Dr. Ezekiel J. Emanuel, one of the brains behind Obamacare, has a blunt message for his fellow physicians:

Only you can save America.

He's not just talking about medicine. As might befit someone who holds a faculty title at the business-oriented Wharton School at the University of Pennsylvania, Dr. Emanuel spent much of his keynote address here at the American College of Physicians' annual meeting in San Francisco talking about the U.S. economy. The enormous impact of runaway spending on U.S. health care threatens "everything we care about," including access to health care, state funds available for education, corporate wages for the middle class, and the fiscal health of the nation, he said.

"More than any other group in America, doctors have the power to solve our long-term economic challenges to ensure a prosperous future," Dr. Emanuel said.

If the U.S. health care system were a country, its nearly $3 trillion economy in 2012 would be the fifth largest in the world, behind only the U.S. as a whole, China, Japan, and Germany. "We spend more on health care in this country than the 66 million French spend on everything in their society," he said. "It is an astounding number how much we spend on health care."

Take just the federal portions of Medicare and Medicaid, excluding state spending, and you've still got the 16th largest economy in the world, bigger than the economies of Switzerland, Turkey, or the Netherlands, for example. The impact of any other fiscal variable on the U.S. economy, including Social Security, is swamped by the impact of health care costs, said Dr. Emanuel, who is also chair of medical ethics and health policy at the University of Pennsylvania, Philadelphia.

Per person, the United States far outspends other countries when it comes to health care, and the proportion of the gross domestic product consumed by health care keeps getting larger and larger.

Dr. Emanuel served as a special adviser for health policy to the director of the federal Office of Management and Budget in 2009-2011 - during the design, passage, and first steps to implementation of the Patient Protection and Affordable Care Act (commonly known as Obamacare) - and he seemed to address some critics in absentia who have claimed that health care reform will lead to unwanted rationing of care. There's no need to ration, Dr. Emanuel said. Switzerland doesn't ration care, and it spends far less per capita for what is considered quality health care. "We can do a better job in this country of controlling costs without the need to ration care," he said.

The only way to really control costs is to transform the way U.S. health care is delivered, he said. Ten percent of U.S. patients account for 63% of dollars spent on health care. "You know who they are - people with congestive heart failure, COPD, diabetes, adult asthma, coronary artery disease, cancer. People with chronic multiple chronic illnesses. That's where the money's going. That's where the uneven quality is," and that's where health care delivery needs to improve, he said.

Dr. Emanuel proposed six essential components to transforming the health care system. Among them: The focus needs to be on cost according to value, and getting rid of services with no value. The system must focus on patients' needs, not on physicians' schedules or other concerns. And the system must evolve toward clinicians working as teams including allied health professionals, not as individuals. "We are not going to be, going forward, one-sies and two-sies in practice" anymore, he said.

Greater emphasis on delivering health care via organizations and systems, standardization of processes, and transparency around price and quality will be essential, he added.

Transparency in pricing and quality isn't just something consumers will want. Physicians will want it in order to refer patients to quality care and set prices appropriately, Dr. Emanuel argued. "I think this is inevitable, and I think it's going to happen faster than you think," he said.

Most U.S. physicians are stuck in fee-for-service payment systems, which don't provide the incentives needed for change, he said. Doctors "as a group" should push for changes to the payment system, which will increase physician autonomy but also will assign more financial risk to physicians. "I see no way of getting out of that," Dr. Emanuel said.

In his eyes, if doctors don't push for changes in how health care is delivered, we basically can kiss the U.S. economy and future prosperity good-bye. "Doctors are the only people who can re-engineer the delivery system," he said. "If you don't do it, it ain't gonna happen. It's that simple," he said. All previous reform efforts that did not have physician leadership have failed.

"You have to lead this," he explained.

No one should expect that reforming the fifth-largest economy in the world could be accomplished in just a few years, however. "It's going to take this decade," Dr. Emanuel predicted.

Dr. Emanuel reported having no financial disclosures.

[email protected]

Twitter: @sherryboschert

Dr. Ezekiel J. Emanuel, one of the brains behind Obamacare, has a blunt message for his fellow physicians:

Only you can save America.

He's not just talking about medicine. As might befit someone who holds a faculty title at the business-oriented Wharton School at the University of Pennsylvania, Dr. Emanuel spent much of his keynote address here at the American College of Physicians' annual meeting in San Francisco talking about the U.S. economy. The enormous impact of runaway spending on U.S. health care threatens "everything we care about," including access to health care, state funds available for education, corporate wages for the middle class, and the fiscal health of the nation, he said.

"More than any other group in America, doctors have the power to solve our long-term economic challenges to ensure a prosperous future," Dr. Emanuel said.

If the U.S. health care system were a country, its nearly $3 trillion economy in 2012 would be the fifth largest in the world, behind only the U.S. as a whole, China, Japan, and Germany. "We spend more on health care in this country than the 66 million French spend on everything in their society," he said. "It is an astounding number how much we spend on health care."

Take just the federal portions of Medicare and Medicaid, excluding state spending, and you've still got the 16th largest economy in the world, bigger than the economies of Switzerland, Turkey, or the Netherlands, for example. The impact of any other fiscal variable on the U.S. economy, including Social Security, is swamped by the impact of health care costs, said Dr. Emanuel, who is also chair of medical ethics and health policy at the University of Pennsylvania, Philadelphia.

Per person, the United States far outspends other countries when it comes to health care, and the proportion of the gross domestic product consumed by health care keeps getting larger and larger.

Dr. Emanuel served as a special adviser for health policy to the director of the federal Office of Management and Budget in 2009-2011 - during the design, passage, and first steps to implementation of the Patient Protection and Affordable Care Act (commonly known as Obamacare) - and he seemed to address some critics in absentia who have claimed that health care reform will lead to unwanted rationing of care. There's no need to ration, Dr. Emanuel said. Switzerland doesn't ration care, and it spends far less per capita for what is considered quality health care. "We can do a better job in this country of controlling costs without the need to ration care," he said.

The only way to really control costs is to transform the way U.S. health care is delivered, he said. Ten percent of U.S. patients account for 63% of dollars spent on health care. "You know who they are - people with congestive heart failure, COPD, diabetes, adult asthma, coronary artery disease, cancer. People with chronic multiple chronic illnesses. That's where the money's going. That's where the uneven quality is," and that's where health care delivery needs to improve, he said.

Dr. Emanuel proposed six essential components to transforming the health care system. Among them: The focus needs to be on cost according to value, and getting rid of services with no value. The system must focus on patients' needs, not on physicians' schedules or other concerns. And the system must evolve toward clinicians working as teams including allied health professionals, not as individuals. "We are not going to be, going forward, one-sies and two-sies in practice" anymore, he said.

Greater emphasis on delivering health care via organizations and systems, standardization of processes, and transparency around price and quality will be essential, he added.

Transparency in pricing and quality isn't just something consumers will want. Physicians will want it in order to refer patients to quality care and set prices appropriately, Dr. Emanuel argued. "I think this is inevitable, and I think it's going to happen faster than you think," he said.

Most U.S. physicians are stuck in fee-for-service payment systems, which don't provide the incentives needed for change, he said. Doctors "as a group" should push for changes to the payment system, which will increase physician autonomy but also will assign more financial risk to physicians. "I see no way of getting out of that," Dr. Emanuel said.

In his eyes, if doctors don't push for changes in how health care is delivered, we basically can kiss the U.S. economy and future prosperity good-bye. "Doctors are the only people who can re-engineer the delivery system," he said. "If you don't do it, it ain't gonna happen. It's that simple," he said. All previous reform efforts that did not have physician leadership have failed.

"You have to lead this," he explained.

No one should expect that reforming the fifth-largest economy in the world could be accomplished in just a few years, however. "It's going to take this decade," Dr. Emanuel predicted.

Dr. Emanuel reported having no financial disclosures.

[email protected]

Twitter: @sherryboschert

Dr. Ezekiel J. Emanuel, one of the brains behind Obamacare, has a blunt message for his fellow physicians:

Only you can save America.

He's not just talking about medicine. As might befit someone who holds a faculty title at the business-oriented Wharton School at the University of Pennsylvania, Dr. Emanuel spent much of his keynote address here at the American College of Physicians' annual meeting in San Francisco talking about the U.S. economy. The enormous impact of runaway spending on U.S. health care threatens "everything we care about," including access to health care, state funds available for education, corporate wages for the middle class, and the fiscal health of the nation, he said.

"More than any other group in America, doctors have the power to solve our long-term economic challenges to ensure a prosperous future," Dr. Emanuel said.

If the U.S. health care system were a country, its nearly $3 trillion economy in 2012 would be the fifth largest in the world, behind only the U.S. as a whole, China, Japan, and Germany. "We spend more on health care in this country than the 66 million French spend on everything in their society," he said. "It is an astounding number how much we spend on health care."

Take just the federal portions of Medicare and Medicaid, excluding state spending, and you've still got the 16th largest economy in the world, bigger than the economies of Switzerland, Turkey, or the Netherlands, for example. The impact of any other fiscal variable on the U.S. economy, including Social Security, is swamped by the impact of health care costs, said Dr. Emanuel, who is also chair of medical ethics and health policy at the University of Pennsylvania, Philadelphia.

Per person, the United States far outspends other countries when it comes to health care, and the proportion of the gross domestic product consumed by health care keeps getting larger and larger.

Dr. Emanuel served as a special adviser for health policy to the director of the federal Office of Management and Budget in 2009-2011 - during the design, passage, and first steps to implementation of the Patient Protection and Affordable Care Act (commonly known as Obamacare) - and he seemed to address some critics in absentia who have claimed that health care reform will lead to unwanted rationing of care. There's no need to ration, Dr. Emanuel said. Switzerland doesn't ration care, and it spends far less per capita for what is considered quality health care. "We can do a better job in this country of controlling costs without the need to ration care," he said.

The only way to really control costs is to transform the way U.S. health care is delivered, he said. Ten percent of U.S. patients account for 63% of dollars spent on health care. "You know who they are - people with congestive heart failure, COPD, diabetes, adult asthma, coronary artery disease, cancer. People with chronic multiple chronic illnesses. That's where the money's going. That's where the uneven quality is," and that's where health care delivery needs to improve, he said.

Dr. Emanuel proposed six essential components to transforming the health care system. Among them: The focus needs to be on cost according to value, and getting rid of services with no value. The system must focus on patients' needs, not on physicians' schedules or other concerns. And the system must evolve toward clinicians working as teams including allied health professionals, not as individuals. "We are not going to be, going forward, one-sies and two-sies in practice" anymore, he said.

Greater emphasis on delivering health care via organizations and systems, standardization of processes, and transparency around price and quality will be essential, he added.

Transparency in pricing and quality isn't just something consumers will want. Physicians will want it in order to refer patients to quality care and set prices appropriately, Dr. Emanuel argued. "I think this is inevitable, and I think it's going to happen faster than you think," he said.

Most U.S. physicians are stuck in fee-for-service payment systems, which don't provide the incentives needed for change, he said. Doctors "as a group" should push for changes to the payment system, which will increase physician autonomy but also will assign more financial risk to physicians. "I see no way of getting out of that," Dr. Emanuel said.

In his eyes, if doctors don't push for changes in how health care is delivered, we basically can kiss the U.S. economy and future prosperity good-bye. "Doctors are the only people who can re-engineer the delivery system," he said. "If you don't do it, it ain't gonna happen. It's that simple," he said. All previous reform efforts that did not have physician leadership have failed.

"You have to lead this," he explained.

No one should expect that reforming the fifth-largest economy in the world could be accomplished in just a few years, however. "It's going to take this decade," Dr. Emanuel predicted.

Dr. Emanuel reported having no financial disclosures.

[email protected]

Twitter: @sherryboschert

A new prediction model that uses a familiar phrase can help identify potentially avoidable hospital patient readmissions, according to a report in JAMA Internal Medicine.

The retrospective cohort study, "Potentially Avoidable 30-Day Hospital Readmissions in Medical Patients," used a model dubbed HOSPITAL to create a score that targets patients most likely to benefit from pre-discharge interventions. The model is based on seven factors: hemoglobin at discharge, discharge from an oncology service, sodium levels at discharge, procedure during the index admission, index type of admission, number of admissions in the prior 12 months, and length of stay. The HOSPITAL score had fair discriminatory power (C statistic 0.71) and good calibration, the authors noted.

"By definition, these [interventions] are expensive and you really want to reserve them for the patients that are most likely to benefit," says study co-author Jeffrey Schnipper, MD, MPH, FHM, director of clinical research and an associate physician in the general medicine division at Brigham and Women's Hospital in Boston.

The study identified 879 potentially avoidable discharges out of 10,731 eligible discharges, or 8.5%. The estimated potentially avoidable readmission risk was 18%. Dr. Schnipper says that in absolute reduction, the model could cut 2% to 3% of readmissions.

"This is an evolution of sophistication in how we think about this work," Dr. Schnipper adds. "Not all patients have a preventable readmission. Maybe some of those patients are more likely to benefit. The next step is to prove it. That's the gold standard and that’s our next study." TH

Visit our website for more information on 30-day readmissions.

A new prediction model that uses a familiar phrase can help identify potentially avoidable hospital patient readmissions, according to a report in JAMA Internal Medicine.

The retrospective cohort study, "Potentially Avoidable 30-Day Hospital Readmissions in Medical Patients," used a model dubbed HOSPITAL to create a score that targets patients most likely to benefit from pre-discharge interventions. The model is based on seven factors: hemoglobin at discharge, discharge from an oncology service, sodium levels at discharge, procedure during the index admission, index type of admission, number of admissions in the prior 12 months, and length of stay. The HOSPITAL score had fair discriminatory power (C statistic 0.71) and good calibration, the authors noted.

"By definition, these [interventions] are expensive and you really want to reserve them for the patients that are most likely to benefit," says study co-author Jeffrey Schnipper, MD, MPH, FHM, director of clinical research and an associate physician in the general medicine division at Brigham and Women's Hospital in Boston.

The study identified 879 potentially avoidable discharges out of 10,731 eligible discharges, or 8.5%. The estimated potentially avoidable readmission risk was 18%. Dr. Schnipper says that in absolute reduction, the model could cut 2% to 3% of readmissions.

"This is an evolution of sophistication in how we think about this work," Dr. Schnipper adds. "Not all patients have a preventable readmission. Maybe some of those patients are more likely to benefit. The next step is to prove it. That's the gold standard and that’s our next study." TH

Visit our website for more information on 30-day readmissions.

A new prediction model that uses a familiar phrase can help identify potentially avoidable hospital patient readmissions, according to a report in JAMA Internal Medicine.

The retrospective cohort study, "Potentially Avoidable 30-Day Hospital Readmissions in Medical Patients," used a model dubbed HOSPITAL to create a score that targets patients most likely to benefit from pre-discharge interventions. The model is based on seven factors: hemoglobin at discharge, discharge from an oncology service, sodium levels at discharge, procedure during the index admission, index type of admission, number of admissions in the prior 12 months, and length of stay. The HOSPITAL score had fair discriminatory power (C statistic 0.71) and good calibration, the authors noted.

"By definition, these [interventions] are expensive and you really want to reserve them for the patients that are most likely to benefit," says study co-author Jeffrey Schnipper, MD, MPH, FHM, director of clinical research and an associate physician in the general medicine division at Brigham and Women's Hospital in Boston.

The study identified 879 potentially avoidable discharges out of 10,731 eligible discharges, or 8.5%. The estimated potentially avoidable readmission risk was 18%. Dr. Schnipper says that in absolute reduction, the model could cut 2% to 3% of readmissions.

"This is an evolution of sophistication in how we think about this work," Dr. Schnipper adds. "Not all patients have a preventable readmission. Maybe some of those patients are more likely to benefit. The next step is to prove it. That's the gold standard and that’s our next study." TH

Visit our website for more information on 30-day readmissions.

Everyone is prone to an angry outburst from time to time, and doctors are no exception. With well-documented, negative effects on morale, nurse retention, and patient safety, it's safe to say anger issues crop up from time to time among the nearly 40,000 practicing hospitalists throughout the U.S.

A recent article in Kaiser Health News describes efforts by hospitals to deal with physicians' tirades, such as a three-day counseling program developed at Vanderbilt University in Nashville, Tenn.

"All physicians need to be aware that there should be a 'zero tolerance' attitude for disruptive behavior, hospitalists included, and that disruptive behavior undermines a culture of safety, and therefore can put patients in danger," says Danielle Scheurer, MD, MSCR, SFHM, hospitalist and chief quality officer at Medical University of South Carolina in Charleston and physician editor of The Hospitalist.

In 2009, The Joint Commission issued a sentinel alert about intimidating and disruptive behaviors by physicians and the ways in which hospitals can address the issue.

The problem is not unique to any physician specialty, including hospitalists, says Alan Rosenstein, MD, an internist and disruptive behavior researcher based in San Francisco. A physician's training or personality might contribute to angry outbursts, but excessive workloads will cause pressure, stress, and burnout, which can lead to poor behavior.

"Hospitals can no longer afford to look the other way," Dr. Rosenstein says. "I look at physicians as a precious resource. The organizations they're affiliated with need to be more proactive and empathetic, intervening before the problem reaches the stage of requiring discipline through techniques such as coaching and stress management." TH

Visit our website for more information about the impact of workloads on hospitalists.

Everyone is prone to an angry outburst from time to time, and doctors are no exception. With well-documented, negative effects on morale, nurse retention, and patient safety, it's safe to say anger issues crop up from time to time among the nearly 40,000 practicing hospitalists throughout the U.S.

A recent article in Kaiser Health News describes efforts by hospitals to deal with physicians' tirades, such as a three-day counseling program developed at Vanderbilt University in Nashville, Tenn.

"All physicians need to be aware that there should be a 'zero tolerance' attitude for disruptive behavior, hospitalists included, and that disruptive behavior undermines a culture of safety, and therefore can put patients in danger," says Danielle Scheurer, MD, MSCR, SFHM, hospitalist and chief quality officer at Medical University of South Carolina in Charleston and physician editor of The Hospitalist.

In 2009, The Joint Commission issued a sentinel alert about intimidating and disruptive behaviors by physicians and the ways in which hospitals can address the issue.

The problem is not unique to any physician specialty, including hospitalists, says Alan Rosenstein, MD, an internist and disruptive behavior researcher based in San Francisco. A physician's training or personality might contribute to angry outbursts, but excessive workloads will cause pressure, stress, and burnout, which can lead to poor behavior.

"Hospitals can no longer afford to look the other way," Dr. Rosenstein says. "I look at physicians as a precious resource. The organizations they're affiliated with need to be more proactive and empathetic, intervening before the problem reaches the stage of requiring discipline through techniques such as coaching and stress management." TH

Visit our website for more information about the impact of workloads on hospitalists.

Everyone is prone to an angry outburst from time to time, and doctors are no exception. With well-documented, negative effects on morale, nurse retention, and patient safety, it's safe to say anger issues crop up from time to time among the nearly 40,000 practicing hospitalists throughout the U.S.

A recent article in Kaiser Health News describes efforts by hospitals to deal with physicians' tirades, such as a three-day counseling program developed at Vanderbilt University in Nashville, Tenn.

"All physicians need to be aware that there should be a 'zero tolerance' attitude for disruptive behavior, hospitalists included, and that disruptive behavior undermines a culture of safety, and therefore can put patients in danger," says Danielle Scheurer, MD, MSCR, SFHM, hospitalist and chief quality officer at Medical University of South Carolina in Charleston and physician editor of The Hospitalist.

In 2009, The Joint Commission issued a sentinel alert about intimidating and disruptive behaviors by physicians and the ways in which hospitals can address the issue.

The problem is not unique to any physician specialty, including hospitalists, says Alan Rosenstein, MD, an internist and disruptive behavior researcher based in San Francisco. A physician's training or personality might contribute to angry outbursts, but excessive workloads will cause pressure, stress, and burnout, which can lead to poor behavior.

"Hospitals can no longer afford to look the other way," Dr. Rosenstein says. "I look at physicians as a precious resource. The organizations they're affiliated with need to be more proactive and empathetic, intervening before the problem reaches the stage of requiring discipline through techniques such as coaching and stress management." TH

Visit our website for more information about the impact of workloads on hospitalists.

Alstonia scholaris, a tree that grows 50-80 feet high and belongs to the Apocynaceae family, has a long history of use in traditional and homeopathic medicine, including Ayurvedic medicine in India, where it is known as sapthaparna (Integr. Cancer Ther. 2009;8:273-9), in traditional Chinese medicine (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81), and in traditional medicine in Africa and Australia (Integr. Cancer Ther. 2010;9:261-9). The bark contains the alkaloids ditamine, echitamine (or ditaine), and echitanines; and decoctions or other preparations of the bark have been used to treat gastrointestinal conditions (Grieve M. A Modern Herbal (Vol. 1). New York, Dover Publications, 1971, p. 29). Often called the devil’s tree, the bark of A. scholaris also has been used to treat malaria, cutaneous diseases, tumors, ulcers, chronic respiratory conditions (such as asthma and bronchitis), helminthiasis, and agalactia (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]).

In the study of A. scholaris most directly pertinent to potential dermatologic treatment, Lee et al. found that ethanolic bark extracts of A. scholaris significantly suppressed retinoid-induced skin irritation in vitro and in vivo, in human HaCat keratinocytes. The investigators identified echitamine and loganin as the primary components likely responsible for the anti-inflammatory effects.

Courtesy Wikimedia Commons/Binh Giang/Public Domain

Data showed that A. scholaris dose-dependently inhibited the all-trans retinoic acid–induced releases of the pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vitro. Also in vitro, A. scholaris extract potently suppressed radiation-induced increases in matrix metalloproteinase-1 (MMP-1). Importantly, in a cumulative irritation patch test, the botanical extract diminished retinol-induced skin irritation while enhancing retinoid activity in blocking MMP-1 expression, which is linked closely to cutaneous aging. The authors concluded that A. scholaris appears to have the dual benefits of decreasing irritation associated with retinoids while augmenting their antiaging impact (Evid. Based Complement. Alternat. Med. 2012;2012:190370).

The leaf extract of A. scholaris has been used to treat cold symptoms and tracheitis, and it has been prescribed in hospitals and approved for commercial over-the-counter sale by the State Food and Drugs Administration of China (SFDA) (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81). The broad range of biological properties associated with A. scholaris has been ascribed to particular constituent categories, including alkaloids, flavonoids, and terpenoids (specifically, phenolic acids) (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). These properties include, but are reportedly not limited to, antioxidant, anticancer, anti-inflammatory, antistress, analgesic, antimutagenic, hepatoprotective, immunomodulatory, and chemopreventive activity (Integr. Cancer Ther. 2010;9:261-9; Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). Antineoplastic effects have been linked directly to phytochemical constituents including echitamine, alstonine, pleiocarpamine, O-methylmacralstonine, macralstonine, and lupeol (Integr. Cancer Ther. 2010;9:261-9).

In 2006, Jagetia and Baliga investigated the anticancer activity of A. scholaris alkaloid fractions in vitro in cultured human neoplastic cell lines. They also conducted in vivo studies in tumor-bearing mice. The in vitro data in HeLa cells revealed a time-dependent rise in antineoplastic activity after 24 hours of exposure (25 mcg/mL). Further, once-daily administration of A. scholaris (240 mg/kg) to tumor-bearing mice yielded dose-dependent remissions, although there were toxic presentations at this dosage. The next-lower dose of 210 mg/kg was found to be most effective, with 20% of the mice surviving for as long as 120 days after tumor cell inoculation, compared with none of the control animals treated with saline (Phytother. Res. 2006;20:103-9).

Using an acute-restraint stress model in mice in 2009, Kulkarni and Juvekar evaluated the effects of stress and the impact of a methanolic extract of A. scholaris bark. Pretreatments with the extract of 100, 250, and 500 mg/kg for 7 days were found to exert significant antistress effects. In addition, nootropic activities were observed, with memory functions clearly enhanced in learning tasks. A. scholaris also was associated with significant antioxidant properties. The extract at 200 mcg/mL exhibited maximum scavenging of the stable radical 1,1-diphenyl-2-picrylhydrazyl at 90.11% and the nitric oxide radical at 62.77% (Indian J. Exp. Biol. 2009;47:47-52).

Later in 2009, Jahan et al. reported on their investigation of potential antioxidant and chemopreventive activity displayed by A. scholaris in a two-stage murine model. Skin carcinogenesis development was initiated in Swiss albino mice through one application of 7, 12-dimethyabenz(a)anthrecene (DMBA) and then promoted two weeks later by repeated application of croton oil three times per week through 16 weeks. The investigators found a lower incidence of tumors, tumor yield, tumor burden, and number of papillomas in mice treated with A. scholaris extract as compared to untreated controls (Integr. Cancer Ther. 2009;8:273-9).

In 2010, Shang et al. conducted multiple studies using A. scholaris. In the first published report, they assessed the anti-inflammatory and analgesic properties of the ethanolic leaf extract to validate its use in traditional Chinese medicine and modern clinical medicine. The investigators first determined that analgesic activity was conferred as the ethyl acetate and alkaloid fractions significantly diminished acetic acid-induced reactions in mice and, along with the ethanolic extract, reduced xylene-induced ear edema.

The researchers also performed in vivo and in vitro assessments of anti-inflammatory activity again on xylene-induced ear edema and carrageenan-induced air pouch formation in mice, as well as cyclooxygenase (COX)-1, -2 and 5-LOX inhibition.

In the air pouch model, A. scholaris alkaloids were found to have significantly spurred superoxide dismutase activity while lowering nitric oxide, prostaglandin E2, and malondialdehyde levels. In vitro tests, supporting evidence from animal models, showed that the three primary alkaloids isolated from A. scholaris leaves (picrinine, vallesamine, and scholaricine) inhibited the inflammatory mediators COX-1, COX-2, and 5-LOX. The researchers also noted that the in vitro anti-inflammatory assay results reinforced the notion of these alkaloids as the bioactive fraction of the plant (J. Ethnopharmacol. 2010;129:174-81).

In their second published report that year, Shang et al. investigated the antitussive and anti-asthmatic activities of the ethanolic extract, fractions, and chief alkaloids of A. scholaris leaf.

The researchers tested for antitussive effects using ammonia-induced or sulfur dioxide-induced coughing in mice and citric acid-induced coughing in guinea pigs. They evaluated anti-asthmatic activity via histamine-induced bronchoconstriction in guinea pigs. They also measured phenol red volume in murine tracheas to assess expectorant activity.

The data indicated antitussive activity, with significant alkaloid suppression of ammonia-induced coughing frequency in mice. Latency periods of sulfur dioxide-induced cough in mice and citric acid-induced cough in guinea pigs increased, and cough frequency in guinea pigs decreased.

Anti-asthmatic effects, such as suppression of convulsion, were observed in guinea pigs. In the expectorant assessment, tracheal phenol red production was increased. The researchers identified picrinine as the primary alkaloid responsible for these activities (J. Ethnopharmacol. 2010;129:293-8).

In addition, Jahan and Goyal showed that pretreatment with A. scholaris bark extract protected the bone marrow of mice against radiation-induced chromosomal damage and micronuclei induction (J Environ. Pathol. Toxicol. Oncol. 2010;29:101-11).

Conclusion

Despite the dearth of research on A. scholaris, the existing data are intriguing, particularly the findings that A. scholaris may have the capacity to amplify the anti-aging activity of retinoids while blunting their irritating effects. Although more research is needed to determine the dermatologic value of A. scholaris, the pursuit may potentially prove fruitful.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Alstonia scholaris, a tree that grows 50-80 feet high and belongs to the Apocynaceae family, has a long history of use in traditional and homeopathic medicine, including Ayurvedic medicine in India, where it is known as sapthaparna (Integr. Cancer Ther. 2009;8:273-9), in traditional Chinese medicine (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81), and in traditional medicine in Africa and Australia (Integr. Cancer Ther. 2010;9:261-9). The bark contains the alkaloids ditamine, echitamine (or ditaine), and echitanines; and decoctions or other preparations of the bark have been used to treat gastrointestinal conditions (Grieve M. A Modern Herbal (Vol. 1). New York, Dover Publications, 1971, p. 29). Often called the devil’s tree, the bark of A. scholaris also has been used to treat malaria, cutaneous diseases, tumors, ulcers, chronic respiratory conditions (such as asthma and bronchitis), helminthiasis, and agalactia (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]).

In the study of A. scholaris most directly pertinent to potential dermatologic treatment, Lee et al. found that ethanolic bark extracts of A. scholaris significantly suppressed retinoid-induced skin irritation in vitro and in vivo, in human HaCat keratinocytes. The investigators identified echitamine and loganin as the primary components likely responsible for the anti-inflammatory effects.

Courtesy Wikimedia Commons/Binh Giang/Public Domain

Data showed that A. scholaris dose-dependently inhibited the all-trans retinoic acid–induced releases of the pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vitro. Also in vitro, A. scholaris extract potently suppressed radiation-induced increases in matrix metalloproteinase-1 (MMP-1). Importantly, in a cumulative irritation patch test, the botanical extract diminished retinol-induced skin irritation while enhancing retinoid activity in blocking MMP-1 expression, which is linked closely to cutaneous aging. The authors concluded that A. scholaris appears to have the dual benefits of decreasing irritation associated with retinoids while augmenting their antiaging impact (Evid. Based Complement. Alternat. Med. 2012;2012:190370).

The leaf extract of A. scholaris has been used to treat cold symptoms and tracheitis, and it has been prescribed in hospitals and approved for commercial over-the-counter sale by the State Food and Drugs Administration of China (SFDA) (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81). The broad range of biological properties associated with A. scholaris has been ascribed to particular constituent categories, including alkaloids, flavonoids, and terpenoids (specifically, phenolic acids) (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). These properties include, but are reportedly not limited to, antioxidant, anticancer, anti-inflammatory, antistress, analgesic, antimutagenic, hepatoprotective, immunomodulatory, and chemopreventive activity (Integr. Cancer Ther. 2010;9:261-9; Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). Antineoplastic effects have been linked directly to phytochemical constituents including echitamine, alstonine, pleiocarpamine, O-methylmacralstonine, macralstonine, and lupeol (Integr. Cancer Ther. 2010;9:261-9).

In 2006, Jagetia and Baliga investigated the anticancer activity of A. scholaris alkaloid fractions in vitro in cultured human neoplastic cell lines. They also conducted in vivo studies in tumor-bearing mice. The in vitro data in HeLa cells revealed a time-dependent rise in antineoplastic activity after 24 hours of exposure (25 mcg/mL). Further, once-daily administration of A. scholaris (240 mg/kg) to tumor-bearing mice yielded dose-dependent remissions, although there were toxic presentations at this dosage. The next-lower dose of 210 mg/kg was found to be most effective, with 20% of the mice surviving for as long as 120 days after tumor cell inoculation, compared with none of the control animals treated with saline (Phytother. Res. 2006;20:103-9).

Using an acute-restraint stress model in mice in 2009, Kulkarni and Juvekar evaluated the effects of stress and the impact of a methanolic extract of A. scholaris bark. Pretreatments with the extract of 100, 250, and 500 mg/kg for 7 days were found to exert significant antistress effects. In addition, nootropic activities were observed, with memory functions clearly enhanced in learning tasks. A. scholaris also was associated with significant antioxidant properties. The extract at 200 mcg/mL exhibited maximum scavenging of the stable radical 1,1-diphenyl-2-picrylhydrazyl at 90.11% and the nitric oxide radical at 62.77% (Indian J. Exp. Biol. 2009;47:47-52).

Later in 2009, Jahan et al. reported on their investigation of potential antioxidant and chemopreventive activity displayed by A. scholaris in a two-stage murine model. Skin carcinogenesis development was initiated in Swiss albino mice through one application of 7, 12-dimethyabenz(a)anthrecene (DMBA) and then promoted two weeks later by repeated application of croton oil three times per week through 16 weeks. The investigators found a lower incidence of tumors, tumor yield, tumor burden, and number of papillomas in mice treated with A. scholaris extract as compared to untreated controls (Integr. Cancer Ther. 2009;8:273-9).

In 2010, Shang et al. conducted multiple studies using A. scholaris. In the first published report, they assessed the anti-inflammatory and analgesic properties of the ethanolic leaf extract to validate its use in traditional Chinese medicine and modern clinical medicine. The investigators first determined that analgesic activity was conferred as the ethyl acetate and alkaloid fractions significantly diminished acetic acid-induced reactions in mice and, along with the ethanolic extract, reduced xylene-induced ear edema.

The researchers also performed in vivo and in vitro assessments of anti-inflammatory activity again on xylene-induced ear edema and carrageenan-induced air pouch formation in mice, as well as cyclooxygenase (COX)-1, -2 and 5-LOX inhibition.

In the air pouch model, A. scholaris alkaloids were found to have significantly spurred superoxide dismutase activity while lowering nitric oxide, prostaglandin E2, and malondialdehyde levels. In vitro tests, supporting evidence from animal models, showed that the three primary alkaloids isolated from A. scholaris leaves (picrinine, vallesamine, and scholaricine) inhibited the inflammatory mediators COX-1, COX-2, and 5-LOX. The researchers also noted that the in vitro anti-inflammatory assay results reinforced the notion of these alkaloids as the bioactive fraction of the plant (J. Ethnopharmacol. 2010;129:174-81).

In their second published report that year, Shang et al. investigated the antitussive and anti-asthmatic activities of the ethanolic extract, fractions, and chief alkaloids of A. scholaris leaf.

The researchers tested for antitussive effects using ammonia-induced or sulfur dioxide-induced coughing in mice and citric acid-induced coughing in guinea pigs. They evaluated anti-asthmatic activity via histamine-induced bronchoconstriction in guinea pigs. They also measured phenol red volume in murine tracheas to assess expectorant activity.

The data indicated antitussive activity, with significant alkaloid suppression of ammonia-induced coughing frequency in mice. Latency periods of sulfur dioxide-induced cough in mice and citric acid-induced cough in guinea pigs increased, and cough frequency in guinea pigs decreased.

Anti-asthmatic effects, such as suppression of convulsion, were observed in guinea pigs. In the expectorant assessment, tracheal phenol red production was increased. The researchers identified picrinine as the primary alkaloid responsible for these activities (J. Ethnopharmacol. 2010;129:293-8).

In addition, Jahan and Goyal showed that pretreatment with A. scholaris bark extract protected the bone marrow of mice against radiation-induced chromosomal damage and micronuclei induction (J Environ. Pathol. Toxicol. Oncol. 2010;29:101-11).

Conclusion

Despite the dearth of research on A. scholaris, the existing data are intriguing, particularly the findings that A. scholaris may have the capacity to amplify the anti-aging activity of retinoids while blunting their irritating effects. Although more research is needed to determine the dermatologic value of A. scholaris, the pursuit may potentially prove fruitful.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Alstonia scholaris, a tree that grows 50-80 feet high and belongs to the Apocynaceae family, has a long history of use in traditional and homeopathic medicine, including Ayurvedic medicine in India, where it is known as sapthaparna (Integr. Cancer Ther. 2009;8:273-9), in traditional Chinese medicine (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81), and in traditional medicine in Africa and Australia (Integr. Cancer Ther. 2010;9:261-9). The bark contains the alkaloids ditamine, echitamine (or ditaine), and echitanines; and decoctions or other preparations of the bark have been used to treat gastrointestinal conditions (Grieve M. A Modern Herbal (Vol. 1). New York, Dover Publications, 1971, p. 29). Often called the devil’s tree, the bark of A. scholaris also has been used to treat malaria, cutaneous diseases, tumors, ulcers, chronic respiratory conditions (such as asthma and bronchitis), helminthiasis, and agalactia (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]).

In the study of A. scholaris most directly pertinent to potential dermatologic treatment, Lee et al. found that ethanolic bark extracts of A. scholaris significantly suppressed retinoid-induced skin irritation in vitro and in vivo, in human HaCat keratinocytes. The investigators identified echitamine and loganin as the primary components likely responsible for the anti-inflammatory effects.

Courtesy Wikimedia Commons/Binh Giang/Public Domain

Data showed that A. scholaris dose-dependently inhibited the all-trans retinoic acid–induced releases of the pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vitro. Also in vitro, A. scholaris extract potently suppressed radiation-induced increases in matrix metalloproteinase-1 (MMP-1). Importantly, in a cumulative irritation patch test, the botanical extract diminished retinol-induced skin irritation while enhancing retinoid activity in blocking MMP-1 expression, which is linked closely to cutaneous aging. The authors concluded that A. scholaris appears to have the dual benefits of decreasing irritation associated with retinoids while augmenting their antiaging impact (Evid. Based Complement. Alternat. Med. 2012;2012:190370).

The leaf extract of A. scholaris has been used to treat cold symptoms and tracheitis, and it has been prescribed in hospitals and approved for commercial over-the-counter sale by the State Food and Drugs Administration of China (SFDA) (J. Ethnopharmacol. 2010;129:293-8; J. Ethnopharmacol. 2010;129:174-81). The broad range of biological properties associated with A. scholaris has been ascribed to particular constituent categories, including alkaloids, flavonoids, and terpenoids (specifically, phenolic acids) (Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). These properties include, but are reportedly not limited to, antioxidant, anticancer, anti-inflammatory, antistress, analgesic, antimutagenic, hepatoprotective, immunomodulatory, and chemopreventive activity (Integr. Cancer Ther. 2010;9:261-9; Chin. J. Integr. Med. 2012 Mar 28 [Epub ahead of print]). Antineoplastic effects have been linked directly to phytochemical constituents including echitamine, alstonine, pleiocarpamine, O-methylmacralstonine, macralstonine, and lupeol (Integr. Cancer Ther. 2010;9:261-9).

In 2006, Jagetia and Baliga investigated the anticancer activity of A. scholaris alkaloid fractions in vitro in cultured human neoplastic cell lines. They also conducted in vivo studies in tumor-bearing mice. The in vitro data in HeLa cells revealed a time-dependent rise in antineoplastic activity after 24 hours of exposure (25 mcg/mL). Further, once-daily administration of A. scholaris (240 mg/kg) to tumor-bearing mice yielded dose-dependent remissions, although there were toxic presentations at this dosage. The next-lower dose of 210 mg/kg was found to be most effective, with 20% of the mice surviving for as long as 120 days after tumor cell inoculation, compared with none of the control animals treated with saline (Phytother. Res. 2006;20:103-9).

Using an acute-restraint stress model in mice in 2009, Kulkarni and Juvekar evaluated the effects of stress and the impact of a methanolic extract of A. scholaris bark. Pretreatments with the extract of 100, 250, and 500 mg/kg for 7 days were found to exert significant antistress effects. In addition, nootropic activities were observed, with memory functions clearly enhanced in learning tasks. A. scholaris also was associated with significant antioxidant properties. The extract at 200 mcg/mL exhibited maximum scavenging of the stable radical 1,1-diphenyl-2-picrylhydrazyl at 90.11% and the nitric oxide radical at 62.77% (Indian J. Exp. Biol. 2009;47:47-52).

Later in 2009, Jahan et al. reported on their investigation of potential antioxidant and chemopreventive activity displayed by A. scholaris in a two-stage murine model. Skin carcinogenesis development was initiated in Swiss albino mice through one application of 7, 12-dimethyabenz(a)anthrecene (DMBA) and then promoted two weeks later by repeated application of croton oil three times per week through 16 weeks. The investigators found a lower incidence of tumors, tumor yield, tumor burden, and number of papillomas in mice treated with A. scholaris extract as compared to untreated controls (Integr. Cancer Ther. 2009;8:273-9).

In 2010, Shang et al. conducted multiple studies using A. scholaris. In the first published report, they assessed the anti-inflammatory and analgesic properties of the ethanolic leaf extract to validate its use in traditional Chinese medicine and modern clinical medicine. The investigators first determined that analgesic activity was conferred as the ethyl acetate and alkaloid fractions significantly diminished acetic acid-induced reactions in mice and, along with the ethanolic extract, reduced xylene-induced ear edema.

The researchers also performed in vivo and in vitro assessments of anti-inflammatory activity again on xylene-induced ear edema and carrageenan-induced air pouch formation in mice, as well as cyclooxygenase (COX)-1, -2 and 5-LOX inhibition.

In the air pouch model, A. scholaris alkaloids were found to have significantly spurred superoxide dismutase activity while lowering nitric oxide, prostaglandin E2, and malondialdehyde levels. In vitro tests, supporting evidence from animal models, showed that the three primary alkaloids isolated from A. scholaris leaves (picrinine, vallesamine, and scholaricine) inhibited the inflammatory mediators COX-1, COX-2, and 5-LOX. The researchers also noted that the in vitro anti-inflammatory assay results reinforced the notion of these alkaloids as the bioactive fraction of the plant (J. Ethnopharmacol. 2010;129:174-81).

In their second published report that year, Shang et al. investigated the antitussive and anti-asthmatic activities of the ethanolic extract, fractions, and chief alkaloids of A. scholaris leaf.

The researchers tested for antitussive effects using ammonia-induced or sulfur dioxide-induced coughing in mice and citric acid-induced coughing in guinea pigs. They evaluated anti-asthmatic activity via histamine-induced bronchoconstriction in guinea pigs. They also measured phenol red volume in murine tracheas to assess expectorant activity.

The data indicated antitussive activity, with significant alkaloid suppression of ammonia-induced coughing frequency in mice. Latency periods of sulfur dioxide-induced cough in mice and citric acid-induced cough in guinea pigs increased, and cough frequency in guinea pigs decreased.

Anti-asthmatic effects, such as suppression of convulsion, were observed in guinea pigs. In the expectorant assessment, tracheal phenol red production was increased. The researchers identified picrinine as the primary alkaloid responsible for these activities (J. Ethnopharmacol. 2010;129:293-8).

In addition, Jahan and Goyal showed that pretreatment with A. scholaris bark extract protected the bone marrow of mice against radiation-induced chromosomal damage and micronuclei induction (J Environ. Pathol. Toxicol. Oncol. 2010;29:101-11).

Conclusion

Despite the dearth of research on A. scholaris, the existing data are intriguing, particularly the findings that A. scholaris may have the capacity to amplify the anti-aging activity of retinoids while blunting their irritating effects. Although more research is needed to determine the dermatologic value of A. scholaris, the pursuit may potentially prove fruitful.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Neil Fishman, MD, associate chief medical officer at the University of Pennsylvania Health System in Philadelphia, sounds like a football coach when he says the best way to fight carbapenem-resistant Enterobacteriaceae (CRE) infections is with a good defense. Hospitalists and others should focus on contact precautions, hand hygiene, removing gowns and gloves before entering new rooms, and even suggest better room cleanings when trying to prevent the spread of CRE, he says. In fact, he has worked with SHM leadership for years to engage hospitalists about the “critical necessity of antimicrobial stewardship.”

“They’re all critical to prevent transmission,” says Dr. Fishman, who chairs the CDC’s Health Infection Control Practices Advisory Committee. “That’s part of the things that can be done in the here and now to try to prevent people from getting infected with these organisms. It’s what the CDC calls ‘detect and prevent.’”

Dr. Fishman’s suggestions echo findings in a new CDC report that shows a threefold increase in the proportion of Enterobacteriaceae bugs that proved resistant to carbapenem in the past decade. The data, in the CDC’s Morbidity and Mortality Weekly Report, showed the proportion of reported Enterobacteriacae that were CRE infections jumped to 4.2% in 2011 from 1.2% in

“It is a very serious public health threat,” says co-author Alex Kallen, MD, MPH, a medical epidemiologist and outbreak response coordinator in the CDC’s Division of Healthcare Quality Promotion. “Maybe it’s not that common now, but with no action, it has the potential to become much more common—like a lot of the other MDROs [multidrug-resistant organisms] that hospitalists see regularly. [Hospitalists] have a lot of control over some of the things that could potentially lead to increased transmission.”

Part of the problem, Dr. Fishman says, is a lack of antibiotic options. Polymyxins briefly showed success against the bacteria, but performance is waning. Dr. Fishman estimates it will be up to eight years before a new antibiotic to combat the infection is in widespread use.

Listen to Dr. Fishman discuss the history of treating CRE infections and importance of antimicrobial stewardship.

Both he and Dr. Kallen say hospitalists can help reduce the spread of CRE through antibiotic stewardship, review of detailed patient histories to ferret out risk factors, and dedication to contact precautions and hand hygiene.

Dr. Kallen notes hospitalists also can play a leadership role in coordinating efforts for patients transferring between hospitals and other institutions (i.e. skilled nursing or assisted-living facilities). Part of being that leader is refusing to dismiss possible CRE cases.

“If you’re a place that doesn’t see this very often, and you see one, that’s a big deal,” Dr. Kallen says. “It needs to be acted on aggressively. Being proactive is much more effective than waiting until it’s common and then trying to intervene.” TH

Richard Quinn is a freelance writer in New Jersey.

Neil Fishman, MD, associate chief medical officer at the University of Pennsylvania Health System in Philadelphia, sounds like a football coach when he says the best way to fight carbapenem-resistant Enterobacteriaceae (CRE) infections is with a good defense. Hospitalists and others should focus on contact precautions, hand hygiene, removing gowns and gloves before entering new rooms, and even suggest better room cleanings when trying to prevent the spread of CRE, he says. In fact, he has worked with SHM leadership for years to engage hospitalists about the “critical necessity of antimicrobial stewardship.”

“They’re all critical to prevent transmission,” says Dr. Fishman, who chairs the CDC’s Health Infection Control Practices Advisory Committee. “That’s part of the things that can be done in the here and now to try to prevent people from getting infected with these organisms. It’s what the CDC calls ‘detect and prevent.’”

Dr. Fishman’s suggestions echo findings in a new CDC report that shows a threefold increase in the proportion of Enterobacteriaceae bugs that proved resistant to carbapenem in the past decade. The data, in the CDC’s Morbidity and Mortality Weekly Report, showed the proportion of reported Enterobacteriacae that were CRE infections jumped to 4.2% in 2011 from 1.2% in

“It is a very serious public health threat,” says co-author Alex Kallen, MD, MPH, a medical epidemiologist and outbreak response coordinator in the CDC’s Division of Healthcare Quality Promotion. “Maybe it’s not that common now, but with no action, it has the potential to become much more common—like a lot of the other MDROs [multidrug-resistant organisms] that hospitalists see regularly. [Hospitalists] have a lot of control over some of the things that could potentially lead to increased transmission.”

Part of the problem, Dr. Fishman says, is a lack of antibiotic options. Polymyxins briefly showed success against the bacteria, but performance is waning. Dr. Fishman estimates it will be up to eight years before a new antibiotic to combat the infection is in widespread use.

Listen to Dr. Fishman discuss the history of treating CRE infections and importance of antimicrobial stewardship.

Both he and Dr. Kallen say hospitalists can help reduce the spread of CRE through antibiotic stewardship, review of detailed patient histories to ferret out risk factors, and dedication to contact precautions and hand hygiene.

Dr. Kallen notes hospitalists also can play a leadership role in coordinating efforts for patients transferring between hospitals and other institutions (i.e. skilled nursing or assisted-living facilities). Part of being that leader is refusing to dismiss possible CRE cases.

“If you’re a place that doesn’t see this very often, and you see one, that’s a big deal,” Dr. Kallen says. “It needs to be acted on aggressively. Being proactive is much more effective than waiting until it’s common and then trying to intervene.” TH

Richard Quinn is a freelance writer in New Jersey.

Neil Fishman, MD, associate chief medical officer at the University of Pennsylvania Health System in Philadelphia, sounds like a football coach when he says the best way to fight carbapenem-resistant Enterobacteriaceae (CRE) infections is with a good defense. Hospitalists and others should focus on contact precautions, hand hygiene, removing gowns and gloves before entering new rooms, and even suggest better room cleanings when trying to prevent the spread of CRE, he says. In fact, he has worked with SHM leadership for years to engage hospitalists about the “critical necessity of antimicrobial stewardship.”

“They’re all critical to prevent transmission,” says Dr. Fishman, who chairs the CDC’s Health Infection Control Practices Advisory Committee. “That’s part of the things that can be done in the here and now to try to prevent people from getting infected with these organisms. It’s what the CDC calls ‘detect and prevent.’”

Dr. Fishman’s suggestions echo findings in a new CDC report that shows a threefold increase in the proportion of Enterobacteriaceae bugs that proved resistant to carbapenem in the past decade. The data, in the CDC’s Morbidity and Mortality Weekly Report, showed the proportion of reported Enterobacteriacae that were CRE infections jumped to 4.2% in 2011 from 1.2% in

“It is a very serious public health threat,” says co-author Alex Kallen, MD, MPH, a medical epidemiologist and outbreak response coordinator in the CDC’s Division of Healthcare Quality Promotion. “Maybe it’s not that common now, but with no action, it has the potential to become much more common—like a lot of the other MDROs [multidrug-resistant organisms] that hospitalists see regularly. [Hospitalists] have a lot of control over some of the things that could potentially lead to increased transmission.”

Part of the problem, Dr. Fishman says, is a lack of antibiotic options. Polymyxins briefly showed success against the bacteria, but performance is waning. Dr. Fishman estimates it will be up to eight years before a new antibiotic to combat the infection is in widespread use.

Listen to Dr. Fishman discuss the history of treating CRE infections and importance of antimicrobial stewardship.

Both he and Dr. Kallen say hospitalists can help reduce the spread of CRE through antibiotic stewardship, review of detailed patient histories to ferret out risk factors, and dedication to contact precautions and hand hygiene.

Dr. Kallen notes hospitalists also can play a leadership role in coordinating efforts for patients transferring between hospitals and other institutions (i.e. skilled nursing or assisted-living facilities). Part of being that leader is refusing to dismiss possible CRE cases.

“If you’re a place that doesn’t see this very often, and you see one, that’s a big deal,” Dr. Kallen says. “It needs to be acted on aggressively. Being proactive is much more effective than waiting until it’s common and then trying to intervene.” TH

Richard Quinn is a freelance writer in New Jersey.

Thirty years ago, many college patients I saw were covered by a school health policy written by a company I will call James S. Fred Insurance. Because this happened long before electronic claims submissions, we knew that ours were handled by someone named Lucille.

For reasons I no longer recall, I found myself strolling in downtown Boston one afternoon, when I saw a large office building that listed none other than James S. Fred Insurance as a major tenant. I took the elevator to the 17th floor, went in, and asked for Lucille.

Sure enough, sitting in a quiet cubicle, there she was: a pleasant older woman who did the college accounts, a small cog in a massive wheel. When I introduced myself, Lucille recognized my name and greeted me warmly.

"I never expected to meet you in person," I said, "But since I have, perhaps I can tell you about a problem we’re having with reimbursement. I described the issue. Lucille took out a large manual, listing the terms of the company’s college coverage. "Here it is," she said, showing me the relevant paragraph.

I thanked her and took the book. But when I read the paragraph, I saw that it didn’t say what she said it said. I pointed this out.

"My goodness," said Lucille. "You’re right. We should be reimbursing you for that, shouldn’t we?"

So that was it. The massive insurance giant in the glass-and-steel skyscraper turned out to be a little old lady in a cubicle who couldn’t read the manual. It was like pulling back the curtain and finding out that the Wizard of Oz was a geezer with a wind machine.

I thought of this last week when I had a talk about my own personal coverage with a Midwest insurer. The issue turned on their responsibility for covering a service provided by a physician who does not participate in Medicare at all. (Yes, I am on Medicare now.)

Last year, I spoke with a human at the company who explained that all I needed to do was confirm that the provider was not Medicare affiliated. This year, after paying a few claims, they apparently changed their mind and sent letters demanding payback and saying they would only pay what Medicare would have, even if Medicare actually didn’t.

I appealed. The appeal was denied. I could not reach a human. I gave up.

Then last week, Jeanette called from Chicago. She described herself as Head of the Appeals Division, in a voice that sounded like Marian, the no-nonsense librarian from "The Music Man."

"Our policy is based on what’s in the manual," she said. "Let me see if I can find it. Oh, here it is." Then she read a passage about doctors who don’t accept Medicare assignments. "We ask them to submit claims anyway," she explained.

"Forgive me," I said, "but a doctor who doesn’t accept assignment is a Medicare provider, just one who won’t accept as full payment what Medicare allows. My doctor is not a Medicare provider at all. He can’t submit a claim, because he doesn’t have a Medicare provider number."

"My goodness," said Jeanette. "I think you may be right. Have you documented this for us?"

"With every claim," I said. "I followed your company’s instructions, and attached to every claim my doctor’s letter saying he doesn’t participate in Medicare. You should have a dozen or so copies of this letter. If you can’t find any, I’ll be happy to send another."

"Oh, here it is!" said Jeanette. "Yes, I see. We need to rectify this."

I danced a mental jig around the room. Lucille must be long retired, but I’d love to invite her and Jeanette for tea.

"I’m really grateful to have the chance to speak to person," I told Jeanette. "Thanks so much for listening."

You could hear Jeanette glow right through the phone. "Why, you’re welcome," she said. "You’ve made my whole day!"

Faceless bureaucracies can seem intimidating, impersonal, malevolent, diabolical, Kafkaesque.

But sometimes, they’re just little old ladies who have trouble reading manuals. To find out, just follow the yellow brick road.

Dr. Rockoff practices dermatology in Brookline, Mass.

Thirty years ago, many college patients I saw were covered by a school health policy written by a company I will call James S. Fred Insurance. Because this happened long before electronic claims submissions, we knew that ours were handled by someone named Lucille.

For reasons I no longer recall, I found myself strolling in downtown Boston one afternoon, when I saw a large office building that listed none other than James S. Fred Insurance as a major tenant. I took the elevator to the 17th floor, went in, and asked for Lucille.

Sure enough, sitting in a quiet cubicle, there she was: a pleasant older woman who did the college accounts, a small cog in a massive wheel. When I introduced myself, Lucille recognized my name and greeted me warmly.

"I never expected to meet you in person," I said, "But since I have, perhaps I can tell you about a problem we’re having with reimbursement. I described the issue. Lucille took out a large manual, listing the terms of the company’s college coverage. "Here it is," she said, showing me the relevant paragraph.

I thanked her and took the book. But when I read the paragraph, I saw that it didn’t say what she said it said. I pointed this out.

"My goodness," said Lucille. "You’re right. We should be reimbursing you for that, shouldn’t we?"

So that was it. The massive insurance giant in the glass-and-steel skyscraper turned out to be a little old lady in a cubicle who couldn’t read the manual. It was like pulling back the curtain and finding out that the Wizard of Oz was a geezer with a wind machine.

I thought of this last week when I had a talk about my own personal coverage with a Midwest insurer. The issue turned on their responsibility for covering a service provided by a physician who does not participate in Medicare at all. (Yes, I am on Medicare now.)

Last year, I spoke with a human at the company who explained that all I needed to do was confirm that the provider was not Medicare affiliated. This year, after paying a few claims, they apparently changed their mind and sent letters demanding payback and saying they would only pay what Medicare would have, even if Medicare actually didn’t.

I appealed. The appeal was denied. I could not reach a human. I gave up.

Then last week, Jeanette called from Chicago. She described herself as Head of the Appeals Division, in a voice that sounded like Marian, the no-nonsense librarian from "The Music Man."

"Our policy is based on what’s in the manual," she said. "Let me see if I can find it. Oh, here it is." Then she read a passage about doctors who don’t accept Medicare assignments. "We ask them to submit claims anyway," she explained.

"Forgive me," I said, "but a doctor who doesn’t accept assignment is a Medicare provider, just one who won’t accept as full payment what Medicare allows. My doctor is not a Medicare provider at all. He can’t submit a claim, because he doesn’t have a Medicare provider number."

"My goodness," said Jeanette. "I think you may be right. Have you documented this for us?"

"With every claim," I said. "I followed your company’s instructions, and attached to every claim my doctor’s letter saying he doesn’t participate in Medicare. You should have a dozen or so copies of this letter. If you can’t find any, I’ll be happy to send another."

"Oh, here it is!" said Jeanette. "Yes, I see. We need to rectify this."

I danced a mental jig around the room. Lucille must be long retired, but I’d love to invite her and Jeanette for tea.

"I’m really grateful to have the chance to speak to person," I told Jeanette. "Thanks so much for listening."

You could hear Jeanette glow right through the phone. "Why, you’re welcome," she said. "You’ve made my whole day!"

Faceless bureaucracies can seem intimidating, impersonal, malevolent, diabolical, Kafkaesque.

But sometimes, they’re just little old ladies who have trouble reading manuals. To find out, just follow the yellow brick road.

Dr. Rockoff practices dermatology in Brookline, Mass.

Thirty years ago, many college patients I saw were covered by a school health policy written by a company I will call James S. Fred Insurance. Because this happened long before electronic claims submissions, we knew that ours were handled by someone named Lucille.

For reasons I no longer recall, I found myself strolling in downtown Boston one afternoon, when I saw a large office building that listed none other than James S. Fred Insurance as a major tenant. I took the elevator to the 17th floor, went in, and asked for Lucille.

Sure enough, sitting in a quiet cubicle, there she was: a pleasant older woman who did the college accounts, a small cog in a massive wheel. When I introduced myself, Lucille recognized my name and greeted me warmly.

"I never expected to meet you in person," I said, "But since I have, perhaps I can tell you about a problem we’re having with reimbursement. I described the issue. Lucille took out a large manual, listing the terms of the company’s college coverage. "Here it is," she said, showing me the relevant paragraph.

I thanked her and took the book. But when I read the paragraph, I saw that it didn’t say what she said it said. I pointed this out.

"My goodness," said Lucille. "You’re right. We should be reimbursing you for that, shouldn’t we?"

So that was it. The massive insurance giant in the glass-and-steel skyscraper turned out to be a little old lady in a cubicle who couldn’t read the manual. It was like pulling back the curtain and finding out that the Wizard of Oz was a geezer with a wind machine.

I thought of this last week when I had a talk about my own personal coverage with a Midwest insurer. The issue turned on their responsibility for covering a service provided by a physician who does not participate in Medicare at all. (Yes, I am on Medicare now.)

Last year, I spoke with a human at the company who explained that all I needed to do was confirm that the provider was not Medicare affiliated. This year, after paying a few claims, they apparently changed their mind and sent letters demanding payback and saying they would only pay what Medicare would have, even if Medicare actually didn’t.

I appealed. The appeal was denied. I could not reach a human. I gave up.

Then last week, Jeanette called from Chicago. She described herself as Head of the Appeals Division, in a voice that sounded like Marian, the no-nonsense librarian from "The Music Man."

"Our policy is based on what’s in the manual," she said. "Let me see if I can find it. Oh, here it is." Then she read a passage about doctors who don’t accept Medicare assignments. "We ask them to submit claims anyway," she explained.

"Forgive me," I said, "but a doctor who doesn’t accept assignment is a Medicare provider, just one who won’t accept as full payment what Medicare allows. My doctor is not a Medicare provider at all. He can’t submit a claim, because he doesn’t have a Medicare provider number."

"My goodness," said Jeanette. "I think you may be right. Have you documented this for us?"

"With every claim," I said. "I followed your company’s instructions, and attached to every claim my doctor’s letter saying he doesn’t participate in Medicare. You should have a dozen or so copies of this letter. If you can’t find any, I’ll be happy to send another."

"Oh, here it is!" said Jeanette. "Yes, I see. We need to rectify this."

I danced a mental jig around the room. Lucille must be long retired, but I’d love to invite her and Jeanette for tea.

"I’m really grateful to have the chance to speak to person," I told Jeanette. "Thanks so much for listening."

You could hear Jeanette glow right through the phone. "Why, you’re welcome," she said. "You’ve made my whole day!"

Faceless bureaucracies can seem intimidating, impersonal, malevolent, diabolical, Kafkaesque.

But sometimes, they’re just little old ladies who have trouble reading manuals. To find out, just follow the yellow brick road.

Dr. Rockoff practices dermatology in Brookline, Mass.

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph
) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph
) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph
) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5