The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

A phenotype approach should be used to diagnose and manage rosacea, according to an expert panel that included 17 dermatologists from North America, Europe, Asia, Africa, and South America.

“As individual treatments do not address multiple features simultaneously, consideration of specific phenotypical issues facilitates individualized optimization of rosacea,” the panel concluded. As individual presentations of rosacea can span more than one of the currently defined disease subtypes, and vary widely in severity, dermatologists have long expressed a need to move to a phenotype-based system for diagnosis and classification.
 

The goal of the panel was “to establish international consensus on diagnosis and severity determination to improve outcomes” for people with rosacea (Br J Dermatol. 2016 Oct 8. doi: 10.1111/bjd.15122).

Jerry L. Tan, MD, of the University of Western Ontario, Windsor, and coauthors, explained why they considered a transition to the phenotype-based approach important: “Subtype classification may not fully cover the range of clinical presentations and is likely to confound severity assessment, whereas a phenotype-based approach could improve patient outcomes by addressing an individual patient’s clinical presentation and concerns.”

The panel identified two phenotypes as independently diagnostic of rosacea: persistent, centrofacial erythema associated with periodic intensification, and phymatous changes. Flushing or transient erythema, telangiectasia, inflammatory lesions, and ocular manifestations – the other phenotypes identified in the study – were not considered individually diagnostic.

Severity measurements for each phenotype were defined with a high degree of consensus, and the panel agreed that the severity of each feature should be rated independently and not grouped into subtype. For flushing or transient erythema, for example, the panel recommended that clinicians consider the intensity and frequency of episodes along with the area of involvement. For phymatous changes, inflammation, skin thickening, and deformation were identified as the key severity measures.

Although the investigators acknowledged that their expert consensus was the product of clinical opinion in the absence of extensive evidence, they cited as one of the study’s strengths its broad expert representation across geographical regions, where rosacea presentations may differ. Erythema and telangiectasia, Dr. Tan and colleagues wrote, “may not be visible in skin phototypes V and VI, an issue that may be overcome with experience and appropriate history taking.” They added that “other techniques, including skin biopsy, can also be considered for diagnostic support.” They recommended the development of new validated scales to be used in darker-skinned patients.

The panel also identified the psychosocial impact of rosacea as one severely understudied area of rosacea, and advocated the development of a new research tool that would assess psychological comorbidities. The proposed tool, they wrote, “should go beyond those currently available and assess the psychosocial impact for all major phenotypes.” The only rosacea-specific quality of life scoring measure, RosaQoL, contains notable deficiencies, they noted, including a lack of a measure for phymatous changes.

“Since clinicians and patients often have disparate views of disease,” the researchers wrote, “objective and practical tools based on individual presenting features are likely to be of value in setting treatment targets and monitoring treatment progress for patients with rosacea.”

The panel included three ophthalmologists from Germany and the United States; their recommendations were considered exploratory.

The study, which consisted of both electronic surveys and in-person meetings, was funded by Galderma. Twelve of its coauthors, including Dr. Tan, disclosed financial relationships with manufacturers.

[email protected]

A phenotype approach should be used to diagnose and manage rosacea, according to an expert panel that included 17 dermatologists from North America, Europe, Asia, Africa, and South America.

“As individual treatments do not address multiple features simultaneously, consideration of specific phenotypical issues facilitates individualized optimization of rosacea,” the panel concluded. As individual presentations of rosacea can span more than one of the currently defined disease subtypes, and vary widely in severity, dermatologists have long expressed a need to move to a phenotype-based system for diagnosis and classification.
 

The goal of the panel was “to establish international consensus on diagnosis and severity determination to improve outcomes” for people with rosacea (Br J Dermatol. 2016 Oct 8. doi: 10.1111/bjd.15122).

Jerry L. Tan, MD, of the University of Western Ontario, Windsor, and coauthors, explained why they considered a transition to the phenotype-based approach important: “Subtype classification may not fully cover the range of clinical presentations and is likely to confound severity assessment, whereas a phenotype-based approach could improve patient outcomes by addressing an individual patient’s clinical presentation and concerns.”

The panel identified two phenotypes as independently diagnostic of rosacea: persistent, centrofacial erythema associated with periodic intensification, and phymatous changes. Flushing or transient erythema, telangiectasia, inflammatory lesions, and ocular manifestations – the other phenotypes identified in the study – were not considered individually diagnostic.

Severity measurements for each phenotype were defined with a high degree of consensus, and the panel agreed that the severity of each feature should be rated independently and not grouped into subtype. For flushing or transient erythema, for example, the panel recommended that clinicians consider the intensity and frequency of episodes along with the area of involvement. For phymatous changes, inflammation, skin thickening, and deformation were identified as the key severity measures.

Although the investigators acknowledged that their expert consensus was the product of clinical opinion in the absence of extensive evidence, they cited as one of the study’s strengths its broad expert representation across geographical regions, where rosacea presentations may differ. Erythema and telangiectasia, Dr. Tan and colleagues wrote, “may not be visible in skin phototypes V and VI, an issue that may be overcome with experience and appropriate history taking.” They added that “other techniques, including skin biopsy, can also be considered for diagnostic support.” They recommended the development of new validated scales to be used in darker-skinned patients.

The panel also identified the psychosocial impact of rosacea as one severely understudied area of rosacea, and advocated the development of a new research tool that would assess psychological comorbidities. The proposed tool, they wrote, “should go beyond those currently available and assess the psychosocial impact for all major phenotypes.” The only rosacea-specific quality of life scoring measure, RosaQoL, contains notable deficiencies, they noted, including a lack of a measure for phymatous changes.

“Since clinicians and patients often have disparate views of disease,” the researchers wrote, “objective and practical tools based on individual presenting features are likely to be of value in setting treatment targets and monitoring treatment progress for patients with rosacea.”

The panel included three ophthalmologists from Germany and the United States; their recommendations were considered exploratory.

The study, which consisted of both electronic surveys and in-person meetings, was funded by Galderma. Twelve of its coauthors, including Dr. Tan, disclosed financial relationships with manufacturers.

[email protected]

A phenotype approach should be used to diagnose and manage rosacea, according to an expert panel that included 17 dermatologists from North America, Europe, Asia, Africa, and South America.

“As individual treatments do not address multiple features simultaneously, consideration of specific phenotypical issues facilitates individualized optimization of rosacea,” the panel concluded. As individual presentations of rosacea can span more than one of the currently defined disease subtypes, and vary widely in severity, dermatologists have long expressed a need to move to a phenotype-based system for diagnosis and classification.
 

The goal of the panel was “to establish international consensus on diagnosis and severity determination to improve outcomes” for people with rosacea (Br J Dermatol. 2016 Oct 8. doi: 10.1111/bjd.15122).

Jerry L. Tan, MD, of the University of Western Ontario, Windsor, and coauthors, explained why they considered a transition to the phenotype-based approach important: “Subtype classification may not fully cover the range of clinical presentations and is likely to confound severity assessment, whereas a phenotype-based approach could improve patient outcomes by addressing an individual patient’s clinical presentation and concerns.”

The panel identified two phenotypes as independently diagnostic of rosacea: persistent, centrofacial erythema associated with periodic intensification, and phymatous changes. Flushing or transient erythema, telangiectasia, inflammatory lesions, and ocular manifestations – the other phenotypes identified in the study – were not considered individually diagnostic.

Severity measurements for each phenotype were defined with a high degree of consensus, and the panel agreed that the severity of each feature should be rated independently and not grouped into subtype. For flushing or transient erythema, for example, the panel recommended that clinicians consider the intensity and frequency of episodes along with the area of involvement. For phymatous changes, inflammation, skin thickening, and deformation were identified as the key severity measures.

Although the investigators acknowledged that their expert consensus was the product of clinical opinion in the absence of extensive evidence, they cited as one of the study’s strengths its broad expert representation across geographical regions, where rosacea presentations may differ. Erythema and telangiectasia, Dr. Tan and colleagues wrote, “may not be visible in skin phototypes V and VI, an issue that may be overcome with experience and appropriate history taking.” They added that “other techniques, including skin biopsy, can also be considered for diagnostic support.” They recommended the development of new validated scales to be used in darker-skinned patients.

The panel also identified the psychosocial impact of rosacea as one severely understudied area of rosacea, and advocated the development of a new research tool that would assess psychological comorbidities. The proposed tool, they wrote, “should go beyond those currently available and assess the psychosocial impact for all major phenotypes.” The only rosacea-specific quality of life scoring measure, RosaQoL, contains notable deficiencies, they noted, including a lack of a measure for phymatous changes.

“Since clinicians and patients often have disparate views of disease,” the researchers wrote, “objective and practical tools based on individual presenting features are likely to be of value in setting treatment targets and monitoring treatment progress for patients with rosacea.”

The panel included three ophthalmologists from Germany and the United States; their recommendations were considered exploratory.

The study, which consisted of both electronic surveys and in-person meetings, was funded by Galderma. Twelve of its coauthors, including Dr. Tan, disclosed financial relationships with manufacturers.

[email protected]

Researchers have identified two distinct molecular subclasses of Crohn’s disease, based on gene expression and phenotype, which could help with better tailoring of treatment.

Crohn’s disease is a chronic inflammatory disorder with a diverse clinical presentation and pattern of progression, yet the molecular and genetic factors underlying the disease are not well understood.

This complicates treatment – which currently relies on doctors’ subjective clinical classification – and makes it difficult to develop an evidence-based personalized approach.

Writing in the Oct. 14 online edition of Gut, Matthew Weiser, a graduate student in the genetics department at the University of North Carolina at Chapel Hill and his coauthors report the results of a genetic and molecular analysis of noninflamed colon tissue from a cohort of 21 adult patients with Crohn’s disease and from healthy controls.

This analysis revealed two distinct molecular phenotypes in colon tissue, which they labeled as “colon-like” and “ileum-like.” They found significant differences in cellular metabolism and immune pathways (Gut. 2016 Oct 14. doi: 10.1136/gutjnl-2016-312518).

In the colon-like subtype, the tissue samples – which were all taken from the colon – showed gene expression patterns that were typical of cells from the colon. However, in the ileum-like subtype, the gene expression patterns in these colon cells more closely resembled the gene expression of ileum cells.

They also saw significant differences in other molecular traits, such as chromatin accessibility, and pathways involved in lipid and xenobiotic metabolism.

“Furthermore, chromatin accessibility data suggest these subclasses exist due to stable molecular transformations of the genomic architecture in colon tissue cells, and not transient differences due to external cellular signaling,” researchers reported.

To rule out the possibility that these differences might be from treatment history, researchers conducted a similar analysis using samples from 201 treatment-naive pediatric patients with Crohn’s disease and found the same molecular and genetic patterns.

“Together, these data strongly suggest that the colon-like and ileum-like molecular signatures define two forms of [Crohn’s disease] present, regardless of tissue sampling location, patient age, or treatment status.”

The researchers also examined the impact the two subtypes might have on the clinical disease and therefore the therapeutic approach taken. In the cohort of treatment-naive pediatric patients, they found that patients with the more colon-like Crohn’s disease were more likely to have both colon and ileum involvement, have deep ulcers, and show more macroscopic inflammation than those with more ileum-like Crohn’s disease.

They also found that adults in the colon-like disease subclass were the only ones who were likely to have rectal disease or require a colectomy, although they noted that the sample size was small.

More patients with the ileum-like disease showed no inflammation and were also more likely to have involvement of the colon only.

“Although our sample size is small, these data suggest that molecular subtypes of [Crohn’s disease] can stratify patients into clinically distinct and relevant subgroups and may prospectively identify those more likely to require intensive medical therapy,” the authors wrote.

“As a first step, molecular stratifications of archived patient tissue and serum from major clinical trials could be performed in the context of response to biological and microbial therapies for [Crohn’s disease].”

The authors pointed out that they did not study samples from both intestinal regions in each patient but suggested that their findings should motivate future studies in larger cohorts using matched tissue samples from both the colon and ileum.

“These data emphasize the need to continue and expand these studies over time to incorporate the evolving clinical phenotype in both adult and pediatric patients, and the need to study both tissues in the same patient.”

The study was supported by the National Institute of Environmental Health Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Gastroenterological Association, Broad Medical Research Program, Crohn’s and Colitis Foundation of America, International Human Microbiome Consortium, UNC Team Translational Science Award, and Helmsley Charitable Trust SHARE 2, Project 3. No conflicts of interest were declared.

Researchers have identified two distinct molecular subclasses of Crohn’s disease, based on gene expression and phenotype, which could help with better tailoring of treatment.

Crohn’s disease is a chronic inflammatory disorder with a diverse clinical presentation and pattern of progression, yet the molecular and genetic factors underlying the disease are not well understood.

This complicates treatment – which currently relies on doctors’ subjective clinical classification – and makes it difficult to develop an evidence-based personalized approach.

Writing in the Oct. 14 online edition of Gut, Matthew Weiser, a graduate student in the genetics department at the University of North Carolina at Chapel Hill and his coauthors report the results of a genetic and molecular analysis of noninflamed colon tissue from a cohort of 21 adult patients with Crohn’s disease and from healthy controls.

This analysis revealed two distinct molecular phenotypes in colon tissue, which they labeled as “colon-like” and “ileum-like.” They found significant differences in cellular metabolism and immune pathways (Gut. 2016 Oct 14. doi: 10.1136/gutjnl-2016-312518).

In the colon-like subtype, the tissue samples – which were all taken from the colon – showed gene expression patterns that were typical of cells from the colon. However, in the ileum-like subtype, the gene expression patterns in these colon cells more closely resembled the gene expression of ileum cells.

They also saw significant differences in other molecular traits, such as chromatin accessibility, and pathways involved in lipid and xenobiotic metabolism.

“Furthermore, chromatin accessibility data suggest these subclasses exist due to stable molecular transformations of the genomic architecture in colon tissue cells, and not transient differences due to external cellular signaling,” researchers reported.

To rule out the possibility that these differences might be from treatment history, researchers conducted a similar analysis using samples from 201 treatment-naive pediatric patients with Crohn’s disease and found the same molecular and genetic patterns.

“Together, these data strongly suggest that the colon-like and ileum-like molecular signatures define two forms of [Crohn’s disease] present, regardless of tissue sampling location, patient age, or treatment status.”

The researchers also examined the impact the two subtypes might have on the clinical disease and therefore the therapeutic approach taken. In the cohort of treatment-naive pediatric patients, they found that patients with the more colon-like Crohn’s disease were more likely to have both colon and ileum involvement, have deep ulcers, and show more macroscopic inflammation than those with more ileum-like Crohn’s disease.

They also found that adults in the colon-like disease subclass were the only ones who were likely to have rectal disease or require a colectomy, although they noted that the sample size was small.

More patients with the ileum-like disease showed no inflammation and were also more likely to have involvement of the colon only.

“Although our sample size is small, these data suggest that molecular subtypes of [Crohn’s disease] can stratify patients into clinically distinct and relevant subgroups and may prospectively identify those more likely to require intensive medical therapy,” the authors wrote.

“As a first step, molecular stratifications of archived patient tissue and serum from major clinical trials could be performed in the context of response to biological and microbial therapies for [Crohn’s disease].”

The authors pointed out that they did not study samples from both intestinal regions in each patient but suggested that their findings should motivate future studies in larger cohorts using matched tissue samples from both the colon and ileum.

“These data emphasize the need to continue and expand these studies over time to incorporate the evolving clinical phenotype in both adult and pediatric patients, and the need to study both tissues in the same patient.”

The study was supported by the National Institute of Environmental Health Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Gastroenterological Association, Broad Medical Research Program, Crohn’s and Colitis Foundation of America, International Human Microbiome Consortium, UNC Team Translational Science Award, and Helmsley Charitable Trust SHARE 2, Project 3. No conflicts of interest were declared.

Researchers have identified two distinct molecular subclasses of Crohn’s disease, based on gene expression and phenotype, which could help with better tailoring of treatment.

Crohn’s disease is a chronic inflammatory disorder with a diverse clinical presentation and pattern of progression, yet the molecular and genetic factors underlying the disease are not well understood.

This complicates treatment – which currently relies on doctors’ subjective clinical classification – and makes it difficult to develop an evidence-based personalized approach.

Writing in the Oct. 14 online edition of Gut, Matthew Weiser, a graduate student in the genetics department at the University of North Carolina at Chapel Hill and his coauthors report the results of a genetic and molecular analysis of noninflamed colon tissue from a cohort of 21 adult patients with Crohn’s disease and from healthy controls.

This analysis revealed two distinct molecular phenotypes in colon tissue, which they labeled as “colon-like” and “ileum-like.” They found significant differences in cellular metabolism and immune pathways (Gut. 2016 Oct 14. doi: 10.1136/gutjnl-2016-312518).

In the colon-like subtype, the tissue samples – which were all taken from the colon – showed gene expression patterns that were typical of cells from the colon. However, in the ileum-like subtype, the gene expression patterns in these colon cells more closely resembled the gene expression of ileum cells.

They also saw significant differences in other molecular traits, such as chromatin accessibility, and pathways involved in lipid and xenobiotic metabolism.

“Furthermore, chromatin accessibility data suggest these subclasses exist due to stable molecular transformations of the genomic architecture in colon tissue cells, and not transient differences due to external cellular signaling,” researchers reported.

To rule out the possibility that these differences might be from treatment history, researchers conducted a similar analysis using samples from 201 treatment-naive pediatric patients with Crohn’s disease and found the same molecular and genetic patterns.

“Together, these data strongly suggest that the colon-like and ileum-like molecular signatures define two forms of [Crohn’s disease] present, regardless of tissue sampling location, patient age, or treatment status.”

The researchers also examined the impact the two subtypes might have on the clinical disease and therefore the therapeutic approach taken. In the cohort of treatment-naive pediatric patients, they found that patients with the more colon-like Crohn’s disease were more likely to have both colon and ileum involvement, have deep ulcers, and show more macroscopic inflammation than those with more ileum-like Crohn’s disease.

They also found that adults in the colon-like disease subclass were the only ones who were likely to have rectal disease or require a colectomy, although they noted that the sample size was small.

More patients with the ileum-like disease showed no inflammation and were also more likely to have involvement of the colon only.

“Although our sample size is small, these data suggest that molecular subtypes of [Crohn’s disease] can stratify patients into clinically distinct and relevant subgroups and may prospectively identify those more likely to require intensive medical therapy,” the authors wrote.

“As a first step, molecular stratifications of archived patient tissue and serum from major clinical trials could be performed in the context of response to biological and microbial therapies for [Crohn’s disease].”

The authors pointed out that they did not study samples from both intestinal regions in each patient but suggested that their findings should motivate future studies in larger cohorts using matched tissue samples from both the colon and ileum.

“These data emphasize the need to continue and expand these studies over time to incorporate the evolving clinical phenotype in both adult and pediatric patients, and the need to study both tissues in the same patient.”

The study was supported by the National Institute of Environmental Health Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Gastroenterological Association, Broad Medical Research Program, Crohn’s and Colitis Foundation of America, International Human Microbiome Consortium, UNC Team Translational Science Award, and Helmsley Charitable Trust SHARE 2, Project 3. No conflicts of interest were declared.

LAS VEGAS – A collaborative care approach to patients with inflammatory bowel disease (IBD) dramatically reduced emergency department visits and hospitalizations and also boosted quality of life.

The IBD patient-centered medical home employs open-access scheduling, remote monitoring, and telemedicine. A patient’s team includes a social worker, a nurse practitioner, a dietitian, a psychiatrist, and other specialists. The gastroenterologist acts as a primary care physician, according to Miguel Regueiro, MD, AGAF, medical director of the IBD Center at the University of Pittsburgh Medical Center, who presented the outcomes at the annual meeting of the American College of Gastroenterology.

LAS VEGAS – A collaborative care approach to patients with inflammatory bowel disease (IBD) dramatically reduced emergency department visits and hospitalizations and also boosted quality of life.

The IBD patient-centered medical home employs open-access scheduling, remote monitoring, and telemedicine. A patient’s team includes a social worker, a nurse practitioner, a dietitian, a psychiatrist, and other specialists. The gastroenterologist acts as a primary care physician, according to Miguel Regueiro, MD, AGAF, medical director of the IBD Center at the University of Pittsburgh Medical Center, who presented the outcomes at the annual meeting of the American College of Gastroenterology.

LAS VEGAS – A collaborative care approach to patients with inflammatory bowel disease (IBD) dramatically reduced emergency department visits and hospitalizations and also boosted quality of life.

The IBD patient-centered medical home employs open-access scheduling, remote monitoring, and telemedicine. A patient’s team includes a social worker, a nurse practitioner, a dietitian, a psychiatrist, and other specialists. The gastroenterologist acts as a primary care physician, according to Miguel Regueiro, MD, AGAF, medical director of the IBD Center at the University of Pittsburgh Medical Center, who presented the outcomes at the annual meeting of the American College of Gastroenterology.

Click here to access the October 2016 Digital Edition. 

Table of Contents

• Walk the Talk: VA Mental Health Care Professionals’ Role in Promoting Physical Activity
• FDA Black Box, VA Red Ink? A Successful Service-Connected Disability Claim for Chronic Neuropsychiatric Adverse Effects From Mefloquine
• Epinephrine-Induced Takotsubo Cardiomyopathy
• Tooth Decay Is the Most Prevalent Disease
• Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male
• Solving the VA Physician Shortage Problem: The Right Thing to Do
• An Electronic Template to Improve Psychotropic Medication Review and Gradual Dose-Reduction Documentation
• Evaluation of a Dementia Resource Fair for Veterans, Caregivers, and Staff
• FDA Boxed Warnings

Click here to access the October 2016 Digital Edition. 

Table of Contents

• Walk the Talk: VA Mental Health Care Professionals’ Role in Promoting Physical Activity
• FDA Black Box, VA Red Ink? A Successful Service-Connected Disability Claim for Chronic Neuropsychiatric Adverse Effects From Mefloquine
• Epinephrine-Induced Takotsubo Cardiomyopathy
• Tooth Decay Is the Most Prevalent Disease
• Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male
• Solving the VA Physician Shortage Problem: The Right Thing to Do
• An Electronic Template to Improve Psychotropic Medication Review and Gradual Dose-Reduction Documentation
• Evaluation of a Dementia Resource Fair for Veterans, Caregivers, and Staff
• FDA Boxed Warnings

Click here to access the October 2016 Digital Edition. 

Table of Contents

• Walk the Talk: VA Mental Health Care Professionals’ Role in Promoting Physical Activity
• FDA Black Box, VA Red Ink? A Successful Service-Connected Disability Claim for Chronic Neuropsychiatric Adverse Effects From Mefloquine
• Epinephrine-Induced Takotsubo Cardiomyopathy
• Tooth Decay Is the Most Prevalent Disease
• Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male
• Solving the VA Physician Shortage Problem: The Right Thing to Do
• An Electronic Template to Improve Psychotropic Medication Review and Gradual Dose-Reduction Documentation
• Evaluation of a Dementia Resource Fair for Veterans, Caregivers, and Staff
• FDA Boxed Warnings

I almost quit my job during my third year as a hospitalist. When I began my first hospitalist job out of residency, I was going to be “just a doctor” forever. After all, being at the bedside, holding my patients’ hands, making them feel better one by one was the reason I went into medicine.

Fast-forward three years. I was now a mom and still “just a doctor,” still holding my patients’ hands. Yet, somehow, it was just not enough. I pondered for a year, at times pessimistically, about my hospitalist future: the endless overnight shifts, the weekends away from family, the “spent” feeling after seven days on service. I needed to do something else. I, and many other hospitalist colleagues, went through this phase. I call this “the three-year itch.”

Fast-forward some more, I am a little better at knowing why the three-year itch occurred. For a lifelong hospitalist, it is a major milestone. It is the moment when you realize you are in love with the field of hospital medicine, want to continue for a long time, but also have this scary revelation that you cannot sustain the current status. I suppose this milestone is a natural occurrence, hardwired in our hospitalist-innovator, hospitalist-writer, hospitalist-mom, hospitalist–IT guy, hospitalist–palliative care physician, hospitalist–soon-to-be chief medical officer mind. While hospitalist groups attempt to improve job satisfaction and sustainability by hiring more nocturnists, increasing compensation, designing flexible schedules for moms, etc., I argue that, for many of us, mentoring is paramount in maintaining job satisfaction and sustainability.

Mentoring Essential

Early-career hospitalist mentoring is essential during the first three years of practice as it ensures a smooth transition and assimilation into hospital medicine. While I was surrounded by accomplished hospitalists early in my career, I never realized how essential it was for me to establish a connection with one of them until I was “attacked” by the itch. What exactly does the three-year itch involve? A Hinami et al study plotted job fit against years in current practice. An inflection point at two years of practice became apparent. These first two years, called the “assimilation period,” are when “rapid learning and attrition took place.” Perhaps some of the observed phenomenon are to be expected and unavoidable. However, providing mentorship resources during this vulnerable period would potentially decrease attrition.

I did not quit my job, but I knew I needed to find direction for myself. I spent countless hours on emails, meetings, and, yes, moping around about my future. I wished so often back then that I had a mentor to guide me. My lack of mentorship was not unique. In a survey of 222 pediatric hospitalists, only 44% said they have “adequate mentorship in their careers.”

For more than a year, I was asking the wrong question: What makes a career in hospital medicine satisfying? The Society of Hospital Medicine Career Satisfaction Task Force paper delineated 13 factors, including optimal workload, substantial pay, control over personal time, and collegiality with other physicians, that contribute to job satisfaction for hospitalists. While there are common trends, factors that affect job satisfaction are highly variable across practice models. How do you reconcile the weight of at least 13 factors that contribute to your happiness at work? Having a mentor to brainstorm ideas about job satisfaction for me would have focused my energy productively early on and, more important, could have led to more career satisfaction.

Finding a Mentor

Finding a mentor takes a lot hard work. It takes boldness, creativity, perseverance, and a bit of luck. My quest to find a mentor started at the hospital’s cafeteria with senior hospitalists. It then led me to a few meetings in the C-suite and the chiefs’ offices. I asked MDs, nurses, and quality officers the same question: “How did you get to where you are?” I emailed everyone and met with many. I suppose I was bold (and some may say ambitious), but for me, it was out of necessity. I was pleasantly surprised at the time generously given to me. The willingness to listen was bestowed even by random strangers whom I had never met. I remember very well the day I decided to email the most “famous” hospitalists in the Boston area. I heard back from all except one. I ended up having coffee on a crisp winter morning at a famous hospitalist’s house in the Boston suburbs. I almost trucked in the textbook she had written for an autograph! My path also led me to an hour-and-a-half conversation in a light-filled office in downtown Boston. Leaving at 6:30 p.m., I remember being giddy. I did not find a mentor that very specific day, but I found direction and purpose, which are what I had been looking for.

Sometimes you just have to do it yourself—build your own mentorship program from scratch. I did it at my own institution. There is a paucity of literature on this subject matter. This problem intensifies manyfold for community hospitals like mine. I was never sure of the right way to start a program. Do I start by identifying senior faculty mentors for the group, providing a list of available mentors for interested hospitalists to choose from, or creating a peer mentor network? I was certain though that doing something, even if not as well from the onset, was an improvement. This is where luck matters: I am lucky to be practicing among the most intelligent, ambitious, like-minded colleagues. We have different priorities, and each of us is blazing a separate career path. Yet I sense that we have one thing in common: We are energized and want productive careers in hospital medicine.

Starting a new program also requires leadership support. I fortunately have had unrelenting support at my hospital. Support from leadership comes in various forms: funds set aside for administrative support, assistance in networking to identify potential mentors, expertise (such as in writing and publishing), feedback on the proposed program structure. At the end of the day though, sometimes you just need to start.

While experienced mentors are desperately needed for academic hospitalist groups, a bigger need for mentors exists at community hospitals like mine compared to academic hospitals. Community hospital programs are typically smaller and more recently established, and hence, the pool of experienced and senior hospitalists typically is limited. In tertiary-care settings, mentors are needed to ensure scholarly productivity and promotion, while mentors are needed in community hospitals to ensure career satisfaction and job sustainability. Two years ago, I conducted a professional development survey of my colleagues. Of the 20 hospitalists (70% response rate) who responded, 19 (95%) answered yes to the question, “Are you professionally satisfied with your current hospitalist job?” This tracks well with the 92% of pediatric hospitalists who reported that they are “pleased with their work.” Yet burnout rate was reported to be 29.9% in 20119 and 52.3% more recently.

Why is there such a discrepancy? I think one of the clues lies in the fact that 85% of my colleagues are thinking of pursuing an interest in addition to practicing clinical hospital medicine in the next 10 years. I want to be clear that my fellow hospitalists and I are not looking to leave clinical medicine. We love it. Most of us envision our professional lives in clinical medicine. Yet we need to fulfill our “diastoles.” We also believe in the intertwined nature of a hospitalist’s life and that of a quality officer, a palliative care physician, a billing and compliance officer, etc. We know that as hospitalists, we are well-positioned to improve the care of our patients even when we are not at the bedside. As community hospital hospitalists, we are the grass-roots hospitalists with tremendous potential to impact the care of patients and the future of hospital medicine. We, as much as academic hospitalists, need a mentoring hand for our professional development.

I am “itching” now, six years after finishing residency. There are many days where the “What now?” phrase echoes in my head. Yet with the mentors who I have found, I know that I will have ready listeners when the restless voice gets loud. What troubles me is that many of the 44,000 hospitalists nationwide are suffering through the restlessness without mentors to guide them. The current call to bolster mentorship resources at academic centers, while important, is not enough. Attention, discussion, research, and definitely resources should be allocated to the development of mentorship programs for community hospitals like mine. Of course, I am interested in academic promotions, grants, and FTE support, but the journey of finding mentorship has been most significant in that it led me back my core value: I still want to be “just a doctor” forever. I just know a little more about what type of doctor I want to be. Mentorship is vital to our professional development, job satisfaction, and sustainability as community hospitalists.

References

1. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB. Person-job fit: an exploratory cross-sectional analysis of hospitalists. J Hosp Med. 2013;8(2):96-101.
2. Pane LA, Davis AB, Ottolini MC. Career satisfaction and the role of mentorship: a survey of pediatric hospitalists. Hosp Pediatr. 2012;2(3):141-148.
3. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB; Society of Hospital Medicine Career Satisfaction Task Force. Job characteristics, satisfaction, and burnout across hospitalist practice models. J Hosp Med. 2012;7(5):402-410.
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3(4):314-318.
5. Tietjen P, Griner PF. Mentoring of physicians at a community-based health system: preliminary findings. J Hosp Med. 2013;8(11):642-643.
6. Varkey P, Jatoi A, Williams A, et al. The positive impact of a facilitated peer mentoring program on academic skills of women faculty. BMC Med Educ. 2012;12:14.
7. Johnson KS, Hastings SN, Purser JL, Whitson HE. The Junior Faculty Laboratory: an innovative model of peer mentoring. Acad Med. 2011;86(12):1577-1582.
8. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27(1):23-27.
9. Hinami K, Whelan CT, Wolosin RJ, Miller JA, Wetterneck TB. Worklife and satisfaction of hospitalists: toward flourishing careers. J Gen Intern Med. 2012;27(1):28-36.
10. Roberts DL, Shanafelt TD, Dyrbye LN, West CP. A national comparison of burnout and work-life balance among internal medicine hospitalists and outpatient general internists. J Hosp Med. 2014;9(3):176-181.
11. Arora V, Fang MC, Kripalani S, Amin AN. Preparing for "diastole": advanced training opportunities for academic hospitalists. J Hosp Med. 2006;1(6):368-377.

I almost quit my job during my third year as a hospitalist. When I began my first hospitalist job out of residency, I was going to be “just a doctor” forever. After all, being at the bedside, holding my patients’ hands, making them feel better one by one was the reason I went into medicine.

Fast-forward three years. I was now a mom and still “just a doctor,” still holding my patients’ hands. Yet, somehow, it was just not enough. I pondered for a year, at times pessimistically, about my hospitalist future: the endless overnight shifts, the weekends away from family, the “spent” feeling after seven days on service. I needed to do something else. I, and many other hospitalist colleagues, went through this phase. I call this “the three-year itch.”

Fast-forward some more, I am a little better at knowing why the three-year itch occurred. For a lifelong hospitalist, it is a major milestone. It is the moment when you realize you are in love with the field of hospital medicine, want to continue for a long time, but also have this scary revelation that you cannot sustain the current status. I suppose this milestone is a natural occurrence, hardwired in our hospitalist-innovator, hospitalist-writer, hospitalist-mom, hospitalist–IT guy, hospitalist–palliative care physician, hospitalist–soon-to-be chief medical officer mind. While hospitalist groups attempt to improve job satisfaction and sustainability by hiring more nocturnists, increasing compensation, designing flexible schedules for moms, etc., I argue that, for many of us, mentoring is paramount in maintaining job satisfaction and sustainability.

Mentoring Essential

Early-career hospitalist mentoring is essential during the first three years of practice as it ensures a smooth transition and assimilation into hospital medicine. While I was surrounded by accomplished hospitalists early in my career, I never realized how essential it was for me to establish a connection with one of them until I was “attacked” by the itch. What exactly does the three-year itch involve? A Hinami et al study plotted job fit against years in current practice. An inflection point at two years of practice became apparent. These first two years, called the “assimilation period,” are when “rapid learning and attrition took place.” Perhaps some of the observed phenomenon are to be expected and unavoidable. However, providing mentorship resources during this vulnerable period would potentially decrease attrition.

I did not quit my job, but I knew I needed to find direction for myself. I spent countless hours on emails, meetings, and, yes, moping around about my future. I wished so often back then that I had a mentor to guide me. My lack of mentorship was not unique. In a survey of 222 pediatric hospitalists, only 44% said they have “adequate mentorship in their careers.”

For more than a year, I was asking the wrong question: What makes a career in hospital medicine satisfying? The Society of Hospital Medicine Career Satisfaction Task Force paper delineated 13 factors, including optimal workload, substantial pay, control over personal time, and collegiality with other physicians, that contribute to job satisfaction for hospitalists. While there are common trends, factors that affect job satisfaction are highly variable across practice models. How do you reconcile the weight of at least 13 factors that contribute to your happiness at work? Having a mentor to brainstorm ideas about job satisfaction for me would have focused my energy productively early on and, more important, could have led to more career satisfaction.

Finding a Mentor

Finding a mentor takes a lot hard work. It takes boldness, creativity, perseverance, and a bit of luck. My quest to find a mentor started at the hospital’s cafeteria with senior hospitalists. It then led me to a few meetings in the C-suite and the chiefs’ offices. I asked MDs, nurses, and quality officers the same question: “How did you get to where you are?” I emailed everyone and met with many. I suppose I was bold (and some may say ambitious), but for me, it was out of necessity. I was pleasantly surprised at the time generously given to me. The willingness to listen was bestowed even by random strangers whom I had never met. I remember very well the day I decided to email the most “famous” hospitalists in the Boston area. I heard back from all except one. I ended up having coffee on a crisp winter morning at a famous hospitalist’s house in the Boston suburbs. I almost trucked in the textbook she had written for an autograph! My path also led me to an hour-and-a-half conversation in a light-filled office in downtown Boston. Leaving at 6:30 p.m., I remember being giddy. I did not find a mentor that very specific day, but I found direction and purpose, which are what I had been looking for.

Sometimes you just have to do it yourself—build your own mentorship program from scratch. I did it at my own institution. There is a paucity of literature on this subject matter. This problem intensifies manyfold for community hospitals like mine. I was never sure of the right way to start a program. Do I start by identifying senior faculty mentors for the group, providing a list of available mentors for interested hospitalists to choose from, or creating a peer mentor network? I was certain though that doing something, even if not as well from the onset, was an improvement. This is where luck matters: I am lucky to be practicing among the most intelligent, ambitious, like-minded colleagues. We have different priorities, and each of us is blazing a separate career path. Yet I sense that we have one thing in common: We are energized and want productive careers in hospital medicine.

Starting a new program also requires leadership support. I fortunately have had unrelenting support at my hospital. Support from leadership comes in various forms: funds set aside for administrative support, assistance in networking to identify potential mentors, expertise (such as in writing and publishing), feedback on the proposed program structure. At the end of the day though, sometimes you just need to start.

While experienced mentors are desperately needed for academic hospitalist groups, a bigger need for mentors exists at community hospitals like mine compared to academic hospitals. Community hospital programs are typically smaller and more recently established, and hence, the pool of experienced and senior hospitalists typically is limited. In tertiary-care settings, mentors are needed to ensure scholarly productivity and promotion, while mentors are needed in community hospitals to ensure career satisfaction and job sustainability. Two years ago, I conducted a professional development survey of my colleagues. Of the 20 hospitalists (70% response rate) who responded, 19 (95%) answered yes to the question, “Are you professionally satisfied with your current hospitalist job?” This tracks well with the 92% of pediatric hospitalists who reported that they are “pleased with their work.” Yet burnout rate was reported to be 29.9% in 20119 and 52.3% more recently.

Why is there such a discrepancy? I think one of the clues lies in the fact that 85% of my colleagues are thinking of pursuing an interest in addition to practicing clinical hospital medicine in the next 10 years. I want to be clear that my fellow hospitalists and I are not looking to leave clinical medicine. We love it. Most of us envision our professional lives in clinical medicine. Yet we need to fulfill our “diastoles.” We also believe in the intertwined nature of a hospitalist’s life and that of a quality officer, a palliative care physician, a billing and compliance officer, etc. We know that as hospitalists, we are well-positioned to improve the care of our patients even when we are not at the bedside. As community hospital hospitalists, we are the grass-roots hospitalists with tremendous potential to impact the care of patients and the future of hospital medicine. We, as much as academic hospitalists, need a mentoring hand for our professional development.

I am “itching” now, six years after finishing residency. There are many days where the “What now?” phrase echoes in my head. Yet with the mentors who I have found, I know that I will have ready listeners when the restless voice gets loud. What troubles me is that many of the 44,000 hospitalists nationwide are suffering through the restlessness without mentors to guide them. The current call to bolster mentorship resources at academic centers, while important, is not enough. Attention, discussion, research, and definitely resources should be allocated to the development of mentorship programs for community hospitals like mine. Of course, I am interested in academic promotions, grants, and FTE support, but the journey of finding mentorship has been most significant in that it led me back my core value: I still want to be “just a doctor” forever. I just know a little more about what type of doctor I want to be. Mentorship is vital to our professional development, job satisfaction, and sustainability as community hospitalists.

References

1. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB. Person-job fit: an exploratory cross-sectional analysis of hospitalists. J Hosp Med. 2013;8(2):96-101.
2. Pane LA, Davis AB, Ottolini MC. Career satisfaction and the role of mentorship: a survey of pediatric hospitalists. Hosp Pediatr. 2012;2(3):141-148.
3. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB; Society of Hospital Medicine Career Satisfaction Task Force. Job characteristics, satisfaction, and burnout across hospitalist practice models. J Hosp Med. 2012;7(5):402-410.
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3(4):314-318.
5. Tietjen P, Griner PF. Mentoring of physicians at a community-based health system: preliminary findings. J Hosp Med. 2013;8(11):642-643.
6. Varkey P, Jatoi A, Williams A, et al. The positive impact of a facilitated peer mentoring program on academic skills of women faculty. BMC Med Educ. 2012;12:14.
7. Johnson KS, Hastings SN, Purser JL, Whitson HE. The Junior Faculty Laboratory: an innovative model of peer mentoring. Acad Med. 2011;86(12):1577-1582.
8. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27(1):23-27.
9. Hinami K, Whelan CT, Wolosin RJ, Miller JA, Wetterneck TB. Worklife and satisfaction of hospitalists: toward flourishing careers. J Gen Intern Med. 2012;27(1):28-36.
10. Roberts DL, Shanafelt TD, Dyrbye LN, West CP. A national comparison of burnout and work-life balance among internal medicine hospitalists and outpatient general internists. J Hosp Med. 2014;9(3):176-181.
11. Arora V, Fang MC, Kripalani S, Amin AN. Preparing for "diastole": advanced training opportunities for academic hospitalists. J Hosp Med. 2006;1(6):368-377.

I almost quit my job during my third year as a hospitalist. When I began my first hospitalist job out of residency, I was going to be “just a doctor” forever. After all, being at the bedside, holding my patients’ hands, making them feel better one by one was the reason I went into medicine.

Fast-forward three years. I was now a mom and still “just a doctor,” still holding my patients’ hands. Yet, somehow, it was just not enough. I pondered for a year, at times pessimistically, about my hospitalist future: the endless overnight shifts, the weekends away from family, the “spent” feeling after seven days on service. I needed to do something else. I, and many other hospitalist colleagues, went through this phase. I call this “the three-year itch.”

Fast-forward some more, I am a little better at knowing why the three-year itch occurred. For a lifelong hospitalist, it is a major milestone. It is the moment when you realize you are in love with the field of hospital medicine, want to continue for a long time, but also have this scary revelation that you cannot sustain the current status. I suppose this milestone is a natural occurrence, hardwired in our hospitalist-innovator, hospitalist-writer, hospitalist-mom, hospitalist–IT guy, hospitalist–palliative care physician, hospitalist–soon-to-be chief medical officer mind. While hospitalist groups attempt to improve job satisfaction and sustainability by hiring more nocturnists, increasing compensation, designing flexible schedules for moms, etc., I argue that, for many of us, mentoring is paramount in maintaining job satisfaction and sustainability.

Mentoring Essential

Early-career hospitalist mentoring is essential during the first three years of practice as it ensures a smooth transition and assimilation into hospital medicine. While I was surrounded by accomplished hospitalists early in my career, I never realized how essential it was for me to establish a connection with one of them until I was “attacked” by the itch. What exactly does the three-year itch involve? A Hinami et al study plotted job fit against years in current practice. An inflection point at two years of practice became apparent. These first two years, called the “assimilation period,” are when “rapid learning and attrition took place.” Perhaps some of the observed phenomenon are to be expected and unavoidable. However, providing mentorship resources during this vulnerable period would potentially decrease attrition.

I did not quit my job, but I knew I needed to find direction for myself. I spent countless hours on emails, meetings, and, yes, moping around about my future. I wished so often back then that I had a mentor to guide me. My lack of mentorship was not unique. In a survey of 222 pediatric hospitalists, only 44% said they have “adequate mentorship in their careers.”

For more than a year, I was asking the wrong question: What makes a career in hospital medicine satisfying? The Society of Hospital Medicine Career Satisfaction Task Force paper delineated 13 factors, including optimal workload, substantial pay, control over personal time, and collegiality with other physicians, that contribute to job satisfaction for hospitalists. While there are common trends, factors that affect job satisfaction are highly variable across practice models. How do you reconcile the weight of at least 13 factors that contribute to your happiness at work? Having a mentor to brainstorm ideas about job satisfaction for me would have focused my energy productively early on and, more important, could have led to more career satisfaction.

Finding a Mentor

Finding a mentor takes a lot hard work. It takes boldness, creativity, perseverance, and a bit of luck. My quest to find a mentor started at the hospital’s cafeteria with senior hospitalists. It then led me to a few meetings in the C-suite and the chiefs’ offices. I asked MDs, nurses, and quality officers the same question: “How did you get to where you are?” I emailed everyone and met with many. I suppose I was bold (and some may say ambitious), but for me, it was out of necessity. I was pleasantly surprised at the time generously given to me. The willingness to listen was bestowed even by random strangers whom I had never met. I remember very well the day I decided to email the most “famous” hospitalists in the Boston area. I heard back from all except one. I ended up having coffee on a crisp winter morning at a famous hospitalist’s house in the Boston suburbs. I almost trucked in the textbook she had written for an autograph! My path also led me to an hour-and-a-half conversation in a light-filled office in downtown Boston. Leaving at 6:30 p.m., I remember being giddy. I did not find a mentor that very specific day, but I found direction and purpose, which are what I had been looking for.

Sometimes you just have to do it yourself—build your own mentorship program from scratch. I did it at my own institution. There is a paucity of literature on this subject matter. This problem intensifies manyfold for community hospitals like mine. I was never sure of the right way to start a program. Do I start by identifying senior faculty mentors for the group, providing a list of available mentors for interested hospitalists to choose from, or creating a peer mentor network? I was certain though that doing something, even if not as well from the onset, was an improvement. This is where luck matters: I am lucky to be practicing among the most intelligent, ambitious, like-minded colleagues. We have different priorities, and each of us is blazing a separate career path. Yet I sense that we have one thing in common: We are energized and want productive careers in hospital medicine.

Starting a new program also requires leadership support. I fortunately have had unrelenting support at my hospital. Support from leadership comes in various forms: funds set aside for administrative support, assistance in networking to identify potential mentors, expertise (such as in writing and publishing), feedback on the proposed program structure. At the end of the day though, sometimes you just need to start.

While experienced mentors are desperately needed for academic hospitalist groups, a bigger need for mentors exists at community hospitals like mine compared to academic hospitals. Community hospital programs are typically smaller and more recently established, and hence, the pool of experienced and senior hospitalists typically is limited. In tertiary-care settings, mentors are needed to ensure scholarly productivity and promotion, while mentors are needed in community hospitals to ensure career satisfaction and job sustainability. Two years ago, I conducted a professional development survey of my colleagues. Of the 20 hospitalists (70% response rate) who responded, 19 (95%) answered yes to the question, “Are you professionally satisfied with your current hospitalist job?” This tracks well with the 92% of pediatric hospitalists who reported that they are “pleased with their work.” Yet burnout rate was reported to be 29.9% in 20119 and 52.3% more recently.

Why is there such a discrepancy? I think one of the clues lies in the fact that 85% of my colleagues are thinking of pursuing an interest in addition to practicing clinical hospital medicine in the next 10 years. I want to be clear that my fellow hospitalists and I are not looking to leave clinical medicine. We love it. Most of us envision our professional lives in clinical medicine. Yet we need to fulfill our “diastoles.” We also believe in the intertwined nature of a hospitalist’s life and that of a quality officer, a palliative care physician, a billing and compliance officer, etc. We know that as hospitalists, we are well-positioned to improve the care of our patients even when we are not at the bedside. As community hospital hospitalists, we are the grass-roots hospitalists with tremendous potential to impact the care of patients and the future of hospital medicine. We, as much as academic hospitalists, need a mentoring hand for our professional development.

I am “itching” now, six years after finishing residency. There are many days where the “What now?” phrase echoes in my head. Yet with the mentors who I have found, I know that I will have ready listeners when the restless voice gets loud. What troubles me is that many of the 44,000 hospitalists nationwide are suffering through the restlessness without mentors to guide them. The current call to bolster mentorship resources at academic centers, while important, is not enough. Attention, discussion, research, and definitely resources should be allocated to the development of mentorship programs for community hospitals like mine. Of course, I am interested in academic promotions, grants, and FTE support, but the journey of finding mentorship has been most significant in that it led me back my core value: I still want to be “just a doctor” forever. I just know a little more about what type of doctor I want to be. Mentorship is vital to our professional development, job satisfaction, and sustainability as community hospitalists.

References

1. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB. Person-job fit: an exploratory cross-sectional analysis of hospitalists. J Hosp Med. 2013;8(2):96-101.
2. Pane LA, Davis AB, Ottolini MC. Career satisfaction and the role of mentorship: a survey of pediatric hospitalists. Hosp Pediatr. 2012;2(3):141-148.
3. Hinami K, Whelan CT, Miller JA, Wolosin RJ, Wetterneck TB; Society of Hospital Medicine Career Satisfaction Task Force. Job characteristics, satisfaction, and burnout across hospitalist practice models. J Hosp Med. 2012;7(5):402-410.
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3(4):314-318.
5. Tietjen P, Griner PF. Mentoring of physicians at a community-based health system: preliminary findings. J Hosp Med. 2013;8(11):642-643.
6. Varkey P, Jatoi A, Williams A, et al. The positive impact of a facilitated peer mentoring program on academic skills of women faculty. BMC Med Educ. 2012;12:14.
7. Johnson KS, Hastings SN, Purser JL, Whitson HE. The Junior Faculty Laboratory: an innovative model of peer mentoring. Acad Med. 2011;86(12):1577-1582.
8. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27(1):23-27.
9. Hinami K, Whelan CT, Wolosin RJ, Miller JA, Wetterneck TB. Worklife and satisfaction of hospitalists: toward flourishing careers. J Gen Intern Med. 2012;27(1):28-36.
10. Roberts DL, Shanafelt TD, Dyrbye LN, West CP. A national comparison of burnout and work-life balance among internal medicine hospitalists and outpatient general internists. J Hosp Med. 2014;9(3):176-181.
11. Arora V, Fang MC, Kripalani S, Amin AN. Preparing for "diastole": advanced training opportunities for academic hospitalists. J Hosp Med. 2006;1(6):368-377.

A 46-year-old white male presented to a civilian general practitioner with an acute bilateral erythemetous, nonurticarial morbilliform rash. The patient initially presented with these symptoms (7 years prior) to a military field medical clinic, and the first presentation was seen by a nurse practitioner. The rash was evident on the lateral aspects of the thorax and on the medial portions of both arms and upper thighs. There was no evidence of involvement of hands or feet. Outside of being quite prominent, the patient reported the rash to be asymptomatic.

The patient also had concomitant symptoms of a typical upper respiratory tract infection (URTI) with fever of 100.3° F. The physical examination was unremarkable except for the pronounced rash as described and URTI-associated nasal congestion/postnasal drainage. Examination of oral mucosa of the head, ears, eyes, nose, and throat also was negative for any evidence of eruption. The patient was in excellent physical condition, took no routine medications, and had no documented underlying medical conditions. His family and social history seemed noncontributory; he reported frequent domestic airline travel associated with reserve duty as well as with his civilian job. Appropriate immunizations were all current, and regularly scheduled physical examinations had been documented in the medical record.

The patient’s rashes associated with URTI began 7 years prior at age 39 after a weeklong (fall season) operational readiness inspection (ORI), which included extended periods wearing ground crew ensemble (GCE) equipment. Protective clothing worn during that ORI included the heavily charcoal-laden over-garment, butyl rubber gloves and boots, and the then current-issue gas mask. The rashes had never appeared before age 39, and the patient reported no previous medical problems after wearing GCE equipment during 16 years of service preceding that initial presentation.

The patient’s rashes typically presented with the similar pattern and intensity at 24 to 36 hours after onset of URTI symptoms, were self-limiting, and resolved in an additional 48 to 72 hours (Figure). The rash was present with each subsequent URTI and occurred on average, about 2 times each year. Similar rashes also appeared twice during the preceding 7 years during episodes of nausea/vomiting/diarrhea consistent with acute gastroenteritis (AGE). No other household members (infant to aged 40 years) showed any similar rash during episodic URTI or AGE during the same period. However, about 2 years after the initial URTI/rash presentation, the patient’s then toddler-aged son was diagnosed with self-limiting unilateral laterothoracic exanthem (ULTE), which completely resolved in 2 to 3 weeks and never reappeared.

Discussion

The author postulated that the patient most likely experienced routine acute episodes of Picornaviridae infection. The overarching diagnosis was presumptive, as biopsy and/or serologies were not obtained on the reservist. The Picornavirus family includes genera such as Rhinovirus and Enterovirus, both significant contributors to URTI (Enterovirus for AGE). Typically, about 50% of URTIs are caused by Rhinovirus (approaches 100% in some seasonal outbreaks) with the remainder of common URTIs being caused by Enterovirus, Coronavirus, Adenovirus, Reovirus, and Parainfluenza virus.¹ Unfortunately, rapid office-based or field medicine diagnostic assays to consistently confirm or differentiate these common URTI viral etiologies (excepting influenza A/B) are simply not economically feasible at this time nor are any standardized laboratory tests recommended for self-limiting URTIs in immunocompetent adults. There are multiplex polymerase chain reaction assays available for many viral URTI pathogens, but cost and the need for laboratory as well as certified medical technologist support may often preclude routine use at the point of care.

Perhaps the more intriguing aspect of this case is the consistent recurrence of the same rash presentation in a middle-aged immunocompetent adult male with every subsequent episode of typical URTI or AGE over a period of 7 years, irrespective of seasonal timing, contact history, or geographic location. There is well-documented evidence of URTI associated with Adenovirus and Coronavirus seen in otherwise healthy adults living in close quarters military environments. Particularly, Adenovirus serotypes 3, 4, 7, and 21 have been associated with respiratory disease in military troop populations.²

There are also numerous viral exanthems shown in young children with probable links to Epstein-Barr virus (EBV), Human herpesvirus (HHV) 6, and parvovirus B19.³ The patient’s then toddler-aged son experiencing ULTE subsequent to the father’s presentation raise the question of a possible link to viruses other than those associated with typical URTI/AGE. Literature review indicated ULTE may be linked to EBV, parvovirus B19, Adenovirus, Parainfluenza virus, or HHV 6 and 7.⁴

Adenovirus and Parainfluenza virus are causative agents for a portion of URTIs as well. However, the likelihood of all of the patient’s subsequent URTIs being caused exclusively by Adenovirus would be exceedingly low. Infections with atypical bacteria, such as mycoplasma, also are frequently associated with rash, fever, and myalgia but are more commonly linked to lower RTI.

All the above etiologies are typically self-limiting (except mycoplasma infections) and usually resolve without specific treatment. This broad differential tends to “muddy the water” when trying to tie a definitive diagnosis to what was a seemingly routine URTI in a healthy adult.

The patient’s status as a member of the reserve complicated obtaining a definitive diagnosis of the recurring rash. Even if a link between the recurring rash and earlier duty could be established, access to an acute-care appointment at a military treatment facility (in nonduty status) was/is not authorized. A timely civilian acute-care appointment for routine URTI with short-lived rash in an adult patient is difficult to book, especially if the rash appears on a weekend or holiday. Likewise, insurance reimbursement for skin biopsy or numerous serologic tests (investigating possible viral etiology) is frequently not covered for such conditions, as even a positive serology likely would not alter the current standard of supportive care.

Evaluation of any patient presenting during or immediately after field exercises or operational deployment must be conducted in full consideration of such conditions. A thorough history relating to geographic location, immunization status, season, environmental or chemical contacts, animal/insect exposure, living conditions, other ill unit personnel, sanitation/hygiene and food/water quality is of paramount importance. Likewise, there may be value in at least having a unit briefing/follow-up with a medical provider 2 to 6 months after deployment/field training activities. A general follow-up such as this may help find any emerging trends or common concerns pertaining to unit members’ health.

Reservists present a unique health maintenance challenge as they may complete a duty tour and drop out of military health system visibility for weeks to months. The inherent design of some reserve component programs makes even the discovery of a case such as this difficult at best. A structured follow-up (be that a group briefing or even a survey-type questionnaire) becomes highly useful for monitoring emerging health trends in reservists.

Conclusion

This patient’s initial field presentation at age 39 was clinically explained and documented in the official medical record as routine URTI. The diagnosis was based on clinical picture, occurrence during fall season, and close quarters/field living conditions. A definitive diagnosis of the recurring rash was never documented in the patient’s military medical records.

Differing somewhat from a typical case report, the purpose of this presentation was to offer “field medicine” points and systematic considerations when faced with the presentation of a seemingly common ailment, not to provide readers with a definitive diagnosis. These considerations along with the need for follow-up health maintenance strategies are especially highlighted by the unique situations presented by reservists. In addition, this case demonstrates the validity of the often forgotten history and physical question of “Has this ever happened before?” These are at least issues that should be considered before signing the disposition as “URTI, OTC meds PRN, quarters for 24 hours, then return to duty.”

A 46-year-old white male presented to a civilian general practitioner with an acute bilateral erythemetous, nonurticarial morbilliform rash. The patient initially presented with these symptoms (7 years prior) to a military field medical clinic, and the first presentation was seen by a nurse practitioner. The rash was evident on the lateral aspects of the thorax and on the medial portions of both arms and upper thighs. There was no evidence of involvement of hands or feet. Outside of being quite prominent, the patient reported the rash to be asymptomatic.

The patient also had concomitant symptoms of a typical upper respiratory tract infection (URTI) with fever of 100.3° F. The physical examination was unremarkable except for the pronounced rash as described and URTI-associated nasal congestion/postnasal drainage. Examination of oral mucosa of the head, ears, eyes, nose, and throat also was negative for any evidence of eruption. The patient was in excellent physical condition, took no routine medications, and had no documented underlying medical conditions. His family and social history seemed noncontributory; he reported frequent domestic airline travel associated with reserve duty as well as with his civilian job. Appropriate immunizations were all current, and regularly scheduled physical examinations had been documented in the medical record.

The patient’s rashes associated with URTI began 7 years prior at age 39 after a weeklong (fall season) operational readiness inspection (ORI), which included extended periods wearing ground crew ensemble (GCE) equipment. Protective clothing worn during that ORI included the heavily charcoal-laden over-garment, butyl rubber gloves and boots, and the then current-issue gas mask. The rashes had never appeared before age 39, and the patient reported no previous medical problems after wearing GCE equipment during 16 years of service preceding that initial presentation.

The patient’s rashes typically presented with the similar pattern and intensity at 24 to 36 hours after onset of URTI symptoms, were self-limiting, and resolved in an additional 48 to 72 hours (Figure). The rash was present with each subsequent URTI and occurred on average, about 2 times each year. Similar rashes also appeared twice during the preceding 7 years during episodes of nausea/vomiting/diarrhea consistent with acute gastroenteritis (AGE). No other household members (infant to aged 40 years) showed any similar rash during episodic URTI or AGE during the same period. However, about 2 years after the initial URTI/rash presentation, the patient’s then toddler-aged son was diagnosed with self-limiting unilateral laterothoracic exanthem (ULTE), which completely resolved in 2 to 3 weeks and never reappeared.

Discussion

The author postulated that the patient most likely experienced routine acute episodes of Picornaviridae infection. The overarching diagnosis was presumptive, as biopsy and/or serologies were not obtained on the reservist. The Picornavirus family includes genera such as Rhinovirus and Enterovirus, both significant contributors to URTI (Enterovirus for AGE). Typically, about 50% of URTIs are caused by Rhinovirus (approaches 100% in some seasonal outbreaks) with the remainder of common URTIs being caused by Enterovirus, Coronavirus, Adenovirus, Reovirus, and Parainfluenza virus.¹ Unfortunately, rapid office-based or field medicine diagnostic assays to consistently confirm or differentiate these common URTI viral etiologies (excepting influenza A/B) are simply not economically feasible at this time nor are any standardized laboratory tests recommended for self-limiting URTIs in immunocompetent adults. There are multiplex polymerase chain reaction assays available for many viral URTI pathogens, but cost and the need for laboratory as well as certified medical technologist support may often preclude routine use at the point of care.

Perhaps the more intriguing aspect of this case is the consistent recurrence of the same rash presentation in a middle-aged immunocompetent adult male with every subsequent episode of typical URTI or AGE over a period of 7 years, irrespective of seasonal timing, contact history, or geographic location. There is well-documented evidence of URTI associated with Adenovirus and Coronavirus seen in otherwise healthy adults living in close quarters military environments. Particularly, Adenovirus serotypes 3, 4, 7, and 21 have been associated with respiratory disease in military troop populations.²

There are also numerous viral exanthems shown in young children with probable links to Epstein-Barr virus (EBV), Human herpesvirus (HHV) 6, and parvovirus B19.³ The patient’s then toddler-aged son experiencing ULTE subsequent to the father’s presentation raise the question of a possible link to viruses other than those associated with typical URTI/AGE. Literature review indicated ULTE may be linked to EBV, parvovirus B19, Adenovirus, Parainfluenza virus, or HHV 6 and 7.⁴

Adenovirus and Parainfluenza virus are causative agents for a portion of URTIs as well. However, the likelihood of all of the patient’s subsequent URTIs being caused exclusively by Adenovirus would be exceedingly low. Infections with atypical bacteria, such as mycoplasma, also are frequently associated with rash, fever, and myalgia but are more commonly linked to lower RTI.

All the above etiologies are typically self-limiting (except mycoplasma infections) and usually resolve without specific treatment. This broad differential tends to “muddy the water” when trying to tie a definitive diagnosis to what was a seemingly routine URTI in a healthy adult.

The patient’s status as a member of the reserve complicated obtaining a definitive diagnosis of the recurring rash. Even if a link between the recurring rash and earlier duty could be established, access to an acute-care appointment at a military treatment facility (in nonduty status) was/is not authorized. A timely civilian acute-care appointment for routine URTI with short-lived rash in an adult patient is difficult to book, especially if the rash appears on a weekend or holiday. Likewise, insurance reimbursement for skin biopsy or numerous serologic tests (investigating possible viral etiology) is frequently not covered for such conditions, as even a positive serology likely would not alter the current standard of supportive care.

Evaluation of any patient presenting during or immediately after field exercises or operational deployment must be conducted in full consideration of such conditions. A thorough history relating to geographic location, immunization status, season, environmental or chemical contacts, animal/insect exposure, living conditions, other ill unit personnel, sanitation/hygiene and food/water quality is of paramount importance. Likewise, there may be value in at least having a unit briefing/follow-up with a medical provider 2 to 6 months after deployment/field training activities. A general follow-up such as this may help find any emerging trends or common concerns pertaining to unit members’ health.

Reservists present a unique health maintenance challenge as they may complete a duty tour and drop out of military health system visibility for weeks to months. The inherent design of some reserve component programs makes even the discovery of a case such as this difficult at best. A structured follow-up (be that a group briefing or even a survey-type questionnaire) becomes highly useful for monitoring emerging health trends in reservists.

Conclusion

This patient’s initial field presentation at age 39 was clinically explained and documented in the official medical record as routine URTI. The diagnosis was based on clinical picture, occurrence during fall season, and close quarters/field living conditions. A definitive diagnosis of the recurring rash was never documented in the patient’s military medical records.

Differing somewhat from a typical case report, the purpose of this presentation was to offer “field medicine” points and systematic considerations when faced with the presentation of a seemingly common ailment, not to provide readers with a definitive diagnosis. These considerations along with the need for follow-up health maintenance strategies are especially highlighted by the unique situations presented by reservists. In addition, this case demonstrates the validity of the often forgotten history and physical question of “Has this ever happened before?” These are at least issues that should be considered before signing the disposition as “URTI, OTC meds PRN, quarters for 24 hours, then return to duty.”

A 46-year-old white male presented to a civilian general practitioner with an acute bilateral erythemetous, nonurticarial morbilliform rash. The patient initially presented with these symptoms (7 years prior) to a military field medical clinic, and the first presentation was seen by a nurse practitioner. The rash was evident on the lateral aspects of the thorax and on the medial portions of both arms and upper thighs. There was no evidence of involvement of hands or feet. Outside of being quite prominent, the patient reported the rash to be asymptomatic.

The patient also had concomitant symptoms of a typical upper respiratory tract infection (URTI) with fever of 100.3° F. The physical examination was unremarkable except for the pronounced rash as described and URTI-associated nasal congestion/postnasal drainage. Examination of oral mucosa of the head, ears, eyes, nose, and throat also was negative for any evidence of eruption. The patient was in excellent physical condition, took no routine medications, and had no documented underlying medical conditions. His family and social history seemed noncontributory; he reported frequent domestic airline travel associated with reserve duty as well as with his civilian job. Appropriate immunizations were all current, and regularly scheduled physical examinations had been documented in the medical record.

The patient’s rashes associated with URTI began 7 years prior at age 39 after a weeklong (fall season) operational readiness inspection (ORI), which included extended periods wearing ground crew ensemble (GCE) equipment. Protective clothing worn during that ORI included the heavily charcoal-laden over-garment, butyl rubber gloves and boots, and the then current-issue gas mask. The rashes had never appeared before age 39, and the patient reported no previous medical problems after wearing GCE equipment during 16 years of service preceding that initial presentation.

The patient’s rashes typically presented with the similar pattern and intensity at 24 to 36 hours after onset of URTI symptoms, were self-limiting, and resolved in an additional 48 to 72 hours (Figure). The rash was present with each subsequent URTI and occurred on average, about 2 times each year. Similar rashes also appeared twice during the preceding 7 years during episodes of nausea/vomiting/diarrhea consistent with acute gastroenteritis (AGE). No other household members (infant to aged 40 years) showed any similar rash during episodic URTI or AGE during the same period. However, about 2 years after the initial URTI/rash presentation, the patient’s then toddler-aged son was diagnosed with self-limiting unilateral laterothoracic exanthem (ULTE), which completely resolved in 2 to 3 weeks and never reappeared.

Discussion

The author postulated that the patient most likely experienced routine acute episodes of Picornaviridae infection. The overarching diagnosis was presumptive, as biopsy and/or serologies were not obtained on the reservist. The Picornavirus family includes genera such as Rhinovirus and Enterovirus, both significant contributors to URTI (Enterovirus for AGE). Typically, about 50% of URTIs are caused by Rhinovirus (approaches 100% in some seasonal outbreaks) with the remainder of common URTIs being caused by Enterovirus, Coronavirus, Adenovirus, Reovirus, and Parainfluenza virus.¹ Unfortunately, rapid office-based or field medicine diagnostic assays to consistently confirm or differentiate these common URTI viral etiologies (excepting influenza A/B) are simply not economically feasible at this time nor are any standardized laboratory tests recommended for self-limiting URTIs in immunocompetent adults. There are multiplex polymerase chain reaction assays available for many viral URTI pathogens, but cost and the need for laboratory as well as certified medical technologist support may often preclude routine use at the point of care.

Perhaps the more intriguing aspect of this case is the consistent recurrence of the same rash presentation in a middle-aged immunocompetent adult male with every subsequent episode of typical URTI or AGE over a period of 7 years, irrespective of seasonal timing, contact history, or geographic location. There is well-documented evidence of URTI associated with Adenovirus and Coronavirus seen in otherwise healthy adults living in close quarters military environments. Particularly, Adenovirus serotypes 3, 4, 7, and 21 have been associated with respiratory disease in military troop populations.²

There are also numerous viral exanthems shown in young children with probable links to Epstein-Barr virus (EBV), Human herpesvirus (HHV) 6, and parvovirus B19.³ The patient’s then toddler-aged son experiencing ULTE subsequent to the father’s presentation raise the question of a possible link to viruses other than those associated with typical URTI/AGE. Literature review indicated ULTE may be linked to EBV, parvovirus B19, Adenovirus, Parainfluenza virus, or HHV 6 and 7.⁴

Adenovirus and Parainfluenza virus are causative agents for a portion of URTIs as well. However, the likelihood of all of the patient’s subsequent URTIs being caused exclusively by Adenovirus would be exceedingly low. Infections with atypical bacteria, such as mycoplasma, also are frequently associated with rash, fever, and myalgia but are more commonly linked to lower RTI.

All the above etiologies are typically self-limiting (except mycoplasma infections) and usually resolve without specific treatment. This broad differential tends to “muddy the water” when trying to tie a definitive diagnosis to what was a seemingly routine URTI in a healthy adult.

The patient’s status as a member of the reserve complicated obtaining a definitive diagnosis of the recurring rash. Even if a link between the recurring rash and earlier duty could be established, access to an acute-care appointment at a military treatment facility (in nonduty status) was/is not authorized. A timely civilian acute-care appointment for routine URTI with short-lived rash in an adult patient is difficult to book, especially if the rash appears on a weekend or holiday. Likewise, insurance reimbursement for skin biopsy or numerous serologic tests (investigating possible viral etiology) is frequently not covered for such conditions, as even a positive serology likely would not alter the current standard of supportive care.

Evaluation of any patient presenting during or immediately after field exercises or operational deployment must be conducted in full consideration of such conditions. A thorough history relating to geographic location, immunization status, season, environmental or chemical contacts, animal/insect exposure, living conditions, other ill unit personnel, sanitation/hygiene and food/water quality is of paramount importance. Likewise, there may be value in at least having a unit briefing/follow-up with a medical provider 2 to 6 months after deployment/field training activities. A general follow-up such as this may help find any emerging trends or common concerns pertaining to unit members’ health.

Reservists present a unique health maintenance challenge as they may complete a duty tour and drop out of military health system visibility for weeks to months. The inherent design of some reserve component programs makes even the discovery of a case such as this difficult at best. A structured follow-up (be that a group briefing or even a survey-type questionnaire) becomes highly useful for monitoring emerging health trends in reservists.

Conclusion

This patient’s initial field presentation at age 39 was clinically explained and documented in the official medical record as routine URTI. The diagnosis was based on clinical picture, occurrence during fall season, and close quarters/field living conditions. A definitive diagnosis of the recurring rash was never documented in the patient’s military medical records.

Differing somewhat from a typical case report, the purpose of this presentation was to offer “field medicine” points and systematic considerations when faced with the presentation of a seemingly common ailment, not to provide readers with a definitive diagnosis. These considerations along with the need for follow-up health maintenance strategies are especially highlighted by the unique situations presented by reservists. In addition, this case demonstrates the validity of the often forgotten history and physical question of “Has this ever happened before?” These are at least issues that should be considered before signing the disposition as “URTI, OTC meds PRN, quarters for 24 hours, then return to duty.”

Platelets in a blood smear

The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.

However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.

The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.

Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.

“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.

“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”

About the FIT studies

Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).

The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.

Patient characteristics

In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).

The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.

In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).

The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.

Efficacy

The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.

In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.

In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.

“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.

Safety

In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).

In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).

Platelets in a blood smear

The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.

However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.

The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.

Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.

“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.

“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”

About the FIT studies

Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).

The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.

Patient characteristics

In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).

The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.

In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).

The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.

Efficacy

The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.

In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.

In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.

“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.

Safety

In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).

In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).

Platelets in a blood smear

The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.

However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.

The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.

Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.

“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.

“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”

About the FIT studies

Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).

The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.

Patient characteristics

In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).

The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.

In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).

The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.

Efficacy

The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.

In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.

In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.

“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.

Safety

In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).

In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.

AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).

Micrograph showing MM

LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.

MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.

Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.

The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).

The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.

Treatment

This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.

Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.

Patients

As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.

Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.

The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.

Safety

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.

The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).

Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.

One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.

There were no treatment-related deaths.

Efficacy

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.

In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).

There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.

“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.

“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”

Micrograph showing MM

LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.

MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.

Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.

The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).

The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.

Treatment

This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.

Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.

Patients

As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.

Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.

The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.

Safety

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.

The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).

Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.

One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.

There were no treatment-related deaths.

Efficacy

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.

In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).

There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.

“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.

“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”

Micrograph showing MM

LEIPZIG, GERMANY—Combination therapies including the investigational drug MOR202 have produced “encouraging and long-lasting responses” in a phase 1/2 trial of patients with relapsed/refractory multiple myeloma (MM), according to researchers.

MOR202 is an antibody targeting CD38. In this trial, researchers are testing the drug in combination with dexamethasone (Dex), lenalidomide (Len) and Dex, or pomalidomide (Pom) and Dex.

Results thus far suggest the combinations are well-tolerated and can produce durable responses in heavily pretreated patients with relapsed/refractory MM.

The results were presented in a poster at the 2016 annual meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (abstract P235).

The study, which is ongoing, is sponsored by MorphoSys AG. The poster is available for download from the company’s website.

Treatment

This 3+3 dose-escalation study started with MOR202 monotherapy given at 0.01 mg/kg every 2 weeks, and the dose was escalated up to 16 mg/kg every 2 weeks and 8 mg/kg every week.

Once the dose-escalation phase was complete, researchers began testing MOR202 in combination with Dex, Pom and Dex, or Len and Dex.

Patients

As of September 05, 2016, 73 patients had been treated with MOR202, but the researchers only reported data on the 38 patients who received MOR202 as part of combination therapy.

Eighteen patients had received MOR202 plus Dex, 7 had received MOR202 plus Pom and Dex, and 13 had received MOR202 plus Len and Dex. The patients’ median age was 67, 64, and 64, respectively.

The median number of prior therapies was 3, 4, and 2, respectively. And the percentage of patients who were refractory to their last therapy was 78%, 100%, and 56%, respectively.

Safety

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, has not yet been reached. However, the data suggest MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

All 38 patients who received MOR202 in combination were evaluable for safety—18 in the Dex arm, 7 in the Pom/Dex arm, and 13 in the Len/Dex arm.

The most frequent grade 3 or higher adverse events were hematologic in nature. These included (in the Dex, Pom/Dex, and Len/Dex arms, respectively) leukopenia (11%, 57%, 31%), lymphopenia (39%, 29%, 54%), neutropenia (22%, 71%, 39%), thrombocytopenia (17%, 43%, 8%), and anemia (11%, 14%, 15%).

Infusion-related reactions occurred in 3 (8%) patients and were mainly limited to the first infusion. One patient developed a transient anti-MOR202 antibody response.

One patient discontinued treatment due to an adverse event that may have been caused by MOR202. However, researchers also said the event (decrease in platelet count) may have been caused by Dex.

There were no treatment-related deaths.

Efficacy

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded, and 12 of these responses are ongoing for up to 56 weeks.

In all, there were 10 partial responses (PRs), 3 very good partial responses (VGPRs), and 2 complete responses (CRs).

There were 5 responses in the Dex arm—3 PRs and 2 VGPRs. There were 3 responses in the Pom/Dex arm—2 CRs and 1 PR. And there were 7 responses in the Len/Dex arm—6 PRs (3 unconfirmed) and 1 VGPR.

“We are very pleased that these results are consistent with earlier data from the ongoing trial and show further improved responses with more patients being evaluable for efficacy and safety assessment,” said Arndt Schottelius, MD, PhD, chief development officer of MorphoSys AG.

“In addition to the very short infusion time, we are particularly interested in the efficacy results in patients treated with MOR202 plus pomalidomide, who had a median of 4 prior therapies. The dose-escalation study is ongoing as planned, currently focusing on the highest dose cohorts of 16 mg/kg MOR202 in combination with pomalidomide and lenalidomide.”