LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

• A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
• Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
• Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
• Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
• Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

• A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
• Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
• Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
• Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
• Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

• A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
• Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
• Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
• Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
• Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

LAS VEGAS – While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

• Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
• Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
• Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
• Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

LAS VEGAS – While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

• Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
• Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
• Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
• Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

LAS VEGAS – While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

• Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
• Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
• Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
• Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

ORLANDO – A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

sworcester@mdedge.com

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

ORLANDO – A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

sworcester@mdedge.com

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

ORLANDO – A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

sworcester@mdedge.com

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.

In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

dbrunk@mdedge.com

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

dbrunk@mdedge.com

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

dbrunk@mdedge.com

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

Systemic acne treatments may be underused in non-Hispanic black patients, women, and Medicaid patients, based on findings from a retrospective, cohort study of 29,928 individuals with acne.

“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.

Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.

For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.

Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).

Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).

Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.

In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).

The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.

“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.

SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.

Systemic acne treatments may be underused in non-Hispanic black patients, women, and Medicaid patients, based on findings from a retrospective, cohort study of 29,928 individuals with acne.

“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.

Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.

For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.

Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).

Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).

Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.

In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).

The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.

“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.

SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.

Systemic acne treatments may be underused in non-Hispanic black patients, women, and Medicaid patients, based on findings from a retrospective, cohort study of 29,928 individuals with acne.

“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.

Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.

For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.

Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).

Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).

Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.

In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).

The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.

“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.

SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.

With myriad complex, high-tech problems facing private practice in this modern era, I am periodically reminded by long-time readers to revisit some of the low-tech issues that will always require our attention.

Few are lower tech (in most cases) and more easily overlooked than theft from within. Embezzlement remains far more common in medical offices than generally assumed – and it often occurs in full view of physicians who think everything is fine. Most embezzlers are not skillful or discreet; their transgressions may go undetected for years, simply because no one suspects it is happening.

Detecting fraud is an inexact science. There is no textbook approach that one can follow, but a few simple measures will prevent or expose the most common forms:

• Make it more difficult. Theft and embezzlement are usually products of opportunity, so minimize those opportunities. No one person should be in charge of the entire bookkeeping process: The person who enters charges should be different from the one who enters payments. The one who writes checks or makes electronic fund transfers should not balance the books, and so on. Internal audits should be done on a regular basis, and all employees should know that. Your accountant can help.
• Reconcile cash receipts daily. Embezzlement does not require sophisticated technology; the most common form is simply taking cash out of the till. In a typical scenario, a patient pays a copay of $15 in cash; the receptionist records the payment as $5, and pockets the rest. Make sure a receipt is generated for every cash transaction, and that someone other than the person accepting cash reconciles the charges, receipts, and cash totals daily.
• Inventory your stock. Cash isn’t the only susceptible commodity. If you sell cosmetics or other products, inventory your stock frequently. And office personnel are not the only potential thieves: Last year, a locum tenens physician down the street conspired with a receptionist to take cash transactions for cosmetic neurotoxins and fillers “off the books” and split the spoils. That office was being ripped off twice; first for the neurotoxin and filler materials themselves, and then for the cash proceeds.
• Separate all accounting duties. Another popular ploy is false invoicing for imaginary supplies. A friend’s experience provides a good example (retold with his permission): His bookkeeper wrote sizable checks to herself, disguising them in the ledger as payments to vendors commonly used by his practice. Since the same employee also balanced the checkbook, she got away with it for years. “It wasn’t at all clever,” he told me, “and I’m embarrassed to admit that it happened to me.” Once again, separation of duties is the key to prevention. One employee should enter invoices into the data system, another should issue the check or make the electronic transfer, and a third should match invoices to goods and services received.
• Verify expense reports. False expense reporting is a subset of the fake invoice scam. When an employee asks for reimbursement of expenses, make sure those expenses are real.
• Consider computer safeguards. Computers facilitate a lot of financial chores, but they also consolidate financial data in one place, where it is potentially accessible to anybody, anywhere. Your computer vendor should be aware of this, and there should be safeguards built into your system. Ask about them. If they aren’t there, ask why.
• Hire honest employees. All applicants look great on paper, so check their references; and with their permission, you can run background checks for a few dollars on any of several public information web sites. My columns on hiring are available on the MDedge Dermatology website.
• Look for “red flags.” Examples include employees who refuse to take vacations, because someone else will have do their work or who insist on posting expenses that are a coworker’s responsibility, “just to be nice.” Anyone obviously living beyond his or her means merits suspicion as well.
• Consider bonding your employees. Dishonesty bonds are relatively inexpensive, and provide assurance of some measure of recovery if your safeguards fail. Also, just knowing that your staff is bonded will scare off most dishonest applicants. One effective screen is a question on your employment application: “Would you object to being bonded?”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

With myriad complex, high-tech problems facing private practice in this modern era, I am periodically reminded by long-time readers to revisit some of the low-tech issues that will always require our attention.

Few are lower tech (in most cases) and more easily overlooked than theft from within. Embezzlement remains far more common in medical offices than generally assumed – and it often occurs in full view of physicians who think everything is fine. Most embezzlers are not skillful or discreet; their transgressions may go undetected for years, simply because no one suspects it is happening.

Detecting fraud is an inexact science. There is no textbook approach that one can follow, but a few simple measures will prevent or expose the most common forms:

• Make it more difficult. Theft and embezzlement are usually products of opportunity, so minimize those opportunities. No one person should be in charge of the entire bookkeeping process: The person who enters charges should be different from the one who enters payments. The one who writes checks or makes electronic fund transfers should not balance the books, and so on. Internal audits should be done on a regular basis, and all employees should know that. Your accountant can help.
• Reconcile cash receipts daily. Embezzlement does not require sophisticated technology; the most common form is simply taking cash out of the till. In a typical scenario, a patient pays a copay of $15 in cash; the receptionist records the payment as $5, and pockets the rest. Make sure a receipt is generated for every cash transaction, and that someone other than the person accepting cash reconciles the charges, receipts, and cash totals daily.
• Inventory your stock. Cash isn’t the only susceptible commodity. If you sell cosmetics or other products, inventory your stock frequently. And office personnel are not the only potential thieves: Last year, a locum tenens physician down the street conspired with a receptionist to take cash transactions for cosmetic neurotoxins and fillers “off the books” and split the spoils. That office was being ripped off twice; first for the neurotoxin and filler materials themselves, and then for the cash proceeds.
• Separate all accounting duties. Another popular ploy is false invoicing for imaginary supplies. A friend’s experience provides a good example (retold with his permission): His bookkeeper wrote sizable checks to herself, disguising them in the ledger as payments to vendors commonly used by his practice. Since the same employee also balanced the checkbook, she got away with it for years. “It wasn’t at all clever,” he told me, “and I’m embarrassed to admit that it happened to me.” Once again, separation of duties is the key to prevention. One employee should enter invoices into the data system, another should issue the check or make the electronic transfer, and a third should match invoices to goods and services received.
• Verify expense reports. False expense reporting is a subset of the fake invoice scam. When an employee asks for reimbursement of expenses, make sure those expenses are real.
• Consider computer safeguards. Computers facilitate a lot of financial chores, but they also consolidate financial data in one place, where it is potentially accessible to anybody, anywhere. Your computer vendor should be aware of this, and there should be safeguards built into your system. Ask about them. If they aren’t there, ask why.
• Hire honest employees. All applicants look great on paper, so check their references; and with their permission, you can run background checks for a few dollars on any of several public information web sites. My columns on hiring are available on the MDedge Dermatology website.
• Look for “red flags.” Examples include employees who refuse to take vacations, because someone else will have do their work or who insist on posting expenses that are a coworker’s responsibility, “just to be nice.” Anyone obviously living beyond his or her means merits suspicion as well.
• Consider bonding your employees. Dishonesty bonds are relatively inexpensive, and provide assurance of some measure of recovery if your safeguards fail. Also, just knowing that your staff is bonded will scare off most dishonest applicants. One effective screen is a question on your employment application: “Would you object to being bonded?”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

With myriad complex, high-tech problems facing private practice in this modern era, I am periodically reminded by long-time readers to revisit some of the low-tech issues that will always require our attention.

Few are lower tech (in most cases) and more easily overlooked than theft from within. Embezzlement remains far more common in medical offices than generally assumed – and it often occurs in full view of physicians who think everything is fine. Most embezzlers are not skillful or discreet; their transgressions may go undetected for years, simply because no one suspects it is happening.

Detecting fraud is an inexact science. There is no textbook approach that one can follow, but a few simple measures will prevent or expose the most common forms:

• Make it more difficult. Theft and embezzlement are usually products of opportunity, so minimize those opportunities. No one person should be in charge of the entire bookkeeping process: The person who enters charges should be different from the one who enters payments. The one who writes checks or makes electronic fund transfers should not balance the books, and so on. Internal audits should be done on a regular basis, and all employees should know that. Your accountant can help.
• Reconcile cash receipts daily. Embezzlement does not require sophisticated technology; the most common form is simply taking cash out of the till. In a typical scenario, a patient pays a copay of $15 in cash; the receptionist records the payment as $5, and pockets the rest. Make sure a receipt is generated for every cash transaction, and that someone other than the person accepting cash reconciles the charges, receipts, and cash totals daily.
• Inventory your stock. Cash isn’t the only susceptible commodity. If you sell cosmetics or other products, inventory your stock frequently. And office personnel are not the only potential thieves: Last year, a locum tenens physician down the street conspired with a receptionist to take cash transactions for cosmetic neurotoxins and fillers “off the books” and split the spoils. That office was being ripped off twice; first for the neurotoxin and filler materials themselves, and then for the cash proceeds.
• Separate all accounting duties. Another popular ploy is false invoicing for imaginary supplies. A friend’s experience provides a good example (retold with his permission): His bookkeeper wrote sizable checks to herself, disguising them in the ledger as payments to vendors commonly used by his practice. Since the same employee also balanced the checkbook, she got away with it for years. “It wasn’t at all clever,” he told me, “and I’m embarrassed to admit that it happened to me.” Once again, separation of duties is the key to prevention. One employee should enter invoices into the data system, another should issue the check or make the electronic transfer, and a third should match invoices to goods and services received.
• Verify expense reports. False expense reporting is a subset of the fake invoice scam. When an employee asks for reimbursement of expenses, make sure those expenses are real.
• Consider computer safeguards. Computers facilitate a lot of financial chores, but they also consolidate financial data in one place, where it is potentially accessible to anybody, anywhere. Your computer vendor should be aware of this, and there should be safeguards built into your system. Ask about them. If they aren’t there, ask why.
• Hire honest employees. All applicants look great on paper, so check their references; and with their permission, you can run background checks for a few dollars on any of several public information web sites. My columns on hiring are available on the MDedge Dermatology website.
• Look for “red flags.” Examples include employees who refuse to take vacations, because someone else will have do their work or who insist on posting expenses that are a coworker’s responsibility, “just to be nice.” Anyone obviously living beyond his or her means merits suspicion as well.
• Consider bonding your employees. Dishonesty bonds are relatively inexpensive, and provide assurance of some measure of recovery if your safeguards fail. Also, just knowing that your staff is bonded will scare off most dishonest applicants. One effective screen is a question on your employment application: “Would you object to being bonded?”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

Smartphone applications (apps) using so-called artificial intelligence (AI) aimed at the general public for use on suspicious skin lesions are unreliable, said U.K. researchers reporting a systematic review.
 

These apps are providing information that could lead to “potentially life-or-death decisions,” commented co-lead author Hywel C. Williams, MD, from the Centre of Evidence Based Dermatology, University of Nottingham (England).

“The one thing you mustn’t do in a situation where early diagnosis can make a difference between life and death is you mustn’t miss the melanoma,” he said in an interview.

“These apps were missing melanomas, and that’s very worrisome,” he commented.

The review included nine studies of skin cancer smartphone apps, including two apps, SkinScan and SkinVision, that have been given Conformit Europenne (CE) marks, allowing them to be marketed across Europe. These apps are also available in Australia and New Zealand, but not in the United States.

The review found that SkinScan was not able to identify any melanomas in the one study that assessed this app, while SkinVision had a relatively low sensitivity and specificity, with 12% of cancerous or precancerous lesions missed and 21% of benign lesions wrongly identified as cancerous.

This means that among 1,000 people with a melanoma prevalence of 3%, 4 of 30 melanomas would be missed, and 200 people would be incorrectly told that a mole was of high concern, the authors estimated.

The research was published by The BMJ on Feb. 10.

“Although I was broad minded on the potential benefit of apps for diagnosing skin cancer, I am now worried given the results of our study and the overall poor quality of studies used to test these apps,” Dr. Williams commented in a statement.

Coauthor Jac Dinnes, PhD, from the Institute of Applied Health Research at the University of Birmingham (England), added it is “really disappointing that there is not better quality evidence available to judge the efficacy of these apps.”

“It is vital that health care professionals are aware of the current limitations both in the technologies and in their evaluations,” she added.

The results also highlight the limitations of the regulatory system governing smartphone apps in that they are currently not subject to assessment by bodies such as the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), the authors commented.

“Regulators need to become alert to the potential harm that poorly performing algorithm-based diagnostic or risk monitoring apps create,” said co-lead author Jonathan J. Deeks, PhD, also at the Institute of Applied Health Research.

“We rely on the CE mark as a sign of quality, but the current CE mark assessment processes are not fit for protecting the public against the risks that these apps present.”

Speaking in an interview, Williams lamented the poor quality of the research that had been conducted. “These studies were not good enough,” he said, adding that “there’s no excuse for really poor study design and poor reporting.”

He would like to see the regulations tightened around AI apps purporting to inform decision making for the general public and suggests that these devices should be assessed by the MHRA. “I really do think a CE mark is not enough,” he said.

The team noted that the skin cancer apps “all include disclaimers that the results should only be used as a guide and cannot replace health care advice,” through which the manufacturers “attempt to evade any responsibility for negative outcomes experienced by users.”

Nevertheless, the “poor and variable performance” of the apps revealed by their review indicates that they “have not yet shown sufficient promise to recommend their use,” they concluded.

The “official approval” implied by a CE mark “will give consumers the impression that the apps have been assessed as effective and safe,” wrote Ben Goldacre, DataLab director, Nuffield Department of Primary Care, University of Oxford (England), and colleagues in an accompanying editorial.

“The implicit assumption is that apps are similarly low-risk technology” to devices such as sticking plasters and reading glasses, they comment.

“But shortcomings in diagnostic apps can have serious implications,” they warn. The “risks include psychological harm from health anxiety or ‘cyberchondria,’ and physical harm from misdiagnosis or overdiagnosis; for clinicians there is a risk of increased workload, and changes to ethical or legal responsibilities around triage, referral, diagnosis, and treatment.” There is also potential for “inappropriate resource use, and even loss of credibility for digital technology in general.”

Details of the review

For their review, the authors searched the Cochrane Central Register on Controlled Trials, the MEDLNE, Embase, Cumulative Index to Nursing and Allied Health Literature, Conference Proceedings Citation index, Zetoc, and Science Citation Index databases, and online trial registers for studies published between August 2016 and April 2019.

From 80 studies identified, 9 met the eligibility criteria.

Of those, six studies, evaluating a total of 725 skin lesions, determined the accuracy of smartphone apps in risk stratifying suspicious skin lesions by comparing them against a histopathological reference standard diagnosis or expert follow-up.

Five of these studies aimed to detect only melanoma, while one sought to differentiate between malignant or premalignant lesions (including melanoma, basal cell carcinoma, and squamous cell carcinoma) and benign lesions.

The three remaining studies, which evaluated 407 lesions in all, compared smartphone app recommendations against a reference standard of expert recommendations for further investigation or intervention.

The researchers found the studies had a string of potential biases and limitations.

For example, only four studies recruited a consecutive sample of study participants and lesions, and only two included lesions selected by study participants, whereas five studies used lesions that had been selected by a clinician.

Three studies reported that it took 5-10 attempts to obtain an adequate image. In seven studies, it was the researchers and not the patients who used the app to photograph the lesions, and two studies used images obtained from dermatology databases.

This “raised concerns that the results of the studies were unlikely to be representative of real life use,” the authors comment.

In addition, the exclusion of unevaluable images “might have systematically inflated the diagnostic performance of the tested apps,” they add.

The independent research was supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham and is an update of one of a collection of reviews funded by the NIHR through its Cochrane Systematic Review Programme Grant.
 

This article first appeared on Medscape.com.

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

sworcester@mdedge.com

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

sworcester@mdedge.com

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

sworcester@mdedge.com

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.