WASHINGTON – Enrolling a transgender man in the iPLEDGE pregnancy prevention program is among the issues dermatologists can face when caring for transgender patients, Dr. Brian Ginsberg said at the annual meeting of the American Academy of Dermatology.*

iPLEDGE requirements are based on an individual’s gender, not only on their potential childbearing potential, “making it a challenge to appropriately classify our transgender patients,” said Dr. Ginsberg, a dermatologist in private practice in New York. Enrolling a transgender man who is experiencing severe acne vulgaris as a result of hormone therapy is one of the hurdles in caring for this patient population, he added.

Dr. Ginsberg provided advice on how to manage adverse effects of hormone therapy on skin and hair, and other dermatologic issues that transgender individuals may experience. Because there is not much information on this topic in the medical literature, he pointed out that his recommendations are based largely on personal and anecdotal experiences.

Transgender men taking testosterone experience significant increases in sebum production, and there are many reports of transgender men with severe acne vulgaris, he noted.

Transgender men may still be of childbearing potential, even if they are on testosterone, and he typically keeps his transgender male patients classified as females of childbearing potential, for the sake of iPLEDGE, and has “a very important and honest conversation with them” about having to register as females.

“It’s unfortunate that for now, we have to have that conversation,” but it must be done, he added.

A member of the audience said he has a transgender male patient who is preparing for reduction mammoplasty, is on testosterone, has severe acne, and was previously registered in the iPLEDGE program as a female. “So what’s my next step?” he asked.

Dr. Ginsberg said he has had patients in the same situation, and after having an honest conversation with the patient, “we realized the priority was getting the patient on isotretinoin and the patient was comfortable in maintaining the registration as a female of childbearing potential.”

This is not an issue for female transgender patients, who do not have a uterus and are not of childbearing potential. These patients are, however, at an increased risk of hormone-associated dermatoses.

“Transgender women taking estrogens experience rapid and prolonged low sebum production, resulting in xerosis and asteatotic eczema,” he said.

Another issue is when to prescribe finasteride for transgender men on testosterone who experience male pattern hair loss. He advised avoiding finasteride until body hair and other desired secondary sex characteristics are fully developed, which could be up to 2 years, Dr. Ginsberg said.

To make transgender patients more comfortable in the office, Dr. Ginsberg recommended the following:

• Modify intake forms. Allow for patients to write in their gender, instead of offering the option of male or female.

• Respect the use of correct pronouns. “If you have a transgender woman sitting in front of you, don’t refer to her as him,” he commented. Consider asking the patient which pronoun is preferred.

• Make no assumptions. “Gender identity has nothing to do with sexual orientation,” he said. “A person’s gender is however they self-identify, period.” It has nothing to do with clothing, hormones, surgery “or any other aspect of transitioning,” he explained. “If a patient sitting in front of you says that they are a man, it doesn’t matter what they look like or what they’ve had done, that person is a man.”

• Be comfortable about being uncomfortable. “The community is coming to understand that we don’t know everything. … and we may have questions, we may not understand the details of the surgery or medications that they’re on. So rather than ignore the issue altogether, ask them about it,” Dr. Ginsberg said. “They will be more excited that you care … and want to help, rather than ignore the issue altogether.” Dr. Ginsberg reported no relevant disclosures.

[email protected]

This article was updated March 8, 2016.

*Correction, 03/15/2016: An earlier version of this article misstated Dr. Brian Ginsberg's name. 

WASHINGTON – Enrolling a transgender man in the iPLEDGE pregnancy prevention program is among the issues dermatologists can face when caring for transgender patients, Dr. Brian Ginsberg said at the annual meeting of the American Academy of Dermatology.*

iPLEDGE requirements are based on an individual’s gender, not only on their potential childbearing potential, “making it a challenge to appropriately classify our transgender patients,” said Dr. Ginsberg, a dermatologist in private practice in New York. Enrolling a transgender man who is experiencing severe acne vulgaris as a result of hormone therapy is one of the hurdles in caring for this patient population, he added.

Dr. Ginsberg provided advice on how to manage adverse effects of hormone therapy on skin and hair, and other dermatologic issues that transgender individuals may experience. Because there is not much information on this topic in the medical literature, he pointed out that his recommendations are based largely on personal and anecdotal experiences.

Transgender men taking testosterone experience significant increases in sebum production, and there are many reports of transgender men with severe acne vulgaris, he noted.

Transgender men may still be of childbearing potential, even if they are on testosterone, and he typically keeps his transgender male patients classified as females of childbearing potential, for the sake of iPLEDGE, and has “a very important and honest conversation with them” about having to register as females.

“It’s unfortunate that for now, we have to have that conversation,” but it must be done, he added.

A member of the audience said he has a transgender male patient who is preparing for reduction mammoplasty, is on testosterone, has severe acne, and was previously registered in the iPLEDGE program as a female. “So what’s my next step?” he asked.

Dr. Ginsberg said he has had patients in the same situation, and after having an honest conversation with the patient, “we realized the priority was getting the patient on isotretinoin and the patient was comfortable in maintaining the registration as a female of childbearing potential.”

This is not an issue for female transgender patients, who do not have a uterus and are not of childbearing potential. These patients are, however, at an increased risk of hormone-associated dermatoses.

“Transgender women taking estrogens experience rapid and prolonged low sebum production, resulting in xerosis and asteatotic eczema,” he said.

Another issue is when to prescribe finasteride for transgender men on testosterone who experience male pattern hair loss. He advised avoiding finasteride until body hair and other desired secondary sex characteristics are fully developed, which could be up to 2 years, Dr. Ginsberg said.

To make transgender patients more comfortable in the office, Dr. Ginsberg recommended the following:

• Modify intake forms. Allow for patients to write in their gender, instead of offering the option of male or female.

• Respect the use of correct pronouns. “If you have a transgender woman sitting in front of you, don’t refer to her as him,” he commented. Consider asking the patient which pronoun is preferred.

• Make no assumptions. “Gender identity has nothing to do with sexual orientation,” he said. “A person’s gender is however they self-identify, period.” It has nothing to do with clothing, hormones, surgery “or any other aspect of transitioning,” he explained. “If a patient sitting in front of you says that they are a man, it doesn’t matter what they look like or what they’ve had done, that person is a man.”

• Be comfortable about being uncomfortable. “The community is coming to understand that we don’t know everything. … and we may have questions, we may not understand the details of the surgery or medications that they’re on. So rather than ignore the issue altogether, ask them about it,” Dr. Ginsberg said. “They will be more excited that you care … and want to help, rather than ignore the issue altogether.” Dr. Ginsberg reported no relevant disclosures.

[email protected]

This article was updated March 8, 2016.

*Correction, 03/15/2016: An earlier version of this article misstated Dr. Brian Ginsberg's name. 

WASHINGTON – Enrolling a transgender man in the iPLEDGE pregnancy prevention program is among the issues dermatologists can face when caring for transgender patients, Dr. Brian Ginsberg said at the annual meeting of the American Academy of Dermatology.*

iPLEDGE requirements are based on an individual’s gender, not only on their potential childbearing potential, “making it a challenge to appropriately classify our transgender patients,” said Dr. Ginsberg, a dermatologist in private practice in New York. Enrolling a transgender man who is experiencing severe acne vulgaris as a result of hormone therapy is one of the hurdles in caring for this patient population, he added.

Dr. Ginsberg provided advice on how to manage adverse effects of hormone therapy on skin and hair, and other dermatologic issues that transgender individuals may experience. Because there is not much information on this topic in the medical literature, he pointed out that his recommendations are based largely on personal and anecdotal experiences.

Transgender men taking testosterone experience significant increases in sebum production, and there are many reports of transgender men with severe acne vulgaris, he noted.

Transgender men may still be of childbearing potential, even if they are on testosterone, and he typically keeps his transgender male patients classified as females of childbearing potential, for the sake of iPLEDGE, and has “a very important and honest conversation with them” about having to register as females.

“It’s unfortunate that for now, we have to have that conversation,” but it must be done, he added.

A member of the audience said he has a transgender male patient who is preparing for reduction mammoplasty, is on testosterone, has severe acne, and was previously registered in the iPLEDGE program as a female. “So what’s my next step?” he asked.

Dr. Ginsberg said he has had patients in the same situation, and after having an honest conversation with the patient, “we realized the priority was getting the patient on isotretinoin and the patient was comfortable in maintaining the registration as a female of childbearing potential.”

This is not an issue for female transgender patients, who do not have a uterus and are not of childbearing potential. These patients are, however, at an increased risk of hormone-associated dermatoses.

“Transgender women taking estrogens experience rapid and prolonged low sebum production, resulting in xerosis and asteatotic eczema,” he said.

Another issue is when to prescribe finasteride for transgender men on testosterone who experience male pattern hair loss. He advised avoiding finasteride until body hair and other desired secondary sex characteristics are fully developed, which could be up to 2 years, Dr. Ginsberg said.

To make transgender patients more comfortable in the office, Dr. Ginsberg recommended the following:

• Modify intake forms. Allow for patients to write in their gender, instead of offering the option of male or female.

• Respect the use of correct pronouns. “If you have a transgender woman sitting in front of you, don’t refer to her as him,” he commented. Consider asking the patient which pronoun is preferred.

• Make no assumptions. “Gender identity has nothing to do with sexual orientation,” he said. “A person’s gender is however they self-identify, period.” It has nothing to do with clothing, hormones, surgery “or any other aspect of transitioning,” he explained. “If a patient sitting in front of you says that they are a man, it doesn’t matter what they look like or what they’ve had done, that person is a man.”

• Be comfortable about being uncomfortable. “The community is coming to understand that we don’t know everything. … and we may have questions, we may not understand the details of the surgery or medications that they’re on. So rather than ignore the issue altogether, ask them about it,” Dr. Ginsberg said. “They will be more excited that you care … and want to help, rather than ignore the issue altogether.” Dr. Ginsberg reported no relevant disclosures.

[email protected]

This article was updated March 8, 2016.

*Correction, 03/15/2016: An earlier version of this article misstated Dr. Brian Ginsberg's name. 

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

[email protected]

On Twitter @richpizzi

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

[email protected]

On Twitter @richpizzi

All kidney transplant recipients with abnormal liver function test results should be tested for hepatitis E virus RNA, according to a recent finding by French investigators.

Hepatitis E virus (HEV) is most often transmitted through the fecal-oral route in contaminated drinking water or food, but it also can be transmitted by blood and blood products. A research letter from Dr. Vincent Mallett of the Université Paris Descartes Sorbonne Paris Cité and colleagues published in Annals of Internal Medicine reported a case of HEV transmission to a kidney transplant recipient through plasma exchange.

CDC/Wikimedia Commons/Public Domain

Nineteen months after a 48-year-old patient received a kidney transplant, Dr. Mallett and his colleagues detected HEV RNA genotype 3f in the patient’s blood based on sequencing, and the patient tested positive for anti-HEV IgG and negative for anti-HEV IgM. The physicians confirmed that the patient had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and the patient’s stored blood samples tested negative for HEV markers before transplantation.

The investigators said that the method of HEV transmission remained undetermined until the investigators tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh frozen plasma from a donor who had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, the researchers recovered a strain of HEV identical to the one infecting the patient. This plasma had been used during a plasma exchange for treating acute humoral rejection.

Plasma exchange typically involves the removal of 2-5 L of plasma several times a week, Dr. Mallett and associates said, which often is replaced with donor plasma. If replacement involves 2.5 L (10 bags) of donor plasma, which is a typical amount, then the risk for HEV is 10 times greater than the risk involving a single bag.

“In some circumstances, replacement procedures use plasma that has been pooled from many donors and then treated with solvents and detergents to inactivate infectious agents,” they wrote. “However, HEV is not affected by this treatment, so pooling multiplies the risk for infection.”

On the basis of these findings, the coauthors said that “all kidney transplant recipients with abnormal liver function test results, especially those treated with plasma exchange, should be tested for HEV RNA.”

Read the letter in Annals of Internal Medicine (2016 Mar 1. doi: 10.7326/L15-0502).

[email protected]

On Twitter @richpizzi

Presenter: Jim Pile, MD, Cleveland Clinic

Summary: The following three infectious diagnoses are relatively uncommon but important not to miss as they are associated with high mortality, especially when diagnosis and treatment are delayed. Remembering these key points can help you make the diagnosis:

• Bacterial meningitis: Many patients do not have the classic triad—fever, nuchal rigidity, and altered mental status—but nearly all have at least one of these signs, and most have headache. The jolt accentuation test—horizontal movement of the head causing exacerbation of the headache—is more sensitive than nuchal rigidity in these cases. Diagnosis is confirmed by lumbar puncture. It appears safe to not to perform head CT in patients

• Spinal epidural abscess: Risk factors include DM, IV drug use, hemodialysis, UTI, trauma, epidural anesthesia, trauma/surgery. Presentation is acute to indolent and usually consists of four stages: central back pain, radicular pain, neurologic deficits, paralysis; fever variable. Checking ESR can be helpful as it is elevated in most cases. MRI is imaging study of choice. Initial management includes antibiotics to coverage Staph Aureus and gram negative rods and surgery consultation.
• Necrotizing soft tissue infection: Risk factors include DM, IV drug use, trauma/surgery, ETOH, immunosuppression (Type I); muscle trauma, skin integrity deficits (Type II). Clinical suspicion is paramount. Specific clues include: pain out of proportion, anesthesia, systemic toxicity, rapid progression, bullae/crepitus, and failure to respond to antibiotics. Initial management includes initiation of B-lactam/lactamase inhibitor or carbapenem plus clindamycin and MRSA coverage, imaging and prompt surgical consultation (as delayed/inadequate surgery associated with poor prognosis.

Key Takeaway

Clinical suspicion is key to diagnosis of bacterial meningitis, spinal epidural abscesses, and necrotizing soft tissue infections, and delays in diagnosis and treatment are associated with increased mortality.TH

Presenter: Jim Pile, MD, Cleveland Clinic

Summary: The following three infectious diagnoses are relatively uncommon but important not to miss as they are associated with high mortality, especially when diagnosis and treatment are delayed. Remembering these key points can help you make the diagnosis:

• Bacterial meningitis: Many patients do not have the classic triad—fever, nuchal rigidity, and altered mental status—but nearly all have at least one of these signs, and most have headache. The jolt accentuation test—horizontal movement of the head causing exacerbation of the headache—is more sensitive than nuchal rigidity in these cases. Diagnosis is confirmed by lumbar puncture. It appears safe to not to perform head CT in patients

• Spinal epidural abscess: Risk factors include DM, IV drug use, hemodialysis, UTI, trauma, epidural anesthesia, trauma/surgery. Presentation is acute to indolent and usually consists of four stages: central back pain, radicular pain, neurologic deficits, paralysis; fever variable. Checking ESR can be helpful as it is elevated in most cases. MRI is imaging study of choice. Initial management includes antibiotics to coverage Staph Aureus and gram negative rods and surgery consultation.
• Necrotizing soft tissue infection: Risk factors include DM, IV drug use, trauma/surgery, ETOH, immunosuppression (Type I); muscle trauma, skin integrity deficits (Type II). Clinical suspicion is paramount. Specific clues include: pain out of proportion, anesthesia, systemic toxicity, rapid progression, bullae/crepitus, and failure to respond to antibiotics. Initial management includes initiation of B-lactam/lactamase inhibitor or carbapenem plus clindamycin and MRSA coverage, imaging and prompt surgical consultation (as delayed/inadequate surgery associated with poor prognosis.

Key Takeaway

Clinical suspicion is key to diagnosis of bacterial meningitis, spinal epidural abscesses, and necrotizing soft tissue infections, and delays in diagnosis and treatment are associated with increased mortality.TH

Presenter: Jim Pile, MD, Cleveland Clinic

Summary: The following three infectious diagnoses are relatively uncommon but important not to miss as they are associated with high mortality, especially when diagnosis and treatment are delayed. Remembering these key points can help you make the diagnosis:

• Bacterial meningitis: Many patients do not have the classic triad—fever, nuchal rigidity, and altered mental status—but nearly all have at least one of these signs, and most have headache. The jolt accentuation test—horizontal movement of the head causing exacerbation of the headache—is more sensitive than nuchal rigidity in these cases. Diagnosis is confirmed by lumbar puncture. It appears safe to not to perform head CT in patients

• Spinal epidural abscess: Risk factors include DM, IV drug use, hemodialysis, UTI, trauma, epidural anesthesia, trauma/surgery. Presentation is acute to indolent and usually consists of four stages: central back pain, radicular pain, neurologic deficits, paralysis; fever variable. Checking ESR can be helpful as it is elevated in most cases. MRI is imaging study of choice. Initial management includes antibiotics to coverage Staph Aureus and gram negative rods and surgery consultation.
• Necrotizing soft tissue infection: Risk factors include DM, IV drug use, trauma/surgery, ETOH, immunosuppression (Type I); muscle trauma, skin integrity deficits (Type II). Clinical suspicion is paramount. Specific clues include: pain out of proportion, anesthesia, systemic toxicity, rapid progression, bullae/crepitus, and failure to respond to antibiotics. Initial management includes initiation of B-lactam/lactamase inhibitor or carbapenem plus clindamycin and MRSA coverage, imaging and prompt surgical consultation (as delayed/inadequate surgery associated with poor prognosis.

Key Takeaway

Clinical suspicion is key to diagnosis of bacterial meningitis, spinal epidural abscesses, and necrotizing soft tissue infections, and delays in diagnosis and treatment are associated with increased mortality.TH

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.

A new tool – a clinical risk score – may help identify which children and adolescents who recently sustained a head injury are at risk for persistent postconcussion symptoms, according to a report published online March 7 in JAMA.

Approximately one-third of pediatric patients with concussion will have ongoing somatic, cognitive, psychological, and/or behavioral symptoms at 28 days, and at present, there are no tools to help predict which patients will be affected. The 5P (Preventing Postconcussive Problems in Pediatrics) study was performed to develop and validate a clinical risk score for this purpose, said Dr. Roger Zemek of Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and his associates (JAMA 2016 Mar 8;315[10]:1014-25).

This prospective cohort study involved patients aged 5-17 years (median age, 12 years) who presented to one of nine Canadian pediatric emergency departments within 48 hours of sustaining a concussion.

In the derivation cohort, 510 of 1,701 participants (30%) met the criteria for persistent postconcussion symptoms (PPCS). A total of 47 possible predictive variables were assessed for their usefulness in predicting PPCS in this cohort. They were collected from demographic data, patient history, injury characteristics, physical examination, results on the Acute Concussion Evaluation Inventory and the Postconcussion Symptom Inventory, and patient/parent responses to weekly follow-up surveys during the month following the injury.

The investigators devised a clinical risk score using the nine predictors they found to be most accurate: patient age, patient gender, the presence or absence of prior concussion, migraine history, the presence or absence of current headache, sensitivity to noise, fatigue, slow responses to questions, and an abnormal tandem stance. They then selected three cutoff points to delineate PPCS risk: 0-3 points indicated low risk, 4-8 points indicated intermediate risk, and 9 or more points indicated high risk.

Treating physicians also were asked to predict the likelihood of PPCS.

In the validation cohort, 291 of 883 participants (33%) met the criteria for PPCS.

For low-risk patients, the sensitivity of the clinical risk score was 94%, the specificity was 18%, the negative predictive value was 85%, and the positive predictive value was 36%. For high-risk patients, the sensitivity of the clinical risk score was 20%, the specificity was 94%, the negative predictive value was 70%, and the positive predictive value was 60%.

In both sets of patients, the clinical risk score was significantly better than physician judgment in predicting PPCS. However, in its present form, it is only modestly accurate at distinguishing who will and who will not have the disorder. This tool could be further refined, perhaps by adding information regarding biomarkers, genetic susceptibility, or advanced neuroimaging, Dr. Zemek and his associates wrote.

“Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility,” they concluded.

This work was supported by the Canadian Institutes of Health Research, the Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team, and the Alberta Children’s Hospital Foundation. Dr. Zemek and his associates reported having no relevant financial disclosures.

The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.

Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.

They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.

“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.

In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.

The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.

The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.

The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.

The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.

Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).

The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.

Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.

They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.

“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.

In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.

The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.

The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.

The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.

The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.

Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).

The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.

Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.

They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.

“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.

In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.

The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.

The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.

The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.

The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.

Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).

HM16 Presenters: Mangla Gulati, MD, FACP, FHM, and Ian Jenkins, MD

Summary: There is some evidence that hospital adverse events may be decreasing. The Agency for Healthcare Research and Quality (AHRQ) report of Partnership for Patients data found that there were 1.3 million hospital-acquired conditions prevented from 2011-2013, translating to 50,000 lives saved and $12 billion in savings. However, there is still much work to be done. Here are some major themes from the recent literature that may inform your own QI projects:

• Electronic medical records (EMR): Increased adoption raises concerns for unintended consequences which could detract from patient safety. These are derived from case reports, claims databases, reports through patient safety organizations. Consider reviewing alerts, advisories, and hard-stops within your hospital’s EMR.
• Improving diagnosis: Misdiagnosis affects 10% of Americans but measurement of this phenomenon remains difficult. Strategies to improve diagnosis include: focus on collaboration, teaching diagnostic skills, IT and algorithmic support, feedback and blame reduction, and reimbursement reform. There is growing recognition that hospitalists are well positioned to engage in these efforts.
• Hand hygiene: Multiple culture and environmental contributors to poor compliance (i.e., 40% compliance rate) and few good intervention studies. Recent studies have focused on the development of cause-specific plans and targeted interventions. Consider applying a targeted solutions tool to a project at your hospital.
• “Second victim”: Healthcare providers frequently experience emotional distress following patient safety events but there is a lack of resources to support providers after such an event. Consider implementing a “care for the caregiver” program at your hospital.
• Sepsis: North Shore-LIJ hospital system (in collaboration with the IHI) received the 2014 Eisenberg Award for developing and implementing a Sepsis Recognition Program and tool-kit. Such collaborations may be useful for driving and magnifying your QI initiatives.
• Patient experience: Recent studies emphasize the importance of patients being actively involved in their medical decisions and providing meaningful feedback. Consider implementing a patient/family council and getting involved with local patient experience initiatives.
• Incident reporting systems (IRS): Widespread under-reporting raises concerns over the value of IRS. Consider modifying or minimizing IRS and/or giving reports to local units to ignite safety culture.
• Discharge before noon (DBN): Delayed discharges may result in lost revenue and poor patient satisfaction. Wertheimer et al. reported on a successful intervention to increase DBN in the Journal of Hospital Medicine. Check out their intervention and consider something similar at your hospital.
• Patient monitoring: Vital sign measurements are often poorly timed, integrated and/or communicated. Recent studies of wireless Electronic Physiologic Surveillance System devices in hospitals have shown positive outcomes.TH

HM16 Presenters: Mangla Gulati, MD, FACP, FHM, and Ian Jenkins, MD

Summary: There is some evidence that hospital adverse events may be decreasing. The Agency for Healthcare Research and Quality (AHRQ) report of Partnership for Patients data found that there were 1.3 million hospital-acquired conditions prevented from 2011-2013, translating to 50,000 lives saved and $12 billion in savings. However, there is still much work to be done. Here are some major themes from the recent literature that may inform your own QI projects:

• Electronic medical records (EMR): Increased adoption raises concerns for unintended consequences which could detract from patient safety. These are derived from case reports, claims databases, reports through patient safety organizations. Consider reviewing alerts, advisories, and hard-stops within your hospital’s EMR.
• Improving diagnosis: Misdiagnosis affects 10% of Americans but measurement of this phenomenon remains difficult. Strategies to improve diagnosis include: focus on collaboration, teaching diagnostic skills, IT and algorithmic support, feedback and blame reduction, and reimbursement reform. There is growing recognition that hospitalists are well positioned to engage in these efforts.
• Hand hygiene: Multiple culture and environmental contributors to poor compliance (i.e., 40% compliance rate) and few good intervention studies. Recent studies have focused on the development of cause-specific plans and targeted interventions. Consider applying a targeted solutions tool to a project at your hospital.
• “Second victim”: Healthcare providers frequently experience emotional distress following patient safety events but there is a lack of resources to support providers after such an event. Consider implementing a “care for the caregiver” program at your hospital.
• Sepsis: North Shore-LIJ hospital system (in collaboration with the IHI) received the 2014 Eisenberg Award for developing and implementing a Sepsis Recognition Program and tool-kit. Such collaborations may be useful for driving and magnifying your QI initiatives.
• Patient experience: Recent studies emphasize the importance of patients being actively involved in their medical decisions and providing meaningful feedback. Consider implementing a patient/family council and getting involved with local patient experience initiatives.
• Incident reporting systems (IRS): Widespread under-reporting raises concerns over the value of IRS. Consider modifying or minimizing IRS and/or giving reports to local units to ignite safety culture.
• Discharge before noon (DBN): Delayed discharges may result in lost revenue and poor patient satisfaction. Wertheimer et al. reported on a successful intervention to increase DBN in the Journal of Hospital Medicine. Check out their intervention and consider something similar at your hospital.
• Patient monitoring: Vital sign measurements are often poorly timed, integrated and/or communicated. Recent studies of wireless Electronic Physiologic Surveillance System devices in hospitals have shown positive outcomes.TH

HM16 Presenters: Mangla Gulati, MD, FACP, FHM, and Ian Jenkins, MD

Summary: There is some evidence that hospital adverse events may be decreasing. The Agency for Healthcare Research and Quality (AHRQ) report of Partnership for Patients data found that there were 1.3 million hospital-acquired conditions prevented from 2011-2013, translating to 50,000 lives saved and $12 billion in savings. However, there is still much work to be done. Here are some major themes from the recent literature that may inform your own QI projects:

• Electronic medical records (EMR): Increased adoption raises concerns for unintended consequences which could detract from patient safety. These are derived from case reports, claims databases, reports through patient safety organizations. Consider reviewing alerts, advisories, and hard-stops within your hospital’s EMR.
• Improving diagnosis: Misdiagnosis affects 10% of Americans but measurement of this phenomenon remains difficult. Strategies to improve diagnosis include: focus on collaboration, teaching diagnostic skills, IT and algorithmic support, feedback and blame reduction, and reimbursement reform. There is growing recognition that hospitalists are well positioned to engage in these efforts.
• Hand hygiene: Multiple culture and environmental contributors to poor compliance (i.e., 40% compliance rate) and few good intervention studies. Recent studies have focused on the development of cause-specific plans and targeted interventions. Consider applying a targeted solutions tool to a project at your hospital.
• “Second victim”: Healthcare providers frequently experience emotional distress following patient safety events but there is a lack of resources to support providers after such an event. Consider implementing a “care for the caregiver” program at your hospital.
• Sepsis: North Shore-LIJ hospital system (in collaboration with the IHI) received the 2014 Eisenberg Award for developing and implementing a Sepsis Recognition Program and tool-kit. Such collaborations may be useful for driving and magnifying your QI initiatives.
• Patient experience: Recent studies emphasize the importance of patients being actively involved in their medical decisions and providing meaningful feedback. Consider implementing a patient/family council and getting involved with local patient experience initiatives.
• Incident reporting systems (IRS): Widespread under-reporting raises concerns over the value of IRS. Consider modifying or minimizing IRS and/or giving reports to local units to ignite safety culture.
• Discharge before noon (DBN): Delayed discharges may result in lost revenue and poor patient satisfaction. Wertheimer et al. reported on a successful intervention to increase DBN in the Journal of Hospital Medicine. Check out their intervention and consider something similar at your hospital.
• Patient monitoring: Vital sign measurements are often poorly timed, integrated and/or communicated. Recent studies of wireless Electronic Physiologic Surveillance System devices in hospitals have shown positive outcomes.TH

Thanks to all who attended HM16 in San Diego! From the featured speakers—Acting Assistant Secretary for Health in the U.S. Department of Health and Human Services Karen DeSalvo, MD, MPH, MSc, and faculty—to the attendees and staff, it would not have been such a success without you and your enthusiasm.

Join us again in 2017! Save the dates for another premier networking and educational event in Las Vegas. HM17 is slated for May 1–4, 2017, at Mandalay Bay Resort and Casino. More details will be coming soon.

Thanks to all who attended HM16 in San Diego! From the featured speakers—Acting Assistant Secretary for Health in the U.S. Department of Health and Human Services Karen DeSalvo, MD, MPH, MSc, and faculty—to the attendees and staff, it would not have been such a success without you and your enthusiasm.

Join us again in 2017! Save the dates for another premier networking and educational event in Las Vegas. HM17 is slated for May 1–4, 2017, at Mandalay Bay Resort and Casino. More details will be coming soon.

Thanks to all who attended HM16 in San Diego! From the featured speakers—Acting Assistant Secretary for Health in the U.S. Department of Health and Human Services Karen DeSalvo, MD, MPH, MSc, and faculty—to the attendees and staff, it would not have been such a success without you and your enthusiasm.

Join us again in 2017! Save the dates for another premier networking and educational event in Las Vegas. HM17 is slated for May 1–4, 2017, at Mandalay Bay Resort and Casino. More details will be coming soon.

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

Pill production

Photo courtesy of the FDA

The European Medicines Agency (EMA) has launched PRIME (PRIority MEdicines), an initiative intended to accelerate the development of drugs that target unmet medical needs.

These “priority medicines” may offer a major therapeutic advantage over existing treatments or benefit patients who currently have no treatment options in the European Union (EU).

Through PRIME, the EMA will offer early support to drug developers to optimize the generation of robust data on a treatment’s benefits and risks and enable accelerated assessment of an application for marketing authorization.

By engaging with developers early, the EMA aims to strengthen the design of clinical trials to facilitate the generation of high quality data to support an application for marketing authorization.

PRIME builds on the existing regulatory framework and available tools such as scientific advice and accelerated assessment.

To be accepted for PRIME, a treatment has to show the potential to benefit patients with unmet medical needs based on early clinical data.

Once a candidate medicine has been selected for PRIME, the EMA:

• Appoints a rapporteur from the Committee for Medicinal Products for Human Use (CHMP), or from the Committee on Advanced Therapies (CAT) in the case of an advanced therapy, to provide continuous support and help to build knowledge before a company submits an application for marketing authorization
• Organizes a kick-off meeting with the CHMP/CAT rapporteur and a multidisciplinary group of experts from relevant EMA scientific committees and working parties, and provides guidance on the overall development plan and regulatory strategy
• Assigns a dedicated EMA contact point
• Provides scientific advice at key development milestones, involving additional stakeholders such as health technology assessment bodies to facilitate quicker access to the new drug
• Confirms potential for accelerated assessment when an application for marketing authorization is submitted.

PRIME is open to all drug companies on the basis of preliminary clinical evidence. However, micro-, small- and medium-sized enterprises and applicants from the academic sector can apply earlier on the basis of compelling non-clinical data and tolerability data from initial clinical trials. They may also request fee waivers for scientific advice.

The EMA has released guidance documents on PRIME as well as a comprehensive overview of the EU early access regulatory tools—ie, accelerated assessment, conditional marketing authorization, and compassionate use.

The agency has also published revised guidelines on the implementation of accelerated assessment and conditional marketing authorization. These tools are reserved for treatments addressing major public health needs, and the revised guidelines provide more detailed information based on past experience.

Although PRIME is specifically designed to promote accelerated assessment, the EMA said the initiative will also help drug developers make the best use of other EU early access tools and initiatives, which can be combined whenever a drug fulfills the respective criteria.

PRIME was developed in consultation with the EMA’s scientific committees, the European Commission and its expert group on Safe and Timely Access to Medicines for Patients, as well as the European medicines regulatory network.

The main principles of PRIME were released for a 2-month public consultation in 2015, and the comments received were taken into account in the final version.

Pill production

Photo courtesy of the FDA

The European Medicines Agency (EMA) has launched PRIME (PRIority MEdicines), an initiative intended to accelerate the development of drugs that target unmet medical needs.

These “priority medicines” may offer a major therapeutic advantage over existing treatments or benefit patients who currently have no treatment options in the European Union (EU).

Through PRIME, the EMA will offer early support to drug developers to optimize the generation of robust data on a treatment’s benefits and risks and enable accelerated assessment of an application for marketing authorization.

By engaging with developers early, the EMA aims to strengthen the design of clinical trials to facilitate the generation of high quality data to support an application for marketing authorization.

PRIME builds on the existing regulatory framework and available tools such as scientific advice and accelerated assessment.

To be accepted for PRIME, a treatment has to show the potential to benefit patients with unmet medical needs based on early clinical data.

Once a candidate medicine has been selected for PRIME, the EMA:

• Appoints a rapporteur from the Committee for Medicinal Products for Human Use (CHMP), or from the Committee on Advanced Therapies (CAT) in the case of an advanced therapy, to provide continuous support and help to build knowledge before a company submits an application for marketing authorization
• Organizes a kick-off meeting with the CHMP/CAT rapporteur and a multidisciplinary group of experts from relevant EMA scientific committees and working parties, and provides guidance on the overall development plan and regulatory strategy
• Assigns a dedicated EMA contact point
• Provides scientific advice at key development milestones, involving additional stakeholders such as health technology assessment bodies to facilitate quicker access to the new drug
• Confirms potential for accelerated assessment when an application for marketing authorization is submitted.

PRIME is open to all drug companies on the basis of preliminary clinical evidence. However, micro-, small- and medium-sized enterprises and applicants from the academic sector can apply earlier on the basis of compelling non-clinical data and tolerability data from initial clinical trials. They may also request fee waivers for scientific advice.

The EMA has released guidance documents on PRIME as well as a comprehensive overview of the EU early access regulatory tools—ie, accelerated assessment, conditional marketing authorization, and compassionate use.

The agency has also published revised guidelines on the implementation of accelerated assessment and conditional marketing authorization. These tools are reserved for treatments addressing major public health needs, and the revised guidelines provide more detailed information based on past experience.

Although PRIME is specifically designed to promote accelerated assessment, the EMA said the initiative will also help drug developers make the best use of other EU early access tools and initiatives, which can be combined whenever a drug fulfills the respective criteria.

PRIME was developed in consultation with the EMA’s scientific committees, the European Commission and its expert group on Safe and Timely Access to Medicines for Patients, as well as the European medicines regulatory network.

The main principles of PRIME were released for a 2-month public consultation in 2015, and the comments received were taken into account in the final version.

Pill production

Photo courtesy of the FDA

The European Medicines Agency (EMA) has launched PRIME (PRIority MEdicines), an initiative intended to accelerate the development of drugs that target unmet medical needs.

These “priority medicines” may offer a major therapeutic advantage over existing treatments or benefit patients who currently have no treatment options in the European Union (EU).

Through PRIME, the EMA will offer early support to drug developers to optimize the generation of robust data on a treatment’s benefits and risks and enable accelerated assessment of an application for marketing authorization.

By engaging with developers early, the EMA aims to strengthen the design of clinical trials to facilitate the generation of high quality data to support an application for marketing authorization.

PRIME builds on the existing regulatory framework and available tools such as scientific advice and accelerated assessment.

To be accepted for PRIME, a treatment has to show the potential to benefit patients with unmet medical needs based on early clinical data.

Once a candidate medicine has been selected for PRIME, the EMA:

• Appoints a rapporteur from the Committee for Medicinal Products for Human Use (CHMP), or from the Committee on Advanced Therapies (CAT) in the case of an advanced therapy, to provide continuous support and help to build knowledge before a company submits an application for marketing authorization
• Organizes a kick-off meeting with the CHMP/CAT rapporteur and a multidisciplinary group of experts from relevant EMA scientific committees and working parties, and provides guidance on the overall development plan and regulatory strategy
• Assigns a dedicated EMA contact point
• Provides scientific advice at key development milestones, involving additional stakeholders such as health technology assessment bodies to facilitate quicker access to the new drug
• Confirms potential for accelerated assessment when an application for marketing authorization is submitted.

PRIME is open to all drug companies on the basis of preliminary clinical evidence. However, micro-, small- and medium-sized enterprises and applicants from the academic sector can apply earlier on the basis of compelling non-clinical data and tolerability data from initial clinical trials. They may also request fee waivers for scientific advice.

The EMA has released guidance documents on PRIME as well as a comprehensive overview of the EU early access regulatory tools—ie, accelerated assessment, conditional marketing authorization, and compassionate use.

The agency has also published revised guidelines on the implementation of accelerated assessment and conditional marketing authorization. These tools are reserved for treatments addressing major public health needs, and the revised guidelines provide more detailed information based on past experience.

Although PRIME is specifically designed to promote accelerated assessment, the EMA said the initiative will also help drug developers make the best use of other EU early access tools and initiatives, which can be combined whenever a drug fulfills the respective criteria.

PRIME was developed in consultation with the EMA’s scientific committees, the European Commission and its expert group on Safe and Timely Access to Medicines for Patients, as well as the European medicines regulatory network.

The main principles of PRIME were released for a 2-month public consultation in 2015, and the comments received were taken into account in the final version.