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Method reveals cells of origin in AML
in the bone marrow
Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.
“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.
“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”
Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.
The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.
The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.
The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.
These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.
The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.
The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.
These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.
The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker. 
in the bone marrow
Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.
“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.
“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”
Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.
The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.
The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.
The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.
These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.
The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.
The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.
These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.
The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker.
in the bone marrow
Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.
“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.
“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”
Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.
The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.
The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.
The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.
These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.
The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.
The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.
These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.
The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker.
US cancer centers spend millions in advertising
chemotherapy
Photo by Rhoda Baer
US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.
The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.
The researchers reported these findings in a letter to JAMA Internal Medicine.
The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.
Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.
According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.
The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).
The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.
Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).
Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.
The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.
The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.
chemotherapy
Photo by Rhoda Baer
US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.
The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.
The researchers reported these findings in a letter to JAMA Internal Medicine.
The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.
Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.
According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.
The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).
The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.
Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).
Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.
The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.
The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.
chemotherapy
Photo by Rhoda Baer
US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.
The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.
The researchers reported these findings in a letter to JAMA Internal Medicine.
The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.
Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.
According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.
The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).
The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.
Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).
Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.
The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.
The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.
Finding could help treat and prevent MM, team says
Photo by Daniel Sone
Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).
This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.
“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.
“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”
With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.
The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).
BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.
It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.
The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.
The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.
“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.
“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”
Photo by Daniel Sone
Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).
This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.
“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.
“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”
With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.
The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).
BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.
It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.
The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.
The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.
“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.
“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”
Photo by Daniel Sone
Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).
This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.
“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.
“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”
With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.
The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).
BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.
It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.
The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.
The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.
“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.
“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”
RBC donor age, gender may affect risk of death
Photo by Elise Amendola
A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.
It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.
“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.
“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”
For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).
The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.
The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).
A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).
“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.
“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”
The study was published in JAMA Internal Medicine.
Photo by Elise Amendola
A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.
It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.
“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.
“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”
For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).
The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.
The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).
A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).
“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.
“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”
The study was published in JAMA Internal Medicine.
Photo by Elise Amendola
A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.
It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.
“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.
“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”
For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).
The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.
The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).
A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).
“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.
“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”
The study was published in JAMA Internal Medicine.
HIV patients with elevated ALT at significant risk of chronic liver disease
Patients with HIV infection should be screened routinely for chronic liver disease if their alanine aminotransferase (ALT) levels are elevated, according to a study published in AIDS Care.
“In HIV-positive individuals, liver disease (mostly due to hepatitis B and C virus [HBV and HCV]) is the third most common cause of mortality after AIDS-related illness and non-AIDS nonviral malignancy,” wrote Sumita Verma, MD, of Brighton and Sussex (U.K.) University Hospital, and her coauthors. “Our aim therefore was to assess prevalence, aetiology, and predictors of nonviral-related chronic liver disease (CLD) in a cohort with HIV monoinfection.”
Investigators recruited 3,872 HIV-positive subjects from a Southeast England teaching hospital between 2005 and 2012, of whom 1,654 (42.7%) were found to be at least two ALT levels above the upper limit of normal. Clinically significant CLD was classified as having at least F2 fibrosis (metavir scoring) on liver biopsy, having a liver stiffness measurement greater than F2 (metavir) on a transient elastography, moderate to severe hepatic steatosis on a liver biopsy, a portal hypertension that was either cirrhotic or noncirrhotic, hepatic decompensation, a liver-related mortality, or any combination of these factors. (AIDS Care. 2016 Ju 5. doi: 10.1080/09540121.2016.1191603)
Of the 1,654 subjects with HIV and elevated ALT levels, 1,047 (27.0%) had elevated ALT levels when tested again after 6 months, with 243 of those (23.2%) having a further radiologic or histologic examination done. The final cohort comprised 222 subjects, of which CLD was found in 147 (66.2%), while only 75 (33.8%) had no CLD despite having elevated ALT and HIV. CLD was determined to be “clinically significant” in one out of every four subjects who had it.
“Potential risk factors for CLD included alcohol use (44.2%), one or more feature of the [metabolic syndrome] (68%) and [antiretroviral] use (74.1%), with 68.7% having [more than one] risk factor [and] serum triglyceride (odds ratio, 1.482; 95% confidence interval. 1.053-2.086; P = .024) was the only independent predictor of CLD,” the investigators noted.
Furthermore, the study shows that “the most striking observation [is] that only 23% with persistently elevated ALT were investigated further, with only 58/1,047 (5.5%) undergoing objective assessment of hepatic fibrosis and 45/1,047 (4.3%) being referred to Hepatology.”
Dr. Verma and her coauthors did not report any relevant financial disclosures.
Patients with HIV infection should be screened routinely for chronic liver disease if their alanine aminotransferase (ALT) levels are elevated, according to a study published in AIDS Care.
“In HIV-positive individuals, liver disease (mostly due to hepatitis B and C virus [HBV and HCV]) is the third most common cause of mortality after AIDS-related illness and non-AIDS nonviral malignancy,” wrote Sumita Verma, MD, of Brighton and Sussex (U.K.) University Hospital, and her coauthors. “Our aim therefore was to assess prevalence, aetiology, and predictors of nonviral-related chronic liver disease (CLD) in a cohort with HIV monoinfection.”
Investigators recruited 3,872 HIV-positive subjects from a Southeast England teaching hospital between 2005 and 2012, of whom 1,654 (42.7%) were found to be at least two ALT levels above the upper limit of normal. Clinically significant CLD was classified as having at least F2 fibrosis (metavir scoring) on liver biopsy, having a liver stiffness measurement greater than F2 (metavir) on a transient elastography, moderate to severe hepatic steatosis on a liver biopsy, a portal hypertension that was either cirrhotic or noncirrhotic, hepatic decompensation, a liver-related mortality, or any combination of these factors. (AIDS Care. 2016 Ju 5. doi: 10.1080/09540121.2016.1191603)
Of the 1,654 subjects with HIV and elevated ALT levels, 1,047 (27.0%) had elevated ALT levels when tested again after 6 months, with 243 of those (23.2%) having a further radiologic or histologic examination done. The final cohort comprised 222 subjects, of which CLD was found in 147 (66.2%), while only 75 (33.8%) had no CLD despite having elevated ALT and HIV. CLD was determined to be “clinically significant” in one out of every four subjects who had it.
“Potential risk factors for CLD included alcohol use (44.2%), one or more feature of the [metabolic syndrome] (68%) and [antiretroviral] use (74.1%), with 68.7% having [more than one] risk factor [and] serum triglyceride (odds ratio, 1.482; 95% confidence interval. 1.053-2.086; P = .024) was the only independent predictor of CLD,” the investigators noted.
Furthermore, the study shows that “the most striking observation [is] that only 23% with persistently elevated ALT were investigated further, with only 58/1,047 (5.5%) undergoing objective assessment of hepatic fibrosis and 45/1,047 (4.3%) being referred to Hepatology.”
Dr. Verma and her coauthors did not report any relevant financial disclosures.
Patients with HIV infection should be screened routinely for chronic liver disease if their alanine aminotransferase (ALT) levels are elevated, according to a study published in AIDS Care.
“In HIV-positive individuals, liver disease (mostly due to hepatitis B and C virus [HBV and HCV]) is the third most common cause of mortality after AIDS-related illness and non-AIDS nonviral malignancy,” wrote Sumita Verma, MD, of Brighton and Sussex (U.K.) University Hospital, and her coauthors. “Our aim therefore was to assess prevalence, aetiology, and predictors of nonviral-related chronic liver disease (CLD) in a cohort with HIV monoinfection.”
Investigators recruited 3,872 HIV-positive subjects from a Southeast England teaching hospital between 2005 and 2012, of whom 1,654 (42.7%) were found to be at least two ALT levels above the upper limit of normal. Clinically significant CLD was classified as having at least F2 fibrosis (metavir scoring) on liver biopsy, having a liver stiffness measurement greater than F2 (metavir) on a transient elastography, moderate to severe hepatic steatosis on a liver biopsy, a portal hypertension that was either cirrhotic or noncirrhotic, hepatic decompensation, a liver-related mortality, or any combination of these factors. (AIDS Care. 2016 Ju 5. doi: 10.1080/09540121.2016.1191603)
Of the 1,654 subjects with HIV and elevated ALT levels, 1,047 (27.0%) had elevated ALT levels when tested again after 6 months, with 243 of those (23.2%) having a further radiologic or histologic examination done. The final cohort comprised 222 subjects, of which CLD was found in 147 (66.2%), while only 75 (33.8%) had no CLD despite having elevated ALT and HIV. CLD was determined to be “clinically significant” in one out of every four subjects who had it.
“Potential risk factors for CLD included alcohol use (44.2%), one or more feature of the [metabolic syndrome] (68%) and [antiretroviral] use (74.1%), with 68.7% having [more than one] risk factor [and] serum triglyceride (odds ratio, 1.482; 95% confidence interval. 1.053-2.086; P = .024) was the only independent predictor of CLD,” the investigators noted.
Furthermore, the study shows that “the most striking observation [is] that only 23% with persistently elevated ALT were investigated further, with only 58/1,047 (5.5%) undergoing objective assessment of hepatic fibrosis and 45/1,047 (4.3%) being referred to Hepatology.”
Dr. Verma and her coauthors did not report any relevant financial disclosures.
FROM AIDS CARE
Key clinical point: Individuals with HIV who also have high levels of alanine aminotransferase (ALT) are at higher risk of having nonviral chronic liver disease.
Major finding: Of 3,872 subjects, 1,047 (27%) had elevated ALT levels; of those 243 (23.2%) were investigated for CLD, and of the 222 finally selected, CLD was found in 66.2%.
Data source: Retrospective, longitudinal cohort study of 3,872 HIV-positive individuals from 2005-2012.
Disclosures: Authors did not report any relevant financial disclosures.
Focused-ultrasound device approved to treat essential tremor
A device that uses transcranial focused ultrasound to destroy the MRI-identified pathologic area of the thalamus in essential tremor patients became the first of its kind to receive Food and Drug Administration approval for use in patients whose condition has been refractory to medications such as beta-blockers or anticonvulsant drugs.
In patients who have undergone evaluation by CT and MRI to determine their suitability for the procedure, the Exablate Neuro device delivers focused ultrasound at incrementally higher energies until patients achieve a reduction of tremor. Patients are awake and responsive during the entire treatment.
“As with other treatments for essential tremor, this new device is not a cure but could help patients enjoy a better quality of life,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in the agency’s announcement of the approval. The device “could help them to avoid more extensive surgical treatments,” such as thalamotomy or a deep brain stimulation device, Dr. Peña said.
The clinical data used to support the approval included a double-blind, controlled trial of 76 patients with essential tremor who had not responded to medication therapy.
The 56 patients who were randomly selected to receive the Exablate Neuro treatment showed nearly a 50% improvement in their tremors and motor function 3 months after treatment, compared with their baseline score. The 20 patients who received a sham control treatment had no improvement, and some experienced a slight worsening after the sham procedure before they crossed over into the treatment group at the 3-month time point.
At 12 months post procedure, the treatment group retained a 40% improvement in those scores, compared with baseline.
Adverse events reported by patients treated with the device were similar to those reported by patients who have undergone thalamotomy. Events included numbness/tingling of the fingers, headache, imbalance/unsteadiness, loss of control of body movements (ataxia), or gait disturbance.
Other side effects identified as possibly related to treatment with MR-guided focused ultrasound treatments include tissue damage in an area other than the treatment area, hemorrhage in the treated area requiring emergency treatment, skin burns with ulceration of the skin, skin retraction, and scar formation and blood clots.
InSightec manufacturers the Exablate Neuro device.
A device that uses transcranial focused ultrasound to destroy the MRI-identified pathologic area of the thalamus in essential tremor patients became the first of its kind to receive Food and Drug Administration approval for use in patients whose condition has been refractory to medications such as beta-blockers or anticonvulsant drugs.
In patients who have undergone evaluation by CT and MRI to determine their suitability for the procedure, the Exablate Neuro device delivers focused ultrasound at incrementally higher energies until patients achieve a reduction of tremor. Patients are awake and responsive during the entire treatment.
“As with other treatments for essential tremor, this new device is not a cure but could help patients enjoy a better quality of life,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in the agency’s announcement of the approval. The device “could help them to avoid more extensive surgical treatments,” such as thalamotomy or a deep brain stimulation device, Dr. Peña said.
The clinical data used to support the approval included a double-blind, controlled trial of 76 patients with essential tremor who had not responded to medication therapy.
The 56 patients who were randomly selected to receive the Exablate Neuro treatment showed nearly a 50% improvement in their tremors and motor function 3 months after treatment, compared with their baseline score. The 20 patients who received a sham control treatment had no improvement, and some experienced a slight worsening after the sham procedure before they crossed over into the treatment group at the 3-month time point.
At 12 months post procedure, the treatment group retained a 40% improvement in those scores, compared with baseline.
Adverse events reported by patients treated with the device were similar to those reported by patients who have undergone thalamotomy. Events included numbness/tingling of the fingers, headache, imbalance/unsteadiness, loss of control of body movements (ataxia), or gait disturbance.
Other side effects identified as possibly related to treatment with MR-guided focused ultrasound treatments include tissue damage in an area other than the treatment area, hemorrhage in the treated area requiring emergency treatment, skin burns with ulceration of the skin, skin retraction, and scar formation and blood clots.
InSightec manufacturers the Exablate Neuro device.
A device that uses transcranial focused ultrasound to destroy the MRI-identified pathologic area of the thalamus in essential tremor patients became the first of its kind to receive Food and Drug Administration approval for use in patients whose condition has been refractory to medications such as beta-blockers or anticonvulsant drugs.
In patients who have undergone evaluation by CT and MRI to determine their suitability for the procedure, the Exablate Neuro device delivers focused ultrasound at incrementally higher energies until patients achieve a reduction of tremor. Patients are awake and responsive during the entire treatment.
“As with other treatments for essential tremor, this new device is not a cure but could help patients enjoy a better quality of life,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in the agency’s announcement of the approval. The device “could help them to avoid more extensive surgical treatments,” such as thalamotomy or a deep brain stimulation device, Dr. Peña said.
The clinical data used to support the approval included a double-blind, controlled trial of 76 patients with essential tremor who had not responded to medication therapy.
The 56 patients who were randomly selected to receive the Exablate Neuro treatment showed nearly a 50% improvement in their tremors and motor function 3 months after treatment, compared with their baseline score. The 20 patients who received a sham control treatment had no improvement, and some experienced a slight worsening after the sham procedure before they crossed over into the treatment group at the 3-month time point.
At 12 months post procedure, the treatment group retained a 40% improvement in those scores, compared with baseline.
Adverse events reported by patients treated with the device were similar to those reported by patients who have undergone thalamotomy. Events included numbness/tingling of the fingers, headache, imbalance/unsteadiness, loss of control of body movements (ataxia), or gait disturbance.
Other side effects identified as possibly related to treatment with MR-guided focused ultrasound treatments include tissue damage in an area other than the treatment area, hemorrhage in the treated area requiring emergency treatment, skin burns with ulceration of the skin, skin retraction, and scar formation and blood clots.
InSightec manufacturers the Exablate Neuro device.
FDA Approves First Retinoid for OTC Acne Treatment
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
FDA approves first retinoid for OTC acne treatment
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
The Food and Drug Administration has approved adapalene gel 0.1% for over-the-counter use, making it the first retinoid for treating acne that will be available in the United States without a prescription.
The approval also makes the product, marketed as Differin Gel 0.1%, “the first new active ingredient for acne treatment for OTC use since the 1980s,” according to an FDA statement announcing the approval July 8. Differin Gel is approved for use in people aged 12 years and older.
The switch to OTC status was supported by postmarketing safety data; by consumer studies data, which included a label comprehension study, a self-selection study, and an “actual use” study; and data from a “maximal use” study submitted by the manufacturer.
“Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately,” according to the FDA statement. “The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area (face, shoulders, upper back, and chest), demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.”
The FDA noted that “some other retinoid drugs have been shown to cause birth defects,” and it advises that women “who are pregnant, planning to become pregnant, or [are] breast-feeding” should ask a doctor before using the product.
“While there have been no adequate and well-controlled studies of Differin Gel 0.1% in pregnant women, there is no specific evidence that Differin Gel 0.1%, when used topically as directed, causes birth defects in humans,” according to the FDA.
Consumers should follow the OTC Drug Facts label “and consult with their health care providers if their symptoms do not improve,” the FDA added.
At an April 2016 meeting, the FDA’s nonprescription drugs advisory committee unanimously voted that the safety of adapalene gel 0.1% for OTC use for treating acne had been “adequately demonstrated.”
Galderma Laboratories markets Differin Gel 0.1%.
Statement Warns of Drugs Causing or Exacerbating Heart Failure
Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.
This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.
Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.
NSAIDs
The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).
“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.
Metformin
Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m2. The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.
Antihypertensives, biologics, and more
Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.
The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.
Managing myriad meds
The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.
“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”
Dr. Page had no disclosures.
Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.
This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.
Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.
NSAIDs
The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).
“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.
Metformin
Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m2. The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.
Antihypertensives, biologics, and more
Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.
The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.
Managing myriad meds
The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.
“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”
Dr. Page had no disclosures.
Many commonly used prescription drugs, many OTC agents, and also several complimentary or alternative medications, can either trigger heart failure or exacerbate the disease in patients with existing heart failure according to a Scientific Statement written by a committee of the American Heart Association and released on July 11.
This first-ever authoritative U.S. overview of what is known about drugs that can affect heart failure was compiled to address an important practice issue for the large and growing number of U.S. patients with heart failure, estimated to be nearly 6 million Americans, and “provide some guidance to health care providers in how to minimize polypharmacy, improve medication safety, as well as identify the medications that could exacerbate or cause heart failure,” said Robert L. Page II, PharmD, chair of the committee and a professor of clinical pharmacy at the University of Colorado at Denver, Aurora.
Although the comprehensive statement lists 88 distinct prescription drugs or drug classes as agents that pose major or moderate threats for causing or worsening heart failure, “from the American public’s perspective, importance should be placed on educating patients regarding the impact that OTC medications can have on their heart failure,” Dr. Page said in an interview. “For example, nonsteroidal anti-inflammatory drugs like ibuprofen or naproxen can cause sodium and water retention and antagonize the effects of evidence-based heart failure pharmacotherapies. Additionally, OTC medications like pseudoephedrine, which many cough and cold products contain, can increase blood pressure and afterload,” he noted. The risks these drugs pose becomes even greater when they are taken at higher doses.
NSAIDs
The statement cites already existing guidance from the American College of Cardiology and American Heart Association that for patients with existing heart failure, use of NSAIDs should either be avoided or withdrawn when possible. The statement advises educating patients to communicate with their health care provider before taking any OTC medication or complimentary or alternative medication, avoid these agents when their efficacy and safety is uncertain, and evaluate the labels of these products for their sodium content (although the sodium content from inactive ingredients may be difficult to find in labeling).
“Currently, we teach patients to read food labels for sodium content, but we also need to educate patients on how to read OTC medication labels for both ingredients and sodium content. Many OTC antacids may have a large sodium load,” Dr. Page said. The statement includes a list of 14 prescription drugs and also highlights several OTC formulations that have an especially high sodium content.
Metformin
Among the many prescription drugs listed, one notable entry is for the oral hypoglycemic agent metformin that today is among the most widely used drugs for treating type 2 diabetes and is especially relevant for heart failure patients because, as the statement notes, 38% also have diabetes. The statement details the long history of metformin and heart failure, noting that until a decade ago, the drug had a contraindication for patients with heart failure, that metformin’s label still carries a black box warning for cautious use in heart failure patients, and that earlier in 2016, the Food and Drug Administration cautioned that metformin should not be used in patients with an estimated glomerular filtration rate of less than 30 mL/minute per 1.73 m2. The statement also endorsed a recommendation from the American Diabetes Association that metformin not be used in patients with unstable heart failure or those hospitalized for heart failure.
Antihypertensives, biologics, and more
Other notable prescription drugs listed as potentially having a major impact on causing or worsening heart failure include the antihypertensive drugs diltiazem, verapamil, and moxonidine, the tumor necrosis factor–inhibitors that are widely used to treat rheumatologic and gastroenterologic diseases, the antipsychotic clozapine, and a long list of anticancer medications, including several anthracyclines and many types of newer biologic agents.
The statement also lists several specific recommendations to health care providers for improving oversight of the drugs taken by patients with heart failure or those at risk for heart failure. These include a comprehensive medication review during each clinical encounter. The statement also suggests a “medication flow sheet” for each patient that contains the basic information regarding the regimen for each medication taken by a patient: the brand and generic name, the purpose of the medication, and its dosage. “These medication flow sheets should be used by patients as a tool to enhance safety and adherence, and they should show their flow sheets at each provider visit,” Dr. Page said.
Managing myriad meds
The statement also calls for stopping medications without a well defined indication for a patient, avoid prescribing new drugs to address side effects of other drugs, and suggests establishing a “captain” among the health care providers seen by each patient who would be particularly responsible for overseeing and keeping track of the medications the patient takes.
“Ideally, this ‘captain’ would be the patient’s primary care provider, who should be in contact with the other specialists that the patient may be seeing. However, this does not always happen,” said Dr. Page. “Therefore, I encourage each patient with heart failure to contact both their primary care provider and their health care provider who is managing their heart failure before taking or stopping any new medication including prescription, OTC, herbal, complimentary or alternative medication or supplement. Health care providers need to encourage patients to be actively engaged in their medication management.”
Dr. Page had no disclosures.
Cord blood cell infusions reduce cGVHD incidence
Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.
The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).
“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).
Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.
The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 107 cells/100 mL per month for four cycles beginning 4 months after HSCT
Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.
The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).
The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.
The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.
The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.
On the basis of the Gao et al. study, future investigations of cGVHD prophylaxis using MSCs should be explored. Approximately 90% of their population was younger than age 40, however, and it will be interesting to observe if this strategy is effective in older adults. The permutations and combinations for using different cell sources for deriving the MSCs, and in the context of different neoplastic disease, type and stage, conditioning regimen intensity, GVHD prophylaxis, graft and donor source, among other variables, are daunting. Nonetheless, the results of their trial encourage us to further explore this approach.
Hillard M. Lazarus, MD, is with Case Western Reserve University, Cleveland. Steven Z. Pavletic, MD, is with the National Institutes of Health, Bethesda, Md. Their comments were taken from an accompanying editorial (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2016.67.7344).
On the basis of the Gao et al. study, future investigations of cGVHD prophylaxis using MSCs should be explored. Approximately 90% of their population was younger than age 40, however, and it will be interesting to observe if this strategy is effective in older adults. The permutations and combinations for using different cell sources for deriving the MSCs, and in the context of different neoplastic disease, type and stage, conditioning regimen intensity, GVHD prophylaxis, graft and donor source, among other variables, are daunting. Nonetheless, the results of their trial encourage us to further explore this approach.
Hillard M. Lazarus, MD, is with Case Western Reserve University, Cleveland. Steven Z. Pavletic, MD, is with the National Institutes of Health, Bethesda, Md. Their comments were taken from an accompanying editorial (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2016.67.7344).
On the basis of the Gao et al. study, future investigations of cGVHD prophylaxis using MSCs should be explored. Approximately 90% of their population was younger than age 40, however, and it will be interesting to observe if this strategy is effective in older adults. The permutations and combinations for using different cell sources for deriving the MSCs, and in the context of different neoplastic disease, type and stage, conditioning regimen intensity, GVHD prophylaxis, graft and donor source, among other variables, are daunting. Nonetheless, the results of their trial encourage us to further explore this approach.
Hillard M. Lazarus, MD, is with Case Western Reserve University, Cleveland. Steven Z. Pavletic, MD, is with the National Institutes of Health, Bethesda, Md. Their comments were taken from an accompanying editorial (J Clin Oncol. 2016 Jul 11. doi: 10.1200/JCO.2016.67.7344).
Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.
The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).
“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).
Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.
The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 107 cells/100 mL per month for four cycles beginning 4 months after HSCT
Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.
The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).
The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.
The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.
The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.
Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.
The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).
“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).
Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.
The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 107 cells/100 mL per month for four cycles beginning 4 months after HSCT
Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.
The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).
The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.
The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.
The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Mesenchymal stromal cell infusions may reduce risk of chronic graft-versus-host disease following allogeneic stem cell transplants.
Major finding: The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27.4%, compared with 49% for placebo-treated controls.
Data source: Randomized, double-blind, controlled trial in 124 patients following HSCT for hematologic malignancies.
Disclosures: The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.