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Alpha-blockers deemed safe in heart failure
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology. 
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
WASHINGTON – Prescribing alpha-adrenergic blocking agents for treatment of benign prostatic hypertrophy in men with heart failure proved to be not only safe, but also was associated with significantly reduced rates of both heart failure readmission and all-cause mortality in a large retrospective cohort study.
“These findings are associative, not necessarily causative. But the novel association between alpha-blocker treatment and improved outcomes may warrant further study,” Alberta L. Warner, MD, said at the annual meeting of the American College of Cardiology.
Many men with heart failure also have benign prostatic hypertrophy (BPH), for which they receive treatment with an alpha-blocker. Yet little is known about the impact of this drug class on safety and outcomes in the setting of heart failure. Of note, the use of alpha-blockers for treatment of hypertension was associated with increased risk of new-onset heart failure in the ALLHAT study.
To shed light on the safety of alpha-blockers in patients with prevalent heart failure, Dr. Warner and her coinvestigators analyzed data on nearly 170,000 men with a primary diagnosis of heart failure discharged from Veterans Affairs hospitals in 2002-2015. They determined that fully 28% of them left the hospital on an alpha-blocker. From this pool of nearly 48,000 heart failure patients, they were able to propensity-score match 38,991 on the basis of 54 baseline clinical characteristics to an equal number of VA heart failure patients who weren’t on an alpha-blocker. The study outcomes were time to first readmission for heart failure or all-cause mortality during 2 years of follow-up.
Patients on an alpha-blocker had a 38% heart failure readmission rate at 2 years, compared with 40% in nonusers, for a modest, albeit statistically significant, 6% reduction in relative risk. The all-cause mortality rate also was significantly lower in patients on an alpha-blocker: 40% versus 44%, for a 9% relative risk reduction.
In a subanalysis restricted to the heart failure patients on an alpha-blocker, higher-dose therapy was associated with a significantly lower incidence of all-cause mortality than was a lower-dose alpha-blocker during 2 years of follow-up, with a 9% relative risk reduction. A high-dose alpha-blocker, however, wasn’t significantly more effective than lower-dose therapy in terms of reducing heart failure readmissions, said Dr. Warner, a cardiologist at the Veterans Affairs Greater Los Angeles Healthcare System and the University of California, Los Angeles.
Similarly, patients treated with a nonspecific, peripherally vasoactive alpha-blocker had a significantly lower mortality rate than those on an alpha-1a-adrenergic–specific agent, with a highly significant 15% reduction in relative risk. The type of alpha-blocker, however, didn’t make a significant difference in terms of heart failure readmissions, where both types of agents were similarly better than not being on an alpha-blocker at all, she said.
Eighty-five percent of study participants were on a beta-blocker. Heart failure readmissions and all-cause mortality were significantly lower with alpha-blocker therapy, regardless of whether patients were on background beta-blocker therapy.
One audience member, however, noting that the beta-blocker carvedilol possesses some alpha-blocking effects, asked if outcomes differed depending on whether a patient was on carvedilol or metoprolol.
Dr. Warner replied that those numbers are still being crunched, and that the final answer isn’t in yet, but her preliminary impression is that the benefits of alpha-blocker therapy in terms of both heart failure readmissions and all-cause mortality were attenuated in the patients on carvedilol, possibly due to that beta-blocker’s alpha-blocking properties.
She reported having no financial conflicts regarding the study.
Key clinical point:
Major finding: The risk of all-cause mortality in heart failure patients on an alpha-blocker was 9% lower than in extensively matched controls during 2 years of follow-up.
Data source: This retrospective cohort study included 38,991 heart failure patients taking an alpha-blocker for benign prostatic hypertrophy who were propensity matched on 54 clinical characteristics to an equal number of heart failure controls not on the medication.
Disclosures: The study presenter reported having no financial conflicts.
NCI to Study African-American Cancer Survivors
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Inhibitor produces durable responses in rel/ref iNHL
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.” 
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.”
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.”
First fossilized mammalian RBCs, Babesia-type pathogens found
An amber specimen found in the Dominican Republic contained the first fossilized mammalian red blood cells (RBCs) and intraerythrocytic hemoparasites, according to an article published in the Journal of Medical Entomology.
The fossil contained an engorged tick and RBCs infected with parasites that resemble existing members of the Babesiidae and Theileriidae families of the order Piroplasmida.
It appears that 2 small holes in the back of the tick allowed blood to ooze out just as the tick became stuck in tree sap that later fossilized into amber.
“These 2 tiny holes indicate that something picked a tick off the mammal it was feeding on, puncturing it in the process and dropping it immediately into tree sap,” said study author George Poinar, Jr, PhD, of Oregon State University in Corvallis.
“This would be consistent with the grooming behavior of monkeys that we know lived at that time in this region. The fossilized blood cells, infected with these parasites, are simply amazing in their detail. This discovery provides the only known fossils of Babesia-type pathogens.”
Dr Poinar said the amber specimen came from mines located in the Cordillera Septentrional of the Dominican Republic. It may have originated anywhere from 15 to 45 million years ago.
The fossil contained an engorged nymphal tick of the genus Ambylomma. The parasites found in the RBCs were also found in the gut epithelial cells and body cavity of the tick.
“The life forms we find in amber can reveal so much about the history and evolution of diseases we still struggle with today,” Dr Poinar said. “This parasite, for instance, was clearly around millions of years before humans and appears to have evolved alongside primates, among other hosts.”
Part of what makes this fossil unique, Dr Poinar said, is the way in which the parasites and RBCs were preserved, almost as if they had been stained and otherwise treated in a lab.
The parasites were different enough in texture and density to stand out clearly within the RBCs during the natural embalming process for which amber is famous.
An amber specimen found in the Dominican Republic contained the first fossilized mammalian red blood cells (RBCs) and intraerythrocytic hemoparasites, according to an article published in the Journal of Medical Entomology.
The fossil contained an engorged tick and RBCs infected with parasites that resemble existing members of the Babesiidae and Theileriidae families of the order Piroplasmida.
It appears that 2 small holes in the back of the tick allowed blood to ooze out just as the tick became stuck in tree sap that later fossilized into amber.
“These 2 tiny holes indicate that something picked a tick off the mammal it was feeding on, puncturing it in the process and dropping it immediately into tree sap,” said study author George Poinar, Jr, PhD, of Oregon State University in Corvallis.
“This would be consistent with the grooming behavior of monkeys that we know lived at that time in this region. The fossilized blood cells, infected with these parasites, are simply amazing in their detail. This discovery provides the only known fossils of Babesia-type pathogens.”
Dr Poinar said the amber specimen came from mines located in the Cordillera Septentrional of the Dominican Republic. It may have originated anywhere from 15 to 45 million years ago.
The fossil contained an engorged nymphal tick of the genus Ambylomma. The parasites found in the RBCs were also found in the gut epithelial cells and body cavity of the tick.
“The life forms we find in amber can reveal so much about the history and evolution of diseases we still struggle with today,” Dr Poinar said. “This parasite, for instance, was clearly around millions of years before humans and appears to have evolved alongside primates, among other hosts.”
Part of what makes this fossil unique, Dr Poinar said, is the way in which the parasites and RBCs were preserved, almost as if they had been stained and otherwise treated in a lab.
The parasites were different enough in texture and density to stand out clearly within the RBCs during the natural embalming process for which amber is famous.
An amber specimen found in the Dominican Republic contained the first fossilized mammalian red blood cells (RBCs) and intraerythrocytic hemoparasites, according to an article published in the Journal of Medical Entomology.
The fossil contained an engorged tick and RBCs infected with parasites that resemble existing members of the Babesiidae and Theileriidae families of the order Piroplasmida.
It appears that 2 small holes in the back of the tick allowed blood to ooze out just as the tick became stuck in tree sap that later fossilized into amber.
“These 2 tiny holes indicate that something picked a tick off the mammal it was feeding on, puncturing it in the process and dropping it immediately into tree sap,” said study author George Poinar, Jr, PhD, of Oregon State University in Corvallis.
“This would be consistent with the grooming behavior of monkeys that we know lived at that time in this region. The fossilized blood cells, infected with these parasites, are simply amazing in their detail. This discovery provides the only known fossils of Babesia-type pathogens.”
Dr Poinar said the amber specimen came from mines located in the Cordillera Septentrional of the Dominican Republic. It may have originated anywhere from 15 to 45 million years ago.
The fossil contained an engorged nymphal tick of the genus Ambylomma. The parasites found in the RBCs were also found in the gut epithelial cells and body cavity of the tick.
“The life forms we find in amber can reveal so much about the history and evolution of diseases we still struggle with today,” Dr Poinar said. “This parasite, for instance, was clearly around millions of years before humans and appears to have evolved alongside primates, among other hosts.”
Part of what makes this fossil unique, Dr Poinar said, is the way in which the parasites and RBCs were preserved, almost as if they had been stained and otherwise treated in a lab.
The parasites were different enough in texture and density to stand out clearly within the RBCs during the natural embalming process for which amber is famous.
Rule identifies women at low risk of VTE recurrence
Results of the REVERSE-II study appear to validate the utility of the HERDOO2 rule to identify women who can safely stop taking anticoagulants after their first unprovoked venous thromboembolism (VTE).
Some women who were classified as low-risk according to HERDOO2 did experience VTE recurrence after they stopped taking anticoagulants.
However, their risk of recurrence was lower than that of women who were classified as high-risk and stopped taking anticoagulants.
These results were published in The BMJ.
“Patients can get very anxious trying to balance the risks of [anticoagulation] with the risks of another blood clot,” said study author Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.
“With this rule, we can confidently tell half of the women we see that they are at low risk of having another blood clot. This means they can stop taking blood thinners once their initial clot is treated, sparing them the cost, inconvenience, and risks of taking life-long medication.”
The HERDOO2 rule suggests a woman has a low risk of VTE if she has 1 or none of the following risk factors:
- HER=Hyperpigmentation, edema, or redness in either leg
- D=High levels of D-dimer in the blood
- O=Obesity (body mass index of 30 kg/m2 or more)
- O=Older age (65+).
To test the rule, Dr Rodgers and his colleagues evaluated 2785 men and women with a first, unprovoked VTE. The patients were recruited between 2008 and 2015 from 44 healthcare centers in 7 countries.
Patients who were found to be at low risk of VTE recurrence were told to stop taking anticoagulants after they completed the initial treatment for their first VTE.
For patients considered at high risk for VTE recurrence, the researchers left the decision of continuing anticoagulation to the patients and their doctors.
Low-risk patients
None of the men in this trial could be identified as low-risk using the HERDOO2 rule.
However, 631 women had a low risk of VTE recurrence according to HERDOO2. Most of these women (n=591) stopped anticoagulant therapy.
Twenty-seven low-risk women decided to continue anticoagulation, 1 patient’s physician decided she required continued anticoagulation, and 3 patients continued for “other” reasons.
Nine patients in this group were lost to follow-up.
High-risk patients
There were 2148 men and women considered at high risk for VTE recurrence. Most of these patients (n=1802) continued anticoagulation.
Of the 323 high-risk patients who stopped anticoagulation, 279 did so because of their own preference, 9 due to physician decision, 15 had a high risk of bleeding, and 20 stopped for “other” reasons.
Twenty-three patients in this group were lost to follow-up.
Results
The researchers followed the patients for a year after they had finished treatment for their first VTE.
The risk of recurrent major VTE per 100 patient-years was:
- 3.0% among low-risk women who discontinued anticoagulants
- 8.1% among men and high-risk women who discontinued anticoagulants
- 7.4% among high-risk women (only) who discontinued anticoagulants
- 1.6% among men and high-risk women who continued anticoagulants.
Among the low-risk women who continued to receive anticoagulants, there were no cases of recurrent, symptomatic VTE.
“We see 2 to 3 patients with unexplained blood clots every day at The Ottawa Hospital,” Dr Rodger said. “If this rule was applied across Canada, we estimate that over 10,000 women a year would be identified as low risk and be able to come off blood thinners.”
Results of the REVERSE-II study appear to validate the utility of the HERDOO2 rule to identify women who can safely stop taking anticoagulants after their first unprovoked venous thromboembolism (VTE).
Some women who were classified as low-risk according to HERDOO2 did experience VTE recurrence after they stopped taking anticoagulants.
However, their risk of recurrence was lower than that of women who were classified as high-risk and stopped taking anticoagulants.
These results were published in The BMJ.
“Patients can get very anxious trying to balance the risks of [anticoagulation] with the risks of another blood clot,” said study author Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.
“With this rule, we can confidently tell half of the women we see that they are at low risk of having another blood clot. This means they can stop taking blood thinners once their initial clot is treated, sparing them the cost, inconvenience, and risks of taking life-long medication.”
The HERDOO2 rule suggests a woman has a low risk of VTE if she has 1 or none of the following risk factors:
- HER=Hyperpigmentation, edema, or redness in either leg
- D=High levels of D-dimer in the blood
- O=Obesity (body mass index of 30 kg/m2 or more)
- O=Older age (65+).
To test the rule, Dr Rodgers and his colleagues evaluated 2785 men and women with a first, unprovoked VTE. The patients were recruited between 2008 and 2015 from 44 healthcare centers in 7 countries.
Patients who were found to be at low risk of VTE recurrence were told to stop taking anticoagulants after they completed the initial treatment for their first VTE.
For patients considered at high risk for VTE recurrence, the researchers left the decision of continuing anticoagulation to the patients and their doctors.
Low-risk patients
None of the men in this trial could be identified as low-risk using the HERDOO2 rule.
However, 631 women had a low risk of VTE recurrence according to HERDOO2. Most of these women (n=591) stopped anticoagulant therapy.
Twenty-seven low-risk women decided to continue anticoagulation, 1 patient’s physician decided she required continued anticoagulation, and 3 patients continued for “other” reasons.
Nine patients in this group were lost to follow-up.
High-risk patients
There were 2148 men and women considered at high risk for VTE recurrence. Most of these patients (n=1802) continued anticoagulation.
Of the 323 high-risk patients who stopped anticoagulation, 279 did so because of their own preference, 9 due to physician decision, 15 had a high risk of bleeding, and 20 stopped for “other” reasons.
Twenty-three patients in this group were lost to follow-up.
Results
The researchers followed the patients for a year after they had finished treatment for their first VTE.
The risk of recurrent major VTE per 100 patient-years was:
- 3.0% among low-risk women who discontinued anticoagulants
- 8.1% among men and high-risk women who discontinued anticoagulants
- 7.4% among high-risk women (only) who discontinued anticoagulants
- 1.6% among men and high-risk women who continued anticoagulants.
Among the low-risk women who continued to receive anticoagulants, there were no cases of recurrent, symptomatic VTE.
“We see 2 to 3 patients with unexplained blood clots every day at The Ottawa Hospital,” Dr Rodger said. “If this rule was applied across Canada, we estimate that over 10,000 women a year would be identified as low risk and be able to come off blood thinners.”
Results of the REVERSE-II study appear to validate the utility of the HERDOO2 rule to identify women who can safely stop taking anticoagulants after their first unprovoked venous thromboembolism (VTE).
Some women who were classified as low-risk according to HERDOO2 did experience VTE recurrence after they stopped taking anticoagulants.
However, their risk of recurrence was lower than that of women who were classified as high-risk and stopped taking anticoagulants.
These results were published in The BMJ.
“Patients can get very anxious trying to balance the risks of [anticoagulation] with the risks of another blood clot,” said study author Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.
“With this rule, we can confidently tell half of the women we see that they are at low risk of having another blood clot. This means they can stop taking blood thinners once their initial clot is treated, sparing them the cost, inconvenience, and risks of taking life-long medication.”
The HERDOO2 rule suggests a woman has a low risk of VTE if she has 1 or none of the following risk factors:
- HER=Hyperpigmentation, edema, or redness in either leg
- D=High levels of D-dimer in the blood
- O=Obesity (body mass index of 30 kg/m2 or more)
- O=Older age (65+).
To test the rule, Dr Rodgers and his colleagues evaluated 2785 men and women with a first, unprovoked VTE. The patients were recruited between 2008 and 2015 from 44 healthcare centers in 7 countries.
Patients who were found to be at low risk of VTE recurrence were told to stop taking anticoagulants after they completed the initial treatment for their first VTE.
For patients considered at high risk for VTE recurrence, the researchers left the decision of continuing anticoagulation to the patients and their doctors.
Low-risk patients
None of the men in this trial could be identified as low-risk using the HERDOO2 rule.
However, 631 women had a low risk of VTE recurrence according to HERDOO2. Most of these women (n=591) stopped anticoagulant therapy.
Twenty-seven low-risk women decided to continue anticoagulation, 1 patient’s physician decided she required continued anticoagulation, and 3 patients continued for “other” reasons.
Nine patients in this group were lost to follow-up.
High-risk patients
There were 2148 men and women considered at high risk for VTE recurrence. Most of these patients (n=1802) continued anticoagulation.
Of the 323 high-risk patients who stopped anticoagulation, 279 did so because of their own preference, 9 due to physician decision, 15 had a high risk of bleeding, and 20 stopped for “other” reasons.
Twenty-three patients in this group were lost to follow-up.
Results
The researchers followed the patients for a year after they had finished treatment for their first VTE.
The risk of recurrent major VTE per 100 patient-years was:
- 3.0% among low-risk women who discontinued anticoagulants
- 8.1% among men and high-risk women who discontinued anticoagulants
- 7.4% among high-risk women (only) who discontinued anticoagulants
- 1.6% among men and high-risk women who continued anticoagulants.
Among the low-risk women who continued to receive anticoagulants, there were no cases of recurrent, symptomatic VTE.
“We see 2 to 3 patients with unexplained blood clots every day at The Ottawa Hospital,” Dr Rodger said. “If this rule was applied across Canada, we estimate that over 10,000 women a year would be identified as low risk and be able to come off blood thinners.”
Pilot Has a Flighty Heart
ANSWER
This ECG is consistent with sinus tachycardia, low-voltage QRS complexes, a posterior infarction, and ST- and T-wave abnormalities suggestive of inferior ischemia.
Sinus tachycardia is evidenced by the equal number of P and QRS complexes with a consistent PR interval. QRS complexes of lower amplitude than one would expect for the patient’s body habitus are deemed low voltage.
A posterior infarct is demonstrated by an R wave with no S wave in V1. Additionally, leads V2 and V3 show a pattern of a dominant R wave wit
Finally, inferior ischemia is identified by ST depressions in anterolateral leads I, aVL, V5, and V6, and T-wave inversions in inferior leads III and aVF.
ANSWER
This ECG is consistent with sinus tachycardia, low-voltage QRS complexes, a posterior infarction, and ST- and T-wave abnormalities suggestive of inferior ischemia.
Sinus tachycardia is evidenced by the equal number of P and QRS complexes with a consistent PR interval. QRS complexes of lower amplitude than one would expect for the patient’s body habitus are deemed low voltage.
A posterior infarct is demonstrated by an R wave with no S wave in V1. Additionally, leads V2 and V3 show a pattern of a dominant R wave wit
Finally, inferior ischemia is identified by ST depressions in anterolateral leads I, aVL, V5, and V6, and T-wave inversions in inferior leads III and aVF.
ANSWER
This ECG is consistent with sinus tachycardia, low-voltage QRS complexes, a posterior infarction, and ST- and T-wave abnormalities suggestive of inferior ischemia.
Sinus tachycardia is evidenced by the equal number of P and QRS complexes with a consistent PR interval. QRS complexes of lower amplitude than one would expect for the patient’s body habitus are deemed low voltage.
A posterior infarct is demonstrated by an R wave with no S wave in V1. Additionally, leads V2 and V3 show a pattern of a dominant R wave wit
Finally, inferior ischemia is identified by ST depressions in anterolateral leads I, aVL, V5, and V6, and T-wave inversions in inferior leads III and aVF.
For the past six hours, a 58-year-old man has been experiencing substernal chest discomfort. He is a commercial airline pilot for a regional carrier. Earlier today, he served as co-pilot on a roundtrip flight; about one hour before take-off, he started to feel a dull aching sensation in his chest that he attributed to his recently diagnosed gastroesophageal reflux disease (GERD). After landing, he purchased antacids in the airport terminal and took several, which provided only mild relief for the return trip. The pilot in command suggested he “get checked out” to make certain he didn’t have a bleeding ulcer.
Upon arrival at your facility, the patient appears uncomfortable but denies pain in his chest; there is no radiation to the neck, back, or arm. He denies palpitations, nausea, vomiting, diarrhea, and constipation. He says he feels more short of breath now than he did earlier, adding that “something just doesn’t feel right.”
The patient is a widower; his wife died of breast cancer at age 40. His daughter and son-in-law live in the same neighborhood so he can be close to his grandson. An avid triathlon participant, he has his own gym at home.
His medical history is remarkable for GERD, which was confirmed two months ago by upper endoscopy following several episodes of epigastric pain. He was prescribed a proton pump inhibitor, which he has forgotten to take for the past two days. His last flight physical, performed one year ago, was normal. Surgical history is remarkable for a tonsillectomy and a left inguinal hernia repair, both during childhood.
His current medication list includes lansoprazole and ibuprofen (as needed for musculoskeletal pain). He does not smoke, and he occasionally has a beer on the weekends when he isn’t working. The review of systems is noncontributory apart from his previously detailed symptoms.
Vital signs include a blood pressure of 130/86 mm Hg; pulse, 128 beats/min; respiratory rate, 12 breaths/min-1; and temperature, 97.9°F. His weight is 189 lb and his height, 73 in.
Physical exam reveals an uncomfortable, anxious-appearing male who is otherwise in excellent physical shape. Pertinent findings include a normal thyroid, no evidence of jugular venous distention, and clear lung fields bilaterally. The cardiac exam reveals a regular rate of 130 beats/min with no evidence of murmurs or rubs. The abdomen is flat and nontender, with no organomegaly. Peripheral pulses are equal bilaterally, and there is no peripheral edema. The neurologic exam is grossly intact.
A chest x-ray, ECG, and bloodwork are obtained. The ECG reveals a ventricular rate of 128 beats/min; PR interval, 136 ms; QRS duration, 72 ms; QT/QTc interval, 326/475 ms; P axis, 44°; R axis, 40°; and T axis, –47°. The ECG obtained during his flight physical one year ago showed normal sinus rhythm with nonspecific ST- and T-wave changes but was otherwise normal. With this history in mind, what is your interpretation of today’s ECG?
Defining high reliability
When the Joint Commission on Accreditation of Healthcare Organizations came to our hospital for a survey last fall, our administration was confident that the review would be favorable. The Joint Commission was stressing the reliability of hospitals and so were we. We had chartered a “High-Reliability Organization Enterprise Steering Committee” that was “empowered to make recommendations to the (executive board) on what is needed to achieve the goals of high reliability across the enterprise.” High reliability was a priority for our administration and for the Joint Commission. Unfortunately, nearly no one else knew what high reliability meant.
In 2001, Karl E. Weick and Kathleen M. Sutcliffe published their book, “Managing the Unexpected: Resilient Performance in an Age of Uncertainty,” (Hoboken, N.J.: Jossey-Bass, 2001), which defined high-reliability organizations as those that reliably prevent error. They included examples from the military and from aviation. They proffered five principles to guide those organizations wishing to become highly reliable:
1. Preoccupation with failure.
2. Reluctance to simplify interpretations.
3. Sensitivity to operations.
4. Commitment to resilience.
5. Deference to expertise.
In September 2005, the Agency for Healthcare Research and Quality created a document to adapt the concepts developed by Mr. Weick and Ms. Sutcliffe to the health care industry, where opportunities to avoid error and prevent catastrophe abound. The eventual result has been steady progress in measuring avoidable health care errors, such as avoiding central line–associated blood stream infections and holding health care organizations accountable for their reduction. However, organizational cultures are difficult to change, and there is still a long way to go.
In contrast to large systems, individual providers can change quickly, especially if there is incentive to do so. What principles would increase our own ability to become a high-reliability individuals (HRIs):
• Recognize failure as systemic, not personal. Health care providers are humans, and humans make mistakes. Unfortunately, we come from a tradition that rewards success and penalizes failure. Research shows that is better to recognize failure as something to be prevented next time rather than to be punished now. Admonitions to pay attention, focus more, and remember better rely on fallible humans and reliably fail. Systems solutions, such as checklists, timeouts, and hard stops reliably succeed. HRIs should blame error less often on people, and more often on system failures.
• Simple solutions are preferred to complex requirements. Chemotherapy was once calculated and written by hand. Every cancer center can recall tragic disasters that occurred as a result of errors either by the ordering physician or by interpretations made by pharmacists and nurses. The introduction of electronic chemotherapy ordering has nearly eliminated these mistakes. HRIs can initiate technology solutions to their work to help reduce the risk of errors.
• Sensitivity to patients. Patients often desire to be included as partners in their care. In addition to being present and attentive to patients, why not enlist them as colleagues in care? For example, the patient who has their own calendar of chemotherapy treatments – complete with agents, doses, and schedules – will be more likely to question perceived errors. HRIs are transparent.
• Resilience in character. Learning to accept the potential for error requires acceptance that others also are trying to prevent error and are not judging your competence. The physician who attacks those who are trying to help reduces the psychological safety required for colleagues to speak up when potential errors are identified. Physicians will become HRIs only when they lower their defenses and become more teammates rather than a soloists.
• Deference to evidence. The “way it has always been” must give way to the way things are. Anecdotes and personal conviction do not meet scientific standards and should be abandoned in the face of evidence. Yet, this seemingly obvious principle often is disregarded when clinicians are presented with standardized treatment pathways and limited formularies in the name of autonomy; autonomy is fine until patients are endangered by it. The HRI practices evidence-based medicine.
Marty Makary, MD, explores most of these principles in his book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care”(London: Bloomsbury Publishing, 2012). While written from a surgeon’s perspective, Dr. Makary exposes the dangerous state of modern medical care across all specialties. I recommend it as a sobering assessment of the way things are and as a prescription for health care systems and physicians to help them become more reliable.
How are you driving safety in your area? What are some best practices we can share with others? I invite you to reply to [email protected] to initiate a broader discussion of patient safety and reliability. Responses will be posted to hematologynews.com.
Dr. Kalaycio is Editor in Chief of Hematology News. Dr. Kalaycio chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].
When the Joint Commission on Accreditation of Healthcare Organizations came to our hospital for a survey last fall, our administration was confident that the review would be favorable. The Joint Commission was stressing the reliability of hospitals and so were we. We had chartered a “High-Reliability Organization Enterprise Steering Committee” that was “empowered to make recommendations to the (executive board) on what is needed to achieve the goals of high reliability across the enterprise.” High reliability was a priority for our administration and for the Joint Commission. Unfortunately, nearly no one else knew what high reliability meant.
In 2001, Karl E. Weick and Kathleen M. Sutcliffe published their book, “Managing the Unexpected: Resilient Performance in an Age of Uncertainty,” (Hoboken, N.J.: Jossey-Bass, 2001), which defined high-reliability organizations as those that reliably prevent error. They included examples from the military and from aviation. They proffered five principles to guide those organizations wishing to become highly reliable:
1. Preoccupation with failure.
2. Reluctance to simplify interpretations.
3. Sensitivity to operations.
4. Commitment to resilience.
5. Deference to expertise.
In September 2005, the Agency for Healthcare Research and Quality created a document to adapt the concepts developed by Mr. Weick and Ms. Sutcliffe to the health care industry, where opportunities to avoid error and prevent catastrophe abound. The eventual result has been steady progress in measuring avoidable health care errors, such as avoiding central line–associated blood stream infections and holding health care organizations accountable for their reduction. However, organizational cultures are difficult to change, and there is still a long way to go.
In contrast to large systems, individual providers can change quickly, especially if there is incentive to do so. What principles would increase our own ability to become a high-reliability individuals (HRIs):
• Recognize failure as systemic, not personal. Health care providers are humans, and humans make mistakes. Unfortunately, we come from a tradition that rewards success and penalizes failure. Research shows that is better to recognize failure as something to be prevented next time rather than to be punished now. Admonitions to pay attention, focus more, and remember better rely on fallible humans and reliably fail. Systems solutions, such as checklists, timeouts, and hard stops reliably succeed. HRIs should blame error less often on people, and more often on system failures.
• Simple solutions are preferred to complex requirements. Chemotherapy was once calculated and written by hand. Every cancer center can recall tragic disasters that occurred as a result of errors either by the ordering physician or by interpretations made by pharmacists and nurses. The introduction of electronic chemotherapy ordering has nearly eliminated these mistakes. HRIs can initiate technology solutions to their work to help reduce the risk of errors.
• Sensitivity to patients. Patients often desire to be included as partners in their care. In addition to being present and attentive to patients, why not enlist them as colleagues in care? For example, the patient who has their own calendar of chemotherapy treatments – complete with agents, doses, and schedules – will be more likely to question perceived errors. HRIs are transparent.
• Resilience in character. Learning to accept the potential for error requires acceptance that others also are trying to prevent error and are not judging your competence. The physician who attacks those who are trying to help reduces the psychological safety required for colleagues to speak up when potential errors are identified. Physicians will become HRIs only when they lower their defenses and become more teammates rather than a soloists.
• Deference to evidence. The “way it has always been” must give way to the way things are. Anecdotes and personal conviction do not meet scientific standards and should be abandoned in the face of evidence. Yet, this seemingly obvious principle often is disregarded when clinicians are presented with standardized treatment pathways and limited formularies in the name of autonomy; autonomy is fine until patients are endangered by it. The HRI practices evidence-based medicine.
Marty Makary, MD, explores most of these principles in his book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care”(London: Bloomsbury Publishing, 2012). While written from a surgeon’s perspective, Dr. Makary exposes the dangerous state of modern medical care across all specialties. I recommend it as a sobering assessment of the way things are and as a prescription for health care systems and physicians to help them become more reliable.
How are you driving safety in your area? What are some best practices we can share with others? I invite you to reply to [email protected] to initiate a broader discussion of patient safety and reliability. Responses will be posted to hematologynews.com.
Dr. Kalaycio is Editor in Chief of Hematology News. Dr. Kalaycio chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].
When the Joint Commission on Accreditation of Healthcare Organizations came to our hospital for a survey last fall, our administration was confident that the review would be favorable. The Joint Commission was stressing the reliability of hospitals and so were we. We had chartered a “High-Reliability Organization Enterprise Steering Committee” that was “empowered to make recommendations to the (executive board) on what is needed to achieve the goals of high reliability across the enterprise.” High reliability was a priority for our administration and for the Joint Commission. Unfortunately, nearly no one else knew what high reliability meant.
In 2001, Karl E. Weick and Kathleen M. Sutcliffe published their book, “Managing the Unexpected: Resilient Performance in an Age of Uncertainty,” (Hoboken, N.J.: Jossey-Bass, 2001), which defined high-reliability organizations as those that reliably prevent error. They included examples from the military and from aviation. They proffered five principles to guide those organizations wishing to become highly reliable:
1. Preoccupation with failure.
2. Reluctance to simplify interpretations.
3. Sensitivity to operations.
4. Commitment to resilience.
5. Deference to expertise.
In September 2005, the Agency for Healthcare Research and Quality created a document to adapt the concepts developed by Mr. Weick and Ms. Sutcliffe to the health care industry, where opportunities to avoid error and prevent catastrophe abound. The eventual result has been steady progress in measuring avoidable health care errors, such as avoiding central line–associated blood stream infections and holding health care organizations accountable for their reduction. However, organizational cultures are difficult to change, and there is still a long way to go.
In contrast to large systems, individual providers can change quickly, especially if there is incentive to do so. What principles would increase our own ability to become a high-reliability individuals (HRIs):
• Recognize failure as systemic, not personal. Health care providers are humans, and humans make mistakes. Unfortunately, we come from a tradition that rewards success and penalizes failure. Research shows that is better to recognize failure as something to be prevented next time rather than to be punished now. Admonitions to pay attention, focus more, and remember better rely on fallible humans and reliably fail. Systems solutions, such as checklists, timeouts, and hard stops reliably succeed. HRIs should blame error less often on people, and more often on system failures.
• Simple solutions are preferred to complex requirements. Chemotherapy was once calculated and written by hand. Every cancer center can recall tragic disasters that occurred as a result of errors either by the ordering physician or by interpretations made by pharmacists and nurses. The introduction of electronic chemotherapy ordering has nearly eliminated these mistakes. HRIs can initiate technology solutions to their work to help reduce the risk of errors.
• Sensitivity to patients. Patients often desire to be included as partners in their care. In addition to being present and attentive to patients, why not enlist them as colleagues in care? For example, the patient who has their own calendar of chemotherapy treatments – complete with agents, doses, and schedules – will be more likely to question perceived errors. HRIs are transparent.
• Resilience in character. Learning to accept the potential for error requires acceptance that others also are trying to prevent error and are not judging your competence. The physician who attacks those who are trying to help reduces the psychological safety required for colleagues to speak up when potential errors are identified. Physicians will become HRIs only when they lower their defenses and become more teammates rather than a soloists.
• Deference to evidence. The “way it has always been” must give way to the way things are. Anecdotes and personal conviction do not meet scientific standards and should be abandoned in the face of evidence. Yet, this seemingly obvious principle often is disregarded when clinicians are presented with standardized treatment pathways and limited formularies in the name of autonomy; autonomy is fine until patients are endangered by it. The HRI practices evidence-based medicine.
Marty Makary, MD, explores most of these principles in his book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care”(London: Bloomsbury Publishing, 2012). While written from a surgeon’s perspective, Dr. Makary exposes the dangerous state of modern medical care across all specialties. I recommend it as a sobering assessment of the way things are and as a prescription for health care systems and physicians to help them become more reliable.
How are you driving safety in your area? What are some best practices we can share with others? I invite you to reply to [email protected] to initiate a broader discussion of patient safety and reliability. Responses will be posted to hematologynews.com.
Dr. Kalaycio is Editor in Chief of Hematology News. Dr. Kalaycio chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].
Cosmetic Corner: Dermatologists Weigh in on Products for Hyperhidrosis
To improve patient care and outcomes, leading dermatologists offered their recommendations on hyperhidrosis products. Consideration must be given to:
- Certain Dri Prescription Strength Clinical Roll-On
Clarion Brands Inc
“This over-the-counter antiperspirant has 12% aluminum chloride, making it very effective in treating hyperhidrosis.”—Shari Lipner, MD, PhD, New York, New York
Recommended by Gary Goldenberg, MD, New York, New York
- miraDry
Miramar Labs, Inc
“miraDry offers a noninvasive reduction of sweating of more than 70% after the first treatment in the underarm area.”—Larisa Ravitskiy, MD, Gahanna, Ohio
- SweatBlock Clinical Strength Antiperspirant Towelettes
SweatBlock
“Each of the towelettes contains 14% aluminum chloride, can be applied to any part of the body, and can last up to 7 days.”—Jeannette Graf, MD, New York, New York
Cutis invites readers to send us their recommendations. Products for athlete’s foot, redness reduction, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.
Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.
[polldaddy:9711250]
To improve patient care and outcomes, leading dermatologists offered their recommendations on hyperhidrosis products. Consideration must be given to:
- Certain Dri Prescription Strength Clinical Roll-On
Clarion Brands Inc
“This over-the-counter antiperspirant has 12% aluminum chloride, making it very effective in treating hyperhidrosis.”—Shari Lipner, MD, PhD, New York, New York
Recommended by Gary Goldenberg, MD, New York, New York
- miraDry
Miramar Labs, Inc
“miraDry offers a noninvasive reduction of sweating of more than 70% after the first treatment in the underarm area.”—Larisa Ravitskiy, MD, Gahanna, Ohio
- SweatBlock Clinical Strength Antiperspirant Towelettes
SweatBlock
“Each of the towelettes contains 14% aluminum chloride, can be applied to any part of the body, and can last up to 7 days.”—Jeannette Graf, MD, New York, New York
Cutis invites readers to send us their recommendations. Products for athlete’s foot, redness reduction, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.
Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.
[polldaddy:9711250]
To improve patient care and outcomes, leading dermatologists offered their recommendations on hyperhidrosis products. Consideration must be given to:
- Certain Dri Prescription Strength Clinical Roll-On
Clarion Brands Inc
“This over-the-counter antiperspirant has 12% aluminum chloride, making it very effective in treating hyperhidrosis.”—Shari Lipner, MD, PhD, New York, New York
Recommended by Gary Goldenberg, MD, New York, New York
- miraDry
Miramar Labs, Inc
“miraDry offers a noninvasive reduction of sweating of more than 70% after the first treatment in the underarm area.”—Larisa Ravitskiy, MD, Gahanna, Ohio
- SweatBlock Clinical Strength Antiperspirant Towelettes
SweatBlock
“Each of the towelettes contains 14% aluminum chloride, can be applied to any part of the body, and can last up to 7 days.”—Jeannette Graf, MD, New York, New York
Cutis invites readers to send us their recommendations. Products for athlete’s foot, redness reduction, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.
Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.
[polldaddy:9711250]
New-onset AF boosts bad HFrEF outcomes
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – New onset atrial fibrillation more than doubled the rate of adverse outcomes in patients with heart failure with reduced ejection fraction in a review of more than 15,000 such patients.
In 9,934 patients with heart failure with reduced ejection fraction (HFrEF) and no history of atrial fibrillation (AF), development of new-onset AF was linked with a greater than twofold increased risk of cardiovascular disease death or hospitalization for heart failure during follow-up, compared with HFrEF patients who did not initially have or later develop heart failure, after adjustment for several demographic and clinical variables, John J.V. McMurray, MD, said at the annual meeting of the American College of Cardiology. This difference for the primary endpoint of his analysis was statistically significant.
The 1,645 patients with paroxysmal AF at the start of their follow-up also had a significantly increased rate of cardiovascular death or heart failure hospitalization, but their increased risk when compared with HFrEF patients who didn’t develop AF was a much more modest 20% in his fully adjusted analysis. The patients who began follow-up with paroxysmal AF also had a relatively increased relative stroke rate of 33% when compared with HFrEF patients without AF at baseline who remained AF free, but the all-cause mortality rate among those with paroxysmal AF wasn’t significantly elevated, compared with the comparator group.
The 3,770 patients with persistent or permanent AF at baseline showed no statistically significant spike in their adverse event rates, compared with patients without AF, for any of the examined endpoints. The study group also included 66 patients with an undefined form of AF who weren’t included in these analyses.
“It’s the first episodes and paroxysmal episodes that cause trouble, and the trouble they cause is stroke,” Dr. McMurray said in an interview. Their stroke risk gets exacerbated in clinical practice, because these patients often don’t receive the stroke prevention they need in the form of anticoagulation treatment.
“We find over and over that patients with paroxysmal AF are not anticoagulated as frequently as they should be,” Dr. McMurray said. And HFrEF patients with a first AF episode need anticoagulation, too, as soon as AF is diagnosed, he advised.
He went a step further and speculated that the reason why HFrEF patients with new onset AF did so poorly in his analysis was because they already had several prior, brief AF episodes that had gone undetected. “Many of these patients probably had undiagnosed, clinically unapparent AF episodes” that then resulted in strokes, he suggested.
The upshot is that patients with HFrEF may need more aggressive monitoring for new-onset AF, possibly in the form of small, implanted arrhythmia-detection devices. Dr. McMurray said that he and other researchers are currently testing whether this hypothesis is correct. “We and others are now looking at this because these new data are convincing that new-onset AF is bad news [for HFrEF patients].”
In the analysis, “we looked only at clinically recognized and adjudicated new-onset AF. Goodness knows how many HFrEF patients are having unrecognized paroxysmal AF. Almost certainly there is a lot that is unrecognized” that potentially could be detected using a small implanted arrhythmia monitor, which could then lead to earlier anticoagulant treatment as well as possible treatment with antiarrhythmic drugs or with catheter ablation, Dr. McMurray said. Looking for undetected AF in HFrEF patients “is where the science is moving.”
The findings that Dr. McMurray reported are “something we should act on,” commented Adrian F. Hernandez, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C. The comorbidity of AF in HFrEF patients requires “aggressive anticoagulation, and also a review of their heart failure medical treatment to be sure that is optimized, because AF could be a sign of worsening heart failure,” Dr. Hernandez said in an interview. “We may need to more aggressively get HFrEF patients with AF into normal sinus rhythm.”
When Mikhail Kosiborod, MD, treats HFrEF patients with a high risk for AF, such as patients with lower ejection fractions, a dilated left ventricle, or a dilated atrium, “I frequently do 30-day loop recordings in these patients because of their risk for incident AF,” Dr. Kosiborod said in an interview. “We don’t yet have convincing evidence for this, but it makes sense.”
Another finding from his analysis was that the HFrEF patients enrolled in these two trials did not get treatment with a mineralocorticoid receptor antagonist – spironolactone or eplerenone – “as often as they should,” with treatment rates of 44%-48%, compared with use of a beta-blocker in 92%-95% of patients. Treatment with eplerenone (Inspra) “has been shown to reduce the risk for new onset AF, so adding eplerenone or spironolactone is an important step that could be taken to try to prevent AF as well as treat the HFrEF and reduce mortality,” Dr. McMurray said.
PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen. Dr. Hernandez has received honoraria from Amgen, AstraZeneca, Janssen, Merck, and Novartis, and has received research support from Amgen, Bayer, Merck, and Portola. Dr. Kosiborod has been a consultant to several drug companies, and he has received research funding from AstraZeneca, Boehringer Ingelheim, Gilead, and Sanofi-Aventis.
[email protected]
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Adverse outcomes were more than twice as frequent in HFrEF patients with incident atrial fibrillation, compared with those without AF.
Data source: Post hoc analysis of 15,415 heart failure patients enrolled in the PARADIGM-HF and ATMOSPHERE trials.
Disclosures: PARADIGM-HF and ATMOSPHERE were funded by Novartis. Dr. McMurray has been a consultant to and has received travel and research support from Novartis, and he has received research and travel support from Amgen.
Bioidentical hormone replacement fares well in phase III trial
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: Four different dose combinations of 17 beta estradiol and progesterone improved hot flashes and menopause-related quality of life, compared with placebo (P less than .05 for all).
Data source: Multicenter randomized, double-blind, placebo-controlled study of 1,835 postmenopausal women with an intact uterus.
Disclosures: Dr. Lobo reported receiving research funding from TherapeuticsMD, which sponsored the study.