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Team tracks blood formation in real time
in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism. 
in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism.
in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism.
CRT may pose long-term risk of hormone deficiencies
Photo by Bill Branson
New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.
The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.
These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.
They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.
The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).
GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.
Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.
The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.
GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.
There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.
“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.
“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”
Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.
He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.
Photo by Bill Branson
New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.
The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.
These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.
They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.
The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).
GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.
Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.
The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.
GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.
There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.
“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.
“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”
Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.
He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.
Photo by Bill Branson
New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.
The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.
These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.
They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.
The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).
GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.
Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.
The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.
GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.
There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.
“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.
“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”
Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.
He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.
NICE rejects pomalidomide as MM treatment
In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).
NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.
For patients who have received 2 prior therapies, the agency recommends lenalidomide.
NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.
The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.
This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.
And pomalidomide is recommended for use within NHS Scotland.
Insufficient evidence
The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.
However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.
Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.
Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.
All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.
A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.
In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).
NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.
For patients who have received 2 prior therapies, the agency recommends lenalidomide.
NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.
The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.
This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.
And pomalidomide is recommended for use within NHS Scotland.
Insufficient evidence
The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.
However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.
Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.
Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.
All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.
A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.
In a final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) has said it cannot recommend pomalidomide (Imnovid) for the treatment of multiple myeloma (MM).
NICE recommends thalidomide for most MM patients as a first-line treatment and bortezomib for patients who are unable to receive thalidomide and those who fail first-line treatment.
For patients who have received 2 prior therapies, the agency recommends lenalidomide.
NICE considered pomalidomide for use in MM patients after their third or subsequent relapse.
The agency said it could not recommend pomalidomide, in combination with dexamethasone, within its marketing authorization, which is to treat adults with relapsed and refractory MM who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
“Unfortunately, we cannot recommend pomalidomide, as the analyses from Celgene, the company that markets pomalidomide, showed that the drug does not offer enough benefit to justify its high price,” said Sir Andrew Dillon, NICE chief executive.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues its final guidance, National Health Service (NHS) bodies should make decisions locally on the funding of specific treatments.
This draft guidance does not mean that patients currently taking pomalidomide will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.
And pomalidomide is recommended for use within NHS Scotland.
Insufficient evidence
The committee advising NICE was not able to judge with any confidence how much more effective pomalidomide was compared with current treatment options based on the evidence provided by Celgene before and after consultation.
However, bearing in mind the magnitude of the differences in the overall survival estimates between pomalidomide and high-dose dexamethasone in the phase 3 MM-003 trial, and all data presented to the committee for comparators, the committee was persuaded that pomalidomide extends life for at least 3 months, on average, when compared with standard NHS care.
Nevertheless, considering the incremental cost-effectiveness ratios, the committee concluded that, even with the end-of-life criteria met, the weighting that would have to be placed on the quality-adjusted life-years (QALYs) gained would be too high to consider pomalidomide a cost-effective use of NHS resources.
Also, the committee concluded that the uncertainty in the relative effectiveness of pomalidomide compared with established NHS practice would affect any weighting that could be placed on the QALYs gained.
All cost-per-QALY figures presented by Celgene were over £50,000 compared with bortezomib and over £70,000 compared with bendamustine plus thalidomide and dexamethasone. And the figures would further increase when a number of more realistic assumptions were included in the model, the committee said.
A pack of pomalidomide (21 tablets of 1 mg, 2 mg, 3 mg, or 4 mg) costs £8884. The recommended dosage of the drug is 4 mg once daily, taken on days 1 to 21 of repeated 28 day cycles. Treatment should continue until disease progression.
PE surgery prevents death in severely ill
Photo courtesy of Medical
College of Georgia
Pulmonary embolectomy, a procedure that was virtually abandoned in the 1950s because it resulted in high mortality rates, may actually prevent more deaths in severely ill patients with pulmonary embolism (PE) than current drug therapies alone, according to research published in the Texas Heart Institute Journal.
More than 2 dozen studies conducted between 1961 and 1984 suggest the death rate associated with pulmonary embolectomy is 32%.
But safer techniques have led to better outcomes, and surgeons continue to take their most seriously ill PE patients into the operating room.
Still, Alan R. Hartman, MD, of North Shore-LIJ Health System in Great Neck, New York, and his colleagues wanted to determine just how successful the surgery is and which patients are the best candidates for surgery.
To find out, the team went back into the surgical archives and identified 96 patients who underwent surgery during a 9-year period (from 2003 to 2011). The researchers assessed how many patients survived in the month following surgery and compared the results to historical mortality data from patients who did not undergo surgery.
All of the patients who had undergone surgery had acute, centrally located PE and severe global hyperkinetic right ventricular dysfunction.
All patients had either a large clot burden in the main pulmonary arteries or a saddle embolism. None of the patients had a history of chronic pulmonary thrombolytic disease or evidence of chronic disease on a computed-tomographic-angiography scan.
They all made it to surgery within an hour of the embolism. The surgery was performed through cardiopulmonary bypass, at normal body temperature, and without aortic cross-clamping, thus avoiding myocardial ischemia.
A pulmonary arteriotomy and clot extraction were performed under direct vision, according to Dr Hartman, which he believes is critical to the success of the procedure.
The mortality rate was 4.2%, which is lower than any other published reports. In addition, 68 patients (73.9%) were discharged home or to rehabilitation facilities.
Those patients with low blood pressure had a higher 30-day mortality rate—12.5% compared to 1.4% in those with normal blood pressure. Patients with low blood pressure also spent a longer time in the hospital—13.4 days compared to 9.1 days in patients with normal blood pressure.
Based on these results, the researchers concluded that acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise.
However, they cautioned that rates of success are dependent upon experience, surgical ability, and careful patient selection.
Photo courtesy of Medical
College of Georgia
Pulmonary embolectomy, a procedure that was virtually abandoned in the 1950s because it resulted in high mortality rates, may actually prevent more deaths in severely ill patients with pulmonary embolism (PE) than current drug therapies alone, according to research published in the Texas Heart Institute Journal.
More than 2 dozen studies conducted between 1961 and 1984 suggest the death rate associated with pulmonary embolectomy is 32%.
But safer techniques have led to better outcomes, and surgeons continue to take their most seriously ill PE patients into the operating room.
Still, Alan R. Hartman, MD, of North Shore-LIJ Health System in Great Neck, New York, and his colleagues wanted to determine just how successful the surgery is and which patients are the best candidates for surgery.
To find out, the team went back into the surgical archives and identified 96 patients who underwent surgery during a 9-year period (from 2003 to 2011). The researchers assessed how many patients survived in the month following surgery and compared the results to historical mortality data from patients who did not undergo surgery.
All of the patients who had undergone surgery had acute, centrally located PE and severe global hyperkinetic right ventricular dysfunction.
All patients had either a large clot burden in the main pulmonary arteries or a saddle embolism. None of the patients had a history of chronic pulmonary thrombolytic disease or evidence of chronic disease on a computed-tomographic-angiography scan.
They all made it to surgery within an hour of the embolism. The surgery was performed through cardiopulmonary bypass, at normal body temperature, and without aortic cross-clamping, thus avoiding myocardial ischemia.
A pulmonary arteriotomy and clot extraction were performed under direct vision, according to Dr Hartman, which he believes is critical to the success of the procedure.
The mortality rate was 4.2%, which is lower than any other published reports. In addition, 68 patients (73.9%) were discharged home or to rehabilitation facilities.
Those patients with low blood pressure had a higher 30-day mortality rate—12.5% compared to 1.4% in those with normal blood pressure. Patients with low blood pressure also spent a longer time in the hospital—13.4 days compared to 9.1 days in patients with normal blood pressure.
Based on these results, the researchers concluded that acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise.
However, they cautioned that rates of success are dependent upon experience, surgical ability, and careful patient selection.
Photo courtesy of Medical
College of Georgia
Pulmonary embolectomy, a procedure that was virtually abandoned in the 1950s because it resulted in high mortality rates, may actually prevent more deaths in severely ill patients with pulmonary embolism (PE) than current drug therapies alone, according to research published in the Texas Heart Institute Journal.
More than 2 dozen studies conducted between 1961 and 1984 suggest the death rate associated with pulmonary embolectomy is 32%.
But safer techniques have led to better outcomes, and surgeons continue to take their most seriously ill PE patients into the operating room.
Still, Alan R. Hartman, MD, of North Shore-LIJ Health System in Great Neck, New York, and his colleagues wanted to determine just how successful the surgery is and which patients are the best candidates for surgery.
To find out, the team went back into the surgical archives and identified 96 patients who underwent surgery during a 9-year period (from 2003 to 2011). The researchers assessed how many patients survived in the month following surgery and compared the results to historical mortality data from patients who did not undergo surgery.
All of the patients who had undergone surgery had acute, centrally located PE and severe global hyperkinetic right ventricular dysfunction.
All patients had either a large clot burden in the main pulmonary arteries or a saddle embolism. None of the patients had a history of chronic pulmonary thrombolytic disease or evidence of chronic disease on a computed-tomographic-angiography scan.
They all made it to surgery within an hour of the embolism. The surgery was performed through cardiopulmonary bypass, at normal body temperature, and without aortic cross-clamping, thus avoiding myocardial ischemia.
A pulmonary arteriotomy and clot extraction were performed under direct vision, according to Dr Hartman, which he believes is critical to the success of the procedure.
The mortality rate was 4.2%, which is lower than any other published reports. In addition, 68 patients (73.9%) were discharged home or to rehabilitation facilities.
Those patients with low blood pressure had a higher 30-day mortality rate—12.5% compared to 1.4% in those with normal blood pressure. Patients with low blood pressure also spent a longer time in the hospital—13.4 days compared to 9.1 days in patients with normal blood pressure.
Based on these results, the researchers concluded that acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise.
However, they cautioned that rates of success are dependent upon experience, surgical ability, and careful patient selection.
Leukemia, lymphoma cause more distress in young adults
patient and her father
Photo by Rhoda Baer
Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).
Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.
In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.
Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.
In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.
These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.
And results showed that survivors younger than 40 had the highest prevalence of distress.
Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.
“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”
“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”
The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.
In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.
“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”
“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”
The interviews also helped to explain why distress lingers even years after treatment ends.
“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.
“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”
Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.
For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.
“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.
patient and her father
Photo by Rhoda Baer
Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).
Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.
In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.
Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.
In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.
These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.
And results showed that survivors younger than 40 had the highest prevalence of distress.
Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.
“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”
“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”
The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.
In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.
“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”
“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”
The interviews also helped to explain why distress lingers even years after treatment ends.
“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.
“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”
Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.
For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.
“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.
patient and her father
Photo by Rhoda Baer
Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).
Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.
In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.
Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.
In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.
These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.
And results showed that survivors younger than 40 had the highest prevalence of distress.
Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.
“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”
“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”
The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.
In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.
“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”
“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”
The interviews also helped to explain why distress lingers even years after treatment ends.
“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.
“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”
Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.
For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.
“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.
Survey results support shared decision-making
Photo by Rhoda Baer
A survey of cancer patients has shown that when physicians make treatment decisions alone, patients tend to rate the quality of care lower than when physicians include patients in the decision-making process.
Researchers found this to be the case even among patients who said they preferred it when physicians made treatment decisions alone.
Kenneth L. Kehl, MD, of MD Anderson Cancer Center in Houston, Texas, and his colleagues reported these findings in JAMA Oncology.
The researchers surveyed 5315 cancer patients who reported decision roles for 10,817 treatment decisions. The team assessed the association between patients’ roles in decisions with their reports on quality of care and physician communication.
Most of the patients (58%) said they preferred shared roles in decision-making, 36% preferred patient-controlled decisions, and 6% preferred physician-controlled decisions.
The patients reported that their actual decision-making process was patient-controlled in 39% of decisions, shared in 44%, and physician-controlled in 17%. Of the treatment decisions made by patients, 42% were regarding surgery, 36% were regarding chemotherapy, and 22% were regarding radiation.
The researchers found that patients’ preferred role in decision-making was not associated with how they rated the quality of care. But when they reported that treatment decisions were controlled by physicians, the patients were less likely to rate the quality of care as excellent, as compared to shared-decision making situations.
Patients said physician care was excellent in 67.8% of cases. And 55.8% of patients gave their physicians the highest possible rating of communication.
However, patients who preferred physician-controlled decisions to shared decision-making were less likely to give top ratings to their physicians, as were patients who reported actually experiencing physician-controlled vs shared decisions.
The researchers said these results highlight the benefits of promoting shared decision-making among all patients with cancer, even those who seem to prefer less active roles in the process.
In a related commentary, Sarah T. Hawley, PhD, and Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said they were intrigued by the fact that the association between shared decision-making and patient appraisal of care quality remained even when controlling for a patient’s preferred role in the decision-making process.
“Kehl and colleagues conclude from this finding that it is important to promote [shared decision-making], even among patients who may seek less active roles,” Drs Hawley and Jagsi wrote.
“Yet . . . prior work . . . has suggested that it is the match between patients’ preferred and actual involvement that contributes to greater satisfaction with care. These conflicting results underscore the need for further work to better quantify and link measures of [shared decision-making] to patient appraisal of care.”
Photo by Rhoda Baer
A survey of cancer patients has shown that when physicians make treatment decisions alone, patients tend to rate the quality of care lower than when physicians include patients in the decision-making process.
Researchers found this to be the case even among patients who said they preferred it when physicians made treatment decisions alone.
Kenneth L. Kehl, MD, of MD Anderson Cancer Center in Houston, Texas, and his colleagues reported these findings in JAMA Oncology.
The researchers surveyed 5315 cancer patients who reported decision roles for 10,817 treatment decisions. The team assessed the association between patients’ roles in decisions with their reports on quality of care and physician communication.
Most of the patients (58%) said they preferred shared roles in decision-making, 36% preferred patient-controlled decisions, and 6% preferred physician-controlled decisions.
The patients reported that their actual decision-making process was patient-controlled in 39% of decisions, shared in 44%, and physician-controlled in 17%. Of the treatment decisions made by patients, 42% were regarding surgery, 36% were regarding chemotherapy, and 22% were regarding radiation.
The researchers found that patients’ preferred role in decision-making was not associated with how they rated the quality of care. But when they reported that treatment decisions were controlled by physicians, the patients were less likely to rate the quality of care as excellent, as compared to shared-decision making situations.
Patients said physician care was excellent in 67.8% of cases. And 55.8% of patients gave their physicians the highest possible rating of communication.
However, patients who preferred physician-controlled decisions to shared decision-making were less likely to give top ratings to their physicians, as were patients who reported actually experiencing physician-controlled vs shared decisions.
The researchers said these results highlight the benefits of promoting shared decision-making among all patients with cancer, even those who seem to prefer less active roles in the process.
In a related commentary, Sarah T. Hawley, PhD, and Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said they were intrigued by the fact that the association between shared decision-making and patient appraisal of care quality remained even when controlling for a patient’s preferred role in the decision-making process.
“Kehl and colleagues conclude from this finding that it is important to promote [shared decision-making], even among patients who may seek less active roles,” Drs Hawley and Jagsi wrote.
“Yet . . . prior work . . . has suggested that it is the match between patients’ preferred and actual involvement that contributes to greater satisfaction with care. These conflicting results underscore the need for further work to better quantify and link measures of [shared decision-making] to patient appraisal of care.”
Photo by Rhoda Baer
A survey of cancer patients has shown that when physicians make treatment decisions alone, patients tend to rate the quality of care lower than when physicians include patients in the decision-making process.
Researchers found this to be the case even among patients who said they preferred it when physicians made treatment decisions alone.
Kenneth L. Kehl, MD, of MD Anderson Cancer Center in Houston, Texas, and his colleagues reported these findings in JAMA Oncology.
The researchers surveyed 5315 cancer patients who reported decision roles for 10,817 treatment decisions. The team assessed the association between patients’ roles in decisions with their reports on quality of care and physician communication.
Most of the patients (58%) said they preferred shared roles in decision-making, 36% preferred patient-controlled decisions, and 6% preferred physician-controlled decisions.
The patients reported that their actual decision-making process was patient-controlled in 39% of decisions, shared in 44%, and physician-controlled in 17%. Of the treatment decisions made by patients, 42% were regarding surgery, 36% were regarding chemotherapy, and 22% were regarding radiation.
The researchers found that patients’ preferred role in decision-making was not associated with how they rated the quality of care. But when they reported that treatment decisions were controlled by physicians, the patients were less likely to rate the quality of care as excellent, as compared to shared-decision making situations.
Patients said physician care was excellent in 67.8% of cases. And 55.8% of patients gave their physicians the highest possible rating of communication.
However, patients who preferred physician-controlled decisions to shared decision-making were less likely to give top ratings to their physicians, as were patients who reported actually experiencing physician-controlled vs shared decisions.
The researchers said these results highlight the benefits of promoting shared decision-making among all patients with cancer, even those who seem to prefer less active roles in the process.
In a related commentary, Sarah T. Hawley, PhD, and Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said they were intrigued by the fact that the association between shared decision-making and patient appraisal of care quality remained even when controlling for a patient’s preferred role in the decision-making process.
“Kehl and colleagues conclude from this finding that it is important to promote [shared decision-making], even among patients who may seek less active roles,” Drs Hawley and Jagsi wrote.
“Yet . . . prior work . . . has suggested that it is the match between patients’ preferred and actual involvement that contributes to greater satisfaction with care. These conflicting results underscore the need for further work to better quantify and link measures of [shared decision-making] to patient appraisal of care.”
Cancer patients rarely make inappropriate requests, study shows
Photo courtesy of NIH
Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.
The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.
Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.
Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues reported these findings in JAMA Oncology.
The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.
The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.
The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.
Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.
Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.
“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.
In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”
“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”
“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”
Photo courtesy of NIH
Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.
The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.
Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.
Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues reported these findings in JAMA Oncology.
The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.
The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.
The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.
Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.
Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.
“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.
In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”
“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”
“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”
Photo courtesy of NIH
Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.
The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.
Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.
Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues reported these findings in JAMA Oncology.
The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.
The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.
The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.
Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.
Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.
“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.
In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”
“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”
“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”
In-flight transfusions enable better outcomes in trauma patients
Photo by Elise Amendola
In-flight red blood cell (RBC) transfusions can improve outcomes in trauma patients, according to a study published in the Journal of the American College of Surgeons.
The research showed that air-lifted trauma victims who received blood transfusions in the helicopter had higher one-day survival rates and a lower risk of shock than air-lifted patients who did not receive transfusions until they arrived at the trauma unit.
Patients who received in-flight transfusions also required fewer RBCs once they arrived at the hospital.
Joshua Brown, MD, and his colleagues at the University of Pittsburgh Medical Center (UPMC) conducted this research, evaluating the air medical evacuation strategy at UPMC, which has a network of 18 helicopter bases in Pennsylvania, Ohio, and Maryland.
The STAT MedEvac helicopter teams have been carrying blood for transfusion on their flights for about 2 decades, but this is the first study that evaluated the use of transfused blood in civilian trauma victims air-evacuated directly from the injury scene and compared them with air-evacuated trauma victims who did not receive transfused blood.
It is also the largest study to date of a civilian in-flight trauma resuscitation protocol that has been used by the military in Iraq and Afghanistan.
The researchers evaluated 240 patients who received in-flight RBC transfusions and 480 patients who were not transfused until they reached the trauma center.
Receiving an in-flight transfusion was associated with better odds of 24-hour survival (adjusted odds ratio=4.92, P=0.01), decreased odds of shock (adjusted odds ratio=0.28, P=0.03), and lower 24-hour RBC requirement (coef -3.6 RBC units, P=0.04).
Based on these data, the UPMC may modify its protocol, Dr Brown said.
“It used to be the paramedics had to give the patient 2 liters of saline before giving them blood, and we dropped that down to only 1 liter of saline,” he noted. “Now, based on this study, we’re actually looking at giving patients blood without any saline who meet the criteria of low blood pressure and elevated heart rate and are clearly in shock.”
The UPMC protocol involves giving guidelines on when to administer transfusions to the paramedics and nurses onboard flights. All the STAT MedEvac flights at the institution carry 2 units of RBCs for transfusion.
Helicopter staff can communicate with the medical command doctor at the trauma center to get the go-ahead order to give blood to patients who may not meet the guidelines for transfusion but still may benefit from receiving it.
However, there are regulatory issues that may prevent such a protocol from being adopted universally, Dr Brown noted. In Pennsylvania, paramedics who have had additional training are allowed to start a blood transfusion without a physician present, but not all states allow this.
Dr Brown also explained the logistics and challenges of storing blood away from the blood bank.
“The blood needs to be refrigerated, the helicopter base must have a freezer, and the helicopters must have coolers when they’re actually out on a mission to keep the blood at an appropriate temperature,” he said.
Meeting these requirements involves close coordination with the blood bank and having a way to return unused blood after it expires in 30 days. The University of Pittsburgh has registered all of its helicopter bases as satellite blood banks to comply with the regulations.
Photo by Elise Amendola
In-flight red blood cell (RBC) transfusions can improve outcomes in trauma patients, according to a study published in the Journal of the American College of Surgeons.
The research showed that air-lifted trauma victims who received blood transfusions in the helicopter had higher one-day survival rates and a lower risk of shock than air-lifted patients who did not receive transfusions until they arrived at the trauma unit.
Patients who received in-flight transfusions also required fewer RBCs once they arrived at the hospital.
Joshua Brown, MD, and his colleagues at the University of Pittsburgh Medical Center (UPMC) conducted this research, evaluating the air medical evacuation strategy at UPMC, which has a network of 18 helicopter bases in Pennsylvania, Ohio, and Maryland.
The STAT MedEvac helicopter teams have been carrying blood for transfusion on their flights for about 2 decades, but this is the first study that evaluated the use of transfused blood in civilian trauma victims air-evacuated directly from the injury scene and compared them with air-evacuated trauma victims who did not receive transfused blood.
It is also the largest study to date of a civilian in-flight trauma resuscitation protocol that has been used by the military in Iraq and Afghanistan.
The researchers evaluated 240 patients who received in-flight RBC transfusions and 480 patients who were not transfused until they reached the trauma center.
Receiving an in-flight transfusion was associated with better odds of 24-hour survival (adjusted odds ratio=4.92, P=0.01), decreased odds of shock (adjusted odds ratio=0.28, P=0.03), and lower 24-hour RBC requirement (coef -3.6 RBC units, P=0.04).
Based on these data, the UPMC may modify its protocol, Dr Brown said.
“It used to be the paramedics had to give the patient 2 liters of saline before giving them blood, and we dropped that down to only 1 liter of saline,” he noted. “Now, based on this study, we’re actually looking at giving patients blood without any saline who meet the criteria of low blood pressure and elevated heart rate and are clearly in shock.”
The UPMC protocol involves giving guidelines on when to administer transfusions to the paramedics and nurses onboard flights. All the STAT MedEvac flights at the institution carry 2 units of RBCs for transfusion.
Helicopter staff can communicate with the medical command doctor at the trauma center to get the go-ahead order to give blood to patients who may not meet the guidelines for transfusion but still may benefit from receiving it.
However, there are regulatory issues that may prevent such a protocol from being adopted universally, Dr Brown noted. In Pennsylvania, paramedics who have had additional training are allowed to start a blood transfusion without a physician present, but not all states allow this.
Dr Brown also explained the logistics and challenges of storing blood away from the blood bank.
“The blood needs to be refrigerated, the helicopter base must have a freezer, and the helicopters must have coolers when they’re actually out on a mission to keep the blood at an appropriate temperature,” he said.
Meeting these requirements involves close coordination with the blood bank and having a way to return unused blood after it expires in 30 days. The University of Pittsburgh has registered all of its helicopter bases as satellite blood banks to comply with the regulations.
Photo by Elise Amendola
In-flight red blood cell (RBC) transfusions can improve outcomes in trauma patients, according to a study published in the Journal of the American College of Surgeons.
The research showed that air-lifted trauma victims who received blood transfusions in the helicopter had higher one-day survival rates and a lower risk of shock than air-lifted patients who did not receive transfusions until they arrived at the trauma unit.
Patients who received in-flight transfusions also required fewer RBCs once they arrived at the hospital.
Joshua Brown, MD, and his colleagues at the University of Pittsburgh Medical Center (UPMC) conducted this research, evaluating the air medical evacuation strategy at UPMC, which has a network of 18 helicopter bases in Pennsylvania, Ohio, and Maryland.
The STAT MedEvac helicopter teams have been carrying blood for transfusion on their flights for about 2 decades, but this is the first study that evaluated the use of transfused blood in civilian trauma victims air-evacuated directly from the injury scene and compared them with air-evacuated trauma victims who did not receive transfused blood.
It is also the largest study to date of a civilian in-flight trauma resuscitation protocol that has been used by the military in Iraq and Afghanistan.
The researchers evaluated 240 patients who received in-flight RBC transfusions and 480 patients who were not transfused until they reached the trauma center.
Receiving an in-flight transfusion was associated with better odds of 24-hour survival (adjusted odds ratio=4.92, P=0.01), decreased odds of shock (adjusted odds ratio=0.28, P=0.03), and lower 24-hour RBC requirement (coef -3.6 RBC units, P=0.04).
Based on these data, the UPMC may modify its protocol, Dr Brown said.
“It used to be the paramedics had to give the patient 2 liters of saline before giving them blood, and we dropped that down to only 1 liter of saline,” he noted. “Now, based on this study, we’re actually looking at giving patients blood without any saline who meet the criteria of low blood pressure and elevated heart rate and are clearly in shock.”
The UPMC protocol involves giving guidelines on when to administer transfusions to the paramedics and nurses onboard flights. All the STAT MedEvac flights at the institution carry 2 units of RBCs for transfusion.
Helicopter staff can communicate with the medical command doctor at the trauma center to get the go-ahead order to give blood to patients who may not meet the guidelines for transfusion but still may benefit from receiving it.
However, there are regulatory issues that may prevent such a protocol from being adopted universally, Dr Brown noted. In Pennsylvania, paramedics who have had additional training are allowed to start a blood transfusion without a physician present, but not all states allow this.
Dr Brown also explained the logistics and challenges of storing blood away from the blood bank.
“The blood needs to be refrigerated, the helicopter base must have a freezer, and the helicopters must have coolers when they’re actually out on a mission to keep the blood at an appropriate temperature,” he said.
Meeting these requirements involves close coordination with the blood bank and having a way to return unused blood after it expires in 30 days. The University of Pittsburgh has registered all of its helicopter bases as satellite blood banks to comply with the regulations.
Order of mutations impacts MPN behavior
essential thrombocythemia
The order in which genetic mutations are acquired determines how myeloproliferative neoplasms (MPNs) behave, according to research published in NEJM.
Investigators found that mutation order impacts everything from the type of MPN a patient develops to how the disease responds to treatment.
“This surprising finding could help us offer more accurate prognoses to MPN patients based on their mutation order and tailor potential therapies towards them,” said study author David Kent, PhD, of the University of Cambridge in the UK.
“For example, our results predict that targeted JAK2 therapy would be more effective in patients with one mutation order but not the other.”
To uncover this finding, Dr Kent and his colleagues screened 246 MPN patients for mutations in JAK2 and TET2. By studying patients who carried both mutations, the team was able to determine which mutation came first and study the effect of mutation order on the behavior of hematopoietic stem cells.
The investigators found that patients who acquired mutations in JAK2 prior to those in TET2 displayed aberrant blood counts more than a decade earlier.
These patients were more likely to present with polycythemia vera than with essential thrombocythemia, and they were more likely to develop thromboses.
At the same time, JAK2-mutant progenitors from these patients exhibited increased sensitivity to the JAK1/2 inhibitor ruxolitinib in vitro.
“This is the first time that mutation order has been shown to affect any cancer, and it is likely that this phenomenon occurs in many types of malignancy,” said study author Tony Green, MD, PhD, of the University of Cambridge.
“These results show how the study of MPNs provides unparalleled access to the earliest stages of tumor development (inaccessible in other cancers, which usually cannot be detected until many mutations have accumulated). This should give us powerful insights into the origins of cancer.”
essential thrombocythemia
The order in which genetic mutations are acquired determines how myeloproliferative neoplasms (MPNs) behave, according to research published in NEJM.
Investigators found that mutation order impacts everything from the type of MPN a patient develops to how the disease responds to treatment.
“This surprising finding could help us offer more accurate prognoses to MPN patients based on their mutation order and tailor potential therapies towards them,” said study author David Kent, PhD, of the University of Cambridge in the UK.
“For example, our results predict that targeted JAK2 therapy would be more effective in patients with one mutation order but not the other.”
To uncover this finding, Dr Kent and his colleagues screened 246 MPN patients for mutations in JAK2 and TET2. By studying patients who carried both mutations, the team was able to determine which mutation came first and study the effect of mutation order on the behavior of hematopoietic stem cells.
The investigators found that patients who acquired mutations in JAK2 prior to those in TET2 displayed aberrant blood counts more than a decade earlier.
These patients were more likely to present with polycythemia vera than with essential thrombocythemia, and they were more likely to develop thromboses.
At the same time, JAK2-mutant progenitors from these patients exhibited increased sensitivity to the JAK1/2 inhibitor ruxolitinib in vitro.
“This is the first time that mutation order has been shown to affect any cancer, and it is likely that this phenomenon occurs in many types of malignancy,” said study author Tony Green, MD, PhD, of the University of Cambridge.
“These results show how the study of MPNs provides unparalleled access to the earliest stages of tumor development (inaccessible in other cancers, which usually cannot be detected until many mutations have accumulated). This should give us powerful insights into the origins of cancer.”
essential thrombocythemia
The order in which genetic mutations are acquired determines how myeloproliferative neoplasms (MPNs) behave, according to research published in NEJM.
Investigators found that mutation order impacts everything from the type of MPN a patient develops to how the disease responds to treatment.
“This surprising finding could help us offer more accurate prognoses to MPN patients based on their mutation order and tailor potential therapies towards them,” said study author David Kent, PhD, of the University of Cambridge in the UK.
“For example, our results predict that targeted JAK2 therapy would be more effective in patients with one mutation order but not the other.”
To uncover this finding, Dr Kent and his colleagues screened 246 MPN patients for mutations in JAK2 and TET2. By studying patients who carried both mutations, the team was able to determine which mutation came first and study the effect of mutation order on the behavior of hematopoietic stem cells.
The investigators found that patients who acquired mutations in JAK2 prior to those in TET2 displayed aberrant blood counts more than a decade earlier.
These patients were more likely to present with polycythemia vera than with essential thrombocythemia, and they were more likely to develop thromboses.
At the same time, JAK2-mutant progenitors from these patients exhibited increased sensitivity to the JAK1/2 inhibitor ruxolitinib in vitro.
“This is the first time that mutation order has been shown to affect any cancer, and it is likely that this phenomenon occurs in many types of malignancy,” said study author Tony Green, MD, PhD, of the University of Cambridge.
“These results show how the study of MPNs provides unparalleled access to the earliest stages of tumor development (inaccessible in other cancers, which usually cannot be detected until many mutations have accumulated). This should give us powerful insights into the origins of cancer.”
Robotic sock could prevent DVT, team says
the bio-inspired robotic sock
Photo courtesy of the National
University of Singapore
Researchers have invented a robotic sock that may be able to prevent deep vein thrombosis (DVT), although it has not yet been tested in clinical trials.
Equipped with soft actuators that mimic the tentacle movements of corals, the robotic sock emulates natural lower leg muscle contractions in the wearer’s leg, thereby promoting blood circulation throughout the body.
The device also allows the patient’s lower leg movements to be monitored to improve therapy outcomes.
The sock was created by Lim Jeong Hoon, MD, PhD, Raye Yeow Chen Hua, PhD, and Low Fanzhe (a PhD student), all from the National University of Singapore.
While exploring a way to prevent DVT, Dr Lim was inspired by the natural role of the human ankle muscles in facilitating venous blood flow back to the heart. He worked with Dr Yeow and Low to identify a way to perform this function for patients who are bedridden or unable to move their legs.
The team turned to nature for inspiration. They found similarities in the structural design of the coral tentacle, which can extend to grab food and contract to bring the food closer for consumption, and invented soft actuators that mimic this push-and-pull mechanism.
By integrating the actuators with a sock and the use of a programmable pneumatic pump-valve control system, the invention can create the desired robot-assisted ankle joint motions to facilitate blood flow in the leg.
“We chose to use only soft components and actuators to increase patient comfort during use, hence minimizing the risk of injury from excessive mechanical forces,” Low said. “Compression stockings are currently used in the hospital wards, so it makes sense to use a similar sock-based approach to provide comfort and minimize bulk on the ankle and foot.”
The researchers noted that the sock complements conventional ankle therapy exercises that therapists perform on patients, thereby optimizing therapy time and productivity.
In addition, the sock can be worn for prolonged periods to provide robot-assisted therapy, on top of the therapist-assisted sessions. The sock is also embedded with sensors to track the ankle joint angle, allowing the patient’s ankle motion to be monitored for better treatment.
“Given its compact size, modular design, and ease of use, the soft robotic sock can be adopted in hospital wards and rehabilitation centers for on-bed applications to prevent DVT among stroke patients or even at home for bedridden patients,” Dr Yeow said. “By reducing the risk of DVT using this device, we hope to improve survival rates of these patients.”
To investigate the effectiveness of the robotic sock, the researchers will be conducting pilot clinical trials with about 30 patients at the National University Hospital over 6 months, starting in March.
They hope the pilot trials will help them obtain patient and clinical feedback to further improve the design and capabilities of the device. The team intends to conduct trials across different local hospitals for better evaluation, and they also hope to commercialize the device in the future.
the bio-inspired robotic sock
Photo courtesy of the National
University of Singapore
Researchers have invented a robotic sock that may be able to prevent deep vein thrombosis (DVT), although it has not yet been tested in clinical trials.
Equipped with soft actuators that mimic the tentacle movements of corals, the robotic sock emulates natural lower leg muscle contractions in the wearer’s leg, thereby promoting blood circulation throughout the body.
The device also allows the patient’s lower leg movements to be monitored to improve therapy outcomes.
The sock was created by Lim Jeong Hoon, MD, PhD, Raye Yeow Chen Hua, PhD, and Low Fanzhe (a PhD student), all from the National University of Singapore.
While exploring a way to prevent DVT, Dr Lim was inspired by the natural role of the human ankle muscles in facilitating venous blood flow back to the heart. He worked with Dr Yeow and Low to identify a way to perform this function for patients who are bedridden or unable to move their legs.
The team turned to nature for inspiration. They found similarities in the structural design of the coral tentacle, which can extend to grab food and contract to bring the food closer for consumption, and invented soft actuators that mimic this push-and-pull mechanism.
By integrating the actuators with a sock and the use of a programmable pneumatic pump-valve control system, the invention can create the desired robot-assisted ankle joint motions to facilitate blood flow in the leg.
“We chose to use only soft components and actuators to increase patient comfort during use, hence minimizing the risk of injury from excessive mechanical forces,” Low said. “Compression stockings are currently used in the hospital wards, so it makes sense to use a similar sock-based approach to provide comfort and minimize bulk on the ankle and foot.”
The researchers noted that the sock complements conventional ankle therapy exercises that therapists perform on patients, thereby optimizing therapy time and productivity.
In addition, the sock can be worn for prolonged periods to provide robot-assisted therapy, on top of the therapist-assisted sessions. The sock is also embedded with sensors to track the ankle joint angle, allowing the patient’s ankle motion to be monitored for better treatment.
“Given its compact size, modular design, and ease of use, the soft robotic sock can be adopted in hospital wards and rehabilitation centers for on-bed applications to prevent DVT among stroke patients or even at home for bedridden patients,” Dr Yeow said. “By reducing the risk of DVT using this device, we hope to improve survival rates of these patients.”
To investigate the effectiveness of the robotic sock, the researchers will be conducting pilot clinical trials with about 30 patients at the National University Hospital over 6 months, starting in March.
They hope the pilot trials will help them obtain patient and clinical feedback to further improve the design and capabilities of the device. The team intends to conduct trials across different local hospitals for better evaluation, and they also hope to commercialize the device in the future.
the bio-inspired robotic sock
Photo courtesy of the National
University of Singapore
Researchers have invented a robotic sock that may be able to prevent deep vein thrombosis (DVT), although it has not yet been tested in clinical trials.
Equipped with soft actuators that mimic the tentacle movements of corals, the robotic sock emulates natural lower leg muscle contractions in the wearer’s leg, thereby promoting blood circulation throughout the body.
The device also allows the patient’s lower leg movements to be monitored to improve therapy outcomes.
The sock was created by Lim Jeong Hoon, MD, PhD, Raye Yeow Chen Hua, PhD, and Low Fanzhe (a PhD student), all from the National University of Singapore.
While exploring a way to prevent DVT, Dr Lim was inspired by the natural role of the human ankle muscles in facilitating venous blood flow back to the heart. He worked with Dr Yeow and Low to identify a way to perform this function for patients who are bedridden or unable to move their legs.
The team turned to nature for inspiration. They found similarities in the structural design of the coral tentacle, which can extend to grab food and contract to bring the food closer for consumption, and invented soft actuators that mimic this push-and-pull mechanism.
By integrating the actuators with a sock and the use of a programmable pneumatic pump-valve control system, the invention can create the desired robot-assisted ankle joint motions to facilitate blood flow in the leg.
“We chose to use only soft components and actuators to increase patient comfort during use, hence minimizing the risk of injury from excessive mechanical forces,” Low said. “Compression stockings are currently used in the hospital wards, so it makes sense to use a similar sock-based approach to provide comfort and minimize bulk on the ankle and foot.”
The researchers noted that the sock complements conventional ankle therapy exercises that therapists perform on patients, thereby optimizing therapy time and productivity.
In addition, the sock can be worn for prolonged periods to provide robot-assisted therapy, on top of the therapist-assisted sessions. The sock is also embedded with sensors to track the ankle joint angle, allowing the patient’s ankle motion to be monitored for better treatment.
“Given its compact size, modular design, and ease of use, the soft robotic sock can be adopted in hospital wards and rehabilitation centers for on-bed applications to prevent DVT among stroke patients or even at home for bedridden patients,” Dr Yeow said. “By reducing the risk of DVT using this device, we hope to improve survival rates of these patients.”
To investigate the effectiveness of the robotic sock, the researchers will be conducting pilot clinical trials with about 30 patients at the National University Hospital over 6 months, starting in March.
They hope the pilot trials will help them obtain patient and clinical feedback to further improve the design and capabilities of the device. The team intends to conduct trials across different local hospitals for better evaluation, and they also hope to commercialize the device in the future.