Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”

Acalabrutinib, an oral drug that is a more specific Bruton tyrosine kinase (BTK) inhibitor related to ibrutinib, produced a high response rate and durable remissions at a median 14 months of follow-up in an uncontrolled phase I/II trial of 61 adults with relapsed chronic lymphocytic leukemia, according to a report published online Jan. 28 in the New England Journal of Medicine.

The study patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletions, and 75% had unmutated immunoglobulin heavy-chain variable genes.

At the analysis, one patient had died from pneumonia at 13 months and CLL had progressed at 16 months in another patient. The overall response rate among the 60 evaluable patients was 95%, with a partial response in 85% and a partial response with lymphocytosis in 10%. The rate of stable disease was 5%. Adverse events were mostly mild and self-limiting; eight patients (13%) discontinued treatment, said Dr. John C. Byrd of the division of hematology, Ohio State University, Columbus, and his associates.

All 18 patients with chromosome 17p13.1 deletions responded to acalabrutinib, with a partial response in 89% and a partial response with lymphocytosis in 11%. One patient with a chromosome 17p13.1 deletion had disease progression, and this patient had a C481S (major clone) mutation in BTK and an L845F (minor clone) mutation in PLCγ2.

No cases of Richter’s transformation occurred.

Patients were treated at six sites in the United States and the United Kingdom. Four different doses of oral acalabrutinib were used in the first phase of the study; the drug’s low toxicity permitted a twice-daily 100-mg dose in phase II of the study. Twice-daily dosing promoted continuous levels of drug binding to BTK, according to the researchers. It is hoped that this approach will decrease drug resistance and will perhaps lower the rate of transformation into large-cell lymphoma.

Among patients who had cytopenia at entry into the study, platelet count improved in 62%, hemoglobin levels improved in 76%, and absolute neutrophil count improved in 80%. Among patients who had B symptoms (weight loss, night sweats, and fever) at study entry, those symptoms resolved in 88% by the third cycle of treatment and in 100% by the ninth cycle, Dr. Byrd and his associates said (N Engl J Med. 2016 Jan 28. doi: 10.1056/NEJMoa1509981). The most common adverse events were headache (43% of patients), diarrhea (39%), weight gain (26%), pyrexia (23%), and upper respiratory tract infection (23%). Fewer than 2% of patients developed severe diarrhea, rash, arthralgia, myalgia, bruising, or bleeding.

These findings offered strong justification to further investigate the efficacy and safety of acalabrutinib for relapsed CLL, and a phase III trial is now underway, the investigators added.

Acalabrutinib, an oral drug that is a more specific Bruton tyrosine kinase (BTK) inhibitor related to ibrutinib, produced a high response rate and durable remissions at a median 14 months of follow-up in an uncontrolled phase I/II trial of 61 adults with relapsed chronic lymphocytic leukemia, according to a report published online Jan. 28 in the New England Journal of Medicine.

The study patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletions, and 75% had unmutated immunoglobulin heavy-chain variable genes.

At the analysis, one patient had died from pneumonia at 13 months and CLL had progressed at 16 months in another patient. The overall response rate among the 60 evaluable patients was 95%, with a partial response in 85% and a partial response with lymphocytosis in 10%. The rate of stable disease was 5%. Adverse events were mostly mild and self-limiting; eight patients (13%) discontinued treatment, said Dr. John C. Byrd of the division of hematology, Ohio State University, Columbus, and his associates.

All 18 patients with chromosome 17p13.1 deletions responded to acalabrutinib, with a partial response in 89% and a partial response with lymphocytosis in 11%. One patient with a chromosome 17p13.1 deletion had disease progression, and this patient had a C481S (major clone) mutation in BTK and an L845F (minor clone) mutation in PLCγ2.

No cases of Richter’s transformation occurred.

Patients were treated at six sites in the United States and the United Kingdom. Four different doses of oral acalabrutinib were used in the first phase of the study; the drug’s low toxicity permitted a twice-daily 100-mg dose in phase II of the study. Twice-daily dosing promoted continuous levels of drug binding to BTK, according to the researchers. It is hoped that this approach will decrease drug resistance and will perhaps lower the rate of transformation into large-cell lymphoma.

Among patients who had cytopenia at entry into the study, platelet count improved in 62%, hemoglobin levels improved in 76%, and absolute neutrophil count improved in 80%. Among patients who had B symptoms (weight loss, night sweats, and fever) at study entry, those symptoms resolved in 88% by the third cycle of treatment and in 100% by the ninth cycle, Dr. Byrd and his associates said (N Engl J Med. 2016 Jan 28. doi: 10.1056/NEJMoa1509981). The most common adverse events were headache (43% of patients), diarrhea (39%), weight gain (26%), pyrexia (23%), and upper respiratory tract infection (23%). Fewer than 2% of patients developed severe diarrhea, rash, arthralgia, myalgia, bruising, or bleeding.

These findings offered strong justification to further investigate the efficacy and safety of acalabrutinib for relapsed CLL, and a phase III trial is now underway, the investigators added.

Acalabrutinib, an oral drug that is a more specific Bruton tyrosine kinase (BTK) inhibitor related to ibrutinib, produced a high response rate and durable remissions at a median 14 months of follow-up in an uncontrolled phase I/II trial of 61 adults with relapsed chronic lymphocytic leukemia, according to a report published online Jan. 28 in the New England Journal of Medicine.

The study patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletions, and 75% had unmutated immunoglobulin heavy-chain variable genes.

At the analysis, one patient had died from pneumonia at 13 months and CLL had progressed at 16 months in another patient. The overall response rate among the 60 evaluable patients was 95%, with a partial response in 85% and a partial response with lymphocytosis in 10%. The rate of stable disease was 5%. Adverse events were mostly mild and self-limiting; eight patients (13%) discontinued treatment, said Dr. John C. Byrd of the division of hematology, Ohio State University, Columbus, and his associates.

All 18 patients with chromosome 17p13.1 deletions responded to acalabrutinib, with a partial response in 89% and a partial response with lymphocytosis in 11%. One patient with a chromosome 17p13.1 deletion had disease progression, and this patient had a C481S (major clone) mutation in BTK and an L845F (minor clone) mutation in PLCγ2.

No cases of Richter’s transformation occurred.

Patients were treated at six sites in the United States and the United Kingdom. Four different doses of oral acalabrutinib were used in the first phase of the study; the drug’s low toxicity permitted a twice-daily 100-mg dose in phase II of the study. Twice-daily dosing promoted continuous levels of drug binding to BTK, according to the researchers. It is hoped that this approach will decrease drug resistance and will perhaps lower the rate of transformation into large-cell lymphoma.

Among patients who had cytopenia at entry into the study, platelet count improved in 62%, hemoglobin levels improved in 76%, and absolute neutrophil count improved in 80%. Among patients who had B symptoms (weight loss, night sweats, and fever) at study entry, those symptoms resolved in 88% by the third cycle of treatment and in 100% by the ninth cycle, Dr. Byrd and his associates said (N Engl J Med. 2016 Jan 28. doi: 10.1056/NEJMoa1509981). The most common adverse events were headache (43% of patients), diarrhea (39%), weight gain (26%), pyrexia (23%), and upper respiratory tract infection (23%). Fewer than 2% of patients developed severe diarrhea, rash, arthralgia, myalgia, bruising, or bleeding.

These findings offered strong justification to further investigate the efficacy and safety of acalabrutinib for relapsed CLL, and a phase III trial is now underway, the investigators added.

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!