A Clinical Psychiatry News reader wrote in recently to object to the use of the term "shrink" in our column name. The writer noted, "We spend a lot of time trying to destigmatize the field, then use terms like this among ourselves. It’s odd and offensive." The feedback made me pause and wonder to myself if the term "shrink" is, in fact, stigmatizing.

Let me first give a little history of the decision to name our column "Shrink Rap News." In 2006, I was sitting at the kitchen table and decided I wanted a blog. I didn’t know what a blog actually was, but I wanted one. I went to blogger.com to set up a free website and was asked what I’d like to call my blog. On an impulse, I titled it "Shrink Rap." There was no debate or consideration, and no consultation. I liked the play on words with "shrink wrap," which is used for food storage, and I liked the connotation of psychiatrists talking, or "rapping." In a matter of hours, my impulsive thought was turned into the Shrink Rap blog.

Over the next few days, I invited Dr. Steve Daviss and Dr. Annette Hanson to join me in this venture, and Shrink Rap has continued to publish regular blog posts for 8.5 years now. Steve initially balked at the use of "shrink," but when he went to start our podcast, he titled it "My Three Shrinks" and modified the logo from an old television show, "My Three Sons." When we went to title our book, I wanted to call it "Off the Couch," but I was told that there was no room for couches anywhere. After many months of lively debate, we ended up in a restaurant with our editor and a whiteboard, and by the end of the evening we were back at Shrink Rap for a title for the book.

When Clinical Psychiatry News and Psychology Today approached us to write for their sites, we decided to remain with an image that was working for us, and used Shrink Rap News and Shrink Rap Today for column titles. Because the term may imply something less than a serious look at psychiatric issues, the umbrella name for all our endeavors is The Accessible Psychiatry Project.

So, is the term "shrink" actually stigmatizing? When I think of words as being part of stigma, I think of racial and religious slurs, and those induce a visceral response of disgust in me. For whatever reason, I personally don’t have a clear negative association to the term "shrink" or even "headshrinker." To me, it evokes something lighthearted and includes having a sense of humor about the field. I imagine if psychiatrists ever had actually shrunken heads, I might feel differently. Others may well have another response to the term, but the emotional link to something negative is just not there for me.

From a site called World Wide Words – Investigating the English Language Across the Globe, which is devoted to linguistics and run by a British etymologist, I found the following history of the term "headshrinker":

The original meaning of the term head-shrinker was in reference to a member of a group in Amazonia, the Jivaro, who preserved the heads of their enemies by stripping the skin from the skull, which resulted in a shrunken mummified remnant the size of a fist. The term isn’t that old – it’s first recorded from 1926.

All the early evidence suggests that the person who invented the psychiatrist sense worked in the movies (no jokes please). We have to assume that the term came about because people regarded the process of psychiatry as being like head-shrinking because it reduced the size of the swollen egos so common in show business. Or perhaps they were suspicious about what psychiatrists actually did to their heads and how they did it and so made a joke to relieve the tension.

The earliest example we have is from an article in Time in November 1950 to which an editor has helpfully added a footnote to say that head-shrinker was Hollywood jargon for a psychiatrist. The term afterward became moderately popular, in part because it was used in the film Rebel Without a Cause in 1955. Robert Heinlein felt his readers needed it to be explained when he introduced it in "Time for the Stars" in 1956: " ‘Dr. Devereaux is the boss head-shrinker.’ I looked puzzled and Uncle Steve went on, ‘You don’t savvy? Psychiatrist.’ " By the time it turns up in West Side Story on Broadway in 1957, it was becoming established.

Shrink, the abbreviation, became popular in the United States in the 1970s, though it had first appeared in one of Thomas Pynchon’s books, "The Crying of Lot 49," in 1965, and there is anecdotal evidence that it was around earlier, which is only to be expected of a slang term that would have been mainly transmitted through the spoken word in its earliest days.

The issue of stigma in mental health has gotten a lot of attention as being one reason that people who have difficulties may not seek help. Certainly, words can be powerful, but I wonder if the term "shrink" might actually be easier for patients to use? "I’m going to see my shrink," might imply a visit with any number of mental health professionals and might disassociate it from the implication that the patient is going to see a psychiatrist for treatment of a mental illness, a condition that the media is all too happy to tell us causes people to commit mass murders.

"Shrink" may have a disparaging tone to it, or it may have a ring of affection, depending on the context. Certainly, there are many negative associations and jokes related to being an attorney, and one friend told me that his son was "going to the dark side" when the son applied to law school. Still, there is no stigma associated with having an appointment with one’s lawyer, leading me to believe that a profession can be stigmatized without stigmatizing the clientele.

Some words have taken on a pervasively negative meaning; others are harder to capture. After 8 years, Shrink Rap is now a platform for our writing, invested with its own meanings to us and our readers. The psychiatrist who wrote in to say it is offensive, odd, and stigmatizing certainly has a different set of associations to the word then we do, or we would never have let this be a title for our work.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

A Clinical Psychiatry News reader wrote in recently to object to the use of the term "shrink" in our column name. The writer noted, "We spend a lot of time trying to destigmatize the field, then use terms like this among ourselves. It’s odd and offensive." The feedback made me pause and wonder to myself if the term "shrink" is, in fact, stigmatizing.

Let me first give a little history of the decision to name our column "Shrink Rap News." In 2006, I was sitting at the kitchen table and decided I wanted a blog. I didn’t know what a blog actually was, but I wanted one. I went to blogger.com to set up a free website and was asked what I’d like to call my blog. On an impulse, I titled it "Shrink Rap." There was no debate or consideration, and no consultation. I liked the play on words with "shrink wrap," which is used for food storage, and I liked the connotation of psychiatrists talking, or "rapping." In a matter of hours, my impulsive thought was turned into the Shrink Rap blog.

Over the next few days, I invited Dr. Steve Daviss and Dr. Annette Hanson to join me in this venture, and Shrink Rap has continued to publish regular blog posts for 8.5 years now. Steve initially balked at the use of "shrink," but when he went to start our podcast, he titled it "My Three Shrinks" and modified the logo from an old television show, "My Three Sons." When we went to title our book, I wanted to call it "Off the Couch," but I was told that there was no room for couches anywhere. After many months of lively debate, we ended up in a restaurant with our editor and a whiteboard, and by the end of the evening we were back at Shrink Rap for a title for the book.

When Clinical Psychiatry News and Psychology Today approached us to write for their sites, we decided to remain with an image that was working for us, and used Shrink Rap News and Shrink Rap Today for column titles. Because the term may imply something less than a serious look at psychiatric issues, the umbrella name for all our endeavors is The Accessible Psychiatry Project.

So, is the term "shrink" actually stigmatizing? When I think of words as being part of stigma, I think of racial and religious slurs, and those induce a visceral response of disgust in me. For whatever reason, I personally don’t have a clear negative association to the term "shrink" or even "headshrinker." To me, it evokes something lighthearted and includes having a sense of humor about the field. I imagine if psychiatrists ever had actually shrunken heads, I might feel differently. Others may well have another response to the term, but the emotional link to something negative is just not there for me.

From a site called World Wide Words – Investigating the English Language Across the Globe, which is devoted to linguistics and run by a British etymologist, I found the following history of the term "headshrinker":

The original meaning of the term head-shrinker was in reference to a member of a group in Amazonia, the Jivaro, who preserved the heads of their enemies by stripping the skin from the skull, which resulted in a shrunken mummified remnant the size of a fist. The term isn’t that old – it’s first recorded from 1926.

All the early evidence suggests that the person who invented the psychiatrist sense worked in the movies (no jokes please). We have to assume that the term came about because people regarded the process of psychiatry as being like head-shrinking because it reduced the size of the swollen egos so common in show business. Or perhaps they were suspicious about what psychiatrists actually did to their heads and how they did it and so made a joke to relieve the tension.

The earliest example we have is from an article in Time in November 1950 to which an editor has helpfully added a footnote to say that head-shrinker was Hollywood jargon for a psychiatrist. The term afterward became moderately popular, in part because it was used in the film Rebel Without a Cause in 1955. Robert Heinlein felt his readers needed it to be explained when he introduced it in "Time for the Stars" in 1956: " ‘Dr. Devereaux is the boss head-shrinker.’ I looked puzzled and Uncle Steve went on, ‘You don’t savvy? Psychiatrist.’ " By the time it turns up in West Side Story on Broadway in 1957, it was becoming established.

Shrink, the abbreviation, became popular in the United States in the 1970s, though it had first appeared in one of Thomas Pynchon’s books, "The Crying of Lot 49," in 1965, and there is anecdotal evidence that it was around earlier, which is only to be expected of a slang term that would have been mainly transmitted through the spoken word in its earliest days.

The issue of stigma in mental health has gotten a lot of attention as being one reason that people who have difficulties may not seek help. Certainly, words can be powerful, but I wonder if the term "shrink" might actually be easier for patients to use? "I’m going to see my shrink," might imply a visit with any number of mental health professionals and might disassociate it from the implication that the patient is going to see a psychiatrist for treatment of a mental illness, a condition that the media is all too happy to tell us causes people to commit mass murders.

"Shrink" may have a disparaging tone to it, or it may have a ring of affection, depending on the context. Certainly, there are many negative associations and jokes related to being an attorney, and one friend told me that his son was "going to the dark side" when the son applied to law school. Still, there is no stigma associated with having an appointment with one’s lawyer, leading me to believe that a profession can be stigmatized without stigmatizing the clientele.

Some words have taken on a pervasively negative meaning; others are harder to capture. After 8 years, Shrink Rap is now a platform for our writing, invested with its own meanings to us and our readers. The psychiatrist who wrote in to say it is offensive, odd, and stigmatizing certainly has a different set of associations to the word then we do, or we would never have let this be a title for our work.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

A Clinical Psychiatry News reader wrote in recently to object to the use of the term "shrink" in our column name. The writer noted, "We spend a lot of time trying to destigmatize the field, then use terms like this among ourselves. It’s odd and offensive." The feedback made me pause and wonder to myself if the term "shrink" is, in fact, stigmatizing.

Let me first give a little history of the decision to name our column "Shrink Rap News." In 2006, I was sitting at the kitchen table and decided I wanted a blog. I didn’t know what a blog actually was, but I wanted one. I went to blogger.com to set up a free website and was asked what I’d like to call my blog. On an impulse, I titled it "Shrink Rap." There was no debate or consideration, and no consultation. I liked the play on words with "shrink wrap," which is used for food storage, and I liked the connotation of psychiatrists talking, or "rapping." In a matter of hours, my impulsive thought was turned into the Shrink Rap blog.

Over the next few days, I invited Dr. Steve Daviss and Dr. Annette Hanson to join me in this venture, and Shrink Rap has continued to publish regular blog posts for 8.5 years now. Steve initially balked at the use of "shrink," but when he went to start our podcast, he titled it "My Three Shrinks" and modified the logo from an old television show, "My Three Sons." When we went to title our book, I wanted to call it "Off the Couch," but I was told that there was no room for couches anywhere. After many months of lively debate, we ended up in a restaurant with our editor and a whiteboard, and by the end of the evening we were back at Shrink Rap for a title for the book.

When Clinical Psychiatry News and Psychology Today approached us to write for their sites, we decided to remain with an image that was working for us, and used Shrink Rap News and Shrink Rap Today for column titles. Because the term may imply something less than a serious look at psychiatric issues, the umbrella name for all our endeavors is The Accessible Psychiatry Project.

So, is the term "shrink" actually stigmatizing? When I think of words as being part of stigma, I think of racial and religious slurs, and those induce a visceral response of disgust in me. For whatever reason, I personally don’t have a clear negative association to the term "shrink" or even "headshrinker." To me, it evokes something lighthearted and includes having a sense of humor about the field. I imagine if psychiatrists ever had actually shrunken heads, I might feel differently. Others may well have another response to the term, but the emotional link to something negative is just not there for me.

From a site called World Wide Words – Investigating the English Language Across the Globe, which is devoted to linguistics and run by a British etymologist, I found the following history of the term "headshrinker":

The original meaning of the term head-shrinker was in reference to a member of a group in Amazonia, the Jivaro, who preserved the heads of their enemies by stripping the skin from the skull, which resulted in a shrunken mummified remnant the size of a fist. The term isn’t that old – it’s first recorded from 1926.

All the early evidence suggests that the person who invented the psychiatrist sense worked in the movies (no jokes please). We have to assume that the term came about because people regarded the process of psychiatry as being like head-shrinking because it reduced the size of the swollen egos so common in show business. Or perhaps they were suspicious about what psychiatrists actually did to their heads and how they did it and so made a joke to relieve the tension.

The earliest example we have is from an article in Time in November 1950 to which an editor has helpfully added a footnote to say that head-shrinker was Hollywood jargon for a psychiatrist. The term afterward became moderately popular, in part because it was used in the film Rebel Without a Cause in 1955. Robert Heinlein felt his readers needed it to be explained when he introduced it in "Time for the Stars" in 1956: " ‘Dr. Devereaux is the boss head-shrinker.’ I looked puzzled and Uncle Steve went on, ‘You don’t savvy? Psychiatrist.’ " By the time it turns up in West Side Story on Broadway in 1957, it was becoming established.

Shrink, the abbreviation, became popular in the United States in the 1970s, though it had first appeared in one of Thomas Pynchon’s books, "The Crying of Lot 49," in 1965, and there is anecdotal evidence that it was around earlier, which is only to be expected of a slang term that would have been mainly transmitted through the spoken word in its earliest days.

The issue of stigma in mental health has gotten a lot of attention as being one reason that people who have difficulties may not seek help. Certainly, words can be powerful, but I wonder if the term "shrink" might actually be easier for patients to use? "I’m going to see my shrink," might imply a visit with any number of mental health professionals and might disassociate it from the implication that the patient is going to see a psychiatrist for treatment of a mental illness, a condition that the media is all too happy to tell us causes people to commit mass murders.

"Shrink" may have a disparaging tone to it, or it may have a ring of affection, depending on the context. Certainly, there are many negative associations and jokes related to being an attorney, and one friend told me that his son was "going to the dark side" when the son applied to law school. Still, there is no stigma associated with having an appointment with one’s lawyer, leading me to believe that a profession can be stigmatized without stigmatizing the clientele.

Some words have taken on a pervasively negative meaning; others are harder to capture. After 8 years, Shrink Rap is now a platform for our writing, invested with its own meanings to us and our readers. The psychiatrist who wrote in to say it is offensive, odd, and stigmatizing certainly has a different set of associations to the word then we do, or we would never have let this be a title for our work.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

The U.S. prevalence of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is about 4 cases per 100,000 Americans, according to the Centers for Disease Control and Prevention.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is usually fatal within 2-5 years of diagnosis. A hereditary form of the disease accounts for between 10% and 15% of cases. In the rest, the cause or causes are unknown, although chemical and infectious exposures are among the suspected triggers.

The new prevalence figures, which the CDC published in its Morbidity and Mortality Weekly Report issued July 25 (MMWR 2014;63[SS07]:1-14), represent the first national prevalence findings for ALS in the United States, and derive from surveillance begun in 2009 by the federal Agency for Toxic Substances and Disease Registry in Atlanta, where Dr. Paul Mehta led the investigation.

Dr. Mehta and his colleagues identified cases from Medicare, Medicaid, Veterans Heath Administration, and Veterans Benefits Administration databases, as well a secure public website through which ALS patients could self-report to the CDC by answering a series of screening questions.

Between October 2010 and the end of 2011, the registry identified 12,187 people 18 years and older with ALS, for a prevalence of 3.9 cases of ALS per 100,000 – findings that are consistent, the researchers said, with those from long-running European ALS registries.

As in other studies, men had a higher prevalence of ALS than did women (4.8 per 100,000 vs. 3.0 per 100,000). "Factors such as occupational history and environmental exposures might be associated with this finding," the researchers wrote in their analysis.

The prevalence of ALS among whites was more than double that of blacks (4.2 per vs. 2.0). "The reason for this difference in prevalence by race is unknown and needs to be investigated further," Dr. Mehta and his associates wrote. However, they noted, the race findings were also consistent with other studies.

The age group 70-79 was associated with the highest prevalence rate, at 17.0 per 100,000, followed by 60-69 at about 12.

Dr. Mehta and his colleagues acknowledged that their study had several limitations, including the fact that the ALS registry was relatively new; that ALS is not a notifiable disease in most states, making it difficult to capture all cases; that data errors or file duplication could have occurred; and that it was not possible to calculate ALS incidence, only prevalence, because most cases in the registry did not have a diagnosis date.

No conflicts of interest were mentioned in the report.

The U.S. prevalence of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is about 4 cases per 100,000 Americans, according to the Centers for Disease Control and Prevention.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is usually fatal within 2-5 years of diagnosis. A hereditary form of the disease accounts for between 10% and 15% of cases. In the rest, the cause or causes are unknown, although chemical and infectious exposures are among the suspected triggers.

The new prevalence figures, which the CDC published in its Morbidity and Mortality Weekly Report issued July 25 (MMWR 2014;63[SS07]:1-14), represent the first national prevalence findings for ALS in the United States, and derive from surveillance begun in 2009 by the federal Agency for Toxic Substances and Disease Registry in Atlanta, where Dr. Paul Mehta led the investigation.

Dr. Mehta and his colleagues identified cases from Medicare, Medicaid, Veterans Heath Administration, and Veterans Benefits Administration databases, as well a secure public website through which ALS patients could self-report to the CDC by answering a series of screening questions.

Between October 2010 and the end of 2011, the registry identified 12,187 people 18 years and older with ALS, for a prevalence of 3.9 cases of ALS per 100,000 – findings that are consistent, the researchers said, with those from long-running European ALS registries.

As in other studies, men had a higher prevalence of ALS than did women (4.8 per 100,000 vs. 3.0 per 100,000). "Factors such as occupational history and environmental exposures might be associated with this finding," the researchers wrote in their analysis.

The prevalence of ALS among whites was more than double that of blacks (4.2 per vs. 2.0). "The reason for this difference in prevalence by race is unknown and needs to be investigated further," Dr. Mehta and his associates wrote. However, they noted, the race findings were also consistent with other studies.

The age group 70-79 was associated with the highest prevalence rate, at 17.0 per 100,000, followed by 60-69 at about 12.

Dr. Mehta and his colleagues acknowledged that their study had several limitations, including the fact that the ALS registry was relatively new; that ALS is not a notifiable disease in most states, making it difficult to capture all cases; that data errors or file duplication could have occurred; and that it was not possible to calculate ALS incidence, only prevalence, because most cases in the registry did not have a diagnosis date.

No conflicts of interest were mentioned in the report.

The U.S. prevalence of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is about 4 cases per 100,000 Americans, according to the Centers for Disease Control and Prevention.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is usually fatal within 2-5 years of diagnosis. A hereditary form of the disease accounts for between 10% and 15% of cases. In the rest, the cause or causes are unknown, although chemical and infectious exposures are among the suspected triggers.

The new prevalence figures, which the CDC published in its Morbidity and Mortality Weekly Report issued July 25 (MMWR 2014;63[SS07]:1-14), represent the first national prevalence findings for ALS in the United States, and derive from surveillance begun in 2009 by the federal Agency for Toxic Substances and Disease Registry in Atlanta, where Dr. Paul Mehta led the investigation.

Dr. Mehta and his colleagues identified cases from Medicare, Medicaid, Veterans Heath Administration, and Veterans Benefits Administration databases, as well a secure public website through which ALS patients could self-report to the CDC by answering a series of screening questions.

Between October 2010 and the end of 2011, the registry identified 12,187 people 18 years and older with ALS, for a prevalence of 3.9 cases of ALS per 100,000 – findings that are consistent, the researchers said, with those from long-running European ALS registries.

As in other studies, men had a higher prevalence of ALS than did women (4.8 per 100,000 vs. 3.0 per 100,000). "Factors such as occupational history and environmental exposures might be associated with this finding," the researchers wrote in their analysis.

The prevalence of ALS among whites was more than double that of blacks (4.2 per vs. 2.0). "The reason for this difference in prevalence by race is unknown and needs to be investigated further," Dr. Mehta and his associates wrote. However, they noted, the race findings were also consistent with other studies.

The age group 70-79 was associated with the highest prevalence rate, at 17.0 per 100,000, followed by 60-69 at about 12.

Dr. Mehta and his colleagues acknowledged that their study had several limitations, including the fact that the ALS registry was relatively new; that ALS is not a notifiable disease in most states, making it difficult to capture all cases; that data errors or file duplication could have occurred; and that it was not possible to calculate ALS incidence, only prevalence, because most cases in the registry did not have a diagnosis date.

No conflicts of interest were mentioned in the report.

Pregnant silhouette

Credit: Ninan Matthews

Low-molecular-weight heparin (LMWH) does not reduce complications in pregnant women with thrombophilia, according to a study published in The Lancet.

Thrombophilia increases the risk of pregnancy-associated venous thromboembolism (VTE), pregnancy loss, and placenta-mediated pregnancy complications.

For years, physicians have believed that daily antepartum injections of LMWH can reduce these complications, but results of a randomized trial suggest this is not the case.

The LMWH dalteparin provided no positive benefits for mothers or their children. In fact, the study indicated that LMWH could actually cause pregnant women minor harm by increasing the risk of bleeding, increasing the rate of induced labor, and reducing access to anesthesia during childbirth.

“These results mean that many women around the world can save themselves a lot of unnecessary pain during pregnancy,” said study author Marc Rodger, MD, of the Ottawa Hospital Research Institute in Canada.

“While I wish we could have shown that LMWH prevents complications, we actually proved it doesn’t help. However, I’m very glad that we can now spare these women all those unnecessary needles.”

To assess the safety and efficacy of LMWH, Dr Rodger and his colleagues analyzed 289 pregnant women with thrombophilia who were at an increased risk of VTE or had previous placenta-mediated pregnancy complications.

The subjects were randomized to no treatment (n=143) or antepartum prophylactic doses of dalteparin (n=146)—5000 IU once daily up to 20 weeks’ gestation and twice daily thereafter until at least 37 weeks’ gestation.

Some patients crossed over during treatment. So for the on-treatment and safety analyses, there were 143 patients in the dalteparin arm and 141 in the control arm.

Patients met the primary efficacy endpoint if they experienced 1 or more of the following: severe or early onset pre-eclampsia, a small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or VTE.

Results showed that dalteparin did not reduce the incidence of this composite outcome in either the intent-to-treat analysis or the on-treatment analysis.

In the intent-to-treat analysis, 17.1% (25/146) of patients in the dalteparin arm met the endpoint, as did 18.9% (27/143) of those in the control arm. In the on-treatment analysis, 19.6% (28/143) of patients in the dalteparin arm met the endpoint, as did 17% (24/141) of those in the control arm.

The safety analysis revealed no significant difference in the incidence of major bleeding between the dalteparin and control arms—2.1% (3/143) and 1.4% (2/141), respectively.

Minor bleeding was more common in the dalteparin arm than the control arm, occurring in 19.6% (28/143) and 9.2% (13/141) of patients, respectively (P=0.01).

Dr Rodger said he hopes these results will prompt physicians to stop prescribing LMWH to pregnant women with thrombophilia and/or previous pregnancy complications when it isn’t warranted.

“These findings allow us to move on, to pursue other potentially effective methods for treating pregnant women with thrombophilia and/or complications from placenta blood clots,” he said.

He and his colleagues noted, however, that patients with one type of thrombophilia—anti-phospholipid antibodies—may benefit from anticoagulant therapy, as it can prevent recurrent pregnancy loss.

Furthermore, some women should take low-dose aspirin while pregnant to help prevent pregnancy complications. And all women with thrombophilia should receive anticoagulant therapy to prevent thrombosis after delivery.

So it seems that some pregnant women might still benefit from taking anticoagulants, but this requires further study.

Pregnant silhouette

Credit: Ninan Matthews

Low-molecular-weight heparin (LMWH) does not reduce complications in pregnant women with thrombophilia, according to a study published in The Lancet.

Thrombophilia increases the risk of pregnancy-associated venous thromboembolism (VTE), pregnancy loss, and placenta-mediated pregnancy complications.

For years, physicians have believed that daily antepartum injections of LMWH can reduce these complications, but results of a randomized trial suggest this is not the case.

The LMWH dalteparin provided no positive benefits for mothers or their children. In fact, the study indicated that LMWH could actually cause pregnant women minor harm by increasing the risk of bleeding, increasing the rate of induced labor, and reducing access to anesthesia during childbirth.

“These results mean that many women around the world can save themselves a lot of unnecessary pain during pregnancy,” said study author Marc Rodger, MD, of the Ottawa Hospital Research Institute in Canada.

“While I wish we could have shown that LMWH prevents complications, we actually proved it doesn’t help. However, I’m very glad that we can now spare these women all those unnecessary needles.”

To assess the safety and efficacy of LMWH, Dr Rodger and his colleagues analyzed 289 pregnant women with thrombophilia who were at an increased risk of VTE or had previous placenta-mediated pregnancy complications.

The subjects were randomized to no treatment (n=143) or antepartum prophylactic doses of dalteparin (n=146)—5000 IU once daily up to 20 weeks’ gestation and twice daily thereafter until at least 37 weeks’ gestation.

Some patients crossed over during treatment. So for the on-treatment and safety analyses, there were 143 patients in the dalteparin arm and 141 in the control arm.

Patients met the primary efficacy endpoint if they experienced 1 or more of the following: severe or early onset pre-eclampsia, a small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or VTE.

Results showed that dalteparin did not reduce the incidence of this composite outcome in either the intent-to-treat analysis or the on-treatment analysis.

In the intent-to-treat analysis, 17.1% (25/146) of patients in the dalteparin arm met the endpoint, as did 18.9% (27/143) of those in the control arm. In the on-treatment analysis, 19.6% (28/143) of patients in the dalteparin arm met the endpoint, as did 17% (24/141) of those in the control arm.

The safety analysis revealed no significant difference in the incidence of major bleeding between the dalteparin and control arms—2.1% (3/143) and 1.4% (2/141), respectively.

Minor bleeding was more common in the dalteparin arm than the control arm, occurring in 19.6% (28/143) and 9.2% (13/141) of patients, respectively (P=0.01).

Dr Rodger said he hopes these results will prompt physicians to stop prescribing LMWH to pregnant women with thrombophilia and/or previous pregnancy complications when it isn’t warranted.

“These findings allow us to move on, to pursue other potentially effective methods for treating pregnant women with thrombophilia and/or complications from placenta blood clots,” he said.

He and his colleagues noted, however, that patients with one type of thrombophilia—anti-phospholipid antibodies—may benefit from anticoagulant therapy, as it can prevent recurrent pregnancy loss.

Furthermore, some women should take low-dose aspirin while pregnant to help prevent pregnancy complications. And all women with thrombophilia should receive anticoagulant therapy to prevent thrombosis after delivery.

So it seems that some pregnant women might still benefit from taking anticoagulants, but this requires further study.

Pregnant silhouette

Credit: Ninan Matthews

Low-molecular-weight heparin (LMWH) does not reduce complications in pregnant women with thrombophilia, according to a study published in The Lancet.

Thrombophilia increases the risk of pregnancy-associated venous thromboembolism (VTE), pregnancy loss, and placenta-mediated pregnancy complications.

For years, physicians have believed that daily antepartum injections of LMWH can reduce these complications, but results of a randomized trial suggest this is not the case.

The LMWH dalteparin provided no positive benefits for mothers or their children. In fact, the study indicated that LMWH could actually cause pregnant women minor harm by increasing the risk of bleeding, increasing the rate of induced labor, and reducing access to anesthesia during childbirth.

“These results mean that many women around the world can save themselves a lot of unnecessary pain during pregnancy,” said study author Marc Rodger, MD, of the Ottawa Hospital Research Institute in Canada.

“While I wish we could have shown that LMWH prevents complications, we actually proved it doesn’t help. However, I’m very glad that we can now spare these women all those unnecessary needles.”

To assess the safety and efficacy of LMWH, Dr Rodger and his colleagues analyzed 289 pregnant women with thrombophilia who were at an increased risk of VTE or had previous placenta-mediated pregnancy complications.

The subjects were randomized to no treatment (n=143) or antepartum prophylactic doses of dalteparin (n=146)—5000 IU once daily up to 20 weeks’ gestation and twice daily thereafter until at least 37 weeks’ gestation.

Some patients crossed over during treatment. So for the on-treatment and safety analyses, there were 143 patients in the dalteparin arm and 141 in the control arm.

Patients met the primary efficacy endpoint if they experienced 1 or more of the following: severe or early onset pre-eclampsia, a small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or VTE.

Results showed that dalteparin did not reduce the incidence of this composite outcome in either the intent-to-treat analysis or the on-treatment analysis.

In the intent-to-treat analysis, 17.1% (25/146) of patients in the dalteparin arm met the endpoint, as did 18.9% (27/143) of those in the control arm. In the on-treatment analysis, 19.6% (28/143) of patients in the dalteparin arm met the endpoint, as did 17% (24/141) of those in the control arm.

The safety analysis revealed no significant difference in the incidence of major bleeding between the dalteparin and control arms—2.1% (3/143) and 1.4% (2/141), respectively.

Minor bleeding was more common in the dalteparin arm than the control arm, occurring in 19.6% (28/143) and 9.2% (13/141) of patients, respectively (P=0.01).

Dr Rodger said he hopes these results will prompt physicians to stop prescribing LMWH to pregnant women with thrombophilia and/or previous pregnancy complications when it isn’t warranted.

“These findings allow us to move on, to pursue other potentially effective methods for treating pregnant women with thrombophilia and/or complications from placenta blood clots,” he said.

He and his colleagues noted, however, that patients with one type of thrombophilia—anti-phospholipid antibodies—may benefit from anticoagulant therapy, as it can prevent recurrent pregnancy loss.

Furthermore, some women should take low-dose aspirin while pregnant to help prevent pregnancy complications. And all women with thrombophilia should receive anticoagulant therapy to prevent thrombosis after delivery.

So it seems that some pregnant women might still benefit from taking anticoagulants, but this requires further study.

Stem cells for transplant

Credit: Chad McNeeley

New research suggests a majority of US patients who need unrelated hematopoietic stem cell transplants can find a suitable donor on the Be The Match Registry.

However, the likelihood of finding an 8/8 HLA-matched adult donor is often low, particularly for patients of diverse ethnic or racial backgrounds.

And finding a 6/6 HLA-matched cord blood donor is a long shot regardless of race or ethnicity, although patients younger than 20 years of age have better odds.

These findings appear in NEJM.

“This research confirms that physicians should identify the best available donor with minimal delay,” said study author Dennis Confer, MD, chief medical officer at National Marrow Donor Program/Be the Match in Minneapolis.

“Transplant should not be postponed in anticipation of finding a perfect match. Using a suitable match reflects current clinical practice.”

Dr Confer and his colleagues built population-based genetic models for 21 racial and ethnic groups to predict the likelihood of identifying a suitable adult or cord blood donor for each group.

The researchers used data on HLA genotypes and cord blood unit cell doses from the National Marrow Donor Program’s Be the Match registry, which included 10,759,087 adult donors and 186,166 cord blood units at the end of 2012.

The team found the likelihood of identifying an 8/8 HLA-matched donor is highest for white patients of European descent, at 75%, but it’s only 46% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the probability of finding an 8/8 matched donor ranges from 16% (the lowest figure) to 19%.

And figures range from 27% to 57% for Hispanics, Asians, Pacific Islanders, and Native Americans (which includes individuals from the Caribbean and North, Central, and South America).

The likelihood of identifying a 7/8 matched donor is, again, highest for white patients of European descent, at 97%. And it’s 90% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the likelihood of finding a 7/8 matched donor ranges from 66% (the lowest figure) to 76%. And it ranges from 72% to 91% for Hispanics, Asians, Pacific Islanders, and Native Americans.

The probability of identifying a 6/6 cord blood match is low for all racial/ethnic groups, but age plays a role. For patients age 20 and older, figures range from 1%—for both African and black Caribbean patients—to 17% for white Europeans. For patients younger than 20, figures range from 6% to 38% for the same groups.

For patients 20 and older, the likelihood of finding a 5/6 cord blood match ranges from 23% for African patients to 66% for white Europeans. And for the younger age group, the figures range from 56% to 87% for the same groups.

“We cannot yet find a suitably matched and available donor for every patient,” Dr Confer noted. “So we cannot slow down our efforts to expand the registry and fund more research to overcome these challenges.”

“To find a match for all patients, it is critical that those who join the registry remain committed to donate when called, and that we continue to add people to the Be The Match Registry for racial and ethnic groups of highest need.”

Stem cells for transplant

Credit: Chad McNeeley

New research suggests a majority of US patients who need unrelated hematopoietic stem cell transplants can find a suitable donor on the Be The Match Registry.

However, the likelihood of finding an 8/8 HLA-matched adult donor is often low, particularly for patients of diverse ethnic or racial backgrounds.

And finding a 6/6 HLA-matched cord blood donor is a long shot regardless of race or ethnicity, although patients younger than 20 years of age have better odds.

These findings appear in NEJM.

“This research confirms that physicians should identify the best available donor with minimal delay,” said study author Dennis Confer, MD, chief medical officer at National Marrow Donor Program/Be the Match in Minneapolis.

“Transplant should not be postponed in anticipation of finding a perfect match. Using a suitable match reflects current clinical practice.”

Dr Confer and his colleagues built population-based genetic models for 21 racial and ethnic groups to predict the likelihood of identifying a suitable adult or cord blood donor for each group.

The researchers used data on HLA genotypes and cord blood unit cell doses from the National Marrow Donor Program’s Be the Match registry, which included 10,759,087 adult donors and 186,166 cord blood units at the end of 2012.

The team found the likelihood of identifying an 8/8 HLA-matched donor is highest for white patients of European descent, at 75%, but it’s only 46% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the probability of finding an 8/8 matched donor ranges from 16% (the lowest figure) to 19%.

And figures range from 27% to 57% for Hispanics, Asians, Pacific Islanders, and Native Americans (which includes individuals from the Caribbean and North, Central, and South America).

The likelihood of identifying a 7/8 matched donor is, again, highest for white patients of European descent, at 97%. And it’s 90% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the likelihood of finding a 7/8 matched donor ranges from 66% (the lowest figure) to 76%. And it ranges from 72% to 91% for Hispanics, Asians, Pacific Islanders, and Native Americans.

The probability of identifying a 6/6 cord blood match is low for all racial/ethnic groups, but age plays a role. For patients age 20 and older, figures range from 1%—for both African and black Caribbean patients—to 17% for white Europeans. For patients younger than 20, figures range from 6% to 38% for the same groups.

For patients 20 and older, the likelihood of finding a 5/6 cord blood match ranges from 23% for African patients to 66% for white Europeans. And for the younger age group, the figures range from 56% to 87% for the same groups.

“We cannot yet find a suitably matched and available donor for every patient,” Dr Confer noted. “So we cannot slow down our efforts to expand the registry and fund more research to overcome these challenges.”

“To find a match for all patients, it is critical that those who join the registry remain committed to donate when called, and that we continue to add people to the Be The Match Registry for racial and ethnic groups of highest need.”

Stem cells for transplant

Credit: Chad McNeeley

New research suggests a majority of US patients who need unrelated hematopoietic stem cell transplants can find a suitable donor on the Be The Match Registry.

However, the likelihood of finding an 8/8 HLA-matched adult donor is often low, particularly for patients of diverse ethnic or racial backgrounds.

And finding a 6/6 HLA-matched cord blood donor is a long shot regardless of race or ethnicity, although patients younger than 20 years of age have better odds.

These findings appear in NEJM.

“This research confirms that physicians should identify the best available donor with minimal delay,” said study author Dennis Confer, MD, chief medical officer at National Marrow Donor Program/Be the Match in Minneapolis.

“Transplant should not be postponed in anticipation of finding a perfect match. Using a suitable match reflects current clinical practice.”

Dr Confer and his colleagues built population-based genetic models for 21 racial and ethnic groups to predict the likelihood of identifying a suitable adult or cord blood donor for each group.

The researchers used data on HLA genotypes and cord blood unit cell doses from the National Marrow Donor Program’s Be the Match registry, which included 10,759,087 adult donors and 186,166 cord blood units at the end of 2012.

The team found the likelihood of identifying an 8/8 HLA-matched donor is highest for white patients of European descent, at 75%, but it’s only 46% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the probability of finding an 8/8 matched donor ranges from 16% (the lowest figure) to 19%.

And figures range from 27% to 57% for Hispanics, Asians, Pacific Islanders, and Native Americans (which includes individuals from the Caribbean and North, Central, and South America).

The likelihood of identifying a 7/8 matched donor is, again, highest for white patients of European descent, at 97%. And it’s 90% for white patients of Middle Eastern or North African descent.

For black Americans of all ethnic backgrounds, the likelihood of finding a 7/8 matched donor ranges from 66% (the lowest figure) to 76%. And it ranges from 72% to 91% for Hispanics, Asians, Pacific Islanders, and Native Americans.

The probability of identifying a 6/6 cord blood match is low for all racial/ethnic groups, but age plays a role. For patients age 20 and older, figures range from 1%—for both African and black Caribbean patients—to 17% for white Europeans. For patients younger than 20, figures range from 6% to 38% for the same groups.

For patients 20 and older, the likelihood of finding a 5/6 cord blood match ranges from 23% for African patients to 66% for white Europeans. And for the younger age group, the figures range from 56% to 87% for the same groups.

“We cannot yet find a suitably matched and available donor for every patient,” Dr Confer noted. “So we cannot slow down our efforts to expand the registry and fund more research to overcome these challenges.”

“To find a match for all patients, it is critical that those who join the registry remain committed to donate when called, and that we continue to add people to the Be The Match Registry for racial and ethnic groups of highest need.”

Audrey Odom, MD, PhD

Credit: Robert Boston

Researchers have uncovered a way in which the malaria parasite Plasmodium falciparum becomes resistant to an investigational drug called fosmidomycin.

The team reported this finding in Nature Communications.

The malaria parasite makes a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy.

Fosmidomycin can be used to block isoprenoid synthesis and kill the malaria parasite.

But over time, the drug often becomes less effective.

“In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study,” said Audrey R. Odom, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?”

Using sequencing technology, she and her colleagues compared the genetics of malaria parasites that responded to the drug to the genetics of parasites that were resistant to it.

This revealed mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

“The PfHAD1 protein is completely unstudied,” Dr Odom said. “It’s a member of a larger family of proteins, and there are almost no biological functions assigned to them.”

Dr Odom’s team showed that, in malaria parasites, the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing.

Since isoprenoids are necessary for life, it’s not clear why the organism would purposefully slow down isoprenoid production.

“We don’t know why the protein puts the brakes on under normal conditions; perhaps simply because it’s an energetically expensive pathway,” Dr Odom said. “But loss of PfHAD1 releases the brakes, increasing the pathway’s activity, so that even when the drug is there, it doesn’t kill the cells.”

Therefore, Dr Odom and her colleagues believe isoprenoid synthesis is an attractive drug target for malaria.

Audrey Odom, MD, PhD

Credit: Robert Boston

Researchers have uncovered a way in which the malaria parasite Plasmodium falciparum becomes resistant to an investigational drug called fosmidomycin.

The team reported this finding in Nature Communications.

The malaria parasite makes a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy.

Fosmidomycin can be used to block isoprenoid synthesis and kill the malaria parasite.

But over time, the drug often becomes less effective.

“In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study,” said Audrey R. Odom, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?”

Using sequencing technology, she and her colleagues compared the genetics of malaria parasites that responded to the drug to the genetics of parasites that were resistant to it.

This revealed mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

“The PfHAD1 protein is completely unstudied,” Dr Odom said. “It’s a member of a larger family of proteins, and there are almost no biological functions assigned to them.”

Dr Odom’s team showed that, in malaria parasites, the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing.

Since isoprenoids are necessary for life, it’s not clear why the organism would purposefully slow down isoprenoid production.

“We don’t know why the protein puts the brakes on under normal conditions; perhaps simply because it’s an energetically expensive pathway,” Dr Odom said. “But loss of PfHAD1 releases the brakes, increasing the pathway’s activity, so that even when the drug is there, it doesn’t kill the cells.”

Therefore, Dr Odom and her colleagues believe isoprenoid synthesis is an attractive drug target for malaria.

Audrey Odom, MD, PhD

Credit: Robert Boston

Researchers have uncovered a way in which the malaria parasite Plasmodium falciparum becomes resistant to an investigational drug called fosmidomycin.

The team reported this finding in Nature Communications.

The malaria parasite makes a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy.

Fosmidomycin can be used to block isoprenoid synthesis and kill the malaria parasite.

But over time, the drug often becomes less effective.

“In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study,” said Audrey R. Odom, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?”

Using sequencing technology, she and her colleagues compared the genetics of malaria parasites that responded to the drug to the genetics of parasites that were resistant to it.

This revealed mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

“The PfHAD1 protein is completely unstudied,” Dr Odom said. “It’s a member of a larger family of proteins, and there are almost no biological functions assigned to them.”

Dr Odom’s team showed that, in malaria parasites, the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing.

Since isoprenoids are necessary for life, it’s not clear why the organism would purposefully slow down isoprenoid production.

“We don’t know why the protein puts the brakes on under normal conditions; perhaps simply because it’s an energetically expensive pathway,” Dr Odom said. “But loss of PfHAD1 releases the brakes, increasing the pathway’s activity, so that even when the drug is there, it doesn’t kill the cells.”

Therefore, Dr Odom and her colleagues believe isoprenoid synthesis is an attractive drug target for malaria.

Patient receiving chemotherapy

Credit: Rhoda Baer

A biosimilar of the erythropoiesis-stimulating agent epoetin alfa can elicit responses in patients with chemotherapy-induced anemia, according to a study published in BMC Cancer.

The agent, epoetin zeta (Retacrit), produced a hemoglobin (Hb) response in more than 80% of patients at 3- and 6-month time points.

Response rates were similar in patients with hematologic malignancies and those with solid tumors.

And the rate of clinically significant adverse events was low. This included thromboembolic events, bleeding, infection, local intolerability, and increased blood pressure.

Mauricette Michallet, MD, PhD, of Centre Hospitalier Lyon in France, and her colleagues conducted this study, known as ORHEO. It was sponsored by Hospira, the makers of epoetin zeta.

The researchers evaluated 2310 adult patients with chemotherapy-induced anemia (Hb<11 g/dL). Patients had solid tumors (n=1838), lymphomas (n=301), or multiple myeloma (n=171).

Patients were taking a number of treatments aside from epoetin zeta and chemotherapy. This included intravenous iron (10%), oral iron (16%), antithrombotic agents (12%), folates (7%), vitamin B (4%), and other vitamins (2%). An additional 17% of patients were reported as being on “other treatments.”

In all, 99.9% of patients received epoetin zeta. The primary endpoint was the rate of response.

Response was defined as an increase in Hb levels to at least 10 g/dL since enrollment, an increase in Hb levels of at least 1 g/dL since enrollment, or reaching target Hb levels set at the start of study, without any blood transfusions in the 3 weeks prior to measurement. In patients with baseline Hb levels of at least 10 g/dL, only those who reached their Hb target or had an increase greater than 1 g/dL were considered responders.

Eighty-two percent of patients achieved a response at 3 months, and 87% had a response at 6 months. The overall mean change in Hb level was 1.52 ± 1.61 at 3 months and 1.72 ± 1.61 g/dL at 6 months. The rate of transfusion was 9% at 3 months and 6% at 6 months.

Between enrollment and month 6, 1202 patients discontinued epoetin zeta. Forty percent stopped because Hb levels were met, 27% stopped because they were stopping or changing chemotherapy, 15% stopped for both of the aforementioned reasons, 11% stopped because epoetin zeta was ineffective, and 2% stopped due to adverse events.

Seventeen percent of patients experienced an adverse event, including thromboembolic events (4%), infection (5%), bleeding (2%), local intolerability (0.2%), increased blood pressure (2%), and “other” events (9%).

Epoetin zeta was approved in Europe in 2007. For epoetin biosimilars to gain approval in the European Union, companies must agree to conduct post-marketing studies.

Patient receiving chemotherapy

Credit: Rhoda Baer

A biosimilar of the erythropoiesis-stimulating agent epoetin alfa can elicit responses in patients with chemotherapy-induced anemia, according to a study published in BMC Cancer.

The agent, epoetin zeta (Retacrit), produced a hemoglobin (Hb) response in more than 80% of patients at 3- and 6-month time points.

Response rates were similar in patients with hematologic malignancies and those with solid tumors.

And the rate of clinically significant adverse events was low. This included thromboembolic events, bleeding, infection, local intolerability, and increased blood pressure.

Mauricette Michallet, MD, PhD, of Centre Hospitalier Lyon in France, and her colleagues conducted this study, known as ORHEO. It was sponsored by Hospira, the makers of epoetin zeta.

The researchers evaluated 2310 adult patients with chemotherapy-induced anemia (Hb<11 g/dL). Patients had solid tumors (n=1838), lymphomas (n=301), or multiple myeloma (n=171).

Patients were taking a number of treatments aside from epoetin zeta and chemotherapy. This included intravenous iron (10%), oral iron (16%), antithrombotic agents (12%), folates (7%), vitamin B (4%), and other vitamins (2%). An additional 17% of patients were reported as being on “other treatments.”

In all, 99.9% of patients received epoetin zeta. The primary endpoint was the rate of response.

Response was defined as an increase in Hb levels to at least 10 g/dL since enrollment, an increase in Hb levels of at least 1 g/dL since enrollment, or reaching target Hb levels set at the start of study, without any blood transfusions in the 3 weeks prior to measurement. In patients with baseline Hb levels of at least 10 g/dL, only those who reached their Hb target or had an increase greater than 1 g/dL were considered responders.

Eighty-two percent of patients achieved a response at 3 months, and 87% had a response at 6 months. The overall mean change in Hb level was 1.52 ± 1.61 at 3 months and 1.72 ± 1.61 g/dL at 6 months. The rate of transfusion was 9% at 3 months and 6% at 6 months.

Between enrollment and month 6, 1202 patients discontinued epoetin zeta. Forty percent stopped because Hb levels were met, 27% stopped because they were stopping or changing chemotherapy, 15% stopped for both of the aforementioned reasons, 11% stopped because epoetin zeta was ineffective, and 2% stopped due to adverse events.

Seventeen percent of patients experienced an adverse event, including thromboembolic events (4%), infection (5%), bleeding (2%), local intolerability (0.2%), increased blood pressure (2%), and “other” events (9%).

Epoetin zeta was approved in Europe in 2007. For epoetin biosimilars to gain approval in the European Union, companies must agree to conduct post-marketing studies.

Patient receiving chemotherapy

Credit: Rhoda Baer

A biosimilar of the erythropoiesis-stimulating agent epoetin alfa can elicit responses in patients with chemotherapy-induced anemia, according to a study published in BMC Cancer.

The agent, epoetin zeta (Retacrit), produced a hemoglobin (Hb) response in more than 80% of patients at 3- and 6-month time points.

Response rates were similar in patients with hematologic malignancies and those with solid tumors.

And the rate of clinically significant adverse events was low. This included thromboembolic events, bleeding, infection, local intolerability, and increased blood pressure.

Mauricette Michallet, MD, PhD, of Centre Hospitalier Lyon in France, and her colleagues conducted this study, known as ORHEO. It was sponsored by Hospira, the makers of epoetin zeta.

The researchers evaluated 2310 adult patients with chemotherapy-induced anemia (Hb<11 g/dL). Patients had solid tumors (n=1838), lymphomas (n=301), or multiple myeloma (n=171).

Patients were taking a number of treatments aside from epoetin zeta and chemotherapy. This included intravenous iron (10%), oral iron (16%), antithrombotic agents (12%), folates (7%), vitamin B (4%), and other vitamins (2%). An additional 17% of patients were reported as being on “other treatments.”

In all, 99.9% of patients received epoetin zeta. The primary endpoint was the rate of response.

Response was defined as an increase in Hb levels to at least 10 g/dL since enrollment, an increase in Hb levels of at least 1 g/dL since enrollment, or reaching target Hb levels set at the start of study, without any blood transfusions in the 3 weeks prior to measurement. In patients with baseline Hb levels of at least 10 g/dL, only those who reached their Hb target or had an increase greater than 1 g/dL were considered responders.

Eighty-two percent of patients achieved a response at 3 months, and 87% had a response at 6 months. The overall mean change in Hb level was 1.52 ± 1.61 at 3 months and 1.72 ± 1.61 g/dL at 6 months. The rate of transfusion was 9% at 3 months and 6% at 6 months.

Between enrollment and month 6, 1202 patients discontinued epoetin zeta. Forty percent stopped because Hb levels were met, 27% stopped because they were stopping or changing chemotherapy, 15% stopped for both of the aforementioned reasons, 11% stopped because epoetin zeta was ineffective, and 2% stopped due to adverse events.

Seventeen percent of patients experienced an adverse event, including thromboembolic events (4%), infection (5%), bleeding (2%), local intolerability (0.2%), increased blood pressure (2%), and “other” events (9%).

Epoetin zeta was approved in Europe in 2007. For epoetin biosimilars to gain approval in the European Union, companies must agree to conduct post-marketing studies.

Clinical question

Does increased hospitalist workload affect efficiency and quality of care?

Bottom line

Increased hospitalist workload is associated with increased cost and length of stay (LOS). Quality metrics such as 30-day readmission rate, in-hospital mortality, and patient satisfaction were not affected by changes in workload. (LOE = 2b)

Reference

Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med 2014;174(5):786-793.

Study design

Cohort (retrospective)

Funding source

Other

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Using data abstracted from the central data warehouse of an academic community health system, these authors examined the association between hospitalist workload and the efficiency and quality of care provided. A private hospitalist group that provided 24-hour care to patients at 2 hospitals within the system was selected for the study. Patients included were those who either had an attending of record or had admission and discharge bills submitted by a physician in this hospitalist group. Physician daily workload was measured using the total number of relative value units (RVUs) generated and the physician’s census as determined by the number of billable encounters submitted. Efficiency was measured by LOS and cost. Quality was measured by in-hospital mortality, rapid response team activation, 30-day readmission rate, and patient satisfaction. Models were adjusted for patient characteristics, including demographics; severity of illness; visit characteristics, including admission day of the week; and hospital-level characteristics, including hospital occupancy. Approximately 20,000 hospitalizations were included in the study. Hospitalists had a mean of 15.5 patient encounters and 28.6 RVUs per day. Results for LOS were stratified by hospital occupancy. For less than 75% occupancy, LOS increased linearly from 5.5 days to 7.5 days as workload increased. For greater than 85% occupancy, the change in LOS was J-shaped with a significant increase around an RVU of 30 or a census of 17. Cost also increased with higher workloads. For every unit increase in RVU, cost increased by $111; for every unit increase in census, cost increased by $205 (after adjustment for LOS). There were no significant associations with change in workload and patient satisfaction, in-hospital mortality, rapid response team activation, or 30-day readmission rate.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does increased hospitalist workload affect efficiency and quality of care?

Bottom line

Increased hospitalist workload is associated with increased cost and length of stay (LOS). Quality metrics such as 30-day readmission rate, in-hospital mortality, and patient satisfaction were not affected by changes in workload. (LOE = 2b)

Reference

Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med 2014;174(5):786-793.

Study design

Cohort (retrospective)

Funding source

Other

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Using data abstracted from the central data warehouse of an academic community health system, these authors examined the association between hospitalist workload and the efficiency and quality of care provided. A private hospitalist group that provided 24-hour care to patients at 2 hospitals within the system was selected for the study. Patients included were those who either had an attending of record or had admission and discharge bills submitted by a physician in this hospitalist group. Physician daily workload was measured using the total number of relative value units (RVUs) generated and the physician’s census as determined by the number of billable encounters submitted. Efficiency was measured by LOS and cost. Quality was measured by in-hospital mortality, rapid response team activation, 30-day readmission rate, and patient satisfaction. Models were adjusted for patient characteristics, including demographics; severity of illness; visit characteristics, including admission day of the week; and hospital-level characteristics, including hospital occupancy. Approximately 20,000 hospitalizations were included in the study. Hospitalists had a mean of 15.5 patient encounters and 28.6 RVUs per day. Results for LOS were stratified by hospital occupancy. For less than 75% occupancy, LOS increased linearly from 5.5 days to 7.5 days as workload increased. For greater than 85% occupancy, the change in LOS was J-shaped with a significant increase around an RVU of 30 or a census of 17. Cost also increased with higher workloads. For every unit increase in RVU, cost increased by $111; for every unit increase in census, cost increased by $205 (after adjustment for LOS). There were no significant associations with change in workload and patient satisfaction, in-hospital mortality, rapid response team activation, or 30-day readmission rate.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does increased hospitalist workload affect efficiency and quality of care?

Bottom line

Increased hospitalist workload is associated with increased cost and length of stay (LOS). Quality metrics such as 30-day readmission rate, in-hospital mortality, and patient satisfaction were not affected by changes in workload. (LOE = 2b)

Reference

Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med 2014;174(5):786-793.

Study design

Cohort (retrospective)

Funding source

Other

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Using data abstracted from the central data warehouse of an academic community health system, these authors examined the association between hospitalist workload and the efficiency and quality of care provided. A private hospitalist group that provided 24-hour care to patients at 2 hospitals within the system was selected for the study. Patients included were those who either had an attending of record or had admission and discharge bills submitted by a physician in this hospitalist group. Physician daily workload was measured using the total number of relative value units (RVUs) generated and the physician’s census as determined by the number of billable encounters submitted. Efficiency was measured by LOS and cost. Quality was measured by in-hospital mortality, rapid response team activation, 30-day readmission rate, and patient satisfaction. Models were adjusted for patient characteristics, including demographics; severity of illness; visit characteristics, including admission day of the week; and hospital-level characteristics, including hospital occupancy. Approximately 20,000 hospitalizations were included in the study. Hospitalists had a mean of 15.5 patient encounters and 28.6 RVUs per day. Results for LOS were stratified by hospital occupancy. For less than 75% occupancy, LOS increased linearly from 5.5 days to 7.5 days as workload increased. For greater than 85% occupancy, the change in LOS was J-shaped with a significant increase around an RVU of 30 or a census of 17. Cost also increased with higher workloads. For every unit increase in RVU, cost increased by $111; for every unit increase in census, cost increased by $205 (after adjustment for LOS). There were no significant associations with change in workload and patient satisfaction, in-hospital mortality, rapid response team activation, or 30-day readmission rate.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients with acute venous thromboembolism, is the use of anticoagulants plus nonsteroidal anti-inflammatory drugs or aspirin associated with an increased risk of bleeding?

Bottom line

For patients treated with anticoagulants for acute venous thromboembolism (VTE), the use of concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin is associated with an increased risk of bleeding. This can occur in patients treated with rivaroxaban, as well as in those treated with enoxaparin plus a vitamin K antagonist (VKA). (LOE = 2b)

Reference

Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014;174(6):947-953.

Study design

Cohort (prospective)

Funding source

Industry

Allocation

Uncertain

Setting

Outpatient (any)

Synopsis

The worldwide EINSTEIN DVT and EINSTEIN PE clinical trials compared rivaroxaban with enoxaparin plus a VKA for the treatment of acute VTE. These investigators used data from this cohort to examine the association between rivaroxaban or enoxaparin-VKA plus concomitant NSAID or aspirin use and the risk of clinically relevant and major bleeding. Clinically relevant bleeding was defined as nonmajor bleeding that resulted in either medical intervention, temporary cessation of study treatment, or patient discomfort. Major bleeding was that which resulted in death, occurred at a critical site, required tranfusion of at least 2 units of red blood cells, or was associated with a 2 g/dL drop in hemoglobin. The cohort comprised 8246 patients, with half receiving rivaroxaban and half receiving enoxaparin-VKA. The NSAID analysis was adjusted for sex, as there were more women in the NSAID group. The aspirin analysis was adjusted for age and creatinine clearance, as patients in the aspirin group tended to be older with worse kidney function than the nonaspirin group. The NSAID or aspirin exposure period included 7 days after stopping the medication to reflect an ongoing risk. Clinically relevant bleeding was more likely to occur in the NSAID group as compared with the non-NSAID group (37.5 bleeding events per 100 patient-years vs 16.6 per 100 patient-years; hazard ratio [HR] = 1.77; 95% CI, 1.46-2.14). Findings were similar for both the NSAID-rivaroxaban-treated patients and NSAID-enoxaparin-VKA-treated patients. In the aspirin group, clinically relevant bleeding was also increased as compared with the nonaspirin group (36.6 bleeding events per 100 patient-years vs 16.9 per 100 patient-years; HR = 1.70; 1.38-2.11). For both the NSAID and the aspirin groups, the bleeding events were spread evenly over the duration of the use, suggesting that longer duration of use does not increase the risk of bleeding. Major bleeding increased 2.4-fold in the NSAID group and 1.5-fold in the aspirin group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients with acute venous thromboembolism, is the use of anticoagulants plus nonsteroidal anti-inflammatory drugs or aspirin associated with an increased risk of bleeding?

Bottom line

For patients treated with anticoagulants for acute venous thromboembolism (VTE), the use of concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin is associated with an increased risk of bleeding. This can occur in patients treated with rivaroxaban, as well as in those treated with enoxaparin plus a vitamin K antagonist (VKA). (LOE = 2b)

Reference

Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014;174(6):947-953.

Study design

Cohort (prospective)

Funding source

Industry

Allocation

Uncertain

Setting

Outpatient (any)

Synopsis

The worldwide EINSTEIN DVT and EINSTEIN PE clinical trials compared rivaroxaban with enoxaparin plus a VKA for the treatment of acute VTE. These investigators used data from this cohort to examine the association between rivaroxaban or enoxaparin-VKA plus concomitant NSAID or aspirin use and the risk of clinically relevant and major bleeding. Clinically relevant bleeding was defined as nonmajor bleeding that resulted in either medical intervention, temporary cessation of study treatment, or patient discomfort. Major bleeding was that which resulted in death, occurred at a critical site, required tranfusion of at least 2 units of red blood cells, or was associated with a 2 g/dL drop in hemoglobin. The cohort comprised 8246 patients, with half receiving rivaroxaban and half receiving enoxaparin-VKA. The NSAID analysis was adjusted for sex, as there were more women in the NSAID group. The aspirin analysis was adjusted for age and creatinine clearance, as patients in the aspirin group tended to be older with worse kidney function than the nonaspirin group. The NSAID or aspirin exposure period included 7 days after stopping the medication to reflect an ongoing risk. Clinically relevant bleeding was more likely to occur in the NSAID group as compared with the non-NSAID group (37.5 bleeding events per 100 patient-years vs 16.6 per 100 patient-years; hazard ratio [HR] = 1.77; 95% CI, 1.46-2.14). Findings were similar for both the NSAID-rivaroxaban-treated patients and NSAID-enoxaparin-VKA-treated patients. In the aspirin group, clinically relevant bleeding was also increased as compared with the nonaspirin group (36.6 bleeding events per 100 patient-years vs 16.9 per 100 patient-years; HR = 1.70; 1.38-2.11). For both the NSAID and the aspirin groups, the bleeding events were spread evenly over the duration of the use, suggesting that longer duration of use does not increase the risk of bleeding. Major bleeding increased 2.4-fold in the NSAID group and 1.5-fold in the aspirin group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients with acute venous thromboembolism, is the use of anticoagulants plus nonsteroidal anti-inflammatory drugs or aspirin associated with an increased risk of bleeding?

Bottom line

For patients treated with anticoagulants for acute venous thromboembolism (VTE), the use of concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin is associated with an increased risk of bleeding. This can occur in patients treated with rivaroxaban, as well as in those treated with enoxaparin plus a vitamin K antagonist (VKA). (LOE = 2b)

Reference

Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014;174(6):947-953.

Study design

Cohort (prospective)

Funding source

Industry

Allocation

Uncertain

Setting

Outpatient (any)

Synopsis

The worldwide EINSTEIN DVT and EINSTEIN PE clinical trials compared rivaroxaban with enoxaparin plus a VKA for the treatment of acute VTE. These investigators used data from this cohort to examine the association between rivaroxaban or enoxaparin-VKA plus concomitant NSAID or aspirin use and the risk of clinically relevant and major bleeding. Clinically relevant bleeding was defined as nonmajor bleeding that resulted in either medical intervention, temporary cessation of study treatment, or patient discomfort. Major bleeding was that which resulted in death, occurred at a critical site, required tranfusion of at least 2 units of red blood cells, or was associated with a 2 g/dL drop in hemoglobin. The cohort comprised 8246 patients, with half receiving rivaroxaban and half receiving enoxaparin-VKA. The NSAID analysis was adjusted for sex, as there were more women in the NSAID group. The aspirin analysis was adjusted for age and creatinine clearance, as patients in the aspirin group tended to be older with worse kidney function than the nonaspirin group. The NSAID or aspirin exposure period included 7 days after stopping the medication to reflect an ongoing risk. Clinically relevant bleeding was more likely to occur in the NSAID group as compared with the non-NSAID group (37.5 bleeding events per 100 patient-years vs 16.6 per 100 patient-years; hazard ratio [HR] = 1.77; 95% CI, 1.46-2.14). Findings were similar for both the NSAID-rivaroxaban-treated patients and NSAID-enoxaparin-VKA-treated patients. In the aspirin group, clinically relevant bleeding was also increased as compared with the nonaspirin group (36.6 bleeding events per 100 patient-years vs 16.9 per 100 patient-years; HR = 1.70; 1.38-2.11). For both the NSAID and the aspirin groups, the bleeding events were spread evenly over the duration of the use, suggesting that longer duration of use does not increase the risk of bleeding. Major bleeding increased 2.4-fold in the NSAID group and 1.5-fold in the aspirin group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Which transitional care interventions are most effective in preventing readmissions in patients hospitalized with heart failure?

Bottom line

Moderate-to-high strength of evidence supports the use of home-visiting programs and outpatient multidisciplinary heart failure (MDS-HF) clinics to reduce readmission rates and mortality for hospitalized HF patients at 3 months to 6 months. Structured telephone support may also decrease mortality and HF-specific readmissions, but does not affect all-cause readmissions.(LOE = 1a)

Reference

Feltner C, Jones CD, Cene CW, et al. Transitional care interventions to prevent readmissions for persons with heart failure. Ann Intern Med 2014;160(11):774-784.

Study design

Meta-analysis (randomized controlled trials)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

These authors searched multiple databases, including MEDLINE and the Cochrane Library, as well as reference lists of pertinent articles to find randomized controlled trials that compared transitional care interventions with either other interventions or usual care for patients hospitalized with HF with a focus on readmission rates and mortality. The interventions had to include at least one of the following components: patient/caregiver education, scheduled outpatient clinic visits, home visits, telemonitoring, structured telephone support, transition coaching, or increased provider continuity. Two authors independently reviewed the 47 selected studies for risk of bias. Studies with high or unclear risk of bias were not included in the meta-analysis. Results for readmission rates and mortality were stratified by intervention category and strength of evidence (SOE) grades were provided. For 30-day outcomes, a high-intensity home-visiting program consisting of 8 scheduled home visits starting at 24 hours after discharge decreased all-cause readmissions (number needed to treat [NNT] = 6) but the SOE was low. For 3-month to 6-month outcomes, data from 9 trials of home-visiting programs with varying intensities showed a reduction in all-cause readmissions (NNT= 9; SOE = high). Similarly, data from 2 trials of scheduled outpatient visits with MDS-HF clinics revealed lower readmission rates (NNT= 8; SOE = high). For HF-specific readmissions, 2 interventions, home-visiting programs and structured telephone support, decreased rates at 3 months to 6 months (home visits: NNT = 7; SOE = moderate; structured telephone support: NNT = 14; SOE = high). Finally, several interventions reduced mortality as compared to usual care at 3 to 6 months with moderate SOE, including home-visiting programs (NNT = 33), MDS-HF clinics (NNT = 18), and structured telephone support (NNT = 27). There were no significant benefits noted with scheduled visits to nurse-led clinics or primary care clinics or with educational interventions, although in most cases, there was insufficient evidence to determine whether these intervention were effective.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Which transitional care interventions are most effective in preventing readmissions in patients hospitalized with heart failure?

Bottom line

Moderate-to-high strength of evidence supports the use of home-visiting programs and outpatient multidisciplinary heart failure (MDS-HF) clinics to reduce readmission rates and mortality for hospitalized HF patients at 3 months to 6 months. Structured telephone support may also decrease mortality and HF-specific readmissions, but does not affect all-cause readmissions.(LOE = 1a)

Reference

Feltner C, Jones CD, Cene CW, et al. Transitional care interventions to prevent readmissions for persons with heart failure. Ann Intern Med 2014;160(11):774-784.

Study design

Meta-analysis (randomized controlled trials)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

These authors searched multiple databases, including MEDLINE and the Cochrane Library, as well as reference lists of pertinent articles to find randomized controlled trials that compared transitional care interventions with either other interventions or usual care for patients hospitalized with HF with a focus on readmission rates and mortality. The interventions had to include at least one of the following components: patient/caregiver education, scheduled outpatient clinic visits, home visits, telemonitoring, structured telephone support, transition coaching, or increased provider continuity. Two authors independently reviewed the 47 selected studies for risk of bias. Studies with high or unclear risk of bias were not included in the meta-analysis. Results for readmission rates and mortality were stratified by intervention category and strength of evidence (SOE) grades were provided. For 30-day outcomes, a high-intensity home-visiting program consisting of 8 scheduled home visits starting at 24 hours after discharge decreased all-cause readmissions (number needed to treat [NNT] = 6) but the SOE was low. For 3-month to 6-month outcomes, data from 9 trials of home-visiting programs with varying intensities showed a reduction in all-cause readmissions (NNT= 9; SOE = high). Similarly, data from 2 trials of scheduled outpatient visits with MDS-HF clinics revealed lower readmission rates (NNT= 8; SOE = high). For HF-specific readmissions, 2 interventions, home-visiting programs and structured telephone support, decreased rates at 3 months to 6 months (home visits: NNT = 7; SOE = moderate; structured telephone support: NNT = 14; SOE = high). Finally, several interventions reduced mortality as compared to usual care at 3 to 6 months with moderate SOE, including home-visiting programs (NNT = 33), MDS-HF clinics (NNT = 18), and structured telephone support (NNT = 27). There were no significant benefits noted with scheduled visits to nurse-led clinics or primary care clinics or with educational interventions, although in most cases, there was insufficient evidence to determine whether these intervention were effective.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Which transitional care interventions are most effective in preventing readmissions in patients hospitalized with heart failure?

Bottom line

Moderate-to-high strength of evidence supports the use of home-visiting programs and outpatient multidisciplinary heart failure (MDS-HF) clinics to reduce readmission rates and mortality for hospitalized HF patients at 3 months to 6 months. Structured telephone support may also decrease mortality and HF-specific readmissions, but does not affect all-cause readmissions.(LOE = 1a)

Reference

Feltner C, Jones CD, Cene CW, et al. Transitional care interventions to prevent readmissions for persons with heart failure. Ann Intern Med 2014;160(11):774-784.

Study design

Meta-analysis (randomized controlled trials)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

These authors searched multiple databases, including MEDLINE and the Cochrane Library, as well as reference lists of pertinent articles to find randomized controlled trials that compared transitional care interventions with either other interventions or usual care for patients hospitalized with HF with a focus on readmission rates and mortality. The interventions had to include at least one of the following components: patient/caregiver education, scheduled outpatient clinic visits, home visits, telemonitoring, structured telephone support, transition coaching, or increased provider continuity. Two authors independently reviewed the 47 selected studies for risk of bias. Studies with high or unclear risk of bias were not included in the meta-analysis. Results for readmission rates and mortality were stratified by intervention category and strength of evidence (SOE) grades were provided. For 30-day outcomes, a high-intensity home-visiting program consisting of 8 scheduled home visits starting at 24 hours after discharge decreased all-cause readmissions (number needed to treat [NNT] = 6) but the SOE was low. For 3-month to 6-month outcomes, data from 9 trials of home-visiting programs with varying intensities showed a reduction in all-cause readmissions (NNT= 9; SOE = high). Similarly, data from 2 trials of scheduled outpatient visits with MDS-HF clinics revealed lower readmission rates (NNT= 8; SOE = high). For HF-specific readmissions, 2 interventions, home-visiting programs and structured telephone support, decreased rates at 3 months to 6 months (home visits: NNT = 7; SOE = moderate; structured telephone support: NNT = 14; SOE = high). Finally, several interventions reduced mortality as compared to usual care at 3 to 6 months with moderate SOE, including home-visiting programs (NNT = 33), MDS-HF clinics (NNT = 18), and structured telephone support (NNT = 27). There were no significant benefits noted with scheduled visits to nurse-led clinics or primary care clinics or with educational interventions, although in most cases, there was insufficient evidence to determine whether these intervention were effective.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Prescription medications

Credit: CDC

A series of papers published in The BMJ have raised concerns about the anticoagulant dabigatran (Pradaxa).

The papers claim the company developing dabigatran has underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.

The company, Boehringer Ingelheim (BI), has denied these allegations.

“During the course of litigation involving Pradaxa, specifically hand-picked fragments of our robust internal discussions were made available to the media by external parties, which resulted in a gross distortion of the facts about Pradaxa and Boehringer Ingelheim,” said John Smith, a regional medical director at BI.

“As a result, some media reports have wrongfully suggested that BI purposefully suppressed data and have questioned the company’s ethics in efforts to alert regulators, healthcare professionals, and patients of the risks associated with Pradaxa.  Some reports have even accused BI of improper trial conduct. All of these allegations are absolutely false . . . .”

Concerns about the RE-LY trial

One of the papers published in The BMJ, “Concerns over data in key dabigatran trial,” said the design and oversight of the RE-LY trial were poor.

The trial compared dabigatran at 110 mg or 150 mg twice daily to dose-adjusted warfarin in patients with atrial fibrillation. Results suggested dabigatran was noninferior, and in some cases superior, to warfarin.

The BMJ article said the open-label design of this trial allowed for bias. And events—such as bleeding and myocardial infarctions—have been misreported.

The article also suggested that reviews by BI have failed to uncover all of the inaccuracies in the trial data, and all of the information has not been released—either to regulators or the public.

BI refuted these claims, saying regulators found RE-LY’s design “robust and valid.” And although reviews have uncovered inaccuracies, the results have not affected the trial’s conclusions.

In fact, the US Food and Drug Administration (FDA) “reaffirmed the positive efficacy-safety profile of Pradaxa” when it reviewed data from more than 134,000 patients.

BI also said it has provided the FDA and the European Medicines Agency (EMA) with the complete data set, and both regulators have affirmed the conclusions of the trial.

Allegations of withheld data

Another article in The BMJ, “Dabigatran: how the drug company withheld important analyses,” suggested BI withheld information indicating that monitoring and dose adjustment could improve the safety of dabigatran.

The article said the company did not provide regulators with data showing a 5.5-fold variation in plasma levels among dabigatran-treated patients. And the company withheld data garnered from analyses calculating how many major bleeds could be prevented by dose adjustment.

The analyses suggested that monitoring and dose adjustment could reduce major bleeds by 30% to 40% compared with well-controlled warfarin. And the adjustment would have little or no effect on the risk of ischemic stroke.

BI conceded that, in 2012, company scientists performed exploratory simulations with mathematical models to understand whether dose adjustments based on plasma concentrations might further improve the efficacy and safety profile of dabigatran.

However, the initial hypothesis “could not be supported when applied to the actual clinical data from the RE-LY population.” So the company did not supply the data to the FDA or EMA.

Furthermore, “the totality of scientific evidence does not support dosing decisions for Pradaxa based solely on blood levels.” Instead, the company said that patient characteristics such as age, kidney function, and certain medications are the critical factors that contribute to the risk of bleeding.

The role of regulators, physicians, and patients

A third article in The BMJ, “Dabigatran, bleeding, and the regulators,” investigated the role the FDA and the EMA have played in all this.

The author said the EMA has made information, tests, and varying strengths of dabigatran available to promote safer use of the drug.

The FDA, on the other hand, has focused on efficacy rather than reducing the risk of bleeding. The agency approved only the 150-mg dose of the drug and has not approved a plasma-level diagnostic test.

The BMJ also published an editorial titled “The trouble with dabigatran.” It suggested that doctors and patients should “tread carefully” due to emerging risks associated with the drug.

Prescription medications

Credit: CDC

A series of papers published in The BMJ have raised concerns about the anticoagulant dabigatran (Pradaxa).

The papers claim the company developing dabigatran has underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.

The company, Boehringer Ingelheim (BI), has denied these allegations.

“During the course of litigation involving Pradaxa, specifically hand-picked fragments of our robust internal discussions were made available to the media by external parties, which resulted in a gross distortion of the facts about Pradaxa and Boehringer Ingelheim,” said John Smith, a regional medical director at BI.

“As a result, some media reports have wrongfully suggested that BI purposefully suppressed data and have questioned the company’s ethics in efforts to alert regulators, healthcare professionals, and patients of the risks associated with Pradaxa.  Some reports have even accused BI of improper trial conduct. All of these allegations are absolutely false . . . .”

Concerns about the RE-LY trial

One of the papers published in The BMJ, “Concerns over data in key dabigatran trial,” said the design and oversight of the RE-LY trial were poor.

The trial compared dabigatran at 110 mg or 150 mg twice daily to dose-adjusted warfarin in patients with atrial fibrillation. Results suggested dabigatran was noninferior, and in some cases superior, to warfarin.

The BMJ article said the open-label design of this trial allowed for bias. And events—such as bleeding and myocardial infarctions—have been misreported.

The article also suggested that reviews by BI have failed to uncover all of the inaccuracies in the trial data, and all of the information has not been released—either to regulators or the public.

BI refuted these claims, saying regulators found RE-LY’s design “robust and valid.” And although reviews have uncovered inaccuracies, the results have not affected the trial’s conclusions.

In fact, the US Food and Drug Administration (FDA) “reaffirmed the positive efficacy-safety profile of Pradaxa” when it reviewed data from more than 134,000 patients.

BI also said it has provided the FDA and the European Medicines Agency (EMA) with the complete data set, and both regulators have affirmed the conclusions of the trial.

Allegations of withheld data

Another article in The BMJ, “Dabigatran: how the drug company withheld important analyses,” suggested BI withheld information indicating that monitoring and dose adjustment could improve the safety of dabigatran.

The article said the company did not provide regulators with data showing a 5.5-fold variation in plasma levels among dabigatran-treated patients. And the company withheld data garnered from analyses calculating how many major bleeds could be prevented by dose adjustment.

The analyses suggested that monitoring and dose adjustment could reduce major bleeds by 30% to 40% compared with well-controlled warfarin. And the adjustment would have little or no effect on the risk of ischemic stroke.

BI conceded that, in 2012, company scientists performed exploratory simulations with mathematical models to understand whether dose adjustments based on plasma concentrations might further improve the efficacy and safety profile of dabigatran.

However, the initial hypothesis “could not be supported when applied to the actual clinical data from the RE-LY population.” So the company did not supply the data to the FDA or EMA.

Furthermore, “the totality of scientific evidence does not support dosing decisions for Pradaxa based solely on blood levels.” Instead, the company said that patient characteristics such as age, kidney function, and certain medications are the critical factors that contribute to the risk of bleeding.

The role of regulators, physicians, and patients

A third article in The BMJ, “Dabigatran, bleeding, and the regulators,” investigated the role the FDA and the EMA have played in all this.

The author said the EMA has made information, tests, and varying strengths of dabigatran available to promote safer use of the drug.

The FDA, on the other hand, has focused on efficacy rather than reducing the risk of bleeding. The agency approved only the 150-mg dose of the drug and has not approved a plasma-level diagnostic test.

The BMJ also published an editorial titled “The trouble with dabigatran.” It suggested that doctors and patients should “tread carefully” due to emerging risks associated with the drug.

Prescription medications

Credit: CDC

A series of papers published in The BMJ have raised concerns about the anticoagulant dabigatran (Pradaxa).

The papers claim the company developing dabigatran has underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.

The company, Boehringer Ingelheim (BI), has denied these allegations.

“During the course of litigation involving Pradaxa, specifically hand-picked fragments of our robust internal discussions were made available to the media by external parties, which resulted in a gross distortion of the facts about Pradaxa and Boehringer Ingelheim,” said John Smith, a regional medical director at BI.

“As a result, some media reports have wrongfully suggested that BI purposefully suppressed data and have questioned the company’s ethics in efforts to alert regulators, healthcare professionals, and patients of the risks associated with Pradaxa.  Some reports have even accused BI of improper trial conduct. All of these allegations are absolutely false . . . .”

Concerns about the RE-LY trial

One of the papers published in The BMJ, “Concerns over data in key dabigatran trial,” said the design and oversight of the RE-LY trial were poor.

The trial compared dabigatran at 110 mg or 150 mg twice daily to dose-adjusted warfarin in patients with atrial fibrillation. Results suggested dabigatran was noninferior, and in some cases superior, to warfarin.

The BMJ article said the open-label design of this trial allowed for bias. And events—such as bleeding and myocardial infarctions—have been misreported.

The article also suggested that reviews by BI have failed to uncover all of the inaccuracies in the trial data, and all of the information has not been released—either to regulators or the public.

BI refuted these claims, saying regulators found RE-LY’s design “robust and valid.” And although reviews have uncovered inaccuracies, the results have not affected the trial’s conclusions.

In fact, the US Food and Drug Administration (FDA) “reaffirmed the positive efficacy-safety profile of Pradaxa” when it reviewed data from more than 134,000 patients.

BI also said it has provided the FDA and the European Medicines Agency (EMA) with the complete data set, and both regulators have affirmed the conclusions of the trial.

Allegations of withheld data

Another article in The BMJ, “Dabigatran: how the drug company withheld important analyses,” suggested BI withheld information indicating that monitoring and dose adjustment could improve the safety of dabigatran.

The article said the company did not provide regulators with data showing a 5.5-fold variation in plasma levels among dabigatran-treated patients. And the company withheld data garnered from analyses calculating how many major bleeds could be prevented by dose adjustment.

The analyses suggested that monitoring and dose adjustment could reduce major bleeds by 30% to 40% compared with well-controlled warfarin. And the adjustment would have little or no effect on the risk of ischemic stroke.

BI conceded that, in 2012, company scientists performed exploratory simulations with mathematical models to understand whether dose adjustments based on plasma concentrations might further improve the efficacy and safety profile of dabigatran.

However, the initial hypothesis “could not be supported when applied to the actual clinical data from the RE-LY population.” So the company did not supply the data to the FDA or EMA.

Furthermore, “the totality of scientific evidence does not support dosing decisions for Pradaxa based solely on blood levels.” Instead, the company said that patient characteristics such as age, kidney function, and certain medications are the critical factors that contribute to the risk of bleeding.

The role of regulators, physicians, and patients

A third article in The BMJ, “Dabigatran, bleeding, and the regulators,” investigated the role the FDA and the EMA have played in all this.

The author said the EMA has made information, tests, and varying strengths of dabigatran available to promote safer use of the drug.

The FDA, on the other hand, has focused on efficacy rather than reducing the risk of bleeding. The agency approved only the 150-mg dose of the drug and has not approved a plasma-level diagnostic test.

The BMJ also published an editorial titled “The trouble with dabigatran.” It suggested that doctors and patients should “tread carefully” due to emerging risks associated with the drug.