THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

THE CASE

A 30-year-old woman presented to our emergency department with severe polyarthralgia, a high-grade fever (102.6º F), and a diffuse maculopapular rash on her trunk and extremities. She had returned from her honeymoon in Jamaica 6 days earlier. During her time there, she ate local cuisine, hiked in the jungle, and was bitten by many mosquitoes. The patient was nauseous, and had been experiencing headaches, generalized weakness, and fatigue. Her physical exam revealed a maculopapular rash on her trunk and upper extremities. She had tenderness and pain, as well as decreased range of motion in her ankles, knees, and wrists. The patient had no erythema, swelling, petechiae, or bruising. She had a past medical history of Graves’ disease and had received all of her childhood immunizations.

THE DIAGNOSIS

Our lab work-up included a complete blood count, liver function tests, blood pathogens for malaria, and serologic tests for dengue fever, measles, mumps, rubella, Lyme disease, human immunodeficiency virus (HIV), and parvovirus. We ruled out dengue fever because the patient had no evidence of hemorrhage, thrombocytopenia, rising hematocrit, or neutropenia. HIV antibody screening tests were performed, although, in retrospect, confirmatory HIV quantitative RNA testing should’ve been obtained because of the acute nature of the patient’s symptoms. Regardless, the work-up was negative, with the exception of a positive parvovirus immunoglobulin G (IgG).

Given our patient’s travel history, unremarkable lab results, and physical exam (notably the rash and joint pain), we suspected that she was infected with the chikungunya virus and tested for it. The results of chikungunya serum titers returned 13 days later and were positive for both immunoglobulin M (IgM) and IgG, confirming our suspicion.

DISCUSSION

Chikungunya is a viral infection that is most commonly transmitted to humans via mosquitoes. The infection was first identified in West Africa in the mid-1900s and predominantly occurs in tropical and subtropical regions due to the numbers of mosquitoes in those areas. Since 2000, outbreaks have been most common in Africa and Asia, with the largest outbreaks occurring from 2005 to 2006.^1,2 Chikungunya has since become more widespread in the Indian Ocean islands, and in 2013, it was first identified in the Caribbean islands. As of March 2017, over one million cases have been reported in the Americas, according to the Pan American Health Organization.³ In 2014, 12 locally transmitted cases were reported in Florida.⁴

The most common mosquito vectors for chikungunya are the Aedes albopictus (Asian tiger mosquito) and Aedes aegypti mosquitoes. These mosquitoes also transmit dengue fever, yellow fever, and Zika virus. Both of these mosquitoes are well-adapted to urban areas and can breed in standing water. A aegypti mosquitoes are found only in the southern United States, while A albopictus mosquitoes can be found in more temperate climates—areas like New York, New Jersey, and Pennsylvania.⁴ Both species are daytime biters, so their activity peaks during the dawn and dusk periods. Because local mosquito vectors exist as far north as New York, local transmission and outbreaks are possible in many parts of the United States.

When to suspect chikungunya, and what to look for

Suspect chikungunya in patients returning from endemic areas. After a 3- to 7-day incubation period, the clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever. Headache, nausea, and conjunctivitis may also occur. Polyarthralgia and arthritis usually present in symmetrical distal joints and are accompanied by face and trunk flushing that is followed by a maculopapular rash. The rash predominantly appears on the trunk and limbs, but can also occur on the face, palms, and soles. Tendons and ligaments—especially the Achilles tendon—may become inflamed, as well. Symptoms typically resolve within 2 to 3 weeks, although polyarthralgia may last for months or even years.

The clinical presentation of chikungunya typically begins with fever and malaise, followed by polyarthralgia that starts 2 to 5 days after the onset of fever.

There is no known risk of transmission through breast milk or in utero, although vertical transmission through vaginal or cesarean birth is common in viremic women. Blood-borne transmission can occur in the laboratory, nosocomially, or through the transfusion of blood products if exposure occurs during the early viremic phase.^1,2 Dual infections are possible (typically with yellow fever, malaria, Zika virus, or dengue fever) and should be considered based on the patient’s travel history.⁵ Abnormal laboratory findings are less common, but may include lymphopenia (most common), thrombocytopenia, elevations in blood urea nitrogen and creatinine (indicating an acute kidney injury), and elevated liver transaminases.

Chikungunya is generally considered a self-limiting disease, but severe atypical manifestations can lead to meningoencephalitis, respiratory failure, and even death. Severe disease is more commonly seen in infants, patients over age 65 years, and in those with chronic medical conditions.

The differential diagnosis for chikungunya virus includes dengue fever, Zika virus, malaria, measles, rubella, parvovirus, primary HIV infection, Lyme disease, and other inflammatory joint conditions. The differential depends on where a patient lives, their travel history, and exposures.

Dengue and chikungunya have similar features, which often make them difficult to distinguish. However, patients with dengue fever present more often with neutropenia, thrombocytopenia, and signs or symptoms of shock or hemorrhage.⁶ The chikungunya rash is typically a maculopapular rash on the trunk, hands, and feet that appears within the first 2 days of illness, as opposed to dengue, which has a similar rash, but appears later in the disease (Days 2-5). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) if dengue fever is suspected, as they can worsen hemorrhaging.⁷

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands.

Zika virus typically presents with milder symptoms compared to chikungunya. Patients may have a skin rash and occasionally, conjunctivitis, but limited high fevers or joint pain. Zika rash is maculopapular, but typically starts on the face on the first day of the illness. Zika has been associated with neurological complications such as Guillain-Barré syndrome and microcephaly in fetuses of infected pregnant woman.⁸

Choice of testing modality depends on when symptoms began

Laboratory diagnosis of chikungunya can be accomplished 3 ways: viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR) viral RNA, and serology.¹ The choice of which modality to use depends on the time between the onset of symptoms and the date on which a serum sample is drawn.

• If the patient presents within the first 3 days of illness, viral culture can detect chikungunya. Chikungunya virus testing is available through the Centers for Disease Control and Prevention (CDC), some state laboratories, and one commercial lab.⁸ Viral cultures are considered the gold standard for diagnosis, but a requirement for an elevated biosafety level, as well as a longer incubation time, make them less useful in the clinical setting.^1,9
• If symptoms started less than 5 to 8 days prior, serum should be sent for RT-PCR for viral RNA.
• If symptoms occurred more than 8 days prior, serum should be sent for IgM and IgG serologic testing.

If the acute sample was negative (and chikungunya is still suspected), a second serum sample should be drawn 2 to 3 weeks later during the convalescent phase and sent for IgG serologic testing.

There are no specific treatments or vaccines available for chikungunya, but both live and inactivated vaccines are being tested. To prevent chikungunya virus infection, advise patients traveling to endemic areas to reduce mosquito exposure by avoiding outdoor activities during dusk and dawn, wearing long-sleeved shirts and long pants, and using an insect repellent that contains DEET. Recommend that patients who will be sleeping in a high-risk area use bed netting treated with permethrin. The CDC Web site has excellent additional information, available at http://www.cdc.gov/chikungunya.¹⁰

Our patient was briefly hospitalized due to intractable pain. She was discharged after 2 days and given prescriptions for motrin 800 mg and percocet 5/325 mg for breakthrough pain. Her wrist and ankle pain persisted after discharge, but slowly resolved after 2 to 3 months.

THE TAKEAWAY

Chikungunya is becoming more common among travelers returning to the United States from the Caribbean islands, and mosquito vectors found in parts of the United States are enhancing the possibility of local outbreaks. Travel to endemic regions—and the classic symptoms of fever, polyarthralgia, and a maculopapular rash—should lead you to put chikungunya high on the differential. Chikungunya is considered a reportable disease and treatment is largely supportive. Co-infections are possible and should be considered based on the patient’s travel history.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.

Air leaks have been reported to be frequent and difficult-to-manage sequelae in some lung resection procedures.  Click here to learn about a new device being used in the thoracic space

Author:

Mark Ellis Ginsburg,

MD, FACS

Associate Clinical Professor of Surgery

Division of Cardiothoracic Surgery

Columbia University Medical Center

New York, NY

Faculty Disclosure: Dr. Ginsburg has received compensation from Medtronic Inc. for his participation in this article. He has no other conflicts of interest to disclose.

A child who has a cold, flu, or other acute illness may be what parents often call “fussy”: irritable, teary, and clingy. Such changes in behavior and mood, or “sickness behavior (SB),” are usually thought to be linked to fever.  Actually, those symptoms are the immune system’s reactions to invasion by a pathogen, say French researchers—and they may be present whether the child has fever or not. The researchers’ say their multicenter study is the first to show dissociation between SB and the severity of the fever.

The researchers evaluated 6 parameters over the 2 hours preceding consultations with the parents of 200 children with and 200 without fever. Children with particularly painful illnesses and chronic diseases were excluded from the study. Parents used rating scales to report degrees of change in the time the child spent playing, the distance covered (ie. how far from the parent the child roamed), time the child spent seeking comfort, time spent whining or crying, time spent in a state of irritation or anger, most distorted facial expression (on a chart). The researchers also assessed time spent sleeping and appetite in the 24 hours before the consultation. Sickness behavior can’t be reduced to the observation of those 8 behavioral parameters, the researchers note, but they were easy for parents to use and assess.

The mean values of the 8 parameters differed significantly between the 2 groups but were independent of the height of fever in the febrile children. That independence suggests that SB and fever are expressions of 2 autonomous metabolic pathways that are activated simultaneously in febrile conditions, the researchers say, which is in accordance with current pathophysiologic knowledge.

Their findings are in harmony with current treatment recommendations, the researchers say. Because it’s hard to know when behavior changes are due to SB, pain, fatigue, or something else in a febrile child—especially one who is too young to talk about it—it’s more important to focus on relieving the discomfort than in reducing the fever.

Source:

Corrard F, Copin C, Wollner A, et al. PLoS One. 2017;12(3): e0171670.
doi: 10.1371/journal.pone.0171670.

A child who has a cold, flu, or other acute illness may be what parents often call “fussy”: irritable, teary, and clingy. Such changes in behavior and mood, or “sickness behavior (SB),” are usually thought to be linked to fever.  Actually, those symptoms are the immune system’s reactions to invasion by a pathogen, say French researchers—and they may be present whether the child has fever or not. The researchers’ say their multicenter study is the first to show dissociation between SB and the severity of the fever.

The researchers evaluated 6 parameters over the 2 hours preceding consultations with the parents of 200 children with and 200 without fever. Children with particularly painful illnesses and chronic diseases were excluded from the study. Parents used rating scales to report degrees of change in the time the child spent playing, the distance covered (ie. how far from the parent the child roamed), time the child spent seeking comfort, time spent whining or crying, time spent in a state of irritation or anger, most distorted facial expression (on a chart). The researchers also assessed time spent sleeping and appetite in the 24 hours before the consultation. Sickness behavior can’t be reduced to the observation of those 8 behavioral parameters, the researchers note, but they were easy for parents to use and assess.

The mean values of the 8 parameters differed significantly between the 2 groups but were independent of the height of fever in the febrile children. That independence suggests that SB and fever are expressions of 2 autonomous metabolic pathways that are activated simultaneously in febrile conditions, the researchers say, which is in accordance with current pathophysiologic knowledge.

Their findings are in harmony with current treatment recommendations, the researchers say. Because it’s hard to know when behavior changes are due to SB, pain, fatigue, or something else in a febrile child—especially one who is too young to talk about it—it’s more important to focus on relieving the discomfort than in reducing the fever.

Source:

Corrard F, Copin C, Wollner A, et al. PLoS One. 2017;12(3): e0171670.
doi: 10.1371/journal.pone.0171670.

A child who has a cold, flu, or other acute illness may be what parents often call “fussy”: irritable, teary, and clingy. Such changes in behavior and mood, or “sickness behavior (SB),” are usually thought to be linked to fever.  Actually, those symptoms are the immune system’s reactions to invasion by a pathogen, say French researchers—and they may be present whether the child has fever or not. The researchers’ say their multicenter study is the first to show dissociation between SB and the severity of the fever.

The researchers evaluated 6 parameters over the 2 hours preceding consultations with the parents of 200 children with and 200 without fever. Children with particularly painful illnesses and chronic diseases were excluded from the study. Parents used rating scales to report degrees of change in the time the child spent playing, the distance covered (ie. how far from the parent the child roamed), time the child spent seeking comfort, time spent whining or crying, time spent in a state of irritation or anger, most distorted facial expression (on a chart). The researchers also assessed time spent sleeping and appetite in the 24 hours before the consultation. Sickness behavior can’t be reduced to the observation of those 8 behavioral parameters, the researchers note, but they were easy for parents to use and assess.

The mean values of the 8 parameters differed significantly between the 2 groups but were independent of the height of fever in the febrile children. That independence suggests that SB and fever are expressions of 2 autonomous metabolic pathways that are activated simultaneously in febrile conditions, the researchers say, which is in accordance with current pathophysiologic knowledge.

Their findings are in harmony with current treatment recommendations, the researchers say. Because it’s hard to know when behavior changes are due to SB, pain, fatigue, or something else in a febrile child—especially one who is too young to talk about it—it’s more important to focus on relieving the discomfort than in reducing the fever.

Source:

Corrard F, Copin C, Wollner A, et al. PLoS One. 2017;12(3): e0171670.
doi: 10.1371/journal.pone.0171670.

Walter Reed National Military Medical Center in Bethesda, Maryland, is one of several military and civilian medical facilities named for a U.S. Army doctor.

Walter Reed, MD, was born September 13, 1851 near Gloucester on Virginia’s middle peninsula. His father was the pastor of the Bellamy Methodist Church. The Reed family frequently moved as was required by the church and thus lived in many areas of southeastern Virginia and North Carolina. After the Civil War, Reverend Reed moved his family to Charlottesville, Virginia, where Walter, 15, and 2 of his older brothers were enrolled in the University of Virginia.

After a successful year of study, Reed summoned enough courage to confront the formidably bearded elders of the medical faculty with a bold proposal: If he passed all the courses, would they award him a medical degree regardless of the time it took or his age when he finished? A little more than 2 months shy of this 18th birthday, Reed graduated standing third in a class of 10 remaining from the original 50. He was, then and now, the youngest person ever to graduate from the University of Virginia School of Medicine. Reed went to Bellevue Hospital Medical School in New York for clinical hospital training. In another year, he earned his second medical degree, though it was not awarded until after he had reached the ripe old age of 21.

Reed joined the U.S. Army in 1875, possibly looking for a secure position that allowed him to marry his sweetheart Emily Lawrence in 1876. Over the first 18 years of marriage, they moved about 15 times throughout the west with some eastern assignments.

The selection of George Miller Steinberg as Army Surgeon General in 1893 turned out to be a watershed in Reed’s career. He joined the faculty of the new Army medical school. Reed lived closer to Washington (Minnesota) than did the other candidate (California), which probably helped his candidacy. Reed took full advantage of this opportunity and became a trusted troubleshooter for Sternberg.

After the Spanish-American War, Reed led a U.S. Army board that investigated typhoid fever in stateside camps, which killed more soldiers than died on the battlefield during the war. The findings of this board alone would have made Reed famous, but before these findings were formally published, Reed was sent to Cuba to lead another U.S. Army board to investigate infectious diseases, including yellow fever. Over the course of a few months, with the input and assistance of many others, he designed and carried out a series of human experiments that proved the mosquito as the vector of yellow fever. Application of his findings quickly led to the control of yellow fever in Cuba and later in Panama and throughout the tropics.

Reed died in Washington, DC, in 1902 at age 51, following surgery that discovered a ruptured appendix, which in that pre-antibiotic era was nearly always fatal. William Borden, his surgeon and friend, campaigned for several years for a new U.S. Army hospital in Washington to be named for Reed. Borden was successful with the opening of Walter Reed Army General Hospital in 1909. Renamed Walter Reed Army Medical Center in 1951 on the 100th anniversary of Reed’s birth, the hospital was closed in 2011 and its name transferred to the new Walter Reed National Military Medical Center. Other facilities named for Reed include the Walter Reed Army Institute of Research in Maryland and the civilian Riverside Walter Reed Hospital in Gloucester Courthouse, Virginia.

A particularly interesting resource to learn more about Reed is the Philip Hench Walter Reed Yellow Fever Collection. Most of the collection is available online (http://yellowfever.lib.virginia.edu/reed).

Walter Reed National Military Medical Center in Bethesda, Maryland, is one of several military and civilian medical facilities named for a U.S. Army doctor.

Walter Reed, MD, was born September 13, 1851 near Gloucester on Virginia’s middle peninsula. His father was the pastor of the Bellamy Methodist Church. The Reed family frequently moved as was required by the church and thus lived in many areas of southeastern Virginia and North Carolina. After the Civil War, Reverend Reed moved his family to Charlottesville, Virginia, where Walter, 15, and 2 of his older brothers were enrolled in the University of Virginia.

After a successful year of study, Reed summoned enough courage to confront the formidably bearded elders of the medical faculty with a bold proposal: If he passed all the courses, would they award him a medical degree regardless of the time it took or his age when he finished? A little more than 2 months shy of this 18th birthday, Reed graduated standing third in a class of 10 remaining from the original 50. He was, then and now, the youngest person ever to graduate from the University of Virginia School of Medicine. Reed went to Bellevue Hospital Medical School in New York for clinical hospital training. In another year, he earned his second medical degree, though it was not awarded until after he had reached the ripe old age of 21.

Reed joined the U.S. Army in 1875, possibly looking for a secure position that allowed him to marry his sweetheart Emily Lawrence in 1876. Over the first 18 years of marriage, they moved about 15 times throughout the west with some eastern assignments.

The selection of George Miller Steinberg as Army Surgeon General in 1893 turned out to be a watershed in Reed’s career. He joined the faculty of the new Army medical school. Reed lived closer to Washington (Minnesota) than did the other candidate (California), which probably helped his candidacy. Reed took full advantage of this opportunity and became a trusted troubleshooter for Sternberg.

After the Spanish-American War, Reed led a U.S. Army board that investigated typhoid fever in stateside camps, which killed more soldiers than died on the battlefield during the war. The findings of this board alone would have made Reed famous, but before these findings were formally published, Reed was sent to Cuba to lead another U.S. Army board to investigate infectious diseases, including yellow fever. Over the course of a few months, with the input and assistance of many others, he designed and carried out a series of human experiments that proved the mosquito as the vector of yellow fever. Application of his findings quickly led to the control of yellow fever in Cuba and later in Panama and throughout the tropics.

Reed died in Washington, DC, in 1902 at age 51, following surgery that discovered a ruptured appendix, which in that pre-antibiotic era was nearly always fatal. William Borden, his surgeon and friend, campaigned for several years for a new U.S. Army hospital in Washington to be named for Reed. Borden was successful with the opening of Walter Reed Army General Hospital in 1909. Renamed Walter Reed Army Medical Center in 1951 on the 100th anniversary of Reed’s birth, the hospital was closed in 2011 and its name transferred to the new Walter Reed National Military Medical Center. Other facilities named for Reed include the Walter Reed Army Institute of Research in Maryland and the civilian Riverside Walter Reed Hospital in Gloucester Courthouse, Virginia.

A particularly interesting resource to learn more about Reed is the Philip Hench Walter Reed Yellow Fever Collection. Most of the collection is available online (http://yellowfever.lib.virginia.edu/reed).

Walter Reed National Military Medical Center in Bethesda, Maryland, is one of several military and civilian medical facilities named for a U.S. Army doctor.

Walter Reed, MD, was born September 13, 1851 near Gloucester on Virginia’s middle peninsula. His father was the pastor of the Bellamy Methodist Church. The Reed family frequently moved as was required by the church and thus lived in many areas of southeastern Virginia and North Carolina. After the Civil War, Reverend Reed moved his family to Charlottesville, Virginia, where Walter, 15, and 2 of his older brothers were enrolled in the University of Virginia.

After a successful year of study, Reed summoned enough courage to confront the formidably bearded elders of the medical faculty with a bold proposal: If he passed all the courses, would they award him a medical degree regardless of the time it took or his age when he finished? A little more than 2 months shy of this 18th birthday, Reed graduated standing third in a class of 10 remaining from the original 50. He was, then and now, the youngest person ever to graduate from the University of Virginia School of Medicine. Reed went to Bellevue Hospital Medical School in New York for clinical hospital training. In another year, he earned his second medical degree, though it was not awarded until after he had reached the ripe old age of 21.

Reed joined the U.S. Army in 1875, possibly looking for a secure position that allowed him to marry his sweetheart Emily Lawrence in 1876. Over the first 18 years of marriage, they moved about 15 times throughout the west with some eastern assignments.

The selection of George Miller Steinberg as Army Surgeon General in 1893 turned out to be a watershed in Reed’s career. He joined the faculty of the new Army medical school. Reed lived closer to Washington (Minnesota) than did the other candidate (California), which probably helped his candidacy. Reed took full advantage of this opportunity and became a trusted troubleshooter for Sternberg.

After the Spanish-American War, Reed led a U.S. Army board that investigated typhoid fever in stateside camps, which killed more soldiers than died on the battlefield during the war. The findings of this board alone would have made Reed famous, but before these findings were formally published, Reed was sent to Cuba to lead another U.S. Army board to investigate infectious diseases, including yellow fever. Over the course of a few months, with the input and assistance of many others, he designed and carried out a series of human experiments that proved the mosquito as the vector of yellow fever. Application of his findings quickly led to the control of yellow fever in Cuba and later in Panama and throughout the tropics.

Reed died in Washington, DC, in 1902 at age 51, following surgery that discovered a ruptured appendix, which in that pre-antibiotic era was nearly always fatal. William Borden, his surgeon and friend, campaigned for several years for a new U.S. Army hospital in Washington to be named for Reed. Borden was successful with the opening of Walter Reed Army General Hospital in 1909. Renamed Walter Reed Army Medical Center in 1951 on the 100th anniversary of Reed’s birth, the hospital was closed in 2011 and its name transferred to the new Walter Reed National Military Medical Center. Other facilities named for Reed include the Walter Reed Army Institute of Research in Maryland and the civilian Riverside Walter Reed Hospital in Gloucester Courthouse, Virginia.

A particularly interesting resource to learn more about Reed is the Philip Hench Walter Reed Yellow Fever Collection. Most of the collection is available online (http://yellowfever.lib.virginia.edu/reed).

Red blood cells

Researchers say they have generated the first human immortalized adult erythroid line that provides a sustainable supply of erythroid cells.

The team says this cell line, known as Bristol Erythroid Line Adult (BEL-A), is the first erythroid line to fully recapitulate normal erythropoiesis.

It produced mature reticulocytes that proved functionally and molecularly similar to adult reticulocytes cultured in vitro.

In addition, in vivo survival rates of BEL-A reticulocytes were similar to the survival rates of red blood cells (RBCs) from adult donors.

The researchers described their generation and testing of the BEL-A line in Nature Communications.

“Previous approaches to producing red blood cells have relied on various sources of stem cells, which can only presently produce very limited quantities,” said study author Jan Frayne, PhD, of the University of Bristol in the UK.

“By taking an alternative approach, we have generated the first human immortalized adult erythroid line (Bristol Erythroid Line Adult or BEL-A), and in doing so, have demonstrated a feasible way to sustainably manufacture red cells for clinical use from in vitro culture.”

Dr Frayne and her colleagues began with CD34+ cells from adult bone marrow. The researchers transduced these cells with an HPV16-E6/E7 construct and maintained them in the primary medium of the team’s erythroid culture system for 4 days.

On day 5, the researchers transferred the cells to an expansion medium containing doxycycline. After 190 days of continuous proliferation, the cells were frozen for storage.

Some cells were frozen throughout this time period as well, and all of the samples re-established efficiently in culture after thawing.

The researchers said these immortalized BEL-A cells were pro- to early basophilic erythroblasts, and there was no change in morphology over time.

After 100 days in continuous culture, the researchers transferred BEL-A cells to the primary erythroid culture medium containing doxycycline. The cells remained there for 6 days and were then moved to a medium without doxycycline to induce differentiation to mature erythroblasts and reticulocytes.

The researchers said the BEL-A cells exhibited an “unchanged ability to differentiate,” and were consistently able to expand.

The team also noted that BEL-A reticulocytes were similar to normal adult reticulocytes. The cells had similar diameters, comparable deformability indexes, and they bound and released oxygen in the same way.

The researchers tested the in vivo survival of BEL-A reticulocytes as well. They transfused BEL-A reticulocytes and donor RBCs into macrophage-depleted NSG mice. There was no difference in survival between the 2 cell types.

Dr Frayne and her colleagues said their results suggest immortalized erythroid lines can be used for the manufacture of RBCs for clinical use and for the study of erythropoiesis.

Red blood cells

Researchers say they have generated the first human immortalized adult erythroid line that provides a sustainable supply of erythroid cells.

The team says this cell line, known as Bristol Erythroid Line Adult (BEL-A), is the first erythroid line to fully recapitulate normal erythropoiesis.

It produced mature reticulocytes that proved functionally and molecularly similar to adult reticulocytes cultured in vitro.

In addition, in vivo survival rates of BEL-A reticulocytes were similar to the survival rates of red blood cells (RBCs) from adult donors.

The researchers described their generation and testing of the BEL-A line in Nature Communications.

“Previous approaches to producing red blood cells have relied on various sources of stem cells, which can only presently produce very limited quantities,” said study author Jan Frayne, PhD, of the University of Bristol in the UK.

“By taking an alternative approach, we have generated the first human immortalized adult erythroid line (Bristol Erythroid Line Adult or BEL-A), and in doing so, have demonstrated a feasible way to sustainably manufacture red cells for clinical use from in vitro culture.”

Dr Frayne and her colleagues began with CD34+ cells from adult bone marrow. The researchers transduced these cells with an HPV16-E6/E7 construct and maintained them in the primary medium of the team’s erythroid culture system for 4 days.

On day 5, the researchers transferred the cells to an expansion medium containing doxycycline. After 190 days of continuous proliferation, the cells were frozen for storage.

Some cells were frozen throughout this time period as well, and all of the samples re-established efficiently in culture after thawing.

The researchers said these immortalized BEL-A cells were pro- to early basophilic erythroblasts, and there was no change in morphology over time.

After 100 days in continuous culture, the researchers transferred BEL-A cells to the primary erythroid culture medium containing doxycycline. The cells remained there for 6 days and were then moved to a medium without doxycycline to induce differentiation to mature erythroblasts and reticulocytes.

The researchers said the BEL-A cells exhibited an “unchanged ability to differentiate,” and were consistently able to expand.

The team also noted that BEL-A reticulocytes were similar to normal adult reticulocytes. The cells had similar diameters, comparable deformability indexes, and they bound and released oxygen in the same way.

The researchers tested the in vivo survival of BEL-A reticulocytes as well. They transfused BEL-A reticulocytes and donor RBCs into macrophage-depleted NSG mice. There was no difference in survival between the 2 cell types.

Dr Frayne and her colleagues said their results suggest immortalized erythroid lines can be used for the manufacture of RBCs for clinical use and for the study of erythropoiesis.

Red blood cells

Researchers say they have generated the first human immortalized adult erythroid line that provides a sustainable supply of erythroid cells.

The team says this cell line, known as Bristol Erythroid Line Adult (BEL-A), is the first erythroid line to fully recapitulate normal erythropoiesis.

It produced mature reticulocytes that proved functionally and molecularly similar to adult reticulocytes cultured in vitro.

In addition, in vivo survival rates of BEL-A reticulocytes were similar to the survival rates of red blood cells (RBCs) from adult donors.

The researchers described their generation and testing of the BEL-A line in Nature Communications.

“Previous approaches to producing red blood cells have relied on various sources of stem cells, which can only presently produce very limited quantities,” said study author Jan Frayne, PhD, of the University of Bristol in the UK.

“By taking an alternative approach, we have generated the first human immortalized adult erythroid line (Bristol Erythroid Line Adult or BEL-A), and in doing so, have demonstrated a feasible way to sustainably manufacture red cells for clinical use from in vitro culture.”

Dr Frayne and her colleagues began with CD34+ cells from adult bone marrow. The researchers transduced these cells with an HPV16-E6/E7 construct and maintained them in the primary medium of the team’s erythroid culture system for 4 days.

On day 5, the researchers transferred the cells to an expansion medium containing doxycycline. After 190 days of continuous proliferation, the cells were frozen for storage.

Some cells were frozen throughout this time period as well, and all of the samples re-established efficiently in culture after thawing.

The researchers said these immortalized BEL-A cells were pro- to early basophilic erythroblasts, and there was no change in morphology over time.

After 100 days in continuous culture, the researchers transferred BEL-A cells to the primary erythroid culture medium containing doxycycline. The cells remained there for 6 days and were then moved to a medium without doxycycline to induce differentiation to mature erythroblasts and reticulocytes.

The researchers said the BEL-A cells exhibited an “unchanged ability to differentiate,” and were consistently able to expand.

The team also noted that BEL-A reticulocytes were similar to normal adult reticulocytes. The cells had similar diameters, comparable deformability indexes, and they bound and released oxygen in the same way.

The researchers tested the in vivo survival of BEL-A reticulocytes as well. They transfused BEL-A reticulocytes and donor RBCs into macrophage-depleted NSG mice. There was no difference in survival between the 2 cell types.

Dr Frayne and her colleagues said their results suggest immortalized erythroid lines can be used for the manufacture of RBCs for clinical use and for the study of erythropoiesis.

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Children’s Research Hospital

A new mathematical model could aid the development of drugs that target malaria parasites’ metabolic processes, according to researchers.

The team said they developed the first model of a malaria parasite that accurately integrates its genetics and metabolism.

They described this model in PLOS Computational Biology.

“The model integrates all available knowledge on the genetics and metabolism of the parasites and allows the formulation of testable hypotheses behind the parasites’ essential functions,” said study author Vassily Hatzimanikatis, PhD, of École Polytechnique Fédérale de Lausanne in Switzerland.

“Ultimately, it can accelerate the discovery toward novel antimalarial drug targets.”

To create the model, Dr Hatzimanikatis and his colleagues studied Plasmodium falciparum parasites, focusing on the way they produce and use energy for their metabolic reactions.

This revealed which metabolic functions were essential at each stage of infection and which were energetically coupled through key metabolites.

The team was therefore able to model the bioenergetics of the metabolism of P falciparum, predicting which genes are indispensable for every biological function in the parasite.

By integrating metabolomics and genetics data, the model revealed the complex interactions between gene products, reactions, and metabolites in the parasite, and it revealed potential mechanisms to target with drugs.

“The design of efficient antimalarial drugs that target the parasite’s and not the patient’s metabolism requires an in-depth understanding of the mechanisms that make a particular enzyme essential,” said Anush Chiappino-Pepe, a PhD student at École Polytechnique Fédérale de Lausanne.

“So mathematical modeling of the parasite’s metabolism becomes a very powerful tool.”

The researchers said they will continue to calibrate and improve the predictive capabilities of their model with additional genetics and metabolomics data.

They hope to reveal the mechanisms behind host-pathogen interactions and gain insight into the physiology of P falciparum while it is dormant. 

Children’s Research Hospital

A new mathematical model could aid the development of drugs that target malaria parasites’ metabolic processes, according to researchers.

The team said they developed the first model of a malaria parasite that accurately integrates its genetics and metabolism.

They described this model in PLOS Computational Biology.

“The model integrates all available knowledge on the genetics and metabolism of the parasites and allows the formulation of testable hypotheses behind the parasites’ essential functions,” said study author Vassily Hatzimanikatis, PhD, of École Polytechnique Fédérale de Lausanne in Switzerland.

“Ultimately, it can accelerate the discovery toward novel antimalarial drug targets.”

To create the model, Dr Hatzimanikatis and his colleagues studied Plasmodium falciparum parasites, focusing on the way they produce and use energy for their metabolic reactions.

This revealed which metabolic functions were essential at each stage of infection and which were energetically coupled through key metabolites.

The team was therefore able to model the bioenergetics of the metabolism of P falciparum, predicting which genes are indispensable for every biological function in the parasite.

By integrating metabolomics and genetics data, the model revealed the complex interactions between gene products, reactions, and metabolites in the parasite, and it revealed potential mechanisms to target with drugs.

“The design of efficient antimalarial drugs that target the parasite’s and not the patient’s metabolism requires an in-depth understanding of the mechanisms that make a particular enzyme essential,” said Anush Chiappino-Pepe, a PhD student at École Polytechnique Fédérale de Lausanne.

“So mathematical modeling of the parasite’s metabolism becomes a very powerful tool.”

The researchers said they will continue to calibrate and improve the predictive capabilities of their model with additional genetics and metabolomics data.

They hope to reveal the mechanisms behind host-pathogen interactions and gain insight into the physiology of P falciparum while it is dormant. 

Children’s Research Hospital

A new mathematical model could aid the development of drugs that target malaria parasites’ metabolic processes, according to researchers.

The team said they developed the first model of a malaria parasite that accurately integrates its genetics and metabolism.

They described this model in PLOS Computational Biology.

“The model integrates all available knowledge on the genetics and metabolism of the parasites and allows the formulation of testable hypotheses behind the parasites’ essential functions,” said study author Vassily Hatzimanikatis, PhD, of École Polytechnique Fédérale de Lausanne in Switzerland.

“Ultimately, it can accelerate the discovery toward novel antimalarial drug targets.”

To create the model, Dr Hatzimanikatis and his colleagues studied Plasmodium falciparum parasites, focusing on the way they produce and use energy for their metabolic reactions.

This revealed which metabolic functions were essential at each stage of infection and which were energetically coupled through key metabolites.

The team was therefore able to model the bioenergetics of the metabolism of P falciparum, predicting which genes are indispensable for every biological function in the parasite.

By integrating metabolomics and genetics data, the model revealed the complex interactions between gene products, reactions, and metabolites in the parasite, and it revealed potential mechanisms to target with drugs.

“The design of efficient antimalarial drugs that target the parasite’s and not the patient’s metabolism requires an in-depth understanding of the mechanisms that make a particular enzyme essential,” said Anush Chiappino-Pepe, a PhD student at École Polytechnique Fédérale de Lausanne.

“So mathematical modeling of the parasite’s metabolism becomes a very powerful tool.”

The researchers said they will continue to calibrate and improve the predictive capabilities of their model with additional genetics and metabolomics data.

They hope to reveal the mechanisms behind host-pathogen interactions and gain insight into the physiology of P falciparum while it is dormant. 

The Food and Drug Administration has approved niraparib, a poly ADP-ribose polymerase (PARP) inhibitor, for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

The indication does not require a suspected or confirmed deleterious BRCA mutation.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved niraparib, a poly ADP-ribose polymerase (PARP) inhibitor, for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

The indication does not require a suspected or confirmed deleterious BRCA mutation.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved niraparib, a poly ADP-ribose polymerase (PARP) inhibitor, for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

The indication does not require a suspected or confirmed deleterious BRCA mutation.

[email protected]

On Twitter @NikolaidesLaura

ORLANDO—Although multiple sclerosis (MS) is more common in women, when men develop MS, it tends to be worse. Studies indicate that MS in men is associated with a faster accrual of disability and worse relapse recovery. In addition, research suggests that male gender is a predictor for more severe forms of MS. Also, there appears to be a higher male-to-female ratio in primary progressive MS (PPMS), compared with relapsing forms of MS.

Role of Sex Chromosomes and Hormones

Studies suggest that women are predisposed to higher rates of MS relapses than men. Kalincik et al found that there was approximately a 1:1 male-to-female ratio in PPMS onset, compared with a 1:3 male-to-female ratio in relapsing-onset MS. “One of the interesting paradigms they looked at was the proportion of relapses or the relapse count over the course of 10 years and the female-to-male ratio and how it has increased to become predominately female with a higher relapse count. This certainly suggests that hormones and sex may be driving a relapsing phenotype,” said Dr. Chitnis.

Raghavan et al found that men appeared to have higher Expanded Disability Status Scale scores over disease duration in relapsing forms of MS compared with PPMS. In addition, when researchers observed optic neuritis as a model of relapse recovery, they found that male gender was associated with worse recovery from optic neuritis despite adjusting for disease severity as well as vitamin D levels.

Is Testosterone Neuroprotective?

Previous studies in MS suggest that low testosterone is associated with worse disability. Studies have also associated low testosterone levels with more cognitive decline in MS. Following up on these clinical observations, Dr. Chitnis and colleagues conducted the CLIMB study, a long-term study of how MS changes over time, to observe testosterone levels in men with MS. Data from the study, which involved nearly 100 men with MS, revealed that there were significantly reduced testosterone levels in a majority of the males.

Although lower levels of testosterone may be a risk factor for rapid disability accrual, testosterone supplementation appears to be neuroprotective. “There is a vast amount of literature now demonstrating in animal models particularly that testosterone does appear to be neuroprotective and anti-inflammatory,” said Dr. Chitnis.

According to Ziehn et al, testosterone seemed to be protective against synaptic preservation in animal models. In addition, research has elucidated that testosterone is able to cross the blood-brain barrier in its free form and directly influence neuronal cells. Other studies suggest that testosterone protects spinal cord neurons from glutamate toxicity, and protects from oxidative stress in neuronal cell lines.

Sex-Stratified MS Risk, Prenatal Exposure, and Puberty

To understand whether testosterone levels predispose men to MS, researchers studied a measure called the second-digit-fourth-digit ratio (2D:4D) and found that it was associated with MS in men. Researchers have also discovered that there may be prenatal risk factors that may increase susceptibility in men. While studies suggest that breast-feeding is associated with a reduced risk of MS in boys, maternal illness and pesticide exposure in pregnancy and during the prenatal stage were associated with an increased risk for pediatric-onset MS.

Puberty also may be a turning point for the initiation of MS in boys, said Dr. Chitnis. “Younger males with MS show evidence of earlier puberty than regional controls. It is unclear if they have lower testosterone, however, research does suggest a disturbance in sex hormones early on,” she said.

Testosterone as an MS Therapy?

Several benefits have been associated with testosterone as a potential therapy, such as improved libido, increased muscle strength, improved bone density, and potentially improved memory and other cognitive measures. However, there are serious risks associated with testosterone therapy such as an increased prostate specific antigen, increased susceptibility to cancer, emotional lability, hypertension, increased hemoglobin, and increased cardiovascular events.

There may be benefits with regard to slowing disease progression and cognitive decline that warrant further study, said Dr. Chitnis. She added that future studies should focus on “mechanisms and interactions of sex hormones and testosterone in boys with MS, as well as safety and efficacy of testosterone in men with MS.”

—Erica Tricarico

Suggested Reading

Bove R, Malik MT, Diaz-Cruz C, et al. The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS. Neurology. 2015;85(14):1209-1213.

Kalincik T, Vivek V, Jokubaitis V, et al. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain. 2013;136(Pt 12):3609-3617.

Raghavan K, Healy BC, Carruthers RL, Chitnis T. Progression rates and sample size estimates for PPMS based on the CLIMB study population. Mult Scler. 2015;21(2):180-188.

Ziehn MO, Avedisian AA, Dervin SM, et al. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012; 32(36):12312-12324.

ORLANDO—Although multiple sclerosis (MS) is more common in women, when men develop MS, it tends to be worse. Studies indicate that MS in men is associated with a faster accrual of disability and worse relapse recovery. In addition, research suggests that male gender is a predictor for more severe forms of MS. Also, there appears to be a higher male-to-female ratio in primary progressive MS (PPMS), compared with relapsing forms of MS.

Role of Sex Chromosomes and Hormones

Studies suggest that women are predisposed to higher rates of MS relapses than men. Kalincik et al found that there was approximately a 1:1 male-to-female ratio in PPMS onset, compared with a 1:3 male-to-female ratio in relapsing-onset MS. “One of the interesting paradigms they looked at was the proportion of relapses or the relapse count over the course of 10 years and the female-to-male ratio and how it has increased to become predominately female with a higher relapse count. This certainly suggests that hormones and sex may be driving a relapsing phenotype,” said Dr. Chitnis.

Raghavan et al found that men appeared to have higher Expanded Disability Status Scale scores over disease duration in relapsing forms of MS compared with PPMS. In addition, when researchers observed optic neuritis as a model of relapse recovery, they found that male gender was associated with worse recovery from optic neuritis despite adjusting for disease severity as well as vitamin D levels.

Is Testosterone Neuroprotective?

Previous studies in MS suggest that low testosterone is associated with worse disability. Studies have also associated low testosterone levels with more cognitive decline in MS. Following up on these clinical observations, Dr. Chitnis and colleagues conducted the CLIMB study, a long-term study of how MS changes over time, to observe testosterone levels in men with MS. Data from the study, which involved nearly 100 men with MS, revealed that there were significantly reduced testosterone levels in a majority of the males.

Although lower levels of testosterone may be a risk factor for rapid disability accrual, testosterone supplementation appears to be neuroprotective. “There is a vast amount of literature now demonstrating in animal models particularly that testosterone does appear to be neuroprotective and anti-inflammatory,” said Dr. Chitnis.

According to Ziehn et al, testosterone seemed to be protective against synaptic preservation in animal models. In addition, research has elucidated that testosterone is able to cross the blood-brain barrier in its free form and directly influence neuronal cells. Other studies suggest that testosterone protects spinal cord neurons from glutamate toxicity, and protects from oxidative stress in neuronal cell lines.

Sex-Stratified MS Risk, Prenatal Exposure, and Puberty

To understand whether testosterone levels predispose men to MS, researchers studied a measure called the second-digit-fourth-digit ratio (2D:4D) and found that it was associated with MS in men. Researchers have also discovered that there may be prenatal risk factors that may increase susceptibility in men. While studies suggest that breast-feeding is associated with a reduced risk of MS in boys, maternal illness and pesticide exposure in pregnancy and during the prenatal stage were associated with an increased risk for pediatric-onset MS.

Puberty also may be a turning point for the initiation of MS in boys, said Dr. Chitnis. “Younger males with MS show evidence of earlier puberty than regional controls. It is unclear if they have lower testosterone, however, research does suggest a disturbance in sex hormones early on,” she said.

Testosterone as an MS Therapy?

Several benefits have been associated with testosterone as a potential therapy, such as improved libido, increased muscle strength, improved bone density, and potentially improved memory and other cognitive measures. However, there are serious risks associated with testosterone therapy such as an increased prostate specific antigen, increased susceptibility to cancer, emotional lability, hypertension, increased hemoglobin, and increased cardiovascular events.

There may be benefits with regard to slowing disease progression and cognitive decline that warrant further study, said Dr. Chitnis. She added that future studies should focus on “mechanisms and interactions of sex hormones and testosterone in boys with MS, as well as safety and efficacy of testosterone in men with MS.”

—Erica Tricarico

Suggested Reading

Bove R, Malik MT, Diaz-Cruz C, et al. The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS. Neurology. 2015;85(14):1209-1213.

Kalincik T, Vivek V, Jokubaitis V, et al. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain. 2013;136(Pt 12):3609-3617.

Raghavan K, Healy BC, Carruthers RL, Chitnis T. Progression rates and sample size estimates for PPMS based on the CLIMB study population. Mult Scler. 2015;21(2):180-188.

Ziehn MO, Avedisian AA, Dervin SM, et al. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012; 32(36):12312-12324.

ORLANDO—Although multiple sclerosis (MS) is more common in women, when men develop MS, it tends to be worse. Studies indicate that MS in men is associated with a faster accrual of disability and worse relapse recovery. In addition, research suggests that male gender is a predictor for more severe forms of MS. Also, there appears to be a higher male-to-female ratio in primary progressive MS (PPMS), compared with relapsing forms of MS.

Role of Sex Chromosomes and Hormones

Studies suggest that women are predisposed to higher rates of MS relapses than men. Kalincik et al found that there was approximately a 1:1 male-to-female ratio in PPMS onset, compared with a 1:3 male-to-female ratio in relapsing-onset MS. “One of the interesting paradigms they looked at was the proportion of relapses or the relapse count over the course of 10 years and the female-to-male ratio and how it has increased to become predominately female with a higher relapse count. This certainly suggests that hormones and sex may be driving a relapsing phenotype,” said Dr. Chitnis.

Raghavan et al found that men appeared to have higher Expanded Disability Status Scale scores over disease duration in relapsing forms of MS compared with PPMS. In addition, when researchers observed optic neuritis as a model of relapse recovery, they found that male gender was associated with worse recovery from optic neuritis despite adjusting for disease severity as well as vitamin D levels.

Is Testosterone Neuroprotective?

Previous studies in MS suggest that low testosterone is associated with worse disability. Studies have also associated low testosterone levels with more cognitive decline in MS. Following up on these clinical observations, Dr. Chitnis and colleagues conducted the CLIMB study, a long-term study of how MS changes over time, to observe testosterone levels in men with MS. Data from the study, which involved nearly 100 men with MS, revealed that there were significantly reduced testosterone levels in a majority of the males.

Although lower levels of testosterone may be a risk factor for rapid disability accrual, testosterone supplementation appears to be neuroprotective. “There is a vast amount of literature now demonstrating in animal models particularly that testosterone does appear to be neuroprotective and anti-inflammatory,” said Dr. Chitnis.

According to Ziehn et al, testosterone seemed to be protective against synaptic preservation in animal models. In addition, research has elucidated that testosterone is able to cross the blood-brain barrier in its free form and directly influence neuronal cells. Other studies suggest that testosterone protects spinal cord neurons from glutamate toxicity, and protects from oxidative stress in neuronal cell lines.

Sex-Stratified MS Risk, Prenatal Exposure, and Puberty

To understand whether testosterone levels predispose men to MS, researchers studied a measure called the second-digit-fourth-digit ratio (2D:4D) and found that it was associated with MS in men. Researchers have also discovered that there may be prenatal risk factors that may increase susceptibility in men. While studies suggest that breast-feeding is associated with a reduced risk of MS in boys, maternal illness and pesticide exposure in pregnancy and during the prenatal stage were associated with an increased risk for pediatric-onset MS.

Puberty also may be a turning point for the initiation of MS in boys, said Dr. Chitnis. “Younger males with MS show evidence of earlier puberty than regional controls. It is unclear if they have lower testosterone, however, research does suggest a disturbance in sex hormones early on,” she said.

Testosterone as an MS Therapy?

Several benefits have been associated with testosterone as a potential therapy, such as improved libido, increased muscle strength, improved bone density, and potentially improved memory and other cognitive measures. However, there are serious risks associated with testosterone therapy such as an increased prostate specific antigen, increased susceptibility to cancer, emotional lability, hypertension, increased hemoglobin, and increased cardiovascular events.

There may be benefits with regard to slowing disease progression and cognitive decline that warrant further study, said Dr. Chitnis. She added that future studies should focus on “mechanisms and interactions of sex hormones and testosterone in boys with MS, as well as safety and efficacy of testosterone in men with MS.”

—Erica Tricarico

Suggested Reading

Bove R, Malik MT, Diaz-Cruz C, et al. The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS. Neurology. 2015;85(14):1209-1213.

Kalincik T, Vivek V, Jokubaitis V, et al. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain. 2013;136(Pt 12):3609-3617.

Raghavan K, Healy BC, Carruthers RL, Chitnis T. Progression rates and sample size estimates for PPMS based on the CLIMB study population. Mult Scler. 2015;21(2):180-188.

Ziehn MO, Avedisian AA, Dervin SM, et al. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012; 32(36):12312-12324.

Substance use disorder should be approached as a chronic medical condition, with treatment programs in place of incarceration and improved training programs with which physicians can treat patients with substance abuse.

Such programs are among the eight major recommendations the American College of Physicians has made to improve the nation’s approach to preventing and treating substance abuse in a position paper released March 27 (Ann Intern Med. 2017. doi: 10.7326/M16-2953).

The ACP’s recommendations address the growing rates of opioid addiction, as well as the financial burden of substance abuse on the medical system.

“In 2014, 22.5 million people in the United States needed treatment for an illicit drug or alcohol use problem, but only 18% received any treatment,” according to the paper’s authors. “The medical complications of untreated substance use disorder also drive up health care system costs. Hospitalizations for opioid use disorder rose from nearly 302,000 to more than 520,000 from 2002 to 2012, and costs for such care quadrupled to $15 billion in 2012.”

The complete list of the ACP’s recommendations are:

1) Substance abuse should be approached as a chronic medical disorder. Substance abuse can be treated through evidence-based health programs, according to the ACP. Effort should be put into developing research initiatives, as well as combating the social stigmas associated with substance use disorders.

2) The ACP encourages the establishment of substance abuse programs as a replacement for incarceration. Treatment for substance abuse is a time-sensitive matter, which should be given to patients as soon as possible, including those found guilty of the sale or possession of illegal substances.

3) Policy makers should consider reducing the punishments for drug-related crimes committed by nonviolent offenders. Officials should consider decriminalization, legalization, or treatment alternatives for crimes regarding certain drugs based on the potential risk associated with that drug, the accessibility of treatment in criminal facilities, any disproportionate affects on different sections of the population, and the potential decrease in rates of abuses.

4) There should be multiple stakeholders involved in the creation of programs to eliminate substance abuse. Physicians, policymakers, advocacy groups, and health care professionals are encouraged to work together to create strategies to combat and prevent substance abuse, including programs that expand naloxone access for opioid users or the establishment of a national prescription drug monitoring program. Extensive education programs on proper pain reduction methods should also be made available to physicians to help prevent future dependencies.

5) Coverage of substance use and mental disorder treatments should be mandatory for health insurance companies. Evidence-based treatments for mental health conditions and substance abuse, including counseling, medications, legal services, and education, should be covered by patients’ health insurance. The ACP asserts strict oversight would be essential; however, it is also essential that patients receive nonpharmacologic treatments, which are usually not covered by insurance.

6) There should be an increase in professionals trained to treat substance abuse. There are 4,500 health care professionals in the United States who have mental health and/or substance abuse training, according to the Health Resources and Services Administration. This number shows a high demand for those qualified to treat mental health conditions and substance abuse. Efforts should also be focused on creating a more ethnically diverse group among trained professionals to further increase access to these services.

7) Substance abuse treatment methods should be added to professionals’ continuing medical education. In 2000, 17% of primary care physicians felt very prepared to identify illegal drug use, and 30% could identify drug misuse, according to a study conducted by the National Center on Addiction and Substance Abuse. In response, education for physicians “should be rigorously evaluated to ensure effectiveness and continued access to care and should be designed to prevent onerous burdens on patients and physicians,” according to the paper’s authors.

8) Further study should be conducted on effectiveness of substance abuse programs. Current substance abuse intervention methods should be evaluated to see how effective they are. Among those, safe injection sites should especially be encouraged, as these initiatives have proven effective in reducing unsafe needle sharing in Canada, Australia, and Denmark.

The researchers had no relevant financial disclosures.

[email protected] On Twitter @EAZTweets

Substance use disorder should be approached as a chronic medical condition, with treatment programs in place of incarceration and improved training programs with which physicians can treat patients with substance abuse.

Such programs are among the eight major recommendations the American College of Physicians has made to improve the nation’s approach to preventing and treating substance abuse in a position paper released March 27 (Ann Intern Med. 2017. doi: 10.7326/M16-2953).

The ACP’s recommendations address the growing rates of opioid addiction, as well as the financial burden of substance abuse on the medical system.

“In 2014, 22.5 million people in the United States needed treatment for an illicit drug or alcohol use problem, but only 18% received any treatment,” according to the paper’s authors. “The medical complications of untreated substance use disorder also drive up health care system costs. Hospitalizations for opioid use disorder rose from nearly 302,000 to more than 520,000 from 2002 to 2012, and costs for such care quadrupled to $15 billion in 2012.”

The complete list of the ACP’s recommendations are:

1) Substance abuse should be approached as a chronic medical disorder. Substance abuse can be treated through evidence-based health programs, according to the ACP. Effort should be put into developing research initiatives, as well as combating the social stigmas associated with substance use disorders.

2) The ACP encourages the establishment of substance abuse programs as a replacement for incarceration. Treatment for substance abuse is a time-sensitive matter, which should be given to patients as soon as possible, including those found guilty of the sale or possession of illegal substances.

3) Policy makers should consider reducing the punishments for drug-related crimes committed by nonviolent offenders. Officials should consider decriminalization, legalization, or treatment alternatives for crimes regarding certain drugs based on the potential risk associated with that drug, the accessibility of treatment in criminal facilities, any disproportionate affects on different sections of the population, and the potential decrease in rates of abuses.

4) There should be multiple stakeholders involved in the creation of programs to eliminate substance abuse. Physicians, policymakers, advocacy groups, and health care professionals are encouraged to work together to create strategies to combat and prevent substance abuse, including programs that expand naloxone access for opioid users or the establishment of a national prescription drug monitoring program. Extensive education programs on proper pain reduction methods should also be made available to physicians to help prevent future dependencies.

5) Coverage of substance use and mental disorder treatments should be mandatory for health insurance companies. Evidence-based treatments for mental health conditions and substance abuse, including counseling, medications, legal services, and education, should be covered by patients’ health insurance. The ACP asserts strict oversight would be essential; however, it is also essential that patients receive nonpharmacologic treatments, which are usually not covered by insurance.

6) There should be an increase in professionals trained to treat substance abuse. There are 4,500 health care professionals in the United States who have mental health and/or substance abuse training, according to the Health Resources and Services Administration. This number shows a high demand for those qualified to treat mental health conditions and substance abuse. Efforts should also be focused on creating a more ethnically diverse group among trained professionals to further increase access to these services.

7) Substance abuse treatment methods should be added to professionals’ continuing medical education. In 2000, 17% of primary care physicians felt very prepared to identify illegal drug use, and 30% could identify drug misuse, according to a study conducted by the National Center on Addiction and Substance Abuse. In response, education for physicians “should be rigorously evaluated to ensure effectiveness and continued access to care and should be designed to prevent onerous burdens on patients and physicians,” according to the paper’s authors.

8) Further study should be conducted on effectiveness of substance abuse programs. Current substance abuse intervention methods should be evaluated to see how effective they are. Among those, safe injection sites should especially be encouraged, as these initiatives have proven effective in reducing unsafe needle sharing in Canada, Australia, and Denmark.

The researchers had no relevant financial disclosures.

[email protected] On Twitter @EAZTweets

Substance use disorder should be approached as a chronic medical condition, with treatment programs in place of incarceration and improved training programs with which physicians can treat patients with substance abuse.

Such programs are among the eight major recommendations the American College of Physicians has made to improve the nation’s approach to preventing and treating substance abuse in a position paper released March 27 (Ann Intern Med. 2017. doi: 10.7326/M16-2953).

The ACP’s recommendations address the growing rates of opioid addiction, as well as the financial burden of substance abuse on the medical system.

“In 2014, 22.5 million people in the United States needed treatment for an illicit drug or alcohol use problem, but only 18% received any treatment,” according to the paper’s authors. “The medical complications of untreated substance use disorder also drive up health care system costs. Hospitalizations for opioid use disorder rose from nearly 302,000 to more than 520,000 from 2002 to 2012, and costs for such care quadrupled to $15 billion in 2012.”

The complete list of the ACP’s recommendations are:

1) Substance abuse should be approached as a chronic medical disorder. Substance abuse can be treated through evidence-based health programs, according to the ACP. Effort should be put into developing research initiatives, as well as combating the social stigmas associated with substance use disorders.

2) The ACP encourages the establishment of substance abuse programs as a replacement for incarceration. Treatment for substance abuse is a time-sensitive matter, which should be given to patients as soon as possible, including those found guilty of the sale or possession of illegal substances.

3) Policy makers should consider reducing the punishments for drug-related crimes committed by nonviolent offenders. Officials should consider decriminalization, legalization, or treatment alternatives for crimes regarding certain drugs based on the potential risk associated with that drug, the accessibility of treatment in criminal facilities, any disproportionate affects on different sections of the population, and the potential decrease in rates of abuses.

4) There should be multiple stakeholders involved in the creation of programs to eliminate substance abuse. Physicians, policymakers, advocacy groups, and health care professionals are encouraged to work together to create strategies to combat and prevent substance abuse, including programs that expand naloxone access for opioid users or the establishment of a national prescription drug monitoring program. Extensive education programs on proper pain reduction methods should also be made available to physicians to help prevent future dependencies.

5) Coverage of substance use and mental disorder treatments should be mandatory for health insurance companies. Evidence-based treatments for mental health conditions and substance abuse, including counseling, medications, legal services, and education, should be covered by patients’ health insurance. The ACP asserts strict oversight would be essential; however, it is also essential that patients receive nonpharmacologic treatments, which are usually not covered by insurance.

6) There should be an increase in professionals trained to treat substance abuse. There are 4,500 health care professionals in the United States who have mental health and/or substance abuse training, according to the Health Resources and Services Administration. This number shows a high demand for those qualified to treat mental health conditions and substance abuse. Efforts should also be focused on creating a more ethnically diverse group among trained professionals to further increase access to these services.

7) Substance abuse treatment methods should be added to professionals’ continuing medical education. In 2000, 17% of primary care physicians felt very prepared to identify illegal drug use, and 30% could identify drug misuse, according to a study conducted by the National Center on Addiction and Substance Abuse. In response, education for physicians “should be rigorously evaluated to ensure effectiveness and continued access to care and should be designed to prevent onerous burdens on patients and physicians,” according to the paper’s authors.

8) Further study should be conducted on effectiveness of substance abuse programs. Current substance abuse intervention methods should be evaluated to see how effective they are. Among those, safe injection sites should especially be encouraged, as these initiatives have proven effective in reducing unsafe needle sharing in Canada, Australia, and Denmark.

The researchers had no relevant financial disclosures.

[email protected] On Twitter @EAZTweets