The greatest impact of new guidelines from the American Heart Association (AHA) that suggest additional therapies for treatment of more serious cases of DVT might be in prodding HM leaders to take ownership of existing standards to ensure greater compliance.

The review aims to help doctors "identify the severity of these disorders and to select who might be eligible for more invasive therapies, such as clot-busting drugs, catheter-based treatments or surgery," M. Sean McMurtry, MD, PhD, co-chair of the writing group said in a prepared statement. The guidelines outline multiple treatment options, including the use of fibrinolytic drugs, catheter-based interventions, treatment with surgery to remove the blood clots and use of filters. Additional guidance for treating pediatric patients is included.

But Gregory A. Maynard, MD, SFHM, hospital medicine division chief at the University of California at San Diego, says most hospitalists deal with more routine cases of DVT and VTE than the research paper highlights. Physicians need to take more control of the existing patchwork of guidelines recommended by various research and established protocols, he adds.

"What's missing in this paper ... is how to make those things happen more reliably," Dr. Maynard says. "To me, the hospitalist needs to look at guidelines like this and say, 'How can we make them happen reliably?'"

For example, Dr. Maynard notes that for the treatment of iliofemoral DVT, it is recommended to both overlap warfarin and heparin, as well as have patients wear elastic compression stockings. Yet, he says, neither of those recommendations is routinely followed. In fact, he says of the former: "I would guess the percentage of patients getting these stockings is a distinct minority."

And while that kind of reliability is tough to guarantee, it's one of the cornerstones of SHM's VTE prevention resource room and mentored implementation program.

The greatest impact of new guidelines from the American Heart Association (AHA) that suggest additional therapies for treatment of more serious cases of DVT might be in prodding HM leaders to take ownership of existing standards to ensure greater compliance.

The review aims to help doctors "identify the severity of these disorders and to select who might be eligible for more invasive therapies, such as clot-busting drugs, catheter-based treatments or surgery," M. Sean McMurtry, MD, PhD, co-chair of the writing group said in a prepared statement. The guidelines outline multiple treatment options, including the use of fibrinolytic drugs, catheter-based interventions, treatment with surgery to remove the blood clots and use of filters. Additional guidance for treating pediatric patients is included.

But Gregory A. Maynard, MD, SFHM, hospital medicine division chief at the University of California at San Diego, says most hospitalists deal with more routine cases of DVT and VTE than the research paper highlights. Physicians need to take more control of the existing patchwork of guidelines recommended by various research and established protocols, he adds.

"What's missing in this paper ... is how to make those things happen more reliably," Dr. Maynard says. "To me, the hospitalist needs to look at guidelines like this and say, 'How can we make them happen reliably?'"

For example, Dr. Maynard notes that for the treatment of iliofemoral DVT, it is recommended to both overlap warfarin and heparin, as well as have patients wear elastic compression stockings. Yet, he says, neither of those recommendations is routinely followed. In fact, he says of the former: "I would guess the percentage of patients getting these stockings is a distinct minority."

And while that kind of reliability is tough to guarantee, it's one of the cornerstones of SHM's VTE prevention resource room and mentored implementation program.

The greatest impact of new guidelines from the American Heart Association (AHA) that suggest additional therapies for treatment of more serious cases of DVT might be in prodding HM leaders to take ownership of existing standards to ensure greater compliance.

The review aims to help doctors "identify the severity of these disorders and to select who might be eligible for more invasive therapies, such as clot-busting drugs, catheter-based treatments or surgery," M. Sean McMurtry, MD, PhD, co-chair of the writing group said in a prepared statement. The guidelines outline multiple treatment options, including the use of fibrinolytic drugs, catheter-based interventions, treatment with surgery to remove the blood clots and use of filters. Additional guidance for treating pediatric patients is included.

But Gregory A. Maynard, MD, SFHM, hospital medicine division chief at the University of California at San Diego, says most hospitalists deal with more routine cases of DVT and VTE than the research paper highlights. Physicians need to take more control of the existing patchwork of guidelines recommended by various research and established protocols, he adds.

"What's missing in this paper ... is how to make those things happen more reliably," Dr. Maynard says. "To me, the hospitalist needs to look at guidelines like this and say, 'How can we make them happen reliably?'"

For example, Dr. Maynard notes that for the treatment of iliofemoral DVT, it is recommended to both overlap warfarin and heparin, as well as have patients wear elastic compression stockings. Yet, he says, neither of those recommendations is routinely followed. In fact, he says of the former: "I would guess the percentage of patients getting these stockings is a distinct minority."

And while that kind of reliability is tough to guarantee, it's one of the cornerstones of SHM's VTE prevention resource room and mentored implementation program.

Apollo Medical Holdings of Glendale, Calif., which provides hospitalist services in 24 California hospitals, recently took a step toward expanding its business model and diversifying its continuum of services by acquiring Los Angeles-based Aligned Healthcare Group, a provider of physician call centers and specialized care management services for health plans.

Call centers provide patients in the community with telephonic access to physicians and other health professionals for help with urgent medical questions, health assessments, and triage. The Aligned call center was developed in 2009 at the request of Anthem Blue Cross, which wanted to provide an ED alternative for its Medi-Cal members who needed access to a physician, explains Bette Jane Reese, RN, MHA, COO of Apollo's Aligned Division.

Apollo's care continuum will include follow-up calls to recently discharged patients, post-discharge calls to PCPs, and early discharge planning. The model partners a hospitalist with a care management nurse; together, they function as a virtual team across settings.

The acquisition gives Apollo a leg up on developing a continuum of care management across settings, she adds. "I believe enhanced hospitalist models will be a trend. As healthcare revenues become tighter, with more entities coming together in what's called accountable healthcare, the name of the game is coordination between settings and providers," she says.

Experts have emphasized the importance of hospitalists looking beyond the four walls of their facility and participating in "cross-continuum teams" as a key to managing care transitions and preventing rehospitalizations. Apollo hopes its new collaboration will help eliminate communication breakdowns between hospitalists and PCPs, Reese says. "By merging these functions, we get a combination of efficient hospitalist care with a bridge to the next setting, and coordination with multiple payer entities. It all wraps around the integrated hospitalist model."

HM's future in Apollo's model might include staffing outpatient clinics located on the hospital campus for patients to return for follow-up care after they are discharged, or even making home visits for patients who need additional medical oversight. "We see the issues and problems that cause patients to go back to the hospital," Reese says. "We can suggest quality improvement approaches to address the root causes of avoidable readmissions."

Apollo Medical Holdings of Glendale, Calif., which provides hospitalist services in 24 California hospitals, recently took a step toward expanding its business model and diversifying its continuum of services by acquiring Los Angeles-based Aligned Healthcare Group, a provider of physician call centers and specialized care management services for health plans.

Call centers provide patients in the community with telephonic access to physicians and other health professionals for help with urgent medical questions, health assessments, and triage. The Aligned call center was developed in 2009 at the request of Anthem Blue Cross, which wanted to provide an ED alternative for its Medi-Cal members who needed access to a physician, explains Bette Jane Reese, RN, MHA, COO of Apollo's Aligned Division.

Apollo's care continuum will include follow-up calls to recently discharged patients, post-discharge calls to PCPs, and early discharge planning. The model partners a hospitalist with a care management nurse; together, they function as a virtual team across settings.

The acquisition gives Apollo a leg up on developing a continuum of care management across settings, she adds. "I believe enhanced hospitalist models will be a trend. As healthcare revenues become tighter, with more entities coming together in what's called accountable healthcare, the name of the game is coordination between settings and providers," she says.

Experts have emphasized the importance of hospitalists looking beyond the four walls of their facility and participating in "cross-continuum teams" as a key to managing care transitions and preventing rehospitalizations. Apollo hopes its new collaboration will help eliminate communication breakdowns between hospitalists and PCPs, Reese says. "By merging these functions, we get a combination of efficient hospitalist care with a bridge to the next setting, and coordination with multiple payer entities. It all wraps around the integrated hospitalist model."

HM's future in Apollo's model might include staffing outpatient clinics located on the hospital campus for patients to return for follow-up care after they are discharged, or even making home visits for patients who need additional medical oversight. "We see the issues and problems that cause patients to go back to the hospital," Reese says. "We can suggest quality improvement approaches to address the root causes of avoidable readmissions."

Apollo Medical Holdings of Glendale, Calif., which provides hospitalist services in 24 California hospitals, recently took a step toward expanding its business model and diversifying its continuum of services by acquiring Los Angeles-based Aligned Healthcare Group, a provider of physician call centers and specialized care management services for health plans.

Call centers provide patients in the community with telephonic access to physicians and other health professionals for help with urgent medical questions, health assessments, and triage. The Aligned call center was developed in 2009 at the request of Anthem Blue Cross, which wanted to provide an ED alternative for its Medi-Cal members who needed access to a physician, explains Bette Jane Reese, RN, MHA, COO of Apollo's Aligned Division.

Apollo's care continuum will include follow-up calls to recently discharged patients, post-discharge calls to PCPs, and early discharge planning. The model partners a hospitalist with a care management nurse; together, they function as a virtual team across settings.

The acquisition gives Apollo a leg up on developing a continuum of care management across settings, she adds. "I believe enhanced hospitalist models will be a trend. As healthcare revenues become tighter, with more entities coming together in what's called accountable healthcare, the name of the game is coordination between settings and providers," she says.

Experts have emphasized the importance of hospitalists looking beyond the four walls of their facility and participating in "cross-continuum teams" as a key to managing care transitions and preventing rehospitalizations. Apollo hopes its new collaboration will help eliminate communication breakdowns between hospitalists and PCPs, Reese says. "By merging these functions, we get a combination of efficient hospitalist care with a bridge to the next setting, and coordination with multiple payer entities. It all wraps around the integrated hospitalist model."

HM's future in Apollo's model might include staffing outpatient clinics located on the hospital campus for patients to return for follow-up care after they are discharged, or even making home visits for patients who need additional medical oversight. "We see the issues and problems that cause patients to go back to the hospital," Reese says. "We can suggest quality improvement approaches to address the root causes of avoidable readmissions."

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

After five years in the department of otolaryngology/head and neck surgery at the University of California at San Francisco (UCSF), Matthew Russell, MD, is joining the faculty as an assistant professor. Normally, such a career arc is commonplace. But Dr. Russell’s new job title—ENT hospitalist—is worth noting. In fact, it could be groundbreaking.

When Dr. Russell begins work this summer, he might be the only otolaryngologist in the country whose entire patient census and surgical pipeline will be generated by admissions to his hospital. Although there are otolaryngologists around the country who spend the majority of their time working with inpatients, nearly all work an clinical outpatient service as well.

“The hospitalist model turns the traditional ENT practice on its head,” Dr. Russell says. “An otolaryngology practice we think of as being centered around the clinic, and the clinic and referrals is where we generate our operative cases and our patient load. The question really becomes: Can you sustain a practice without a clinic-based model?”

David Nielsen, MD, executive vice president and CEO of the American Academy of Otolaryngology-Head and Neck Surgery, says that while there is no current groundswell for the model, he can envision physicians being drawn to it for two reasons: an aging cohort of otolaryngologists and younger physicians looking for work-life balance.

The hospitalist model turns the traditional ENT practice on its head.

—Matthew Russell, MD, oto-hospitalist, University of California at San Francisco

And while the otolaryngology world at large has not yet answered in unison, the presence of what some are calling an oto-hospitalist is the latest in a series of what HM pioneer Robert Wachter, MD, MHM, has termed “hyphenated hospitalists.” Dr. Wachter, chief of hospital medicine and chief of the medical service at UCSF Medical Center, a former SHM board member, and author of the Wachter’s World blog, says the needs of otolaryngology present the same set of circumstances that allowed internal-medicine-based HM to flourish.

“The forces,” Dr. Wachter wrote in January on his blog, “are the same: sick patients, highly specialized providers who may not be comfortable with all the issues that arise in the hospital, and the need to focus on system improvement.”

But just adding hospitalist to a job title is not the mark of HM’s presence.

“You can have any hyphenated medical specialist managing patients, but the question is, What are you getting out of it as a hospital or a hospitalist, or as an institution?” adds Gulshan Sharma MD, MPH, associate professor at the University of Texas Medical Branch at Galveston. “The hospitalists really have to figure out their boundaries.”

Dr. Russell says some physicians could be dismissive of the idea of an oto-hospitalist because they’re not clear about the role. They might picture a glorified resident constantly walking between wards to serve as a secondary opinion for other specialists. “There is a perception that this may not be a glamorous position,” he adds. “There’s an assumption that the position is nonsurgical.”

Dr. Russell’s workflow will include rounding and consultations across different wards, and he will assist with complex airway issues. But he also will perform surgeries and work on quality-improvement (QI) initiatives. For those who doubt the variety that a purely inpatient setting can deliver, Dr. Russell eagerly quotes statistics from a two-year pilot program UCSF ran before hiring him as a full-time ENT hospitalist:

• 300 inpatient consultations the first year, not including ED and urgent care;
• Sinonasal and laryngotracheal were the most common consults;
• 200 procedures generated billings; and
• 45% of procedures were laryngotracheal, 33% were sinonasal/anterior skull base, and 10% were otologic.

"The hospitalist movement, in general, fills a need for the acute-care setting and manages a different set of problems than is seen in the ambulatory clinics,” Dr. Russell says. “That same basic issue is found in otolaryngology. I think it’s an area that is perhaps underappreciated.”

Richard Quinn is a freelance writer based in New Jersey.

After five years in the department of otolaryngology/head and neck surgery at the University of California at San Francisco (UCSF), Matthew Russell, MD, is joining the faculty as an assistant professor. Normally, such a career arc is commonplace. But Dr. Russell’s new job title—ENT hospitalist—is worth noting. In fact, it could be groundbreaking.

When Dr. Russell begins work this summer, he might be the only otolaryngologist in the country whose entire patient census and surgical pipeline will be generated by admissions to his hospital. Although there are otolaryngologists around the country who spend the majority of their time working with inpatients, nearly all work an clinical outpatient service as well.

“The hospitalist model turns the traditional ENT practice on its head,” Dr. Russell says. “An otolaryngology practice we think of as being centered around the clinic, and the clinic and referrals is where we generate our operative cases and our patient load. The question really becomes: Can you sustain a practice without a clinic-based model?”

David Nielsen, MD, executive vice president and CEO of the American Academy of Otolaryngology-Head and Neck Surgery, says that while there is no current groundswell for the model, he can envision physicians being drawn to it for two reasons: an aging cohort of otolaryngologists and younger physicians looking for work-life balance.

The hospitalist model turns the traditional ENT practice on its head.

—Matthew Russell, MD, oto-hospitalist, University of California at San Francisco

And while the otolaryngology world at large has not yet answered in unison, the presence of what some are calling an oto-hospitalist is the latest in a series of what HM pioneer Robert Wachter, MD, MHM, has termed “hyphenated hospitalists.” Dr. Wachter, chief of hospital medicine and chief of the medical service at UCSF Medical Center, a former SHM board member, and author of the Wachter’s World blog, says the needs of otolaryngology present the same set of circumstances that allowed internal-medicine-based HM to flourish.

“The forces,” Dr. Wachter wrote in January on his blog, “are the same: sick patients, highly specialized providers who may not be comfortable with all the issues that arise in the hospital, and the need to focus on system improvement.”

But just adding hospitalist to a job title is not the mark of HM’s presence.

“You can have any hyphenated medical specialist managing patients, but the question is, What are you getting out of it as a hospital or a hospitalist, or as an institution?” adds Gulshan Sharma MD, MPH, associate professor at the University of Texas Medical Branch at Galveston. “The hospitalists really have to figure out their boundaries.”

Dr. Russell says some physicians could be dismissive of the idea of an oto-hospitalist because they’re not clear about the role. They might picture a glorified resident constantly walking between wards to serve as a secondary opinion for other specialists. “There is a perception that this may not be a glamorous position,” he adds. “There’s an assumption that the position is nonsurgical.”

Dr. Russell’s workflow will include rounding and consultations across different wards, and he will assist with complex airway issues. But he also will perform surgeries and work on quality-improvement (QI) initiatives. For those who doubt the variety that a purely inpatient setting can deliver, Dr. Russell eagerly quotes statistics from a two-year pilot program UCSF ran before hiring him as a full-time ENT hospitalist:

• 300 inpatient consultations the first year, not including ED and urgent care;
• Sinonasal and laryngotracheal were the most common consults;
• 200 procedures generated billings; and
• 45% of procedures were laryngotracheal, 33% were sinonasal/anterior skull base, and 10% were otologic.

"The hospitalist movement, in general, fills a need for the acute-care setting and manages a different set of problems than is seen in the ambulatory clinics,” Dr. Russell says. “That same basic issue is found in otolaryngology. I think it’s an area that is perhaps underappreciated.”

Richard Quinn is a freelance writer based in New Jersey.

After five years in the department of otolaryngology/head and neck surgery at the University of California at San Francisco (UCSF), Matthew Russell, MD, is joining the faculty as an assistant professor. Normally, such a career arc is commonplace. But Dr. Russell’s new job title—ENT hospitalist—is worth noting. In fact, it could be groundbreaking.

When Dr. Russell begins work this summer, he might be the only otolaryngologist in the country whose entire patient census and surgical pipeline will be generated by admissions to his hospital. Although there are otolaryngologists around the country who spend the majority of their time working with inpatients, nearly all work an clinical outpatient service as well.

“The hospitalist model turns the traditional ENT practice on its head,” Dr. Russell says. “An otolaryngology practice we think of as being centered around the clinic, and the clinic and referrals is where we generate our operative cases and our patient load. The question really becomes: Can you sustain a practice without a clinic-based model?”

David Nielsen, MD, executive vice president and CEO of the American Academy of Otolaryngology-Head and Neck Surgery, says that while there is no current groundswell for the model, he can envision physicians being drawn to it for two reasons: an aging cohort of otolaryngologists and younger physicians looking for work-life balance.

The hospitalist model turns the traditional ENT practice on its head.

—Matthew Russell, MD, oto-hospitalist, University of California at San Francisco

And while the otolaryngology world at large has not yet answered in unison, the presence of what some are calling an oto-hospitalist is the latest in a series of what HM pioneer Robert Wachter, MD, MHM, has termed “hyphenated hospitalists.” Dr. Wachter, chief of hospital medicine and chief of the medical service at UCSF Medical Center, a former SHM board member, and author of the Wachter’s World blog, says the needs of otolaryngology present the same set of circumstances that allowed internal-medicine-based HM to flourish.

“The forces,” Dr. Wachter wrote in January on his blog, “are the same: sick patients, highly specialized providers who may not be comfortable with all the issues that arise in the hospital, and the need to focus on system improvement.”

But just adding hospitalist to a job title is not the mark of HM’s presence.

“You can have any hyphenated medical specialist managing patients, but the question is, What are you getting out of it as a hospital or a hospitalist, or as an institution?” adds Gulshan Sharma MD, MPH, associate professor at the University of Texas Medical Branch at Galveston. “The hospitalists really have to figure out their boundaries.”

Dr. Russell says some physicians could be dismissive of the idea of an oto-hospitalist because they’re not clear about the role. They might picture a glorified resident constantly walking between wards to serve as a secondary opinion for other specialists. “There is a perception that this may not be a glamorous position,” he adds. “There’s an assumption that the position is nonsurgical.”

Dr. Russell’s workflow will include rounding and consultations across different wards, and he will assist with complex airway issues. But he also will perform surgeries and work on quality-improvement (QI) initiatives. For those who doubt the variety that a purely inpatient setting can deliver, Dr. Russell eagerly quotes statistics from a two-year pilot program UCSF ran before hiring him as a full-time ENT hospitalist:

• 300 inpatient consultations the first year, not including ED and urgent care;
• Sinonasal and laryngotracheal were the most common consults;
• 200 procedures generated billings; and
• 45% of procedures were laryngotracheal, 33% were sinonasal/anterior skull base, and 10% were otologic.

"The hospitalist movement, in general, fills a need for the acute-care setting and manages a different set of problems than is seen in the ambulatory clinics,” Dr. Russell says. “That same basic issue is found in otolaryngology. I think it’s an area that is perhaps underappreciated.”

Richard Quinn is a freelance writer based in New Jersey.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.