PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

[email protected]

On Twitter @whitneymcknight

PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

[email protected]

On Twitter @whitneymcknight

PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

[email protected]

On Twitter @whitneymcknight

The Diagnosis: Congenital Folliculosebaceous Cystic Hamartoma

Folliculosebaceous cystic hamartoma (FSCH) is a rare skin condition that is either congenital or acquired. It presents as a slow-growing and flesh-colored papulonodular lesion¹ that mainly occurs on the head and neck. Involvement of the nipples, perineum, back, forearms, genital areas, and subcutaneous tissue also has been reported but usually indicates a larger lesion.^1,2

Histologically, FSCH is considered a hamartoma composed of both ectodermal and mesodermal elements.¹ Folliculosebaceous cystic hamartoma is a more complex lesion composed of infundibulocystic structures connected to maloriented folliculosebaceous units surrounded by whorls of highly vascularized fibrous stroma and adipocytes. Clefts between fibroepithelial units and surrounding stroma usually are present.¹

Epithelial components contribute to the adnexal and folliculosebaceous cystic proliferations, and mesenchymal elements include vascular tissue, adipose tissue, and fibroblast-rich stroma.^1,2 Acquired lesions arising in adults have been described,^1-5 but the congenital presentation of FSCH in infancy is rare.

Histopathologically, some variations of FSCH are mainly composed of epithelial components while others are composed of nonepithelial components. Nonepithelial components include neural proliferation, muscle components, vascular proliferation, and mucin deposition.^1-4 In some cases, FSCH may coexist with other diseases, such as nevus lipomatosus cutaneous superficialis and neurofibromatosis type I.^4,5

In our case, histopathology showed several dermal infundibulocystic structures that were lined by stratified squamous epithelium and contained horny material (Figure 1). Numerous immature sebaceous lobules and rudimentary hair follicles emanated from some of the cyst walls. Mesenchymal changes around the fibroepithelial units included fibrillary bundles of collagen, clusters of adipocytes, and an increased number of small venules (Figure 2). In addition, the stroma adjacent to the malformed perifollicle contained some amount of mucin. Prominent clefts formed between fibroepithelial units and the surrounding altered stroma.
 

The differential diagnosis mainly includes sebaceous trichofolliculoma, molluscum contagiosum, dermoid cysts, pilomatrixoma, Spitz nevus, and nevus lipomatosus superficialis. The differential diagnosis between FSCH and sebaceous trichofolliculoma is challenging. Both lesions show an infundibular cyst and surrounding sebaceous nodules. According to Plewig,⁶ trichofolliculoma has a wide spectrum ranging from low to high differentiation represented by trichofolliculoma, sebaceous trichofolliculoma, and FSCH, respectively. It is not difficult to distinguish FSCH from other diseases according to its peculiar histopathologic features.

The clinicopathologic features of our case were similar to those of reported FSCH cases, except for the following unique characteristics: congenital lesion, lack of terminal hair, and no sebaceous material extrusion. These features of hair and sebaceous material may be correlated with the patient’s age and hormonal level.¹ Androgen may play a key role in sebaceous gland development at puberty, which leads to sebaceous gland hyperplasia and hypertrophy. Therefore, slight pressure from the lesions can make ivory-white sebaceous material discharge. Hence, the dermatologist and pediatrician must be poised and sensitive while making an initial diagnosis of FSCH.

The Diagnosis: Congenital Folliculosebaceous Cystic Hamartoma

Folliculosebaceous cystic hamartoma (FSCH) is a rare skin condition that is either congenital or acquired. It presents as a slow-growing and flesh-colored papulonodular lesion¹ that mainly occurs on the head and neck. Involvement of the nipples, perineum, back, forearms, genital areas, and subcutaneous tissue also has been reported but usually indicates a larger lesion.^1,2

Histologically, FSCH is considered a hamartoma composed of both ectodermal and mesodermal elements.¹ Folliculosebaceous cystic hamartoma is a more complex lesion composed of infundibulocystic structures connected to maloriented folliculosebaceous units surrounded by whorls of highly vascularized fibrous stroma and adipocytes. Clefts between fibroepithelial units and surrounding stroma usually are present.¹

Epithelial components contribute to the adnexal and folliculosebaceous cystic proliferations, and mesenchymal elements include vascular tissue, adipose tissue, and fibroblast-rich stroma.^1,2 Acquired lesions arising in adults have been described,^1-5 but the congenital presentation of FSCH in infancy is rare.

Histopathologically, some variations of FSCH are mainly composed of epithelial components while others are composed of nonepithelial components. Nonepithelial components include neural proliferation, muscle components, vascular proliferation, and mucin deposition.^1-4 In some cases, FSCH may coexist with other diseases, such as nevus lipomatosus cutaneous superficialis and neurofibromatosis type I.^4,5

In our case, histopathology showed several dermal infundibulocystic structures that were lined by stratified squamous epithelium and contained horny material (Figure 1). Numerous immature sebaceous lobules and rudimentary hair follicles emanated from some of the cyst walls. Mesenchymal changes around the fibroepithelial units included fibrillary bundles of collagen, clusters of adipocytes, and an increased number of small venules (Figure 2). In addition, the stroma adjacent to the malformed perifollicle contained some amount of mucin. Prominent clefts formed between fibroepithelial units and the surrounding altered stroma.
 

The differential diagnosis mainly includes sebaceous trichofolliculoma, molluscum contagiosum, dermoid cysts, pilomatrixoma, Spitz nevus, and nevus lipomatosus superficialis. The differential diagnosis between FSCH and sebaceous trichofolliculoma is challenging. Both lesions show an infundibular cyst and surrounding sebaceous nodules. According to Plewig,⁶ trichofolliculoma has a wide spectrum ranging from low to high differentiation represented by trichofolliculoma, sebaceous trichofolliculoma, and FSCH, respectively. It is not difficult to distinguish FSCH from other diseases according to its peculiar histopathologic features.

The clinicopathologic features of our case were similar to those of reported FSCH cases, except for the following unique characteristics: congenital lesion, lack of terminal hair, and no sebaceous material extrusion. These features of hair and sebaceous material may be correlated with the patient’s age and hormonal level.¹ Androgen may play a key role in sebaceous gland development at puberty, which leads to sebaceous gland hyperplasia and hypertrophy. Therefore, slight pressure from the lesions can make ivory-white sebaceous material discharge. Hence, the dermatologist and pediatrician must be poised and sensitive while making an initial diagnosis of FSCH.

The Diagnosis: Congenital Folliculosebaceous Cystic Hamartoma

Folliculosebaceous cystic hamartoma (FSCH) is a rare skin condition that is either congenital or acquired. It presents as a slow-growing and flesh-colored papulonodular lesion¹ that mainly occurs on the head and neck. Involvement of the nipples, perineum, back, forearms, genital areas, and subcutaneous tissue also has been reported but usually indicates a larger lesion.^1,2

Histologically, FSCH is considered a hamartoma composed of both ectodermal and mesodermal elements.¹ Folliculosebaceous cystic hamartoma is a more complex lesion composed of infundibulocystic structures connected to maloriented folliculosebaceous units surrounded by whorls of highly vascularized fibrous stroma and adipocytes. Clefts between fibroepithelial units and surrounding stroma usually are present.¹

Epithelial components contribute to the adnexal and folliculosebaceous cystic proliferations, and mesenchymal elements include vascular tissue, adipose tissue, and fibroblast-rich stroma.^1,2 Acquired lesions arising in adults have been described,^1-5 but the congenital presentation of FSCH in infancy is rare.

Histopathologically, some variations of FSCH are mainly composed of epithelial components while others are composed of nonepithelial components. Nonepithelial components include neural proliferation, muscle components, vascular proliferation, and mucin deposition.^1-4 In some cases, FSCH may coexist with other diseases, such as nevus lipomatosus cutaneous superficialis and neurofibromatosis type I.^4,5

In our case, histopathology showed several dermal infundibulocystic structures that were lined by stratified squamous epithelium and contained horny material (Figure 1). Numerous immature sebaceous lobules and rudimentary hair follicles emanated from some of the cyst walls. Mesenchymal changes around the fibroepithelial units included fibrillary bundles of collagen, clusters of adipocytes, and an increased number of small venules (Figure 2). In addition, the stroma adjacent to the malformed perifollicle contained some amount of mucin. Prominent clefts formed between fibroepithelial units and the surrounding altered stroma.
 

The differential diagnosis mainly includes sebaceous trichofolliculoma, molluscum contagiosum, dermoid cysts, pilomatrixoma, Spitz nevus, and nevus lipomatosus superficialis. The differential diagnosis between FSCH and sebaceous trichofolliculoma is challenging. Both lesions show an infundibular cyst and surrounding sebaceous nodules. According to Plewig,⁶ trichofolliculoma has a wide spectrum ranging from low to high differentiation represented by trichofolliculoma, sebaceous trichofolliculoma, and FSCH, respectively. It is not difficult to distinguish FSCH from other diseases according to its peculiar histopathologic features.

The clinicopathologic features of our case were similar to those of reported FSCH cases, except for the following unique characteristics: congenital lesion, lack of terminal hair, and no sebaceous material extrusion. These features of hair and sebaceous material may be correlated with the patient’s age and hormonal level.¹ Androgen may play a key role in sebaceous gland development at puberty, which leads to sebaceous gland hyperplasia and hypertrophy. Therefore, slight pressure from the lesions can make ivory-white sebaceous material discharge. Hence, the dermatologist and pediatrician must be poised and sensitive while making an initial diagnosis of FSCH.

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The list of nonatopic comorbid conditions associated with atopic dermatitis is rapidly expanding.

Just in the past year, published studies have linked pediatric atopic dermatitis to increased risks of obesity, high blood pressure, headaches, anemia, and speech disorders. Meanwhile, adult atopic dermatitis was reported to be associated with increased rates of fracture and cardiovascular disease. And in the dermatologic arena, a link between atopic dermatitis, vitiligo, and alopecia areata was identified, Dr. Lawrence F. Eichenfield noted at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Actually, these reported associations published in 2015-2016 might best be termed “emerging comorbidities,” as they are first reports and thus need confirmation, said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital San Diego.

Much of this work on emerging comorbidities has been done by dermatologist Dr. Jonathan I. Silverberg of Northwestern University, Chicago, and various coinvestigators. They have been prolific.

For example, in a multivariate logistic regression analysis of 207,007 children and adolescents included in the cross-sectional 1997-2013 U.S. National Health Interview Survey, Dr. Silverberg and coinvestigators found that eczema was independently associated with a 1.83-fold increased odds of anemia. They bolstered this observation with an analysis of more than 30,000 children and adolescents in the 1992-2012 National Health and Nutrition Examination Survey (NHANES) in which they found that current eczema was associated with a 1.93-fold increased odds of anemia, particularly microcytic anemia. The underlying mechanism is unknown; however, the investigators noted that chronic inflammation and systemic immunosuppressant drugs have been shown to be associated with anemia (JAMA Pediatr. 2016;170[1]:29-34).

Dr. Silverberg also found in a multivariate logistic regression analysis of data on more than 400,000 pediatric participants in the National Survey of Children’s Health and the National Health Interview Survey that mild and severe eczema were independently associated with 1.79-fold and 2.72-fold, respectively, increased odds of headaches (J Allergy Clin Immunol. 2016 Feb;137[2]:492-9).

Using these same two data sources, with multivariate analysis adjusted for potential confounders, the investigators found that eczema was associated with a 1.81-fold increased risk of speech disorder (J Pediatr. 2016 Jan;168:185-92).

In a case-control study involving 132 children and adolescents with current moderate to severe atopic dermatitis and 143 healthy controls, Dr. Silverberg and coinvestigators found in a logistic regression analysis that atopic dermatitis was independently associated with a doubled risk of having a systolic blood pressure in the 90th percentile or higher – as well as 3.92-fold increased odds of central obesity, as defined by a waist circumference in the 85th percentile or higher (JAMA Dermatol. 2015 Feb;151[2]:144-52).

In a systematic review and meta-analysis of 16 published vitiligo studies and 17 published studies of alopecia areata, Dr. Silverberg and medical student Girish C. Mohan found that patients with vitiligo or alopecia areata were respectively 7.8 and 2.6 times more likely to have atopic dermatitis than controls without those disorders (JAMA Dermatol. 2015 May;151[5]:522-8).

In a logistic regression analysis of data on 34,500 adults with a history of eczema within the prior year who participated in the 2012 National Health Interview Survey, Drs. Nitin Garg and Dr. Silverberg concluded that the results suggested that adult atopic dermatitis is a previously unrecognized risk factor for fracture and other bone or joint injuries causing limitation. Adults with atopic dermatitis were at a 1.67-fold increased risk for such injuries in an analysis controlling for sociodemographics, other forms of atopic disease, and psychiatric and behavioral disorders (JAMA Dermatol. 2015 Jan;151[1]:33-41).

In another large cross-sectional study, Dr. Silverberg found that adults with atopic dermatitis had significantly higher odds of a history of acute MI, coronary artery disease, heart failure, and stroke (Allergy. 2015 Oct;70[10]:1300-8).

Dr. Eichenfield said that while he would like to see these hot-off-the-presses 2015-2016 findings on nonatopic comorbidities backed up by confirmatory studies in other populations, the evidence is stronger for an association between pediatric atopic dermatitis and several mental health disorders. The initial reports came mainly from Europe, but were then supported by a large study by Dr. Eric L. Simpson and coinvestigators at Oregon Health and Science University, Portland.

In their analysis of data on nearly 93,000 noninstitutionalized children and adolescents included in the 2007 National Survey of Children’s Health, the investigators found after controlling for potential confounders that atopic dermatitis was associated with a 1.87-fold increased risk of having attention-deficit/hyperactivity disorder, a 3-fold increased risk of diagnosed autism, an adjusted 1.81-fold increase in depression, and 1.87-fold increased odds of conduct disorder. The Oregon group found a clear dose-dependent relationship between the reported severity of the skin disease and the likelihood of those mental health disorders (J Allergy Clin Immunol. 2013 Feb;131[2]:428-33).

The hope is that emerging strategies to prevent atopic dermatitis or aggressively treat it early on will reduce the risk of many of these comorbid conditions, Dr. Eichenfield said.

SDEF and this news organization are owned by the same parent company.

[email protected]

Researcher in the lab

Photo by Daniel Sone

SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.

The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.

They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.

However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.

John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.

“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”

Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.

The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.

However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.

“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”

The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.

Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.

However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.

Researcher in the lab

Photo by Daniel Sone

SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.

The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.

They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.

However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.

John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.

“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”

Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.

The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.

However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.

“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”

The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.

Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.

However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.

Researcher in the lab

Photo by Daniel Sone

SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.

The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.

They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.

However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.

John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.

“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”

Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.

The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.

However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.

“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”

The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.

Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.

However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.

Case

A 33-year-old male with a history of opioid overdose and opioid use disorder is admitted with IV heroin use complicated by injection site cellulitis. He is started on antibiotics with improvement in his cellulitis; however, his hospitalization is complicated by acute opioid withdrawal. Despite his history of opioid overdose and opioid use disorder, he has never seen a substance use disorder specialist nor received any education or treatment for his addiction. He reports that he will stop using illicit drugs but declines any further addiction treatment.

What strategies can be employed to reduce his risk of future harm from opioid misuse?

Background

Over the past decade, the U.S. has experienced a rapid increase in the rates of opioid prescriptions and opioid misuse.1 Consequently, the number of ED visits and hospitalizations for opioid-related complications has also increased.2 Many complications result from the practice of injection drug use (IDU), which predisposes individuals to serious blood-borne viral infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) as well as bacterial infections such as infective endocarditis. In addition, individuals who misuse opioids are at risk of death related to opioid overdose. In 2013, there were more than 24,000 deaths in the U.S. due to opioid overdose (see Figure 1).3

In response to the opioid epidemic, there have been a number of local, state, and federal public health initiatives to monitor and secure the opioid drug supply, improve treatment resources, and promulgate harm-reduction interventions. At a more individual level, hospitalists have an important role to play in combating the opioid epidemic. As frontline providers, hospitalists have access to hospitalized individuals with opioid misuse who may not otherwise be exposed to the healthcare system. Therefore, inpatient hospitalizations serve as a unique and important opportunity to engage individuals in the management of their addiction.

There are a number of interventions that hospitalists and substance use disorder specialists can pursue. Psychiatric evaluation and initiation of medication-assisted treatment often aim to aid patients in abstaining from further opioid misuse. However, many individuals with opioid use disorder are not ready for treatment or experience relapses of opioid misuse despite treatment. Given this, a secondary goal is to reduce any harm that may result from opioid misuse. This is done through the implementation of harm-reduction strategies. These strategies include teaching safe injection practices, facilitating the use of syringe exchange programs, and providing opioid overdose education and naloxone distribution.

Overview of Data

Safe Injection Education. People who inject drugs are at risk for viral, bacterial, and fungal infections. These infections are often the result of nonsterile injection and may be minimized by the utilization of safe injection practices. In order to educate people who inject drugs on safe injection practices, the hospitalist must first understand the process involved in injecting drugs. In Table 1, the process of injecting heroin is outlined (of note, other illicit drugs can be injected, and processes may vary).4

As evidenced by Table 1, the process of sterile injection can be complicated, especially for an individual who may be withdrawing from opioids. Table 1 is also optimistic in that it recommends new and sterile products be used with every injection. If new and sterile equipment is not available, another option is to clean the equipment after every use, which can be done by using bleach and water. This may mitigate the risk of viral, bacterial, and fungal infections. However, the risk is still present, so users should not share or use another individual’s equipment even if it has been cleaned. Due to the risk of viral, bacterial, and fungal infections, all hospitalized individuals who inject drugs should receive education on safe injection practices.

Syringe Exchange Programs. IDU accounts for up to 15% of all new HIV infections and is the primary risk factor for the transmission of HCV.5 These infections occur when people inject using equipment contaminated with blood that contains HIV and/or HCV. Given this, if people who inject drugs could access and consistently use sterile syringes and other injection paraphernalia, the risk of transmitting blood-borne infections would be dramatically reduced. This is the concept behind syringe exchange programs (also known as needle exchange programs), which serve to increase access to sterile syringes while removing contaminated or used syringes from the community.

There is compelling evidence that syringe exchange programs decrease the rate of HIV transmission and likely reduce the rate of HCV transmission as well.6 In addition, syringe exchange programs often provide other beneficial services, such as counseling, testing, and prevention efforts for HIV, HCV, and sexually transmitted infections; distribution of condoms; and referrals to treatment services for substance use disorder.5

Unfortunately, in the U.S., restrictive state laws and lack of funding limit the number of established syringe exchange programs. According to the North American Syringe Exchange Network, there are only 226 programs in 33 states and the District of Columbia. Hospitalists and social workers should be aware of available local resources, including syringe exchange programs, and distribute this information to hospitalized individuals who inject drugs.

Opioid Overdose Education and Naloxone Distribution. Syringe exchange programs and safe injection education aim to reduce harm by decreasing the transmission of infections; however, they do not address the problem of deaths related to opioid overdose. The primary harm-reduction strategy used to address deaths related to opioid overdose in the U.S is opioid overdose education and naloxone distribution (OEND). Naloxone is an opioid antagonist that reverses the respiratory depression and decreased consciousness caused by opioids. The OEND strategy involves educating first responders— including individuals and friends and family of individuals who use opioids—to recognize the signs of an opioid overdose, seek help, provide rescue breathing, administer naloxone, and stay with the individual until emergency medical services arrive.7 This strategy has been observed to decrease rates of death related to opioid overdose.7

Given the evolving opioid epidemic and effectiveness of the OEND strategy, it is not surprising that the number of local opioid overdose prevention programs adopting OEND has risen dramatically. As of 2014, there were 140 organizations, with 644 local sites providing naloxone in 29 states and the District of Columbia. These organizations have distributed 152,000 naloxone kits and have reported more than 26,000 reversals.8 Certainly, OEND has prevented morbidity and mortality in some of these patients.

The adoption of OEND can be performed by individual prescribers as well. Naloxone is U.S. FDA-approved for the treatment of opioid overdose, and thus the liability to prescribers is similar to that of other FDA-approved drugs. However, the distribution of naloxone to third parties, such as friends and family of individuals with opioid misuse, is more complex and regulated by state laws. Many states have created liability protection for naloxone prescription to third parties. Individual state laws and additional information can be found at prescribetoprevent.org.

Hospitalists should provide opioid overdose education to all individuals with opioid misuse and friends and family of individuals with opioid misuse. In addition, hospitalists should prescribe naloxone to individuals with opioid misuse and, in states where the law allows, distribute naloxone to friends and family of individuals with opioid misuse as well.

Controversies. In general, opioid use disorder treatment providers; public health officials; and local, state, and federal government agencies have increasingly embraced harm-reduction strategies. However, some feel that harm-reduction strategies are misguided or even detrimental due to concern that they implicitly condone or enable the use of illicit substances. There have been a number of studies to evaluate the potential unintended consequences of harm-reduction strategies, and overwhelmingly, these have been either neutral or have shown the benefit of harm-reduction interventions. At this point, there is no good evidence to prevent the widespread adoption of harm-reduction strategies for hospitalists.

Back to the Case

The case involves an individual who has already had at least two complications of his IV heroin use, including cellulitis and opioid overdose. Ideally, this individual would be willing to see an addiction specialist and start medication-assisted treatment. Unfortunately, he is unwilling to be further evaluated by a specialist at this time. Regardless, he remains at risk of future complications, and it is the hospitalist’s responsibility to intervene with a goal of reducing future harm that may result from his IV heroin use.

The hospitalist in this case advises the patient to abstain from heroin and IDU, encourages him to seek treatment for his opioid use disorder, and gives him resources for linkage to care if he becomes interested. In addition, the hospitalist educates the patient on safe injection practices and provides a list of local syringe exchange programs to decrease future risk of viral, bacterial, and fungal infections. Furthermore, the hospitalist provides opioid overdose education and distributes naloxone to the patient, along with friends and family of the patient, to reduce the risk of death related to opioid overdose.

Bottom Line

Hospitalists should utilize harm-reduction interventions in individuals hospitalized with opioid misuse. TH

Dr. Theisen-Toupal is a hospitalist at the Veterans Affairs Medical Center and assistant professor of medicine at the George Washington University School of Medicine & Health Sciences, both in Washington, D.C.

References

1. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm. Published November 4, 2011.
2. Drug abuse warning network, 2011: national estimates of drug-related emergency department visits. Substance Abuse and Mental Health Services Administration website. Available at: http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#5. Accessed July 29, 2015.
3. Hedergaard H, Chen LH, Warner M. Drug-poisoning deaths involving heroin: United States, 2000–2013. National Center for Health Statistics Data Brief. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/nchs/data/databriefs/db190.htm. Published March 2015.
4. Getting off right: a safety manual for injection drug users. Harm Reduction Coalition website. Available at: http://harmreduction.org/wp-content/uploads/2011/12/getting-off-right.pdf.
5. Syringe exchange programs—United States, 2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5945a4.htm/Syringe-Exchange-Programs-United-States-2008. Published November 19, 2010.
6. Wodak A, Conney A. Effectiveness of sterile needle and syringe programming in reducing HIV/AIDS among injecting drug users. World Health Organization website. Available at: http://apps.who.int/iris/bitstream/10665/43107/1/9241591641.pdf. Published 2004.
7. Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174.
8. Wheeler E, Jones TS, Gilbert MK, Davidson PJ. Opioid overdose prevention programs providing naloxone to laypersons—United States, 2014. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a2.htm. Published June 19, 2015.

Case

A 33-year-old male with a history of opioid overdose and opioid use disorder is admitted with IV heroin use complicated by injection site cellulitis. He is started on antibiotics with improvement in his cellulitis; however, his hospitalization is complicated by acute opioid withdrawal. Despite his history of opioid overdose and opioid use disorder, he has never seen a substance use disorder specialist nor received any education or treatment for his addiction. He reports that he will stop using illicit drugs but declines any further addiction treatment.

What strategies can be employed to reduce his risk of future harm from opioid misuse?

Background

Over the past decade, the U.S. has experienced a rapid increase in the rates of opioid prescriptions and opioid misuse.1 Consequently, the number of ED visits and hospitalizations for opioid-related complications has also increased.2 Many complications result from the practice of injection drug use (IDU), which predisposes individuals to serious blood-borne viral infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) as well as bacterial infections such as infective endocarditis. In addition, individuals who misuse opioids are at risk of death related to opioid overdose. In 2013, there were more than 24,000 deaths in the U.S. due to opioid overdose (see Figure 1).3

In response to the opioid epidemic, there have been a number of local, state, and federal public health initiatives to monitor and secure the opioid drug supply, improve treatment resources, and promulgate harm-reduction interventions. At a more individual level, hospitalists have an important role to play in combating the opioid epidemic. As frontline providers, hospitalists have access to hospitalized individuals with opioid misuse who may not otherwise be exposed to the healthcare system. Therefore, inpatient hospitalizations serve as a unique and important opportunity to engage individuals in the management of their addiction.

There are a number of interventions that hospitalists and substance use disorder specialists can pursue. Psychiatric evaluation and initiation of medication-assisted treatment often aim to aid patients in abstaining from further opioid misuse. However, many individuals with opioid use disorder are not ready for treatment or experience relapses of opioid misuse despite treatment. Given this, a secondary goal is to reduce any harm that may result from opioid misuse. This is done through the implementation of harm-reduction strategies. These strategies include teaching safe injection practices, facilitating the use of syringe exchange programs, and providing opioid overdose education and naloxone distribution.

Overview of Data

Safe Injection Education. People who inject drugs are at risk for viral, bacterial, and fungal infections. These infections are often the result of nonsterile injection and may be minimized by the utilization of safe injection practices. In order to educate people who inject drugs on safe injection practices, the hospitalist must first understand the process involved in injecting drugs. In Table 1, the process of injecting heroin is outlined (of note, other illicit drugs can be injected, and processes may vary).4

As evidenced by Table 1, the process of sterile injection can be complicated, especially for an individual who may be withdrawing from opioids. Table 1 is also optimistic in that it recommends new and sterile products be used with every injection. If new and sterile equipment is not available, another option is to clean the equipment after every use, which can be done by using bleach and water. This may mitigate the risk of viral, bacterial, and fungal infections. However, the risk is still present, so users should not share or use another individual’s equipment even if it has been cleaned. Due to the risk of viral, bacterial, and fungal infections, all hospitalized individuals who inject drugs should receive education on safe injection practices.

Syringe Exchange Programs. IDU accounts for up to 15% of all new HIV infections and is the primary risk factor for the transmission of HCV.5 These infections occur when people inject using equipment contaminated with blood that contains HIV and/or HCV. Given this, if people who inject drugs could access and consistently use sterile syringes and other injection paraphernalia, the risk of transmitting blood-borne infections would be dramatically reduced. This is the concept behind syringe exchange programs (also known as needle exchange programs), which serve to increase access to sterile syringes while removing contaminated or used syringes from the community.

There is compelling evidence that syringe exchange programs decrease the rate of HIV transmission and likely reduce the rate of HCV transmission as well.6 In addition, syringe exchange programs often provide other beneficial services, such as counseling, testing, and prevention efforts for HIV, HCV, and sexually transmitted infections; distribution of condoms; and referrals to treatment services for substance use disorder.5

Unfortunately, in the U.S., restrictive state laws and lack of funding limit the number of established syringe exchange programs. According to the North American Syringe Exchange Network, there are only 226 programs in 33 states and the District of Columbia. Hospitalists and social workers should be aware of available local resources, including syringe exchange programs, and distribute this information to hospitalized individuals who inject drugs.

Opioid Overdose Education and Naloxone Distribution. Syringe exchange programs and safe injection education aim to reduce harm by decreasing the transmission of infections; however, they do not address the problem of deaths related to opioid overdose. The primary harm-reduction strategy used to address deaths related to opioid overdose in the U.S is opioid overdose education and naloxone distribution (OEND). Naloxone is an opioid antagonist that reverses the respiratory depression and decreased consciousness caused by opioids. The OEND strategy involves educating first responders— including individuals and friends and family of individuals who use opioids—to recognize the signs of an opioid overdose, seek help, provide rescue breathing, administer naloxone, and stay with the individual until emergency medical services arrive.7 This strategy has been observed to decrease rates of death related to opioid overdose.7

Given the evolving opioid epidemic and effectiveness of the OEND strategy, it is not surprising that the number of local opioid overdose prevention programs adopting OEND has risen dramatically. As of 2014, there were 140 organizations, with 644 local sites providing naloxone in 29 states and the District of Columbia. These organizations have distributed 152,000 naloxone kits and have reported more than 26,000 reversals.8 Certainly, OEND has prevented morbidity and mortality in some of these patients.

The adoption of OEND can be performed by individual prescribers as well. Naloxone is U.S. FDA-approved for the treatment of opioid overdose, and thus the liability to prescribers is similar to that of other FDA-approved drugs. However, the distribution of naloxone to third parties, such as friends and family of individuals with opioid misuse, is more complex and regulated by state laws. Many states have created liability protection for naloxone prescription to third parties. Individual state laws and additional information can be found at prescribetoprevent.org.

Hospitalists should provide opioid overdose education to all individuals with opioid misuse and friends and family of individuals with opioid misuse. In addition, hospitalists should prescribe naloxone to individuals with opioid misuse and, in states where the law allows, distribute naloxone to friends and family of individuals with opioid misuse as well.

Controversies. In general, opioid use disorder treatment providers; public health officials; and local, state, and federal government agencies have increasingly embraced harm-reduction strategies. However, some feel that harm-reduction strategies are misguided or even detrimental due to concern that they implicitly condone or enable the use of illicit substances. There have been a number of studies to evaluate the potential unintended consequences of harm-reduction strategies, and overwhelmingly, these have been either neutral or have shown the benefit of harm-reduction interventions. At this point, there is no good evidence to prevent the widespread adoption of harm-reduction strategies for hospitalists.

Back to the Case

The case involves an individual who has already had at least two complications of his IV heroin use, including cellulitis and opioid overdose. Ideally, this individual would be willing to see an addiction specialist and start medication-assisted treatment. Unfortunately, he is unwilling to be further evaluated by a specialist at this time. Regardless, he remains at risk of future complications, and it is the hospitalist’s responsibility to intervene with a goal of reducing future harm that may result from his IV heroin use.

The hospitalist in this case advises the patient to abstain from heroin and IDU, encourages him to seek treatment for his opioid use disorder, and gives him resources for linkage to care if he becomes interested. In addition, the hospitalist educates the patient on safe injection practices and provides a list of local syringe exchange programs to decrease future risk of viral, bacterial, and fungal infections. Furthermore, the hospitalist provides opioid overdose education and distributes naloxone to the patient, along with friends and family of the patient, to reduce the risk of death related to opioid overdose.

Bottom Line

Hospitalists should utilize harm-reduction interventions in individuals hospitalized with opioid misuse. TH

Dr. Theisen-Toupal is a hospitalist at the Veterans Affairs Medical Center and assistant professor of medicine at the George Washington University School of Medicine & Health Sciences, both in Washington, D.C.

References

1. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm. Published November 4, 2011.
2. Drug abuse warning network, 2011: national estimates of drug-related emergency department visits. Substance Abuse and Mental Health Services Administration website. Available at: http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#5. Accessed July 29, 2015.
3. Hedergaard H, Chen LH, Warner M. Drug-poisoning deaths involving heroin: United States, 2000–2013. National Center for Health Statistics Data Brief. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/nchs/data/databriefs/db190.htm. Published March 2015.
4. Getting off right: a safety manual for injection drug users. Harm Reduction Coalition website. Available at: http://harmreduction.org/wp-content/uploads/2011/12/getting-off-right.pdf.
5. Syringe exchange programs—United States, 2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5945a4.htm/Syringe-Exchange-Programs-United-States-2008. Published November 19, 2010.
6. Wodak A, Conney A. Effectiveness of sterile needle and syringe programming in reducing HIV/AIDS among injecting drug users. World Health Organization website. Available at: http://apps.who.int/iris/bitstream/10665/43107/1/9241591641.pdf. Published 2004.
7. Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174.
8. Wheeler E, Jones TS, Gilbert MK, Davidson PJ. Opioid overdose prevention programs providing naloxone to laypersons—United States, 2014. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a2.htm. Published June 19, 2015.

Case

A 33-year-old male with a history of opioid overdose and opioid use disorder is admitted with IV heroin use complicated by injection site cellulitis. He is started on antibiotics with improvement in his cellulitis; however, his hospitalization is complicated by acute opioid withdrawal. Despite his history of opioid overdose and opioid use disorder, he has never seen a substance use disorder specialist nor received any education or treatment for his addiction. He reports that he will stop using illicit drugs but declines any further addiction treatment.

What strategies can be employed to reduce his risk of future harm from opioid misuse?

Background

Over the past decade, the U.S. has experienced a rapid increase in the rates of opioid prescriptions and opioid misuse.1 Consequently, the number of ED visits and hospitalizations for opioid-related complications has also increased.2 Many complications result from the practice of injection drug use (IDU), which predisposes individuals to serious blood-borne viral infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) as well as bacterial infections such as infective endocarditis. In addition, individuals who misuse opioids are at risk of death related to opioid overdose. In 2013, there were more than 24,000 deaths in the U.S. due to opioid overdose (see Figure 1).3

In response to the opioid epidemic, there have been a number of local, state, and federal public health initiatives to monitor and secure the opioid drug supply, improve treatment resources, and promulgate harm-reduction interventions. At a more individual level, hospitalists have an important role to play in combating the opioid epidemic. As frontline providers, hospitalists have access to hospitalized individuals with opioid misuse who may not otherwise be exposed to the healthcare system. Therefore, inpatient hospitalizations serve as a unique and important opportunity to engage individuals in the management of their addiction.

There are a number of interventions that hospitalists and substance use disorder specialists can pursue. Psychiatric evaluation and initiation of medication-assisted treatment often aim to aid patients in abstaining from further opioid misuse. However, many individuals with opioid use disorder are not ready for treatment or experience relapses of opioid misuse despite treatment. Given this, a secondary goal is to reduce any harm that may result from opioid misuse. This is done through the implementation of harm-reduction strategies. These strategies include teaching safe injection practices, facilitating the use of syringe exchange programs, and providing opioid overdose education and naloxone distribution.

Overview of Data

Safe Injection Education. People who inject drugs are at risk for viral, bacterial, and fungal infections. These infections are often the result of nonsterile injection and may be minimized by the utilization of safe injection practices. In order to educate people who inject drugs on safe injection practices, the hospitalist must first understand the process involved in injecting drugs. In Table 1, the process of injecting heroin is outlined (of note, other illicit drugs can be injected, and processes may vary).4

As evidenced by Table 1, the process of sterile injection can be complicated, especially for an individual who may be withdrawing from opioids. Table 1 is also optimistic in that it recommends new and sterile products be used with every injection. If new and sterile equipment is not available, another option is to clean the equipment after every use, which can be done by using bleach and water. This may mitigate the risk of viral, bacterial, and fungal infections. However, the risk is still present, so users should not share or use another individual’s equipment even if it has been cleaned. Due to the risk of viral, bacterial, and fungal infections, all hospitalized individuals who inject drugs should receive education on safe injection practices.

Syringe Exchange Programs. IDU accounts for up to 15% of all new HIV infections and is the primary risk factor for the transmission of HCV.5 These infections occur when people inject using equipment contaminated with blood that contains HIV and/or HCV. Given this, if people who inject drugs could access and consistently use sterile syringes and other injection paraphernalia, the risk of transmitting blood-borne infections would be dramatically reduced. This is the concept behind syringe exchange programs (also known as needle exchange programs), which serve to increase access to sterile syringes while removing contaminated or used syringes from the community.

There is compelling evidence that syringe exchange programs decrease the rate of HIV transmission and likely reduce the rate of HCV transmission as well.6 In addition, syringe exchange programs often provide other beneficial services, such as counseling, testing, and prevention efforts for HIV, HCV, and sexually transmitted infections; distribution of condoms; and referrals to treatment services for substance use disorder.5

Unfortunately, in the U.S., restrictive state laws and lack of funding limit the number of established syringe exchange programs. According to the North American Syringe Exchange Network, there are only 226 programs in 33 states and the District of Columbia. Hospitalists and social workers should be aware of available local resources, including syringe exchange programs, and distribute this information to hospitalized individuals who inject drugs.

Opioid Overdose Education and Naloxone Distribution. Syringe exchange programs and safe injection education aim to reduce harm by decreasing the transmission of infections; however, they do not address the problem of deaths related to opioid overdose. The primary harm-reduction strategy used to address deaths related to opioid overdose in the U.S is opioid overdose education and naloxone distribution (OEND). Naloxone is an opioid antagonist that reverses the respiratory depression and decreased consciousness caused by opioids. The OEND strategy involves educating first responders— including individuals and friends and family of individuals who use opioids—to recognize the signs of an opioid overdose, seek help, provide rescue breathing, administer naloxone, and stay with the individual until emergency medical services arrive.7 This strategy has been observed to decrease rates of death related to opioid overdose.7

Given the evolving opioid epidemic and effectiveness of the OEND strategy, it is not surprising that the number of local opioid overdose prevention programs adopting OEND has risen dramatically. As of 2014, there were 140 organizations, with 644 local sites providing naloxone in 29 states and the District of Columbia. These organizations have distributed 152,000 naloxone kits and have reported more than 26,000 reversals.8 Certainly, OEND has prevented morbidity and mortality in some of these patients.

The adoption of OEND can be performed by individual prescribers as well. Naloxone is U.S. FDA-approved for the treatment of opioid overdose, and thus the liability to prescribers is similar to that of other FDA-approved drugs. However, the distribution of naloxone to third parties, such as friends and family of individuals with opioid misuse, is more complex and regulated by state laws. Many states have created liability protection for naloxone prescription to third parties. Individual state laws and additional information can be found at prescribetoprevent.org.

Hospitalists should provide opioid overdose education to all individuals with opioid misuse and friends and family of individuals with opioid misuse. In addition, hospitalists should prescribe naloxone to individuals with opioid misuse and, in states where the law allows, distribute naloxone to friends and family of individuals with opioid misuse as well.

Controversies. In general, opioid use disorder treatment providers; public health officials; and local, state, and federal government agencies have increasingly embraced harm-reduction strategies. However, some feel that harm-reduction strategies are misguided or even detrimental due to concern that they implicitly condone or enable the use of illicit substances. There have been a number of studies to evaluate the potential unintended consequences of harm-reduction strategies, and overwhelmingly, these have been either neutral or have shown the benefit of harm-reduction interventions. At this point, there is no good evidence to prevent the widespread adoption of harm-reduction strategies for hospitalists.

Back to the Case

The case involves an individual who has already had at least two complications of his IV heroin use, including cellulitis and opioid overdose. Ideally, this individual would be willing to see an addiction specialist and start medication-assisted treatment. Unfortunately, he is unwilling to be further evaluated by a specialist at this time. Regardless, he remains at risk of future complications, and it is the hospitalist’s responsibility to intervene with a goal of reducing future harm that may result from his IV heroin use.

The hospitalist in this case advises the patient to abstain from heroin and IDU, encourages him to seek treatment for his opioid use disorder, and gives him resources for linkage to care if he becomes interested. In addition, the hospitalist educates the patient on safe injection practices and provides a list of local syringe exchange programs to decrease future risk of viral, bacterial, and fungal infections. Furthermore, the hospitalist provides opioid overdose education and distributes naloxone to the patient, along with friends and family of the patient, to reduce the risk of death related to opioid overdose.

Bottom Line

Hospitalists should utilize harm-reduction interventions in individuals hospitalized with opioid misuse. TH

Dr. Theisen-Toupal is a hospitalist at the Veterans Affairs Medical Center and assistant professor of medicine at the George Washington University School of Medicine & Health Sciences, both in Washington, D.C.

References

1. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm. Published November 4, 2011.
2. Drug abuse warning network, 2011: national estimates of drug-related emergency department visits. Substance Abuse and Mental Health Services Administration website. Available at: http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#5. Accessed July 29, 2015.
3. Hedergaard H, Chen LH, Warner M. Drug-poisoning deaths involving heroin: United States, 2000–2013. National Center for Health Statistics Data Brief. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/nchs/data/databriefs/db190.htm. Published March 2015.
4. Getting off right: a safety manual for injection drug users. Harm Reduction Coalition website. Available at: http://harmreduction.org/wp-content/uploads/2011/12/getting-off-right.pdf.
5. Syringe exchange programs—United States, 2008. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5945a4.htm/Syringe-Exchange-Programs-United-States-2008. Published November 19, 2010.
6. Wodak A, Conney A. Effectiveness of sterile needle and syringe programming in reducing HIV/AIDS among injecting drug users. World Health Organization website. Available at: http://apps.who.int/iris/bitstream/10665/43107/1/9241591641.pdf. Published 2004.
7. Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174.
8. Wheeler E, Jones TS, Gilbert MK, Davidson PJ. Opioid overdose prevention programs providing naloxone to laypersons—United States, 2014. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a2.htm. Published June 19, 2015.

With the rolling out of the Health IT track on the second full day of HM16, The Hospitalist asked: What problem do you hope health IT solves or helps you solve over the next five years?

Farhanaz Chowdhury, MD, hospitalist, HSHS St. Elizabeth’s Hospital, Belleville, Ill.

“I think that hospital health systems are very primitive. When they make that software, physicians should be more involved so that in everyday life, what we see when we are facing all those problems, you have an algorithm if you want to do something. It should pop up so that you don’t have to write it down and scroll all over.”

Michael Lintner, MD, hospitalist, Aspen Valley Hospital, Colo.

“I think probably the main thing would be work flow, facilitating work flow. I think today hospitalists are just getting more and more and more work. Patient loads are getting increasingly bigger. I think with IT, [we need] systems that facilitate and help with the work flow and help the hospitalist’s day go smoother because there are so many things that we do.”

Miguel Lizardo, MD, hospitalist, University of Massachusetts Memorial Medical Center, Worcester

“It takes a lot of time to interact with the EMRs and all the technology that we have to use. If they can find a way that we can use it in a more user-friendly [way] so that it takes not a long time, that would be great. At least the EMRs that I’ve been in contact with are too cumbersome, too many clicks to get where you want, a bunch of steps to document what you need to. You really are away from the patient and spending a lot of time trying to document.”

Sandeep Palikhel, PA-C, Baylor University Medical Center, Waco, Tex.

“Definitely accuracy. In Texas, where I practice, we get a lot of transfers from rural areas because we are a Level 1 trauma hospital. We get these discharge summaries or progress notes from other hospitals that are handwritten. A lot of information gets missed whenever we’re reading it because it’s not legible, first thing, and it’s not as detail-oriented as the EHRs would be. So that definitely helps. Even going through a medication list, it helps so much to go through an EHR versus going through a handwritten medication list. That’s what I mean by accuracy.”

With the rolling out of the Health IT track on the second full day of HM16, The Hospitalist asked: What problem do you hope health IT solves or helps you solve over the next five years?

Farhanaz Chowdhury, MD, hospitalist, HSHS St. Elizabeth’s Hospital, Belleville, Ill.

“I think that hospital health systems are very primitive. When they make that software, physicians should be more involved so that in everyday life, what we see when we are facing all those problems, you have an algorithm if you want to do something. It should pop up so that you don’t have to write it down and scroll all over.”

Michael Lintner, MD, hospitalist, Aspen Valley Hospital, Colo.

“I think probably the main thing would be work flow, facilitating work flow. I think today hospitalists are just getting more and more and more work. Patient loads are getting increasingly bigger. I think with IT, [we need] systems that facilitate and help with the work flow and help the hospitalist’s day go smoother because there are so many things that we do.”

Miguel Lizardo, MD, hospitalist, University of Massachusetts Memorial Medical Center, Worcester

“It takes a lot of time to interact with the EMRs and all the technology that we have to use. If they can find a way that we can use it in a more user-friendly [way] so that it takes not a long time, that would be great. At least the EMRs that I’ve been in contact with are too cumbersome, too many clicks to get where you want, a bunch of steps to document what you need to. You really are away from the patient and spending a lot of time trying to document.”

Sandeep Palikhel, PA-C, Baylor University Medical Center, Waco, Tex.

“Definitely accuracy. In Texas, where I practice, we get a lot of transfers from rural areas because we are a Level 1 trauma hospital. We get these discharge summaries or progress notes from other hospitals that are handwritten. A lot of information gets missed whenever we’re reading it because it’s not legible, first thing, and it’s not as detail-oriented as the EHRs would be. So that definitely helps. Even going through a medication list, it helps so much to go through an EHR versus going through a handwritten medication list. That’s what I mean by accuracy.”

With the rolling out of the Health IT track on the second full day of HM16, The Hospitalist asked: What problem do you hope health IT solves or helps you solve over the next five years?

Farhanaz Chowdhury, MD, hospitalist, HSHS St. Elizabeth’s Hospital, Belleville, Ill.

“I think that hospital health systems are very primitive. When they make that software, physicians should be more involved so that in everyday life, what we see when we are facing all those problems, you have an algorithm if you want to do something. It should pop up so that you don’t have to write it down and scroll all over.”

Michael Lintner, MD, hospitalist, Aspen Valley Hospital, Colo.

“I think probably the main thing would be work flow, facilitating work flow. I think today hospitalists are just getting more and more and more work. Patient loads are getting increasingly bigger. I think with IT, [we need] systems that facilitate and help with the work flow and help the hospitalist’s day go smoother because there are so many things that we do.”

Miguel Lizardo, MD, hospitalist, University of Massachusetts Memorial Medical Center, Worcester

“It takes a lot of time to interact with the EMRs and all the technology that we have to use. If they can find a way that we can use it in a more user-friendly [way] so that it takes not a long time, that would be great. At least the EMRs that I’ve been in contact with are too cumbersome, too many clicks to get where you want, a bunch of steps to document what you need to. You really are away from the patient and spending a lot of time trying to document.”

Sandeep Palikhel, PA-C, Baylor University Medical Center, Waco, Tex.

“Definitely accuracy. In Texas, where I practice, we get a lot of transfers from rural areas because we are a Level 1 trauma hospital. We get these discharge summaries or progress notes from other hospitals that are handwritten. A lot of information gets missed whenever we’re reading it because it’s not legible, first thing, and it’s not as detail-oriented as the EHRs would be. So that definitely helps. Even going through a medication list, it helps so much to go through an EHR versus going through a handwritten medication list. That’s what I mean by accuracy.”

NEW YORK (Reuters Health) - About one in 20 bariatric surgery patients are readmitted to the hospital within 30 days of having the procedure, according to new findings.

Readmissions are increasingly being used as a quality metric for surgical procedures, Dr. John Morton of Stanford University in California and colleagues note in their report, published online March 19 in the American Journal of Surgery.

"While (the Centers for Medicare and Medicaid Services) has not addressed bariatric surgery readmissions to date, other payors have made readmissions a priority," they add. "Data regarding bariatric surgery readmissions are critical to help better understand and drive quality improvement in this area.

"To investigate the prevalence, causes and risk factors for readmission following bariatric surgery, the researchers looked at data from the 2012 American College of Surgeons National Surgical Quality Improvement Program Public Use File dataset on nearly 18,300 bariatric patients, of whom 55% had laparoscopic Roux-en-Y gastric bypass (LRYGB), 10% had laparoscopic adjustable gastric banding (LAGB), and 35% had laparoscopic sleeve gastrectomy (LSG).

There were 955 readmissions (5.22%), most commonly for gastrointestinal causes (45%), dietary reasons (34%) and bleeding (7%). Readmission rates were nearly 7% for LRYGB; just under 2% for LAGB; and 4% for LSG.

The patients who were readmitted had a significantly longer average operating time (132 vs. 115 minutes) and length of stay (2.76 days vs. 2.23). Forty percent had a complication, versus 4% of patients who were not readmitted. Patients who were readmitted were also more likely to have a body mass index above 50, preoperative diabetes, chronic obstructive pulmonary disease, and hypertension.

Factors independently associated with readmission included African-American race (odds ratio, 1.53), complication (OR, 11.3) and resident involvement (OR, 0.53).

"Other studies have also demonstrated similar predictors of readmission and have also demonstrated that length of stay may also play a role in readmission rates," Dr. Morton and his team state. "This study helps demonstrate that bariatric surgery readmissions are prevalent and potentially preventable."

NEW YORK (Reuters Health) - About one in 20 bariatric surgery patients are readmitted to the hospital within 30 days of having the procedure, according to new findings.

Readmissions are increasingly being used as a quality metric for surgical procedures, Dr. John Morton of Stanford University in California and colleagues note in their report, published online March 19 in the American Journal of Surgery.

"While (the Centers for Medicare and Medicaid Services) has not addressed bariatric surgery readmissions to date, other payors have made readmissions a priority," they add. "Data regarding bariatric surgery readmissions are critical to help better understand and drive quality improvement in this area.

"To investigate the prevalence, causes and risk factors for readmission following bariatric surgery, the researchers looked at data from the 2012 American College of Surgeons National Surgical Quality Improvement Program Public Use File dataset on nearly 18,300 bariatric patients, of whom 55% had laparoscopic Roux-en-Y gastric bypass (LRYGB), 10% had laparoscopic adjustable gastric banding (LAGB), and 35% had laparoscopic sleeve gastrectomy (LSG).

There were 955 readmissions (5.22%), most commonly for gastrointestinal causes (45%), dietary reasons (34%) and bleeding (7%). Readmission rates were nearly 7% for LRYGB; just under 2% for LAGB; and 4% for LSG.

The patients who were readmitted had a significantly longer average operating time (132 vs. 115 minutes) and length of stay (2.76 days vs. 2.23). Forty percent had a complication, versus 4% of patients who were not readmitted. Patients who were readmitted were also more likely to have a body mass index above 50, preoperative diabetes, chronic obstructive pulmonary disease, and hypertension.

Factors independently associated with readmission included African-American race (odds ratio, 1.53), complication (OR, 11.3) and resident involvement (OR, 0.53).

"Other studies have also demonstrated similar predictors of readmission and have also demonstrated that length of stay may also play a role in readmission rates," Dr. Morton and his team state. "This study helps demonstrate that bariatric surgery readmissions are prevalent and potentially preventable."

NEW YORK (Reuters Health) - About one in 20 bariatric surgery patients are readmitted to the hospital within 30 days of having the procedure, according to new findings.

Readmissions are increasingly being used as a quality metric for surgical procedures, Dr. John Morton of Stanford University in California and colleagues note in their report, published online March 19 in the American Journal of Surgery.

"While (the Centers for Medicare and Medicaid Services) has not addressed bariatric surgery readmissions to date, other payors have made readmissions a priority," they add. "Data regarding bariatric surgery readmissions are critical to help better understand and drive quality improvement in this area.

"To investigate the prevalence, causes and risk factors for readmission following bariatric surgery, the researchers looked at data from the 2012 American College of Surgeons National Surgical Quality Improvement Program Public Use File dataset on nearly 18,300 bariatric patients, of whom 55% had laparoscopic Roux-en-Y gastric bypass (LRYGB), 10% had laparoscopic adjustable gastric banding (LAGB), and 35% had laparoscopic sleeve gastrectomy (LSG).

There were 955 readmissions (5.22%), most commonly for gastrointestinal causes (45%), dietary reasons (34%) and bleeding (7%). Readmission rates were nearly 7% for LRYGB; just under 2% for LAGB; and 4% for LSG.

The patients who were readmitted had a significantly longer average operating time (132 vs. 115 minutes) and length of stay (2.76 days vs. 2.23). Forty percent had a complication, versus 4% of patients who were not readmitted. Patients who were readmitted were also more likely to have a body mass index above 50, preoperative diabetes, chronic obstructive pulmonary disease, and hypertension.

Factors independently associated with readmission included African-American race (odds ratio, 1.53), complication (OR, 11.3) and resident involvement (OR, 0.53).

"Other studies have also demonstrated similar predictors of readmission and have also demonstrated that length of stay may also play a role in readmission rates," Dr. Morton and his team state. "This study helps demonstrate that bariatric surgery readmissions are prevalent and potentially preventable."

Micrograph showing AML

The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients

with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).

The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.

The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.

Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.

About the vaccine

The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.

The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.

The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.

In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.

SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.

Micrograph showing AML

The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients

with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).

The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.

The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.

Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.

About the vaccine

The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.

The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.

The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.

In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.

SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.

Micrograph showing AML

The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients

with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).

The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.

The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.

Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.

About the vaccine

The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.

The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.

The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.

In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.

SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.

T cells

Image courtesy of NIAID

VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.

Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.

At a median follow-up of 7 months, all 24 were still alive and disease-free.

In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”

Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, investigators reported results in 41 patients treated on this trial.

Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.

Results

The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).

At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.

All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.

The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).

This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.

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

T cells

Image courtesy of NIAID

VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.

Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.

At a median follow-up of 7 months, all 24 were still alive and disease-free.

In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”

Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, investigators reported results in 41 patients treated on this trial.

Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.

Results

The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).

At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.

All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.

The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).

This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.

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

T cells

Image courtesy of NIAID

VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.

Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.

At a median follow-up of 7 months, all 24 were still alive and disease-free.

In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”

Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, investigators reported results in 41 patients treated on this trial.

Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.

Results

The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).

At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.

All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.

The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).

This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.

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

Leukemia patient

Photo by Bill Branson

VALENCIA, SPAIN—The adjunct T-cell therapy BPX-501 can make haploidentical hematopoietic stem cell transplant (haplo-HSCT) an “attractive option” for pediatric patients with acute leukemia, according to a presentation at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).

Acute leukemia patients who received BPX-501 after haplo-HSCT in a phase 1/2 trial tended to have favorable outcomes.

At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free.

There were several cases of graft-versus-host disease (GVHD), but nearly all of these resolved.

Franco Locatelli, MD, PhD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results at the EBMT meeting as abstract WP16.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, researchers reported results in 41 patients treated on this trial.

Dr Locatelli presented data on 17 patients with acute leukemias—13 with acute lymphoblastic leukemia and 4 with acute myeloid leukemia. Their median age at HSCT was 6.5 years (range, 0.9-16.1)

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis. All were in complete remission at the time of transplant.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only used in the event of uncontrollable GVHD.

Results

The median follow-up was 7 months (range, 1-15.6). The median time to platelet recovery was 11 days (range, 9-13), and the median time to neutrophil recovery was 17 days (range, 10-22).

Three patients developed skin-only acute GVHD, were treated with topical steroids, and the GVHD resolved. Two patients developed acute grade 3 GVHD, were treated with systemic steroids, and the GVHD resolved.

Two patients developed mild chronic GVHD, received systemic steroids, and the GVHD resolved. And 1 patient developed severe chronic GVHD, received systemic steroids and rimiducid, and the GVHD improved.

One patient relapsed. The estimated 1-year disease-free survival was 92.9%. Dr Locatelli noted that, although the follow-up is still limited, these results compare favorably to results in historical controls.

“These interim results continue to be very encouraging and indicate that a haploidentical transplant, with the addition of BPX-501-modified donor T cells, can be an attractive option for children in need of a transplant,” he said.

“Future studies will address the role of repeated infusions or higher numbers of BPX-501 cells in malignant patients with resistant disease.”

The BP-004 trial also included 24 patients with nonmalignant disorders. Results in these patients were presented at the EBMT meeting as abstract O007.

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

Leukemia patient

Photo by Bill Branson

VALENCIA, SPAIN—The adjunct T-cell therapy BPX-501 can make haploidentical hematopoietic stem cell transplant (haplo-HSCT) an “attractive option” for pediatric patients with acute leukemia, according to a presentation at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).

Acute leukemia patients who received BPX-501 after haplo-HSCT in a phase 1/2 trial tended to have favorable outcomes.

At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free.

There were several cases of graft-versus-host disease (GVHD), but nearly all of these resolved.

Franco Locatelli, MD, PhD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results at the EBMT meeting as abstract WP16.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, researchers reported results in 41 patients treated on this trial.

Dr Locatelli presented data on 17 patients with acute leukemias—13 with acute lymphoblastic leukemia and 4 with acute myeloid leukemia. Their median age at HSCT was 6.5 years (range, 0.9-16.1)

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis. All were in complete remission at the time of transplant.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only used in the event of uncontrollable GVHD.

Results

The median follow-up was 7 months (range, 1-15.6). The median time to platelet recovery was 11 days (range, 9-13), and the median time to neutrophil recovery was 17 days (range, 10-22).

Three patients developed skin-only acute GVHD, were treated with topical steroids, and the GVHD resolved. Two patients developed acute grade 3 GVHD, were treated with systemic steroids, and the GVHD resolved.

Two patients developed mild chronic GVHD, received systemic steroids, and the GVHD resolved. And 1 patient developed severe chronic GVHD, received systemic steroids and rimiducid, and the GVHD improved.

One patient relapsed. The estimated 1-year disease-free survival was 92.9%. Dr Locatelli noted that, although the follow-up is still limited, these results compare favorably to results in historical controls.

“These interim results continue to be very encouraging and indicate that a haploidentical transplant, with the addition of BPX-501-modified donor T cells, can be an attractive option for children in need of a transplant,” he said.

“Future studies will address the role of repeated infusions or higher numbers of BPX-501 cells in malignant patients with resistant disease.”

The BP-004 trial also included 24 patients with nonmalignant disorders. Results in these patients were presented at the EBMT meeting as abstract O007.

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

Leukemia patient

Photo by Bill Branson

VALENCIA, SPAIN—The adjunct T-cell therapy BPX-501 can make haploidentical hematopoietic stem cell transplant (haplo-HSCT) an “attractive option” for pediatric patients with acute leukemia, according to a presentation at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).

Acute leukemia patients who received BPX-501 after haplo-HSCT in a phase 1/2 trial tended to have favorable outcomes.

At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free.

There were several cases of graft-versus-host disease (GVHD), but nearly all of these resolved.

Franco Locatelli, MD, PhD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results at the EBMT meeting as abstract WP16.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, researchers reported results in 41 patients treated on this trial.

Dr Locatelli presented data on 17 patients with acute leukemias—13 with acute lymphoblastic leukemia and 4 with acute myeloid leukemia. Their median age at HSCT was 6.5 years (range, 0.9-16.1)

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis. All were in complete remission at the time of transplant.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only used in the event of uncontrollable GVHD.

Results

The median follow-up was 7 months (range, 1-15.6). The median time to platelet recovery was 11 days (range, 9-13), and the median time to neutrophil recovery was 17 days (range, 10-22).

Three patients developed skin-only acute GVHD, were treated with topical steroids, and the GVHD resolved. Two patients developed acute grade 3 GVHD, were treated with systemic steroids, and the GVHD resolved.

Two patients developed mild chronic GVHD, received systemic steroids, and the GVHD resolved. And 1 patient developed severe chronic GVHD, received systemic steroids and rimiducid, and the GVHD improved.

One patient relapsed. The estimated 1-year disease-free survival was 92.9%. Dr Locatelli noted that, although the follow-up is still limited, these results compare favorably to results in historical controls.

“These interim results continue to be very encouraging and indicate that a haploidentical transplant, with the addition of BPX-501-modified donor T cells, can be an attractive option for children in need of a transplant,” he said.

“Future studies will address the role of repeated infusions or higher numbers of BPX-501 cells in malignant patients with resistant disease.”

The BP-004 trial also included 24 patients with nonmalignant disorders. Results in these patients were presented at the EBMT meeting as abstract O007.

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