CHICAGO – Asymptomatic chronic lymphocytic leukemia (CLL) patients should be observed, but consider therapy when symptoms develop, said Paul M. Barr, MD.

Courtesy Matt Wittmeyer/University of Rochester Medical Center

He described a patient who had been observed for 7 years when he began to complain of increasing fatigue and lost work time. A complete blood count (CBC) showed thrombocytopenia.

The recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines state that assessments before treatment in this type of patient should include history and physical, evaluation of infectious disease status, and routine laboratory testing – including CBC and differential, chemistry, serum immunoglobulin, and direct antiglobulin test.

“Bone marrow biopsies and [computed tomography] scans are listed as ‘not necessarily required,’ ” Dr. Barr, medical director of the Clinical Trials Office for Wilmot Cancer Institute at the University of Rochester (N.Y.) said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

He added that he opts for CT scans prior to therapy “to understand the patient’s disease burden and potentially to compare to later” and that bone marrow biopsy is “still very reasonable” for understanding the source of a patient’s cytopenias.

“Is it marrow failure or [immune thrombocytopenia]? Could the patient have [myelodysplastic syndrome]? All important considerations,” he said.

Positron emission tomography (PET) scans, however, are only considered when there is concern about transformation, he noted.

Predictive tests that should be conducted before initiating therapy, and that could help in guiding therapy decisions, include TP53 mutation testing and immunoglobulin heavy chain variable region gene (IGHV) mutational status testing (although this doesn’t need to be repeated if it was done at diagnosis because mutational status doesn’t change). Another helpful test is molecular cytogenetics using fluorescence in situ hybridization (FISH) for del(13q), del(17p), and trisomy 12 in peripheral blood lymphocytes. This should be repeated even it was done at diagnosis because patients can acquire additional molecular aberrations over time, Dr. Barr said.

Among the data that justify this advice for predictive testing are studies showing the curative potential of fludarabine/cyclophosphamide/rituximab (FCR) in mutated IGHV CLL, the progression-free survival (PFS) benefits of ibrutinib for patients with del(17p), and the activity of idelalisib in relapsed/refractory CLL patients, including those with TP53 dysfunction.

“The IGHV mutation status is useful to know what to expect from chemoimmunotherapy over time,” Dr. Barr said, explaining that several analyses demonstrate that patients with mutated IGHV genes (patients with low-risk disease) respond exceptionally well to chemoimmunotherapy, especially FCR.

In fact, studies, including a 2016 study by Philip A. Thompson and his colleagues and another by Kirsten Fischer and her colleagues, show that nearly 60% of patients with IGHV mutation remain in remission 10 years after FCR treatment, he said. However, the same is not necessarily true for bendamustine/rituximab (BR); the CLL10 study showed a significantly greater PFS with FCR, compared with that seen with BR.

Unmutated patients in that study had lower PFS, but the outcomes were still better with FCR than with BR, he said.

Studies of novel agents, including ibrutinib and idelalisib, suggest they may have particular benefit in higher-risk patients.

Ibrutinib was shown in a phase 2 study to be of benefit regardless of IGHV status, and this was replicated in the first-line RESONATE 2 study, which compared ibrutinib with chlorambucil and showed it had better PFS than that seen in unmutated patients treated with FCR in other studies, said Dr. Barr, the first author on that study.

“So you can see how the treatment paradigms are starting to evolve. It does look like ... comparing across trials, that ibrutinib leads to better remission durations, compared to chemoimmunotherapy, so far,” he said.

Ibrutinib has also been shown to be of benefit for patients with del(17p). A single-arm phase 2 study showed 79% PFS in relapsed, high-risk patients, which is much better than has been seen with chemoimmunotherapy, he noted.

“Venetoclax is also a very good option for this patient population in the relapse setting,” he said, adding that the PFS with venetoclax has been shown to be very similar to that with ibrutinib.

Similarly, idelalisib has been shown to provide comparable benefit in relapsed/refractory CLL patients, with and without del(17p)/TP53 mutation, he said.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

CHICAGO – Asymptomatic chronic lymphocytic leukemia (CLL) patients should be observed, but consider therapy when symptoms develop, said Paul M. Barr, MD.

Courtesy Matt Wittmeyer/University of Rochester Medical Center

He described a patient who had been observed for 7 years when he began to complain of increasing fatigue and lost work time. A complete blood count (CBC) showed thrombocytopenia.

The recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines state that assessments before treatment in this type of patient should include history and physical, evaluation of infectious disease status, and routine laboratory testing – including CBC and differential, chemistry, serum immunoglobulin, and direct antiglobulin test.

“Bone marrow biopsies and [computed tomography] scans are listed as ‘not necessarily required,’ ” Dr. Barr, medical director of the Clinical Trials Office for Wilmot Cancer Institute at the University of Rochester (N.Y.) said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

He added that he opts for CT scans prior to therapy “to understand the patient’s disease burden and potentially to compare to later” and that bone marrow biopsy is “still very reasonable” for understanding the source of a patient’s cytopenias.

“Is it marrow failure or [immune thrombocytopenia]? Could the patient have [myelodysplastic syndrome]? All important considerations,” he said.

Positron emission tomography (PET) scans, however, are only considered when there is concern about transformation, he noted.

Predictive tests that should be conducted before initiating therapy, and that could help in guiding therapy decisions, include TP53 mutation testing and immunoglobulin heavy chain variable region gene (IGHV) mutational status testing (although this doesn’t need to be repeated if it was done at diagnosis because mutational status doesn’t change). Another helpful test is molecular cytogenetics using fluorescence in situ hybridization (FISH) for del(13q), del(17p), and trisomy 12 in peripheral blood lymphocytes. This should be repeated even it was done at diagnosis because patients can acquire additional molecular aberrations over time, Dr. Barr said.

Among the data that justify this advice for predictive testing are studies showing the curative potential of fludarabine/cyclophosphamide/rituximab (FCR) in mutated IGHV CLL, the progression-free survival (PFS) benefits of ibrutinib for patients with del(17p), and the activity of idelalisib in relapsed/refractory CLL patients, including those with TP53 dysfunction.

“The IGHV mutation status is useful to know what to expect from chemoimmunotherapy over time,” Dr. Barr said, explaining that several analyses demonstrate that patients with mutated IGHV genes (patients with low-risk disease) respond exceptionally well to chemoimmunotherapy, especially FCR.

In fact, studies, including a 2016 study by Philip A. Thompson and his colleagues and another by Kirsten Fischer and her colleagues, show that nearly 60% of patients with IGHV mutation remain in remission 10 years after FCR treatment, he said. However, the same is not necessarily true for bendamustine/rituximab (BR); the CLL10 study showed a significantly greater PFS with FCR, compared with that seen with BR.

Unmutated patients in that study had lower PFS, but the outcomes were still better with FCR than with BR, he said.

Studies of novel agents, including ibrutinib and idelalisib, suggest they may have particular benefit in higher-risk patients.

Ibrutinib was shown in a phase 2 study to be of benefit regardless of IGHV status, and this was replicated in the first-line RESONATE 2 study, which compared ibrutinib with chlorambucil and showed it had better PFS than that seen in unmutated patients treated with FCR in other studies, said Dr. Barr, the first author on that study.

“So you can see how the treatment paradigms are starting to evolve. It does look like ... comparing across trials, that ibrutinib leads to better remission durations, compared to chemoimmunotherapy, so far,” he said.

Ibrutinib has also been shown to be of benefit for patients with del(17p). A single-arm phase 2 study showed 79% PFS in relapsed, high-risk patients, which is much better than has been seen with chemoimmunotherapy, he noted.

“Venetoclax is also a very good option for this patient population in the relapse setting,” he said, adding that the PFS with venetoclax has been shown to be very similar to that with ibrutinib.

Similarly, idelalisib has been shown to provide comparable benefit in relapsed/refractory CLL patients, with and without del(17p)/TP53 mutation, he said.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

CHICAGO – Asymptomatic chronic lymphocytic leukemia (CLL) patients should be observed, but consider therapy when symptoms develop, said Paul M. Barr, MD.

Courtesy Matt Wittmeyer/University of Rochester Medical Center

He described a patient who had been observed for 7 years when he began to complain of increasing fatigue and lost work time. A complete blood count (CBC) showed thrombocytopenia.

The recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines state that assessments before treatment in this type of patient should include history and physical, evaluation of infectious disease status, and routine laboratory testing – including CBC and differential, chemistry, serum immunoglobulin, and direct antiglobulin test.

“Bone marrow biopsies and [computed tomography] scans are listed as ‘not necessarily required,’ ” Dr. Barr, medical director of the Clinical Trials Office for Wilmot Cancer Institute at the University of Rochester (N.Y.) said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

He added that he opts for CT scans prior to therapy “to understand the patient’s disease burden and potentially to compare to later” and that bone marrow biopsy is “still very reasonable” for understanding the source of a patient’s cytopenias.

“Is it marrow failure or [immune thrombocytopenia]? Could the patient have [myelodysplastic syndrome]? All important considerations,” he said.

Positron emission tomography (PET) scans, however, are only considered when there is concern about transformation, he noted.

Predictive tests that should be conducted before initiating therapy, and that could help in guiding therapy decisions, include TP53 mutation testing and immunoglobulin heavy chain variable region gene (IGHV) mutational status testing (although this doesn’t need to be repeated if it was done at diagnosis because mutational status doesn’t change). Another helpful test is molecular cytogenetics using fluorescence in situ hybridization (FISH) for del(13q), del(17p), and trisomy 12 in peripheral blood lymphocytes. This should be repeated even it was done at diagnosis because patients can acquire additional molecular aberrations over time, Dr. Barr said.

Among the data that justify this advice for predictive testing are studies showing the curative potential of fludarabine/cyclophosphamide/rituximab (FCR) in mutated IGHV CLL, the progression-free survival (PFS) benefits of ibrutinib for patients with del(17p), and the activity of idelalisib in relapsed/refractory CLL patients, including those with TP53 dysfunction.

“The IGHV mutation status is useful to know what to expect from chemoimmunotherapy over time,” Dr. Barr said, explaining that several analyses demonstrate that patients with mutated IGHV genes (patients with low-risk disease) respond exceptionally well to chemoimmunotherapy, especially FCR.

In fact, studies, including a 2016 study by Philip A. Thompson and his colleagues and another by Kirsten Fischer and her colleagues, show that nearly 60% of patients with IGHV mutation remain in remission 10 years after FCR treatment, he said. However, the same is not necessarily true for bendamustine/rituximab (BR); the CLL10 study showed a significantly greater PFS with FCR, compared with that seen with BR.

Unmutated patients in that study had lower PFS, but the outcomes were still better with FCR than with BR, he said.

Studies of novel agents, including ibrutinib and idelalisib, suggest they may have particular benefit in higher-risk patients.

Ibrutinib was shown in a phase 2 study to be of benefit regardless of IGHV status, and this was replicated in the first-line RESONATE 2 study, which compared ibrutinib with chlorambucil and showed it had better PFS than that seen in unmutated patients treated with FCR in other studies, said Dr. Barr, the first author on that study.

“So you can see how the treatment paradigms are starting to evolve. It does look like ... comparing across trials, that ibrutinib leads to better remission durations, compared to chemoimmunotherapy, so far,” he said.

Ibrutinib has also been shown to be of benefit for patients with del(17p). A single-arm phase 2 study showed 79% PFS in relapsed, high-risk patients, which is much better than has been seen with chemoimmunotherapy, he noted.

“Venetoclax is also a very good option for this patient population in the relapse setting,” he said, adding that the PFS with venetoclax has been shown to be very similar to that with ibrutinib.

Similarly, idelalisib has been shown to provide comparable benefit in relapsed/refractory CLL patients, with and without del(17p)/TP53 mutation, he said.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

Physician stress and burnout remain major concerns for the U.S. health care system, with frustrations over the electronic health record (EHR) driving much of the dissatisfaction experienced by hospitalists and other physicians in the hospital.¹ Underlying the EHR conundrum is a deeper question: Is entering clinical data on a computer the best use of a doctor’s time and professional skills? Or could a portion of that clerical function be delegated to nonphysicians?

Trained medical scribes, charting specialists who input EHR data for physicians on rounds, have been offered as a solution to potentially affect job stress for physicians and shorten their work days. But while scribes have been used and tested by different hospitalist groups around the country, the concept has not taken off in hospital medicine the way it has in certain other settings, such as emergency departments.

“The demand for scribes doesn’t seem to have materialized in a big way for hospital medicine,” said John Nelson, MD, MHM, a hospitalist and consultant in Bellevue, Wash., and a cofounder of the Society of Hospital Medicine. “I’m not convinced that scribes have had a big impact on hospitalist burnout.” It’s difficult to share scribes between doctors on a shift, and it’s a problem if the scribe and doctor get physically separated in the hospital. There’s also the question of who should pay the scribe’s salary, Dr. Nelson said.

Frustrations with the EHR can be a major factor in the experience of physician burnout, but Dr. Nelson said hospitalists can get proficient more quickly because they’re using the same computer system all day. “The bigger problem is that other doctors like surgeons don’t learn how to use the EHR and dump their routine tasks involving the EHR on the hospitalist, which means more work that is less satisfying.”

Could pairing a scribe with a hospitalist improve efficiency and decrease costs relative to the expense of employing the scribe? Are there specific settings, applications, and caseloads in hospital medicine where it makes more sense to use a scribe to support and assist doctors while they’re meeting with patients, with the doctor reviewing and editing the scribe’s work for accuracy? Could the scribe even help with physician staffing shortages by making doctors more productive?

TeamHealth, a national physician services company based in Knoxville, Tenn., has used scribes in emergency departments for years but had concluded that they made less sense for its hospitalist groups after a failure to document significant net increases in productivity, according to a 2015 report in The Hospitalist.² Michael Corvini, MD, FACP, FACEP, TeamHealth’s new regional medical director for acute care services, said he brought extensive positive experience with scribes to his new job and is quite excited about their potential for hospital medicine. “When I came to TeamHealth in July, I began to suggest that there was unrealized potential for scribes,” he said.

Dr. Corvini noted that a potential benefit of scribes for patients is that their presence may allow for more face time with the doctor. Providers, relieved of worrying about completing the chart in its entirety would be more able to focus on the patient and critical thinking. There are even benefits for scribes themselves. Often scribes are medical students, and those who are interested in pursuing a future in the health professions gain invaluable experience in the workings of medicine. “They are making a real contribution to patient care. They are a member of the health care team,” he said.

Dr. Corvini sees two primary areas in which scribes can contribute to hospital medicine. The first is shadowing the physician who is admitting patients during a high-volume admissions shift. Regular tasks like capturing the patient’s medication list and populating the History and Physical document lend themselves well to data entry by scribes, in contrast to completing more routine daily progress notes, which does not.

“They can also be helpful when there is a major transition from paper charting to the EHR or from one EHR system to another, when there is a lot of stress on the physician and risk for lost billing revenue,” Dr. Corvini said. “If scribes are trained in a particular EHR, they could help teach the physician how to use it.” TeamHealth is now in the process of running a trial of scribes at one of its sites, and the organization plans to measure productivity, provider satisfaction, and HCAHPS patient satisfaction scores.


 

A workaround – or a problem solver?

In a 2015 Viewpoint article in JAMA,³ George Gellert, MD, MPH, MPA, former chief medical information officer for the CHRISTUS Santa Rosa health system in San Antonio, Texas, and his coauthors labeled the use of scribes as a “workaround” that could curtail efforts to make EHRs more functionally operational because their use allows physicians to be satisfied with inferior EHR products.

In an interview, Dr. Gellert stated that he hasn’t changed his views about the negative consequences of scribes on EHR improvement. “The work of clinicians in using and advancing EHR technology is presently the only method we have for massively distributing and ensuring the use of evidence-based medicine,” he said. “That in turn is a critical strategy for reducing high rates of medical errors through a variety of decision-support applications.”

For better or worse, EHRs are an essential part of the solution to the epidemic of preventable, medical error–caused patient deaths, Dr. Gellert said. He also believes that substantial progress has already been made in advancing EHR usability, as reflected in the most recent product releases by leading EHR companies. However, considerable evolution is still needed in both usability and optimization of clinical decision support.

“With respect to your readers, my recommendation is to not use medical scribes, or else delimit their use to only where absolutely required. Instead, develop systematic processes to regularly capture specific physician concerns with the EHR being used, and transmit that critical information to their EHR vendor with a clear expectation that the manufacturer will address the issue in the near term, or at least in their next major product iteration or generation,” Dr. Gellert said.

By contrast, at the Management of the Hospitalized Patient conference in San Francisco in October 2015, Christine Sinsky, MD, FACP, vice president for professional satisfaction at the American Medical Association, identified documentation assistance as a helpful intervention for physician stress and burnout.⁴ In a recent email, Dr. Sinsky called documentation assistance “the most powerful intervention to give patients the time, attention, and care they need from their physicians. The data entry and data retrieval work of health care has grown over the last decade. Sharing this work with nonphysicians allows society to get the most value for its investment in physicians’ training.”

Dr. Sinsky calls documentation assistance – such as that provided by medical scribes – “a logical and strategic delegation of work according to ability for greater value,” not a workaround. She said it makes patient care safer by allowing physicians to focus on medical decision making and relationship building – rather than record keeping.
 

Experience from the front lines

Eric Edwards, MD, FAAP, FHM, of the division of hospital medicine at the University of North Carolina’s Hillsborough Hospital campus, recently presented a poster on his group’s experience with medical scribes at a meeting of the North Carolina Triangle Chapter of SHM. Their research concluded that scribes can be successfully incorporated into an inpatient hospital medicine practice and thus increase provider satisfaction and decrease the time clinicians spend charting.

“We were able to get the support of the hospital administration to pilot the use of scribes 3 days per week, which we’ve now done for almost a year,” Dr. Edwards said. Scribes are employed through a local company, MedScribes, and they work alongside admitting hospitalists during their 10-hour shifts. The hospitalists have been overwhelmingly positive about their experience, he said. “We established that it saves the physician 15 minutes per patient encounter by helping with documentation.”

It’s important that the scribe gets to know an individual provider’s personal preferences, Dr. Edwards said. Some hospitalists create their own charting templates. There’s also a need to train the clinician in how to use the medical scribe. For example, physicians are instructed to call out physical findings during their exam, which simultaneously informs the patient while allowing the scribe to document the exam.

“We are working on getting more formal data about the scribe experience,” he added. “But we have found that our providers love it, and it improves their efficiency and productivity. The danger is if the physician becomes too reliant on the scribe and fails to exercise due diligence in reviewing the scribe’s notes to ensure that all relevant information is in the chart and irrelevant information is not. We need to make sure we are carefully reviewing and signing off on the scribe’s notes,” he explained.

“I think we’re years away from improving the EHR to the point that would allow us to call it doctor friendly,” Dr. Edwards said. “For now, the scribe is a great way to alleviate some of the physician’s burden. But for hospitalist groups to use scribes successfully, it can’t be done haphazardly. We are lucky to have an experienced local scribe company to partner with. They provide systematic training and orientation. It’s also important that scribes are trained in the specific EHR that they will be using.”

Christine Lum Lung, MD, SFHM, CEO and medical director of Northern Colorado Hospitalists, a hospital medicine group at the University of Colorado’s North Campus hospitals in Fort Collins, has been studying the use of scribes since 2014. “We had a gap in bringing on new doctors fast enough for our group’s needs, so I looked into the return on investment from scribes and pitched it to our group,” she said. “It’s difficult to say what has been the actual impact on caseload, but we all think it has reduced physician workdays by an hour or greater.”

The 32-member hospitalist group, which covers two facilities, has a designated director of scribes who periodically surveys the hospitalists’ satisfaction with the scribes. “Now we all embrace the use of scribes. Satisfaction is high, and quality of life has improved,” Dr. Lum Lung said. “It’s hard to quantify, but we feel like it helps with burnout for us to be able to leave work earlier, and it alleviates some of the other stresses in our workday.”

She said scribes are important to the medical team not just with managing the EHR but also with other burdens such as documenting compliance with code status, VTEs, and other quality requirements, and to help with other regulatory issues. Scribes can look up lab values and radiology reports. When there are downtimes, they can prepare discharge plans.

Typically, there are five scribes on duty for 18 hours a day at each hospital, Dr. Lum Lung said. But only those doctors primarily doing admissions are assured of having a scribe to round with them. “Most doctors in the group would say the greatest efficiency of scribes is with admitting,” she said. The company that provides scribes to the UC hospitals, ScribeAmerica, handles administration, training, and human resource issues, and the scribe team has a designated Lead Scribe and Quality Scribe at their facility.


 

Studying the benefits

Andrew Friedson, PhD, a health care economist at the University of Colorado in Denver, recently conducted a 9-month randomized experiment in three hospital emergency rooms in the Denver area to determine the effects of scribes on measures of emergency physician productivity.⁵ He found that scribes reduced patient wait times in the emergency department by about 13 minutes per patient, while greatly decreasing the amount of time physicians spent after a shift completing their charting, which thus lowered overtime costs for ED physicians.

“This is one of the first times medical scribes have been studied with a randomized, controlled trial,” Dr. Friedson said. “I tracked the amount of overtime, patient waiting, and charge capture for each encounter. These were hospitals where the emergency doctors weren’t allowed to go home until their charting was done.” He discovered that there was a large drop in the time between when patients arrived at the ED and when a decision was made regarding whether to admit them. Additionally, charge capture increased significantly, and physicians had more time to perform medical procedures. Dr. Friedson believes that his findings hold implications for other settings and medical groups, including hospital medicine. To the extent that scribes free up hospitalists to perform tasks other than charting, they should provide an efficiency benefit.

So why hasn’t the medical scribe caught on in a bigger way for hospitalists, compared with ED physicians? For Dr. Corvini, the ED is an obvious, high-pressure, high-volume setting where the cost of the scribe can be easily recouped. “That doesn’t exist in such an obvious fashion in hospital medicine, except where high-volume admissions are concentrated in a single physician’s caseload,” he said. Not all hospitalist groups will fit that model. Some may divide admissions between hospitalists on a shift, and others may not be large enough to experience significant caseload pressures.

“EDs are obviously time pressured, and once scribes demonstrate the ability to produce documentation in a high-quality fashion, they are quickly accepted. In hospital medicine, the time pressures are different – not necessarily less, but different,” Dr. Corvini said. There are also differences in physician responsibilities between the ED and hospital medicine, as well as in physicians’ willingness to let go of documentation responsibilities. “My prediction, if the scribe test is rolled out successfully in TeamHealth, with measurable benefits, it will be adopted in other settings where it fits.”
 

References

1. Shanafelt TD et al. Relationship between clerical burden and characteristics of the electronic environment with physician burnout and professional satisfaction. Mayo Clin Proc. 2016 Jul;91(7):836-48.

2. Collins TR. Use of medical scribes spurs debate about costs, difficulties of electronic health records. The Hospitalist; 2015 Oct.

3. Gellert GA et al. The rise of the medical scribe industry: Implications for the advancement of electronic health records. JAMA; 2015;313(13):1315-6.

4. Beresford L. Electronic Health Records Key Driver of Physician Burnout. The Hospitalist; 2015 Dec.

5. Friedson AI. Medical scribes as an input in healthcare production: Evidence from a randomized experiment. Am J Health Econ. 2017 Oct 2. doi: /10.1162/ajhe_a_00103.






 

Physician stress and burnout remain major concerns for the U.S. health care system, with frustrations over the electronic health record (EHR) driving much of the dissatisfaction experienced by hospitalists and other physicians in the hospital.¹ Underlying the EHR conundrum is a deeper question: Is entering clinical data on a computer the best use of a doctor’s time and professional skills? Or could a portion of that clerical function be delegated to nonphysicians?

Trained medical scribes, charting specialists who input EHR data for physicians on rounds, have been offered as a solution to potentially affect job stress for physicians and shorten their work days. But while scribes have been used and tested by different hospitalist groups around the country, the concept has not taken off in hospital medicine the way it has in certain other settings, such as emergency departments.

“The demand for scribes doesn’t seem to have materialized in a big way for hospital medicine,” said John Nelson, MD, MHM, a hospitalist and consultant in Bellevue, Wash., and a cofounder of the Society of Hospital Medicine. “I’m not convinced that scribes have had a big impact on hospitalist burnout.” It’s difficult to share scribes between doctors on a shift, and it’s a problem if the scribe and doctor get physically separated in the hospital. There’s also the question of who should pay the scribe’s salary, Dr. Nelson said.

Frustrations with the EHR can be a major factor in the experience of physician burnout, but Dr. Nelson said hospitalists can get proficient more quickly because they’re using the same computer system all day. “The bigger problem is that other doctors like surgeons don’t learn how to use the EHR and dump their routine tasks involving the EHR on the hospitalist, which means more work that is less satisfying.”

Could pairing a scribe with a hospitalist improve efficiency and decrease costs relative to the expense of employing the scribe? Are there specific settings, applications, and caseloads in hospital medicine where it makes more sense to use a scribe to support and assist doctors while they’re meeting with patients, with the doctor reviewing and editing the scribe’s work for accuracy? Could the scribe even help with physician staffing shortages by making doctors more productive?

TeamHealth, a national physician services company based in Knoxville, Tenn., has used scribes in emergency departments for years but had concluded that they made less sense for its hospitalist groups after a failure to document significant net increases in productivity, according to a 2015 report in The Hospitalist.² Michael Corvini, MD, FACP, FACEP, TeamHealth’s new regional medical director for acute care services, said he brought extensive positive experience with scribes to his new job and is quite excited about their potential for hospital medicine. “When I came to TeamHealth in July, I began to suggest that there was unrealized potential for scribes,” he said.

Dr. Corvini noted that a potential benefit of scribes for patients is that their presence may allow for more face time with the doctor. Providers, relieved of worrying about completing the chart in its entirety would be more able to focus on the patient and critical thinking. There are even benefits for scribes themselves. Often scribes are medical students, and those who are interested in pursuing a future in the health professions gain invaluable experience in the workings of medicine. “They are making a real contribution to patient care. They are a member of the health care team,” he said.

Dr. Corvini sees two primary areas in which scribes can contribute to hospital medicine. The first is shadowing the physician who is admitting patients during a high-volume admissions shift. Regular tasks like capturing the patient’s medication list and populating the History and Physical document lend themselves well to data entry by scribes, in contrast to completing more routine daily progress notes, which does not.

“They can also be helpful when there is a major transition from paper charting to the EHR or from one EHR system to another, when there is a lot of stress on the physician and risk for lost billing revenue,” Dr. Corvini said. “If scribes are trained in a particular EHR, they could help teach the physician how to use it.” TeamHealth is now in the process of running a trial of scribes at one of its sites, and the organization plans to measure productivity, provider satisfaction, and HCAHPS patient satisfaction scores.


 

A workaround – or a problem solver?

In a 2015 Viewpoint article in JAMA,³ George Gellert, MD, MPH, MPA, former chief medical information officer for the CHRISTUS Santa Rosa health system in San Antonio, Texas, and his coauthors labeled the use of scribes as a “workaround” that could curtail efforts to make EHRs more functionally operational because their use allows physicians to be satisfied with inferior EHR products.

In an interview, Dr. Gellert stated that he hasn’t changed his views about the negative consequences of scribes on EHR improvement. “The work of clinicians in using and advancing EHR technology is presently the only method we have for massively distributing and ensuring the use of evidence-based medicine,” he said. “That in turn is a critical strategy for reducing high rates of medical errors through a variety of decision-support applications.”

For better or worse, EHRs are an essential part of the solution to the epidemic of preventable, medical error–caused patient deaths, Dr. Gellert said. He also believes that substantial progress has already been made in advancing EHR usability, as reflected in the most recent product releases by leading EHR companies. However, considerable evolution is still needed in both usability and optimization of clinical decision support.

“With respect to your readers, my recommendation is to not use medical scribes, or else delimit their use to only where absolutely required. Instead, develop systematic processes to regularly capture specific physician concerns with the EHR being used, and transmit that critical information to their EHR vendor with a clear expectation that the manufacturer will address the issue in the near term, or at least in their next major product iteration or generation,” Dr. Gellert said.

By contrast, at the Management of the Hospitalized Patient conference in San Francisco in October 2015, Christine Sinsky, MD, FACP, vice president for professional satisfaction at the American Medical Association, identified documentation assistance as a helpful intervention for physician stress and burnout.⁴ In a recent email, Dr. Sinsky called documentation assistance “the most powerful intervention to give patients the time, attention, and care they need from their physicians. The data entry and data retrieval work of health care has grown over the last decade. Sharing this work with nonphysicians allows society to get the most value for its investment in physicians’ training.”

Dr. Sinsky calls documentation assistance – such as that provided by medical scribes – “a logical and strategic delegation of work according to ability for greater value,” not a workaround. She said it makes patient care safer by allowing physicians to focus on medical decision making and relationship building – rather than record keeping.
 

Experience from the front lines

Eric Edwards, MD, FAAP, FHM, of the division of hospital medicine at the University of North Carolina’s Hillsborough Hospital campus, recently presented a poster on his group’s experience with medical scribes at a meeting of the North Carolina Triangle Chapter of SHM. Their research concluded that scribes can be successfully incorporated into an inpatient hospital medicine practice and thus increase provider satisfaction and decrease the time clinicians spend charting.

“We were able to get the support of the hospital administration to pilot the use of scribes 3 days per week, which we’ve now done for almost a year,” Dr. Edwards said. Scribes are employed through a local company, MedScribes, and they work alongside admitting hospitalists during their 10-hour shifts. The hospitalists have been overwhelmingly positive about their experience, he said. “We established that it saves the physician 15 minutes per patient encounter by helping with documentation.”

It’s important that the scribe gets to know an individual provider’s personal preferences, Dr. Edwards said. Some hospitalists create their own charting templates. There’s also a need to train the clinician in how to use the medical scribe. For example, physicians are instructed to call out physical findings during their exam, which simultaneously informs the patient while allowing the scribe to document the exam.

“We are working on getting more formal data about the scribe experience,” he added. “But we have found that our providers love it, and it improves their efficiency and productivity. The danger is if the physician becomes too reliant on the scribe and fails to exercise due diligence in reviewing the scribe’s notes to ensure that all relevant information is in the chart and irrelevant information is not. We need to make sure we are carefully reviewing and signing off on the scribe’s notes,” he explained.

“I think we’re years away from improving the EHR to the point that would allow us to call it doctor friendly,” Dr. Edwards said. “For now, the scribe is a great way to alleviate some of the physician’s burden. But for hospitalist groups to use scribes successfully, it can’t be done haphazardly. We are lucky to have an experienced local scribe company to partner with. They provide systematic training and orientation. It’s also important that scribes are trained in the specific EHR that they will be using.”

Christine Lum Lung, MD, SFHM, CEO and medical director of Northern Colorado Hospitalists, a hospital medicine group at the University of Colorado’s North Campus hospitals in Fort Collins, has been studying the use of scribes since 2014. “We had a gap in bringing on new doctors fast enough for our group’s needs, so I looked into the return on investment from scribes and pitched it to our group,” she said. “It’s difficult to say what has been the actual impact on caseload, but we all think it has reduced physician workdays by an hour or greater.”

The 32-member hospitalist group, which covers two facilities, has a designated director of scribes who periodically surveys the hospitalists’ satisfaction with the scribes. “Now we all embrace the use of scribes. Satisfaction is high, and quality of life has improved,” Dr. Lum Lung said. “It’s hard to quantify, but we feel like it helps with burnout for us to be able to leave work earlier, and it alleviates some of the other stresses in our workday.”

She said scribes are important to the medical team not just with managing the EHR but also with other burdens such as documenting compliance with code status, VTEs, and other quality requirements, and to help with other regulatory issues. Scribes can look up lab values and radiology reports. When there are downtimes, they can prepare discharge plans.

Typically, there are five scribes on duty for 18 hours a day at each hospital, Dr. Lum Lung said. But only those doctors primarily doing admissions are assured of having a scribe to round with them. “Most doctors in the group would say the greatest efficiency of scribes is with admitting,” she said. The company that provides scribes to the UC hospitals, ScribeAmerica, handles administration, training, and human resource issues, and the scribe team has a designated Lead Scribe and Quality Scribe at their facility.


 

Studying the benefits

Andrew Friedson, PhD, a health care economist at the University of Colorado in Denver, recently conducted a 9-month randomized experiment in three hospital emergency rooms in the Denver area to determine the effects of scribes on measures of emergency physician productivity.⁵ He found that scribes reduced patient wait times in the emergency department by about 13 minutes per patient, while greatly decreasing the amount of time physicians spent after a shift completing their charting, which thus lowered overtime costs for ED physicians.

“This is one of the first times medical scribes have been studied with a randomized, controlled trial,” Dr. Friedson said. “I tracked the amount of overtime, patient waiting, and charge capture for each encounter. These were hospitals where the emergency doctors weren’t allowed to go home until their charting was done.” He discovered that there was a large drop in the time between when patients arrived at the ED and when a decision was made regarding whether to admit them. Additionally, charge capture increased significantly, and physicians had more time to perform medical procedures. Dr. Friedson believes that his findings hold implications for other settings and medical groups, including hospital medicine. To the extent that scribes free up hospitalists to perform tasks other than charting, they should provide an efficiency benefit.

So why hasn’t the medical scribe caught on in a bigger way for hospitalists, compared with ED physicians? For Dr. Corvini, the ED is an obvious, high-pressure, high-volume setting where the cost of the scribe can be easily recouped. “That doesn’t exist in such an obvious fashion in hospital medicine, except where high-volume admissions are concentrated in a single physician’s caseload,” he said. Not all hospitalist groups will fit that model. Some may divide admissions between hospitalists on a shift, and others may not be large enough to experience significant caseload pressures.

“EDs are obviously time pressured, and once scribes demonstrate the ability to produce documentation in a high-quality fashion, they are quickly accepted. In hospital medicine, the time pressures are different – not necessarily less, but different,” Dr. Corvini said. There are also differences in physician responsibilities between the ED and hospital medicine, as well as in physicians’ willingness to let go of documentation responsibilities. “My prediction, if the scribe test is rolled out successfully in TeamHealth, with measurable benefits, it will be adopted in other settings where it fits.”
 

References

1. Shanafelt TD et al. Relationship between clerical burden and characteristics of the electronic environment with physician burnout and professional satisfaction. Mayo Clin Proc. 2016 Jul;91(7):836-48.

2. Collins TR. Use of medical scribes spurs debate about costs, difficulties of electronic health records. The Hospitalist; 2015 Oct.

3. Gellert GA et al. The rise of the medical scribe industry: Implications for the advancement of electronic health records. JAMA; 2015;313(13):1315-6.

4. Beresford L. Electronic Health Records Key Driver of Physician Burnout. The Hospitalist; 2015 Dec.

5. Friedson AI. Medical scribes as an input in healthcare production: Evidence from a randomized experiment. Am J Health Econ. 2017 Oct 2. doi: /10.1162/ajhe_a_00103.






 

Physician stress and burnout remain major concerns for the U.S. health care system, with frustrations over the electronic health record (EHR) driving much of the dissatisfaction experienced by hospitalists and other physicians in the hospital.¹ Underlying the EHR conundrum is a deeper question: Is entering clinical data on a computer the best use of a doctor’s time and professional skills? Or could a portion of that clerical function be delegated to nonphysicians?

Trained medical scribes, charting specialists who input EHR data for physicians on rounds, have been offered as a solution to potentially affect job stress for physicians and shorten their work days. But while scribes have been used and tested by different hospitalist groups around the country, the concept has not taken off in hospital medicine the way it has in certain other settings, such as emergency departments.

“The demand for scribes doesn’t seem to have materialized in a big way for hospital medicine,” said John Nelson, MD, MHM, a hospitalist and consultant in Bellevue, Wash., and a cofounder of the Society of Hospital Medicine. “I’m not convinced that scribes have had a big impact on hospitalist burnout.” It’s difficult to share scribes between doctors on a shift, and it’s a problem if the scribe and doctor get physically separated in the hospital. There’s also the question of who should pay the scribe’s salary, Dr. Nelson said.

Frustrations with the EHR can be a major factor in the experience of physician burnout, but Dr. Nelson said hospitalists can get proficient more quickly because they’re using the same computer system all day. “The bigger problem is that other doctors like surgeons don’t learn how to use the EHR and dump their routine tasks involving the EHR on the hospitalist, which means more work that is less satisfying.”

Could pairing a scribe with a hospitalist improve efficiency and decrease costs relative to the expense of employing the scribe? Are there specific settings, applications, and caseloads in hospital medicine where it makes more sense to use a scribe to support and assist doctors while they’re meeting with patients, with the doctor reviewing and editing the scribe’s work for accuracy? Could the scribe even help with physician staffing shortages by making doctors more productive?

TeamHealth, a national physician services company based in Knoxville, Tenn., has used scribes in emergency departments for years but had concluded that they made less sense for its hospitalist groups after a failure to document significant net increases in productivity, according to a 2015 report in The Hospitalist.² Michael Corvini, MD, FACP, FACEP, TeamHealth’s new regional medical director for acute care services, said he brought extensive positive experience with scribes to his new job and is quite excited about their potential for hospital medicine. “When I came to TeamHealth in July, I began to suggest that there was unrealized potential for scribes,” he said.

Dr. Corvini noted that a potential benefit of scribes for patients is that their presence may allow for more face time with the doctor. Providers, relieved of worrying about completing the chart in its entirety would be more able to focus on the patient and critical thinking. There are even benefits for scribes themselves. Often scribes are medical students, and those who are interested in pursuing a future in the health professions gain invaluable experience in the workings of medicine. “They are making a real contribution to patient care. They are a member of the health care team,” he said.

Dr. Corvini sees two primary areas in which scribes can contribute to hospital medicine. The first is shadowing the physician who is admitting patients during a high-volume admissions shift. Regular tasks like capturing the patient’s medication list and populating the History and Physical document lend themselves well to data entry by scribes, in contrast to completing more routine daily progress notes, which does not.

“They can also be helpful when there is a major transition from paper charting to the EHR or from one EHR system to another, when there is a lot of stress on the physician and risk for lost billing revenue,” Dr. Corvini said. “If scribes are trained in a particular EHR, they could help teach the physician how to use it.” TeamHealth is now in the process of running a trial of scribes at one of its sites, and the organization plans to measure productivity, provider satisfaction, and HCAHPS patient satisfaction scores.


 

A workaround – or a problem solver?

In a 2015 Viewpoint article in JAMA,³ George Gellert, MD, MPH, MPA, former chief medical information officer for the CHRISTUS Santa Rosa health system in San Antonio, Texas, and his coauthors labeled the use of scribes as a “workaround” that could curtail efforts to make EHRs more functionally operational because their use allows physicians to be satisfied with inferior EHR products.

In an interview, Dr. Gellert stated that he hasn’t changed his views about the negative consequences of scribes on EHR improvement. “The work of clinicians in using and advancing EHR technology is presently the only method we have for massively distributing and ensuring the use of evidence-based medicine,” he said. “That in turn is a critical strategy for reducing high rates of medical errors through a variety of decision-support applications.”

For better or worse, EHRs are an essential part of the solution to the epidemic of preventable, medical error–caused patient deaths, Dr. Gellert said. He also believes that substantial progress has already been made in advancing EHR usability, as reflected in the most recent product releases by leading EHR companies. However, considerable evolution is still needed in both usability and optimization of clinical decision support.

“With respect to your readers, my recommendation is to not use medical scribes, or else delimit their use to only where absolutely required. Instead, develop systematic processes to regularly capture specific physician concerns with the EHR being used, and transmit that critical information to their EHR vendor with a clear expectation that the manufacturer will address the issue in the near term, or at least in their next major product iteration or generation,” Dr. Gellert said.

By contrast, at the Management of the Hospitalized Patient conference in San Francisco in October 2015, Christine Sinsky, MD, FACP, vice president for professional satisfaction at the American Medical Association, identified documentation assistance as a helpful intervention for physician stress and burnout.⁴ In a recent email, Dr. Sinsky called documentation assistance “the most powerful intervention to give patients the time, attention, and care they need from their physicians. The data entry and data retrieval work of health care has grown over the last decade. Sharing this work with nonphysicians allows society to get the most value for its investment in physicians’ training.”

Dr. Sinsky calls documentation assistance – such as that provided by medical scribes – “a logical and strategic delegation of work according to ability for greater value,” not a workaround. She said it makes patient care safer by allowing physicians to focus on medical decision making and relationship building – rather than record keeping.
 

Experience from the front lines

Eric Edwards, MD, FAAP, FHM, of the division of hospital medicine at the University of North Carolina’s Hillsborough Hospital campus, recently presented a poster on his group’s experience with medical scribes at a meeting of the North Carolina Triangle Chapter of SHM. Their research concluded that scribes can be successfully incorporated into an inpatient hospital medicine practice and thus increase provider satisfaction and decrease the time clinicians spend charting.

“We were able to get the support of the hospital administration to pilot the use of scribes 3 days per week, which we’ve now done for almost a year,” Dr. Edwards said. Scribes are employed through a local company, MedScribes, and they work alongside admitting hospitalists during their 10-hour shifts. The hospitalists have been overwhelmingly positive about their experience, he said. “We established that it saves the physician 15 minutes per patient encounter by helping with documentation.”

It’s important that the scribe gets to know an individual provider’s personal preferences, Dr. Edwards said. Some hospitalists create their own charting templates. There’s also a need to train the clinician in how to use the medical scribe. For example, physicians are instructed to call out physical findings during their exam, which simultaneously informs the patient while allowing the scribe to document the exam.

“We are working on getting more formal data about the scribe experience,” he added. “But we have found that our providers love it, and it improves their efficiency and productivity. The danger is if the physician becomes too reliant on the scribe and fails to exercise due diligence in reviewing the scribe’s notes to ensure that all relevant information is in the chart and irrelevant information is not. We need to make sure we are carefully reviewing and signing off on the scribe’s notes,” he explained.

“I think we’re years away from improving the EHR to the point that would allow us to call it doctor friendly,” Dr. Edwards said. “For now, the scribe is a great way to alleviate some of the physician’s burden. But for hospitalist groups to use scribes successfully, it can’t be done haphazardly. We are lucky to have an experienced local scribe company to partner with. They provide systematic training and orientation. It’s also important that scribes are trained in the specific EHR that they will be using.”

Christine Lum Lung, MD, SFHM, CEO and medical director of Northern Colorado Hospitalists, a hospital medicine group at the University of Colorado’s North Campus hospitals in Fort Collins, has been studying the use of scribes since 2014. “We had a gap in bringing on new doctors fast enough for our group’s needs, so I looked into the return on investment from scribes and pitched it to our group,” she said. “It’s difficult to say what has been the actual impact on caseload, but we all think it has reduced physician workdays by an hour or greater.”

The 32-member hospitalist group, which covers two facilities, has a designated director of scribes who periodically surveys the hospitalists’ satisfaction with the scribes. “Now we all embrace the use of scribes. Satisfaction is high, and quality of life has improved,” Dr. Lum Lung said. “It’s hard to quantify, but we feel like it helps with burnout for us to be able to leave work earlier, and it alleviates some of the other stresses in our workday.”

She said scribes are important to the medical team not just with managing the EHR but also with other burdens such as documenting compliance with code status, VTEs, and other quality requirements, and to help with other regulatory issues. Scribes can look up lab values and radiology reports. When there are downtimes, they can prepare discharge plans.

Typically, there are five scribes on duty for 18 hours a day at each hospital, Dr. Lum Lung said. But only those doctors primarily doing admissions are assured of having a scribe to round with them. “Most doctors in the group would say the greatest efficiency of scribes is with admitting,” she said. The company that provides scribes to the UC hospitals, ScribeAmerica, handles administration, training, and human resource issues, and the scribe team has a designated Lead Scribe and Quality Scribe at their facility.


 

Studying the benefits

Andrew Friedson, PhD, a health care economist at the University of Colorado in Denver, recently conducted a 9-month randomized experiment in three hospital emergency rooms in the Denver area to determine the effects of scribes on measures of emergency physician productivity.⁵ He found that scribes reduced patient wait times in the emergency department by about 13 minutes per patient, while greatly decreasing the amount of time physicians spent after a shift completing their charting, which thus lowered overtime costs for ED physicians.

“This is one of the first times medical scribes have been studied with a randomized, controlled trial,” Dr. Friedson said. “I tracked the amount of overtime, patient waiting, and charge capture for each encounter. These were hospitals where the emergency doctors weren’t allowed to go home until their charting was done.” He discovered that there was a large drop in the time between when patients arrived at the ED and when a decision was made regarding whether to admit them. Additionally, charge capture increased significantly, and physicians had more time to perform medical procedures. Dr. Friedson believes that his findings hold implications for other settings and medical groups, including hospital medicine. To the extent that scribes free up hospitalists to perform tasks other than charting, they should provide an efficiency benefit.

So why hasn’t the medical scribe caught on in a bigger way for hospitalists, compared with ED physicians? For Dr. Corvini, the ED is an obvious, high-pressure, high-volume setting where the cost of the scribe can be easily recouped. “That doesn’t exist in such an obvious fashion in hospital medicine, except where high-volume admissions are concentrated in a single physician’s caseload,” he said. Not all hospitalist groups will fit that model. Some may divide admissions between hospitalists on a shift, and others may not be large enough to experience significant caseload pressures.

“EDs are obviously time pressured, and once scribes demonstrate the ability to produce documentation in a high-quality fashion, they are quickly accepted. In hospital medicine, the time pressures are different – not necessarily less, but different,” Dr. Corvini said. There are also differences in physician responsibilities between the ED and hospital medicine, as well as in physicians’ willingness to let go of documentation responsibilities. “My prediction, if the scribe test is rolled out successfully in TeamHealth, with measurable benefits, it will be adopted in other settings where it fits.”
 

References

1. Shanafelt TD et al. Relationship between clerical burden and characteristics of the electronic environment with physician burnout and professional satisfaction. Mayo Clin Proc. 2016 Jul;91(7):836-48.

2. Collins TR. Use of medical scribes spurs debate about costs, difficulties of electronic health records. The Hospitalist; 2015 Oct.

3. Gellert GA et al. The rise of the medical scribe industry: Implications for the advancement of electronic health records. JAMA; 2015;313(13):1315-6.

4. Beresford L. Electronic Health Records Key Driver of Physician Burnout. The Hospitalist; 2015 Dec.

5. Friedson AI. Medical scribes as an input in healthcare production: Evidence from a randomized experiment. Am J Health Econ. 2017 Oct 2. doi: /10.1162/ajhe_a_00103.






 

CHICAGO – A 50-year old otherwise healthy man was found on routine history and physical to have lymphocytosis and was referred for additional work-up. He denied recent infection, had no lymphadenopathy, organomegaly, or rash or other concerning skin lesions. A complete blood count showed a white cell count of 23 x 10⁹/Land absolute lymphocyte count of 19 x 10⁹/L and normal hemoglobin and platelets.

Based on recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines, additional work-up for this patient might include peripheral smear and flow cytometry, according to Paul Barr, MD.

“A peripheral smear is still useful in this day and age just to ensure that a patient has a typical look under the microscope. We expect to see small mature lymphocytes, smudge cells, and perhaps a smaller number of prolymphocytes. But to mark CLL based on flow cytometry we need to see greater than 5 x 10⁹/L clonal B lymphocytes in the peripheral blood sustained over time,” Dr. Barr, medical director of the clinical trials office for Wilmot Cancer Institute at the University of Rochester (N.Y.), said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

A nuance in the iwCLL guidelines is that CLL also can be defined by a cytopenia caused by a typical marrow infiltrate, regardless of the number of circulating B lymphocytes, he noted.

Immunophenotype

As for CLL immunophenotype, the cells are CD5- and CD23-positive, and additional B cell markers like CD20 are “often dim, and – understandably – the cells are light-chain restricted,” he said.

A subtle difference between the World Health Organization classification of CLL and the iwCLL guidelines is that, by the former, patients can have “a somewhat atypical immunophenotype.”


“So our pathologists, I like to think, use a commonsense approach where, if there are very minor differences, they will still call it CLL, but not if there are major differences in the immunophenotype,” Dr. Barr said.

Patients with lymphadenopathy, without the critical threshold of circulating B lymphocytes, are considered to have small lymphocytic lymphoma (SLL).

“In this day and age we treat CLL and SLL relatively similarly, however, monoclonal B lymphocytosis (MBL) is the precursor lesion to CLL where we see less than 5 x 10⁹/L of circulating B lymphocytes and an absence of adenopathy and disease-related cytopenias,” he noted.

Staging

It is still common practice to stage patients given the prognostic value of staging and given that treatment is provided in advanced disease, Dr. Barr said.

“This is simple, easy to apply, applicable worldwide, and only requires laboratory testing and a physical exam,” he said.

The stages include:

• Stage 0: Lymphocytosis, peripheral lymphocyte count greater than 15,000/mcL and greater than 40% lymphocytes in bone marrow (low-risk disease status).
• Stage I: Stage 0 disease plus enlarged lymph nodes (intermediate-risk disease status).
• Stage II: Stage 0-I disease with splenomegaly and/or hepatomegaly (intermediate-risk disease status).
• Stage III: Stage 0-II disease with hemoglobin less than 11g/dL or hematocrit less than 33% (high-risk disease status).
• Stage IV: Stage 0-III disease with platelet count less than 100,000/mcL (high-risk disease status).

Prognostic testing

Once a patient is diagnosed with CLL, as was the case with the 50-year-old patient Dr. Barr described, a number of tests can be considered to assess prognosis.

There’s no “perfect answer” when it comes to which tests are considered a reasonable standard of care, he noted.

“I would typically perform [immunoglobulin variable heavy-chain gene] mutation testing, a [fluorescence in situ hybridization] panel, and TP53 mutation testing,” he said.

Scoring systems such as CLL-IPI, which combine prognostic factors to divide patients into various risk categories, can be useful.

For example, such systems may identify high-risk patients who might be appropriate candidates for clinical trials, or low-risk patients who could be expected to do well over time despite having advanced stage disease, he explained.

“I do think it’s a useful process to go through to understand a patient’s risk over time,” he added.

However, treatment for CLL still is not based on molecular aberrations/prognostic features. In fact, the treatment indications according to the updated iwCLL guidelines remain exactly the same, he said.

Therefore, the case of the 50-year-old man described earlier would be observed as long as he remained asymptomatic.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

CHICAGO – A 50-year old otherwise healthy man was found on routine history and physical to have lymphocytosis and was referred for additional work-up. He denied recent infection, had no lymphadenopathy, organomegaly, or rash or other concerning skin lesions. A complete blood count showed a white cell count of 23 x 10⁹/Land absolute lymphocyte count of 19 x 10⁹/L and normal hemoglobin and platelets.

Based on recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines, additional work-up for this patient might include peripheral smear and flow cytometry, according to Paul Barr, MD.

“A peripheral smear is still useful in this day and age just to ensure that a patient has a typical look under the microscope. We expect to see small mature lymphocytes, smudge cells, and perhaps a smaller number of prolymphocytes. But to mark CLL based on flow cytometry we need to see greater than 5 x 10⁹/L clonal B lymphocytes in the peripheral blood sustained over time,” Dr. Barr, medical director of the clinical trials office for Wilmot Cancer Institute at the University of Rochester (N.Y.), said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

A nuance in the iwCLL guidelines is that CLL also can be defined by a cytopenia caused by a typical marrow infiltrate, regardless of the number of circulating B lymphocytes, he noted.

Immunophenotype

As for CLL immunophenotype, the cells are CD5- and CD23-positive, and additional B cell markers like CD20 are “often dim, and – understandably – the cells are light-chain restricted,” he said.

A subtle difference between the World Health Organization classification of CLL and the iwCLL guidelines is that, by the former, patients can have “a somewhat atypical immunophenotype.”


“So our pathologists, I like to think, use a commonsense approach where, if there are very minor differences, they will still call it CLL, but not if there are major differences in the immunophenotype,” Dr. Barr said.

Patients with lymphadenopathy, without the critical threshold of circulating B lymphocytes, are considered to have small lymphocytic lymphoma (SLL).

“In this day and age we treat CLL and SLL relatively similarly, however, monoclonal B lymphocytosis (MBL) is the precursor lesion to CLL where we see less than 5 x 10⁹/L of circulating B lymphocytes and an absence of adenopathy and disease-related cytopenias,” he noted.

Staging

It is still common practice to stage patients given the prognostic value of staging and given that treatment is provided in advanced disease, Dr. Barr said.

“This is simple, easy to apply, applicable worldwide, and only requires laboratory testing and a physical exam,” he said.

The stages include:

• Stage 0: Lymphocytosis, peripheral lymphocyte count greater than 15,000/mcL and greater than 40% lymphocytes in bone marrow (low-risk disease status).
• Stage I: Stage 0 disease plus enlarged lymph nodes (intermediate-risk disease status).
• Stage II: Stage 0-I disease with splenomegaly and/or hepatomegaly (intermediate-risk disease status).
• Stage III: Stage 0-II disease with hemoglobin less than 11g/dL or hematocrit less than 33% (high-risk disease status).
• Stage IV: Stage 0-III disease with platelet count less than 100,000/mcL (high-risk disease status).

Prognostic testing

Once a patient is diagnosed with CLL, as was the case with the 50-year-old patient Dr. Barr described, a number of tests can be considered to assess prognosis.

There’s no “perfect answer” when it comes to which tests are considered a reasonable standard of care, he noted.

“I would typically perform [immunoglobulin variable heavy-chain gene] mutation testing, a [fluorescence in situ hybridization] panel, and TP53 mutation testing,” he said.

Scoring systems such as CLL-IPI, which combine prognostic factors to divide patients into various risk categories, can be useful.

For example, such systems may identify high-risk patients who might be appropriate candidates for clinical trials, or low-risk patients who could be expected to do well over time despite having advanced stage disease, he explained.

“I do think it’s a useful process to go through to understand a patient’s risk over time,” he added.

However, treatment for CLL still is not based on molecular aberrations/prognostic features. In fact, the treatment indications according to the updated iwCLL guidelines remain exactly the same, he said.

Therefore, the case of the 50-year-old man described earlier would be observed as long as he remained asymptomatic.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

CHICAGO – A 50-year old otherwise healthy man was found on routine history and physical to have lymphocytosis and was referred for additional work-up. He denied recent infection, had no lymphadenopathy, organomegaly, or rash or other concerning skin lesions. A complete blood count showed a white cell count of 23 x 10⁹/Land absolute lymphocyte count of 19 x 10⁹/L and normal hemoglobin and platelets.

Based on recently updated International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines, additional work-up for this patient might include peripheral smear and flow cytometry, according to Paul Barr, MD.

“A peripheral smear is still useful in this day and age just to ensure that a patient has a typical look under the microscope. We expect to see small mature lymphocytes, smudge cells, and perhaps a smaller number of prolymphocytes. But to mark CLL based on flow cytometry we need to see greater than 5 x 10⁹/L clonal B lymphocytes in the peripheral blood sustained over time,” Dr. Barr, medical director of the clinical trials office for Wilmot Cancer Institute at the University of Rochester (N.Y.), said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

A nuance in the iwCLL guidelines is that CLL also can be defined by a cytopenia caused by a typical marrow infiltrate, regardless of the number of circulating B lymphocytes, he noted.

Immunophenotype

As for CLL immunophenotype, the cells are CD5- and CD23-positive, and additional B cell markers like CD20 are “often dim, and – understandably – the cells are light-chain restricted,” he said.

A subtle difference between the World Health Organization classification of CLL and the iwCLL guidelines is that, by the former, patients can have “a somewhat atypical immunophenotype.”


“So our pathologists, I like to think, use a commonsense approach where, if there are very minor differences, they will still call it CLL, but not if there are major differences in the immunophenotype,” Dr. Barr said.

Patients with lymphadenopathy, without the critical threshold of circulating B lymphocytes, are considered to have small lymphocytic lymphoma (SLL).

“In this day and age we treat CLL and SLL relatively similarly, however, monoclonal B lymphocytosis (MBL) is the precursor lesion to CLL where we see less than 5 x 10⁹/L of circulating B lymphocytes and an absence of adenopathy and disease-related cytopenias,” he noted.

Staging

It is still common practice to stage patients given the prognostic value of staging and given that treatment is provided in advanced disease, Dr. Barr said.

“This is simple, easy to apply, applicable worldwide, and only requires laboratory testing and a physical exam,” he said.

The stages include:

• Stage 0: Lymphocytosis, peripheral lymphocyte count greater than 15,000/mcL and greater than 40% lymphocytes in bone marrow (low-risk disease status).
• Stage I: Stage 0 disease plus enlarged lymph nodes (intermediate-risk disease status).
• Stage II: Stage 0-I disease with splenomegaly and/or hepatomegaly (intermediate-risk disease status).
• Stage III: Stage 0-II disease with hemoglobin less than 11g/dL or hematocrit less than 33% (high-risk disease status).
• Stage IV: Stage 0-III disease with platelet count less than 100,000/mcL (high-risk disease status).

Prognostic testing

Once a patient is diagnosed with CLL, as was the case with the 50-year-old patient Dr. Barr described, a number of tests can be considered to assess prognosis.

There’s no “perfect answer” when it comes to which tests are considered a reasonable standard of care, he noted.

“I would typically perform [immunoglobulin variable heavy-chain gene] mutation testing, a [fluorescence in situ hybridization] panel, and TP53 mutation testing,” he said.

Scoring systems such as CLL-IPI, which combine prognostic factors to divide patients into various risk categories, can be useful.

For example, such systems may identify high-risk patients who might be appropriate candidates for clinical trials, or low-risk patients who could be expected to do well over time despite having advanced stage disease, he explained.

“I do think it’s a useful process to go through to understand a patient’s risk over time,” he added.

However, treatment for CLL still is not based on molecular aberrations/prognostic features. In fact, the treatment indications according to the updated iwCLL guidelines remain exactly the same, he said.

Therefore, the case of the 50-year-old man described earlier would be observed as long as he remained asymptomatic.

Dr. Barr is a consultant for Pharmacyclics, AbbVie, Celgene, Gilead, Infinity, Novartis, and Seattle Genetics and has received research funding from Pharmacyclics and AbbVie.

sworcester@mdedge.com

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

It may not seem intuitive, but to understand some of the new skin care claims, you need to know a bit about the gut microbiome and its role in skin health. The skin and gut host a copious and disparate array of bacteria, fungi, viruses, and mites. New research shows us that these microbes play an important role in skin health. The gut and skin play a balancing act between beneficial, neutral, and harmful flora that are interrelated with the innate and adaptive immune systems.¹ The skin and gut seem to be intertwined and express several comorbidities.² In this column, the focus is on the cutaneous microbiome’s role in skin health. To understand the cosmeceutical claims about pre- and probiotics, you first need to familiarize yourself with skin microbiome science. The skin-gut nexus will be discussed in next month’s column, which will address the role of the skin microbiome in skin diseases.

ChrisChrisW/Getty Images

Why is the microbiome such a hot topic?

Genetic sequencing has spurred advances in the study of the microbiome and has provided intriguing clues that the gut and skin microbiome have influences on each other. Sequencing assays that focus on bacterial 16S ribosomal RNA genes have been used by investigators to distinguish and describe the wide variety of resident and transient microorganisms on the skin and elucidate their roles in skin health and disease.¹ Genomic sequencing has identified species in the skin and gut that were not found previously by cultivating microbial isolates.^3,4 Advances in technologies such as whole-genome shotgun sequencing, metagenomics, and functional metabolomics will further contribute to our understanding of the effects of the skin microbiome on skin health and skin type. Of course, many supplement and cosmeceutical companies have jumped on this bandwagon prematurely and claim that their products increase “good bacteria while diminishing bad bacteria.” While there are interesting data that have emerged, we still cannot say which bacteria are “good” and ‘bad” as far as the skin is concerned – with a few exceptions that we have known all along. For example, Cutibacterium acnes and Staphylococcus aureus still remain in the undesirable category. (P. acnes has been renamed and now is officially referred to as C. acnes.) While it is premature to recommend probiotic– or prebiotic–containing cosmeceuticals, your patients will ask you about them. New studies about rosacea and the microbiome have generated a lot of patient questions in my practice, so I am writing several blogs about how to answer patient questions, which can be found at STSFranchise.com/blog. I’m also educating consumers on Facebook and Instagram @skintypesolutions so that they will not be taken advantage of by the too early “pseudoscience.” So now that you have heard that it is too early to recommend pre- and probiotic skin care to target skin issues, let’s look at the science that does exist.

Terminology

• Microbiome: Microbes that live in a particular environment or biome.
• Microbiota: The collection of living microbes that live in or on an environment. This term includes the microorganisms only and not the characteristics of their environment.
• Prebiotics: A nondigestible food ingredient that promotes the growth of microorganisms in the intestines. These can promote the growth of beneficial or harmful microorganisms. Think of them as a type of “fertilizer” for the microbiome.
• Probiotics: Living microorganisms that can provide beneficial qualities when used orally or topically. What probiotics are not? Microbes naturally found in your body and on your skin; microbes that are no longer alive; fermented foods that contain an unknown amount of bacteria.

Skin surface area

Richard Gallo, MD, a dermatologist from the University of California, San Diego, who is a leader in the microbiome field of study, says that estimates of the cutaneous microbiome’s impact on human health via skin have failed to acknowledge the inner follicular surface, thus drastically undervaluing the potential of the cutaneous microbiome to influence systemic health.⁵ He suggests that the surface area of skin has been miscalculated as measuring 2 m² because it is considered a flat surface. This ignores the plethora of hair follicles and sweat ducts that significantly broaden the epithelial surface to measure closer to 25 m² and underscores that the expansive skin microbiome is much larger than previously recognized.⁵ Taking the hair follicle surface area into account, the skin has vast space to harbor various organisms and microbiome environments. What our patients use on their skin certainly influences these environments. The key is trying to figure out how to manipulate the microbiome to our patient’s advantage.

Microbes have environmental preferences

Different microbial species thrive on particular regions of the diverse topography of the expansive surface area and choose their preferred environments from among sebaceous or nonsebaceous, hairy or smooth, moist or dry, and creased or noncreased areas.^6,7 Other host factors that affect which microorganisms colonize the skin include hair follicle thickness, age, sex, diet (especially high fat and sugar intake), climate, occupation, and personal hygiene.^7-10 Gene sequencing has revealed that these variations are partially because of factors such as ultraviolet exposure, pH, and temperature.^4,6,11 For example, C. acnes has been found to be more prevalent in highly sebaceous sites on the head and upper torso.⁴ In general, Propionibacteriaceae (Cutibacterium) prefer sebaceous areas, whereas Corynebacteriaceae and Staphylococcaceae prevail in moist regions, such as the navel or axilla. Dry areas host the widest diversity of microbes, including Corynebacterium, Staphylococcus, and Streptococcus species.^1,7,12

Impact of sebum and skin hydration on microbiome

In 2016, Mukherjee et al. measured sebum and hydration from the forehead and cheeks of 30 healthy female volunteers in a study that tested the hypothesis that differences in sebum and hydration levels in specific facial areas account for interindividual variation in facial skin microbiome. They found that the most significant predictor of microbiome composition was cheek sebum level, followed by forehead hydration level, while cheek hydration and forehead sebum levels were not predictive. The prevalence of Actinobacteria/Propionibacterium rose, while microbiome diversity diminished with an increase in cheek sebum, with such trends reversed in relation to forehead hydration. The investigators concluded that site-specific sebum and water levels impact the nature and diversity of the facial skin microbiome.¹³

Lability of the cutaneous microbiome

The skin microbiome changes during various times of life. For example, in puberty, more lipophilic species such as Propionibacteriaceae and Cornebacteriaceae predominate, while prior to puberty there is a preponderance of Firmicutes, Bacteroidetes, and Proteobacteria.^4,14 However, in the absence of lifestyle changes, cutaneous microbial communities have been found through longitudinal studies to be relatively stable over a 2-year period.⁶ A person’s skin microbiome is subject to influence from an adjacent skin microbiome, such as between cohabiting couples or the influence of breastfeeding mothers.¹⁵ It is never too early to consider the role of the microbiome in health and disease. For example, infant microbiomes play a role in eczema and the atopic march.¹⁶ For this reason, those of us who treat children need to be familiar with studies that have demonstrate how the cutaneous microbiome is affected by childbirth delivery method, breastfeeding, the mother’s diet antibiotic use during pregnancy and breastfeeding.^4,17

Microbiome effects on skin function

The skin barrier, a bilayer lipid-laden membrane that surrounds keratinocytes and prevents transepidermal water loss, is affected by resident microbial communities and has been shown by research to be influenced by the volume and diversity of such microbes.¹⁸ Organisms on the skin’s surface play an important role in communicating with and educating the cutaneous arm of the immune system.¹⁹ In 2017, Maguire and Maguire reviewed recent studies of the gut and skin microbiomes and suggested that Nitrobacter, Lactobacillus, and Bifidobacterium can improve skin health and could be useful bacterial adjuvants in a probiotic and prebiotic strategy in homeostatic renormalization when skin health is compromised.²⁰Nitrobacter has displayed antifungal activity against dermatophytes and Staphylococcus; Lactobacillus has exhibited anti-inflammatory effects and was shown to improve adult acne in a small study; Bifidobacterium combined with Lactobacillus lowered the incidence of atopic eczema in early childhood; and Bifidobacterium and the prebiotic galacto-oligosaccharide prevented hydration level losses in the stratum corneum among other beneficial effects in a double-blind, placebo-controlled, randomized trial.²⁰

Microbiome diversity is key

Microbes interact, collaborate, and oppose one another while exerting influence and being affected by the host. Effective communication among the innate and adaptive parts of the immune system, epithelial cells, and cutaneous microbiota is essential for optimal functioning of the skin.^6,7 Studies on subjects with atopic dermatitis showed a strong association between decreased diversity and increased disease severity. This suggests that a diverse microbiome is associated with skin health.²¹ For this reason, use of pre- and probiotics for skin issues is discouraged at this time. If we replace the normal diverse flora with one organism, we do not yet know the consequences. It is much more likely that successful treatments in the future will contain a diverse group of organisms.

Cosmeceutical effects on the skin microbiome

Cleansing and use of emollients certainly affect the skin biome, but we do not yet know to what extent. A study that looked at the effects of emollients on infants with atopic dermatitis showed that the emollient group has a lower skin pH and a more diverse microbiome.²² In a 2016 study on the impact of acute treatment with topical skin cleansers on the cutaneous microbiome, investigators evaluated multiple common skin cleansers in the washing of human forearms. Group A Streptococcus growth was reduced after washing with soaps infused with such antimicrobial compounds as benzalkonium chloride or triclocarban. The researchers stipulated that much more research is necessary to ascertain the effects of chronic washing as well as the that role skin care products may play in skin homeostasis or dysbiosis in some individuals.²³

In a 2017 analysis of the effects of cosmetics on the skin microbiome of facial cheeks with high- and low-hydration levels over 4 weeks, Lee et al. found that bacterial diversity was higher in the low-hydration group, with increases in both observed after the use of cosmetics. The high-hydration group showed a greater supply of Propionibacterium. Cosmetic use was found not to have caused a shift in bacterial communities in the low-hydration group.²⁴

Conclusion

We are in the early stages as we strive to learn more about the microbiome to leverage such knowledge to improve skin health. In the meantime, there is not enough evidence to suggest the use of any oral or topical prebiotics or probiotics to improve skin health. In fact, we may be causing harm by lessening diversity. The New York Times recently published an article called “The Problem with Probiotics” that referenced a JAMA Internal Medicine article entitled “Probiotic Safety – No Guarantees.”²⁵ I recommend that you read those. Next month, I will look more closely at microbiome research pertaining to skin disease.
 

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Dréno B et al. J Eur Acad Dermatol Venereol. 2016 Dec;30(12):2038-47.

2. O’Neill CA et al. Bioessays. 2016 Nov;38(11):1167-76.

3. Kong HH. Trends Mol Med. 2011 Jun;17(6):320-8.

4. Kong HH et al. J Invest Dermatol. 2017 May;137(5):e119-22.

5. Gallo RL. J Invest Dermatol. 2017 Jun;137(6):1213-4.

6. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

7. Grice EA et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

8. Rodrigues Hoffmann A. Vet Dermatol. 2017 Feb;28(1):60-e15.

9. Moestrup KS et al. J Invest Dermatol. 2018 May;138(5):1225-8.

10. Prescott SL et al. World Allergy Organ J. 2017 Aug 22;10(1):29.

11. Costello EK et al. Science. 2009 Dec 18;326(5960):1694-7.

12. Zeeuwen PL et al. Genome Biol. 2012 Nov 15;13(11):R101.

13. Mukherjee S et al. Sci Rep. 2016 Oct 27;6:36062.

14. Oh J et al. Genome Med. 2012 Oct 10;4(10):77.

15. Ross AA et al. mSystems. 2017 Jul 20;2(4).

16. Blázquez AB et al. Transl Res. 2017 Jan;179:199-203.

17. Rock R et al. Open Forum Infect Dis. 2017 Oct;4(1):S232.

18. Baldwin HE et al. J Drugs Dermatol. 2017 Jan 1;16(1):12-8.

19. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

20. Maguire M et al. Arch Dermatol Res. 2017 Aug;309(6):411-21.

21. Kong HH et al. Genome Res. 2012 May;22(5):850-9.

22. Glatz M et al. PLoS One. 2018 Feb 28;13(2):e0192443.

23. Two AM et al. J Invest Dermatol. 2016 Oct;136(10):1950-4.

24. Lee HJ et al. MicrobiologyOpen. 2018 Apr;7(2):e00557. doi: 10.1002/mbo3.557.

25. Cohen PA. JAMA Intern Med. 2018 Sep 17. doi: 10.1001/jamainternmed.2018.5403.






 

It may not seem intuitive, but to understand some of the new skin care claims, you need to know a bit about the gut microbiome and its role in skin health. The skin and gut host a copious and disparate array of bacteria, fungi, viruses, and mites. New research shows us that these microbes play an important role in skin health. The gut and skin play a balancing act between beneficial, neutral, and harmful flora that are interrelated with the innate and adaptive immune systems.¹ The skin and gut seem to be intertwined and express several comorbidities.² In this column, the focus is on the cutaneous microbiome’s role in skin health. To understand the cosmeceutical claims about pre- and probiotics, you first need to familiarize yourself with skin microbiome science. The skin-gut nexus will be discussed in next month’s column, which will address the role of the skin microbiome in skin diseases.

ChrisChrisW/Getty Images

Why is the microbiome such a hot topic?

Genetic sequencing has spurred advances in the study of the microbiome and has provided intriguing clues that the gut and skin microbiome have influences on each other. Sequencing assays that focus on bacterial 16S ribosomal RNA genes have been used by investigators to distinguish and describe the wide variety of resident and transient microorganisms on the skin and elucidate their roles in skin health and disease.¹ Genomic sequencing has identified species in the skin and gut that were not found previously by cultivating microbial isolates.^3,4 Advances in technologies such as whole-genome shotgun sequencing, metagenomics, and functional metabolomics will further contribute to our understanding of the effects of the skin microbiome on skin health and skin type. Of course, many supplement and cosmeceutical companies have jumped on this bandwagon prematurely and claim that their products increase “good bacteria while diminishing bad bacteria.” While there are interesting data that have emerged, we still cannot say which bacteria are “good” and ‘bad” as far as the skin is concerned – with a few exceptions that we have known all along. For example, Cutibacterium acnes and Staphylococcus aureus still remain in the undesirable category. (P. acnes has been renamed and now is officially referred to as C. acnes.) While it is premature to recommend probiotic– or prebiotic–containing cosmeceuticals, your patients will ask you about them. New studies about rosacea and the microbiome have generated a lot of patient questions in my practice, so I am writing several blogs about how to answer patient questions, which can be found at STSFranchise.com/blog. I’m also educating consumers on Facebook and Instagram @skintypesolutions so that they will not be taken advantage of by the too early “pseudoscience.” So now that you have heard that it is too early to recommend pre- and probiotic skin care to target skin issues, let’s look at the science that does exist.

Terminology

• Microbiome: Microbes that live in a particular environment or biome.
• Microbiota: The collection of living microbes that live in or on an environment. This term includes the microorganisms only and not the characteristics of their environment.
• Prebiotics: A nondigestible food ingredient that promotes the growth of microorganisms in the intestines. These can promote the growth of beneficial or harmful microorganisms. Think of them as a type of “fertilizer” for the microbiome.
• Probiotics: Living microorganisms that can provide beneficial qualities when used orally or topically. What probiotics are not? Microbes naturally found in your body and on your skin; microbes that are no longer alive; fermented foods that contain an unknown amount of bacteria.

Skin surface area

Richard Gallo, MD, a dermatologist from the University of California, San Diego, who is a leader in the microbiome field of study, says that estimates of the cutaneous microbiome’s impact on human health via skin have failed to acknowledge the inner follicular surface, thus drastically undervaluing the potential of the cutaneous microbiome to influence systemic health.⁵ He suggests that the surface area of skin has been miscalculated as measuring 2 m² because it is considered a flat surface. This ignores the plethora of hair follicles and sweat ducts that significantly broaden the epithelial surface to measure closer to 25 m² and underscores that the expansive skin microbiome is much larger than previously recognized.⁵ Taking the hair follicle surface area into account, the skin has vast space to harbor various organisms and microbiome environments. What our patients use on their skin certainly influences these environments. The key is trying to figure out how to manipulate the microbiome to our patient’s advantage.

Microbes have environmental preferences

Different microbial species thrive on particular regions of the diverse topography of the expansive surface area and choose their preferred environments from among sebaceous or nonsebaceous, hairy or smooth, moist or dry, and creased or noncreased areas.^6,7 Other host factors that affect which microorganisms colonize the skin include hair follicle thickness, age, sex, diet (especially high fat and sugar intake), climate, occupation, and personal hygiene.^7-10 Gene sequencing has revealed that these variations are partially because of factors such as ultraviolet exposure, pH, and temperature.^4,6,11 For example, C. acnes has been found to be more prevalent in highly sebaceous sites on the head and upper torso.⁴ In general, Propionibacteriaceae (Cutibacterium) prefer sebaceous areas, whereas Corynebacteriaceae and Staphylococcaceae prevail in moist regions, such as the navel or axilla. Dry areas host the widest diversity of microbes, including Corynebacterium, Staphylococcus, and Streptococcus species.^1,7,12

Impact of sebum and skin hydration on microbiome

In 2016, Mukherjee et al. measured sebum and hydration from the forehead and cheeks of 30 healthy female volunteers in a study that tested the hypothesis that differences in sebum and hydration levels in specific facial areas account for interindividual variation in facial skin microbiome. They found that the most significant predictor of microbiome composition was cheek sebum level, followed by forehead hydration level, while cheek hydration and forehead sebum levels were not predictive. The prevalence of Actinobacteria/Propionibacterium rose, while microbiome diversity diminished with an increase in cheek sebum, with such trends reversed in relation to forehead hydration. The investigators concluded that site-specific sebum and water levels impact the nature and diversity of the facial skin microbiome.¹³

Lability of the cutaneous microbiome

The skin microbiome changes during various times of life. For example, in puberty, more lipophilic species such as Propionibacteriaceae and Cornebacteriaceae predominate, while prior to puberty there is a preponderance of Firmicutes, Bacteroidetes, and Proteobacteria.^4,14 However, in the absence of lifestyle changes, cutaneous microbial communities have been found through longitudinal studies to be relatively stable over a 2-year period.⁶ A person’s skin microbiome is subject to influence from an adjacent skin microbiome, such as between cohabiting couples or the influence of breastfeeding mothers.¹⁵ It is never too early to consider the role of the microbiome in health and disease. For example, infant microbiomes play a role in eczema and the atopic march.¹⁶ For this reason, those of us who treat children need to be familiar with studies that have demonstrate how the cutaneous microbiome is affected by childbirth delivery method, breastfeeding, the mother’s diet antibiotic use during pregnancy and breastfeeding.^4,17

Microbiome effects on skin function

The skin barrier, a bilayer lipid-laden membrane that surrounds keratinocytes and prevents transepidermal water loss, is affected by resident microbial communities and has been shown by research to be influenced by the volume and diversity of such microbes.¹⁸ Organisms on the skin’s surface play an important role in communicating with and educating the cutaneous arm of the immune system.¹⁹ In 2017, Maguire and Maguire reviewed recent studies of the gut and skin microbiomes and suggested that Nitrobacter, Lactobacillus, and Bifidobacterium can improve skin health and could be useful bacterial adjuvants in a probiotic and prebiotic strategy in homeostatic renormalization when skin health is compromised.²⁰Nitrobacter has displayed antifungal activity against dermatophytes and Staphylococcus; Lactobacillus has exhibited anti-inflammatory effects and was shown to improve adult acne in a small study; Bifidobacterium combined with Lactobacillus lowered the incidence of atopic eczema in early childhood; and Bifidobacterium and the prebiotic galacto-oligosaccharide prevented hydration level losses in the stratum corneum among other beneficial effects in a double-blind, placebo-controlled, randomized trial.²⁰

Microbiome diversity is key

Microbes interact, collaborate, and oppose one another while exerting influence and being affected by the host. Effective communication among the innate and adaptive parts of the immune system, epithelial cells, and cutaneous microbiota is essential for optimal functioning of the skin.^6,7 Studies on subjects with atopic dermatitis showed a strong association between decreased diversity and increased disease severity. This suggests that a diverse microbiome is associated with skin health.²¹ For this reason, use of pre- and probiotics for skin issues is discouraged at this time. If we replace the normal diverse flora with one organism, we do not yet know the consequences. It is much more likely that successful treatments in the future will contain a diverse group of organisms.

Cosmeceutical effects on the skin microbiome

Cleansing and use of emollients certainly affect the skin biome, but we do not yet know to what extent. A study that looked at the effects of emollients on infants with atopic dermatitis showed that the emollient group has a lower skin pH and a more diverse microbiome.²² In a 2016 study on the impact of acute treatment with topical skin cleansers on the cutaneous microbiome, investigators evaluated multiple common skin cleansers in the washing of human forearms. Group A Streptococcus growth was reduced after washing with soaps infused with such antimicrobial compounds as benzalkonium chloride or triclocarban. The researchers stipulated that much more research is necessary to ascertain the effects of chronic washing as well as the that role skin care products may play in skin homeostasis or dysbiosis in some individuals.²³

In a 2017 analysis of the effects of cosmetics on the skin microbiome of facial cheeks with high- and low-hydration levels over 4 weeks, Lee et al. found that bacterial diversity was higher in the low-hydration group, with increases in both observed after the use of cosmetics. The high-hydration group showed a greater supply of Propionibacterium. Cosmetic use was found not to have caused a shift in bacterial communities in the low-hydration group.²⁴

Conclusion

We are in the early stages as we strive to learn more about the microbiome to leverage such knowledge to improve skin health. In the meantime, there is not enough evidence to suggest the use of any oral or topical prebiotics or probiotics to improve skin health. In fact, we may be causing harm by lessening diversity. The New York Times recently published an article called “The Problem with Probiotics” that referenced a JAMA Internal Medicine article entitled “Probiotic Safety – No Guarantees.”²⁵ I recommend that you read those. Next month, I will look more closely at microbiome research pertaining to skin disease.
 

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Dréno B et al. J Eur Acad Dermatol Venereol. 2016 Dec;30(12):2038-47.

2. O’Neill CA et al. Bioessays. 2016 Nov;38(11):1167-76.

3. Kong HH. Trends Mol Med. 2011 Jun;17(6):320-8.

4. Kong HH et al. J Invest Dermatol. 2017 May;137(5):e119-22.

5. Gallo RL. J Invest Dermatol. 2017 Jun;137(6):1213-4.

6. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

7. Grice EA et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

8. Rodrigues Hoffmann A. Vet Dermatol. 2017 Feb;28(1):60-e15.

9. Moestrup KS et al. J Invest Dermatol. 2018 May;138(5):1225-8.

10. Prescott SL et al. World Allergy Organ J. 2017 Aug 22;10(1):29.

11. Costello EK et al. Science. 2009 Dec 18;326(5960):1694-7.

12. Zeeuwen PL et al. Genome Biol. 2012 Nov 15;13(11):R101.

13. Mukherjee S et al. Sci Rep. 2016 Oct 27;6:36062.

14. Oh J et al. Genome Med. 2012 Oct 10;4(10):77.

15. Ross AA et al. mSystems. 2017 Jul 20;2(4).

16. Blázquez AB et al. Transl Res. 2017 Jan;179:199-203.

17. Rock R et al. Open Forum Infect Dis. 2017 Oct;4(1):S232.

18. Baldwin HE et al. J Drugs Dermatol. 2017 Jan 1;16(1):12-8.

19. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

20. Maguire M et al. Arch Dermatol Res. 2017 Aug;309(6):411-21.

21. Kong HH et al. Genome Res. 2012 May;22(5):850-9.

22. Glatz M et al. PLoS One. 2018 Feb 28;13(2):e0192443.

23. Two AM et al. J Invest Dermatol. 2016 Oct;136(10):1950-4.

24. Lee HJ et al. MicrobiologyOpen. 2018 Apr;7(2):e00557. doi: 10.1002/mbo3.557.

25. Cohen PA. JAMA Intern Med. 2018 Sep 17. doi: 10.1001/jamainternmed.2018.5403.






 

It may not seem intuitive, but to understand some of the new skin care claims, you need to know a bit about the gut microbiome and its role in skin health. The skin and gut host a copious and disparate array of bacteria, fungi, viruses, and mites. New research shows us that these microbes play an important role in skin health. The gut and skin play a balancing act between beneficial, neutral, and harmful flora that are interrelated with the innate and adaptive immune systems.¹ The skin and gut seem to be intertwined and express several comorbidities.² In this column, the focus is on the cutaneous microbiome’s role in skin health. To understand the cosmeceutical claims about pre- and probiotics, you first need to familiarize yourself with skin microbiome science. The skin-gut nexus will be discussed in next month’s column, which will address the role of the skin microbiome in skin diseases.

ChrisChrisW/Getty Images

Why is the microbiome such a hot topic?

Genetic sequencing has spurred advances in the study of the microbiome and has provided intriguing clues that the gut and skin microbiome have influences on each other. Sequencing assays that focus on bacterial 16S ribosomal RNA genes have been used by investigators to distinguish and describe the wide variety of resident and transient microorganisms on the skin and elucidate their roles in skin health and disease.¹ Genomic sequencing has identified species in the skin and gut that were not found previously by cultivating microbial isolates.^3,4 Advances in technologies such as whole-genome shotgun sequencing, metagenomics, and functional metabolomics will further contribute to our understanding of the effects of the skin microbiome on skin health and skin type. Of course, many supplement and cosmeceutical companies have jumped on this bandwagon prematurely and claim that their products increase “good bacteria while diminishing bad bacteria.” While there are interesting data that have emerged, we still cannot say which bacteria are “good” and ‘bad” as far as the skin is concerned – with a few exceptions that we have known all along. For example, Cutibacterium acnes and Staphylococcus aureus still remain in the undesirable category. (P. acnes has been renamed and now is officially referred to as C. acnes.) While it is premature to recommend probiotic– or prebiotic–containing cosmeceuticals, your patients will ask you about them. New studies about rosacea and the microbiome have generated a lot of patient questions in my practice, so I am writing several blogs about how to answer patient questions, which can be found at STSFranchise.com/blog. I’m also educating consumers on Facebook and Instagram @skintypesolutions so that they will not be taken advantage of by the too early “pseudoscience.” So now that you have heard that it is too early to recommend pre- and probiotic skin care to target skin issues, let’s look at the science that does exist.

Terminology

• Microbiome: Microbes that live in a particular environment or biome.
• Microbiota: The collection of living microbes that live in or on an environment. This term includes the microorganisms only and not the characteristics of their environment.
• Prebiotics: A nondigestible food ingredient that promotes the growth of microorganisms in the intestines. These can promote the growth of beneficial or harmful microorganisms. Think of them as a type of “fertilizer” for the microbiome.
• Probiotics: Living microorganisms that can provide beneficial qualities when used orally or topically. What probiotics are not? Microbes naturally found in your body and on your skin; microbes that are no longer alive; fermented foods that contain an unknown amount of bacteria.

Skin surface area

Richard Gallo, MD, a dermatologist from the University of California, San Diego, who is a leader in the microbiome field of study, says that estimates of the cutaneous microbiome’s impact on human health via skin have failed to acknowledge the inner follicular surface, thus drastically undervaluing the potential of the cutaneous microbiome to influence systemic health.⁵ He suggests that the surface area of skin has been miscalculated as measuring 2 m² because it is considered a flat surface. This ignores the plethora of hair follicles and sweat ducts that significantly broaden the epithelial surface to measure closer to 25 m² and underscores that the expansive skin microbiome is much larger than previously recognized.⁵ Taking the hair follicle surface area into account, the skin has vast space to harbor various organisms and microbiome environments. What our patients use on their skin certainly influences these environments. The key is trying to figure out how to manipulate the microbiome to our patient’s advantage.

Microbes have environmental preferences

Different microbial species thrive on particular regions of the diverse topography of the expansive surface area and choose their preferred environments from among sebaceous or nonsebaceous, hairy or smooth, moist or dry, and creased or noncreased areas.^6,7 Other host factors that affect which microorganisms colonize the skin include hair follicle thickness, age, sex, diet (especially high fat and sugar intake), climate, occupation, and personal hygiene.^7-10 Gene sequencing has revealed that these variations are partially because of factors such as ultraviolet exposure, pH, and temperature.^4,6,11 For example, C. acnes has been found to be more prevalent in highly sebaceous sites on the head and upper torso.⁴ In general, Propionibacteriaceae (Cutibacterium) prefer sebaceous areas, whereas Corynebacteriaceae and Staphylococcaceae prevail in moist regions, such as the navel or axilla. Dry areas host the widest diversity of microbes, including Corynebacterium, Staphylococcus, and Streptococcus species.^1,7,12

Impact of sebum and skin hydration on microbiome

In 2016, Mukherjee et al. measured sebum and hydration from the forehead and cheeks of 30 healthy female volunteers in a study that tested the hypothesis that differences in sebum and hydration levels in specific facial areas account for interindividual variation in facial skin microbiome. They found that the most significant predictor of microbiome composition was cheek sebum level, followed by forehead hydration level, while cheek hydration and forehead sebum levels were not predictive. The prevalence of Actinobacteria/Propionibacterium rose, while microbiome diversity diminished with an increase in cheek sebum, with such trends reversed in relation to forehead hydration. The investigators concluded that site-specific sebum and water levels impact the nature and diversity of the facial skin microbiome.¹³

Lability of the cutaneous microbiome

The skin microbiome changes during various times of life. For example, in puberty, more lipophilic species such as Propionibacteriaceae and Cornebacteriaceae predominate, while prior to puberty there is a preponderance of Firmicutes, Bacteroidetes, and Proteobacteria.^4,14 However, in the absence of lifestyle changes, cutaneous microbial communities have been found through longitudinal studies to be relatively stable over a 2-year period.⁶ A person’s skin microbiome is subject to influence from an adjacent skin microbiome, such as between cohabiting couples or the influence of breastfeeding mothers.¹⁵ It is never too early to consider the role of the microbiome in health and disease. For example, infant microbiomes play a role in eczema and the atopic march.¹⁶ For this reason, those of us who treat children need to be familiar with studies that have demonstrate how the cutaneous microbiome is affected by childbirth delivery method, breastfeeding, the mother’s diet antibiotic use during pregnancy and breastfeeding.^4,17

Microbiome effects on skin function

The skin barrier, a bilayer lipid-laden membrane that surrounds keratinocytes and prevents transepidermal water loss, is affected by resident microbial communities and has been shown by research to be influenced by the volume and diversity of such microbes.¹⁸ Organisms on the skin’s surface play an important role in communicating with and educating the cutaneous arm of the immune system.¹⁹ In 2017, Maguire and Maguire reviewed recent studies of the gut and skin microbiomes and suggested that Nitrobacter, Lactobacillus, and Bifidobacterium can improve skin health and could be useful bacterial adjuvants in a probiotic and prebiotic strategy in homeostatic renormalization when skin health is compromised.²⁰Nitrobacter has displayed antifungal activity against dermatophytes and Staphylococcus; Lactobacillus has exhibited anti-inflammatory effects and was shown to improve adult acne in a small study; Bifidobacterium combined with Lactobacillus lowered the incidence of atopic eczema in early childhood; and Bifidobacterium and the prebiotic galacto-oligosaccharide prevented hydration level losses in the stratum corneum among other beneficial effects in a double-blind, placebo-controlled, randomized trial.²⁰

Microbiome diversity is key

Microbes interact, collaborate, and oppose one another while exerting influence and being affected by the host. Effective communication among the innate and adaptive parts of the immune system, epithelial cells, and cutaneous microbiota is essential for optimal functioning of the skin.^6,7 Studies on subjects with atopic dermatitis showed a strong association between decreased diversity and increased disease severity. This suggests that a diverse microbiome is associated with skin health.²¹ For this reason, use of pre- and probiotics for skin issues is discouraged at this time. If we replace the normal diverse flora with one organism, we do not yet know the consequences. It is much more likely that successful treatments in the future will contain a diverse group of organisms.

Cosmeceutical effects on the skin microbiome

Cleansing and use of emollients certainly affect the skin biome, but we do not yet know to what extent. A study that looked at the effects of emollients on infants with atopic dermatitis showed that the emollient group has a lower skin pH and a more diverse microbiome.²² In a 2016 study on the impact of acute treatment with topical skin cleansers on the cutaneous microbiome, investigators evaluated multiple common skin cleansers in the washing of human forearms. Group A Streptococcus growth was reduced after washing with soaps infused with such antimicrobial compounds as benzalkonium chloride or triclocarban. The researchers stipulated that much more research is necessary to ascertain the effects of chronic washing as well as the that role skin care products may play in skin homeostasis or dysbiosis in some individuals.²³

In a 2017 analysis of the effects of cosmetics on the skin microbiome of facial cheeks with high- and low-hydration levels over 4 weeks, Lee et al. found that bacterial diversity was higher in the low-hydration group, with increases in both observed after the use of cosmetics. The high-hydration group showed a greater supply of Propionibacterium. Cosmetic use was found not to have caused a shift in bacterial communities in the low-hydration group.²⁴

Conclusion

We are in the early stages as we strive to learn more about the microbiome to leverage such knowledge to improve skin health. In the meantime, there is not enough evidence to suggest the use of any oral or topical prebiotics or probiotics to improve skin health. In fact, we may be causing harm by lessening diversity. The New York Times recently published an article called “The Problem with Probiotics” that referenced a JAMA Internal Medicine article entitled “Probiotic Safety – No Guarantees.”²⁵ I recommend that you read those. Next month, I will look more closely at microbiome research pertaining to skin disease.
 

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Dréno B et al. J Eur Acad Dermatol Venereol. 2016 Dec;30(12):2038-47.

2. O’Neill CA et al. Bioessays. 2016 Nov;38(11):1167-76.

3. Kong HH. Trends Mol Med. 2011 Jun;17(6):320-8.

4. Kong HH et al. J Invest Dermatol. 2017 May;137(5):e119-22.

5. Gallo RL. J Invest Dermatol. 2017 Jun;137(6):1213-4.

6. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

7. Grice EA et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

8. Rodrigues Hoffmann A. Vet Dermatol. 2017 Feb;28(1):60-e15.

9. Moestrup KS et al. J Invest Dermatol. 2018 May;138(5):1225-8.

10. Prescott SL et al. World Allergy Organ J. 2017 Aug 22;10(1):29.

11. Costello EK et al. Science. 2009 Dec 18;326(5960):1694-7.

12. Zeeuwen PL et al. Genome Biol. 2012 Nov 15;13(11):R101.

13. Mukherjee S et al. Sci Rep. 2016 Oct 27;6:36062.

14. Oh J et al. Genome Med. 2012 Oct 10;4(10):77.

15. Ross AA et al. mSystems. 2017 Jul 20;2(4).

16. Blázquez AB et al. Transl Res. 2017 Jan;179:199-203.

17. Rock R et al. Open Forum Infect Dis. 2017 Oct;4(1):S232.

18. Baldwin HE et al. J Drugs Dermatol. 2017 Jan 1;16(1):12-8.

19. Byrd AL et al. Nat Rev Microbiol. 2018 Mar;16(3):143-55.

20. Maguire M et al. Arch Dermatol Res. 2017 Aug;309(6):411-21.

21. Kong HH et al. Genome Res. 2012 May;22(5):850-9.

22. Glatz M et al. PLoS One. 2018 Feb 28;13(2):e0192443.

23. Two AM et al. J Invest Dermatol. 2016 Oct;136(10):1950-4.

24. Lee HJ et al. MicrobiologyOpen. 2018 Apr;7(2):e00557. doi: 10.1002/mbo3.557.

25. Cohen PA. JAMA Intern Med. 2018 Sep 17. doi: 10.1001/jamainternmed.2018.5403.






 

CHICAGO – Rituximab demonstrated a high degree of effectiveness with no safety surprises in the first-ever major clinical trial of the potent B-cell inhibitor conducted in pediatric patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis, Jennifer Cooper, MD, PharmD, said at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“This is exciting news. We know that rituximab is very effective in treating adults with GPA and MPA, both in terms of inducing remission and even for maintenance therapy for this rare and severe disease. A lot of pediatric rheumatologists would like to have access to rituximab. Some are even using it for this condition. But until now there were no data in children. I hope this study improves access to rituximab for pediatric patients with ANCA-associated vasculitis,” said Dr. Cooper, a pediatric rheumatologist at the University of Colorado, Denver.

She presented the results of the PePRS (Pediatric Polyangiitis and Rituximab Study), a phase 2a, single-arm, open-label, long-term study of 25 patients in six countries. She anticipates the results will be practice changing, given that pediatric GPA and MPA are recognized as severe systemic autoimmune disorders with a high unmet need for new therapies.

“I don’t believe there are plans for a randomized, controlled trial. Since we now have the pharmacokinetic and safety data in children, we’ll hopefully be able to use extrapolation and our exploratory efficacy endpoints to gain a pediatric indication, or at least a label update for these patients based on this study,” Dr. Cooper continued.


A total of 19 patients had GPA and 6 had MPA, with a median disease duration of 6 months at study entry. All received three pulsed doses of methylprednisolone during the screening period. Then for induction remission they got four once-weekly intravenous infusions of rituximab (Rituxan) at 375 mg/m² as well as oral corticosteroids, which were tapered from 1 mg/kg per day to 0.2 mg/kg per day over the course of the first 6 months. After that, two-thirds of patients received additional rituximab at their provider’s discretion.

The remission rate by 6 months as defined by Pediatric Vasculitis Activity Score (PVAS) criteria was 56%. At 12 months, the rate was 92%, and at 18 months the rate of remission and sustained disease control was 100%. The mean and median durations of remission were 72 and 56 weeks, respectively.

These results in pediatric patients are comparable to those seen in adults in the landmark RAVE (Rituximab in ANCA-Associated Vasculitis) trial (N Engl J Med. 2013 Aug 1;369[5]:417-27), where 64% of patients reached remission at 6 months, Dr. Cooper noted.

All 25 patients were able to tolerate the four rituximab infusions for remission induction. The main side effect was infusion-related reactions. Overall, 32% of patients experienced such reactions in response to their first infusion, 20% with the second, 12% with the third, and only 8% with the fourth.

Eight patients withdrew from the study after 18 months, mostly because of transfer to adult care. The remaining participants were followed for as long as 4.5 years.

F. Hoffmann-La Roche and Genentech sponsored the PePRS study. Dr. Cooper was a Genentech clinical research fellow at the time.

bjancin@mdedge.com

SOURCE: Brogan P at al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L04.

CHICAGO – Rituximab demonstrated a high degree of effectiveness with no safety surprises in the first-ever major clinical trial of the potent B-cell inhibitor conducted in pediatric patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis, Jennifer Cooper, MD, PharmD, said at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“This is exciting news. We know that rituximab is very effective in treating adults with GPA and MPA, both in terms of inducing remission and even for maintenance therapy for this rare and severe disease. A lot of pediatric rheumatologists would like to have access to rituximab. Some are even using it for this condition. But until now there were no data in children. I hope this study improves access to rituximab for pediatric patients with ANCA-associated vasculitis,” said Dr. Cooper, a pediatric rheumatologist at the University of Colorado, Denver.

She presented the results of the PePRS (Pediatric Polyangiitis and Rituximab Study), a phase 2a, single-arm, open-label, long-term study of 25 patients in six countries. She anticipates the results will be practice changing, given that pediatric GPA and MPA are recognized as severe systemic autoimmune disorders with a high unmet need for new therapies.

“I don’t believe there are plans for a randomized, controlled trial. Since we now have the pharmacokinetic and safety data in children, we’ll hopefully be able to use extrapolation and our exploratory efficacy endpoints to gain a pediatric indication, or at least a label update for these patients based on this study,” Dr. Cooper continued.


A total of 19 patients had GPA and 6 had MPA, with a median disease duration of 6 months at study entry. All received three pulsed doses of methylprednisolone during the screening period. Then for induction remission they got four once-weekly intravenous infusions of rituximab (Rituxan) at 375 mg/m² as well as oral corticosteroids, which were tapered from 1 mg/kg per day to 0.2 mg/kg per day over the course of the first 6 months. After that, two-thirds of patients received additional rituximab at their provider’s discretion.

The remission rate by 6 months as defined by Pediatric Vasculitis Activity Score (PVAS) criteria was 56%. At 12 months, the rate was 92%, and at 18 months the rate of remission and sustained disease control was 100%. The mean and median durations of remission were 72 and 56 weeks, respectively.

These results in pediatric patients are comparable to those seen in adults in the landmark RAVE (Rituximab in ANCA-Associated Vasculitis) trial (N Engl J Med. 2013 Aug 1;369[5]:417-27), where 64% of patients reached remission at 6 months, Dr. Cooper noted.

All 25 patients were able to tolerate the four rituximab infusions for remission induction. The main side effect was infusion-related reactions. Overall, 32% of patients experienced such reactions in response to their first infusion, 20% with the second, 12% with the third, and only 8% with the fourth.

Eight patients withdrew from the study after 18 months, mostly because of transfer to adult care. The remaining participants were followed for as long as 4.5 years.

F. Hoffmann-La Roche and Genentech sponsored the PePRS study. Dr. Cooper was a Genentech clinical research fellow at the time.

bjancin@mdedge.com

SOURCE: Brogan P at al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L04.

CHICAGO – Rituximab demonstrated a high degree of effectiveness with no safety surprises in the first-ever major clinical trial of the potent B-cell inhibitor conducted in pediatric patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis, Jennifer Cooper, MD, PharmD, said at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“This is exciting news. We know that rituximab is very effective in treating adults with GPA and MPA, both in terms of inducing remission and even for maintenance therapy for this rare and severe disease. A lot of pediatric rheumatologists would like to have access to rituximab. Some are even using it for this condition. But until now there were no data in children. I hope this study improves access to rituximab for pediatric patients with ANCA-associated vasculitis,” said Dr. Cooper, a pediatric rheumatologist at the University of Colorado, Denver.

She presented the results of the PePRS (Pediatric Polyangiitis and Rituximab Study), a phase 2a, single-arm, open-label, long-term study of 25 patients in six countries. She anticipates the results will be practice changing, given that pediatric GPA and MPA are recognized as severe systemic autoimmune disorders with a high unmet need for new therapies.

“I don’t believe there are plans for a randomized, controlled trial. Since we now have the pharmacokinetic and safety data in children, we’ll hopefully be able to use extrapolation and our exploratory efficacy endpoints to gain a pediatric indication, or at least a label update for these patients based on this study,” Dr. Cooper continued.


A total of 19 patients had GPA and 6 had MPA, with a median disease duration of 6 months at study entry. All received three pulsed doses of methylprednisolone during the screening period. Then for induction remission they got four once-weekly intravenous infusions of rituximab (Rituxan) at 375 mg/m² as well as oral corticosteroids, which were tapered from 1 mg/kg per day to 0.2 mg/kg per day over the course of the first 6 months. After that, two-thirds of patients received additional rituximab at their provider’s discretion.

The remission rate by 6 months as defined by Pediatric Vasculitis Activity Score (PVAS) criteria was 56%. At 12 months, the rate was 92%, and at 18 months the rate of remission and sustained disease control was 100%. The mean and median durations of remission were 72 and 56 weeks, respectively.

These results in pediatric patients are comparable to those seen in adults in the landmark RAVE (Rituximab in ANCA-Associated Vasculitis) trial (N Engl J Med. 2013 Aug 1;369[5]:417-27), where 64% of patients reached remission at 6 months, Dr. Cooper noted.

All 25 patients were able to tolerate the four rituximab infusions for remission induction. The main side effect was infusion-related reactions. Overall, 32% of patients experienced such reactions in response to their first infusion, 20% with the second, 12% with the third, and only 8% with the fourth.

Eight patients withdrew from the study after 18 months, mostly because of transfer to adult care. The remaining participants were followed for as long as 4.5 years.

F. Hoffmann-La Roche and Genentech sponsored the PePRS study. Dr. Cooper was a Genentech clinical research fellow at the time.

bjancin@mdedge.com

SOURCE: Brogan P at al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L04.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

jensmith@mdedge.com

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

jensmith@mdedge.com

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

jensmith@mdedge.com