Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.

The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.