Doug Brunk

SAN DIEGO – Various T₂*-weighted MRI techniques are improving the ability to detect microbleeds, which are clear markers of hypertensive vasculopathy, cerebral amyloid angiopathy, and other underlying small vessel disease.

In fact, the more clinicians like Dr. Steven M. Greenberg look for them, the more they're finding.

“At some point we will not be able to get any more sensitive,” Dr. Greenberg said at the International Stroke Conference. “The brain is not one big micro-bleed. There will be some limit to how many we pick up, but for now the harder we look the more we find.”

Dr. Greenberg, a neurologist with the Hemorrhagic Stroke Research Program at Massachusetts General Hospital and Harvard Medical School, Boston, noted that advances in detection are coming at a time when the incidence of hypertensive vasculopathy and cerebral amyloid angiopathy are expected to rise as the Baby Boom generation continues to age. “These are not the only causes of microbleed, but these two processes are common and highly age associated,” he said. “With the aging of the population these have become important entities.”

Histology remains the accepted standard for detecting micro-bleeds, but Dr. Greenberg considers MRI superior to pathology from a practical standpoint because it has “tremendous sampling ability. Because of the sensitivity of MRI for iron deposits, we're able to get a full survey of the brain. While we'll never be able to replace the specificity of pathology for either identifying the bleeds themselves or the vascular diseases that go along with them, the sensitivity of MRI will supersede what is practical in an autopsy exam.”

Compared with conventional T₂-weighted MRI, T₂*-weighted MRI does not use a refocusing pulse, “so the dephasing caused by the paramagnetic iron is accentuated by the T₂*-weighted technique,” Dr. Greenberg explained. “Lesions that are entirely invisible on T₂ sequence become highly visible on the T₂* technique. So until you've looked with a T₂* technique you really haven't done a proper test to look for microbleeds.”

The most common micro-bleed mimics seen on MRI include mineral deposits, flow voids, bone/air artifacts, cavernous malformations, metastatic melanoma, and diffuse axonal injury.

According to detection criteria outlined by a group of experts including Dr. Greenberg, microbleeds should be black on T₂*-weighted MRI; blooming on T₂*-weighted MRI; devoid of signal hyperintensity on T₁- or T₂-weighted sequences; round or ovoid rather than linear; at least half surrounded by brain parenchyma; and be distinct from other potential mimics such as iron/calcium deposits, bone, or flow void; and should have a clinical history that excludes traumatic brain injury (Lancet Neurol. 2009;8:165-74).

The best clue to underlying disease may be location, Dr. Greenberg said. A deep hemispheric/brainstem pattern is suggestive of hypertensive vasculopathy while a strictly lobar pattern is suggestive of cerebral amyloid angiopathy.

Advances in T₂*-weighted MRI techniques are leading to further improvements in detection rates. These include increasing the echo time, which allows greater time for the dephasing of the paramagnetic signal; thinner scanning sections, which increase the signal-to-noise ratio; increasing the magnetic field strength; and image postprocessing techniques such as susceptibility-weighted imaging, which “incorporates the phase shift as well as the magnitude effects of the iron deposits to increase their visibility.”

Such advances in detection “will change our understanding of the prevalence of microbleed lesions,” Dr. Greenberg said. “This is a story that has to play itself out before we'll know where we land.

“It's a growth area–one that we as researchers and clinicians need to better understand the implications of.”

Dr. Greenberg disclosed that he has received grant and research support from the National Institutes of Health and the Alzheimer's Association.

T₂*-weighted, standard slice shows microbleeds in a 74-year-old woman.

A thin slice from the same woman identifies many more microbleeds. IMAGES COURTESY DR. STEVEN M. GREENBERG

There will be some limit to how many microbleeds we pick up, but for now the harder we look the more we find. DR. GREENBERG

SAN DIEGO – Various T₂*-weighted MRI techniques are improving the ability to detect microbleeds, which are clear markers of hypertensive vasculopathy, cerebral amyloid angiopathy, and other underlying small vessel disease.

In fact, the more clinicians like Dr. Steven M. Greenberg look for them, the more they're finding.

“At some point we will not be able to get any more sensitive,” Dr. Greenberg said at the International Stroke Conference. “The brain is not one big micro-bleed. There will be some limit to how many we pick up, but for now the harder we look the more we find.”

Dr. Greenberg, a neurologist with the Hemorrhagic Stroke Research Program at Massachusetts General Hospital and Harvard Medical School, Boston, noted that advances in detection are coming at a time when the incidence of hypertensive vasculopathy and cerebral amyloid angiopathy are expected to rise as the Baby Boom generation continues to age. “These are not the only causes of microbleed, but these two processes are common and highly age associated,” he said. “With the aging of the population these have become important entities.”

Histology remains the accepted standard for detecting micro-bleeds, but Dr. Greenberg considers MRI superior to pathology from a practical standpoint because it has “tremendous sampling ability. Because of the sensitivity of MRI for iron deposits, we're able to get a full survey of the brain. While we'll never be able to replace the specificity of pathology for either identifying the bleeds themselves or the vascular diseases that go along with them, the sensitivity of MRI will supersede what is practical in an autopsy exam.”

Compared with conventional T₂-weighted MRI, T₂*-weighted MRI does not use a refocusing pulse, “so the dephasing caused by the paramagnetic iron is accentuated by the T₂*-weighted technique,” Dr. Greenberg explained. “Lesions that are entirely invisible on T₂ sequence become highly visible on the T₂* technique. So until you've looked with a T₂* technique you really haven't done a proper test to look for microbleeds.”

The most common micro-bleed mimics seen on MRI include mineral deposits, flow voids, bone/air artifacts, cavernous malformations, metastatic melanoma, and diffuse axonal injury.

According to detection criteria outlined by a group of experts including Dr. Greenberg, microbleeds should be black on T₂*-weighted MRI; blooming on T₂*-weighted MRI; devoid of signal hyperintensity on T₁- or T₂-weighted sequences; round or ovoid rather than linear; at least half surrounded by brain parenchyma; and be distinct from other potential mimics such as iron/calcium deposits, bone, or flow void; and should have a clinical history that excludes traumatic brain injury (Lancet Neurol. 2009;8:165-74).

The best clue to underlying disease may be location, Dr. Greenberg said. A deep hemispheric/brainstem pattern is suggestive of hypertensive vasculopathy while a strictly lobar pattern is suggestive of cerebral amyloid angiopathy.

Advances in T₂*-weighted MRI techniques are leading to further improvements in detection rates. These include increasing the echo time, which allows greater time for the dephasing of the paramagnetic signal; thinner scanning sections, which increase the signal-to-noise ratio; increasing the magnetic field strength; and image postprocessing techniques such as susceptibility-weighted imaging, which “incorporates the phase shift as well as the magnitude effects of the iron deposits to increase their visibility.”

Such advances in detection “will change our understanding of the prevalence of microbleed lesions,” Dr. Greenberg said. “This is a story that has to play itself out before we'll know where we land.

“It's a growth area–one that we as researchers and clinicians need to better understand the implications of.”

Dr. Greenberg disclosed that he has received grant and research support from the National Institutes of Health and the Alzheimer's Association.

T₂*-weighted, standard slice shows microbleeds in a 74-year-old woman.

A thin slice from the same woman identifies many more microbleeds. IMAGES COURTESY DR. STEVEN M. GREENBERG

There will be some limit to how many microbleeds we pick up, but for now the harder we look the more we find. DR. GREENBERG

SAN DIEGO – Various T₂*-weighted MRI techniques are improving the ability to detect microbleeds, which are clear markers of hypertensive vasculopathy, cerebral amyloid angiopathy, and other underlying small vessel disease.

In fact, the more clinicians like Dr. Steven M. Greenberg look for them, the more they're finding.

“At some point we will not be able to get any more sensitive,” Dr. Greenberg said at the International Stroke Conference. “The brain is not one big micro-bleed. There will be some limit to how many we pick up, but for now the harder we look the more we find.”

Dr. Greenberg, a neurologist with the Hemorrhagic Stroke Research Program at Massachusetts General Hospital and Harvard Medical School, Boston, noted that advances in detection are coming at a time when the incidence of hypertensive vasculopathy and cerebral amyloid angiopathy are expected to rise as the Baby Boom generation continues to age. “These are not the only causes of microbleed, but these two processes are common and highly age associated,” he said. “With the aging of the population these have become important entities.”

Histology remains the accepted standard for detecting micro-bleeds, but Dr. Greenberg considers MRI superior to pathology from a practical standpoint because it has “tremendous sampling ability. Because of the sensitivity of MRI for iron deposits, we're able to get a full survey of the brain. While we'll never be able to replace the specificity of pathology for either identifying the bleeds themselves or the vascular diseases that go along with them, the sensitivity of MRI will supersede what is practical in an autopsy exam.”

Compared with conventional T₂-weighted MRI, T₂*-weighted MRI does not use a refocusing pulse, “so the dephasing caused by the paramagnetic iron is accentuated by the T₂*-weighted technique,” Dr. Greenberg explained. “Lesions that are entirely invisible on T₂ sequence become highly visible on the T₂* technique. So until you've looked with a T₂* technique you really haven't done a proper test to look for microbleeds.”

The most common micro-bleed mimics seen on MRI include mineral deposits, flow voids, bone/air artifacts, cavernous malformations, metastatic melanoma, and diffuse axonal injury.

According to detection criteria outlined by a group of experts including Dr. Greenberg, microbleeds should be black on T₂*-weighted MRI; blooming on T₂*-weighted MRI; devoid of signal hyperintensity on T₁- or T₂-weighted sequences; round or ovoid rather than linear; at least half surrounded by brain parenchyma; and be distinct from other potential mimics such as iron/calcium deposits, bone, or flow void; and should have a clinical history that excludes traumatic brain injury (Lancet Neurol. 2009;8:165-74).

The best clue to underlying disease may be location, Dr. Greenberg said. A deep hemispheric/brainstem pattern is suggestive of hypertensive vasculopathy while a strictly lobar pattern is suggestive of cerebral amyloid angiopathy.

Advances in T₂*-weighted MRI techniques are leading to further improvements in detection rates. These include increasing the echo time, which allows greater time for the dephasing of the paramagnetic signal; thinner scanning sections, which increase the signal-to-noise ratio; increasing the magnetic field strength; and image postprocessing techniques such as susceptibility-weighted imaging, which “incorporates the phase shift as well as the magnitude effects of the iron deposits to increase their visibility.”

Such advances in detection “will change our understanding of the prevalence of microbleed lesions,” Dr. Greenberg said. “This is a story that has to play itself out before we'll know where we land.

“It's a growth area–one that we as researchers and clinicians need to better understand the implications of.”

Dr. Greenberg disclosed that he has received grant and research support from the National Institutes of Health and the Alzheimer's Association.

T₂*-weighted, standard slice shows microbleeds in a 74-year-old woman.

A thin slice from the same woman identifies many more microbleeds. IMAGES COURTESY DR. STEVEN M. GREENBERG

There will be some limit to how many microbleeds we pick up, but for now the harder we look the more we find. DR. GREENBERG

SAN DIEGO — Community-associated methicillin-resistant Staphylococcus aureus genotypes have emerged as a cause of MRSA nares colonization among patients admitted to adult ICUs in the United States.

In addition, patients with a history of previous hospitalization and those older in age were significantly less likely to be colonized with community-associated MRSA (CA-MRSA) genotypes.

Those are the key findings from an effort to examine the molecular epidemiology and assess the prevalence of and risk factors for CA-MRSA genotype carriage among patients admitted to adult ICUs.

The molecular epidemiology of MRSA in the health care setting is incompletely defined, Dr. Henry M. Blumberg said at the annual meeting of the Society for Healthcare Epidemiology of America.

Dr. Blumberg and his associates studied 5,512 adult ICU visits at 18 academic medical centers that participated in the STAR-ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial. STAR-ICU, a National Institutes of Health-funded trial, is designed to evaluate the effectiveness of a package of infection control strategies focused on active surveillance cultures and barrier precautions in reducing transmission of MRSA and vancomycin-resistant enterococci (VRE) among adults in ICUs for 3 or more days.

CA-MRSA genotypes were defined as USA300, USA400, and USA1000 while health care-associated MRSA genotypes (HA-MRSA) were defined as USA100, USA200, USA500, USA600, USA800, the epidemic strain EMRSA-15, and the Brazilian clone.

Of the 5,512 patients, 626 (11%) had a positive culture for MRSA, reported Dr. Blumberg, professor of medicine and epidemiology in the division of infectious diseases at Emory University, Atlanta.

Of 210 isolates available for molecular typing, 70% were the USA100 clone, 12% were USA300, 6% were USA500, 4% were USA800, 3% were the Brazilian clone, 2% were USA600, 1% were USA1000, 1% were USA-200, 0.5% were USA400, and 0.5% were EMRSA-15.

Overall, 14% of patients had CA-MRSA colonization.

Univariate analysis revealed that compared with patients colonized with HA-MRSA genotypes, those colonized with CA-MRSA genotypes were significantly younger (51 years vs. 65 years), significantly less likely to have been hospitalized in the previous 12 months (47% vs. 74%), and significantly less likely to have a history of MRSA or VRE colonization or infection (13% vs. 37%). Multivariate analysis revealed similar findings.

“These findings suggest that the predominant site of MRSA acquisition remains in the community,” Dr. Blumberg concluded.

He said he had no conflicts of interest to disclose.

SAN DIEGO — Community-associated methicillin-resistant Staphylococcus aureus genotypes have emerged as a cause of MRSA nares colonization among patients admitted to adult ICUs in the United States.

In addition, patients with a history of previous hospitalization and those older in age were significantly less likely to be colonized with community-associated MRSA (CA-MRSA) genotypes.

Those are the key findings from an effort to examine the molecular epidemiology and assess the prevalence of and risk factors for CA-MRSA genotype carriage among patients admitted to adult ICUs.

The molecular epidemiology of MRSA in the health care setting is incompletely defined, Dr. Henry M. Blumberg said at the annual meeting of the Society for Healthcare Epidemiology of America.

Dr. Blumberg and his associates studied 5,512 adult ICU visits at 18 academic medical centers that participated in the STAR-ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial. STAR-ICU, a National Institutes of Health-funded trial, is designed to evaluate the effectiveness of a package of infection control strategies focused on active surveillance cultures and barrier precautions in reducing transmission of MRSA and vancomycin-resistant enterococci (VRE) among adults in ICUs for 3 or more days.

CA-MRSA genotypes were defined as USA300, USA400, and USA1000 while health care-associated MRSA genotypes (HA-MRSA) were defined as USA100, USA200, USA500, USA600, USA800, the epidemic strain EMRSA-15, and the Brazilian clone.

Of the 5,512 patients, 626 (11%) had a positive culture for MRSA, reported Dr. Blumberg, professor of medicine and epidemiology in the division of infectious diseases at Emory University, Atlanta.

Of 210 isolates available for molecular typing, 70% were the USA100 clone, 12% were USA300, 6% were USA500, 4% were USA800, 3% were the Brazilian clone, 2% were USA600, 1% were USA1000, 1% were USA-200, 0.5% were USA400, and 0.5% were EMRSA-15.

Overall, 14% of patients had CA-MRSA colonization.

Univariate analysis revealed that compared with patients colonized with HA-MRSA genotypes, those colonized with CA-MRSA genotypes were significantly younger (51 years vs. 65 years), significantly less likely to have been hospitalized in the previous 12 months (47% vs. 74%), and significantly less likely to have a history of MRSA or VRE colonization or infection (13% vs. 37%). Multivariate analysis revealed similar findings.

“These findings suggest that the predominant site of MRSA acquisition remains in the community,” Dr. Blumberg concluded.

He said he had no conflicts of interest to disclose.

SAN DIEGO — Community-associated methicillin-resistant Staphylococcus aureus genotypes have emerged as a cause of MRSA nares colonization among patients admitted to adult ICUs in the United States.

In addition, patients with a history of previous hospitalization and those older in age were significantly less likely to be colonized with community-associated MRSA (CA-MRSA) genotypes.

Those are the key findings from an effort to examine the molecular epidemiology and assess the prevalence of and risk factors for CA-MRSA genotype carriage among patients admitted to adult ICUs.

The molecular epidemiology of MRSA in the health care setting is incompletely defined, Dr. Henry M. Blumberg said at the annual meeting of the Society for Healthcare Epidemiology of America.

Dr. Blumberg and his associates studied 5,512 adult ICU visits at 18 academic medical centers that participated in the STAR-ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial. STAR-ICU, a National Institutes of Health-funded trial, is designed to evaluate the effectiveness of a package of infection control strategies focused on active surveillance cultures and barrier precautions in reducing transmission of MRSA and vancomycin-resistant enterococci (VRE) among adults in ICUs for 3 or more days.

CA-MRSA genotypes were defined as USA300, USA400, and USA1000 while health care-associated MRSA genotypes (HA-MRSA) were defined as USA100, USA200, USA500, USA600, USA800, the epidemic strain EMRSA-15, and the Brazilian clone.

Of the 5,512 patients, 626 (11%) had a positive culture for MRSA, reported Dr. Blumberg, professor of medicine and epidemiology in the division of infectious diseases at Emory University, Atlanta.

Of 210 isolates available for molecular typing, 70% were the USA100 clone, 12% were USA300, 6% were USA500, 4% were USA800, 3% were the Brazilian clone, 2% were USA600, 1% were USA1000, 1% were USA-200, 0.5% were USA400, and 0.5% were EMRSA-15.

Overall, 14% of patients had CA-MRSA colonization.

Univariate analysis revealed that compared with patients colonized with HA-MRSA genotypes, those colonized with CA-MRSA genotypes were significantly younger (51 years vs. 65 years), significantly less likely to have been hospitalized in the previous 12 months (47% vs. 74%), and significantly less likely to have a history of MRSA or VRE colonization or infection (13% vs. 37%). Multivariate analysis revealed similar findings.

“These findings suggest that the predominant site of MRSA acquisition remains in the community,” Dr. Blumberg concluded.

He said he had no conflicts of interest to disclose.

SAN DIEGO — Two medical centers of similar size located in the northeastern United States that use different methicillin-resistant Staphylococcus aureus infection control strategies have very similar rates of hospital-onset MRSA infection, results from a year-long analysis showed.

“Our study illustrates the need for these kinds of comparisons so we can decide which MRSA infection control strategies work best,” lead investigator Dr. Kathryn B. Kirkland said at the annual meeting of the Society for Healthcare Epidemiology of America. “We need to expand the set of measures that we have that will allow us to do ongoing comparisons across a range of settings. We also need to have better national benchmarks.”

Researchers set out to compare the incidence of MRSA and other health care-acquired infections at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Fletcher Allen Health Care, Burlington, Vt., between October 2007 and September 2008. Both are academic medical centers, with an average daily census of 295 and 387, respectively, said Dr. Kirkland, medical director of infection prevention at Dartmouth-Hitchcock Medical Center.

Fletcher Allen Health Care staff screen for MRSA upon admission and screen all ICU patients on a weekly basis; the staff also uses contact precautions when providing care for any inpatient known to be colonized or infected with MRSA. In contrast, although Dartmouth-Hitchcock staff maintain an aggressive hand hygiene protocol, they do not screen for MRSA and use contact precautions only for patients with open wounds, uncontrolled secretions, or diarrhea, regardless of causative organism.

The researchers used National Healthcare Safety Network definitions to track hospital-onset primary bloodstream infections and MRSA infections, as well as Clostridium difficile infections with onset during or within 30 days of hospitalization. They calculated rates as per 1,000 patient days and used direct observation to estimate hand hygiene compliance.

During the study period, the number of inpatient days at Dartmouth-Hitchcock Medical Center and Fletcher Allen Health Care were 114,828 and 126,600, respectively, while the estimated hand hygiene compliance was 84% and 93%.

Dartmouth-Hitchcock and Fletcher Allen did not differ significantly in the rate of new hospital-onset infections (0.48 vs. 0.54 per 1,000 patient days, respectively), the rate of primary MRSA bloodstream infections (0.06 vs. 0.08 per 1,000 patient days), the rate of primary methicillin-sensitive S. aureus bloodstream infections (0.1 vs. 0.07 per 1,000 patient days), or the rate of primary bloodstream infections due to non-S. aureus organisms (0.49 vs. 0.52 per 1,000 patient days).

The only significant difference between the two medical centers was in the rate of C. difficile infection, which was higher at Fletcher Allen Health Care (0.81 vs. 0.55 patient days).

“Both programs could be said to successfully control health care-associated infections, including invasive MRSA, primary bloodstream infections due to all pathogens, and C. difficile infection,” Dr. Kirkland concluded. “Both strategies are effective in controlling a range of health care-associated infections. It may be that the hand hygiene rates, which were high at both institutions, are the key to the low observed rates that we saw. Contributors to the difference in the rates of C. difficile infection are unexplained, as our control programs differ in almost every aspect.”

Dr. Kirkland had no conflicts of interest to disclose.

SAN DIEGO — Two medical centers of similar size located in the northeastern United States that use different methicillin-resistant Staphylococcus aureus infection control strategies have very similar rates of hospital-onset MRSA infection, results from a year-long analysis showed.

“Our study illustrates the need for these kinds of comparisons so we can decide which MRSA infection control strategies work best,” lead investigator Dr. Kathryn B. Kirkland said at the annual meeting of the Society for Healthcare Epidemiology of America. “We need to expand the set of measures that we have that will allow us to do ongoing comparisons across a range of settings. We also need to have better national benchmarks.”

Researchers set out to compare the incidence of MRSA and other health care-acquired infections at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Fletcher Allen Health Care, Burlington, Vt., between October 2007 and September 2008. Both are academic medical centers, with an average daily census of 295 and 387, respectively, said Dr. Kirkland, medical director of infection prevention at Dartmouth-Hitchcock Medical Center.

Fletcher Allen Health Care staff screen for MRSA upon admission and screen all ICU patients on a weekly basis; the staff also uses contact precautions when providing care for any inpatient known to be colonized or infected with MRSA. In contrast, although Dartmouth-Hitchcock staff maintain an aggressive hand hygiene protocol, they do not screen for MRSA and use contact precautions only for patients with open wounds, uncontrolled secretions, or diarrhea, regardless of causative organism.

The researchers used National Healthcare Safety Network definitions to track hospital-onset primary bloodstream infections and MRSA infections, as well as Clostridium difficile infections with onset during or within 30 days of hospitalization. They calculated rates as per 1,000 patient days and used direct observation to estimate hand hygiene compliance.

During the study period, the number of inpatient days at Dartmouth-Hitchcock Medical Center and Fletcher Allen Health Care were 114,828 and 126,600, respectively, while the estimated hand hygiene compliance was 84% and 93%.

Dartmouth-Hitchcock and Fletcher Allen did not differ significantly in the rate of new hospital-onset infections (0.48 vs. 0.54 per 1,000 patient days, respectively), the rate of primary MRSA bloodstream infections (0.06 vs. 0.08 per 1,000 patient days), the rate of primary methicillin-sensitive S. aureus bloodstream infections (0.1 vs. 0.07 per 1,000 patient days), or the rate of primary bloodstream infections due to non-S. aureus organisms (0.49 vs. 0.52 per 1,000 patient days).

The only significant difference between the two medical centers was in the rate of C. difficile infection, which was higher at Fletcher Allen Health Care (0.81 vs. 0.55 patient days).

“Both programs could be said to successfully control health care-associated infections, including invasive MRSA, primary bloodstream infections due to all pathogens, and C. difficile infection,” Dr. Kirkland concluded. “Both strategies are effective in controlling a range of health care-associated infections. It may be that the hand hygiene rates, which were high at both institutions, are the key to the low observed rates that we saw. Contributors to the difference in the rates of C. difficile infection are unexplained, as our control programs differ in almost every aspect.”

Dr. Kirkland had no conflicts of interest to disclose.

SAN DIEGO — Two medical centers of similar size located in the northeastern United States that use different methicillin-resistant Staphylococcus aureus infection control strategies have very similar rates of hospital-onset MRSA infection, results from a year-long analysis showed.

“Our study illustrates the need for these kinds of comparisons so we can decide which MRSA infection control strategies work best,” lead investigator Dr. Kathryn B. Kirkland said at the annual meeting of the Society for Healthcare Epidemiology of America. “We need to expand the set of measures that we have that will allow us to do ongoing comparisons across a range of settings. We also need to have better national benchmarks.”

Researchers set out to compare the incidence of MRSA and other health care-acquired infections at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Fletcher Allen Health Care, Burlington, Vt., between October 2007 and September 2008. Both are academic medical centers, with an average daily census of 295 and 387, respectively, said Dr. Kirkland, medical director of infection prevention at Dartmouth-Hitchcock Medical Center.

Fletcher Allen Health Care staff screen for MRSA upon admission and screen all ICU patients on a weekly basis; the staff also uses contact precautions when providing care for any inpatient known to be colonized or infected with MRSA. In contrast, although Dartmouth-Hitchcock staff maintain an aggressive hand hygiene protocol, they do not screen for MRSA and use contact precautions only for patients with open wounds, uncontrolled secretions, or diarrhea, regardless of causative organism.

The researchers used National Healthcare Safety Network definitions to track hospital-onset primary bloodstream infections and MRSA infections, as well as Clostridium difficile infections with onset during or within 30 days of hospitalization. They calculated rates as per 1,000 patient days and used direct observation to estimate hand hygiene compliance.

During the study period, the number of inpatient days at Dartmouth-Hitchcock Medical Center and Fletcher Allen Health Care were 114,828 and 126,600, respectively, while the estimated hand hygiene compliance was 84% and 93%.

Dartmouth-Hitchcock and Fletcher Allen did not differ significantly in the rate of new hospital-onset infections (0.48 vs. 0.54 per 1,000 patient days, respectively), the rate of primary MRSA bloodstream infections (0.06 vs. 0.08 per 1,000 patient days), the rate of primary methicillin-sensitive S. aureus bloodstream infections (0.1 vs. 0.07 per 1,000 patient days), or the rate of primary bloodstream infections due to non-S. aureus organisms (0.49 vs. 0.52 per 1,000 patient days).

The only significant difference between the two medical centers was in the rate of C. difficile infection, which was higher at Fletcher Allen Health Care (0.81 vs. 0.55 patient days).

“Both programs could be said to successfully control health care-associated infections, including invasive MRSA, primary bloodstream infections due to all pathogens, and C. difficile infection,” Dr. Kirkland concluded. “Both strategies are effective in controlling a range of health care-associated infections. It may be that the hand hygiene rates, which were high at both institutions, are the key to the low observed rates that we saw. Contributors to the difference in the rates of C. difficile infection are unexplained, as our control programs differ in almost every aspect.”

Dr. Kirkland had no conflicts of interest to disclose.

SAN DIEGO — Implementation of a multifaceted methicillin-resistant Staphylococcus aureus prevention program at three hospitals triggered significant reductions in MRSA incidence that ranged from 26% to 62%.

“There are few reports of successful multicenter interventions to reduce endemic MRSA in U.S. health care settings,” lead investigator Katherine Ellingson, Ph.D., said at the annual meeting of the Society for Healthcare Epidemiology of America.

One novel approach to implementation is positive deviance, a concept that “highlights uncommon but effective solutions to persistent problems using existing resources. Once identified, solutions that work are scaled up to change new behavior.”

In the context of MRSA prevention, positive deviance “encourages hospital employees to uncover, create, and diffuse effective infection-control solutions that work in the context of a given ward or a given hospital,” said Dr. Ellingson, an epidemiologist with the Centers for Disease Control and Prevention.

In 2006 six hospitals partnered with the CDC and the Plexus Institute, a nonprofit based in Bordentown, N.J., to implement MRSA prevention programs in acute care settings. Hospitals used a combination of strategies, including enhanced emphasis on hand hygiene, contact precautions for known MRSA carriers, environmental cleaning, selective application of active surveillance testing, and positive deviance.

As a way to foster positive deviance at the hospitals, hundreds of frontline workers “were asked for their ideas on how to stop MRSA transmission, who among them was practicing good infection control, and what actions they could take to improve adherence to precautions,” according to a report available at the Web site of the Plexus Institute, which funded the study with the Robert Wood Johnson Foundation.

When a group of clinicians visited one of the hospitals participating in the study, it saw an example of positive deviance in action. As recounted in the report, the group members “saw a physician entering an isolation room without washing his hands or donning gowns and gloves. A housekeeper politely reminded the physician to wash his hands and handed him a gown and gloves. The physician complied.”

The hospitals shared electronic data for objective, third-party evaluation of the impact of the prevention efforts. At the meeting, Dr. Ellingson presented complete data from three of the six hospitals that took part in the analysis: the 272-bed Billings (Mont.) Clinic (hospital A), the 844-bed Albert Einstein Network in Philadelphia (hospital B), and the 404-bed University of Louisville (Ky.) Hospital (hospital C).

The study's primary objective was to analyze the impact of the interventions on the incidence of MRSA in hospitalized patients. The researchers extracted 12-32 months of data from the preintervention period and 20-24 months of data from the postintervention period.

When Dr. Ellingson and her associates compared the preintervention period with the postintervention period, they observed a 31% reduction in MRSA incidence in hospital A, a 62% reduction in hospital B, and a 26% reduction in hospital C. All three reductions were statistically significant.

Though the results are encouraging, Dr. Ellingson acknowledged the study had several limitations.

Positive deviance 'highlights uncommon but effective solutions to persistent problems.' DR. ELLINGSON

SAN DIEGO — Implementation of a multifaceted methicillin-resistant Staphylococcus aureus prevention program at three hospitals triggered significant reductions in MRSA incidence that ranged from 26% to 62%.

“There are few reports of successful multicenter interventions to reduce endemic MRSA in U.S. health care settings,” lead investigator Katherine Ellingson, Ph.D., said at the annual meeting of the Society for Healthcare Epidemiology of America.

One novel approach to implementation is positive deviance, a concept that “highlights uncommon but effective solutions to persistent problems using existing resources. Once identified, solutions that work are scaled up to change new behavior.”

In the context of MRSA prevention, positive deviance “encourages hospital employees to uncover, create, and diffuse effective infection-control solutions that work in the context of a given ward or a given hospital,” said Dr. Ellingson, an epidemiologist with the Centers for Disease Control and Prevention.

In 2006 six hospitals partnered with the CDC and the Plexus Institute, a nonprofit based in Bordentown, N.J., to implement MRSA prevention programs in acute care settings. Hospitals used a combination of strategies, including enhanced emphasis on hand hygiene, contact precautions for known MRSA carriers, environmental cleaning, selective application of active surveillance testing, and positive deviance.

As a way to foster positive deviance at the hospitals, hundreds of frontline workers “were asked for their ideas on how to stop MRSA transmission, who among them was practicing good infection control, and what actions they could take to improve adherence to precautions,” according to a report available at the Web site of the Plexus Institute, which funded the study with the Robert Wood Johnson Foundation.

When a group of clinicians visited one of the hospitals participating in the study, it saw an example of positive deviance in action. As recounted in the report, the group members “saw a physician entering an isolation room without washing his hands or donning gowns and gloves. A housekeeper politely reminded the physician to wash his hands and handed him a gown and gloves. The physician complied.”

The hospitals shared electronic data for objective, third-party evaluation of the impact of the prevention efforts. At the meeting, Dr. Ellingson presented complete data from three of the six hospitals that took part in the analysis: the 272-bed Billings (Mont.) Clinic (hospital A), the 844-bed Albert Einstein Network in Philadelphia (hospital B), and the 404-bed University of Louisville (Ky.) Hospital (hospital C).

The study's primary objective was to analyze the impact of the interventions on the incidence of MRSA in hospitalized patients. The researchers extracted 12-32 months of data from the preintervention period and 20-24 months of data from the postintervention period.

When Dr. Ellingson and her associates compared the preintervention period with the postintervention period, they observed a 31% reduction in MRSA incidence in hospital A, a 62% reduction in hospital B, and a 26% reduction in hospital C. All three reductions were statistically significant.

Though the results are encouraging, Dr. Ellingson acknowledged the study had several limitations.

Positive deviance 'highlights uncommon but effective solutions to persistent problems.' DR. ELLINGSON

SAN DIEGO — Implementation of a multifaceted methicillin-resistant Staphylococcus aureus prevention program at three hospitals triggered significant reductions in MRSA incidence that ranged from 26% to 62%.

“There are few reports of successful multicenter interventions to reduce endemic MRSA in U.S. health care settings,” lead investigator Katherine Ellingson, Ph.D., said at the annual meeting of the Society for Healthcare Epidemiology of America.

One novel approach to implementation is positive deviance, a concept that “highlights uncommon but effective solutions to persistent problems using existing resources. Once identified, solutions that work are scaled up to change new behavior.”

In the context of MRSA prevention, positive deviance “encourages hospital employees to uncover, create, and diffuse effective infection-control solutions that work in the context of a given ward or a given hospital,” said Dr. Ellingson, an epidemiologist with the Centers for Disease Control and Prevention.

In 2006 six hospitals partnered with the CDC and the Plexus Institute, a nonprofit based in Bordentown, N.J., to implement MRSA prevention programs in acute care settings. Hospitals used a combination of strategies, including enhanced emphasis on hand hygiene, contact precautions for known MRSA carriers, environmental cleaning, selective application of active surveillance testing, and positive deviance.

As a way to foster positive deviance at the hospitals, hundreds of frontline workers “were asked for their ideas on how to stop MRSA transmission, who among them was practicing good infection control, and what actions they could take to improve adherence to precautions,” according to a report available at the Web site of the Plexus Institute, which funded the study with the Robert Wood Johnson Foundation.

When a group of clinicians visited one of the hospitals participating in the study, it saw an example of positive deviance in action. As recounted in the report, the group members “saw a physician entering an isolation room without washing his hands or donning gowns and gloves. A housekeeper politely reminded the physician to wash his hands and handed him a gown and gloves. The physician complied.”

The hospitals shared electronic data for objective, third-party evaluation of the impact of the prevention efforts. At the meeting, Dr. Ellingson presented complete data from three of the six hospitals that took part in the analysis: the 272-bed Billings (Mont.) Clinic (hospital A), the 844-bed Albert Einstein Network in Philadelphia (hospital B), and the 404-bed University of Louisville (Ky.) Hospital (hospital C).

The study's primary objective was to analyze the impact of the interventions on the incidence of MRSA in hospitalized patients. The researchers extracted 12-32 months of data from the preintervention period and 20-24 months of data from the postintervention period.

When Dr. Ellingson and her associates compared the preintervention period with the postintervention period, they observed a 31% reduction in MRSA incidence in hospital A, a 62% reduction in hospital B, and a 26% reduction in hospital C. All three reductions were statistically significant.

Though the results are encouraging, Dr. Ellingson acknowledged the study had several limitations.

Positive deviance 'highlights uncommon but effective solutions to persistent problems.' DR. ELLINGSON

SAN DIEGO — Dr. Mitchell Shiffman views therapy for hepatitis C as an accordion in which treatment with pegylated interferon and ribavirin is compressed for early responders and extended for slow responders.

“The single best predictor for sustained viral response is the time at which the patient becomes HCV RNA undetectable,” he said at a meeting on chronic liver disease sponsored by Scripps Clinic. “Time to response is everything.”

Clinicians are starting to modify the duration of therapy with pegylated interferon and ribavirin based on time to respond. Five published studies have examined extending therapy to 72 weeks in patients who are slow to respond. The best-designed study found that the sustained virologic response (SVR) in these patients was 52% by week 48 and 69% by week 72. Other studies have shown that rapid responders may not require therapy beyond 24 weeks (Hepatology 2006;43:954-60).

“So if you have a complete early virologic responder who is negative for disease at 12 weeks, then the optimal duration of therapy appears to be 48 weeks. On the other hand, if you [have] a rapid responder who is negative for disease at 4 weeks, you can compress that therapy down to 24 weeks in most of these patients, with minimal risk of relapse. The worst that can happen is that if you do have a relapse, you can re-treat for 48 weeks. We've done that on occasion,” said Dr. Shiffman, chief of the hepatology section at Virginia Commonwealth University, Richmond.

For patients who do not become virus negative until week 24, “you stretch out the duration of therapy to 72 weeks to limit relapse,” he said.

Among patients treated with pegylated interferon and ribavirin, those with a virologic response by week 4 are referred to as rapid virologic responders and have the highest SVR and the lowest rates of relapse. Because of that, a shorter period of treatment may suffice, Dr. Shiffman said.

Complete early virologic responders have a virologic response by week 12. “You would not expect this group to have as high a cure rate as the rapid responders,” he said.

Among slow responders, HCV becomes undetectable by week 24 and a log2 drop is reached by week 12. “Therefore, you continue therapy in these patients” and monitor viral load, he said. “It's important to differentiate the slow responder from the partial responder.”

Patients with a partial response also have a log2 drop by week 12, he said, “but then the virus does not continue to fall; it plateaus. … They never become virus negative. It is irrational to treat this patient beyond week 24.”

Recognizing response patterns enables clinicians to predict a patient's chances of achieving a virologic response. Among patients with genotype 1 disease, 15% achieve a virologic response by week 4, compared with 35% by week 12 and 15% by week 24 (J. Hepatol. 2005;43:453-71). The remainder has a null response (20%) or partial response (15%). The SVR rate is highest among those who achieve a virologic response by week 4 (91%), compared with those who achieve a virologic response by weeks 12 and 24 (66% and 45%, respectively).

“So if you have a patient who is slow to respond, they become virus negative at week 24, their chance of relapsing is higher than their chance of getting a sustained response,” Dr. Shiffman said.

Among patients with genotypes 2 and 3 disease, 66% achieve a virologic response by week 4, 31% achieve virologic response by week 12, and 3% are nonresponders (N. Engl. J. Med. 2007;357:124-34). The SVR rate is highest among those who achieve a virologic response by week 4 (90%), compared with those who achieve a virologic response by week 12 (49%).

Poor prognostic features that are correlated with a low SVR rate include African American race, body mass index of greater than 27 kg/m2, viral loads that exceed 400,000 IU/mL, and cirrhosis. “The reason this occurs is because these features are associated with slower responses,” Dr. Shiffman explained. “But if a patient with a poor prognostic factor achieves a rapid response, their cure rate is just as good as anybody else with a rapid response,” Dr. Shiffman said, citing data from a retrospective analysis of six studies that he and his associates conducted involving a total of 894 patients with HCV infection; the SVR rates were similar among patients who achieved a virologic response by week 4 “regardless of any of these poor prognostic factors” (75%, compared with 63% and 33% for those who achieved a virologic response by weeks 12 and 24, respectively).

Dr. Shiffman disclosed that he has received research grants from Hoffmann-La Roche Inc., Schering-Plough Corp., and Vertex Pharmaceuticals, and has received speaker fees from Roche and Schering-Plough.

The single best predictor for sustained viral response is the time when HCV RNA becomes undetectable. DR. SHIFFMAN

SAN DIEGO — Dr. Mitchell Shiffman views therapy for hepatitis C as an accordion in which treatment with pegylated interferon and ribavirin is compressed for early responders and extended for slow responders.

“The single best predictor for sustained viral response is the time at which the patient becomes HCV RNA undetectable,” he said at a meeting on chronic liver disease sponsored by Scripps Clinic. “Time to response is everything.”

Clinicians are starting to modify the duration of therapy with pegylated interferon and ribavirin based on time to respond. Five published studies have examined extending therapy to 72 weeks in patients who are slow to respond. The best-designed study found that the sustained virologic response (SVR) in these patients was 52% by week 48 and 69% by week 72. Other studies have shown that rapid responders may not require therapy beyond 24 weeks (Hepatology 2006;43:954-60).

“So if you have a complete early virologic responder who is negative for disease at 12 weeks, then the optimal duration of therapy appears to be 48 weeks. On the other hand, if you [have] a rapid responder who is negative for disease at 4 weeks, you can compress that therapy down to 24 weeks in most of these patients, with minimal risk of relapse. The worst that can happen is that if you do have a relapse, you can re-treat for 48 weeks. We've done that on occasion,” said Dr. Shiffman, chief of the hepatology section at Virginia Commonwealth University, Richmond.

For patients who do not become virus negative until week 24, “you stretch out the duration of therapy to 72 weeks to limit relapse,” he said.

Among patients treated with pegylated interferon and ribavirin, those with a virologic response by week 4 are referred to as rapid virologic responders and have the highest SVR and the lowest rates of relapse. Because of that, a shorter period of treatment may suffice, Dr. Shiffman said.

Complete early virologic responders have a virologic response by week 12. “You would not expect this group to have as high a cure rate as the rapid responders,” he said.

Among slow responders, HCV becomes undetectable by week 24 and a log2 drop is reached by week 12. “Therefore, you continue therapy in these patients” and monitor viral load, he said. “It's important to differentiate the slow responder from the partial responder.”

Patients with a partial response also have a log2 drop by week 12, he said, “but then the virus does not continue to fall; it plateaus. … They never become virus negative. It is irrational to treat this patient beyond week 24.”

Recognizing response patterns enables clinicians to predict a patient's chances of achieving a virologic response. Among patients with genotype 1 disease, 15% achieve a virologic response by week 4, compared with 35% by week 12 and 15% by week 24 (J. Hepatol. 2005;43:453-71). The remainder has a null response (20%) or partial response (15%). The SVR rate is highest among those who achieve a virologic response by week 4 (91%), compared with those who achieve a virologic response by weeks 12 and 24 (66% and 45%, respectively).

“So if you have a patient who is slow to respond, they become virus negative at week 24, their chance of relapsing is higher than their chance of getting a sustained response,” Dr. Shiffman said.

Among patients with genotypes 2 and 3 disease, 66% achieve a virologic response by week 4, 31% achieve virologic response by week 12, and 3% are nonresponders (N. Engl. J. Med. 2007;357:124-34). The SVR rate is highest among those who achieve a virologic response by week 4 (90%), compared with those who achieve a virologic response by week 12 (49%).

Poor prognostic features that are correlated with a low SVR rate include African American race, body mass index of greater than 27 kg/m2, viral loads that exceed 400,000 IU/mL, and cirrhosis. “The reason this occurs is because these features are associated with slower responses,” Dr. Shiffman explained. “But if a patient with a poor prognostic factor achieves a rapid response, their cure rate is just as good as anybody else with a rapid response,” Dr. Shiffman said, citing data from a retrospective analysis of six studies that he and his associates conducted involving a total of 894 patients with HCV infection; the SVR rates were similar among patients who achieved a virologic response by week 4 “regardless of any of these poor prognostic factors” (75%, compared with 63% and 33% for those who achieved a virologic response by weeks 12 and 24, respectively).

Dr. Shiffman disclosed that he has received research grants from Hoffmann-La Roche Inc., Schering-Plough Corp., and Vertex Pharmaceuticals, and has received speaker fees from Roche and Schering-Plough.

The single best predictor for sustained viral response is the time when HCV RNA becomes undetectable. DR. SHIFFMAN

SAN DIEGO — Dr. Mitchell Shiffman views therapy for hepatitis C as an accordion in which treatment with pegylated interferon and ribavirin is compressed for early responders and extended for slow responders.

“The single best predictor for sustained viral response is the time at which the patient becomes HCV RNA undetectable,” he said at a meeting on chronic liver disease sponsored by Scripps Clinic. “Time to response is everything.”

Clinicians are starting to modify the duration of therapy with pegylated interferon and ribavirin based on time to respond. Five published studies have examined extending therapy to 72 weeks in patients who are slow to respond. The best-designed study found that the sustained virologic response (SVR) in these patients was 52% by week 48 and 69% by week 72. Other studies have shown that rapid responders may not require therapy beyond 24 weeks (Hepatology 2006;43:954-60).

“So if you have a complete early virologic responder who is negative for disease at 12 weeks, then the optimal duration of therapy appears to be 48 weeks. On the other hand, if you [have] a rapid responder who is negative for disease at 4 weeks, you can compress that therapy down to 24 weeks in most of these patients, with minimal risk of relapse. The worst that can happen is that if you do have a relapse, you can re-treat for 48 weeks. We've done that on occasion,” said Dr. Shiffman, chief of the hepatology section at Virginia Commonwealth University, Richmond.

For patients who do not become virus negative until week 24, “you stretch out the duration of therapy to 72 weeks to limit relapse,” he said.

Among patients treated with pegylated interferon and ribavirin, those with a virologic response by week 4 are referred to as rapid virologic responders and have the highest SVR and the lowest rates of relapse. Because of that, a shorter period of treatment may suffice, Dr. Shiffman said.

Complete early virologic responders have a virologic response by week 12. “You would not expect this group to have as high a cure rate as the rapid responders,” he said.

Among slow responders, HCV becomes undetectable by week 24 and a log2 drop is reached by week 12. “Therefore, you continue therapy in these patients” and monitor viral load, he said. “It's important to differentiate the slow responder from the partial responder.”

Patients with a partial response also have a log2 drop by week 12, he said, “but then the virus does not continue to fall; it plateaus. … They never become virus negative. It is irrational to treat this patient beyond week 24.”

Recognizing response patterns enables clinicians to predict a patient's chances of achieving a virologic response. Among patients with genotype 1 disease, 15% achieve a virologic response by week 4, compared with 35% by week 12 and 15% by week 24 (J. Hepatol. 2005;43:453-71). The remainder has a null response (20%) or partial response (15%). The SVR rate is highest among those who achieve a virologic response by week 4 (91%), compared with those who achieve a virologic response by weeks 12 and 24 (66% and 45%, respectively).

“So if you have a patient who is slow to respond, they become virus negative at week 24, their chance of relapsing is higher than their chance of getting a sustained response,” Dr. Shiffman said.

Among patients with genotypes 2 and 3 disease, 66% achieve a virologic response by week 4, 31% achieve virologic response by week 12, and 3% are nonresponders (N. Engl. J. Med. 2007;357:124-34). The SVR rate is highest among those who achieve a virologic response by week 4 (90%), compared with those who achieve a virologic response by week 12 (49%).

Poor prognostic features that are correlated with a low SVR rate include African American race, body mass index of greater than 27 kg/m2, viral loads that exceed 400,000 IU/mL, and cirrhosis. “The reason this occurs is because these features are associated with slower responses,” Dr. Shiffman explained. “But if a patient with a poor prognostic factor achieves a rapid response, their cure rate is just as good as anybody else with a rapid response,” Dr. Shiffman said, citing data from a retrospective analysis of six studies that he and his associates conducted involving a total of 894 patients with HCV infection; the SVR rates were similar among patients who achieved a virologic response by week 4 “regardless of any of these poor prognostic factors” (75%, compared with 63% and 33% for those who achieved a virologic response by weeks 12 and 24, respectively).

Dr. Shiffman disclosed that he has received research grants from Hoffmann-La Roche Inc., Schering-Plough Corp., and Vertex Pharmaceuticals, and has received speaker fees from Roche and Schering-Plough.

The single best predictor for sustained viral response is the time when HCV RNA becomes undetectable. DR. SHIFFMAN

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

"I use public transportation, but the nice thing about a bike is you're kind of out there on your own," said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. "It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation." Every day she bikes 5 miles to work "if it's not actively precipitating and the wind is not more than 20 miles an hour against me."

Even Chicago's harsh winter days don't stop her. "I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet," she said.

No special tires are required during her winter commutes because the route she takes includes a network of bike lanes that "get cleared out pretty well" by the city's snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip "was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan," she said.

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance, a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

"Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around," she said. "Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2."

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. "Fortunately, I was just outside the hospital emergency room," she said. "I got a fair number of facial lacerations, but I didn't have any head injury."

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

Dr. Christiane Stahl bikes 5 miles to work every day in Chicago. COURTESY DR. CHRISTIANE STAHL

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

"I use public transportation, but the nice thing about a bike is you're kind of out there on your own," said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. "It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation." Every day she bikes 5 miles to work "if it's not actively precipitating and the wind is not more than 20 miles an hour against me."

Even Chicago's harsh winter days don't stop her. "I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet," she said.

No special tires are required during her winter commutes because the route she takes includes a network of bike lanes that "get cleared out pretty well" by the city's snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip "was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan," she said.

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance, a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

"Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around," she said. "Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2."

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. "Fortunately, I was just outside the hospital emergency room," she said. "I got a fair number of facial lacerations, but I didn't have any head injury."

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

Dr. Christiane Stahl bikes 5 miles to work every day in Chicago. COURTESY DR. CHRISTIANE STAHL

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

"I use public transportation, but the nice thing about a bike is you're kind of out there on your own," said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. "It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation." Every day she bikes 5 miles to work "if it's not actively precipitating and the wind is not more than 20 miles an hour against me."

Even Chicago's harsh winter days don't stop her. "I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet," she said.

No special tires are required during her winter commutes because the route she takes includes a network of bike lanes that "get cleared out pretty well" by the city's snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip "was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan," she said.

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance, a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

"Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around," she said. "Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2."

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. "Fortunately, I was just outside the hospital emergency room," she said. "I got a fair number of facial lacerations, but I didn't have any head injury."

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

Dr. Christiane Stahl bikes 5 miles to work every day in Chicago. COURTESY DR. CHRISTIANE STAHL

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

“I use public transportation, but the nice thing about a bike is you're kind of out there on your own,” said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. “It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation.”

Every day she bikes 5 miles to work “if it's not actively precipitating and the wind is not more than 20 miles an hour against me.”

Even Chicago's harsh winter days don't stop her. “I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet,” she said.

No special tires are required during her winter commutes because her route includes a network of bike lanes that “get cleared out pretty well” by city snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip “was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan,” she said. “Plus, I was in beeper range the whole time, and it's easy to make callbacks from the back of a tandem so no cross-coverage arrangements were required.”

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance (formerly the Chicagoland Bicycle Federation), a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

“Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around,” she said. “Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2.”

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. “Fortunately, I was just outside the hospital emergency room,” she said. “I got a fair number of facial lacerations, but I didn't have any head injury.”

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

“For me, biking is not goal oriented,” she said. “That's part of what I like about it. On the rare occasions when I'm sitting around and want to get out of the house, I'm just as likely to jump up on my bike and head out aimlessly. That's one of the chief joys of riding my bike: to explore, look around, and see things.”

Dr. Christiane Stahl, a pediatrician based in Chicago, bikes 5 miles to work every day. Courtesy Dr. Christiane Stahl

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

“I use public transportation, but the nice thing about a bike is you're kind of out there on your own,” said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. “It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation.”

Every day she bikes 5 miles to work “if it's not actively precipitating and the wind is not more than 20 miles an hour against me.”

Even Chicago's harsh winter days don't stop her. “I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet,” she said.

No special tires are required during her winter commutes because her route includes a network of bike lanes that “get cleared out pretty well” by city snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip “was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan,” she said. “Plus, I was in beeper range the whole time, and it's easy to make callbacks from the back of a tandem so no cross-coverage arrangements were required.”

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance (formerly the Chicagoland Bicycle Federation), a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

“Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around,” she said. “Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2.”

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. “Fortunately, I was just outside the hospital emergency room,” she said. “I got a fair number of facial lacerations, but I didn't have any head injury.”

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

“For me, biking is not goal oriented,” she said. “That's part of what I like about it. On the rare occasions when I'm sitting around and want to get out of the house, I'm just as likely to jump up on my bike and head out aimlessly. That's one of the chief joys of riding my bike: to explore, look around, and see things.”

Dr. Christiane Stahl, a pediatrician based in Chicago, bikes 5 miles to work every day. Courtesy Dr. Christiane Stahl

For Dr. Christiane Stahl, bicycling is not so much a hobby as a way of life. She's been commuting by bike to school or work since she was 8 years old.

“I use public transportation, but the nice thing about a bike is you're kind of out there on your own,” said Dr. Stahl of the department of pediatrics at the University of Illinois at Chicago. “It's a little more individual and gives you more time for reflection. You're not distracted by all the social interactions that are going on when you take public transportation.”

Every day she bikes 5 miles to work “if it's not actively precipitating and the wind is not more than 20 miles an hour against me.”

Even Chicago's harsh winter days don't stop her. “I have little booties that I put over my bike shoes and big puffy bike gloves and hats to wear under my helmet,” she said.

No special tires are required during her winter commutes because her route includes a network of bike lanes that “get cleared out pretty well” by city snowplows. However, degradation of the bike chain from road salt is an ongoing issue.

Among her favorite vacations are bike trips she's taken through Germany, Wisconsin, and South Carolina. Her easiest and most spontaneous trip “was on the back of a tandem bicycle around the Chicago area—taking advantage of the great trail system, the outdoor concert area of Ravinia Park, and views of Lake Michigan,” she said. “Plus, I was in beeper range the whole time, and it's easy to make callbacks from the back of a tandem so no cross-coverage arrangements were required.”

An advocate for bike safety, Dr. Stahl has served as a medical volunteer for Bank of America's Bike the Drive, an annual bike ride along scenic Lake Shore Drive that benefits the Active Transportation Alliance (formerly the Chicagoland Bicycle Federation), a not-for-profit biking, walking, and transit advocacy organization.

She noted that as more people take up bicycling as an inexpensive and environmentally friendly commuting tactic, upgrades in the separation of auto and bicycle traffic will be needed.

“Until we do that, we're going to see rising rates of injury, because I think more people will turn to bicycling as a way of getting around,” she said. “Compared with Europe, we have so far to go in terms of creating safer bikeways. I'm hopeful that will occur over the next decade or 2.”

A self-described devoted helmet wearer, Dr. Stahl had one serious injury on a bike: a low-speed face plant when she dropped a wheel into a grate on the sidewalk. “Fortunately, I was just outside the hospital emergency room,” she said. “I got a fair number of facial lacerations, but I didn't have any head injury.”

While she knows her share of bicyclists who set goals to improve their speed or endurance—and fret about reaching those goals—Dr. Stahl is content to enjoy bicycling on her terms.

“For me, biking is not goal oriented,” she said. “That's part of what I like about it. On the rare occasions when I'm sitting around and want to get out of the house, I'm just as likely to jump up on my bike and head out aimlessly. That's one of the chief joys of riding my bike: to explore, look around, and see things.”

Dr. Christiane Stahl, a pediatrician based in Chicago, bikes 5 miles to work every day. Courtesy Dr. Christiane Stahl

SAN DIEGO — Women are more susceptible to the lung-damaging effects of smoking, compared with men, results from a large case-control study demonstrated.

The gender effect seemed to be most pronounced when the level of smoking exposure was low and decreased in magnitude with an increasing number of pack-years, lead investigator Dr. Dawn L. DeMeo reported in a poster session at an international conference of the American Thoracic Society.

“This is crucial, especially from a public health standpoint, because many people feel that one, two, or five cigarettes per day is fine,” Dr. DeMeo, assistant professor of medicine at Harvard Medical School and the Channing Laboratory, Boston, said in an interview. “What we want to promulgate from this study is that there is no safe exposure to cigarette smoke, especially for young women.”

She and her associates evaluated data from a case-control study performed at Haukeland University Hospital in Bergen, Norway, between 2003 and 2005 that involved 583 men and 371 women with chronic obstructive pulmonary disease (COPD). To be eligible for the trial, participants had to be white, at least 40 years of age, and current or ex-smokers with a history of 2.5 pack-years or more, and they had to have no severe alpha-1 antitrypsin deficiency.

The researchers observed no differences between men and women with respect to lung function and COPD severity, but the women were younger (a mean of 64 vs. 66 years) and had smoked significantly less than men (a mean of 24 vs. 32 pack-years).

Dr. DeMeo and her associates then restricted the analysis to two subgroups: an early-onset group of 316 patients who were younger than age 60 at the time of the study and a lower-exposure group of 241 patients with a smoking history of fewer than 20 pack-years. Analysis of these subgroups revealed that females had a later smoking onset and fewer pack-years compared with males.

Women in the study also had a more severe reduction of forced expiratory volume in 1 second for lower levels of smoking exposure, but after 25–30 pack-years the curves for males and females converged and showed a similar dose-response relationship.

“There seems to be a female predominance for the lung-damaging effects of cigarette smoke, but it seems to be most pronounced when the cigarette smoke exposure is on the lower end,” said Dr. DeMeo, who is also with Brigham and Women's Hospital's lung transplantation program and the COPD center at the Center for Chest Diseases.

Reasons for the gender differences remain unclear, but could be related to the fact that women have smaller lungs than men. “That likely doesn't explain all of the potential impact here,” she commented.

“There have been hormonal arguments cited and also social constructs associated with gender differences. Perhaps women are underreporting [their cigarette smoking]. One of the goals of our research group at the Channing Laboratory is to address what may be going on from genetic and epigenetic points of views. More research is needed,” she said.

For now, Dr. DeMeo added, “the onus is on clinicians to think about COPD early, especially in women who report lower exposures to cigarette smoking.”

She acknowledged certain limitations of the study, including its retrospective design and the fact that it was conducted only in Norwegian whites.

The study received funding from the Research Council of Norway, GlaxoSmithKline, and the Foundation for Respiratory Research at Haukeland University Hospital. Dr. DeMeo was supported by a grant from the National Institutes of Health and an award from the Doris Duke Charitable Foundation.

In smokers with similar COPD severity, women had less exposure to cigarettes. ©

SAN DIEGO — Women are more susceptible to the lung-damaging effects of smoking, compared with men, results from a large case-control study demonstrated.

The gender effect seemed to be most pronounced when the level of smoking exposure was low and decreased in magnitude with an increasing number of pack-years, lead investigator Dr. Dawn L. DeMeo reported in a poster session at an international conference of the American Thoracic Society.

“This is crucial, especially from a public health standpoint, because many people feel that one, two, or five cigarettes per day is fine,” Dr. DeMeo, assistant professor of medicine at Harvard Medical School and the Channing Laboratory, Boston, said in an interview. “What we want to promulgate from this study is that there is no safe exposure to cigarette smoke, especially for young women.”

She and her associates evaluated data from a case-control study performed at Haukeland University Hospital in Bergen, Norway, between 2003 and 2005 that involved 583 men and 371 women with chronic obstructive pulmonary disease (COPD). To be eligible for the trial, participants had to be white, at least 40 years of age, and current or ex-smokers with a history of 2.5 pack-years or more, and they had to have no severe alpha-1 antitrypsin deficiency.

The researchers observed no differences between men and women with respect to lung function and COPD severity, but the women were younger (a mean of 64 vs. 66 years) and had smoked significantly less than men (a mean of 24 vs. 32 pack-years).

Dr. DeMeo and her associates then restricted the analysis to two subgroups: an early-onset group of 316 patients who were younger than age 60 at the time of the study and a lower-exposure group of 241 patients with a smoking history of fewer than 20 pack-years. Analysis of these subgroups revealed that females had a later smoking onset and fewer pack-years compared with males.

Women in the study also had a more severe reduction of forced expiratory volume in 1 second for lower levels of smoking exposure, but after 25–30 pack-years the curves for males and females converged and showed a similar dose-response relationship.

“There seems to be a female predominance for the lung-damaging effects of cigarette smoke, but it seems to be most pronounced when the cigarette smoke exposure is on the lower end,” said Dr. DeMeo, who is also with Brigham and Women's Hospital's lung transplantation program and the COPD center at the Center for Chest Diseases.

Reasons for the gender differences remain unclear, but could be related to the fact that women have smaller lungs than men. “That likely doesn't explain all of the potential impact here,” she commented.

“There have been hormonal arguments cited and also social constructs associated with gender differences. Perhaps women are underreporting [their cigarette smoking]. One of the goals of our research group at the Channing Laboratory is to address what may be going on from genetic and epigenetic points of views. More research is needed,” she said.

For now, Dr. DeMeo added, “the onus is on clinicians to think about COPD early, especially in women who report lower exposures to cigarette smoking.”

She acknowledged certain limitations of the study, including its retrospective design and the fact that it was conducted only in Norwegian whites.

The study received funding from the Research Council of Norway, GlaxoSmithKline, and the Foundation for Respiratory Research at Haukeland University Hospital. Dr. DeMeo was supported by a grant from the National Institutes of Health and an award from the Doris Duke Charitable Foundation.

In smokers with similar COPD severity, women had less exposure to cigarettes. ©

SAN DIEGO — Women are more susceptible to the lung-damaging effects of smoking, compared with men, results from a large case-control study demonstrated.

The gender effect seemed to be most pronounced when the level of smoking exposure was low and decreased in magnitude with an increasing number of pack-years, lead investigator Dr. Dawn L. DeMeo reported in a poster session at an international conference of the American Thoracic Society.

“This is crucial, especially from a public health standpoint, because many people feel that one, two, or five cigarettes per day is fine,” Dr. DeMeo, assistant professor of medicine at Harvard Medical School and the Channing Laboratory, Boston, said in an interview. “What we want to promulgate from this study is that there is no safe exposure to cigarette smoke, especially for young women.”

She and her associates evaluated data from a case-control study performed at Haukeland University Hospital in Bergen, Norway, between 2003 and 2005 that involved 583 men and 371 women with chronic obstructive pulmonary disease (COPD). To be eligible for the trial, participants had to be white, at least 40 years of age, and current or ex-smokers with a history of 2.5 pack-years or more, and they had to have no severe alpha-1 antitrypsin deficiency.

The researchers observed no differences between men and women with respect to lung function and COPD severity, but the women were younger (a mean of 64 vs. 66 years) and had smoked significantly less than men (a mean of 24 vs. 32 pack-years).

Dr. DeMeo and her associates then restricted the analysis to two subgroups: an early-onset group of 316 patients who were younger than age 60 at the time of the study and a lower-exposure group of 241 patients with a smoking history of fewer than 20 pack-years. Analysis of these subgroups revealed that females had a later smoking onset and fewer pack-years compared with males.

Women in the study also had a more severe reduction of forced expiratory volume in 1 second for lower levels of smoking exposure, but after 25–30 pack-years the curves for males and females converged and showed a similar dose-response relationship.

“There seems to be a female predominance for the lung-damaging effects of cigarette smoke, but it seems to be most pronounced when the cigarette smoke exposure is on the lower end,” said Dr. DeMeo, who is also with Brigham and Women's Hospital's lung transplantation program and the COPD center at the Center for Chest Diseases.

Reasons for the gender differences remain unclear, but could be related to the fact that women have smaller lungs than men. “That likely doesn't explain all of the potential impact here,” she commented.

“There have been hormonal arguments cited and also social constructs associated with gender differences. Perhaps women are underreporting [their cigarette smoking]. One of the goals of our research group at the Channing Laboratory is to address what may be going on from genetic and epigenetic points of views. More research is needed,” she said.

For now, Dr. DeMeo added, “the onus is on clinicians to think about COPD early, especially in women who report lower exposures to cigarette smoking.”

She acknowledged certain limitations of the study, including its retrospective design and the fact that it was conducted only in Norwegian whites.

The study received funding from the Research Council of Norway, GlaxoSmithKline, and the Foundation for Respiratory Research at Haukeland University Hospital. Dr. DeMeo was supported by a grant from the National Institutes of Health and an award from the Doris Duke Charitable Foundation.

In smokers with similar COPD severity, women had less exposure to cigarettes. ©

SAN DIEGO — The Alair Bronchial Thermoplasty System produced significant improvements in quality of life in 79% of patients with severe asthma who underwent treatment, compared with 64% of sham controls, results from a randomized, multicenter pivotal trial demonstrated.

Moreover, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, and a 66% reduction in days lost from work, school, or other activities due to respiratory symptoms.

The findings exceeded the expectations of principal investigator Dr. Mario Castro, professor of medicine and pediatrics at Washington University, St. Louis. “These patients were getting maximal treatment with the standard of care,” Dr. Castro said during an interview at an international conference of the American Thoracic Society, where the work was presented. “Beyond that we were able to get a marked improvement in quality of life, health care utilization, and days lost from school or work. Those are meaningful end points for our patients.”

One of the patients Dr. Castro treated was a long-distance runner who had been sidelined because of the severity of his asthma. After undergoing bronchial thermoplasty he returned to running and went on to compete in a marathon.

“You can't get more of a testament than that,” he said.

Developed by Asthmatx Inc. of Sunnyvale, Calif., the Alair Bronchial Thermoplasty system is an investigational device that delivers radiofrequency energy to the airway walls during a bronchoscopic procedure in an effort to reduce the amount of airway smooth muscle.

The procedure, which takes 30–45 minutes to perform, is not designed to replace standard of care therapy, Dr. Castro said, but rather as “an add-on treatment we can do once patients are not achieving good control with the standard of therapy. It's nice to have something else to look forward to with these patients, because they come to your office and they're really desperate for something new in treatment.”

After their first treatment patients return for two additional bronchoscopic treatments spaced 2–3 weeks apart. “It's definitely a time commitment in terms of getting the treatment, recovering, and getting the two additional treatments,” noted Dr. Castro, who also directs Washington University's Asthma and Airway Translational Research Unit. “But you compare that to having to take a drug every day for the rest of your life, it's a small investment.”

The Alair System has received a CE mark for use in the European Union. In the United States a premarket approval application has been submitted to the Food and Drug Administration, which is expected to review the application this summer.

The purpose of the Asthma Intervention Research 2 (AIR2) trial was to evaluate the safety and effectiveness of the Alair System in 297 patients with severe asthma at 30 centers in six countries who were symptomatic despite being treated with high doses of inhaled corticosteroids and long-acting bronchodilators.

The trial was randomized, double blind, and sham controlled, and the primary effectiveness end point was significant improvement from baseline in Asthma Quality of Life Questionnaire (AQLQ) score.

Of the 297 patients 196 received bronchial thermoplasty while 101 received a sham bronchoscopy in which no radiofrequency energy was applied. The average age of patients was 41 years, and more than half were female.

Dr. Castro reported that 79% of patients in the treatment group had significant clinical improvements in their average AQLQ scores at 12 months, compared with 64% of patients in the sham group, a difference that was statistically significant.

Compared with patients in the sham group, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, a 36% reduction in patients reporting asthma (multiple symptoms) as an adverse event, and a 66% reduction in days lost from work, school, or other activities caused by respiratory symptoms.

If the Alair system is approved for use, Dr. Castro expects a significant impact on the pulmonology field.

“This is a new treatment for a lung disease that is very common, so our field is going to have to get comfortable with this new device and new treatment,” he commented.

“I think it's going to have a significant impact on how pulmonologists are trained on this new device. If this gets approved there will be a need for training workshops so that physicians are comfortable with its use. I think it's going to have a profound impact on our care of these patients with disabling asthma.”

While the cost of the procedure will vary by practice setting, he expects it to be in the ballpark of a bronchoscopy.

Dr. Castro disclosed that he is a paid consultant for Asthmatx, which funded the study.

There was marked improvement in patients who were already 'getting maximal treatment with the standard of care.' DR. CASTRO

SAN DIEGO — The Alair Bronchial Thermoplasty System produced significant improvements in quality of life in 79% of patients with severe asthma who underwent treatment, compared with 64% of sham controls, results from a randomized, multicenter pivotal trial demonstrated.

Moreover, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, and a 66% reduction in days lost from work, school, or other activities due to respiratory symptoms.

The findings exceeded the expectations of principal investigator Dr. Mario Castro, professor of medicine and pediatrics at Washington University, St. Louis. “These patients were getting maximal treatment with the standard of care,” Dr. Castro said during an interview at an international conference of the American Thoracic Society, where the work was presented. “Beyond that we were able to get a marked improvement in quality of life, health care utilization, and days lost from school or work. Those are meaningful end points for our patients.”

One of the patients Dr. Castro treated was a long-distance runner who had been sidelined because of the severity of his asthma. After undergoing bronchial thermoplasty he returned to running and went on to compete in a marathon.

“You can't get more of a testament than that,” he said.

Developed by Asthmatx Inc. of Sunnyvale, Calif., the Alair Bronchial Thermoplasty system is an investigational device that delivers radiofrequency energy to the airway walls during a bronchoscopic procedure in an effort to reduce the amount of airway smooth muscle.

The procedure, which takes 30–45 minutes to perform, is not designed to replace standard of care therapy, Dr. Castro said, but rather as “an add-on treatment we can do once patients are not achieving good control with the standard of therapy. It's nice to have something else to look forward to with these patients, because they come to your office and they're really desperate for something new in treatment.”

After their first treatment patients return for two additional bronchoscopic treatments spaced 2–3 weeks apart. “It's definitely a time commitment in terms of getting the treatment, recovering, and getting the two additional treatments,” noted Dr. Castro, who also directs Washington University's Asthma and Airway Translational Research Unit. “But you compare that to having to take a drug every day for the rest of your life, it's a small investment.”

The Alair System has received a CE mark for use in the European Union. In the United States a premarket approval application has been submitted to the Food and Drug Administration, which is expected to review the application this summer.

The purpose of the Asthma Intervention Research 2 (AIR2) trial was to evaluate the safety and effectiveness of the Alair System in 297 patients with severe asthma at 30 centers in six countries who were symptomatic despite being treated with high doses of inhaled corticosteroids and long-acting bronchodilators.

The trial was randomized, double blind, and sham controlled, and the primary effectiveness end point was significant improvement from baseline in Asthma Quality of Life Questionnaire (AQLQ) score.

Of the 297 patients 196 received bronchial thermoplasty while 101 received a sham bronchoscopy in which no radiofrequency energy was applied. The average age of patients was 41 years, and more than half were female.

Dr. Castro reported that 79% of patients in the treatment group had significant clinical improvements in their average AQLQ scores at 12 months, compared with 64% of patients in the sham group, a difference that was statistically significant.

Compared with patients in the sham group, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, a 36% reduction in patients reporting asthma (multiple symptoms) as an adverse event, and a 66% reduction in days lost from work, school, or other activities caused by respiratory symptoms.

If the Alair system is approved for use, Dr. Castro expects a significant impact on the pulmonology field.

“This is a new treatment for a lung disease that is very common, so our field is going to have to get comfortable with this new device and new treatment,” he commented.

“I think it's going to have a significant impact on how pulmonologists are trained on this new device. If this gets approved there will be a need for training workshops so that physicians are comfortable with its use. I think it's going to have a profound impact on our care of these patients with disabling asthma.”

While the cost of the procedure will vary by practice setting, he expects it to be in the ballpark of a bronchoscopy.

Dr. Castro disclosed that he is a paid consultant for Asthmatx, which funded the study.

There was marked improvement in patients who were already 'getting maximal treatment with the standard of care.' DR. CASTRO

SAN DIEGO — The Alair Bronchial Thermoplasty System produced significant improvements in quality of life in 79% of patients with severe asthma who underwent treatment, compared with 64% of sham controls, results from a randomized, multicenter pivotal trial demonstrated.

Moreover, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, and a 66% reduction in days lost from work, school, or other activities due to respiratory symptoms.

The findings exceeded the expectations of principal investigator Dr. Mario Castro, professor of medicine and pediatrics at Washington University, St. Louis. “These patients were getting maximal treatment with the standard of care,” Dr. Castro said during an interview at an international conference of the American Thoracic Society, where the work was presented. “Beyond that we were able to get a marked improvement in quality of life, health care utilization, and days lost from school or work. Those are meaningful end points for our patients.”

One of the patients Dr. Castro treated was a long-distance runner who had been sidelined because of the severity of his asthma. After undergoing bronchial thermoplasty he returned to running and went on to compete in a marathon.

“You can't get more of a testament than that,” he said.

Developed by Asthmatx Inc. of Sunnyvale, Calif., the Alair Bronchial Thermoplasty system is an investigational device that delivers radiofrequency energy to the airway walls during a bronchoscopic procedure in an effort to reduce the amount of airway smooth muscle.

The procedure, which takes 30–45 minutes to perform, is not designed to replace standard of care therapy, Dr. Castro said, but rather as “an add-on treatment we can do once patients are not achieving good control with the standard of therapy. It's nice to have something else to look forward to with these patients, because they come to your office and they're really desperate for something new in treatment.”

After their first treatment patients return for two additional bronchoscopic treatments spaced 2–3 weeks apart. “It's definitely a time commitment in terms of getting the treatment, recovering, and getting the two additional treatments,” noted Dr. Castro, who also directs Washington University's Asthma and Airway Translational Research Unit. “But you compare that to having to take a drug every day for the rest of your life, it's a small investment.”

The Alair System has received a CE mark for use in the European Union. In the United States a premarket approval application has been submitted to the Food and Drug Administration, which is expected to review the application this summer.

The purpose of the Asthma Intervention Research 2 (AIR2) trial was to evaluate the safety and effectiveness of the Alair System in 297 patients with severe asthma at 30 centers in six countries who were symptomatic despite being treated with high doses of inhaled corticosteroids and long-acting bronchodilators.

The trial was randomized, double blind, and sham controlled, and the primary effectiveness end point was significant improvement from baseline in Asthma Quality of Life Questionnaire (AQLQ) score.

Of the 297 patients 196 received bronchial thermoplasty while 101 received a sham bronchoscopy in which no radiofrequency energy was applied. The average age of patients was 41 years, and more than half were female.

Dr. Castro reported that 79% of patients in the treatment group had significant clinical improvements in their average AQLQ scores at 12 months, compared with 64% of patients in the sham group, a difference that was statistically significant.

Compared with patients in the sham group, patients in the treatment group had a 32% reduction in asthma attacks, an 84% reduction in emergency room visits for respiratory symptoms, a 36% reduction in patients reporting asthma (multiple symptoms) as an adverse event, and a 66% reduction in days lost from work, school, or other activities caused by respiratory symptoms.

If the Alair system is approved for use, Dr. Castro expects a significant impact on the pulmonology field.

“This is a new treatment for a lung disease that is very common, so our field is going to have to get comfortable with this new device and new treatment,” he commented.

“I think it's going to have a significant impact on how pulmonologists are trained on this new device. If this gets approved there will be a need for training workshops so that physicians are comfortable with its use. I think it's going to have a profound impact on our care of these patients with disabling asthma.”

While the cost of the procedure will vary by practice setting, he expects it to be in the ballpark of a bronchoscopy.

Dr. Castro disclosed that he is a paid consultant for Asthmatx, which funded the study.

There was marked improvement in patients who were already 'getting maximal treatment with the standard of care.' DR. CASTRO

No screening biomarker appears to work better than CA 125 alone in detecting ovarian cancer, according to an analysis of prediagnostic specimens from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

During a teleconference from the annual meeting of the American Association for Cancer Research, Dr. Daniel W. Cramer reported on a collaboration between the National Cancer Institute's Early Detection Research Network (EDRN) and the Specialized Programs of Research Excellence (SPORE) to compare the best screening markers for ovarian cancer, first in case-control specimens that were drawn at the time of diagnosis (phase II specimens from 160 cases), then in blood that was drawn months or years prior to diagnosis (phase III specimens from 119 cases) among women enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial.

Funded by the NCI, the PLCO trial enrolled more than 150,000 men and women aged 55–74 years to be studied by various screening arms, including one to test CA 125 (cancer antigen 125) and pelvic ultrasound for ovarian cancer, between 1992 and 2001.

“The first question we wished to answer was how much we can infer about a test's performance in prediagnostic specimens based upon their performance at the time of diagnosis,” said Dr. Cramer, professor of obstetrics and gynecology at the Brigham and Women's Hospital and Harvard Medical School, both in Boston. “The second question we wished to answer was whether a panel of markers can add value over a single marker alone, with the current standard being CA 125.”

More than 24 different markers and 4 panels of markers were studied. Dr. Cramer reported that the top-performing marker was CA 125, followed by human epididymis protein 4 (HE4) and CA 72–4.

“Moving from the phase II specimens to the phase III specimens, there was a predictable loss in the performance soonest for markers that might be identified as acute phase reactants,” he said. “But we also found that even the standard markers like CA 125 seemed to lose their value as you got more remote from diagnosis.”

At best, marker panels and algorithms tested in the study added “marginal improvement” over CA 125 alone.

Although the PLCO concluded that general population screening with combined CA 125 and transvaginal ultrasound cannot be recommended, a larger trial in the United Kingdom recently concluded that screening was “feasible” (Lancet Oncol. 2009;10:327–40). In that trial, measurement of CA 125 followed by transvaginal ultrasound as a second-line test was able to achieve a sensitivity of 89.5%, a specificity of 99.8%, a positive predictive value of 35%, and a ratio of surgeries to detected cases of 2.3.

“The differences between the two trials were due to the use of CA 125 before referral for ultrasound and improvement in sensitivity and specificity with serial CA 125 testing,” Dr. Cramer explained.

Although general population screening for ovarian cancer cannot be recommended now, he said, “I think the foundations for moving it forward can be clearer.” This can be accomplished, he proposed, by conducting blood tests followed by ultrasound for positives, not imaging as a primary modality; by using serial CA 125 rather than a static cutoff, and by investigating whether serial markers or the addition of epidemiologic variables can further improve performance.

“I think the NCI should form a stakeholder panel to explore the feasibility of starting a screening trial of ovarian cancer, or at least a demonstration project,” he concluded.

The study was sponsored by the NCI's EDRN and SPORE. Dr. Cramer reported that he had no conflicts to disclose.

No screening biomarker appears to work better than CA 125 alone in detecting ovarian cancer, according to an analysis of prediagnostic specimens from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

During a teleconference from the annual meeting of the American Association for Cancer Research, Dr. Daniel W. Cramer reported on a collaboration between the National Cancer Institute's Early Detection Research Network (EDRN) and the Specialized Programs of Research Excellence (SPORE) to compare the best screening markers for ovarian cancer, first in case-control specimens that were drawn at the time of diagnosis (phase II specimens from 160 cases), then in blood that was drawn months or years prior to diagnosis (phase III specimens from 119 cases) among women enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial.

Funded by the NCI, the PLCO trial enrolled more than 150,000 men and women aged 55–74 years to be studied by various screening arms, including one to test CA 125 (cancer antigen 125) and pelvic ultrasound for ovarian cancer, between 1992 and 2001.

“The first question we wished to answer was how much we can infer about a test's performance in prediagnostic specimens based upon their performance at the time of diagnosis,” said Dr. Cramer, professor of obstetrics and gynecology at the Brigham and Women's Hospital and Harvard Medical School, both in Boston. “The second question we wished to answer was whether a panel of markers can add value over a single marker alone, with the current standard being CA 125.”

More than 24 different markers and 4 panels of markers were studied. Dr. Cramer reported that the top-performing marker was CA 125, followed by human epididymis protein 4 (HE4) and CA 72–4.

“Moving from the phase II specimens to the phase III specimens, there was a predictable loss in the performance soonest for markers that might be identified as acute phase reactants,” he said. “But we also found that even the standard markers like CA 125 seemed to lose their value as you got more remote from diagnosis.”

At best, marker panels and algorithms tested in the study added “marginal improvement” over CA 125 alone.

Although the PLCO concluded that general population screening with combined CA 125 and transvaginal ultrasound cannot be recommended, a larger trial in the United Kingdom recently concluded that screening was “feasible” (Lancet Oncol. 2009;10:327–40). In that trial, measurement of CA 125 followed by transvaginal ultrasound as a second-line test was able to achieve a sensitivity of 89.5%, a specificity of 99.8%, a positive predictive value of 35%, and a ratio of surgeries to detected cases of 2.3.

“The differences between the two trials were due to the use of CA 125 before referral for ultrasound and improvement in sensitivity and specificity with serial CA 125 testing,” Dr. Cramer explained.

Although general population screening for ovarian cancer cannot be recommended now, he said, “I think the foundations for moving it forward can be clearer.” This can be accomplished, he proposed, by conducting blood tests followed by ultrasound for positives, not imaging as a primary modality; by using serial CA 125 rather than a static cutoff, and by investigating whether serial markers or the addition of epidemiologic variables can further improve performance.

“I think the NCI should form a stakeholder panel to explore the feasibility of starting a screening trial of ovarian cancer, or at least a demonstration project,” he concluded.

The study was sponsored by the NCI's EDRN and SPORE. Dr. Cramer reported that he had no conflicts to disclose.

No screening biomarker appears to work better than CA 125 alone in detecting ovarian cancer, according to an analysis of prediagnostic specimens from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

During a teleconference from the annual meeting of the American Association for Cancer Research, Dr. Daniel W. Cramer reported on a collaboration between the National Cancer Institute's Early Detection Research Network (EDRN) and the Specialized Programs of Research Excellence (SPORE) to compare the best screening markers for ovarian cancer, first in case-control specimens that were drawn at the time of diagnosis (phase II specimens from 160 cases), then in blood that was drawn months or years prior to diagnosis (phase III specimens from 119 cases) among women enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial.

Funded by the NCI, the PLCO trial enrolled more than 150,000 men and women aged 55–74 years to be studied by various screening arms, including one to test CA 125 (cancer antigen 125) and pelvic ultrasound for ovarian cancer, between 1992 and 2001.

“The first question we wished to answer was how much we can infer about a test's performance in prediagnostic specimens based upon their performance at the time of diagnosis,” said Dr. Cramer, professor of obstetrics and gynecology at the Brigham and Women's Hospital and Harvard Medical School, both in Boston. “The second question we wished to answer was whether a panel of markers can add value over a single marker alone, with the current standard being CA 125.”

More than 24 different markers and 4 panels of markers were studied. Dr. Cramer reported that the top-performing marker was CA 125, followed by human epididymis protein 4 (HE4) and CA 72–4.

“Moving from the phase II specimens to the phase III specimens, there was a predictable loss in the performance soonest for markers that might be identified as acute phase reactants,” he said. “But we also found that even the standard markers like CA 125 seemed to lose their value as you got more remote from diagnosis.”

At best, marker panels and algorithms tested in the study added “marginal improvement” over CA 125 alone.

Although the PLCO concluded that general population screening with combined CA 125 and transvaginal ultrasound cannot be recommended, a larger trial in the United Kingdom recently concluded that screening was “feasible” (Lancet Oncol. 2009;10:327–40). In that trial, measurement of CA 125 followed by transvaginal ultrasound as a second-line test was able to achieve a sensitivity of 89.5%, a specificity of 99.8%, a positive predictive value of 35%, and a ratio of surgeries to detected cases of 2.3.

“The differences between the two trials were due to the use of CA 125 before referral for ultrasound and improvement in sensitivity and specificity with serial CA 125 testing,” Dr. Cramer explained.

Although general population screening for ovarian cancer cannot be recommended now, he said, “I think the foundations for moving it forward can be clearer.” This can be accomplished, he proposed, by conducting blood tests followed by ultrasound for positives, not imaging as a primary modality; by using serial CA 125 rather than a static cutoff, and by investigating whether serial markers or the addition of epidemiologic variables can further improve performance.

“I think the NCI should form a stakeholder panel to explore the feasibility of starting a screening trial of ovarian cancer, or at least a demonstration project,” he concluded.

The study was sponsored by the NCI's EDRN and SPORE. Dr. Cramer reported that he had no conflicts to disclose.