Blood smear showing

thalassemia

VIENNA—Data from a phase 2a trial suggest the activin receptor sotatercept can effectively treat patients with ß-thalassemia.

However, the companies developing the drug have decided not to advance sotatercept to phase 3 trials in this patient population.

Instead, the companies are initiating a phase 3 program with sotatercept’s “twin” activin receptor, luspatercept, in patients with ß-thalassemia or myelodysplastic syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing both compounds. The companies plan to continue developing sotatercept for patients with chronic kidney disease.

Maria Domenica Cappellini, MD, of the University of Milan in Italy, presented results from the phase 2a study of sotatercept in ß-thalassemia at the 20th Congress of the European Hematology Association (abstract S137*).

Phase 2 results with luspatercept in ß-thalassemia were also presented at the meeting.

The dose-finding study of sotatercept had enrolled 46 patients at the time of Dr Cappellini’s presentation. The drug was given subcutaneously at doses ranging from 0.1 mg/kg to 1.0 mg/kg every 3 weeks.

The 30 non-transfusion-dependent (NTD) patients received 4 or fewer red blood cell (RBC) units in the 6 months prior to study enrollment. The 16 transfusion-dependent (TD) patients had received 2 or more RBC units every 30 days for 6 months or more prior to study enrollment.

Twenty-five of the 46 patients remain on treatment, with a median exposure time of 12.4 months.

NTD patients

The patients’ median age was 42, and 53% were female. Fifty-three percent had had a splenectomy, and the median baseline hemoglobin level was 8.4 g/dL.

Treatment with sotatercept produced a dose-dependent hemoglobin increase.

“[W]hat I found quite interesting is that the increase is consistent and persistent, [even] after 1 year,” Dr Cappellini said. “And they are still maintained on treatment, of course, but it is a sustained response.”

At the 0.75 mg/kg dose, 86% of patients had a hemoglobin increase of 1 g/dL for 12 weeks or more, and 71% had an increase of 1.5 g/dL.

TD patients

The patients’ median age was 36 years, and 38% were female. Three-quarters of patients had ß-thalassemia major, and a quarter had ß-thalassemia intermedia.

Nearly a third of patients had had a splenectomy, and their transfusion burden at baseline ranged from 8 RBC units to 35 RBC units every 24 weeks.

The mean reduction in transfusion burden among patients treated with sotatercept at doses of 0.5 mg/kg or higher was 32.25%. And the 1.0 mg/kg dose of sotatercept reduced one patient’s transfusion burden by 61.6%.

Dr Cappellini noted that the pharmacokinetic analysis showed a correlation with exposure. The investigators observed no apparent effects of weight, sex, age, or transfusion burden on drug clearance.

“So the relationship was probably more related to long-term exposure than to the real dosage,” she said.

Safety

Hypertension and bone pain were the most common grade 2-4, treatment-related adverse events.

Seven patients discontinued the study due to adverse events, one patient each with bone pain, superficial thrombophlebitis, ventricular extrasystole, spinal extramedullary erythropoietic tissue, and erythema at the injection site/allergic reaction. Two patients discontinued due to hypertension.

Dr Cappellini concluded that sotatercept and the related molecule, luspatercept, may provide a favorable risk-benefit profile for patients with ß-thalassemia.

“These 2 molecules are merging now for a phase 3 trial in either TD or NTD thalassemia cohorts,” she said. “The two drugs are actually very, very similar, and, in fact, for the trial, we decided to use only one. There is no way to go on with 2 molecules.”

In April, Acceleron and Celgene announced plans to initiate a phase 3 program with luspatercept in myelodysplastic syndromes and β-thalassemia by the end of this year. The companies said they will continue to develop sotatercept for patients with chronic kidney disease.

*Data in the abstract differ from the presentation.

Blood smear showing

thalassemia

VIENNA—Data from a phase 2a trial suggest the activin receptor sotatercept can effectively treat patients with ß-thalassemia.

However, the companies developing the drug have decided not to advance sotatercept to phase 3 trials in this patient population.

Instead, the companies are initiating a phase 3 program with sotatercept’s “twin” activin receptor, luspatercept, in patients with ß-thalassemia or myelodysplastic syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing both compounds. The companies plan to continue developing sotatercept for patients with chronic kidney disease.

Maria Domenica Cappellini, MD, of the University of Milan in Italy, presented results from the phase 2a study of sotatercept in ß-thalassemia at the 20th Congress of the European Hematology Association (abstract S137*).

Phase 2 results with luspatercept in ß-thalassemia were also presented at the meeting.

The dose-finding study of sotatercept had enrolled 46 patients at the time of Dr Cappellini’s presentation. The drug was given subcutaneously at doses ranging from 0.1 mg/kg to 1.0 mg/kg every 3 weeks.

The 30 non-transfusion-dependent (NTD) patients received 4 or fewer red blood cell (RBC) units in the 6 months prior to study enrollment. The 16 transfusion-dependent (TD) patients had received 2 or more RBC units every 30 days for 6 months or more prior to study enrollment.

Twenty-five of the 46 patients remain on treatment, with a median exposure time of 12.4 months.

NTD patients

The patients’ median age was 42, and 53% were female. Fifty-three percent had had a splenectomy, and the median baseline hemoglobin level was 8.4 g/dL.

Treatment with sotatercept produced a dose-dependent hemoglobin increase.

“[W]hat I found quite interesting is that the increase is consistent and persistent, [even] after 1 year,” Dr Cappellini said. “And they are still maintained on treatment, of course, but it is a sustained response.”

At the 0.75 mg/kg dose, 86% of patients had a hemoglobin increase of 1 g/dL for 12 weeks or more, and 71% had an increase of 1.5 g/dL.

TD patients

The patients’ median age was 36 years, and 38% were female. Three-quarters of patients had ß-thalassemia major, and a quarter had ß-thalassemia intermedia.

Nearly a third of patients had had a splenectomy, and their transfusion burden at baseline ranged from 8 RBC units to 35 RBC units every 24 weeks.

The mean reduction in transfusion burden among patients treated with sotatercept at doses of 0.5 mg/kg or higher was 32.25%. And the 1.0 mg/kg dose of sotatercept reduced one patient’s transfusion burden by 61.6%.

Dr Cappellini noted that the pharmacokinetic analysis showed a correlation with exposure. The investigators observed no apparent effects of weight, sex, age, or transfusion burden on drug clearance.

“So the relationship was probably more related to long-term exposure than to the real dosage,” she said.

Safety

Hypertension and bone pain were the most common grade 2-4, treatment-related adverse events.

Seven patients discontinued the study due to adverse events, one patient each with bone pain, superficial thrombophlebitis, ventricular extrasystole, spinal extramedullary erythropoietic tissue, and erythema at the injection site/allergic reaction. Two patients discontinued due to hypertension.

Dr Cappellini concluded that sotatercept and the related molecule, luspatercept, may provide a favorable risk-benefit profile for patients with ß-thalassemia.

“These 2 molecules are merging now for a phase 3 trial in either TD or NTD thalassemia cohorts,” she said. “The two drugs are actually very, very similar, and, in fact, for the trial, we decided to use only one. There is no way to go on with 2 molecules.”

In April, Acceleron and Celgene announced plans to initiate a phase 3 program with luspatercept in myelodysplastic syndromes and β-thalassemia by the end of this year. The companies said they will continue to develop sotatercept for patients with chronic kidney disease.

*Data in the abstract differ from the presentation.

Blood smear showing

thalassemia

VIENNA—Data from a phase 2a trial suggest the activin receptor sotatercept can effectively treat patients with ß-thalassemia.

However, the companies developing the drug have decided not to advance sotatercept to phase 3 trials in this patient population.

Instead, the companies are initiating a phase 3 program with sotatercept’s “twin” activin receptor, luspatercept, in patients with ß-thalassemia or myelodysplastic syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing both compounds. The companies plan to continue developing sotatercept for patients with chronic kidney disease.

Maria Domenica Cappellini, MD, of the University of Milan in Italy, presented results from the phase 2a study of sotatercept in ß-thalassemia at the 20th Congress of the European Hematology Association (abstract S137*).

Phase 2 results with luspatercept in ß-thalassemia were also presented at the meeting.

The dose-finding study of sotatercept had enrolled 46 patients at the time of Dr Cappellini’s presentation. The drug was given subcutaneously at doses ranging from 0.1 mg/kg to 1.0 mg/kg every 3 weeks.

The 30 non-transfusion-dependent (NTD) patients received 4 or fewer red blood cell (RBC) units in the 6 months prior to study enrollment. The 16 transfusion-dependent (TD) patients had received 2 or more RBC units every 30 days for 6 months or more prior to study enrollment.

Twenty-five of the 46 patients remain on treatment, with a median exposure time of 12.4 months.

NTD patients

The patients’ median age was 42, and 53% were female. Fifty-three percent had had a splenectomy, and the median baseline hemoglobin level was 8.4 g/dL.

Treatment with sotatercept produced a dose-dependent hemoglobin increase.

“[W]hat I found quite interesting is that the increase is consistent and persistent, [even] after 1 year,” Dr Cappellini said. “And they are still maintained on treatment, of course, but it is a sustained response.”

At the 0.75 mg/kg dose, 86% of patients had a hemoglobin increase of 1 g/dL for 12 weeks or more, and 71% had an increase of 1.5 g/dL.

TD patients

The patients’ median age was 36 years, and 38% were female. Three-quarters of patients had ß-thalassemia major, and a quarter had ß-thalassemia intermedia.

Nearly a third of patients had had a splenectomy, and their transfusion burden at baseline ranged from 8 RBC units to 35 RBC units every 24 weeks.

The mean reduction in transfusion burden among patients treated with sotatercept at doses of 0.5 mg/kg or higher was 32.25%. And the 1.0 mg/kg dose of sotatercept reduced one patient’s transfusion burden by 61.6%.

Dr Cappellini noted that the pharmacokinetic analysis showed a correlation with exposure. The investigators observed no apparent effects of weight, sex, age, or transfusion burden on drug clearance.

“So the relationship was probably more related to long-term exposure than to the real dosage,” she said.

Safety

Hypertension and bone pain were the most common grade 2-4, treatment-related adverse events.

Seven patients discontinued the study due to adverse events, one patient each with bone pain, superficial thrombophlebitis, ventricular extrasystole, spinal extramedullary erythropoietic tissue, and erythema at the injection site/allergic reaction. Two patients discontinued due to hypertension.

Dr Cappellini concluded that sotatercept and the related molecule, luspatercept, may provide a favorable risk-benefit profile for patients with ß-thalassemia.

“These 2 molecules are merging now for a phase 3 trial in either TD or NTD thalassemia cohorts,” she said. “The two drugs are actually very, very similar, and, in fact, for the trial, we decided to use only one. There is no way to go on with 2 molecules.”

In April, Acceleron and Celgene announced plans to initiate a phase 3 program with luspatercept in myelodysplastic syndromes and β-thalassemia by the end of this year. The companies said they will continue to develop sotatercept for patients with chronic kidney disease.

*Data in the abstract differ from the presentation.

WASHINGTON – Soldiers who experience traumatic brain injury (TBI) while deployed have a much higher rate of unemployment than those who experience no TBI during their tour of duty, according to a study presented at the annual meeting of the American Headache Society.

“We know that TBI and PTSD [post-traumatic stress disorder] can lead to headaches, depression, and loss of libido, but there’s very little data on the long-term effects of TBI on [veterans], and therefore very little control data,” explained Dr. James R. Couch of the University of Oklahoma in Oklahoma City.

Dr. Couch and his coinvestigators looked at 5,743 veterans of Operation Iraqi Freedom and Operation Enduring Freedom who had been deployed between June 2008 and April 2011, 1,325 (23%) of whom had experienced TBI while serving. The first 500 subjects seen were then frequency matched with a control subject who did not experience TBI, based on age, sex, race, and deployment length.

From this pool, 67 pairs were finally selected for inclusion, all of whom were 2-11 years post TBI: 39 pairs were 2-7 years post TBI and the remaining 28 pairs were 8-11 years post TBI. All subjects were 25-60 years old. Marital and employment data were collected from each subject, and each subject completed a TBI questionnaire, headache questionnaire, Beck Depression Inventory 2, and post-traumatic stress disorder questionnaire, from which bivariate analyses were performed.

Although marital status was not found to be significantly tied to TBI experience while deployed, unemployment rates were consistently and significantly higher in the TBI cohort, compared with their non-TBI counterparts. In the 2-7 years post-TBI group, 35.9% of subjects were unemployed, while only 10.3% of non-TBI subjects were without a job (P = .014). In the 8-11 years post-TBI cohort, 50.0% of subjects were unemployed, compared with 7.1% of controls who were unemployed. No significant association, however, was found between frequency of headache or severity of TBI with either unemployment or marital status.

The most important thing to take away, said Dr. Couch, is “the marked difference in unemployment from 4-11 years after TBI, and that things seem to be getting worse as time goes along. Headache, depression, PTSD – none of these stand out as singular causes but are all known to be related to [TBI], and severity of TBI was not strongly associated.”

Dr. Couch disclosed receiving consulting fees/honoraria from St. Jude Medical.

[email protected]

WASHINGTON – Soldiers who experience traumatic brain injury (TBI) while deployed have a much higher rate of unemployment than those who experience no TBI during their tour of duty, according to a study presented at the annual meeting of the American Headache Society.

“We know that TBI and PTSD [post-traumatic stress disorder] can lead to headaches, depression, and loss of libido, but there’s very little data on the long-term effects of TBI on [veterans], and therefore very little control data,” explained Dr. James R. Couch of the University of Oklahoma in Oklahoma City.

Dr. Couch and his coinvestigators looked at 5,743 veterans of Operation Iraqi Freedom and Operation Enduring Freedom who had been deployed between June 2008 and April 2011, 1,325 (23%) of whom had experienced TBI while serving. The first 500 subjects seen were then frequency matched with a control subject who did not experience TBI, based on age, sex, race, and deployment length.

From this pool, 67 pairs were finally selected for inclusion, all of whom were 2-11 years post TBI: 39 pairs were 2-7 years post TBI and the remaining 28 pairs were 8-11 years post TBI. All subjects were 25-60 years old. Marital and employment data were collected from each subject, and each subject completed a TBI questionnaire, headache questionnaire, Beck Depression Inventory 2, and post-traumatic stress disorder questionnaire, from which bivariate analyses were performed.

Although marital status was not found to be significantly tied to TBI experience while deployed, unemployment rates were consistently and significantly higher in the TBI cohort, compared with their non-TBI counterparts. In the 2-7 years post-TBI group, 35.9% of subjects were unemployed, while only 10.3% of non-TBI subjects were without a job (P = .014). In the 8-11 years post-TBI cohort, 50.0% of subjects were unemployed, compared with 7.1% of controls who were unemployed. No significant association, however, was found between frequency of headache or severity of TBI with either unemployment or marital status.

The most important thing to take away, said Dr. Couch, is “the marked difference in unemployment from 4-11 years after TBI, and that things seem to be getting worse as time goes along. Headache, depression, PTSD – none of these stand out as singular causes but are all known to be related to [TBI], and severity of TBI was not strongly associated.”

Dr. Couch disclosed receiving consulting fees/honoraria from St. Jude Medical.

[email protected]

WASHINGTON – Soldiers who experience traumatic brain injury (TBI) while deployed have a much higher rate of unemployment than those who experience no TBI during their tour of duty, according to a study presented at the annual meeting of the American Headache Society.

“We know that TBI and PTSD [post-traumatic stress disorder] can lead to headaches, depression, and loss of libido, but there’s very little data on the long-term effects of TBI on [veterans], and therefore very little control data,” explained Dr. James R. Couch of the University of Oklahoma in Oklahoma City.

Dr. Couch and his coinvestigators looked at 5,743 veterans of Operation Iraqi Freedom and Operation Enduring Freedom who had been deployed between June 2008 and April 2011, 1,325 (23%) of whom had experienced TBI while serving. The first 500 subjects seen were then frequency matched with a control subject who did not experience TBI, based on age, sex, race, and deployment length.

From this pool, 67 pairs were finally selected for inclusion, all of whom were 2-11 years post TBI: 39 pairs were 2-7 years post TBI and the remaining 28 pairs were 8-11 years post TBI. All subjects were 25-60 years old. Marital and employment data were collected from each subject, and each subject completed a TBI questionnaire, headache questionnaire, Beck Depression Inventory 2, and post-traumatic stress disorder questionnaire, from which bivariate analyses were performed.

Although marital status was not found to be significantly tied to TBI experience while deployed, unemployment rates were consistently and significantly higher in the TBI cohort, compared with their non-TBI counterparts. In the 2-7 years post-TBI group, 35.9% of subjects were unemployed, while only 10.3% of non-TBI subjects were without a job (P = .014). In the 8-11 years post-TBI cohort, 50.0% of subjects were unemployed, compared with 7.1% of controls who were unemployed. No significant association, however, was found between frequency of headache or severity of TBI with either unemployment or marital status.

The most important thing to take away, said Dr. Couch, is “the marked difference in unemployment from 4-11 years after TBI, and that things seem to be getting worse as time goes along. Headache, depression, PTSD – none of these stand out as singular causes but are all known to be related to [TBI], and severity of TBI was not strongly associated.”

Dr. Couch disclosed receiving consulting fees/honoraria from St. Jude Medical.

[email protected]

For those of us who appreciate the value of science and accept its limitations, it is sometimes difficult to understand how parents can choose to not immunize their children against serious and life-threatening diseases. To some extent, the explanation may be that immunizations simply have become victims of their own success.

How many adults have a relative, friend, or neighbor whose child has died as the result of bacterial meningitis or epiglottitis? They might have had a friend whose month-long cough was eventually diagnosed as whooping cough, but how many parents know of an infant who succumbed to pertussis? If you were trained in the last decade, you may not have had first-hand experience with most of the diseases for which we now have immunizations.

Reading a recent review of a new biography of Jonas Salk triggered a stream of memories of what it was like when polio descended on the landscape of North America – unchecked by an effective immunization. Moving through communities, choosing victims seemingly at random, it was every parent’s nightmare.

I grew up in a small town in New York State, so small that its inhabitants refer to it as a “village.” Everyone in Pleasantville knew at least one family that had been touched by polio. I don’t recall being aware of anyone in my family’s extended network of acquaintances who had died of the disease, but I suspect there may have been some fatalities that my parents avoided discussing in my presence. But I knew it was a disease with a significant mortality rate, and I knew of children and adults who had luckily survived several weeks or months in an iron lung. One of my parents’ closest friends walked with a limp as a result of polio.

There was rumor in town that all five members in one family had contracted polio and incredibly survived. Their cat had allegedly died of the disease. Our community was said to be particularly vulnerable because we had a public pool. This gift from the federal government’s Works Progress Administration provided a multi-lane superhighway for the virus to spread from child to child.

Even as a young child, I could sense that a blanket of fear hung over our little village during the summer when the disease was at its most prevalent. Now, as a parent, I am surprised how well my own parents disguised the fears that they and their peers must have harbored. My sister and I were still allowed to go swimming at the pool on the hottest days, but we knew that there were other families who stayed away.

When a vaccine trial began at our school, there was no question that we would participate. In fact, I don’t recall bringing home any permission slips to be signed. Nor do I remember hearing of any families who had opted out. We always wondered whether we had received the real vaccine or the placebo. But when the trials were over and the real vaccine was available, what parent in his or her right mind would even consider depriving his or her child from protection against this scourge that had taken up residence among us? I’m sure that Dr. Blum, my pediatrician, never needed to spend more than 30 seconds trying to convince my parents or any other parents, for that matter, of the need to vaccinate against polio.

My childhood ended before the development of the vaccines against the other common viral illnesses, and as a result I contracted and survived measles, mumps, rubella, and varicella. Of course, there must have been a few children who died of the diseases that had left me unscathed, but the number of fatalities was so small that I’m sure my parents would have wondered why we would need vaccines for these “usual diseases of childhood.”

But polio was different, and while it pales in comparison to Ebola, polio and its successful eradication created a generation of parents with a respect for science and the value of immunization. However, that generation has passed, and with it the stories they could have told the parents of today. Unfortunately, vaccine refusers seem to be immune to education and deaf to the lessons history can teach. I suspect that they would have foolishly ignored my parents’ stories about polio as just so much when-I-was-your-age mumbling.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

For those of us who appreciate the value of science and accept its limitations, it is sometimes difficult to understand how parents can choose to not immunize their children against serious and life-threatening diseases. To some extent, the explanation may be that immunizations simply have become victims of their own success.

How many adults have a relative, friend, or neighbor whose child has died as the result of bacterial meningitis or epiglottitis? They might have had a friend whose month-long cough was eventually diagnosed as whooping cough, but how many parents know of an infant who succumbed to pertussis? If you were trained in the last decade, you may not have had first-hand experience with most of the diseases for which we now have immunizations.

Reading a recent review of a new biography of Jonas Salk triggered a stream of memories of what it was like when polio descended on the landscape of North America – unchecked by an effective immunization. Moving through communities, choosing victims seemingly at random, it was every parent’s nightmare.

I grew up in a small town in New York State, so small that its inhabitants refer to it as a “village.” Everyone in Pleasantville knew at least one family that had been touched by polio. I don’t recall being aware of anyone in my family’s extended network of acquaintances who had died of the disease, but I suspect there may have been some fatalities that my parents avoided discussing in my presence. But I knew it was a disease with a significant mortality rate, and I knew of children and adults who had luckily survived several weeks or months in an iron lung. One of my parents’ closest friends walked with a limp as a result of polio.

There was rumor in town that all five members in one family had contracted polio and incredibly survived. Their cat had allegedly died of the disease. Our community was said to be particularly vulnerable because we had a public pool. This gift from the federal government’s Works Progress Administration provided a multi-lane superhighway for the virus to spread from child to child.

Even as a young child, I could sense that a blanket of fear hung over our little village during the summer when the disease was at its most prevalent. Now, as a parent, I am surprised how well my own parents disguised the fears that they and their peers must have harbored. My sister and I were still allowed to go swimming at the pool on the hottest days, but we knew that there were other families who stayed away.

When a vaccine trial began at our school, there was no question that we would participate. In fact, I don’t recall bringing home any permission slips to be signed. Nor do I remember hearing of any families who had opted out. We always wondered whether we had received the real vaccine or the placebo. But when the trials were over and the real vaccine was available, what parent in his or her right mind would even consider depriving his or her child from protection against this scourge that had taken up residence among us? I’m sure that Dr. Blum, my pediatrician, never needed to spend more than 30 seconds trying to convince my parents or any other parents, for that matter, of the need to vaccinate against polio.

My childhood ended before the development of the vaccines against the other common viral illnesses, and as a result I contracted and survived measles, mumps, rubella, and varicella. Of course, there must have been a few children who died of the diseases that had left me unscathed, but the number of fatalities was so small that I’m sure my parents would have wondered why we would need vaccines for these “usual diseases of childhood.”

But polio was different, and while it pales in comparison to Ebola, polio and its successful eradication created a generation of parents with a respect for science and the value of immunization. However, that generation has passed, and with it the stories they could have told the parents of today. Unfortunately, vaccine refusers seem to be immune to education and deaf to the lessons history can teach. I suspect that they would have foolishly ignored my parents’ stories about polio as just so much when-I-was-your-age mumbling.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

For those of us who appreciate the value of science and accept its limitations, it is sometimes difficult to understand how parents can choose to not immunize their children against serious and life-threatening diseases. To some extent, the explanation may be that immunizations simply have become victims of their own success.

How many adults have a relative, friend, or neighbor whose child has died as the result of bacterial meningitis or epiglottitis? They might have had a friend whose month-long cough was eventually diagnosed as whooping cough, but how many parents know of an infant who succumbed to pertussis? If you were trained in the last decade, you may not have had first-hand experience with most of the diseases for which we now have immunizations.

Reading a recent review of a new biography of Jonas Salk triggered a stream of memories of what it was like when polio descended on the landscape of North America – unchecked by an effective immunization. Moving through communities, choosing victims seemingly at random, it was every parent’s nightmare.

I grew up in a small town in New York State, so small that its inhabitants refer to it as a “village.” Everyone in Pleasantville knew at least one family that had been touched by polio. I don’t recall being aware of anyone in my family’s extended network of acquaintances who had died of the disease, but I suspect there may have been some fatalities that my parents avoided discussing in my presence. But I knew it was a disease with a significant mortality rate, and I knew of children and adults who had luckily survived several weeks or months in an iron lung. One of my parents’ closest friends walked with a limp as a result of polio.

There was rumor in town that all five members in one family had contracted polio and incredibly survived. Their cat had allegedly died of the disease. Our community was said to be particularly vulnerable because we had a public pool. This gift from the federal government’s Works Progress Administration provided a multi-lane superhighway for the virus to spread from child to child.

Even as a young child, I could sense that a blanket of fear hung over our little village during the summer when the disease was at its most prevalent. Now, as a parent, I am surprised how well my own parents disguised the fears that they and their peers must have harbored. My sister and I were still allowed to go swimming at the pool on the hottest days, but we knew that there were other families who stayed away.

When a vaccine trial began at our school, there was no question that we would participate. In fact, I don’t recall bringing home any permission slips to be signed. Nor do I remember hearing of any families who had opted out. We always wondered whether we had received the real vaccine or the placebo. But when the trials were over and the real vaccine was available, what parent in his or her right mind would even consider depriving his or her child from protection against this scourge that had taken up residence among us? I’m sure that Dr. Blum, my pediatrician, never needed to spend more than 30 seconds trying to convince my parents or any other parents, for that matter, of the need to vaccinate against polio.

My childhood ended before the development of the vaccines against the other common viral illnesses, and as a result I contracted and survived measles, mumps, rubella, and varicella. Of course, there must have been a few children who died of the diseases that had left me unscathed, but the number of fatalities was so small that I’m sure my parents would have wondered why we would need vaccines for these “usual diseases of childhood.”

But polio was different, and while it pales in comparison to Ebola, polio and its successful eradication created a generation of parents with a respect for science and the value of immunization. However, that generation has passed, and with it the stories they could have told the parents of today. Unfortunately, vaccine refusers seem to be immune to education and deaf to the lessons history can teach. I suspect that they would have foolishly ignored my parents’ stories about polio as just so much when-I-was-your-age mumbling.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

Hematopoietic stem cells

in the bone marrow

Scientists say they have identified a family of multipotent progenitor (MPP) cells that are the first to arise from hematopoietic stem cells (HSCs).

The team said their discovery, published in Cell Stem Cell, raises the possibility that, by manipulating the fates of MPPs or HSCs, researchers could one day help overcome imbalances and deficiencies that can arise in the blood system due to aging or leukemia.

Similar imbalances can render patients vulnerable immediately following HSC transplants, especially following umbilical cord transplants, said study author Emmanuelle Passegué, PhD, of the University of California San Francisco.

Via experiments in mice, Dr Passegué and her colleagues found that HSCs “make educated decisions” when it comes time to differentiate.

“Previously, researchers thought that the developmental paths of daughter cells were randomly specified by the HSC, but we conclude that the HSC normally responds appropriately to signals in the environment, making the different MPPs in parallel, but at different speeds and in different amounts to meet the body’s needs,” Dr Passegué said.

To uncover these findings, she and her colleagues investigated patterns of gene expression and cell signaling that determine which developmental paths are favored when relatively rare HSCs spin off daughter cells. The team also explored HSCs’ responses during transplant.

The researchers found that the first daughter cells that arise from HSCs are already distinct, favoring the development of different specialized cell lineages.

The team identified two types of daughter cells, MPP2 and MPP3, which, under normal conditions, are rare. These cells work together with more common daughter cells, MPP4 cells, to control blood production.

MPP2 cells favor the production of platelets and red blood cells, while MPP3 cells favor production of inflammatory cells.

MPP4 cells are the main producers of lymphocytes that fight specific disease pathogens, but the researchers showed that MPP4 cells can easily be re-educated to make many inflammatory cells when regenerative needs are high, as they are following a transplant.

The team found that, during transplant, regenerating HSCs limit their own self-renewal and instead go to work overproducing MPP2 and MPP3 cells that quickly produce needed red blood cells, platelets, and inflammatory cells. Only later does MPP4 production return to normal, enabling the immune system to replenish lymphocytes.

“It will be compelling to test whether the developmental pathways leading to cell specialization can be manipulated to favor production of specific lineage-biased MPPs in order to optimize blood recovery following hematopoietic injury or to rebalance the output of various cell lineages in an aging or deregulated blood system,” Dr Passegué said.

Hematopoietic stem cells

in the bone marrow

Scientists say they have identified a family of multipotent progenitor (MPP) cells that are the first to arise from hematopoietic stem cells (HSCs).

The team said their discovery, published in Cell Stem Cell, raises the possibility that, by manipulating the fates of MPPs or HSCs, researchers could one day help overcome imbalances and deficiencies that can arise in the blood system due to aging or leukemia.

Similar imbalances can render patients vulnerable immediately following HSC transplants, especially following umbilical cord transplants, said study author Emmanuelle Passegué, PhD, of the University of California San Francisco.

Via experiments in mice, Dr Passegué and her colleagues found that HSCs “make educated decisions” when it comes time to differentiate.

“Previously, researchers thought that the developmental paths of daughter cells were randomly specified by the HSC, but we conclude that the HSC normally responds appropriately to signals in the environment, making the different MPPs in parallel, but at different speeds and in different amounts to meet the body’s needs,” Dr Passegué said.

To uncover these findings, she and her colleagues investigated patterns of gene expression and cell signaling that determine which developmental paths are favored when relatively rare HSCs spin off daughter cells. The team also explored HSCs’ responses during transplant.

The researchers found that the first daughter cells that arise from HSCs are already distinct, favoring the development of different specialized cell lineages.

The team identified two types of daughter cells, MPP2 and MPP3, which, under normal conditions, are rare. These cells work together with more common daughter cells, MPP4 cells, to control blood production.

MPP2 cells favor the production of platelets and red blood cells, while MPP3 cells favor production of inflammatory cells.

MPP4 cells are the main producers of lymphocytes that fight specific disease pathogens, but the researchers showed that MPP4 cells can easily be re-educated to make many inflammatory cells when regenerative needs are high, as they are following a transplant.

The team found that, during transplant, regenerating HSCs limit their own self-renewal and instead go to work overproducing MPP2 and MPP3 cells that quickly produce needed red blood cells, platelets, and inflammatory cells. Only later does MPP4 production return to normal, enabling the immune system to replenish lymphocytes.

“It will be compelling to test whether the developmental pathways leading to cell specialization can be manipulated to favor production of specific lineage-biased MPPs in order to optimize blood recovery following hematopoietic injury or to rebalance the output of various cell lineages in an aging or deregulated blood system,” Dr Passegué said.

Hematopoietic stem cells

in the bone marrow

Scientists say they have identified a family of multipotent progenitor (MPP) cells that are the first to arise from hematopoietic stem cells (HSCs).

The team said their discovery, published in Cell Stem Cell, raises the possibility that, by manipulating the fates of MPPs or HSCs, researchers could one day help overcome imbalances and deficiencies that can arise in the blood system due to aging or leukemia.

Similar imbalances can render patients vulnerable immediately following HSC transplants, especially following umbilical cord transplants, said study author Emmanuelle Passegué, PhD, of the University of California San Francisco.

Via experiments in mice, Dr Passegué and her colleagues found that HSCs “make educated decisions” when it comes time to differentiate.

“Previously, researchers thought that the developmental paths of daughter cells were randomly specified by the HSC, but we conclude that the HSC normally responds appropriately to signals in the environment, making the different MPPs in parallel, but at different speeds and in different amounts to meet the body’s needs,” Dr Passegué said.

To uncover these findings, she and her colleagues investigated patterns of gene expression and cell signaling that determine which developmental paths are favored when relatively rare HSCs spin off daughter cells. The team also explored HSCs’ responses during transplant.

The researchers found that the first daughter cells that arise from HSCs are already distinct, favoring the development of different specialized cell lineages.

The team identified two types of daughter cells, MPP2 and MPP3, which, under normal conditions, are rare. These cells work together with more common daughter cells, MPP4 cells, to control blood production.

MPP2 cells favor the production of platelets and red blood cells, while MPP3 cells favor production of inflammatory cells.

MPP4 cells are the main producers of lymphocytes that fight specific disease pathogens, but the researchers showed that MPP4 cells can easily be re-educated to make many inflammatory cells when regenerative needs are high, as they are following a transplant.

The team found that, during transplant, regenerating HSCs limit their own self-renewal and instead go to work overproducing MPP2 and MPP3 cells that quickly produce needed red blood cells, platelets, and inflammatory cells. Only later does MPP4 production return to normal, enabling the immune system to replenish lymphocytes.

“It will be compelling to test whether the developmental pathways leading to cell specialization can be manipulated to favor production of specific lineage-biased MPPs in order to optimize blood recovery following hematopoietic injury or to rebalance the output of various cell lineages in an aging or deregulated blood system,” Dr Passegué said.

It is widely known and taught that maternal blood lipid levels increase slightly during pregnancy. Lipid values throughout pregnancy, however, have not been well described, making it difficult to ascertain which changes are normal and which changes may be potentially troubling for the mother and/or the baby.

Similarly, the association between pregnancy outcomes and lipid levels prior to conception and during pregnancy has been studied only minimally. In both areas, more research is needed.

Yet despite the need for more research, it now appears that the mother’s lipid profile – particularly her triglyceride levels before and during pregnancy – warrants our attention. Results from several clinical studies suggest that elevated maternal triglyceride (TG) levels may be associated with gestational diabetes mellitus (GDM) and preeclampsia. Since these conditions can contribute to the development of peri- and postpartum complications and increase the mother’s risk of developing subsequent type 2 diabetes and systemic hypertension, a mother’s lipid profile – just like her glucose levels – may help us define who is at high risk of pregnancy complications and later adverse effects.

Research findings

In addition to assessing fetal health during pregnancy, ob.gyns. routinely measure and monitor maternal blood pressure, weight gain, and blood sugar, which fluctuate during normal pregnancies.

We have found that lipid levels, notably maternal TG, total cholesterol, and the major particles of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) also vary during pregnancy, with a nadir during the first trimester, followed by a gradual increase and a peaking before delivery.

It is well known that severely elevated blood pressure, gestational weight, or glucose can signify a pregnancy at risk for adverse outcomes. However, our research has shown that high levels of TGs, but not the levels of HDLs, LDLs, or total cholesterol, during pregnancy also are associated with an increased risk for preeclampsia and gestational diabetes mellitus (Am. J. Obstet. Gynecol. 2009;201:482.e1-8).

In our study, the rate of preeclampsia or GDM increased with maternal TG level, from 7.2% in women who had the lowest levels (<25^th percentile) to 19.8% in women who had the highest levels (>75^th percentile).

We found that TG levels in the upper quartile also were associated with a significantly higher risk of preeclampsia, compared with the lower quartile (relative risk, 1.87).

Similarly, among women without diagnosed GDM, those with TG levels in the upper quartile were more likely to have a fasting glucose level of 100 mg/dL or more, compared with the intermediate group (TG level between the 25^th and 75^th percentiles) and the lower quartile. Women with the highest TG levels also were more likely to have infants classified as large for gestational age.

Our findings are consistent with a review that showed a positive association between elevated maternal TG and the risk of preeclampsia (BJOG 2006;113:379-86), as well as a cohort study that found plasma TG levels in the first trimester were independently and linearly associated with pregnancy-induced hypertension, preeclampsia, and large-for-gestational age (J. Clin. Endocrinol. Metab. 2012;97:3917-25).

Interestingly, the cohort study did not show an association between elevated maternal TG levels, adverse pregnancy outcomes, and body mass index. This suggests that weight gain and TG may be independent risk factors.

In practice

At this point in time, without defined cut-off values and well-tested interventions, there is no recommendation regarding maternal lipid measurement during pregnancy. We have shown, however, that maternal TG levels above 140 mg/dL at 3 months’ gestation and TG levels of 200 mg/dL or more at 6 months’ gestation are very high and may indicate a high-risk pregnancy.

Like all ob.gyns., we advise women before pregnancy to lose weight and to normalize blood glucose levels before attempting to conceive to reduce pregnancy complications, but we also encourage our patients to lower their TG levels. Given the observed associations between higher TG levels and adverse pregnancy outcomes, we now routinely measure maternal lipids as well as blood glucose in our pregnant patients. We also test lipid levels in pregnant women who have other risk factors such as GDM in a prior pregnancy or chronic high blood pressure.

It is possible that lifestyle programs (such as those involving diet, weight reduction, and physical activity) prior to and during pregnancy, with a focus not only on maintaining a healthy weight but also on lowering TG levels, may help to further prevent complications during pregnancy and adverse birth outcomes. Although more research is needed, lowering TGs with cholesterol-reducing drugs also may help improve pregnancy outcomes. Indeed, there is currently a study investigating the pharmacologic treatment of high lipids during pregnancy.

For now, we should advise our patients who have higher TG levels in pregnancy to improve their diets and levels of physical activity. We also should monitor these patients for the increased likelihood of developing GDM and preeclampsia because higher lipid profiles appear to equate to a higher risk of adverse outcomes.

Finally, our attention to lipid profiles should extend beyond birth, since the long-term risk of cardiovascular disease may be influenced by preeclampsia and potentially by the lipid changes that escalate with the condition.

Dr. Wiznitzer reported having no financial disclosures related to this Master Class.

It is widely known and taught that maternal blood lipid levels increase slightly during pregnancy. Lipid values throughout pregnancy, however, have not been well described, making it difficult to ascertain which changes are normal and which changes may be potentially troubling for the mother and/or the baby.

Similarly, the association between pregnancy outcomes and lipid levels prior to conception and during pregnancy has been studied only minimally. In both areas, more research is needed.

Yet despite the need for more research, it now appears that the mother’s lipid profile – particularly her triglyceride levels before and during pregnancy – warrants our attention. Results from several clinical studies suggest that elevated maternal triglyceride (TG) levels may be associated with gestational diabetes mellitus (GDM) and preeclampsia. Since these conditions can contribute to the development of peri- and postpartum complications and increase the mother’s risk of developing subsequent type 2 diabetes and systemic hypertension, a mother’s lipid profile – just like her glucose levels – may help us define who is at high risk of pregnancy complications and later adverse effects.

Research findings

In addition to assessing fetal health during pregnancy, ob.gyns. routinely measure and monitor maternal blood pressure, weight gain, and blood sugar, which fluctuate during normal pregnancies.

We have found that lipid levels, notably maternal TG, total cholesterol, and the major particles of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) also vary during pregnancy, with a nadir during the first trimester, followed by a gradual increase and a peaking before delivery.

It is well known that severely elevated blood pressure, gestational weight, or glucose can signify a pregnancy at risk for adverse outcomes. However, our research has shown that high levels of TGs, but not the levels of HDLs, LDLs, or total cholesterol, during pregnancy also are associated with an increased risk for preeclampsia and gestational diabetes mellitus (Am. J. Obstet. Gynecol. 2009;201:482.e1-8).

In our study, the rate of preeclampsia or GDM increased with maternal TG level, from 7.2% in women who had the lowest levels (<25^th percentile) to 19.8% in women who had the highest levels (>75^th percentile).

We found that TG levels in the upper quartile also were associated with a significantly higher risk of preeclampsia, compared with the lower quartile (relative risk, 1.87).

Similarly, among women without diagnosed GDM, those with TG levels in the upper quartile were more likely to have a fasting glucose level of 100 mg/dL or more, compared with the intermediate group (TG level between the 25^th and 75^th percentiles) and the lower quartile. Women with the highest TG levels also were more likely to have infants classified as large for gestational age.

Our findings are consistent with a review that showed a positive association between elevated maternal TG and the risk of preeclampsia (BJOG 2006;113:379-86), as well as a cohort study that found plasma TG levels in the first trimester were independently and linearly associated with pregnancy-induced hypertension, preeclampsia, and large-for-gestational age (J. Clin. Endocrinol. Metab. 2012;97:3917-25).

Interestingly, the cohort study did not show an association between elevated maternal TG levels, adverse pregnancy outcomes, and body mass index. This suggests that weight gain and TG may be independent risk factors.

In practice

At this point in time, without defined cut-off values and well-tested interventions, there is no recommendation regarding maternal lipid measurement during pregnancy. We have shown, however, that maternal TG levels above 140 mg/dL at 3 months’ gestation and TG levels of 200 mg/dL or more at 6 months’ gestation are very high and may indicate a high-risk pregnancy.

Like all ob.gyns., we advise women before pregnancy to lose weight and to normalize blood glucose levels before attempting to conceive to reduce pregnancy complications, but we also encourage our patients to lower their TG levels. Given the observed associations between higher TG levels and adverse pregnancy outcomes, we now routinely measure maternal lipids as well as blood glucose in our pregnant patients. We also test lipid levels in pregnant women who have other risk factors such as GDM in a prior pregnancy or chronic high blood pressure.

It is possible that lifestyle programs (such as those involving diet, weight reduction, and physical activity) prior to and during pregnancy, with a focus not only on maintaining a healthy weight but also on lowering TG levels, may help to further prevent complications during pregnancy and adverse birth outcomes. Although more research is needed, lowering TGs with cholesterol-reducing drugs also may help improve pregnancy outcomes. Indeed, there is currently a study investigating the pharmacologic treatment of high lipids during pregnancy.

For now, we should advise our patients who have higher TG levels in pregnancy to improve their diets and levels of physical activity. We also should monitor these patients for the increased likelihood of developing GDM and preeclampsia because higher lipid profiles appear to equate to a higher risk of adverse outcomes.

Finally, our attention to lipid profiles should extend beyond birth, since the long-term risk of cardiovascular disease may be influenced by preeclampsia and potentially by the lipid changes that escalate with the condition.

Dr. Wiznitzer reported having no financial disclosures related to this Master Class.

It is widely known and taught that maternal blood lipid levels increase slightly during pregnancy. Lipid values throughout pregnancy, however, have not been well described, making it difficult to ascertain which changes are normal and which changes may be potentially troubling for the mother and/or the baby.

Similarly, the association between pregnancy outcomes and lipid levels prior to conception and during pregnancy has been studied only minimally. In both areas, more research is needed.

Yet despite the need for more research, it now appears that the mother’s lipid profile – particularly her triglyceride levels before and during pregnancy – warrants our attention. Results from several clinical studies suggest that elevated maternal triglyceride (TG) levels may be associated with gestational diabetes mellitus (GDM) and preeclampsia. Since these conditions can contribute to the development of peri- and postpartum complications and increase the mother’s risk of developing subsequent type 2 diabetes and systemic hypertension, a mother’s lipid profile – just like her glucose levels – may help us define who is at high risk of pregnancy complications and later adverse effects.

Research findings

In addition to assessing fetal health during pregnancy, ob.gyns. routinely measure and monitor maternal blood pressure, weight gain, and blood sugar, which fluctuate during normal pregnancies.

We have found that lipid levels, notably maternal TG, total cholesterol, and the major particles of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) also vary during pregnancy, with a nadir during the first trimester, followed by a gradual increase and a peaking before delivery.

It is well known that severely elevated blood pressure, gestational weight, or glucose can signify a pregnancy at risk for adverse outcomes. However, our research has shown that high levels of TGs, but not the levels of HDLs, LDLs, or total cholesterol, during pregnancy also are associated with an increased risk for preeclampsia and gestational diabetes mellitus (Am. J. Obstet. Gynecol. 2009;201:482.e1-8).

In our study, the rate of preeclampsia or GDM increased with maternal TG level, from 7.2% in women who had the lowest levels (<25^th percentile) to 19.8% in women who had the highest levels (>75^th percentile).

We found that TG levels in the upper quartile also were associated with a significantly higher risk of preeclampsia, compared with the lower quartile (relative risk, 1.87).

Similarly, among women without diagnosed GDM, those with TG levels in the upper quartile were more likely to have a fasting glucose level of 100 mg/dL or more, compared with the intermediate group (TG level between the 25^th and 75^th percentiles) and the lower quartile. Women with the highest TG levels also were more likely to have infants classified as large for gestational age.

Our findings are consistent with a review that showed a positive association between elevated maternal TG and the risk of preeclampsia (BJOG 2006;113:379-86), as well as a cohort study that found plasma TG levels in the first trimester were independently and linearly associated with pregnancy-induced hypertension, preeclampsia, and large-for-gestational age (J. Clin. Endocrinol. Metab. 2012;97:3917-25).

Interestingly, the cohort study did not show an association between elevated maternal TG levels, adverse pregnancy outcomes, and body mass index. This suggests that weight gain and TG may be independent risk factors.

In practice

At this point in time, without defined cut-off values and well-tested interventions, there is no recommendation regarding maternal lipid measurement during pregnancy. We have shown, however, that maternal TG levels above 140 mg/dL at 3 months’ gestation and TG levels of 200 mg/dL or more at 6 months’ gestation are very high and may indicate a high-risk pregnancy.

Like all ob.gyns., we advise women before pregnancy to lose weight and to normalize blood glucose levels before attempting to conceive to reduce pregnancy complications, but we also encourage our patients to lower their TG levels. Given the observed associations between higher TG levels and adverse pregnancy outcomes, we now routinely measure maternal lipids as well as blood glucose in our pregnant patients. We also test lipid levels in pregnant women who have other risk factors such as GDM in a prior pregnancy or chronic high blood pressure.

It is possible that lifestyle programs (such as those involving diet, weight reduction, and physical activity) prior to and during pregnancy, with a focus not only on maintaining a healthy weight but also on lowering TG levels, may help to further prevent complications during pregnancy and adverse birth outcomes. Although more research is needed, lowering TGs with cholesterol-reducing drugs also may help improve pregnancy outcomes. Indeed, there is currently a study investigating the pharmacologic treatment of high lipids during pregnancy.

For now, we should advise our patients who have higher TG levels in pregnancy to improve their diets and levels of physical activity. We also should monitor these patients for the increased likelihood of developing GDM and preeclampsia because higher lipid profiles appear to equate to a higher risk of adverse outcomes.

Finally, our attention to lipid profiles should extend beyond birth, since the long-term risk of cardiovascular disease may be influenced by preeclampsia and potentially by the lipid changes that escalate with the condition.

Dr. Wiznitzer reported having no financial disclosures related to this Master Class.

As ob.gyns., we often focus on optimizing our patients’ reproductive health. Research has shown, however, that the condition of a woman’s health prior to conception can be just as – if not more – important to her pregnancy and her lifelong well-being. For example, we have established that women who take the daily recommended dose of folic acid (400 mcg), even outside of pregnancy, have a reduced risk for neural tube defects in their infants.

Last year, we devoted a series of Master Class columns to the crucial need to properly manage maternal weight gain and blood sugar levels before, during, and after gestation to improve pregnancy outcomes. We also have seen that intensive glycemic and weight control in women can reduce their risk of fetal and maternal complications.

However, the leading causes of morbidity and mortality remain cardiovascular diseases, both in the developing and developed world. One of the key contributors to poor heart and vascular health is high cholesterol. Although the body needs cholesterol, just as it needs sugar, excess lipids in the blood can lead to infarction and stroke.

According to the U.S. Centers for Disease Control and Prevention, the desirable total cholesterol levels, including low- and high-density lipids and triglycerides, for men and nonpregnant women fall below 200 mg/dL. What remain less clear are the desired lipid levels for pregnant women.

We have known for decades that cholesterol concentrations increase during pregnancy, possibly by as much as 50%. We do not, however, have a firm understanding of what may constitute normally higher lipid concentrations and what may signal risk to the health of the baby or mother. Additionally, while we may run a lipid panel when we order a blood test, ob.gyns. do not routinely monitor a women’s cholesterol.

Since excess lipids, obesity, and heart disease often occur in the same patient and have become increasingly prevalent in our society, it may be time to reexamine any correlations between maternal lipid levels and adverse pregnancy outcomes.

To comment on this reemerging area, we invited Dr. Arnon Wiznitzer, professor and chairman of the department of obstetrics and gynecology at Helen Schneider Hospital for Women and deputy director of the Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University. Dr. Wiznitzer’s extensive experience working with women who have diabetes in pregnancy led him to examine other comorbidities, including lipids, which might confound good pregnancy outcomes.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

As ob.gyns., we often focus on optimizing our patients’ reproductive health. Research has shown, however, that the condition of a woman’s health prior to conception can be just as – if not more – important to her pregnancy and her lifelong well-being. For example, we have established that women who take the daily recommended dose of folic acid (400 mcg), even outside of pregnancy, have a reduced risk for neural tube defects in their infants.

Last year, we devoted a series of Master Class columns to the crucial need to properly manage maternal weight gain and blood sugar levels before, during, and after gestation to improve pregnancy outcomes. We also have seen that intensive glycemic and weight control in women can reduce their risk of fetal and maternal complications.

However, the leading causes of morbidity and mortality remain cardiovascular diseases, both in the developing and developed world. One of the key contributors to poor heart and vascular health is high cholesterol. Although the body needs cholesterol, just as it needs sugar, excess lipids in the blood can lead to infarction and stroke.

According to the U.S. Centers for Disease Control and Prevention, the desirable total cholesterol levels, including low- and high-density lipids and triglycerides, for men and nonpregnant women fall below 200 mg/dL. What remain less clear are the desired lipid levels for pregnant women.

We have known for decades that cholesterol concentrations increase during pregnancy, possibly by as much as 50%. We do not, however, have a firm understanding of what may constitute normally higher lipid concentrations and what may signal risk to the health of the baby or mother. Additionally, while we may run a lipid panel when we order a blood test, ob.gyns. do not routinely monitor a women’s cholesterol.

Since excess lipids, obesity, and heart disease often occur in the same patient and have become increasingly prevalent in our society, it may be time to reexamine any correlations between maternal lipid levels and adverse pregnancy outcomes.

To comment on this reemerging area, we invited Dr. Arnon Wiznitzer, professor and chairman of the department of obstetrics and gynecology at Helen Schneider Hospital for Women and deputy director of the Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University. Dr. Wiznitzer’s extensive experience working with women who have diabetes in pregnancy led him to examine other comorbidities, including lipids, which might confound good pregnancy outcomes.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

As ob.gyns., we often focus on optimizing our patients’ reproductive health. Research has shown, however, that the condition of a woman’s health prior to conception can be just as – if not more – important to her pregnancy and her lifelong well-being. For example, we have established that women who take the daily recommended dose of folic acid (400 mcg), even outside of pregnancy, have a reduced risk for neural tube defects in their infants.

Last year, we devoted a series of Master Class columns to the crucial need to properly manage maternal weight gain and blood sugar levels before, during, and after gestation to improve pregnancy outcomes. We also have seen that intensive glycemic and weight control in women can reduce their risk of fetal and maternal complications.

However, the leading causes of morbidity and mortality remain cardiovascular diseases, both in the developing and developed world. One of the key contributors to poor heart and vascular health is high cholesterol. Although the body needs cholesterol, just as it needs sugar, excess lipids in the blood can lead to infarction and stroke.

According to the U.S. Centers for Disease Control and Prevention, the desirable total cholesterol levels, including low- and high-density lipids and triglycerides, for men and nonpregnant women fall below 200 mg/dL. What remain less clear are the desired lipid levels for pregnant women.

We have known for decades that cholesterol concentrations increase during pregnancy, possibly by as much as 50%. We do not, however, have a firm understanding of what may constitute normally higher lipid concentrations and what may signal risk to the health of the baby or mother. Additionally, while we may run a lipid panel when we order a blood test, ob.gyns. do not routinely monitor a women’s cholesterol.

Since excess lipids, obesity, and heart disease often occur in the same patient and have become increasingly prevalent in our society, it may be time to reexamine any correlations between maternal lipid levels and adverse pregnancy outcomes.

To comment on this reemerging area, we invited Dr. Arnon Wiznitzer, professor and chairman of the department of obstetrics and gynecology at Helen Schneider Hospital for Women and deputy director of the Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University. Dr. Wiznitzer’s extensive experience working with women who have diabetes in pregnancy led him to examine other comorbidities, including lipids, which might confound good pregnancy outcomes.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Doctor and patient

Photo courtesy of NIH

VIENNA—A 2-drug combination can produce complete responses (CRs) in elderly patients with newly diagnosed acute myeloid leukemia (AML), but whether the treatment confers a survival benefit remains to be seen.

The combination consists of the HDAC inhibitor pracinostat and the antineoplastic agent azacitidine.

In a phase 2 study, the treatment produced CRs in nearly a third of AML patients, and follow-up has shown that responses improve over time.

However, the median overall survival has not been reached.

“The combination of pracinostat and azacitidine continues to demonstrate compelling clinical activity in these elderly patients with newly diagnosed AML,” said Daniel P. Gold, PhD, President and Chief Executive Officer of MEI Pharma, the company developing pracinostat.

“While the overall survival trend in this study is encouraging, we believe that longer follow-up is needed to gain an accurate survival estimate. Ultimately, this survival estimate will be critical in determining the development path forward for this combination. We look forward to providing an update when these data mature, which we expect to occur later this year.”

The current data were presented at the 20th Congress of the European Hematology Association (abstract P568*). The trial was sponsored by MEI Pharma.

The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML. Fifty-four percent of patients had intermediate-risk cytogenetics, 42% had high-risk, and 4% were not evaluable.

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

To date, half of patients have discontinued treatment, 8% due to death, 36% because of progressive disease, 32% due to adverse events, and 24% for other reasons.

Response and survival

Thus far, 54% of patients (n=27) have achieved the primary endpoint of CR plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).

Thirty-two percent of patients had a CR, 14% had a CRi, 8% achieved MLFS, and 6% had a partial response (PR) or PR with incomplete count recovery (PRi).

Among the 27 patients with intermediate-risk cytogenetics, 63% achieved a CR/CRi/MLFS, and 7% had a PR/PRi. Among the 21 patients with high-risk cytogenetics, 48% achieved a CR/CRi/MLFS, and none had a PR/PRi.

The researchers said these response rates compare favorably with previous studies of azacitidine alone in this patient population. In this trial, most responses occurred within the first 2 cycles of therapy and continued to improve with ongoing therapy.

The median overall survival has not yet been reached. Sixty-four percent of patients (n=32) are still being followed (range, 6-15 months).

The survival rate of patients with intermediate-risk cytogenetics appears greater than that for patients with high-risk cytogenetics, though neither subset of patients has reached median survival.

The 60-day mortality rate was 10% (n=5).

Safety and tolerability

The most common treatment-emergent adverse events (AEs) were nausea (66%), constipation (58%), fatigue (48%), febrile neutropenia (40%), thrombocytopenia (32%), diarrhea (30%), vomiting (28%), decreased appetite (28%), anemia (26%), hypokalemia (26%), neutropenia (24%), pyrexia (24%), dizziness (24%), dyspnea (24%), and rash (20%).

Treatment-emergent AEs led to discontinuation in 8 patients. Two of these patients developed sepsis that proved fatal.

The other events included grade 3 peripheral motor neuropathy (which was resolved), grade 3 parainfluenza (resolved with sequelae), grade 3 prolonged QTc/atrial fibrillation (resolved), grade 2 failure to thrive (not resolved), grade 3 mucositis (not resolved), and grade 2 fatigue (not resolved).

AEs resulting in dose reductions were frequently due to disease, according to the researchers.

The team also noted that nearly half of the patients in this study (n=22) have received pracinostat and azacitidine beyond 6 months, and 5 patients have received it for more than a year, which reflects long-term tolerability.

*Information in the abstract differs from that presented at the meeting.

Doctor and patient

Photo courtesy of NIH

VIENNA—A 2-drug combination can produce complete responses (CRs) in elderly patients with newly diagnosed acute myeloid leukemia (AML), but whether the treatment confers a survival benefit remains to be seen.

The combination consists of the HDAC inhibitor pracinostat and the antineoplastic agent azacitidine.

In a phase 2 study, the treatment produced CRs in nearly a third of AML patients, and follow-up has shown that responses improve over time.

However, the median overall survival has not been reached.

“The combination of pracinostat and azacitidine continues to demonstrate compelling clinical activity in these elderly patients with newly diagnosed AML,” said Daniel P. Gold, PhD, President and Chief Executive Officer of MEI Pharma, the company developing pracinostat.

“While the overall survival trend in this study is encouraging, we believe that longer follow-up is needed to gain an accurate survival estimate. Ultimately, this survival estimate will be critical in determining the development path forward for this combination. We look forward to providing an update when these data mature, which we expect to occur later this year.”

The current data were presented at the 20th Congress of the European Hematology Association (abstract P568*). The trial was sponsored by MEI Pharma.

The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML. Fifty-four percent of patients had intermediate-risk cytogenetics, 42% had high-risk, and 4% were not evaluable.

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

To date, half of patients have discontinued treatment, 8% due to death, 36% because of progressive disease, 32% due to adverse events, and 24% for other reasons.

Response and survival

Thus far, 54% of patients (n=27) have achieved the primary endpoint of CR plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).

Thirty-two percent of patients had a CR, 14% had a CRi, 8% achieved MLFS, and 6% had a partial response (PR) or PR with incomplete count recovery (PRi).

Among the 27 patients with intermediate-risk cytogenetics, 63% achieved a CR/CRi/MLFS, and 7% had a PR/PRi. Among the 21 patients with high-risk cytogenetics, 48% achieved a CR/CRi/MLFS, and none had a PR/PRi.

The researchers said these response rates compare favorably with previous studies of azacitidine alone in this patient population. In this trial, most responses occurred within the first 2 cycles of therapy and continued to improve with ongoing therapy.

The median overall survival has not yet been reached. Sixty-four percent of patients (n=32) are still being followed (range, 6-15 months).

The survival rate of patients with intermediate-risk cytogenetics appears greater than that for patients with high-risk cytogenetics, though neither subset of patients has reached median survival.

The 60-day mortality rate was 10% (n=5).

Safety and tolerability

The most common treatment-emergent adverse events (AEs) were nausea (66%), constipation (58%), fatigue (48%), febrile neutropenia (40%), thrombocytopenia (32%), diarrhea (30%), vomiting (28%), decreased appetite (28%), anemia (26%), hypokalemia (26%), neutropenia (24%), pyrexia (24%), dizziness (24%), dyspnea (24%), and rash (20%).

Treatment-emergent AEs led to discontinuation in 8 patients. Two of these patients developed sepsis that proved fatal.

The other events included grade 3 peripheral motor neuropathy (which was resolved), grade 3 parainfluenza (resolved with sequelae), grade 3 prolonged QTc/atrial fibrillation (resolved), grade 2 failure to thrive (not resolved), grade 3 mucositis (not resolved), and grade 2 fatigue (not resolved).

AEs resulting in dose reductions were frequently due to disease, according to the researchers.

The team also noted that nearly half of the patients in this study (n=22) have received pracinostat and azacitidine beyond 6 months, and 5 patients have received it for more than a year, which reflects long-term tolerability.

*Information in the abstract differs from that presented at the meeting.

Doctor and patient

Photo courtesy of NIH

VIENNA—A 2-drug combination can produce complete responses (CRs) in elderly patients with newly diagnosed acute myeloid leukemia (AML), but whether the treatment confers a survival benefit remains to be seen.

The combination consists of the HDAC inhibitor pracinostat and the antineoplastic agent azacitidine.

In a phase 2 study, the treatment produced CRs in nearly a third of AML patients, and follow-up has shown that responses improve over time.

However, the median overall survival has not been reached.

“The combination of pracinostat and azacitidine continues to demonstrate compelling clinical activity in these elderly patients with newly diagnosed AML,” said Daniel P. Gold, PhD, President and Chief Executive Officer of MEI Pharma, the company developing pracinostat.

“While the overall survival trend in this study is encouraging, we believe that longer follow-up is needed to gain an accurate survival estimate. Ultimately, this survival estimate will be critical in determining the development path forward for this combination. We look forward to providing an update when these data mature, which we expect to occur later this year.”

The current data were presented at the 20th Congress of the European Hematology Association (abstract P568*). The trial was sponsored by MEI Pharma.

The study included 50 patients who had a median age of 75 (range, 66-84). Sixty-six percent of patients had de novo AML, and 34% had secondary AML. Fifty-four percent of patients had intermediate-risk cytogenetics, 42% had high-risk, and 4% were not evaluable.

The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.

To date, half of patients have discontinued treatment, 8% due to death, 36% because of progressive disease, 32% due to adverse events, and 24% for other reasons.

Response and survival

Thus far, 54% of patients (n=27) have achieved the primary endpoint of CR plus CR with incomplete count recovery (CRi) plus morphologic leukemia-free state (MLFS).

Thirty-two percent of patients had a CR, 14% had a CRi, 8% achieved MLFS, and 6% had a partial response (PR) or PR with incomplete count recovery (PRi).

Among the 27 patients with intermediate-risk cytogenetics, 63% achieved a CR/CRi/MLFS, and 7% had a PR/PRi. Among the 21 patients with high-risk cytogenetics, 48% achieved a CR/CRi/MLFS, and none had a PR/PRi.

The researchers said these response rates compare favorably with previous studies of azacitidine alone in this patient population. In this trial, most responses occurred within the first 2 cycles of therapy and continued to improve with ongoing therapy.

The median overall survival has not yet been reached. Sixty-four percent of patients (n=32) are still being followed (range, 6-15 months).

The survival rate of patients with intermediate-risk cytogenetics appears greater than that for patients with high-risk cytogenetics, though neither subset of patients has reached median survival.

The 60-day mortality rate was 10% (n=5).

Safety and tolerability

The most common treatment-emergent adverse events (AEs) were nausea (66%), constipation (58%), fatigue (48%), febrile neutropenia (40%), thrombocytopenia (32%), diarrhea (30%), vomiting (28%), decreased appetite (28%), anemia (26%), hypokalemia (26%), neutropenia (24%), pyrexia (24%), dizziness (24%), dyspnea (24%), and rash (20%).

Treatment-emergent AEs led to discontinuation in 8 patients. Two of these patients developed sepsis that proved fatal.

The other events included grade 3 peripheral motor neuropathy (which was resolved), grade 3 parainfluenza (resolved with sequelae), grade 3 prolonged QTc/atrial fibrillation (resolved), grade 2 failure to thrive (not resolved), grade 3 mucositis (not resolved), and grade 2 fatigue (not resolved).

AEs resulting in dose reductions were frequently due to disease, according to the researchers.

The team also noted that nearly half of the patients in this study (n=22) have received pracinostat and azacitidine beyond 6 months, and 5 patients have received it for more than a year, which reflects long-term tolerability.

*Information in the abstract differs from that presented at the meeting.

I was 7 years old when my family got its first television. I can’t recall the year, but I know that we were one of the last houses in our neighborhood to have a color TV. As parents, my wife and I kept our children on a moderate viewing diet, mostly “Captain Kangaroo” and “Sesame Street” when they were young. Until they were teenagers, they believed that only televisions in motel rooms received cartoons. Now, as parents, they are more restrictive with their children than we were with them. One family doesn’t even own a television.

A few years ago, my wife and I cut back our cable service to “basic” and, other than a few sporting events and a rare show on PBS, our TV sits unused in our living room. Five months out of the year, we have no television at all – when we’re in our cottage by the ocean.

Our trajectory from being enthusiastic viewers to television abstainers seems to be not that unusual among our peers. At dinner parties, I often hear, “There is nothing worth watching on television. It’s all junk and commercials.” Could the same condemnation be voiced about television for young children? Could there be some benefit for preschoolers in watching an “educational” show such as “Sesame Street”? Or is it all garbage, even for the very young?

A recently and much ballyhooed study by two economists suggests that, at least as “Sesame Street” is concerned, television can have a positive effect on young children. You may have read the headline: “Study: Kids can learn as much from ‘Sesame Street’ as from preschool” (Washington Post, June 7, 2015).

The researchers exploited a quirk of the precable landscape when some markets could not tune into some shows, including “Sesame Street,” because they were receiving only a UHF signal. Analyzing the data over several years, the economists found that, in communities where children had the opportunity to watch “Sesame Street,” those children had a “14% drop in the likelihood of being behind in school.” That association appeared to fade by the time the children reached high school. To claim that “Sesame Street” is at least as good as preschool based on these numbers seems to me to be a bit of a stretch. It may be that UHF-watching kids watched more professional wrestling, and this encouraged them to be more disruptive in school.

We must remember that these researchers are economists, and we should take anything they conclude with a grain of salt. But let’s say that there may be something to their conclusion that there is an association between “Sesame Street” viewing and school readiness. Does this mean that we should be developing more shows on the “Sesame Street” model, and that young children should be watching educational television several hours a day? Is there a dose effect? Or does this apparent association simply suggest that we should be improving preschools?

For decades, pediatricians and the American Academy of Pediatrics were focused on content and giving too little attention to the amount of screen time. This has improved slightly in the last few years, but the fact remains that television is a passive and sedentary activity that is threatening the health of our nation. It is robbing millions of Americans of precious hours of restorative sleep. It is giving even more millions an easy and addictive way to avoid doing something else. Instead, the addicts spend hours each day watching other people doing something. I always have suspected that the introduction of color to television is the culprit. Black-and-white TV was interesting to a point, but I don’t recall it being addictive. Most of us will watch for hours anything that is colorful and moves.

“Sesame Street” is and has been a wonderful show, and I suspect it has helped millions of children learn things they may not have been exposed to at home. But in one sense, educational programming could be considered a gateway drug. Once the set goes on, many parents don’t have the fortitude to shut it off. We should think twice before claiming that it is on a par with preschool.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

I was 7 years old when my family got its first television. I can’t recall the year, but I know that we were one of the last houses in our neighborhood to have a color TV. As parents, my wife and I kept our children on a moderate viewing diet, mostly “Captain Kangaroo” and “Sesame Street” when they were young. Until they were teenagers, they believed that only televisions in motel rooms received cartoons. Now, as parents, they are more restrictive with their children than we were with them. One family doesn’t even own a television.

A few years ago, my wife and I cut back our cable service to “basic” and, other than a few sporting events and a rare show on PBS, our TV sits unused in our living room. Five months out of the year, we have no television at all – when we’re in our cottage by the ocean.

Our trajectory from being enthusiastic viewers to television abstainers seems to be not that unusual among our peers. At dinner parties, I often hear, “There is nothing worth watching on television. It’s all junk and commercials.” Could the same condemnation be voiced about television for young children? Could there be some benefit for preschoolers in watching an “educational” show such as “Sesame Street”? Or is it all garbage, even for the very young?

A recently and much ballyhooed study by two economists suggests that, at least as “Sesame Street” is concerned, television can have a positive effect on young children. You may have read the headline: “Study: Kids can learn as much from ‘Sesame Street’ as from preschool” (Washington Post, June 7, 2015).

The researchers exploited a quirk of the precable landscape when some markets could not tune into some shows, including “Sesame Street,” because they were receiving only a UHF signal. Analyzing the data over several years, the economists found that, in communities where children had the opportunity to watch “Sesame Street,” those children had a “14% drop in the likelihood of being behind in school.” That association appeared to fade by the time the children reached high school. To claim that “Sesame Street” is at least as good as preschool based on these numbers seems to me to be a bit of a stretch. It may be that UHF-watching kids watched more professional wrestling, and this encouraged them to be more disruptive in school.

We must remember that these researchers are economists, and we should take anything they conclude with a grain of salt. But let’s say that there may be something to their conclusion that there is an association between “Sesame Street” viewing and school readiness. Does this mean that we should be developing more shows on the “Sesame Street” model, and that young children should be watching educational television several hours a day? Is there a dose effect? Or does this apparent association simply suggest that we should be improving preschools?

For decades, pediatricians and the American Academy of Pediatrics were focused on content and giving too little attention to the amount of screen time. This has improved slightly in the last few years, but the fact remains that television is a passive and sedentary activity that is threatening the health of our nation. It is robbing millions of Americans of precious hours of restorative sleep. It is giving even more millions an easy and addictive way to avoid doing something else. Instead, the addicts spend hours each day watching other people doing something. I always have suspected that the introduction of color to television is the culprit. Black-and-white TV was interesting to a point, but I don’t recall it being addictive. Most of us will watch for hours anything that is colorful and moves.

“Sesame Street” is and has been a wonderful show, and I suspect it has helped millions of children learn things they may not have been exposed to at home. But in one sense, educational programming could be considered a gateway drug. Once the set goes on, many parents don’t have the fortitude to shut it off. We should think twice before claiming that it is on a par with preschool.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

I was 7 years old when my family got its first television. I can’t recall the year, but I know that we were one of the last houses in our neighborhood to have a color TV. As parents, my wife and I kept our children on a moderate viewing diet, mostly “Captain Kangaroo” and “Sesame Street” when they were young. Until they were teenagers, they believed that only televisions in motel rooms received cartoons. Now, as parents, they are more restrictive with their children than we were with them. One family doesn’t even own a television.

A few years ago, my wife and I cut back our cable service to “basic” and, other than a few sporting events and a rare show on PBS, our TV sits unused in our living room. Five months out of the year, we have no television at all – when we’re in our cottage by the ocean.

Our trajectory from being enthusiastic viewers to television abstainers seems to be not that unusual among our peers. At dinner parties, I often hear, “There is nothing worth watching on television. It’s all junk and commercials.” Could the same condemnation be voiced about television for young children? Could there be some benefit for preschoolers in watching an “educational” show such as “Sesame Street”? Or is it all garbage, even for the very young?

A recently and much ballyhooed study by two economists suggests that, at least as “Sesame Street” is concerned, television can have a positive effect on young children. You may have read the headline: “Study: Kids can learn as much from ‘Sesame Street’ as from preschool” (Washington Post, June 7, 2015).

The researchers exploited a quirk of the precable landscape when some markets could not tune into some shows, including “Sesame Street,” because they were receiving only a UHF signal. Analyzing the data over several years, the economists found that, in communities where children had the opportunity to watch “Sesame Street,” those children had a “14% drop in the likelihood of being behind in school.” That association appeared to fade by the time the children reached high school. To claim that “Sesame Street” is at least as good as preschool based on these numbers seems to me to be a bit of a stretch. It may be that UHF-watching kids watched more professional wrestling, and this encouraged them to be more disruptive in school.

We must remember that these researchers are economists, and we should take anything they conclude with a grain of salt. But let’s say that there may be something to their conclusion that there is an association between “Sesame Street” viewing and school readiness. Does this mean that we should be developing more shows on the “Sesame Street” model, and that young children should be watching educational television several hours a day? Is there a dose effect? Or does this apparent association simply suggest that we should be improving preschools?

For decades, pediatricians and the American Academy of Pediatrics were focused on content and giving too little attention to the amount of screen time. This has improved slightly in the last few years, but the fact remains that television is a passive and sedentary activity that is threatening the health of our nation. It is robbing millions of Americans of precious hours of restorative sleep. It is giving even more millions an easy and addictive way to avoid doing something else. Instead, the addicts spend hours each day watching other people doing something. I always have suspected that the introduction of color to television is the culprit. Black-and-white TV was interesting to a point, but I don’t recall it being addictive. Most of us will watch for hours anything that is colorful and moves.

“Sesame Street” is and has been a wonderful show, and I suspect it has helped millions of children learn things they may not have been exposed to at home. But in one sense, educational programming could be considered a gateway drug. Once the set goes on, many parents don’t have the fortitude to shut it off. We should think twice before claiming that it is on a par with preschool.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.”

As late as mid-April 2015, a survey of 121 orthopedic practices indicated that 30% had done nothing to start preparing for ICD-10 (International Classification of Diseases, Tenth Revision).¹  That’s scary. And even the practices that had begun to prepare had not completed a number of key tasks (Figure 1).

Certainly, the will-they-or-won’t-they possibility of another congressional delay had many practices sitting on their hands this year. But now that the October 1, 2015, implementation is set in stone, this lack of inertia has many practices woefully behind. If your practice is one of many that hasn’t mapped your common ICD-9 (International Classification of Diseases, Ninth Revision) codes to ICD-10 codes, completed payer testing, or attended training, it’s time for a “full-court press.”

Being unprepared for ICD-10 will cause more than just an increase in claim denials. If your surgery schedule is booked a few months out, your staff will need to pre-authorize cases using ICD-10 as early as August 1—and they won’t be able to do that if you haven’t dictated the clinical terms required to choose an ICD-10 code. Without an understanding of ICD-10, severity of illness coding will suffer, and that will affect your bundled and value-based payments. And, if you don’t provide an adequate diagnosis when sending patients off-site for physical therapy, you’ll soon be getting phone calls from their billing staff demanding more specifics.

The clock is ticking and time is short. Here’s a prioritized list of what needs to get done.

1. Generate an ICD-9 frequency report

Identifying which diagnosis codes are the most frequently used, and therefore drive a significant portion of practice revenue, is an absolute must. The data will help prioritize training and code-mapping activities.

Most practices generate Current Procedural Terminology (CPT) code-frequency reports regularly, but few have ever run an ICD-9 code-frequency report. Call your vendor and ask for assistance, as there are multiple ways to run this report and they vary by practice management system. Sort the data elements and generate the ICD-9 frequency report by:

• Primary diagnosis.
• Unique patient.
• Revenue. (If your practice management system can’t give you diagnosis data by revenue, which enables you to focus on the codes that generate the most revenue, generate it by charges.)

The result should be a report that identifies the 20 to 25 diagnosis codes (or charges, depending on the reports generated) that drive the most revenue for the practice. Use the data to focus and prioritize your training and code-mapping activities.

 2. Schedule training

Forget about “general” ICD-10 training courses. You need orthopedic-specific guidance. That’s because ICD-10 for orthopedics is more complex than for other specialties. Dictating fractures under ICD-10 is not so simple. Selecting an injury code requires confidence in correctly using the seventh character.

“Everyone who uses diagnosis codes must have baseline knowledge: surgeons, billing staff, surgical coordinators, and clinical team,” according to Sarah Wiskerchen, MBA, CPC, consultant and ICD-10 educator with KarenZupko & Associates (KZA). Training must include the practical details of ICD-10, such as assigning laterality, understanding the system architecture, and limiting the use of unspecified codes.

The American Academy of Orthopaedic Surgeons (AAOS) offers a self-paced, online training series that provides details for the top 3 diagnosis codes for each subspecialty. The 10-program course, ICD-10-CM: By the Numbers, is available at www.aaos.org ($299 for members, $399 for nonmembers). If you prefer live instruction, there is one more AAOS-sponsored, regional ICD-10 workshop left before the October 1 deadline, and more may be added. (Details at www.karenzupko.com)

These courses provide highly specific and granular ICD-10 knowledge and incorporate the use of Code-X, an AAOS-developed software tool. They also feature tools for handling the complexities of fractures and injury codes, such as Leo C. Far, an acronym developed by KZA consultant and coding educator Margie Maley, BSN, MS, to make ICD-10 diagnosis coding for fractures easier (Figure 2).

Some subspecialty societies also offer ICD-10 training. The American Society for Surgery of the Hand (www.assh.org), for example, offers a series of webinars and member-developed ICD-9-to-ICD-10 code maps.  

 3. Crosswalk your common codes from ICD-9 to ICD-10

Crosswalking is the process of mapping your most commonly used ICD-9 codes to their equivalent ICD-10 codes. This exercise familiarizes your team with ICD-10 language and terms, and gives a sense of which ICD-9 codes expand to just 1 or 2 ICD-10 codes and which codes expand into 10 or more codes—as some injury codes do (Table).

“Attempting to map the codes before completing ICD-10 training is like trying to write a letter in Greek when you only speak English,” Wiskerchen warns. “So start this process after at least some of your team have grasped the fundamentals of ICD-10.” This is where the data from your ICD-9 frequency report comes in. Use it to prioritize which codes to map first with a goal of mapping your top 25 ICD-9 codes to their ICD-10 equivalents by August 31.

Invest in good tools to support your mapping efforts. Avoid general mapping equivalent (GEM) coding tools, which are free for a good reason—they are incomplete and don’t always lead you to the correct ICD-10 code. Instead, purchase resources from credible sources, such as the American Medical Association (AMA; www.ama-assn.org). The AMA publishes ICD-10-CM 2016: The Complete Official Codebook as well as ICD-10-CM Mappings 2016, which links ICD-9 codes to all valid ICD-10 alternatives. The AMA also offers electronic ICD-10-CM Express Reference Mapping Cards for multiple specialties.

Practice makes perfect and crosswalking from ICD-9 to ICD-10 is one of the best ways for your team to become aware of the nuances in the new coding system. Like learning a new language, “speaking” ICD-10 does not become automatic just because you’ve attended training or completed the coding maps. Training teaches the architecture of the new coding system. Mapping provides a structured way to become familiar with the codes the practice will use most often. Once these 2 primary pieces are understood and assimilated, most physicians find that dictating the necessary new terms becomes quite easy.  

 4. Conduct a gap analysis to identify the ICD-10 terms missing from each provider’s current documentation

Conduct the gap analysis after your team has completed training, and once you’ve at least begun the process of mapping codes from ICD-9 to ICD-10. Here’s how:

• Generate a CPT frequency report.
• Select the top 5 procedures for each physician.
• Pull 2 patients’ notes for each of the top procedures.
• Review the notes and try to select ICD-10 code(s).

If key ICD-10 terms are not included in current documentation, physicians should modify the templates or macros they rely on for dictation.

“This simple exercise makes it obvious which clinical information physicians must add for ICD-10,” Wiskerchen says. For example, if the patient had an arthroscopy, but the note doesn’t specify on which leg, that’s a clear indication that the physician must dictate laterality. “The gap analysis is a great way to coach physicians about the clinical details to document, so staff can bill under ICD-10,” Wiskerchen says.

 5. Contact technology vendors

Given the number of new ICD-10 codes in orthopedics, paper cheat sheets will be obsolete. Instead, you’ll need to rely on pull-down menus and/or search fields in the electronic health record (EHR) and practice management systems.

“Get clarity about how the new features and workflow processes will work in your systems,” suggests Wiskerchen. “Ask questions such as: Which features will be added or changed to accommodate the new codes? Will there be new screens or pick lists for ICD-10, or search fields? How will new screens and features change our current workflow? And schedule any necessary training as soon as possible.”

In addition to software upgrades and training, vendors and clearinghouses offer an array of services to help practices make the transition. Some vendors even provide help coordinating your internal plan with their new product features and training. Contact vendors to find out what they offer.

 6. Use completed code maps to build diagnosis code databases, EHR templates, charge tickets, pick lists, prompters, and other coding tools

“Provide the code crosswalks and results of your documentation gap analysis to the IT [information technology] team so they can get started,” Wiskerchen advises. “And assign a physician or midlevel provider to work with IT so that the tools are clinically accurate.”

 7. Schedule testing with clearinghouses and payers

“Successful testing indicates that your hard work has paid off, and that claims will be processed with few, if any, ICD-10–related hiccups,” Wiskerchen says. Essentially, the testing confirms that your ICD-10 code database, pick lists, vendor features, and other coding fields are working properly. “Testing with a clearinghouse is good. Testing directly with the payer is even better, if you are a direct submitter and it is allowed,” Wiskerchen suggests. Contact your clearinghouse and/or payers for testing opportunities prior to October 1.

 8. Develop a plan for a potential cash flow crunch

So what happens if your best efforts in the 11th hour still aren’t enough to get your practice to the ICD-10 finish line? Prepare for the possibility of increased claim denials and temporary cash flow stalls, and put a plan in place to deal with them.

Start now by cleaning up as much of the accounts receivable as possible, and moving patient collections up front. Ask the billing team for a weekly status update of the largest unpaid balances in the 60-day aging column, and what has been done to appeal or otherwise address them. Analyze denial patterns and trends and fix their causes at the source—some may be ICD-10–related, others may simply be a gap in the reimbursement process that needs improvement.

Use payer cost estimators to calculate patient out-of-pocket cost and to collect unmet deductibles, coinsurance, and noncovered services prior to surgery. The surgeon-developed iPhone app Health Insurance Arithmetic² ($1.99 in the iTunes Store) can help staff do this math on one, simple screen.

Finally, secure a line of credit to guard against a claim denial pile up this fall. A line of credit mitigates financial risk by making cash available quickly, should you need it to cover temporary revenue shortfalls, meet payroll, or pay operational expenses. It’s not too late to meet with your banker and apply for this protection, and the peace of mind may even help you sleep better.

As late as mid-April 2015, a survey of 121 orthopedic practices indicated that 30% had done nothing to start preparing for ICD-10 (International Classification of Diseases, Tenth Revision).¹  That’s scary. And even the practices that had begun to prepare had not completed a number of key tasks (Figure 1).

Certainly, the will-they-or-won’t-they possibility of another congressional delay had many practices sitting on their hands this year. But now that the October 1, 2015, implementation is set in stone, this lack of inertia has many practices woefully behind. If your practice is one of many that hasn’t mapped your common ICD-9 (International Classification of Diseases, Ninth Revision) codes to ICD-10 codes, completed payer testing, or attended training, it’s time for a “full-court press.”

Being unprepared for ICD-10 will cause more than just an increase in claim denials. If your surgery schedule is booked a few months out, your staff will need to pre-authorize cases using ICD-10 as early as August 1—and they won’t be able to do that if you haven’t dictated the clinical terms required to choose an ICD-10 code. Without an understanding of ICD-10, severity of illness coding will suffer, and that will affect your bundled and value-based payments. And, if you don’t provide an adequate diagnosis when sending patients off-site for physical therapy, you’ll soon be getting phone calls from their billing staff demanding more specifics.

The clock is ticking and time is short. Here’s a prioritized list of what needs to get done.

1. Generate an ICD-9 frequency report

Identifying which diagnosis codes are the most frequently used, and therefore drive a significant portion of practice revenue, is an absolute must. The data will help prioritize training and code-mapping activities.

Most practices generate Current Procedural Terminology (CPT) code-frequency reports regularly, but few have ever run an ICD-9 code-frequency report. Call your vendor and ask for assistance, as there are multiple ways to run this report and they vary by practice management system. Sort the data elements and generate the ICD-9 frequency report by:

• Primary diagnosis.
• Unique patient.
• Revenue. (If your practice management system can’t give you diagnosis data by revenue, which enables you to focus on the codes that generate the most revenue, generate it by charges.)

The result should be a report that identifies the 20 to 25 diagnosis codes (or charges, depending on the reports generated) that drive the most revenue for the practice. Use the data to focus and prioritize your training and code-mapping activities.

 2. Schedule training

Forget about “general” ICD-10 training courses. You need orthopedic-specific guidance. That’s because ICD-10 for orthopedics is more complex than for other specialties. Dictating fractures under ICD-10 is not so simple. Selecting an injury code requires confidence in correctly using the seventh character.

“Everyone who uses diagnosis codes must have baseline knowledge: surgeons, billing staff, surgical coordinators, and clinical team,” according to Sarah Wiskerchen, MBA, CPC, consultant and ICD-10 educator with KarenZupko & Associates (KZA). Training must include the practical details of ICD-10, such as assigning laterality, understanding the system architecture, and limiting the use of unspecified codes.

The American Academy of Orthopaedic Surgeons (AAOS) offers a self-paced, online training series that provides details for the top 3 diagnosis codes for each subspecialty. The 10-program course, ICD-10-CM: By the Numbers, is available at www.aaos.org ($299 for members, $399 for nonmembers). If you prefer live instruction, there is one more AAOS-sponsored, regional ICD-10 workshop left before the October 1 deadline, and more may be added. (Details at www.karenzupko.com)

These courses provide highly specific and granular ICD-10 knowledge and incorporate the use of Code-X, an AAOS-developed software tool. They also feature tools for handling the complexities of fractures and injury codes, such as Leo C. Far, an acronym developed by KZA consultant and coding educator Margie Maley, BSN, MS, to make ICD-10 diagnosis coding for fractures easier (Figure 2).

Some subspecialty societies also offer ICD-10 training. The American Society for Surgery of the Hand (www.assh.org), for example, offers a series of webinars and member-developed ICD-9-to-ICD-10 code maps.  

 3. Crosswalk your common codes from ICD-9 to ICD-10

Crosswalking is the process of mapping your most commonly used ICD-9 codes to their equivalent ICD-10 codes. This exercise familiarizes your team with ICD-10 language and terms, and gives a sense of which ICD-9 codes expand to just 1 or 2 ICD-10 codes and which codes expand into 10 or more codes—as some injury codes do (Table).

“Attempting to map the codes before completing ICD-10 training is like trying to write a letter in Greek when you only speak English,” Wiskerchen warns. “So start this process after at least some of your team have grasped the fundamentals of ICD-10.” This is where the data from your ICD-9 frequency report comes in. Use it to prioritize which codes to map first with a goal of mapping your top 25 ICD-9 codes to their ICD-10 equivalents by August 31.

Invest in good tools to support your mapping efforts. Avoid general mapping equivalent (GEM) coding tools, which are free for a good reason—they are incomplete and don’t always lead you to the correct ICD-10 code. Instead, purchase resources from credible sources, such as the American Medical Association (AMA; www.ama-assn.org). The AMA publishes ICD-10-CM 2016: The Complete Official Codebook as well as ICD-10-CM Mappings 2016, which links ICD-9 codes to all valid ICD-10 alternatives. The AMA also offers electronic ICD-10-CM Express Reference Mapping Cards for multiple specialties.

Practice makes perfect and crosswalking from ICD-9 to ICD-10 is one of the best ways for your team to become aware of the nuances in the new coding system. Like learning a new language, “speaking” ICD-10 does not become automatic just because you’ve attended training or completed the coding maps. Training teaches the architecture of the new coding system. Mapping provides a structured way to become familiar with the codes the practice will use most often. Once these 2 primary pieces are understood and assimilated, most physicians find that dictating the necessary new terms becomes quite easy.  

 4. Conduct a gap analysis to identify the ICD-10 terms missing from each provider’s current documentation

Conduct the gap analysis after your team has completed training, and once you’ve at least begun the process of mapping codes from ICD-9 to ICD-10. Here’s how:

• Generate a CPT frequency report.
• Select the top 5 procedures for each physician.
• Pull 2 patients’ notes for each of the top procedures.
• Review the notes and try to select ICD-10 code(s).

If key ICD-10 terms are not included in current documentation, physicians should modify the templates or macros they rely on for dictation.

“This simple exercise makes it obvious which clinical information physicians must add for ICD-10,” Wiskerchen says. For example, if the patient had an arthroscopy, but the note doesn’t specify on which leg, that’s a clear indication that the physician must dictate laterality. “The gap analysis is a great way to coach physicians about the clinical details to document, so staff can bill under ICD-10,” Wiskerchen says.

 5. Contact technology vendors

Given the number of new ICD-10 codes in orthopedics, paper cheat sheets will be obsolete. Instead, you’ll need to rely on pull-down menus and/or search fields in the electronic health record (EHR) and practice management systems.

“Get clarity about how the new features and workflow processes will work in your systems,” suggests Wiskerchen. “Ask questions such as: Which features will be added or changed to accommodate the new codes? Will there be new screens or pick lists for ICD-10, or search fields? How will new screens and features change our current workflow? And schedule any necessary training as soon as possible.”

In addition to software upgrades and training, vendors and clearinghouses offer an array of services to help practices make the transition. Some vendors even provide help coordinating your internal plan with their new product features and training. Contact vendors to find out what they offer.

 6. Use completed code maps to build diagnosis code databases, EHR templates, charge tickets, pick lists, prompters, and other coding tools

“Provide the code crosswalks and results of your documentation gap analysis to the IT [information technology] team so they can get started,” Wiskerchen advises. “And assign a physician or midlevel provider to work with IT so that the tools are clinically accurate.”

 7. Schedule testing with clearinghouses and payers

“Successful testing indicates that your hard work has paid off, and that claims will be processed with few, if any, ICD-10–related hiccups,” Wiskerchen says. Essentially, the testing confirms that your ICD-10 code database, pick lists, vendor features, and other coding fields are working properly. “Testing with a clearinghouse is good. Testing directly with the payer is even better, if you are a direct submitter and it is allowed,” Wiskerchen suggests. Contact your clearinghouse and/or payers for testing opportunities prior to October 1.

 8. Develop a plan for a potential cash flow crunch

So what happens if your best efforts in the 11th hour still aren’t enough to get your practice to the ICD-10 finish line? Prepare for the possibility of increased claim denials and temporary cash flow stalls, and put a plan in place to deal with them.

Start now by cleaning up as much of the accounts receivable as possible, and moving patient collections up front. Ask the billing team for a weekly status update of the largest unpaid balances in the 60-day aging column, and what has been done to appeal or otherwise address them. Analyze denial patterns and trends and fix their causes at the source—some may be ICD-10–related, others may simply be a gap in the reimbursement process that needs improvement.

Use payer cost estimators to calculate patient out-of-pocket cost and to collect unmet deductibles, coinsurance, and noncovered services prior to surgery. The surgeon-developed iPhone app Health Insurance Arithmetic² ($1.99 in the iTunes Store) can help staff do this math on one, simple screen.

Finally, secure a line of credit to guard against a claim denial pile up this fall. A line of credit mitigates financial risk by making cash available quickly, should you need it to cover temporary revenue shortfalls, meet payroll, or pay operational expenses. It’s not too late to meet with your banker and apply for this protection, and the peace of mind may even help you sleep better.

As late as mid-April 2015, a survey of 121 orthopedic practices indicated that 30% had done nothing to start preparing for ICD-10 (International Classification of Diseases, Tenth Revision).¹  That’s scary. And even the practices that had begun to prepare had not completed a number of key tasks (Figure 1).

Certainly, the will-they-or-won’t-they possibility of another congressional delay had many practices sitting on their hands this year. But now that the October 1, 2015, implementation is set in stone, this lack of inertia has many practices woefully behind. If your practice is one of many that hasn’t mapped your common ICD-9 (International Classification of Diseases, Ninth Revision) codes to ICD-10 codes, completed payer testing, or attended training, it’s time for a “full-court press.”

Being unprepared for ICD-10 will cause more than just an increase in claim denials. If your surgery schedule is booked a few months out, your staff will need to pre-authorize cases using ICD-10 as early as August 1—and they won’t be able to do that if you haven’t dictated the clinical terms required to choose an ICD-10 code. Without an understanding of ICD-10, severity of illness coding will suffer, and that will affect your bundled and value-based payments. And, if you don’t provide an adequate diagnosis when sending patients off-site for physical therapy, you’ll soon be getting phone calls from their billing staff demanding more specifics.

The clock is ticking and time is short. Here’s a prioritized list of what needs to get done.

1. Generate an ICD-9 frequency report

Identifying which diagnosis codes are the most frequently used, and therefore drive a significant portion of practice revenue, is an absolute must. The data will help prioritize training and code-mapping activities.

Most practices generate Current Procedural Terminology (CPT) code-frequency reports regularly, but few have ever run an ICD-9 code-frequency report. Call your vendor and ask for assistance, as there are multiple ways to run this report and they vary by practice management system. Sort the data elements and generate the ICD-9 frequency report by:

• Primary diagnosis.
• Unique patient.
• Revenue. (If your practice management system can’t give you diagnosis data by revenue, which enables you to focus on the codes that generate the most revenue, generate it by charges.)

The result should be a report that identifies the 20 to 25 diagnosis codes (or charges, depending on the reports generated) that drive the most revenue for the practice. Use the data to focus and prioritize your training and code-mapping activities.

 2. Schedule training

Forget about “general” ICD-10 training courses. You need orthopedic-specific guidance. That’s because ICD-10 for orthopedics is more complex than for other specialties. Dictating fractures under ICD-10 is not so simple. Selecting an injury code requires confidence in correctly using the seventh character.

“Everyone who uses diagnosis codes must have baseline knowledge: surgeons, billing staff, surgical coordinators, and clinical team,” according to Sarah Wiskerchen, MBA, CPC, consultant and ICD-10 educator with KarenZupko & Associates (KZA). Training must include the practical details of ICD-10, such as assigning laterality, understanding the system architecture, and limiting the use of unspecified codes.

The American Academy of Orthopaedic Surgeons (AAOS) offers a self-paced, online training series that provides details for the top 3 diagnosis codes for each subspecialty. The 10-program course, ICD-10-CM: By the Numbers, is available at www.aaos.org ($299 for members, $399 for nonmembers). If you prefer live instruction, there is one more AAOS-sponsored, regional ICD-10 workshop left before the October 1 deadline, and more may be added. (Details at www.karenzupko.com)

These courses provide highly specific and granular ICD-10 knowledge and incorporate the use of Code-X, an AAOS-developed software tool. They also feature tools for handling the complexities of fractures and injury codes, such as Leo C. Far, an acronym developed by KZA consultant and coding educator Margie Maley, BSN, MS, to make ICD-10 diagnosis coding for fractures easier (Figure 2).

Some subspecialty societies also offer ICD-10 training. The American Society for Surgery of the Hand (www.assh.org), for example, offers a series of webinars and member-developed ICD-9-to-ICD-10 code maps.  

 3. Crosswalk your common codes from ICD-9 to ICD-10

Crosswalking is the process of mapping your most commonly used ICD-9 codes to their equivalent ICD-10 codes. This exercise familiarizes your team with ICD-10 language and terms, and gives a sense of which ICD-9 codes expand to just 1 or 2 ICD-10 codes and which codes expand into 10 or more codes—as some injury codes do (Table).

“Attempting to map the codes before completing ICD-10 training is like trying to write a letter in Greek when you only speak English,” Wiskerchen warns. “So start this process after at least some of your team have grasped the fundamentals of ICD-10.” This is where the data from your ICD-9 frequency report comes in. Use it to prioritize which codes to map first with a goal of mapping your top 25 ICD-9 codes to their ICD-10 equivalents by August 31.

Invest in good tools to support your mapping efforts. Avoid general mapping equivalent (GEM) coding tools, which are free for a good reason—they are incomplete and don’t always lead you to the correct ICD-10 code. Instead, purchase resources from credible sources, such as the American Medical Association (AMA; www.ama-assn.org). The AMA publishes ICD-10-CM 2016: The Complete Official Codebook as well as ICD-10-CM Mappings 2016, which links ICD-9 codes to all valid ICD-10 alternatives. The AMA also offers electronic ICD-10-CM Express Reference Mapping Cards for multiple specialties.

Practice makes perfect and crosswalking from ICD-9 to ICD-10 is one of the best ways for your team to become aware of the nuances in the new coding system. Like learning a new language, “speaking” ICD-10 does not become automatic just because you’ve attended training or completed the coding maps. Training teaches the architecture of the new coding system. Mapping provides a structured way to become familiar with the codes the practice will use most often. Once these 2 primary pieces are understood and assimilated, most physicians find that dictating the necessary new terms becomes quite easy.  

 4. Conduct a gap analysis to identify the ICD-10 terms missing from each provider’s current documentation

Conduct the gap analysis after your team has completed training, and once you’ve at least begun the process of mapping codes from ICD-9 to ICD-10. Here’s how:

• Generate a CPT frequency report.
• Select the top 5 procedures for each physician.
• Pull 2 patients’ notes for each of the top procedures.
• Review the notes and try to select ICD-10 code(s).

If key ICD-10 terms are not included in current documentation, physicians should modify the templates or macros they rely on for dictation.

“This simple exercise makes it obvious which clinical information physicians must add for ICD-10,” Wiskerchen says. For example, if the patient had an arthroscopy, but the note doesn’t specify on which leg, that’s a clear indication that the physician must dictate laterality. “The gap analysis is a great way to coach physicians about the clinical details to document, so staff can bill under ICD-10,” Wiskerchen says.

 5. Contact technology vendors

Given the number of new ICD-10 codes in orthopedics, paper cheat sheets will be obsolete. Instead, you’ll need to rely on pull-down menus and/or search fields in the electronic health record (EHR) and practice management systems.

“Get clarity about how the new features and workflow processes will work in your systems,” suggests Wiskerchen. “Ask questions such as: Which features will be added or changed to accommodate the new codes? Will there be new screens or pick lists for ICD-10, or search fields? How will new screens and features change our current workflow? And schedule any necessary training as soon as possible.”

In addition to software upgrades and training, vendors and clearinghouses offer an array of services to help practices make the transition. Some vendors even provide help coordinating your internal plan with their new product features and training. Contact vendors to find out what they offer.

 6. Use completed code maps to build diagnosis code databases, EHR templates, charge tickets, pick lists, prompters, and other coding tools

“Provide the code crosswalks and results of your documentation gap analysis to the IT [information technology] team so they can get started,” Wiskerchen advises. “And assign a physician or midlevel provider to work with IT so that the tools are clinically accurate.”

 7. Schedule testing with clearinghouses and payers

“Successful testing indicates that your hard work has paid off, and that claims will be processed with few, if any, ICD-10–related hiccups,” Wiskerchen says. Essentially, the testing confirms that your ICD-10 code database, pick lists, vendor features, and other coding fields are working properly. “Testing with a clearinghouse is good. Testing directly with the payer is even better, if you are a direct submitter and it is allowed,” Wiskerchen suggests. Contact your clearinghouse and/or payers for testing opportunities prior to October 1.

 8. Develop a plan for a potential cash flow crunch

So what happens if your best efforts in the 11th hour still aren’t enough to get your practice to the ICD-10 finish line? Prepare for the possibility of increased claim denials and temporary cash flow stalls, and put a plan in place to deal with them.

Start now by cleaning up as much of the accounts receivable as possible, and moving patient collections up front. Ask the billing team for a weekly status update of the largest unpaid balances in the 60-day aging column, and what has been done to appeal or otherwise address them. Analyze denial patterns and trends and fix their causes at the source—some may be ICD-10–related, others may simply be a gap in the reimbursement process that needs improvement.

Use payer cost estimators to calculate patient out-of-pocket cost and to collect unmet deductibles, coinsurance, and noncovered services prior to surgery. The surgeon-developed iPhone app Health Insurance Arithmetic² ($1.99 in the iTunes Store) can help staff do this math on one, simple screen.

Finally, secure a line of credit to guard against a claim denial pile up this fall. A line of credit mitigates financial risk by making cash available quickly, should you need it to cover temporary revenue shortfalls, meet payroll, or pay operational expenses. It’s not too late to meet with your banker and apply for this protection, and the peace of mind may even help you sleep better.