Photo from UNSW

Researchers have used CRISPR-Cas9 gene editing to reproduce naturally occurring mutations that boost the production of fetal hemoglobin.

The mutations are associated with hereditary persistence of fetal hemoglobin (HPFH), and the researchers believe that introducing these mutations into erythroid cells could be a safe way to treat β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia.

This research was published in Nature Genetics.

“Our new approach can be seen as a forerunner to ‘organic gene therapy’ for a range of common inherited blood disorders, including β-thalassemia and sickle cell anemia,” said study author Merlin Crossley, DPhil, of the University of New South Wales in Sydney, Australia.

“It is organic because no new DNA is introduced into the cells; rather, we engineer in naturally occurring, benign mutations that are known to be beneficial to people with these conditions. It should prove to be a safe and effective therapy, although more research would be needed to scale the processes up into effective treatments.”

Dr Crossley and his colleagues noted that reactivating fetal hemoglobin production has long been a therapeutic goal for SCD and β-thalassemia.

“The fetal hemoglobin gene is naturally silenced after birth,” Dr Crossley explained. “For 50 years, researchers have been competing furiously to find out how it is switched off, so it can be turned back on. Our study, which is the culmination of many years of work, solves that mystery.”

“We have found that 2 genes, called BCL11A and ZBTB7A, switch off the fetal hemoglobin gene by binding directly to it. And the beneficial mutations work by disrupting the 2 sites where these 2 genes bind.”

The “beneficial mutations,” which cause some forms of HPFH, are point mutations in the γ-globin gene promoter at -115 and -200 bp upstream of the transcription start site.

Dr Crossley and his colleagues found that BCL11A31 and ZBTB7A23—2 well-established fetal globin repressors—bind these regions of the γ-globin gene proximal promoter, and mutations at –115 and –200 bp disrupt the binding.

The researchers used CRISPR-Cas9 to introduce the HPFH-associated mutations into erythroid cells and observed both disruption of repressor binding and increased γ-globin gene expression.

“This landmark finding not only contributes to our appreciation of how these globin genes are regulated,” Dr Crossley said. “It means we can now shift our focus to developing therapies for these genetic diseases using CRISPR to target precise changes in the genome.”

Photo from UNSW

Researchers have used CRISPR-Cas9 gene editing to reproduce naturally occurring mutations that boost the production of fetal hemoglobin.

The mutations are associated with hereditary persistence of fetal hemoglobin (HPFH), and the researchers believe that introducing these mutations into erythroid cells could be a safe way to treat β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia.

This research was published in Nature Genetics.

“Our new approach can be seen as a forerunner to ‘organic gene therapy’ for a range of common inherited blood disorders, including β-thalassemia and sickle cell anemia,” said study author Merlin Crossley, DPhil, of the University of New South Wales in Sydney, Australia.

“It is organic because no new DNA is introduced into the cells; rather, we engineer in naturally occurring, benign mutations that are known to be beneficial to people with these conditions. It should prove to be a safe and effective therapy, although more research would be needed to scale the processes up into effective treatments.”

Dr Crossley and his colleagues noted that reactivating fetal hemoglobin production has long been a therapeutic goal for SCD and β-thalassemia.

“The fetal hemoglobin gene is naturally silenced after birth,” Dr Crossley explained. “For 50 years, researchers have been competing furiously to find out how it is switched off, so it can be turned back on. Our study, which is the culmination of many years of work, solves that mystery.”

“We have found that 2 genes, called BCL11A and ZBTB7A, switch off the fetal hemoglobin gene by binding directly to it. And the beneficial mutations work by disrupting the 2 sites where these 2 genes bind.”

The “beneficial mutations,” which cause some forms of HPFH, are point mutations in the γ-globin gene promoter at -115 and -200 bp upstream of the transcription start site.

Dr Crossley and his colleagues found that BCL11A31 and ZBTB7A23—2 well-established fetal globin repressors—bind these regions of the γ-globin gene proximal promoter, and mutations at –115 and –200 bp disrupt the binding.

The researchers used CRISPR-Cas9 to introduce the HPFH-associated mutations into erythroid cells and observed both disruption of repressor binding and increased γ-globin gene expression.

“This landmark finding not only contributes to our appreciation of how these globin genes are regulated,” Dr Crossley said. “It means we can now shift our focus to developing therapies for these genetic diseases using CRISPR to target precise changes in the genome.”

Photo from UNSW

Researchers have used CRISPR-Cas9 gene editing to reproduce naturally occurring mutations that boost the production of fetal hemoglobin.

The mutations are associated with hereditary persistence of fetal hemoglobin (HPFH), and the researchers believe that introducing these mutations into erythroid cells could be a safe way to treat β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia.

This research was published in Nature Genetics.

“Our new approach can be seen as a forerunner to ‘organic gene therapy’ for a range of common inherited blood disorders, including β-thalassemia and sickle cell anemia,” said study author Merlin Crossley, DPhil, of the University of New South Wales in Sydney, Australia.

“It is organic because no new DNA is introduced into the cells; rather, we engineer in naturally occurring, benign mutations that are known to be beneficial to people with these conditions. It should prove to be a safe and effective therapy, although more research would be needed to scale the processes up into effective treatments.”

Dr Crossley and his colleagues noted that reactivating fetal hemoglobin production has long been a therapeutic goal for SCD and β-thalassemia.

“The fetal hemoglobin gene is naturally silenced after birth,” Dr Crossley explained. “For 50 years, researchers have been competing furiously to find out how it is switched off, so it can be turned back on. Our study, which is the culmination of many years of work, solves that mystery.”

“We have found that 2 genes, called BCL11A and ZBTB7A, switch off the fetal hemoglobin gene by binding directly to it. And the beneficial mutations work by disrupting the 2 sites where these 2 genes bind.”

The “beneficial mutations,” which cause some forms of HPFH, are point mutations in the γ-globin gene promoter at -115 and -200 bp upstream of the transcription start site.

Dr Crossley and his colleagues found that BCL11A31 and ZBTB7A23—2 well-established fetal globin repressors—bind these regions of the γ-globin gene proximal promoter, and mutations at –115 and –200 bp disrupt the binding.

The researchers used CRISPR-Cas9 to introduce the HPFH-associated mutations into erythroid cells and observed both disruption of repressor binding and increased γ-globin gene expression.

“This landmark finding not only contributes to our appreciation of how these globin genes are regulated,” Dr Crossley said. “It means we can now shift our focus to developing therapies for these genetic diseases using CRISPR to target precise changes in the genome.”

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has expanded the approved indication for blinatumomab (Blincyto®).

The drug is now approved to treat adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%.

Blinatumomab received accelerated approval for this indication because the drug has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on surrogate or intermediate endpoints—in this case, MRD response rate and hematologic relapse-free survival (RFS)—that are reasonably likely to predict clinical benefit.

Continued approval of blinatumomab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

“Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer. We look forward to furthering our understanding about the reduction in MRD after treatment with Blincyto. Studies are being conducted to assess how Blincyto affects long-term survival outcomes in patients with MRD.”

About blinatumomab

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed/refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Last year, the FDA granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a risk evaluation and mitigation strategy program in the US.

BLAST study

The new accelerated approval for blinatumomab was supported by results from the phase 2 BLAST study, which were published in Blood in January.

The study enrolled adults with MRD-positive BCP-ALL in complete hematologic remission after 3 or more cycles of intensive chemotherapy.

Patients received continuous intravenous infusions of blinatumomab at 15 μg/m²/day for 4 weeks, followed by 2 weeks off. They received up to 4 cycles of treatment and could undergo hematopoietic stem cell transplant (HSCT) at any time after the first cycle.

In all, there were 116 patients who received at least 1 infusion of blinatumomab. Seventy-six patients went on to HSCT while in continuous CR after cycle 1 (n=27), 2 (n=36), or 3/4 (n=13).

The study’s primary endpoint was the rate of complete MRD response within the first treatment cycle, and 78% of evaluable patients (88/113) achieved this endpoint.

A key secondary endpoint was RFS at 18 months. There were 110 patients evaluable for this endpoint. They all had Ph- BCP-ALL and <5% blasts at baseline.

The estimated RFS at 18 months was 54%, and the median RFS was 18.9 months. The median RFS was 24.6 months for patients treated in first CR and 11.0 months for patients treated in a later CR (P=0.004).

Another key endpoint was overall survival (OS). The median OS was 36.5 months, both for the 110 patients in the RFS analysis and for the entire study population.

In a landmark analysis, complete MRD responders had longer OS than MRD nonresponders—38.9 months and 12.5 months, respectively (P=0.002). And complete MRD responders had longer RFS than nonresponders—23.6 months and 5.7 months, respectively (P=0.002).

All 116 patients who started cycle 1 had at least 1 adverse event (AE). The rate of grade 3 AEs was 33%, and the rate of grade 4 AEs was 27%. These AEs were considered treatment-related in 29% (grade 3) and 22% (grade 4) of patients.

Four (3%) patients developed cytokine release syndrome—2 with grade 1 and 2 with grade 3. All of these events occurred during cycle 1.

Fifty-three percent of patients (n=61) had neurologic events. In most cases (97%, n=59), these events resolved.

There were 2 fatal AEs during the treatment period, both in cycle 1. One of these events—atypical pneumonitis with H1N1 influenza—was considered treatment-related. The other event—subdural hemorrhage—was considered unrelated to treatment.

There were 4 fatal AEs reported after blinatumomab treatment. Two of these deaths—due to multifocal CNS lesions and graft-versus-host disease—occurred in HSCT recipients. The other 2 deaths—due to disease progression and multi-organ failure—occurred in nontransplanted patients after relapse.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan designation to MAX-40279 for the treatment of acute myeloid leukemia (AML).

MAX-40279 is a multi-target kinase inhibitor being developed by MaxiNovel Pharmaceuticals, Inc.

The drug mainly targets FMS-related tyrosine kinase 3 (FLT3) and fibroblast growth factor receptor (FGFR).

MAX-40279 demonstrated “potent” inhibition of FLT3 and FGFR in preclinical testing, according to MaxiNovel Pharmaceuticals, Inc.

The company is currently testing MAX-40279 in a phase 1 trial of patients with AML (NCT03412292).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

It’s no secret that health care providers are at high risk for burnout. In my time as a provider, a patient, and a supportive companion to family members, I have witnessed too many of what I call “walking dead” providers—those who barely function in their jobs, leave the profession reluctantly, or count the days until retirement.

One key to avoiding burnout is self-care. I know, you’ve heard this before. But knowing something and acting on it are entirely different.

In my case, it was my employer who broke down my self-care barrier. Through the hospital I work for, I received repeated invitations to participate in free workshops. The first email read: “Healing loss workshops provided for interested staff.” The workshops were based on the Kübler-Ross model (otherwise known as the five stages of grief). First introduced by Swiss psychiatrist Elisabeth Kübler-Ross in 1969, the model postulates a series of emotional reactions to loss.

At the time, I thought grief and loss were only about someone dying. I didn’t know that it could encompass other forms of loss, such as relationships, jobs, physical mobility, major rejection, childhood dreams, or children. So, even though around this time I was in the middle of a divorce, ending a 20-year relationship, breaking up a family, and leaving a house I had lived in for two decades (talk about grief and loss!), I deleted several of these messages before I decided to consider the invitation.

Even when I did, my reason for filling out an application was based on the fact that the workshop, food, and lodgings were free—and I would receive continuing education credit! My mindset was focused on what I could gain tangibly rather than emotionally. I was surprised when I was accepted as a participant—and unaware of how much this experience would change both my personal and professional lives.

I arrived for the two-and-a-half-day seminar with no expectations. I knew that the workshop was touted as providing a safe, comfortable, and confidential environment in which facilitators and staff would provide education on and tools for healing. It was emphasized that this was not a form of medical therapy and that participants could choose to discontinue the workshop at any time. The goal was for participants to learn how to resolve inner issues they have built up and carried around with them.

It is difficult to explain in words the internal change that took place within me during my first workshop. The group participation helped me to recognize that everyone carries a mask. Behind that mask, every individual—strangers, colleagues, patients, even family—has his or her own story and journey. Witnessing others sharing their personal pain and grief in a confidential, nonjudgmental environment made me more compassionate.

Continue to: But I also learned more about myself ...

But I also learned more about myself than I expected to, including that I need to continually take care of myself. Otherwise, I will carry baggage with me wherever I am. And the contents of that baggage came as a surprise to me. Yes, I was dealing with loss in my immediate life—divorce, moving, etc—but I became aware that my earlier life experiences were impacting my current behaviors and relationships.

It was difficult for me to conceive that my loving parents, who had given me food and shelter, had neglected my emotional needs. I love my parents, but the resentments I uncovered during that first workshop startled me. I realized that, while they did not overtly teach me prejudice, their actions caused me to cultivate a general distrust of others. They would often say, “Don’t tell anyone.” I now understand that this cast others as untrustworthy and suspicious.

The memory that encapsulated this best for me was of one summer, when I returned home from traveling abroad and was unable to find my old toys (which were always in a large cardboard box in our garage). My parents didn’t have any explanation for where they had gone. I continued to search the garage for years, literally, not understanding how the toys had disappeared. It was only many years later, when the subject of the toys came up in a conversation with my mother, that she replied, nonchalantly, “Oh, your father threw them out.” It’s no wonder I had issues with trust!

I often hear people say, “I just want to forget about what happened to me,” “I don’t want to think about my past,” or “I buried all that old stuff.” But if I learned one thing from these workshops, it’s that life experiences do not stay buried. I carry the effects of my experiences around with me without being conscious of it. The workshop taught me how to acknowledge my grief and loss and work on becoming more emotionally available. I learned that it is OK to be angry about my parents’ behavior and to express my emotions about it, while still loving my parents very much. Acknowledging these suppressed emotions and the effects they had on my life has helped me to grow and move forward.

By the time the workshop ended, I had recognized just how much anxiety, anger, fear, and stress I was carrying. I started to understand how to “unpack” this extra weight. Although I was exhausted as I left the workshop, I also felt much less stressed and lighter.

Continue to: Some of the changes I've made ...

Some of the changes I’ve made as a result might seem subtle to an outsider, but they have made a huge difference to me internally—and that seems to reflect onto the people surrounding me.

The biggest complaints I hear from hospitalized patients are that “nobody tells me anything” or “they come in with one leg out the door.” So now I ask for permission to enter the patient’s room. I introduce myself, then ask if it’s OK to sit down with them. This seemingly small action makes such an impact. I began to notice that, in response, patients were thanking me for coming to see them, for listening, and for spending time with them.

The best example I have is a hospitalized patient who had undergone major surgery. She was upset about her care and getting frustrated with staff. I had seen her once before, and when she looked up and saw me at the door of her room, she said, “Oh, let her in! I know she’s really ‘here’ with me.” What a confirmation that this simple change of mindset on my part is helping to make a difference in the care I deliver to my patients!

I realize many of you might be as skeptical as I was when I read the first workshop invitation. You may be thinking, “This won’t help me.” I understand your doubts—I shared them. But that first workshop was so inspiring that I felt compelled to share my experience with others. I believe in the benefits so completely that I pursued training to become a voluntary facilitator. It is indescribable the results I witness in participants. I can only encourage you to give these types of workshops a chance. (If you are uncomfortable about doing a workshop with coworkers in attendance, or just want to do some traveling, workshops are available in many states and different countries.) A simple search for “internalization/externalization workshops” could change your life as much as it did mine!

It’s no secret that health care providers are at high risk for burnout. In my time as a provider, a patient, and a supportive companion to family members, I have witnessed too many of what I call “walking dead” providers—those who barely function in their jobs, leave the profession reluctantly, or count the days until retirement.

One key to avoiding burnout is self-care. I know, you’ve heard this before. But knowing something and acting on it are entirely different.

In my case, it was my employer who broke down my self-care barrier. Through the hospital I work for, I received repeated invitations to participate in free workshops. The first email read: “Healing loss workshops provided for interested staff.” The workshops were based on the Kübler-Ross model (otherwise known as the five stages of grief). First introduced by Swiss psychiatrist Elisabeth Kübler-Ross in 1969, the model postulates a series of emotional reactions to loss.

At the time, I thought grief and loss were only about someone dying. I didn’t know that it could encompass other forms of loss, such as relationships, jobs, physical mobility, major rejection, childhood dreams, or children. So, even though around this time I was in the middle of a divorce, ending a 20-year relationship, breaking up a family, and leaving a house I had lived in for two decades (talk about grief and loss!), I deleted several of these messages before I decided to consider the invitation.

Even when I did, my reason for filling out an application was based on the fact that the workshop, food, and lodgings were free—and I would receive continuing education credit! My mindset was focused on what I could gain tangibly rather than emotionally. I was surprised when I was accepted as a participant—and unaware of how much this experience would change both my personal and professional lives.

I arrived for the two-and-a-half-day seminar with no expectations. I knew that the workshop was touted as providing a safe, comfortable, and confidential environment in which facilitators and staff would provide education on and tools for healing. It was emphasized that this was not a form of medical therapy and that participants could choose to discontinue the workshop at any time. The goal was for participants to learn how to resolve inner issues they have built up and carried around with them.

It is difficult to explain in words the internal change that took place within me during my first workshop. The group participation helped me to recognize that everyone carries a mask. Behind that mask, every individual—strangers, colleagues, patients, even family—has his or her own story and journey. Witnessing others sharing their personal pain and grief in a confidential, nonjudgmental environment made me more compassionate.

Continue to: But I also learned more about myself ...

But I also learned more about myself than I expected to, including that I need to continually take care of myself. Otherwise, I will carry baggage with me wherever I am. And the contents of that baggage came as a surprise to me. Yes, I was dealing with loss in my immediate life—divorce, moving, etc—but I became aware that my earlier life experiences were impacting my current behaviors and relationships.

It was difficult for me to conceive that my loving parents, who had given me food and shelter, had neglected my emotional needs. I love my parents, but the resentments I uncovered during that first workshop startled me. I realized that, while they did not overtly teach me prejudice, their actions caused me to cultivate a general distrust of others. They would often say, “Don’t tell anyone.” I now understand that this cast others as untrustworthy and suspicious.

The memory that encapsulated this best for me was of one summer, when I returned home from traveling abroad and was unable to find my old toys (which were always in a large cardboard box in our garage). My parents didn’t have any explanation for where they had gone. I continued to search the garage for years, literally, not understanding how the toys had disappeared. It was only many years later, when the subject of the toys came up in a conversation with my mother, that she replied, nonchalantly, “Oh, your father threw them out.” It’s no wonder I had issues with trust!

I often hear people say, “I just want to forget about what happened to me,” “I don’t want to think about my past,” or “I buried all that old stuff.” But if I learned one thing from these workshops, it’s that life experiences do not stay buried. I carry the effects of my experiences around with me without being conscious of it. The workshop taught me how to acknowledge my grief and loss and work on becoming more emotionally available. I learned that it is OK to be angry about my parents’ behavior and to express my emotions about it, while still loving my parents very much. Acknowledging these suppressed emotions and the effects they had on my life has helped me to grow and move forward.

By the time the workshop ended, I had recognized just how much anxiety, anger, fear, and stress I was carrying. I started to understand how to “unpack” this extra weight. Although I was exhausted as I left the workshop, I also felt much less stressed and lighter.

Continue to: Some of the changes I've made ...

Some of the changes I’ve made as a result might seem subtle to an outsider, but they have made a huge difference to me internally—and that seems to reflect onto the people surrounding me.

The biggest complaints I hear from hospitalized patients are that “nobody tells me anything” or “they come in with one leg out the door.” So now I ask for permission to enter the patient’s room. I introduce myself, then ask if it’s OK to sit down with them. This seemingly small action makes such an impact. I began to notice that, in response, patients were thanking me for coming to see them, for listening, and for spending time with them.

The best example I have is a hospitalized patient who had undergone major surgery. She was upset about her care and getting frustrated with staff. I had seen her once before, and when she looked up and saw me at the door of her room, she said, “Oh, let her in! I know she’s really ‘here’ with me.” What a confirmation that this simple change of mindset on my part is helping to make a difference in the care I deliver to my patients!

I realize many of you might be as skeptical as I was when I read the first workshop invitation. You may be thinking, “This won’t help me.” I understand your doubts—I shared them. But that first workshop was so inspiring that I felt compelled to share my experience with others. I believe in the benefits so completely that I pursued training to become a voluntary facilitator. It is indescribable the results I witness in participants. I can only encourage you to give these types of workshops a chance. (If you are uncomfortable about doing a workshop with coworkers in attendance, or just want to do some traveling, workshops are available in many states and different countries.) A simple search for “internalization/externalization workshops” could change your life as much as it did mine!

It’s no secret that health care providers are at high risk for burnout. In my time as a provider, a patient, and a supportive companion to family members, I have witnessed too many of what I call “walking dead” providers—those who barely function in their jobs, leave the profession reluctantly, or count the days until retirement.

One key to avoiding burnout is self-care. I know, you’ve heard this before. But knowing something and acting on it are entirely different.

In my case, it was my employer who broke down my self-care barrier. Through the hospital I work for, I received repeated invitations to participate in free workshops. The first email read: “Healing loss workshops provided for interested staff.” The workshops were based on the Kübler-Ross model (otherwise known as the five stages of grief). First introduced by Swiss psychiatrist Elisabeth Kübler-Ross in 1969, the model postulates a series of emotional reactions to loss.

At the time, I thought grief and loss were only about someone dying. I didn’t know that it could encompass other forms of loss, such as relationships, jobs, physical mobility, major rejection, childhood dreams, or children. So, even though around this time I was in the middle of a divorce, ending a 20-year relationship, breaking up a family, and leaving a house I had lived in for two decades (talk about grief and loss!), I deleted several of these messages before I decided to consider the invitation.

Even when I did, my reason for filling out an application was based on the fact that the workshop, food, and lodgings were free—and I would receive continuing education credit! My mindset was focused on what I could gain tangibly rather than emotionally. I was surprised when I was accepted as a participant—and unaware of how much this experience would change both my personal and professional lives.

I arrived for the two-and-a-half-day seminar with no expectations. I knew that the workshop was touted as providing a safe, comfortable, and confidential environment in which facilitators and staff would provide education on and tools for healing. It was emphasized that this was not a form of medical therapy and that participants could choose to discontinue the workshop at any time. The goal was for participants to learn how to resolve inner issues they have built up and carried around with them.

It is difficult to explain in words the internal change that took place within me during my first workshop. The group participation helped me to recognize that everyone carries a mask. Behind that mask, every individual—strangers, colleagues, patients, even family—has his or her own story and journey. Witnessing others sharing their personal pain and grief in a confidential, nonjudgmental environment made me more compassionate.

Continue to: But I also learned more about myself ...

But I also learned more about myself than I expected to, including that I need to continually take care of myself. Otherwise, I will carry baggage with me wherever I am. And the contents of that baggage came as a surprise to me. Yes, I was dealing with loss in my immediate life—divorce, moving, etc—but I became aware that my earlier life experiences were impacting my current behaviors and relationships.

It was difficult for me to conceive that my loving parents, who had given me food and shelter, had neglected my emotional needs. I love my parents, but the resentments I uncovered during that first workshop startled me. I realized that, while they did not overtly teach me prejudice, their actions caused me to cultivate a general distrust of others. They would often say, “Don’t tell anyone.” I now understand that this cast others as untrustworthy and suspicious.

The memory that encapsulated this best for me was of one summer, when I returned home from traveling abroad and was unable to find my old toys (which were always in a large cardboard box in our garage). My parents didn’t have any explanation for where they had gone. I continued to search the garage for years, literally, not understanding how the toys had disappeared. It was only many years later, when the subject of the toys came up in a conversation with my mother, that she replied, nonchalantly, “Oh, your father threw them out.” It’s no wonder I had issues with trust!

I often hear people say, “I just want to forget about what happened to me,” “I don’t want to think about my past,” or “I buried all that old stuff.” But if I learned one thing from these workshops, it’s that life experiences do not stay buried. I carry the effects of my experiences around with me without being conscious of it. The workshop taught me how to acknowledge my grief and loss and work on becoming more emotionally available. I learned that it is OK to be angry about my parents’ behavior and to express my emotions about it, while still loving my parents very much. Acknowledging these suppressed emotions and the effects they had on my life has helped me to grow and move forward.

By the time the workshop ended, I had recognized just how much anxiety, anger, fear, and stress I was carrying. I started to understand how to “unpack” this extra weight. Although I was exhausted as I left the workshop, I also felt much less stressed and lighter.

Continue to: Some of the changes I've made ...

Some of the changes I’ve made as a result might seem subtle to an outsider, but they have made a huge difference to me internally—and that seems to reflect onto the people surrounding me.

The biggest complaints I hear from hospitalized patients are that “nobody tells me anything” or “they come in with one leg out the door.” So now I ask for permission to enter the patient’s room. I introduce myself, then ask if it’s OK to sit down with them. This seemingly small action makes such an impact. I began to notice that, in response, patients were thanking me for coming to see them, for listening, and for spending time with them.

The best example I have is a hospitalized patient who had undergone major surgery. She was upset about her care and getting frustrated with staff. I had seen her once before, and when she looked up and saw me at the door of her room, she said, “Oh, let her in! I know she’s really ‘here’ with me.” What a confirmation that this simple change of mindset on my part is helping to make a difference in the care I deliver to my patients!

I realize many of you might be as skeptical as I was when I read the first workshop invitation. You may be thinking, “This won’t help me.” I understand your doubts—I shared them. But that first workshop was so inspiring that I felt compelled to share my experience with others. I believe in the benefits so completely that I pursued training to become a voluntary facilitator. It is indescribable the results I witness in participants. I can only encourage you to give these types of workshops a chance. (If you are uncomfortable about doing a workshop with coworkers in attendance, or just want to do some traveling, workshops are available in many states and different countries.) A simple search for “internalization/externalization workshops” could change your life as much as it did mine!

Obstetrician-gynecologists have a central role in helping pregnant patients maintain employment by writing appropriate notes to employers and informing patients of their rights, according to a new committee opinion by the American College of Obstetricians and Gynecologists.

The opinion, released March 28, outlines key considerations for ob.gyns. in assisting pregnant patients with employment maintenance and helping protect them from employment discrimination. The most common employment issues that pregnant women face include pregnancy-related discrimination, work accommodations that allow continued employment, job-protected leave, and wage replacement while on leave, according to the opinion. After delivery, top employment concerns involve lactation, and accommodations and leave for recovery, bonding, and caring for the infant.

“It’s important that ob.gyns. discuss workplace expectations with their working pregnant patient,” Yasser El-Sayed, MD, vice chair of the ACOG’s committee on obstetric practice said in a statement. “Some women may be unaware of attendant risks to pregnancy at their job, while others may be unaware that their ob.gyn. can offer both support and potential solutions or resources, whether in the form of slight modifications or a formal medical note detailing the need for an accommodation to protect the patient’s health.”

To address these issues, ACOG recommends that ob.gyns. reassure patients that working during pregnancy is generally safe. In the case of high-risk or complicated pregnancy, ob.gyns. should inform patients that work accommodations often can allow for continued safe employment. Appropriately drafted notes by physicians to employers are key, the opinion stresses.

“By writing appropriate notes to employers, obstetrician-gynecologists and other obstetric care providers can be instrumental in obtaining accommodations for their patients who are able to continue working,” the authors wrote. “Accommodations that allow a woman to keep working are the most reliable way to guarantee pay, benefits, and job protection.”

Because the way in which medical certification paperwork is written can greatly affect whether employers comply with medical suggestions, physicians should familiarize themselves with the most effective ways to write such notes, according to ACOG. The recent opinion provides an overview of the necessary structure and contents of medical notes to optimize their effects. The opinion highlights the work of Pregnant@Work, an online note-writing resource developed by the University of California’s Hastings Center for WorkLife Law, San Francisco, that assists health providers in writing legally appropriate work accommodations letters.

Also important for ob.gyns. is knowing the relevant state and federal protections for pregnant patients and new mothers who work or take medical leave. In some instances, it may be necessary for women to consult with a legal counselor in cases in which discrimination has occurred, accommodations are denied, or complex legal questions arise, according to the opinion.

The ACOG opinion is timely because more women than ever before are a part of the workforce, said Rebecca Jackson, MD, a member of ACOG’s committee on obstetric practice and a coauthor of the opinion. Dr. Jackson recently participated in a multidisciplinary work group that addressed legal issues around employment accommodations for pregnant women. Dr. Jackson said she approached ACOG about creating formal guidance on the subject after hearing about the many employment challenges pregnant women experience and how the way physician notes are written can greatly influence accommodations.

“As health care providers responsible for caring for women, it’s essential our guidance addresses the key considerations for maintaining women’s health – this often includes work environments, particularly for pregnant and immediately postpartum women who may have specific health care needs requiring adjustments or accommodations,” Dr. Jackson said in an interview. “Obstetric care providers must be equipped with the necessary and relevant guidance to appropriately support their patients or refer them to additional resources, like legal assistance. This guidance is an important component in building that knowledge among women’s health care providers and ensuring more women can access the care and treatment they need when they need it without compromising their careers or income.”

Obstetrician-gynecologists have a central role in helping pregnant patients maintain employment by writing appropriate notes to employers and informing patients of their rights, according to a new committee opinion by the American College of Obstetricians and Gynecologists.

The opinion, released March 28, outlines key considerations for ob.gyns. in assisting pregnant patients with employment maintenance and helping protect them from employment discrimination. The most common employment issues that pregnant women face include pregnancy-related discrimination, work accommodations that allow continued employment, job-protected leave, and wage replacement while on leave, according to the opinion. After delivery, top employment concerns involve lactation, and accommodations and leave for recovery, bonding, and caring for the infant.

“It’s important that ob.gyns. discuss workplace expectations with their working pregnant patient,” Yasser El-Sayed, MD, vice chair of the ACOG’s committee on obstetric practice said in a statement. “Some women may be unaware of attendant risks to pregnancy at their job, while others may be unaware that their ob.gyn. can offer both support and potential solutions or resources, whether in the form of slight modifications or a formal medical note detailing the need for an accommodation to protect the patient’s health.”

To address these issues, ACOG recommends that ob.gyns. reassure patients that working during pregnancy is generally safe. In the case of high-risk or complicated pregnancy, ob.gyns. should inform patients that work accommodations often can allow for continued safe employment. Appropriately drafted notes by physicians to employers are key, the opinion stresses.

“By writing appropriate notes to employers, obstetrician-gynecologists and other obstetric care providers can be instrumental in obtaining accommodations for their patients who are able to continue working,” the authors wrote. “Accommodations that allow a woman to keep working are the most reliable way to guarantee pay, benefits, and job protection.”

Because the way in which medical certification paperwork is written can greatly affect whether employers comply with medical suggestions, physicians should familiarize themselves with the most effective ways to write such notes, according to ACOG. The recent opinion provides an overview of the necessary structure and contents of medical notes to optimize their effects. The opinion highlights the work of Pregnant@Work, an online note-writing resource developed by the University of California’s Hastings Center for WorkLife Law, San Francisco, that assists health providers in writing legally appropriate work accommodations letters.

Also important for ob.gyns. is knowing the relevant state and federal protections for pregnant patients and new mothers who work or take medical leave. In some instances, it may be necessary for women to consult with a legal counselor in cases in which discrimination has occurred, accommodations are denied, or complex legal questions arise, according to the opinion.

The ACOG opinion is timely because more women than ever before are a part of the workforce, said Rebecca Jackson, MD, a member of ACOG’s committee on obstetric practice and a coauthor of the opinion. Dr. Jackson recently participated in a multidisciplinary work group that addressed legal issues around employment accommodations for pregnant women. Dr. Jackson said she approached ACOG about creating formal guidance on the subject after hearing about the many employment challenges pregnant women experience and how the way physician notes are written can greatly influence accommodations.

“As health care providers responsible for caring for women, it’s essential our guidance addresses the key considerations for maintaining women’s health – this often includes work environments, particularly for pregnant and immediately postpartum women who may have specific health care needs requiring adjustments or accommodations,” Dr. Jackson said in an interview. “Obstetric care providers must be equipped with the necessary and relevant guidance to appropriately support their patients or refer them to additional resources, like legal assistance. This guidance is an important component in building that knowledge among women’s health care providers and ensuring more women can access the care and treatment they need when they need it without compromising their careers or income.”

Obstetrician-gynecologists have a central role in helping pregnant patients maintain employment by writing appropriate notes to employers and informing patients of their rights, according to a new committee opinion by the American College of Obstetricians and Gynecologists.

The opinion, released March 28, outlines key considerations for ob.gyns. in assisting pregnant patients with employment maintenance and helping protect them from employment discrimination. The most common employment issues that pregnant women face include pregnancy-related discrimination, work accommodations that allow continued employment, job-protected leave, and wage replacement while on leave, according to the opinion. After delivery, top employment concerns involve lactation, and accommodations and leave for recovery, bonding, and caring for the infant.

“It’s important that ob.gyns. discuss workplace expectations with their working pregnant patient,” Yasser El-Sayed, MD, vice chair of the ACOG’s committee on obstetric practice said in a statement. “Some women may be unaware of attendant risks to pregnancy at their job, while others may be unaware that their ob.gyn. can offer both support and potential solutions or resources, whether in the form of slight modifications or a formal medical note detailing the need for an accommodation to protect the patient’s health.”

To address these issues, ACOG recommends that ob.gyns. reassure patients that working during pregnancy is generally safe. In the case of high-risk or complicated pregnancy, ob.gyns. should inform patients that work accommodations often can allow for continued safe employment. Appropriately drafted notes by physicians to employers are key, the opinion stresses.

“By writing appropriate notes to employers, obstetrician-gynecologists and other obstetric care providers can be instrumental in obtaining accommodations for their patients who are able to continue working,” the authors wrote. “Accommodations that allow a woman to keep working are the most reliable way to guarantee pay, benefits, and job protection.”

Because the way in which medical certification paperwork is written can greatly affect whether employers comply with medical suggestions, physicians should familiarize themselves with the most effective ways to write such notes, according to ACOG. The recent opinion provides an overview of the necessary structure and contents of medical notes to optimize their effects. The opinion highlights the work of Pregnant@Work, an online note-writing resource developed by the University of California’s Hastings Center for WorkLife Law, San Francisco, that assists health providers in writing legally appropriate work accommodations letters.

Also important for ob.gyns. is knowing the relevant state and federal protections for pregnant patients and new mothers who work or take medical leave. In some instances, it may be necessary for women to consult with a legal counselor in cases in which discrimination has occurred, accommodations are denied, or complex legal questions arise, according to the opinion.

The ACOG opinion is timely because more women than ever before are a part of the workforce, said Rebecca Jackson, MD, a member of ACOG’s committee on obstetric practice and a coauthor of the opinion. Dr. Jackson recently participated in a multidisciplinary work group that addressed legal issues around employment accommodations for pregnant women. Dr. Jackson said she approached ACOG about creating formal guidance on the subject after hearing about the many employment challenges pregnant women experience and how the way physician notes are written can greatly influence accommodations.

“As health care providers responsible for caring for women, it’s essential our guidance addresses the key considerations for maintaining women’s health – this often includes work environments, particularly for pregnant and immediately postpartum women who may have specific health care needs requiring adjustments or accommodations,” Dr. Jackson said in an interview. “Obstetric care providers must be equipped with the necessary and relevant guidance to appropriately support their patients or refer them to additional resources, like legal assistance. This guidance is an important component in building that knowledge among women’s health care providers and ensuring more women can access the care and treatment they need when they need it without compromising their careers or income.”

Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.

Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.

Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).

Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.

The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.

mschneider@mdedge.com

SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.

Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.

Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.

Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).

Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.

The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.

mschneider@mdedge.com

SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.

Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.

Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.

Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).

Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.

The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.

mschneider@mdedge.com

SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.

In order to distinguish neurogenic from nonneurogenic causes of orthostatic hypotension, looking at the change in heart rate (cHR) in relation to the change in systolic blood pressure (cSBP) may be superior to looking at heart rate alone.

A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.

Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.

The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.

Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.

They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.

By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).

“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”

The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.

“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.

The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.

“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.

The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.

SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.

In order to distinguish neurogenic from nonneurogenic causes of orthostatic hypotension, looking at the change in heart rate (cHR) in relation to the change in systolic blood pressure (cSBP) may be superior to looking at heart rate alone.

A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.

Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.

The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.

Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.

They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.

By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).

“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”

The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.

“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.

The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.

“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.

The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.

SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.

In order to distinguish neurogenic from nonneurogenic causes of orthostatic hypotension, looking at the change in heart rate (cHR) in relation to the change in systolic blood pressure (cSBP) may be superior to looking at heart rate alone.

A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.

Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.

The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.

Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.

They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.

By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).

“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”

The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.

“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.

The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.

“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.

The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.

SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.

SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.

When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.

Brigit A. de Jong, MD, PhD, a neurologist at Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues found decreased miR-219 expression in the tissue of patients with MS, compared with healthy controls. To investigate whether CSF levels of miR-219 could be a biomarker of MS, the investigators performed quantitative polymerase chain reaction on samples taken from patients with MS and controls.

An Analysis of Three Cohorts

Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.

The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.

Advantages of miRNAs

Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.

—Erik Greb

Suggested Reading

Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.

Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.

Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.

SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.

When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.

Brigit A. de Jong, MD, PhD, a neurologist at Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues found decreased miR-219 expression in the tissue of patients with MS, compared with healthy controls. To investigate whether CSF levels of miR-219 could be a biomarker of MS, the investigators performed quantitative polymerase chain reaction on samples taken from patients with MS and controls.

An Analysis of Three Cohorts

Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.

The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.

Advantages of miRNAs

Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.

—Erik Greb

Suggested Reading

Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.

Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.

Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.

SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.

When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.

Brigit A. de Jong, MD, PhD, a neurologist at Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues found decreased miR-219 expression in the tissue of patients with MS, compared with healthy controls. To investigate whether CSF levels of miR-219 could be a biomarker of MS, the investigators performed quantitative polymerase chain reaction on samples taken from patients with MS and controls.

An Analysis of Three Cohorts

Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.

The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.

Advantages of miRNAs

Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.

—Erik Greb

Suggested Reading

Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.

Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.

Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.

SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.

Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.

“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.

The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.

Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
 

The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Amin A et al. THSNA 2018, Poster 51.

SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.

Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.

“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.

The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.

Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
 

The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Amin A et al. THSNA 2018, Poster 51.

SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.

Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.

“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.

The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.

Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
 

The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Amin A et al. THSNA 2018, Poster 51.

WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..

“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.

Ted Bosworth/Frontline Medical News

“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”

His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.

Ted Bosworth/Frontline Medical News

However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.

“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.

Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.

The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”

Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.

WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..

“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.

Ted Bosworth/Frontline Medical News

“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”

His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.

Ted Bosworth/Frontline Medical News

However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.

“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.

Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.

The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”

Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.

WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..

“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.

Ted Bosworth/Frontline Medical News

“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”

His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.

Ted Bosworth/Frontline Medical News

However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.

“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.

Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.

The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”

Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.