Italian Ministry of Health, Italian Association for Cancer Research, and a grant from Biodesix. Dr. Gregorc reported no financial conflicts; several coauthors reported ties with Biodesix. DELTA was funded by the Japanese National Health Organization. Dr. Okano reported no conflicts; several coauthors reported ties with Chugai Pharma and Sanofi.

pwendling@frontlinemedcom.com

CHICAGO – The VeriStrat test is useful in guiding second-line treatment decisions in non–small-cell lung cancer patients with unknown or wild-type epidermal growth factor receptor status, according to results from the prospective phase III PROSE trial.

Patients classified as VeriStrat "good" had the same median overall survival of 10.92 months with chemotherapy and of 10.95 months with erlotinib (Tarceva) (hazard ratio 1.06; P = .714).

VeriStrat "poor" patients, however, derived a significant survival benefit from chemotherapy, with a median survival of 6.38 months vs. 2.98 months with erlotinib (HR 1.72; P = .022).

The interaction between treatment outcome and VeriStrat classification was statistically significant (HR 1.85; P = .031), Dr. Vanessa Gregorc reported at the annual meeting of the American Society of Clinical Oncology.

Erlotinib, an antiepidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is frequently used in patients who harbor an EGFR mutation, but about 90% of non-Asian patients are EGFR wild-type and 35%-45% are never tested for EGFR status.

Patrice Wendling/IMNG Medical Media

VeriStrat is a serum protein test that uses mass spectrometry technique – Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) – and proprietary algorithms to analyze proteins in a patient’s serum, according to the manufacturer, Biodesix.

The VeriStrat test is already known to be of value in identifying good versus poor prognosis in NSCLC patients. Initial retrospective validation studies showed that pretreatment classification with VeriStrat correlated with overall survival after treatment with EGFR-TKIs, but not with chemotherapy. Additional retrospective studies have shown the test to be both predictive and prognostic, explained Dr. Gregorc of the San Raffaele Scientific Institute, Milan.

There have been some doubts about whether the VeriStrat signature was only prognostic, but now "... we know VeriStrat is also predictive," said Dr. Luis Paz-Ares of Virgen Del Rocio University Hospital, Seville, Spain, who was invited to discuss the study.

Possibly more important, in a subanalysis restricted to only EGFR wild-type patients, the hazard ratio was even higher (1.94) and the VeriStrat treatment interaction was significant (P = .024), he added.

PROSE study

PROSE (Randomized Proteomic Stratified Phase III Study of Second Line Erlotinib versus Chemotherapy in Patients with Inoperable Non–Small-Cell Lung Cancer) involved 285 patients at 14 centers across Italy who had stage IIIb or IV inoperable NSCLC treated with one previous line of platinum-based chemotherapy and no EGFR-TKIs. Patients were stratified by ECOG performance status, smoking status, and blinded pretreatment VeriStrat classification, and randomly assigned within 5 working days of their blood draw to receive erlotinib or chemotherapy with pemetrexed or docetaxel at standard doses.

Among the 263 patients evaluable for the primary analysis, 129 received chemotherapy, of which 88 were VeriStrat classified as good and 41 as poor, and 134 received erlotinib, of which 96 were VeriStrat classified as good and 38 as poor.

EGFR mutation status analysis was performed in 190 of the 263 evaluable patients and indicated that 91 of 97 (94%) chemotherapy patients tested and 85 of 93 (91%) erlotinib patients tested were EGFR wild-type.

Median overall survival was 9.0 months with chemotherapy and 7.7 months with erlotinib (HR 1.14; P = .313), Dr. Gregorc reported.

In a survival analysis adjusted for several potential confounding factors, ECOG performance status 2 vs. 0-1 (HR 2.55; P less than .001) and VeriStrat poor vs. good classification (HR 1.89; P = .002) were prognostic for outcome independent of treatment. VeriStrat was predictive of a significant differential treatment benefit between chemotherapy and erlotinib (HR 1.98; P = .022).

During a discussion of the study, Dr. Tony Mok, lead investigator for the pivotal IPASS (Iressa Pan Asian Study), said he agreed that VeriStrat was predictive in patients with EGFR-negative status, but wasn’t sure about this conclusion for patients with unknown mutation status "because the proportion with EGFR-mutation positive likely had higher predictive power than what the VeriStrat can offer."

Dr. Gregorc said the sample sizes aren’t representative of what they’d planned to show, but that additional analyses are supportive of the findings.

"Our suggestion is, if you can, do the analysis with tissue," she said. "If you can’t or the patients have EGFR mutations, this is what you have to drive your clinical decision."

Another attendee described PROSE as an important trial, but said it "feels like the cake is only half baked" without data on progression-free survival and response rates. Dr. Gregorc responded that they didn’t have sufficient time to complete a thorough progression-free survival analysis before the meeting, and that these data will be presented at the European Society for Medical Oncology meeting this fall.

DELTA study

Data presented during the same session from the phase III DELTA (Docetaxel and Erlotinib Lung Cancer Trial) reinforced the role of chemotherapy over erlotinib in the second- and third-line setting of advanced NSCLC patients with EGFR wild-type status.

Among all 301 EGFR-unselected Japanese patients, docetaxel chemotherapy and erlotinib resulted in similar median progression-free (3.2 months vs. 2.0 months; HR 1.22; P = .092) and overall survival (12.2 months vs. 14.8 months; HR 0.90; P = .527).

Among the subset of 199 patients found to be EGFR wild-type, however, median progression-free survival was significantly longer at 2.9 months with chemotherapy vs. 1.3 months with erlotinib (HR 1.45; P = .01). A Cox regression analysis that adjusted for gender, performance status, and histology confirmed this benefit of chemotherapy on progression (HR 1.57; no P value given), said Dr. Yoshio Okana of Kochi (Japan) National Hospital.

Further, EGFR wild-type patients given chemotherapy had significantly better response rates (20% vs. 5.6%; P = .003) and disease control (70.6% vs. 53%; P = .017), although overall survival was similar (10.1 months vs. 9.0 months; HR 0.97; P .907), he said.

PROSE was funded by the Italian Ministry of Health, Italian Association for Cancer Research, and a grant from Biodesix. Dr. Gregorc reported no financial conflicts; several coauthors reported ties with Biodesix. DELTA was funded by the Japanese National Health Organization. Dr. Okano reported no conflicts; several coauthors reported ties with Chugai Pharma and Sanofi.

pwendling@frontlinemedcom.com

CHICAGO – The VeriStrat test is useful in guiding second-line treatment decisions in non–small-cell lung cancer patients with unknown or wild-type epidermal growth factor receptor status, according to results from the prospective phase III PROSE trial.

Patients classified as VeriStrat "good" had the same median overall survival of 10.92 months with chemotherapy and of 10.95 months with erlotinib (Tarceva) (hazard ratio 1.06; P = .714).

VeriStrat "poor" patients, however, derived a significant survival benefit from chemotherapy, with a median survival of 6.38 months vs. 2.98 months with erlotinib (HR 1.72; P = .022).

The interaction between treatment outcome and VeriStrat classification was statistically significant (HR 1.85; P = .031), Dr. Vanessa Gregorc reported at the annual meeting of the American Society of Clinical Oncology.

Erlotinib, an antiepidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is frequently used in patients who harbor an EGFR mutation, but about 90% of non-Asian patients are EGFR wild-type and 35%-45% are never tested for EGFR status.

Patrice Wendling/IMNG Medical Media

VeriStrat is a serum protein test that uses mass spectrometry technique – Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) – and proprietary algorithms to analyze proteins in a patient’s serum, according to the manufacturer, Biodesix.

The VeriStrat test is already known to be of value in identifying good versus poor prognosis in NSCLC patients. Initial retrospective validation studies showed that pretreatment classification with VeriStrat correlated with overall survival after treatment with EGFR-TKIs, but not with chemotherapy. Additional retrospective studies have shown the test to be both predictive and prognostic, explained Dr. Gregorc of the San Raffaele Scientific Institute, Milan.

There have been some doubts about whether the VeriStrat signature was only prognostic, but now "... we know VeriStrat is also predictive," said Dr. Luis Paz-Ares of Virgen Del Rocio University Hospital, Seville, Spain, who was invited to discuss the study.

Possibly more important, in a subanalysis restricted to only EGFR wild-type patients, the hazard ratio was even higher (1.94) and the VeriStrat treatment interaction was significant (P = .024), he added.

PROSE study

PROSE (Randomized Proteomic Stratified Phase III Study of Second Line Erlotinib versus Chemotherapy in Patients with Inoperable Non–Small-Cell Lung Cancer) involved 285 patients at 14 centers across Italy who had stage IIIb or IV inoperable NSCLC treated with one previous line of platinum-based chemotherapy and no EGFR-TKIs. Patients were stratified by ECOG performance status, smoking status, and blinded pretreatment VeriStrat classification, and randomly assigned within 5 working days of their blood draw to receive erlotinib or chemotherapy with pemetrexed or docetaxel at standard doses.

Among the 263 patients evaluable for the primary analysis, 129 received chemotherapy, of which 88 were VeriStrat classified as good and 41 as poor, and 134 received erlotinib, of which 96 were VeriStrat classified as good and 38 as poor.

EGFR mutation status analysis was performed in 190 of the 263 evaluable patients and indicated that 91 of 97 (94%) chemotherapy patients tested and 85 of 93 (91%) erlotinib patients tested were EGFR wild-type.

Median overall survival was 9.0 months with chemotherapy and 7.7 months with erlotinib (HR 1.14; P = .313), Dr. Gregorc reported.

In a survival analysis adjusted for several potential confounding factors, ECOG performance status 2 vs. 0-1 (HR 2.55; P less than .001) and VeriStrat poor vs. good classification (HR 1.89; P = .002) were prognostic for outcome independent of treatment. VeriStrat was predictive of a significant differential treatment benefit between chemotherapy and erlotinib (HR 1.98; P = .022).

During a discussion of the study, Dr. Tony Mok, lead investigator for the pivotal IPASS (Iressa Pan Asian Study), said he agreed that VeriStrat was predictive in patients with EGFR-negative status, but wasn’t sure about this conclusion for patients with unknown mutation status "because the proportion with EGFR-mutation positive likely had higher predictive power than what the VeriStrat can offer."

Dr. Gregorc said the sample sizes aren’t representative of what they’d planned to show, but that additional analyses are supportive of the findings.

"Our suggestion is, if you can, do the analysis with tissue," she said. "If you can’t or the patients have EGFR mutations, this is what you have to drive your clinical decision."

Another attendee described PROSE as an important trial, but said it "feels like the cake is only half baked" without data on progression-free survival and response rates. Dr. Gregorc responded that they didn’t have sufficient time to complete a thorough progression-free survival analysis before the meeting, and that these data will be presented at the European Society for Medical Oncology meeting this fall.

DELTA study

Data presented during the same session from the phase III DELTA (Docetaxel and Erlotinib Lung Cancer Trial) reinforced the role of chemotherapy over erlotinib in the second- and third-line setting of advanced NSCLC patients with EGFR wild-type status.

Among all 301 EGFR-unselected Japanese patients, docetaxel chemotherapy and erlotinib resulted in similar median progression-free (3.2 months vs. 2.0 months; HR 1.22; P = .092) and overall survival (12.2 months vs. 14.8 months; HR 0.90; P = .527).

Among the subset of 199 patients found to be EGFR wild-type, however, median progression-free survival was significantly longer at 2.9 months with chemotherapy vs. 1.3 months with erlotinib (HR 1.45; P = .01). A Cox regression analysis that adjusted for gender, performance status, and histology confirmed this benefit of chemotherapy on progression (HR 1.57; no P value given), said Dr. Yoshio Okana of Kochi (Japan) National Hospital.

Further, EGFR wild-type patients given chemotherapy had significantly better response rates (20% vs. 5.6%; P = .003) and disease control (70.6% vs. 53%; P = .017), although overall survival was similar (10.1 months vs. 9.0 months; HR 0.97; P .907), he said.

PROSE was funded by the Italian Ministry of Health, Italian Association for Cancer Research, and a grant from Biodesix. Dr. Gregorc reported no financial conflicts; several coauthors reported ties with Biodesix. DELTA was funded by the Japanese National Health Organization. Dr. Okano reported no conflicts; several coauthors reported ties with Chugai Pharma and Sanofi.

pwendling@frontlinemedcom.com

WASHINGTON – Beta-lactam monotherapy is likely to be just as effective as a combination of beta-lactam and macrolide therapy for the majority of children hospitalized with pneumonia, a study has shown.

A subanalysis of a large national study found no difference in the length of hospital stay for children with pneumonia, whether they had received ceftriaxone alone or in combination with azithromycin, Dr. Derek J. Williams said at the annual meeting of the Pediatric Academic Societies.

"This is an important finding, because we know that limiting antimicrobial use to the narrowest-spectrum agent for the shortest duration is imperative to slow the epidemic of antimicrobial resistance," said Dr. Williams, a pediatrician in the division of hospital medicine at Vanderbilt University, Nashville, Tenn.

His large retrospective study used data collected in the Etiology of Pneumonia in the Community (EPIC) study. Sponsored by the Centers for Disease Control and Prevention, EPIC now contains information on 1,496 children.

Dr. Williams’ study involved 941 children who were admitted to hospitals with presumed community-acquired pneumonia. Most of these (678) were treated with ceftriaxone alone; 263 received combination therapy with ceftriaxone and azithromycin.

There were some important baseline differences between the groups, Dr. Williams noted. Children in the combination group were significantly older than those in the monotherapy* group (median, 64 months vs. 19 months). They were also significantly more likely to have asthma (44% vs. 35%) or other high-risk comorbidities including cardiopulmonary, oncologic, or immunosuppressive conditions; hepatic or renal problems; metabolic or genetic issues; and neurodevelopmental disorders.

The median length of hospital stay was 64 hours in both groups. Neither an unadjusted nor adjusted analysis found any significant relationship between therapy type and length of stay.

A propensity score matching looked at the outcome in 190 children in each exposure group. It too found no significant relationships.

The results are in line with a national pediatric pneumonia treatment guideline, published in 2011 in Clinical Infectious Diseases (53:617-30),Dr. Williams said.

During discussion, however, he noted that the conclusions may be somewhat marred by the nature of the EPIC cohort. "Although more than 80% of EPIC children received antibiotics, a bacterial pathogen was identified in only 15%."

This prompted some comment from pediatric hospitalist Mark W. Shen of the Dell Children’s Medical Center of Central Texas, Austin.

"The EPIC study is probably one of our most robust studies looking at the etiology of community-acquired pneumonia in hospitalized kids," he said. "But it seems now that you could argue that potentially more than 85% of these could have a viral etiology for their disease. So that would make it exceedingly difficult to find any inherent differences in antibiotic treatment. Is there any gold standard for figuring out how we can assess the comparative effectiveness, if most of these cases could be viral?

"This is the big issue that we struggle with," said Dr. Williams. "How do we define bacterial pneumonia? Our methods for detecting viruses are far superior to those we use to detect bacteria. I think this is coming with biomarkers, but we are not there yet. I think we’re underestimating bacterial disease and coinfections, but I also think that retrospective data are just not as good as prospective. Until we are able to really define this, that’s going to be a difficult question to answer."

Dr. Shen was also an author on a poster at the meeting. His study found that the hospitalist changed or stopped antibiotics in 93% of children with pneumonia who were started on one during the emergency department visit. "Sixty percent of the time, we found that there was no difference in their outcomes," he said.

The EPIC study is funded by the Centers for Disease Control and Prevention. Dr. Williams said he had no relevant financial disclosures. Dr. Shen was listed in the program as having no financial disclosures.

msullivan@frontlinemedcom.com

*Correction, 6/26/13: An earlier version of this story misstated the type of therapy group in the description of the study.

WASHINGTON – Beta-lactam monotherapy is likely to be just as effective as a combination of beta-lactam and macrolide therapy for the majority of children hospitalized with pneumonia, a study has shown.

A subanalysis of a large national study found no difference in the length of hospital stay for children with pneumonia, whether they had received ceftriaxone alone or in combination with azithromycin, Dr. Derek J. Williams said at the annual meeting of the Pediatric Academic Societies.

"This is an important finding, because we know that limiting antimicrobial use to the narrowest-spectrum agent for the shortest duration is imperative to slow the epidemic of antimicrobial resistance," said Dr. Williams, a pediatrician in the division of hospital medicine at Vanderbilt University, Nashville, Tenn.

His large retrospective study used data collected in the Etiology of Pneumonia in the Community (EPIC) study. Sponsored by the Centers for Disease Control and Prevention, EPIC now contains information on 1,496 children.

Dr. Williams’ study involved 941 children who were admitted to hospitals with presumed community-acquired pneumonia. Most of these (678) were treated with ceftriaxone alone; 263 received combination therapy with ceftriaxone and azithromycin.

There were some important baseline differences between the groups, Dr. Williams noted. Children in the combination group were significantly older than those in the monotherapy* group (median, 64 months vs. 19 months). They were also significantly more likely to have asthma (44% vs. 35%) or other high-risk comorbidities including cardiopulmonary, oncologic, or immunosuppressive conditions; hepatic or renal problems; metabolic or genetic issues; and neurodevelopmental disorders.

The median length of hospital stay was 64 hours in both groups. Neither an unadjusted nor adjusted analysis found any significant relationship between therapy type and length of stay.

A propensity score matching looked at the outcome in 190 children in each exposure group. It too found no significant relationships.

The results are in line with a national pediatric pneumonia treatment guideline, published in 2011 in Clinical Infectious Diseases (53:617-30),Dr. Williams said.

During discussion, however, he noted that the conclusions may be somewhat marred by the nature of the EPIC cohort. "Although more than 80% of EPIC children received antibiotics, a bacterial pathogen was identified in only 15%."

This prompted some comment from pediatric hospitalist Mark W. Shen of the Dell Children’s Medical Center of Central Texas, Austin.

"The EPIC study is probably one of our most robust studies looking at the etiology of community-acquired pneumonia in hospitalized kids," he said. "But it seems now that you could argue that potentially more than 85% of these could have a viral etiology for their disease. So that would make it exceedingly difficult to find any inherent differences in antibiotic treatment. Is there any gold standard for figuring out how we can assess the comparative effectiveness, if most of these cases could be viral?

"This is the big issue that we struggle with," said Dr. Williams. "How do we define bacterial pneumonia? Our methods for detecting viruses are far superior to those we use to detect bacteria. I think this is coming with biomarkers, but we are not there yet. I think we’re underestimating bacterial disease and coinfections, but I also think that retrospective data are just not as good as prospective. Until we are able to really define this, that’s going to be a difficult question to answer."

Dr. Shen was also an author on a poster at the meeting. His study found that the hospitalist changed or stopped antibiotics in 93% of children with pneumonia who were started on one during the emergency department visit. "Sixty percent of the time, we found that there was no difference in their outcomes," he said.

The EPIC study is funded by the Centers for Disease Control and Prevention. Dr. Williams said he had no relevant financial disclosures. Dr. Shen was listed in the program as having no financial disclosures.

msullivan@frontlinemedcom.com

*Correction, 6/26/13: An earlier version of this story misstated the type of therapy group in the description of the study.

WASHINGTON – Beta-lactam monotherapy is likely to be just as effective as a combination of beta-lactam and macrolide therapy for the majority of children hospitalized with pneumonia, a study has shown.

A subanalysis of a large national study found no difference in the length of hospital stay for children with pneumonia, whether they had received ceftriaxone alone or in combination with azithromycin, Dr. Derek J. Williams said at the annual meeting of the Pediatric Academic Societies.

"This is an important finding, because we know that limiting antimicrobial use to the narrowest-spectrum agent for the shortest duration is imperative to slow the epidemic of antimicrobial resistance," said Dr. Williams, a pediatrician in the division of hospital medicine at Vanderbilt University, Nashville, Tenn.

His large retrospective study used data collected in the Etiology of Pneumonia in the Community (EPIC) study. Sponsored by the Centers for Disease Control and Prevention, EPIC now contains information on 1,496 children.

Dr. Williams’ study involved 941 children who were admitted to hospitals with presumed community-acquired pneumonia. Most of these (678) were treated with ceftriaxone alone; 263 received combination therapy with ceftriaxone and azithromycin.

There were some important baseline differences between the groups, Dr. Williams noted. Children in the combination group were significantly older than those in the monotherapy* group (median, 64 months vs. 19 months). They were also significantly more likely to have asthma (44% vs. 35%) or other high-risk comorbidities including cardiopulmonary, oncologic, or immunosuppressive conditions; hepatic or renal problems; metabolic or genetic issues; and neurodevelopmental disorders.

The median length of hospital stay was 64 hours in both groups. Neither an unadjusted nor adjusted analysis found any significant relationship between therapy type and length of stay.

A propensity score matching looked at the outcome in 190 children in each exposure group. It too found no significant relationships.

The results are in line with a national pediatric pneumonia treatment guideline, published in 2011 in Clinical Infectious Diseases (53:617-30),Dr. Williams said.

During discussion, however, he noted that the conclusions may be somewhat marred by the nature of the EPIC cohort. "Although more than 80% of EPIC children received antibiotics, a bacterial pathogen was identified in only 15%."

This prompted some comment from pediatric hospitalist Mark W. Shen of the Dell Children’s Medical Center of Central Texas, Austin.

"The EPIC study is probably one of our most robust studies looking at the etiology of community-acquired pneumonia in hospitalized kids," he said. "But it seems now that you could argue that potentially more than 85% of these could have a viral etiology for their disease. So that would make it exceedingly difficult to find any inherent differences in antibiotic treatment. Is there any gold standard for figuring out how we can assess the comparative effectiveness, if most of these cases could be viral?

"This is the big issue that we struggle with," said Dr. Williams. "How do we define bacterial pneumonia? Our methods for detecting viruses are far superior to those we use to detect bacteria. I think this is coming with biomarkers, but we are not there yet. I think we’re underestimating bacterial disease and coinfections, but I also think that retrospective data are just not as good as prospective. Until we are able to really define this, that’s going to be a difficult question to answer."

Dr. Shen was also an author on a poster at the meeting. His study found that the hospitalist changed or stopped antibiotics in 93% of children with pneumonia who were started on one during the emergency department visit. "Sixty percent of the time, we found that there was no difference in their outcomes," he said.

The EPIC study is funded by the Centers for Disease Control and Prevention. Dr. Williams said he had no relevant financial disclosures. Dr. Shen was listed in the program as having no financial disclosures.

msullivan@frontlinemedcom.com

*Correction, 6/26/13: An earlier version of this story misstated the type of therapy group in the description of the study.

The Centers for Disease Control and Prevention and the World Health Organization are continuing to monitor the spread of the newly named Middle East Respiratory Syndrome (MERS) caused by the MERS-Coronavirus (MERS-CoV). As of June 5, 2013, there were 55 confirmed cases worldwide (mostly in the Middle East) resulting in 30 fatalities (54.5%), according to the two organizations.

There is clear evidence of human-to-human transmission, the CDC reported in an overview presented on its website, with aerosol droplet and contact transmission both considered possible. As yet there have been no reports of infection in the United States, although the virus has reached Europe, including France, Italy, and the United Kingdom. The three cases reported in Italy in May were the most recent of the eight reported clusters and resulted from an index case that had recently traveled from Jordan after a 40-day visit. Two more patients were infected after having close contact with that individual.

Courtesy of Cynthia Goldsmith/Maureen Metcalfe/Azaibi Tamin

MERS-CoV (originally referred to as novel coronavirus or nCoV) genetic sequencing has shown that it is similar to coronaviruses found in bats and is not the same as the virus that caused severe acute respiratory syndrome (SARS) in 2003. Patients with MERS typically develop severe acute respiratory illness with symptoms of fever, cough, and shortness of breath, although some patients were reported as having only a mild respiratory illness.

The CDC has developed molecular diagnostic kits for MERS-CoV, which are being made available to state health departments. Although there are currently no travel advisories in place, the CDC is advising individuals who develop a fever and symptoms of lower respiratory illness (such as cough and shortness of breath) within 10 days of traveling from countries in the Arabian Peninsula or neighboring countries to see their health care providers and mention their recent travel. State and local health departments are advised to report patients under investigation (PUI) for MERS-CoV to CDC. These include patients who have all of the following characteristics:

• Acute respiratory infection, which may include a fever greater than or equal to 38° C and cough.

• Suspicion of pulmonary parenchymal disease.

• A history of travel from the Arabian Peninsula and neighboring countries (Bahrain, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen).

• No other etiology for the illness, including all clinically indicated tests for community acquired pneumonia.

Interim guidance documents for health care providers, health departments, and laboratories are available on the CDC website.

As yet, CDC officials have issued no travel advisories for the countries in which MERS has been detected, and they reported that they are in the process of discussing the development of possible vaccines with industry.

mlesney@frontlinemedcom.com

The Centers for Disease Control and Prevention and the World Health Organization are continuing to monitor the spread of the newly named Middle East Respiratory Syndrome (MERS) caused by the MERS-Coronavirus (MERS-CoV). As of June 5, 2013, there were 55 confirmed cases worldwide (mostly in the Middle East) resulting in 30 fatalities (54.5%), according to the two organizations.

There is clear evidence of human-to-human transmission, the CDC reported in an overview presented on its website, with aerosol droplet and contact transmission both considered possible. As yet there have been no reports of infection in the United States, although the virus has reached Europe, including France, Italy, and the United Kingdom. The three cases reported in Italy in May were the most recent of the eight reported clusters and resulted from an index case that had recently traveled from Jordan after a 40-day visit. Two more patients were infected after having close contact with that individual.

Courtesy of Cynthia Goldsmith/Maureen Metcalfe/Azaibi Tamin

MERS-CoV (originally referred to as novel coronavirus or nCoV) genetic sequencing has shown that it is similar to coronaviruses found in bats and is not the same as the virus that caused severe acute respiratory syndrome (SARS) in 2003. Patients with MERS typically develop severe acute respiratory illness with symptoms of fever, cough, and shortness of breath, although some patients were reported as having only a mild respiratory illness.

The CDC has developed molecular diagnostic kits for MERS-CoV, which are being made available to state health departments. Although there are currently no travel advisories in place, the CDC is advising individuals who develop a fever and symptoms of lower respiratory illness (such as cough and shortness of breath) within 10 days of traveling from countries in the Arabian Peninsula or neighboring countries to see their health care providers and mention their recent travel. State and local health departments are advised to report patients under investigation (PUI) for MERS-CoV to CDC. These include patients who have all of the following characteristics:

• Acute respiratory infection, which may include a fever greater than or equal to 38° C and cough.

• Suspicion of pulmonary parenchymal disease.

• A history of travel from the Arabian Peninsula and neighboring countries (Bahrain, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen).

• No other etiology for the illness, including all clinically indicated tests for community acquired pneumonia.

Interim guidance documents for health care providers, health departments, and laboratories are available on the CDC website.

As yet, CDC officials have issued no travel advisories for the countries in which MERS has been detected, and they reported that they are in the process of discussing the development of possible vaccines with industry.

mlesney@frontlinemedcom.com

The Centers for Disease Control and Prevention and the World Health Organization are continuing to monitor the spread of the newly named Middle East Respiratory Syndrome (MERS) caused by the MERS-Coronavirus (MERS-CoV). As of June 5, 2013, there were 55 confirmed cases worldwide (mostly in the Middle East) resulting in 30 fatalities (54.5%), according to the two organizations.

There is clear evidence of human-to-human transmission, the CDC reported in an overview presented on its website, with aerosol droplet and contact transmission both considered possible. As yet there have been no reports of infection in the United States, although the virus has reached Europe, including France, Italy, and the United Kingdom. The three cases reported in Italy in May were the most recent of the eight reported clusters and resulted from an index case that had recently traveled from Jordan after a 40-day visit. Two more patients were infected after having close contact with that individual.

Courtesy of Cynthia Goldsmith/Maureen Metcalfe/Azaibi Tamin

MERS-CoV (originally referred to as novel coronavirus or nCoV) genetic sequencing has shown that it is similar to coronaviruses found in bats and is not the same as the virus that caused severe acute respiratory syndrome (SARS) in 2003. Patients with MERS typically develop severe acute respiratory illness with symptoms of fever, cough, and shortness of breath, although some patients were reported as having only a mild respiratory illness.

The CDC has developed molecular diagnostic kits for MERS-CoV, which are being made available to state health departments. Although there are currently no travel advisories in place, the CDC is advising individuals who develop a fever and symptoms of lower respiratory illness (such as cough and shortness of breath) within 10 days of traveling from countries in the Arabian Peninsula or neighboring countries to see their health care providers and mention their recent travel. State and local health departments are advised to report patients under investigation (PUI) for MERS-CoV to CDC. These include patients who have all of the following characteristics:

• Acute respiratory infection, which may include a fever greater than or equal to 38° C and cough.

• Suspicion of pulmonary parenchymal disease.

• A history of travel from the Arabian Peninsula and neighboring countries (Bahrain, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen).

• No other etiology for the illness, including all clinically indicated tests for community acquired pneumonia.

Interim guidance documents for health care providers, health departments, and laboratories are available on the CDC website.

As yet, CDC officials have issued no travel advisories for the countries in which MERS has been detected, and they reported that they are in the process of discussing the development of possible vaccines with industry.

mlesney@frontlinemedcom.com