NEW ORLEANS – The visual system is relevant and accessible for the study of multiple sclerosis and can aid in the measurement of neuronal and axonal injury.

Capturing primary neuronal loss in the afferent visual pathway was among the topics addressed during a session focused on novel methods for measuring disease progression in MS at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In this video interview at the meeting, session chair Dr. Fiona Costello of the University of Calgary, Alta., discussed the presentation on the visual pathway, as well as presentations on the use of microRNA biomarkers and the use of MRI as an outcome measure in progressive MS.

“The gestalt is that the field is moving in a new direction; the field is looking for not only a better understanding of what causes disability in MS, but also more reliable, objective, accessible means of capturing the same thing that is relevant and meaningful to patients and their caretakers,” she said.

sworcester@frontlinemedcom.com

NEW ORLEANS – The visual system is relevant and accessible for the study of multiple sclerosis and can aid in the measurement of neuronal and axonal injury.

Capturing primary neuronal loss in the afferent visual pathway was among the topics addressed during a session focused on novel methods for measuring disease progression in MS at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In this video interview at the meeting, session chair Dr. Fiona Costello of the University of Calgary, Alta., discussed the presentation on the visual pathway, as well as presentations on the use of microRNA biomarkers and the use of MRI as an outcome measure in progressive MS.

“The gestalt is that the field is moving in a new direction; the field is looking for not only a better understanding of what causes disability in MS, but also more reliable, objective, accessible means of capturing the same thing that is relevant and meaningful to patients and their caretakers,” she said.

sworcester@frontlinemedcom.com

NEW ORLEANS – The visual system is relevant and accessible for the study of multiple sclerosis and can aid in the measurement of neuronal and axonal injury.

Capturing primary neuronal loss in the afferent visual pathway was among the topics addressed during a session focused on novel methods for measuring disease progression in MS at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In this video interview at the meeting, session chair Dr. Fiona Costello of the University of Calgary, Alta., discussed the presentation on the visual pathway, as well as presentations on the use of microRNA biomarkers and the use of MRI as an outcome measure in progressive MS.

“The gestalt is that the field is moving in a new direction; the field is looking for not only a better understanding of what causes disability in MS, but also more reliable, objective, accessible means of capturing the same thing that is relevant and meaningful to patients and their caretakers,” she said.

sworcester@frontlinemedcom.com

ABSTRACT

Objective Medical scribes are increasingly employed to improve physician efficiency with regard to the electronic medical record (EMR). The impact of scribes on the quality of outpatient visit notes is not known. To assess the effect, we conducted a retrospective review of ambulatory progress notes written before and after 8 practice sites transitioned to the use of medical assistants as scribes.

Methods The Physician Documentation Quality Instrument 9 (PDQI-9) was used to compare the quality of outpatient progress notes written by medical assistant scribes with the quality of notes written by 18 primary care physicians working without a scribe. The notes pertained to diabetes encounters and same-day appointments and were written during the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after scribes were employed (scribe period).

Results One hundred eight notes from the pre-scribe period and 109 from the scribe period were reviewed. Scribed notes were rated higher in overall quality than unscribed notes (mean total PDQI-9 score 30.3 for scribed notes vs 28.9 for nonscribed notes; P=.01) and more up-to-date, thorough, useful, and comprehensible. The differences were limited to diabetes encounters. For same-day appointments, scribed and nonscribed notes did not differ in quality. The total word count of all scribed and nonscribed notes was similar (mean words 618, standard deviation (SD) 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

Conclusions In this retrospective review, ambulatory notes were of higher quality when medical assistants acted as scribes than when physicians wrote them alone, at least for diabetes visits. Our findings may not apply to professional scribes who are not part of the clinical care team. As the use of medical scribes expands, additional studies should examine the impact of scribes on other aspects of care quality.

Team-based models of primary care delivery may incorporate medical scribes to improve efficiency of electronic documentation.^1-4 The employment of medical scribes has grown rapidly, and it is estimated that within several years there may be one scribe for every 9 physicians.³

Accurate documentation is important to providing high-quality patient care but can take a significant amount of time. Attending physicians have been estimated to spend as long as 52 minutes per day authoring notes.⁵ Medical scribes can help physicians improve the efficiency of electronic documentation⁶ and save time.² Using scribes can also improve physician productivity^7-10 and thereby potentially increase access to care. The impact of scribes on the quality of outpatient visit notes, however, is unknown.

A team-based care delivery model in our health system’s primary care clinics uses medical assistants to scribe notes during the outpatient encounter. We hypothesized that outpatient notes written by medical assistant scribes would be of similar quality to notes written by the same group of physicians without a scribe.

METHODS

Study design and sample

We conducted a retrospective review of ambulatory notes from 18 primary care physicians at 8 practice sites in our health system who had adopted a care model in which medical assistants act as scribes. Each physician works with 2 medical assistants. To train for the new model, the physician and medical assistants participated in 2 training sessions of 2 hours each and a half day of clinic observation and evaluation with a project manager.

Scribed notes were more up-to-date, thorough, useful, and comprehensible for diabetes encounters.

Of the 18 primary care physicians included in this study, none had less than one year of experience in our health system. Tenure ranged from one to 24 years with a mean of 11.3 years.

For each participating provider, we requested all available outpatient progress notes with either an International Classification of Diseases, 9th revision (ICD-9) code for diabetes or a designation of “same day” for the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after employing scribes (scribe period). We chose diabetes encounters as examples of notes addressing chronic disease management and same-day encounters as examples of problem-focused notes because these 2 types of encounters are common in outpatient primary care practice.

Note quality was evaluated using the Physician Documentation Quality Instrument 9 (PDQI-9), a validated instrument designed for this purpose, comprising 9 items rated subjectively on a 5-point Likert scale (1= not at all, 5= extremely). The items assess whether notes are up-to-date, accurate, thorough, useful, organized, comprehensible, succinct, synthesized, and internally consistent.^11,12 The PDQI-9 has been applied previously in inpatient¹² and outpatient settings.¹³

While the PDQI-9 is a validated tool, it relies on subjective ratings of note quality by the reviewer. To control for the subjective nature of the ratings, an experienced internist and an internal medicine resident coded 10 progress notes separately using the PDQI-9 and discussed the results. The process was repeated for a total of 20 notes, after which consensus was reached with >70% agreement on each attribute of the PDQI-9, suggesting that the resident’s ratings were reliable when compared with those of an experienced practicing physician.

The resident then evaluated a random sample of notes written by each physician for diabetes or same-day appointments in the pre-scribe and scribe periods. Word counts for the entire note were measured. The notes used to establish the reliability of the ratings were excluded from the analysis for this study.

Data analysis

We used linear mixed-effects models to examine note quality measures by adjusting for possible correlations of notes from the same physician. Least-squares estimates were derived; the results were not adjusted for multiple comparisons.

RESULTS

One hundred eight notes from the pre-scribe period and 109 notes from the scribe period were reviewed. Compared with notes written by a physician alone, scribed notes were rated slightly higher in overall quality (mean total PDQI-9 score 30.3 for scribe notes vs 28.9 for pre-scribe notes; P=.01) and more up-to-date, thorough, useful, and comprehensible (TABLES 1 AND 2). The differences were limited to diabetes encounters. For same day appointments, scribed notes did not differ in quality from nonscribed notes (TABLE 2). Total word count did not vary significantly between all scribe and pre-scribe notes (mean words 618, SD 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

DISCUSSION

In this retrospective review of ambulatory notes, progress notes written by medical assistant scribes were of higher quality than notes physicians wrote alone, at least for diabetes visits. Scribe and pre-scribe notes were of similar quality for problem-focused same-day visits. This is the first study of which we are aware that compares the quality of scribed notes with notes written by physicians.

Quality scribe notes can save physician time. The progress note is an important vehicle for describing care provided and transferring information among physicians caring for the same patient. Writing a note, however, adds a considerable amount of time to the physician’s workflow. Using a scribe can decrease the time burden of note writing, and if scribed notes are of similar or better quality, this practice innovation can allow the physician to focus more on clinical than clerical tasks.

Over-documentation is a possible concern. While implementation of the EMR may improve certain aspects of quality of care delivered^14,15 and note quality,¹⁶ concern has been raised about over-documentation related to the connection between documentation and reimbursement.¹⁷ In our study, we found that physician notes and scribed notes for both diabetes and same-day encounters often used EMR-based note templates, which can lead to over-documentation.

Future EMR development might best focus on planned utilization by physician-scribe teams.

In general, both physician and scribed notes were rated to be of average to low quality because none of the mean scores on the 9 individual components of the PDQI-9 reached 4.0. Scribed notes were not inaccurate and had word counts similar to physician notes.

Scribing has potential drawbacks—and benefits. Drawbacks to scribing have not been well-studied. It has been suggested that using scribes to work around the EMR may actually hinder its further advancement because scribing insulates physicians from the inefficiencies of current EMRs and will not spur demands for improvements.³ Inaccurate or poor-quality notes could represent another downside to scribing, although concern about the quality of notes has not been documented. Our results suggest the opposite may be true.

Note quality has not been associated with quality of care as assessed by clinical quality scores,¹³ but using scribes may improve the quality of care in other ways. For example, the EMR may negatively affect patient-physician communication,^18,19 and freeing the physician from documentation may improve the interaction.^8,20 Incorporating scribing into practice may also improve the physician experience,^9,10,21,22 a possible benefit that we did not measure.

We also did not measure the cost of using a scribe to assist in EMR documentation compared with the cost of physician time spent in performing this task. If the scribe model were associated with cost savings through increased physician productivity, as well as improved physician experience, future EMR development might best focus on planned utilization by physician-scribe teams.

Study limitations. The study was conducted in a single health system, although at 8 different practice sites. The sites all used the same EMR, but templates used for documentation could be individualized by the physician and medical assistant team, so our findings may reflect variation in template design. Our analysis did adjust for possible correlations of notes from the same physician. The selection of note types in our study may make our results less generalizable to other encounter types. Our sample was not large enough to detect variations in note quality among different providers and scribes.

The ratings on the PDQI-9 may be subjective, and the reviewers were not blinded to whether a scribe was used to write the note. The differences in PDQI-9 scores were small. Although statistically significant, they may not significantly affect clinical practice. Our care model is unique in that scribes are active members of the clinical care team; the higher quality of scribed notes we found may not apply to professional scribes who are not part of the team.

Future research directions. In our study, medical assistants acting as scribes composed progress notes of similar or higher quality than physicians who wrote notes alone, although all notes were of generally average quality. As the use of scribes in medicine expands, additional studies should examine the impact of scribes on primary care workflow, quality and cost of care delivered, and quality of physician experience.

CORRESPONDENCE
Anita D. Misra-Hebert, MD, MPH, Center for Value-Based Care Research, Medicine Institute, 9500 Euclid Avenue, G10, Cleveland, OH 44195; misraa@ccf.org.

ABSTRACT

Objective Medical scribes are increasingly employed to improve physician efficiency with regard to the electronic medical record (EMR). The impact of scribes on the quality of outpatient visit notes is not known. To assess the effect, we conducted a retrospective review of ambulatory progress notes written before and after 8 practice sites transitioned to the use of medical assistants as scribes.

Methods The Physician Documentation Quality Instrument 9 (PDQI-9) was used to compare the quality of outpatient progress notes written by medical assistant scribes with the quality of notes written by 18 primary care physicians working without a scribe. The notes pertained to diabetes encounters and same-day appointments and were written during the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after scribes were employed (scribe period).

Results One hundred eight notes from the pre-scribe period and 109 from the scribe period were reviewed. Scribed notes were rated higher in overall quality than unscribed notes (mean total PDQI-9 score 30.3 for scribed notes vs 28.9 for nonscribed notes; P=.01) and more up-to-date, thorough, useful, and comprehensible. The differences were limited to diabetes encounters. For same-day appointments, scribed and nonscribed notes did not differ in quality. The total word count of all scribed and nonscribed notes was similar (mean words 618, standard deviation (SD) 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

Conclusions In this retrospective review, ambulatory notes were of higher quality when medical assistants acted as scribes than when physicians wrote them alone, at least for diabetes visits. Our findings may not apply to professional scribes who are not part of the clinical care team. As the use of medical scribes expands, additional studies should examine the impact of scribes on other aspects of care quality.

Team-based models of primary care delivery may incorporate medical scribes to improve efficiency of electronic documentation.^1-4 The employment of medical scribes has grown rapidly, and it is estimated that within several years there may be one scribe for every 9 physicians.³

Accurate documentation is important to providing high-quality patient care but can take a significant amount of time. Attending physicians have been estimated to spend as long as 52 minutes per day authoring notes.⁵ Medical scribes can help physicians improve the efficiency of electronic documentation⁶ and save time.² Using scribes can also improve physician productivity^7-10 and thereby potentially increase access to care. The impact of scribes on the quality of outpatient visit notes, however, is unknown.

A team-based care delivery model in our health system’s primary care clinics uses medical assistants to scribe notes during the outpatient encounter. We hypothesized that outpatient notes written by medical assistant scribes would be of similar quality to notes written by the same group of physicians without a scribe.

METHODS

Study design and sample

We conducted a retrospective review of ambulatory notes from 18 primary care physicians at 8 practice sites in our health system who had adopted a care model in which medical assistants act as scribes. Each physician works with 2 medical assistants. To train for the new model, the physician and medical assistants participated in 2 training sessions of 2 hours each and a half day of clinic observation and evaluation with a project manager.

Scribed notes were more up-to-date, thorough, useful, and comprehensible for diabetes encounters.

Of the 18 primary care physicians included in this study, none had less than one year of experience in our health system. Tenure ranged from one to 24 years with a mean of 11.3 years.

For each participating provider, we requested all available outpatient progress notes with either an International Classification of Diseases, 9th revision (ICD-9) code for diabetes or a designation of “same day” for the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after employing scribes (scribe period). We chose diabetes encounters as examples of notes addressing chronic disease management and same-day encounters as examples of problem-focused notes because these 2 types of encounters are common in outpatient primary care practice.

Note quality was evaluated using the Physician Documentation Quality Instrument 9 (PDQI-9), a validated instrument designed for this purpose, comprising 9 items rated subjectively on a 5-point Likert scale (1= not at all, 5= extremely). The items assess whether notes are up-to-date, accurate, thorough, useful, organized, comprehensible, succinct, synthesized, and internally consistent.^11,12 The PDQI-9 has been applied previously in inpatient¹² and outpatient settings.¹³

While the PDQI-9 is a validated tool, it relies on subjective ratings of note quality by the reviewer. To control for the subjective nature of the ratings, an experienced internist and an internal medicine resident coded 10 progress notes separately using the PDQI-9 and discussed the results. The process was repeated for a total of 20 notes, after which consensus was reached with >70% agreement on each attribute of the PDQI-9, suggesting that the resident’s ratings were reliable when compared with those of an experienced practicing physician.

The resident then evaluated a random sample of notes written by each physician for diabetes or same-day appointments in the pre-scribe and scribe periods. Word counts for the entire note were measured. The notes used to establish the reliability of the ratings were excluded from the analysis for this study.

Data analysis

We used linear mixed-effects models to examine note quality measures by adjusting for possible correlations of notes from the same physician. Least-squares estimates were derived; the results were not adjusted for multiple comparisons.

RESULTS

One hundred eight notes from the pre-scribe period and 109 notes from the scribe period were reviewed. Compared with notes written by a physician alone, scribed notes were rated slightly higher in overall quality (mean total PDQI-9 score 30.3 for scribe notes vs 28.9 for pre-scribe notes; P=.01) and more up-to-date, thorough, useful, and comprehensible (TABLES 1 AND 2). The differences were limited to diabetes encounters. For same day appointments, scribed notes did not differ in quality from nonscribed notes (TABLE 2). Total word count did not vary significantly between all scribe and pre-scribe notes (mean words 618, SD 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

DISCUSSION

In this retrospective review of ambulatory notes, progress notes written by medical assistant scribes were of higher quality than notes physicians wrote alone, at least for diabetes visits. Scribe and pre-scribe notes were of similar quality for problem-focused same-day visits. This is the first study of which we are aware that compares the quality of scribed notes with notes written by physicians.

Quality scribe notes can save physician time. The progress note is an important vehicle for describing care provided and transferring information among physicians caring for the same patient. Writing a note, however, adds a considerable amount of time to the physician’s workflow. Using a scribe can decrease the time burden of note writing, and if scribed notes are of similar or better quality, this practice innovation can allow the physician to focus more on clinical than clerical tasks.

Over-documentation is a possible concern. While implementation of the EMR may improve certain aspects of quality of care delivered^14,15 and note quality,¹⁶ concern has been raised about over-documentation related to the connection between documentation and reimbursement.¹⁷ In our study, we found that physician notes and scribed notes for both diabetes and same-day encounters often used EMR-based note templates, which can lead to over-documentation.

Future EMR development might best focus on planned utilization by physician-scribe teams.

In general, both physician and scribed notes were rated to be of average to low quality because none of the mean scores on the 9 individual components of the PDQI-9 reached 4.0. Scribed notes were not inaccurate and had word counts similar to physician notes.

Scribing has potential drawbacks—and benefits. Drawbacks to scribing have not been well-studied. It has been suggested that using scribes to work around the EMR may actually hinder its further advancement because scribing insulates physicians from the inefficiencies of current EMRs and will not spur demands for improvements.³ Inaccurate or poor-quality notes could represent another downside to scribing, although concern about the quality of notes has not been documented. Our results suggest the opposite may be true.

Note quality has not been associated with quality of care as assessed by clinical quality scores,¹³ but using scribes may improve the quality of care in other ways. For example, the EMR may negatively affect patient-physician communication,^18,19 and freeing the physician from documentation may improve the interaction.^8,20 Incorporating scribing into practice may also improve the physician experience,^9,10,21,22 a possible benefit that we did not measure.

We also did not measure the cost of using a scribe to assist in EMR documentation compared with the cost of physician time spent in performing this task. If the scribe model were associated with cost savings through increased physician productivity, as well as improved physician experience, future EMR development might best focus on planned utilization by physician-scribe teams.

Study limitations. The study was conducted in a single health system, although at 8 different practice sites. The sites all used the same EMR, but templates used for documentation could be individualized by the physician and medical assistant team, so our findings may reflect variation in template design. Our analysis did adjust for possible correlations of notes from the same physician. The selection of note types in our study may make our results less generalizable to other encounter types. Our sample was not large enough to detect variations in note quality among different providers and scribes.

The ratings on the PDQI-9 may be subjective, and the reviewers were not blinded to whether a scribe was used to write the note. The differences in PDQI-9 scores were small. Although statistically significant, they may not significantly affect clinical practice. Our care model is unique in that scribes are active members of the clinical care team; the higher quality of scribed notes we found may not apply to professional scribes who are not part of the team.

Future research directions. In our study, medical assistants acting as scribes composed progress notes of similar or higher quality than physicians who wrote notes alone, although all notes were of generally average quality. As the use of scribes in medicine expands, additional studies should examine the impact of scribes on primary care workflow, quality and cost of care delivered, and quality of physician experience.

CORRESPONDENCE
Anita D. Misra-Hebert, MD, MPH, Center for Value-Based Care Research, Medicine Institute, 9500 Euclid Avenue, G10, Cleveland, OH 44195; misraa@ccf.org.

ABSTRACT

Objective Medical scribes are increasingly employed to improve physician efficiency with regard to the electronic medical record (EMR). The impact of scribes on the quality of outpatient visit notes is not known. To assess the effect, we conducted a retrospective review of ambulatory progress notes written before and after 8 practice sites transitioned to the use of medical assistants as scribes.

Methods The Physician Documentation Quality Instrument 9 (PDQI-9) was used to compare the quality of outpatient progress notes written by medical assistant scribes with the quality of notes written by 18 primary care physicians working without a scribe. The notes pertained to diabetes encounters and same-day appointments and were written during the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after scribes were employed (scribe period).

Results One hundred eight notes from the pre-scribe period and 109 from the scribe period were reviewed. Scribed notes were rated higher in overall quality than unscribed notes (mean total PDQI-9 score 30.3 for scribed notes vs 28.9 for nonscribed notes; P=.01) and more up-to-date, thorough, useful, and comprehensible. The differences were limited to diabetes encounters. For same-day appointments, scribed and nonscribed notes did not differ in quality. The total word count of all scribed and nonscribed notes was similar (mean words 618, standard deviation (SD) 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

Conclusions In this retrospective review, ambulatory notes were of higher quality when medical assistants acted as scribes than when physicians wrote them alone, at least for diabetes visits. Our findings may not apply to professional scribes who are not part of the clinical care team. As the use of medical scribes expands, additional studies should examine the impact of scribes on other aspects of care quality.

Team-based models of primary care delivery may incorporate medical scribes to improve efficiency of electronic documentation.^1-4 The employment of medical scribes has grown rapidly, and it is estimated that within several years there may be one scribe for every 9 physicians.³

Accurate documentation is important to providing high-quality patient care but can take a significant amount of time. Attending physicians have been estimated to spend as long as 52 minutes per day authoring notes.⁵ Medical scribes can help physicians improve the efficiency of electronic documentation⁶ and save time.² Using scribes can also improve physician productivity^7-10 and thereby potentially increase access to care. The impact of scribes on the quality of outpatient visit notes, however, is unknown.

A team-based care delivery model in our health system’s primary care clinics uses medical assistants to scribe notes during the outpatient encounter. We hypothesized that outpatient notes written by medical assistant scribes would be of similar quality to notes written by the same group of physicians without a scribe.

METHODS

Study design and sample

We conducted a retrospective review of ambulatory notes from 18 primary care physicians at 8 practice sites in our health system who had adopted a care model in which medical assistants act as scribes. Each physician works with 2 medical assistants. To train for the new model, the physician and medical assistants participated in 2 training sessions of 2 hours each and a half day of clinic observation and evaluation with a project manager.

Scribed notes were more up-to-date, thorough, useful, and comprehensible for diabetes encounters.

Of the 18 primary care physicians included in this study, none had less than one year of experience in our health system. Tenure ranged from one to 24 years with a mean of 11.3 years.

For each participating provider, we requested all available outpatient progress notes with either an International Classification of Diseases, 9th revision (ICD-9) code for diabetes or a designation of “same day” for the 3 to 6 months preceding the use of scribes (pre-scribe period) and the 3 to 6 months after employing scribes (scribe period). We chose diabetes encounters as examples of notes addressing chronic disease management and same-day encounters as examples of problem-focused notes because these 2 types of encounters are common in outpatient primary care practice.

Note quality was evaluated using the Physician Documentation Quality Instrument 9 (PDQI-9), a validated instrument designed for this purpose, comprising 9 items rated subjectively on a 5-point Likert scale (1= not at all, 5= extremely). The items assess whether notes are up-to-date, accurate, thorough, useful, organized, comprehensible, succinct, synthesized, and internally consistent.^11,12 The PDQI-9 has been applied previously in inpatient¹² and outpatient settings.¹³

While the PDQI-9 is a validated tool, it relies on subjective ratings of note quality by the reviewer. To control for the subjective nature of the ratings, an experienced internist and an internal medicine resident coded 10 progress notes separately using the PDQI-9 and discussed the results. The process was repeated for a total of 20 notes, after which consensus was reached with >70% agreement on each attribute of the PDQI-9, suggesting that the resident’s ratings were reliable when compared with those of an experienced practicing physician.

The resident then evaluated a random sample of notes written by each physician for diabetes or same-day appointments in the pre-scribe and scribe periods. Word counts for the entire note were measured. The notes used to establish the reliability of the ratings were excluded from the analysis for this study.

Data analysis

We used linear mixed-effects models to examine note quality measures by adjusting for possible correlations of notes from the same physician. Least-squares estimates were derived; the results were not adjusted for multiple comparisons.

RESULTS

One hundred eight notes from the pre-scribe period and 109 notes from the scribe period were reviewed. Compared with notes written by a physician alone, scribed notes were rated slightly higher in overall quality (mean total PDQI-9 score 30.3 for scribe notes vs 28.9 for pre-scribe notes; P=.01) and more up-to-date, thorough, useful, and comprehensible (TABLES 1 AND 2). The differences were limited to diabetes encounters. For same day appointments, scribed notes did not differ in quality from nonscribed notes (TABLE 2). Total word count did not vary significantly between all scribe and pre-scribe notes (mean words 618, SD 273 for scribed notes vs 558 words, SD 289 for nonscribed notes; P=.12).

DISCUSSION

In this retrospective review of ambulatory notes, progress notes written by medical assistant scribes were of higher quality than notes physicians wrote alone, at least for diabetes visits. Scribe and pre-scribe notes were of similar quality for problem-focused same-day visits. This is the first study of which we are aware that compares the quality of scribed notes with notes written by physicians.

Quality scribe notes can save physician time. The progress note is an important vehicle for describing care provided and transferring information among physicians caring for the same patient. Writing a note, however, adds a considerable amount of time to the physician’s workflow. Using a scribe can decrease the time burden of note writing, and if scribed notes are of similar or better quality, this practice innovation can allow the physician to focus more on clinical than clerical tasks.

Over-documentation is a possible concern. While implementation of the EMR may improve certain aspects of quality of care delivered^14,15 and note quality,¹⁶ concern has been raised about over-documentation related to the connection between documentation and reimbursement.¹⁷ In our study, we found that physician notes and scribed notes for both diabetes and same-day encounters often used EMR-based note templates, which can lead to over-documentation.

Future EMR development might best focus on planned utilization by physician-scribe teams.

In general, both physician and scribed notes were rated to be of average to low quality because none of the mean scores on the 9 individual components of the PDQI-9 reached 4.0. Scribed notes were not inaccurate and had word counts similar to physician notes.

Scribing has potential drawbacks—and benefits. Drawbacks to scribing have not been well-studied. It has been suggested that using scribes to work around the EMR may actually hinder its further advancement because scribing insulates physicians from the inefficiencies of current EMRs and will not spur demands for improvements.³ Inaccurate or poor-quality notes could represent another downside to scribing, although concern about the quality of notes has not been documented. Our results suggest the opposite may be true.

Note quality has not been associated with quality of care as assessed by clinical quality scores,¹³ but using scribes may improve the quality of care in other ways. For example, the EMR may negatively affect patient-physician communication,^18,19 and freeing the physician from documentation may improve the interaction.^8,20 Incorporating scribing into practice may also improve the physician experience,^9,10,21,22 a possible benefit that we did not measure.

We also did not measure the cost of using a scribe to assist in EMR documentation compared with the cost of physician time spent in performing this task. If the scribe model were associated with cost savings through increased physician productivity, as well as improved physician experience, future EMR development might best focus on planned utilization by physician-scribe teams.

Study limitations. The study was conducted in a single health system, although at 8 different practice sites. The sites all used the same EMR, but templates used for documentation could be individualized by the physician and medical assistant team, so our findings may reflect variation in template design. Our analysis did adjust for possible correlations of notes from the same physician. The selection of note types in our study may make our results less generalizable to other encounter types. Our sample was not large enough to detect variations in note quality among different providers and scribes.

The ratings on the PDQI-9 may be subjective, and the reviewers were not blinded to whether a scribe was used to write the note. The differences in PDQI-9 scores were small. Although statistically significant, they may not significantly affect clinical practice. Our care model is unique in that scribes are active members of the clinical care team; the higher quality of scribed notes we found may not apply to professional scribes who are not part of the team.

Future research directions. In our study, medical assistants acting as scribes composed progress notes of similar or higher quality than physicians who wrote notes alone, although all notes were of generally average quality. As the use of scribes in medicine expands, additional studies should examine the impact of scribes on primary care workflow, quality and cost of care delivered, and quality of physician experience.

CORRESPONDENCE
Anita D. Misra-Hebert, MD, MPH, Center for Value-Based Care Research, Medicine Institute, 9500 Euclid Avenue, G10, Cleveland, OH 44195; misraa@ccf.org.

In patients with acute liver failure (ALF), decreasing platelet counts after hospital admission signaled systemic inflammation and a greater likelihood of systemic complications, such as high-grade hepatic encephalopathy, cardiovascular collapse, the need for liver transplant, and death, according to researchers.

Patients with systemic inflammatory response syndrome (SIRS) had significantly lower platelet counts at admission, compared with those without SIRS, and their platelet counts decreased dramatically (from 182 plus or minus 27 times 10⁹/L on admission to 103 plus or minus 3.20 times 10⁹/L on day 6) compared with stable platelet counts in patients without SIRS. For days 2-7 postadmission, lower platelet counts were associated with high-grade hepatic encephalopathy, as well as the need for vasopressor support and renal replacement therapy (P less than or equal to .001 for all).

©pixologicstudio/thinkstockphotos.com

“We hypothesize that the decrease in platelet count represents an integral event in the pathogenesis of the ALF syndrome rather than a nonspecific marker of suppressed bone marrow production. Further studies will be needed to prove the pivotal role of platelets in mediating the proinflammatory and prothrombotic features of the ALF syndrome,” wrote Dr. R. Todd Stravitz, professor of medicine, section of hepatology, Virginia Commonwealth University, Richmond, and his colleagues (Clin Gastroenterol Hepatol. 2016 Feb 25. doi: 10.1016/j.cgh.2015.09.029).

Results showed that SIRS and multiorgan system failure (MOSF) were more closely linked to a decrease in platelet counts than to an increase in the international normalized ratio (INR), a laboratory marker for liver injury. The INR was similar in patients with and without SIRS, in high-grade and low-grade hepatic encephalopathy, and in patients with and without requirements for vasopressor support and renal replacement therapy (indicators of MOSF). Given that both platelet counts and INR were associated with prognosis, the investigators suggest that these laboratory parameters may reflect different types of injury, with INR signaling primary liver injury and platelets reflecting the severity of systemic inflammation secondary to liver injury.

Platelet counts varied according to outcome on day 21. Spontaneous survivors had higher mean platelet counts than patients who underwent liver transplant, and patients who died had the lowest platelet counts. Platelet counts in spontaneous survivors decreased from day 1 to 2, then subsequently recovered; platelets decreased progressively in patients who underwent liver transplant or died. The INR trend over time according to 21-day outcome was similar to that of platelet counts.

The retrospective study evaluated data from 1598 patients who enrolled in the ALF Study Group from 1998 to 2012. The mean age was 41 years, 76% were Caucasian, and 70% were female. Nearly one-half of participants (47%) had ALF due to acetaminophen overdose, 85% had at least one positive element of SIRS on admission, 32% required vasopressors, 33% required renal replacement therapy, and 50% developed high-grade (3 or 4) hepatic encephalopathy. In total, 47% of patients recovered without liver transplant, 24% underwent liver transplant, and 32% died.

The mechanism underlying development of thrombocytopenia in patients with ALF is poorly understood. Previous findings by the investigators showed that platelet-derived, prothrombotic microparticles increased in proportion to SIRS severity, and concentration of microparticles increased in parallel with laboratory markers of poor outcome. Current results suggest the converse to be true as well: platelet counts decreased in proportion to the severity of SIRS, the development of MOSF and poor outcome at 21 days.

The researchers proposed that deficiencies in the number of platelets or in liver-derived, prohemostatic coagulation factors may be compensated by systemic inflammation. Increased levels of platelet-derived microparticles in patients with ALF may overcompensate for thrombocytopenia due to a nearly 40-fold higher prothrombotic potential in tissue factor–dependent assays, compared with healthy control populations.

The findings point to the importance of platelet count in signaling impending complications in patients with ALF.

Dr. Stravitz and his coauthors reported having no disclosures.

In patients with acute liver failure (ALF), decreasing platelet counts after hospital admission signaled systemic inflammation and a greater likelihood of systemic complications, such as high-grade hepatic encephalopathy, cardiovascular collapse, the need for liver transplant, and death, according to researchers.

Patients with systemic inflammatory response syndrome (SIRS) had significantly lower platelet counts at admission, compared with those without SIRS, and their platelet counts decreased dramatically (from 182 plus or minus 27 times 10⁹/L on admission to 103 plus or minus 3.20 times 10⁹/L on day 6) compared with stable platelet counts in patients without SIRS. For days 2-7 postadmission, lower platelet counts were associated with high-grade hepatic encephalopathy, as well as the need for vasopressor support and renal replacement therapy (P less than or equal to .001 for all).

©pixologicstudio/thinkstockphotos.com

“We hypothesize that the decrease in platelet count represents an integral event in the pathogenesis of the ALF syndrome rather than a nonspecific marker of suppressed bone marrow production. Further studies will be needed to prove the pivotal role of platelets in mediating the proinflammatory and prothrombotic features of the ALF syndrome,” wrote Dr. R. Todd Stravitz, professor of medicine, section of hepatology, Virginia Commonwealth University, Richmond, and his colleagues (Clin Gastroenterol Hepatol. 2016 Feb 25. doi: 10.1016/j.cgh.2015.09.029).

Results showed that SIRS and multiorgan system failure (MOSF) were more closely linked to a decrease in platelet counts than to an increase in the international normalized ratio (INR), a laboratory marker for liver injury. The INR was similar in patients with and without SIRS, in high-grade and low-grade hepatic encephalopathy, and in patients with and without requirements for vasopressor support and renal replacement therapy (indicators of MOSF). Given that both platelet counts and INR were associated with prognosis, the investigators suggest that these laboratory parameters may reflect different types of injury, with INR signaling primary liver injury and platelets reflecting the severity of systemic inflammation secondary to liver injury.

Platelet counts varied according to outcome on day 21. Spontaneous survivors had higher mean platelet counts than patients who underwent liver transplant, and patients who died had the lowest platelet counts. Platelet counts in spontaneous survivors decreased from day 1 to 2, then subsequently recovered; platelets decreased progressively in patients who underwent liver transplant or died. The INR trend over time according to 21-day outcome was similar to that of platelet counts.

The retrospective study evaluated data from 1598 patients who enrolled in the ALF Study Group from 1998 to 2012. The mean age was 41 years, 76% were Caucasian, and 70% were female. Nearly one-half of participants (47%) had ALF due to acetaminophen overdose, 85% had at least one positive element of SIRS on admission, 32% required vasopressors, 33% required renal replacement therapy, and 50% developed high-grade (3 or 4) hepatic encephalopathy. In total, 47% of patients recovered without liver transplant, 24% underwent liver transplant, and 32% died.

The mechanism underlying development of thrombocytopenia in patients with ALF is poorly understood. Previous findings by the investigators showed that platelet-derived, prothrombotic microparticles increased in proportion to SIRS severity, and concentration of microparticles increased in parallel with laboratory markers of poor outcome. Current results suggest the converse to be true as well: platelet counts decreased in proportion to the severity of SIRS, the development of MOSF and poor outcome at 21 days.

The researchers proposed that deficiencies in the number of platelets or in liver-derived, prohemostatic coagulation factors may be compensated by systemic inflammation. Increased levels of platelet-derived microparticles in patients with ALF may overcompensate for thrombocytopenia due to a nearly 40-fold higher prothrombotic potential in tissue factor–dependent assays, compared with healthy control populations.

The findings point to the importance of platelet count in signaling impending complications in patients with ALF.

Dr. Stravitz and his coauthors reported having no disclosures.

In patients with acute liver failure (ALF), decreasing platelet counts after hospital admission signaled systemic inflammation and a greater likelihood of systemic complications, such as high-grade hepatic encephalopathy, cardiovascular collapse, the need for liver transplant, and death, according to researchers.

Patients with systemic inflammatory response syndrome (SIRS) had significantly lower platelet counts at admission, compared with those without SIRS, and their platelet counts decreased dramatically (from 182 plus or minus 27 times 10⁹/L on admission to 103 plus or minus 3.20 times 10⁹/L on day 6) compared with stable platelet counts in patients without SIRS. For days 2-7 postadmission, lower platelet counts were associated with high-grade hepatic encephalopathy, as well as the need for vasopressor support and renal replacement therapy (P less than or equal to .001 for all).

©pixologicstudio/thinkstockphotos.com

“We hypothesize that the decrease in platelet count represents an integral event in the pathogenesis of the ALF syndrome rather than a nonspecific marker of suppressed bone marrow production. Further studies will be needed to prove the pivotal role of platelets in mediating the proinflammatory and prothrombotic features of the ALF syndrome,” wrote Dr. R. Todd Stravitz, professor of medicine, section of hepatology, Virginia Commonwealth University, Richmond, and his colleagues (Clin Gastroenterol Hepatol. 2016 Feb 25. doi: 10.1016/j.cgh.2015.09.029).

Results showed that SIRS and multiorgan system failure (MOSF) were more closely linked to a decrease in platelet counts than to an increase in the international normalized ratio (INR), a laboratory marker for liver injury. The INR was similar in patients with and without SIRS, in high-grade and low-grade hepatic encephalopathy, and in patients with and without requirements for vasopressor support and renal replacement therapy (indicators of MOSF). Given that both platelet counts and INR were associated with prognosis, the investigators suggest that these laboratory parameters may reflect different types of injury, with INR signaling primary liver injury and platelets reflecting the severity of systemic inflammation secondary to liver injury.

Platelet counts varied according to outcome on day 21. Spontaneous survivors had higher mean platelet counts than patients who underwent liver transplant, and patients who died had the lowest platelet counts. Platelet counts in spontaneous survivors decreased from day 1 to 2, then subsequently recovered; platelets decreased progressively in patients who underwent liver transplant or died. The INR trend over time according to 21-day outcome was similar to that of platelet counts.

The retrospective study evaluated data from 1598 patients who enrolled in the ALF Study Group from 1998 to 2012. The mean age was 41 years, 76% were Caucasian, and 70% were female. Nearly one-half of participants (47%) had ALF due to acetaminophen overdose, 85% had at least one positive element of SIRS on admission, 32% required vasopressors, 33% required renal replacement therapy, and 50% developed high-grade (3 or 4) hepatic encephalopathy. In total, 47% of patients recovered without liver transplant, 24% underwent liver transplant, and 32% died.

The mechanism underlying development of thrombocytopenia in patients with ALF is poorly understood. Previous findings by the investigators showed that platelet-derived, prothrombotic microparticles increased in proportion to SIRS severity, and concentration of microparticles increased in parallel with laboratory markers of poor outcome. Current results suggest the converse to be true as well: platelet counts decreased in proportion to the severity of SIRS, the development of MOSF and poor outcome at 21 days.

The researchers proposed that deficiencies in the number of platelets or in liver-derived, prohemostatic coagulation factors may be compensated by systemic inflammation. Increased levels of platelet-derived microparticles in patients with ALF may overcompensate for thrombocytopenia due to a nearly 40-fold higher prothrombotic potential in tissue factor–dependent assays, compared with healthy control populations.

The findings point to the importance of platelet count in signaling impending complications in patients with ALF.

Dr. Stravitz and his coauthors reported having no disclosures.

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

dchitnis@frontlinemedcom.com

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

dchitnis@frontlinemedcom.com

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

dchitnis@frontlinemedcom.com

Review the PDF of the fact sheet on allergic contact dermatitis

Practice Questions

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Practice Question Answers

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Review the PDF of the fact sheet on allergic contact dermatitis

Practice Questions

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Practice Question Answers

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Review the PDF of the fact sheet on allergic contact dermatitis

Practice Questions

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Practice Question Answers

1. The most common allergen of hand dermatitis in hairdressers can cross-react with which of the following allergens?

a. benzocaine
b. para-aminobenzoic acid
c. procaine
d. sulfanomides
e. all of the above

2. Patients with a documented allergy to quaternium-15 should avoid all of the following ingredients except:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. imidazolidinyl urea
e. paraben mix

3. Which of the following is a screening agent for hydrocortisone allergy?

a. budesonide
b. clobetasol
c. desoximetasone
d. paraben mix
e. tixocortol pivalate

4. This allergen often is found in black synthetic henna tattoos:

a. paraben mix
b. potassium dichromate
c. PPD
d. quaternium-15
e. thimerosol

5. A patient with a documented allergy to paraben mix also should avoid the following agent:

a. bronopol
b. diazolidinyl urea
c. DMDM hydantoin
d. PPD
e. thiuram mix

Live attenuated influenza vaccine (LAIV) is likely to be an option for all individuals with egg allergies, regardless of allergy severity, because the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to approve proposed amendments to the existing recommendations regarding administration of LAIV in individuals with egg allergies.

With 11 members voting “yes” and three choosing to abstain, the committee agreed to leave sections 1, 2, and 3 as they currently are, with a slight change to section 1 so that it will now include the latter half of recommendations that were previously placed under section 4. Therefore, section 1 of the recommendations for influenza vaccination of persons with egg allergy – which already states that “Regardless of a recipient’s allergy history, all vaccines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available” – will now also include text stating that the vaccine should be administered in a medical setting and supervised by a health care provider with “experience in the recognition and management of severe allergic conditions,” or that such a medical professional should be “immediately available.”

©pressdigital/iStock

Sections 2 and 3 will remain the same. Section 2 states that a previous allergic reaction to the influenza vaccine is a contraindication to ever receiving the vaccine again in the future. Section 3 states that individuals with egg allergy who have only experienced hives due to eggs still should be administered the influenza vaccine.

The committee voted to strike section 5 of the existing recommendations, which calls for a 30-minute postvaccination observation period. However, the committee still advises that health care providers monitor all patients, particularly adolescents, for 15 minutes immediately after vaccination, and that individuals should be seated or lying down “to decrease the risk for injury should syncopy occur.”

The CDC generally follows ACIP’s recommendations.

dchitnis@frontlinemedcom.com

Live attenuated influenza vaccine (LAIV) is likely to be an option for all individuals with egg allergies, regardless of allergy severity, because the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to approve proposed amendments to the existing recommendations regarding administration of LAIV in individuals with egg allergies.

With 11 members voting “yes” and three choosing to abstain, the committee agreed to leave sections 1, 2, and 3 as they currently are, with a slight change to section 1 so that it will now include the latter half of recommendations that were previously placed under section 4. Therefore, section 1 of the recommendations for influenza vaccination of persons with egg allergy – which already states that “Regardless of a recipient’s allergy history, all vaccines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available” – will now also include text stating that the vaccine should be administered in a medical setting and supervised by a health care provider with “experience in the recognition and management of severe allergic conditions,” or that such a medical professional should be “immediately available.”

©pressdigital/iStock

Sections 2 and 3 will remain the same. Section 2 states that a previous allergic reaction to the influenza vaccine is a contraindication to ever receiving the vaccine again in the future. Section 3 states that individuals with egg allergy who have only experienced hives due to eggs still should be administered the influenza vaccine.

The committee voted to strike section 5 of the existing recommendations, which calls for a 30-minute postvaccination observation period. However, the committee still advises that health care providers monitor all patients, particularly adolescents, for 15 minutes immediately after vaccination, and that individuals should be seated or lying down “to decrease the risk for injury should syncopy occur.”

The CDC generally follows ACIP’s recommendations.

dchitnis@frontlinemedcom.com

Live attenuated influenza vaccine (LAIV) is likely to be an option for all individuals with egg allergies, regardless of allergy severity, because the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to approve proposed amendments to the existing recommendations regarding administration of LAIV in individuals with egg allergies.

With 11 members voting “yes” and three choosing to abstain, the committee agreed to leave sections 1, 2, and 3 as they currently are, with a slight change to section 1 so that it will now include the latter half of recommendations that were previously placed under section 4. Therefore, section 1 of the recommendations for influenza vaccination of persons with egg allergy – which already states that “Regardless of a recipient’s allergy history, all vaccines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available” – will now also include text stating that the vaccine should be administered in a medical setting and supervised by a health care provider with “experience in the recognition and management of severe allergic conditions,” or that such a medical professional should be “immediately available.”

©pressdigital/iStock

Sections 2 and 3 will remain the same. Section 2 states that a previous allergic reaction to the influenza vaccine is a contraindication to ever receiving the vaccine again in the future. Section 3 states that individuals with egg allergy who have only experienced hives due to eggs still should be administered the influenza vaccine.

The committee voted to strike section 5 of the existing recommendations, which calls for a 30-minute postvaccination observation period. However, the committee still advises that health care providers monitor all patients, particularly adolescents, for 15 minutes immediately after vaccination, and that individuals should be seated or lying down “to decrease the risk for injury should syncopy occur.”

The CDC generally follows ACIP’s recommendations.

dchitnis@frontlinemedcom.com

“The greatest hazard of all, losing one’s self, can occur very quietly in the world, as if it were nothing at all. No other loss can occur so quietly”

—Søren Kierkegaard

In our interactions with patients we often focus on the medical issue at hand, forgetting the other dimensions of our patients’ lives. Yet these invisible dimensions can have a huge impact on their humanity. I humbly submit that it can be profoundly meaningful, for them and for us, if we paid close attention.

1. JV has rheumatoid arthritis. He is not the most compliant, and I had not seen him in over a year. He was well controlled on Enbrel.

He came to the office one day last week to make an appointment. We gave him one for the next day, but he missed the appointment. When he finally came a week later, I got the real story. He had gotten arrested.

The day he came into my office to ask for an appointment after a prolonged absence, it was because his insurance was denying coverage for his Enbrel. His next stop, after making his appointment, was to the Social Security office to try to sort out his coverage. When asked about whether or not he needed special accommodations, he made a point to mention his hearing loss. However, the person ultimately assigned to help him was not a native English speaker. This made for a very confusing and loud exchange that led to a heated argument with security. It ended with him being led out of the office in handcuffs, and spending the night in jail.

2. Tyler has inflammatory arthritis. He received his diagnosis in Arizona 5 years ago. He was stable on Plaquenil when I met him a year ago, and I only see him every 6 months.

On our third visit, I noticed he had gained weight. He attributed this to the discontinuation of his Dexedrine, in the interest of adjusting his medications for bipolar disorder. I couldn’t remember our second visit very well, but he apologized profusely for having been “lit.” He apparently was so manic that it drove his family crazy. In an effort to get him to take medications for the problem, his sister said: “It’s like living with Vincent van Gogh, except now we have meds for it.”

Now he takes his medications. As a result, his body feels foreign. In the summer, he ran around the backyard all day and night constructing an obstacle course for his dog that he knew he would never get right. Now he is lucky if he gets a few days a week of productive work on his art. He feels dulled; he is not as quick-witted. It is sad, but, he says, this is what society expects of him.

3. Judy is in her mid-70s. That’s not old these days, but she is somewhat crippled by her rheumatoid arthritis. She lived in Manhattan with her husband and enjoyed the city immensely. After her husband passed away, she managed to live in her Manhattan apartment independently for a little bit, but after suffering a fall, she let her children move her to Rhode Island to be closer to them. She has struggled to find her own apartment with amenities that will allow her to remain independent. For the past 3 years she has been in an assisted living facility.

She is so unhappy there. She doesn’t like forced interactions, doesn’t like to gossip, doesn’t like when her neighbors behave like they’re in middle school. It has taken 3 years for the people around her to finally respect her desire to be left alone, to spend her time reading and listening to the opera rather than engaging in idle chitchat that does not interest her at all.

Dr. Chan practices rheumatology in Pawtucket, R.I.

“The greatest hazard of all, losing one’s self, can occur very quietly in the world, as if it were nothing at all. No other loss can occur so quietly”

—Søren Kierkegaard

In our interactions with patients we often focus on the medical issue at hand, forgetting the other dimensions of our patients’ lives. Yet these invisible dimensions can have a huge impact on their humanity. I humbly submit that it can be profoundly meaningful, for them and for us, if we paid close attention.

1. JV has rheumatoid arthritis. He is not the most compliant, and I had not seen him in over a year. He was well controlled on Enbrel.

He came to the office one day last week to make an appointment. We gave him one for the next day, but he missed the appointment. When he finally came a week later, I got the real story. He had gotten arrested.

The day he came into my office to ask for an appointment after a prolonged absence, it was because his insurance was denying coverage for his Enbrel. His next stop, after making his appointment, was to the Social Security office to try to sort out his coverage. When asked about whether or not he needed special accommodations, he made a point to mention his hearing loss. However, the person ultimately assigned to help him was not a native English speaker. This made for a very confusing and loud exchange that led to a heated argument with security. It ended with him being led out of the office in handcuffs, and spending the night in jail.

2. Tyler has inflammatory arthritis. He received his diagnosis in Arizona 5 years ago. He was stable on Plaquenil when I met him a year ago, and I only see him every 6 months.

On our third visit, I noticed he had gained weight. He attributed this to the discontinuation of his Dexedrine, in the interest of adjusting his medications for bipolar disorder. I couldn’t remember our second visit very well, but he apologized profusely for having been “lit.” He apparently was so manic that it drove his family crazy. In an effort to get him to take medications for the problem, his sister said: “It’s like living with Vincent van Gogh, except now we have meds for it.”

Now he takes his medications. As a result, his body feels foreign. In the summer, he ran around the backyard all day and night constructing an obstacle course for his dog that he knew he would never get right. Now he is lucky if he gets a few days a week of productive work on his art. He feels dulled; he is not as quick-witted. It is sad, but, he says, this is what society expects of him.

3. Judy is in her mid-70s. That’s not old these days, but she is somewhat crippled by her rheumatoid arthritis. She lived in Manhattan with her husband and enjoyed the city immensely. After her husband passed away, she managed to live in her Manhattan apartment independently for a little bit, but after suffering a fall, she let her children move her to Rhode Island to be closer to them. She has struggled to find her own apartment with amenities that will allow her to remain independent. For the past 3 years she has been in an assisted living facility.

She is so unhappy there. She doesn’t like forced interactions, doesn’t like to gossip, doesn’t like when her neighbors behave like they’re in middle school. It has taken 3 years for the people around her to finally respect her desire to be left alone, to spend her time reading and listening to the opera rather than engaging in idle chitchat that does not interest her at all.

Dr. Chan practices rheumatology in Pawtucket, R.I.

“The greatest hazard of all, losing one’s self, can occur very quietly in the world, as if it were nothing at all. No other loss can occur so quietly”

—Søren Kierkegaard

In our interactions with patients we often focus on the medical issue at hand, forgetting the other dimensions of our patients’ lives. Yet these invisible dimensions can have a huge impact on their humanity. I humbly submit that it can be profoundly meaningful, for them and for us, if we paid close attention.

1. JV has rheumatoid arthritis. He is not the most compliant, and I had not seen him in over a year. He was well controlled on Enbrel.

He came to the office one day last week to make an appointment. We gave him one for the next day, but he missed the appointment. When he finally came a week later, I got the real story. He had gotten arrested.

The day he came into my office to ask for an appointment after a prolonged absence, it was because his insurance was denying coverage for his Enbrel. His next stop, after making his appointment, was to the Social Security office to try to sort out his coverage. When asked about whether or not he needed special accommodations, he made a point to mention his hearing loss. However, the person ultimately assigned to help him was not a native English speaker. This made for a very confusing and loud exchange that led to a heated argument with security. It ended with him being led out of the office in handcuffs, and spending the night in jail.

2. Tyler has inflammatory arthritis. He received his diagnosis in Arizona 5 years ago. He was stable on Plaquenil when I met him a year ago, and I only see him every 6 months.

On our third visit, I noticed he had gained weight. He attributed this to the discontinuation of his Dexedrine, in the interest of adjusting his medications for bipolar disorder. I couldn’t remember our second visit very well, but he apologized profusely for having been “lit.” He apparently was so manic that it drove his family crazy. In an effort to get him to take medications for the problem, his sister said: “It’s like living with Vincent van Gogh, except now we have meds for it.”

Now he takes his medications. As a result, his body feels foreign. In the summer, he ran around the backyard all day and night constructing an obstacle course for his dog that he knew he would never get right. Now he is lucky if he gets a few days a week of productive work on his art. He feels dulled; he is not as quick-witted. It is sad, but, he says, this is what society expects of him.

3. Judy is in her mid-70s. That’s not old these days, but she is somewhat crippled by her rheumatoid arthritis. She lived in Manhattan with her husband and enjoyed the city immensely. After her husband passed away, she managed to live in her Manhattan apartment independently for a little bit, but after suffering a fall, she let her children move her to Rhode Island to be closer to them. She has struggled to find her own apartment with amenities that will allow her to remain independent. For the past 3 years she has been in an assisted living facility.

She is so unhappy there. She doesn’t like forced interactions, doesn’t like to gossip, doesn’t like when her neighbors behave like they’re in middle school. It has taken 3 years for the people around her to finally respect her desire to be left alone, to spend her time reading and listening to the opera rather than engaging in idle chitchat that does not interest her at all.

Dr. Chan practices rheumatology in Pawtucket, R.I.

 Federal Practitioner talks one-on-one with Louis Fiore, MD, MPH, the executive director of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), which the VA created as 1 of 3 epidemiological research centers. At MAVERIC Fiore is spearheading a precision oncology program, which is developing precision oncology best practices; enhancing patient and provider engagement; and fostering collaboration among the VA, National Cancer Institute, academia, and other health care systems to provide cancer patients with access to clinical trial participation.

 Federal Practitioner talks one-on-one with Louis Fiore, MD, MPH, the executive director of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), which the VA created as 1 of 3 epidemiological research centers. At MAVERIC Fiore is spearheading a precision oncology program, which is developing precision oncology best practices; enhancing patient and provider engagement; and fostering collaboration among the VA, National Cancer Institute, academia, and other health care systems to provide cancer patients with access to clinical trial participation.

 Federal Practitioner talks one-on-one with Louis Fiore, MD, MPH, the executive director of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), which the VA created as 1 of 3 epidemiological research centers. At MAVERIC Fiore is spearheading a precision oncology program, which is developing precision oncology best practices; enhancing patient and provider engagement; and fostering collaboration among the VA, National Cancer Institute, academia, and other health care systems to provide cancer patients with access to clinical trial participation.

When patients are diagnosed with cervical cancer at the locally advanced stage, the standard care is concurrent chemoradiotherapy (CCRT). But what if that isn’t the right choice?

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

Ineffective treatment is associated with increased toxicity, accelerated tumor growth, and a delay in starting any alternative potentially effective treatment, according to researchers from Nanjing Drum Tower Hospital in China. These researchers suggest a role for intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI), which is an extension of diffusion-weighted MRI (DWI).

Related: How Much Is Too Much Cancer Screening?

To date MRI has been established as the most effective imaging method in cervical cancer. However, DWI has shown potential as an early predictor based on morphologic, physiologic, and metabolic information. In turn, IVIM imaging, which assesses microscopic changes in diffusion and perfusion, has been used to provide clues to cancers in the head and neck, prostate, breast, and kidney—but not cervical cancer.

In their study, the researchers enrolled 21 patients about to undergo CCRT for advanced cervical cancer. These patients received MR examinations, including IVIM imaging, 1 week before CCRT, 2 and 4 weeks during CCRT, and after 1 week post-CCRT to address the use of IVIM imaging in cervical cancer.

Related: Early Cancer Detection Helps Underserved Women

The IVIM MR imaging showed “dynamic changes” of cervical cancers during treatment, making IVIM parameters possible biomarkers for tumor response following CCRT for cervical cancer. With technological advances the researchers say, IVIM could become “a valuable imaging tool,” in the clinic as well as in cancer research.

Source: 

Zhu L, Zhu L, Shi H, et al. BMC Cancer. 2016;16:79
doi 10.1186/s12885-016-2116-5

When patients are diagnosed with cervical cancer at the locally advanced stage, the standard care is concurrent chemoradiotherapy (CCRT). But what if that isn’t the right choice?

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

Ineffective treatment is associated with increased toxicity, accelerated tumor growth, and a delay in starting any alternative potentially effective treatment, according to researchers from Nanjing Drum Tower Hospital in China. These researchers suggest a role for intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI), which is an extension of diffusion-weighted MRI (DWI).

Related: How Much Is Too Much Cancer Screening?

To date MRI has been established as the most effective imaging method in cervical cancer. However, DWI has shown potential as an early predictor based on morphologic, physiologic, and metabolic information. In turn, IVIM imaging, which assesses microscopic changes in diffusion and perfusion, has been used to provide clues to cancers in the head and neck, prostate, breast, and kidney—but not cervical cancer.

In their study, the researchers enrolled 21 patients about to undergo CCRT for advanced cervical cancer. These patients received MR examinations, including IVIM imaging, 1 week before CCRT, 2 and 4 weeks during CCRT, and after 1 week post-CCRT to address the use of IVIM imaging in cervical cancer.

Related: Early Cancer Detection Helps Underserved Women

The IVIM MR imaging showed “dynamic changes” of cervical cancers during treatment, making IVIM parameters possible biomarkers for tumor response following CCRT for cervical cancer. With technological advances the researchers say, IVIM could become “a valuable imaging tool,” in the clinic as well as in cancer research.

Source: 

Zhu L, Zhu L, Shi H, et al. BMC Cancer. 2016;16:79
doi 10.1186/s12885-016-2116-5

When patients are diagnosed with cervical cancer at the locally advanced stage, the standard care is concurrent chemoradiotherapy (CCRT). But what if that isn’t the right choice?

Related: Using a Multiplex of Biomarkers to Detect Prostate Cancer

Ineffective treatment is associated with increased toxicity, accelerated tumor growth, and a delay in starting any alternative potentially effective treatment, according to researchers from Nanjing Drum Tower Hospital in China. These researchers suggest a role for intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI), which is an extension of diffusion-weighted MRI (DWI).

Related: How Much Is Too Much Cancer Screening?

To date MRI has been established as the most effective imaging method in cervical cancer. However, DWI has shown potential as an early predictor based on morphologic, physiologic, and metabolic information. In turn, IVIM imaging, which assesses microscopic changes in diffusion and perfusion, has been used to provide clues to cancers in the head and neck, prostate, breast, and kidney—but not cervical cancer.

In their study, the researchers enrolled 21 patients about to undergo CCRT for advanced cervical cancer. These patients received MR examinations, including IVIM imaging, 1 week before CCRT, 2 and 4 weeks during CCRT, and after 1 week post-CCRT to address the use of IVIM imaging in cervical cancer.

Related: Early Cancer Detection Helps Underserved Women

The IVIM MR imaging showed “dynamic changes” of cervical cancers during treatment, making IVIM parameters possible biomarkers for tumor response following CCRT for cervical cancer. With technological advances the researchers say, IVIM could become “a valuable imaging tool,” in the clinic as well as in cancer research.

Source: 

Zhu L, Zhu L, Shi H, et al. BMC Cancer. 2016;16:79
doi 10.1186/s12885-016-2116-5

NEW ORLEANS – On top of the first success with an investigational pharmaceutical agent for primary progressive multiple sclerosis reported last year, the otherwise negative results from recent clinical trials in progressive disease are at least informing the field of which direction to take in future research, Dr. Fred D. Lublin said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“The breaking news is that we are making headway. Two years ago we didn’t have a clue. Now we have clues,” said Dr. Lublin, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York.

In the ORATORIO trial, the selective B-cell–targeting monoclonal antibody ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with primary progressive MS (PPMS) in a 120-week blinded treatment continued for at least 120 weeks. After 24 weeks of treatment, ocrelizumab lessened the risk of progression in clinical disability by 25%, compared with placebo. Over the 2-year blinded treatment, the volume of hyperintense T2 lesions was reduced by 3.4% in the treatment arm, compared with a 7% increase in the placebo arm. Rate of whole brain volume loss was also reduced. A subgroup analysis presented at the ACTRIMS Forum revealed the influence of gadolinium-enhanced lesions on treatment efficacy.

“ORATORIO has opened the door to the problem of solving progressive MS”, said Dr. Lublin. Yet, considerable challenges remain. This was true even in the ORATORIO trial, where the treatment success was tempered by a 2.3% rate of malignancies in patients receiving ocrelizumab, which was more than double the 0.8% rate in the placebo arm.

Impact of trial design

The ORATORIO trial also highlighted another conundrum of trials to date, namely patient selection. The trial was designed to include young people with brain inflammation, a population that can respond well to treatment. But, in real life, patients with progressive MS can be older without signs of inflammation. For them, and for patients with a longer history of progressive MS, treatment might be less effective.

Other aspects of trial design that can bear on the outcome include the target (inflammation or degeneration), who to target, how to measure treatment outcome, and whether the endpoint is a confirmed decline that persists for a defined time or the more rigorous sustained decline, in which the decline is maintained for the course of the study. The disease phenotypes can also be important in trial design when it comes to screening patients. For example, one recognized MS phenotype is an active form that features clinical relapses and/or gadolinium-enhancing lesions on MRI, but which does not progress. Inclusion of this phenotype in a study can dilute the power of the study to detect a treatment effect if the progressive disease is in a nonprogressive phase during the study period.

Subgroup analysis of a trial with a failed primary outcome may reveal some patients who respond better to treatment, as in the OLYMPUS randomized, placebo-controlled trial. While the difference to confirmed disease progression in PPMS between rituximab and placebo was not significant overall, disease progression was significantly delayed in older patients.

Informative negative trials

With a solid trial design, a failed outcome can be informative, as it is likely because of a biological reason rather than a faulty trial design. The randomized, double-blind, phase III INFORMS trial of fingolimod versus placebo in PPMS is an example. While the primary and secondary outcomes involving delay to 3-month confirmed disease progression were not met, fingolimod treatment was associated with significantly fewer T2 and gadolinium-enhanced T1 lesions. Scrutiny of the study results could inform future trials.

A second example is the ASCEND trial of natalizumab in patients with secondary progressive MS. The trial’s failure likely reflected the very rigorous primary endpoint of a delay of confirmed disease progression at 3 months that was sustained up to 6 months or longer.

The MS-SPI randomized, multicenter, double-blind, placebo-controlled study that evaluated oral biotin in patients with PPMS or secondary progressive MS was especially noteworthy for its primary endpoint of improvement in disease at 1 year. The endpoint was met by 13% of those in the treatment arm versus 0% in the placebo arm (P = .0051).

“I wish I had more breaking news to report. But we are making progress with progressive disease. We learn from each study, and we are developing a clearer understanding of how to more effectively approach progression,” Dr. Lublin said.

Dr. Lublin reported receiving research support and/or serving as a consultant for many companies marketing MS drugs, including Biogen, Genentech, and Novartis.

NEW ORLEANS – On top of the first success with an investigational pharmaceutical agent for primary progressive multiple sclerosis reported last year, the otherwise negative results from recent clinical trials in progressive disease are at least informing the field of which direction to take in future research, Dr. Fred D. Lublin said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“The breaking news is that we are making headway. Two years ago we didn’t have a clue. Now we have clues,” said Dr. Lublin, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York.

In the ORATORIO trial, the selective B-cell–targeting monoclonal antibody ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with primary progressive MS (PPMS) in a 120-week blinded treatment continued for at least 120 weeks. After 24 weeks of treatment, ocrelizumab lessened the risk of progression in clinical disability by 25%, compared with placebo. Over the 2-year blinded treatment, the volume of hyperintense T2 lesions was reduced by 3.4% in the treatment arm, compared with a 7% increase in the placebo arm. Rate of whole brain volume loss was also reduced. A subgroup analysis presented at the ACTRIMS Forum revealed the influence of gadolinium-enhanced lesions on treatment efficacy.

“ORATORIO has opened the door to the problem of solving progressive MS”, said Dr. Lublin. Yet, considerable challenges remain. This was true even in the ORATORIO trial, where the treatment success was tempered by a 2.3% rate of malignancies in patients receiving ocrelizumab, which was more than double the 0.8% rate in the placebo arm.

Impact of trial design

The ORATORIO trial also highlighted another conundrum of trials to date, namely patient selection. The trial was designed to include young people with brain inflammation, a population that can respond well to treatment. But, in real life, patients with progressive MS can be older without signs of inflammation. For them, and for patients with a longer history of progressive MS, treatment might be less effective.

Other aspects of trial design that can bear on the outcome include the target (inflammation or degeneration), who to target, how to measure treatment outcome, and whether the endpoint is a confirmed decline that persists for a defined time or the more rigorous sustained decline, in which the decline is maintained for the course of the study. The disease phenotypes can also be important in trial design when it comes to screening patients. For example, one recognized MS phenotype is an active form that features clinical relapses and/or gadolinium-enhancing lesions on MRI, but which does not progress. Inclusion of this phenotype in a study can dilute the power of the study to detect a treatment effect if the progressive disease is in a nonprogressive phase during the study period.

Subgroup analysis of a trial with a failed primary outcome may reveal some patients who respond better to treatment, as in the OLYMPUS randomized, placebo-controlled trial. While the difference to confirmed disease progression in PPMS between rituximab and placebo was not significant overall, disease progression was significantly delayed in older patients.

Informative negative trials

With a solid trial design, a failed outcome can be informative, as it is likely because of a biological reason rather than a faulty trial design. The randomized, double-blind, phase III INFORMS trial of fingolimod versus placebo in PPMS is an example. While the primary and secondary outcomes involving delay to 3-month confirmed disease progression were not met, fingolimod treatment was associated with significantly fewer T2 and gadolinium-enhanced T1 lesions. Scrutiny of the study results could inform future trials.

A second example is the ASCEND trial of natalizumab in patients with secondary progressive MS. The trial’s failure likely reflected the very rigorous primary endpoint of a delay of confirmed disease progression at 3 months that was sustained up to 6 months or longer.

The MS-SPI randomized, multicenter, double-blind, placebo-controlled study that evaluated oral biotin in patients with PPMS or secondary progressive MS was especially noteworthy for its primary endpoint of improvement in disease at 1 year. The endpoint was met by 13% of those in the treatment arm versus 0% in the placebo arm (P = .0051).

“I wish I had more breaking news to report. But we are making progress with progressive disease. We learn from each study, and we are developing a clearer understanding of how to more effectively approach progression,” Dr. Lublin said.

Dr. Lublin reported receiving research support and/or serving as a consultant for many companies marketing MS drugs, including Biogen, Genentech, and Novartis.

NEW ORLEANS – On top of the first success with an investigational pharmaceutical agent for primary progressive multiple sclerosis reported last year, the otherwise negative results from recent clinical trials in progressive disease are at least informing the field of which direction to take in future research, Dr. Fred D. Lublin said at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“The breaking news is that we are making headway. Two years ago we didn’t have a clue. Now we have clues,” said Dr. Lublin, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York.

In the ORATORIO trial, the selective B-cell–targeting monoclonal antibody ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with primary progressive MS (PPMS) in a 120-week blinded treatment continued for at least 120 weeks. After 24 weeks of treatment, ocrelizumab lessened the risk of progression in clinical disability by 25%, compared with placebo. Over the 2-year blinded treatment, the volume of hyperintense T2 lesions was reduced by 3.4% in the treatment arm, compared with a 7% increase in the placebo arm. Rate of whole brain volume loss was also reduced. A subgroup analysis presented at the ACTRIMS Forum revealed the influence of gadolinium-enhanced lesions on treatment efficacy.

“ORATORIO has opened the door to the problem of solving progressive MS”, said Dr. Lublin. Yet, considerable challenges remain. This was true even in the ORATORIO trial, where the treatment success was tempered by a 2.3% rate of malignancies in patients receiving ocrelizumab, which was more than double the 0.8% rate in the placebo arm.

Impact of trial design

The ORATORIO trial also highlighted another conundrum of trials to date, namely patient selection. The trial was designed to include young people with brain inflammation, a population that can respond well to treatment. But, in real life, patients with progressive MS can be older without signs of inflammation. For them, and for patients with a longer history of progressive MS, treatment might be less effective.

Other aspects of trial design that can bear on the outcome include the target (inflammation or degeneration), who to target, how to measure treatment outcome, and whether the endpoint is a confirmed decline that persists for a defined time or the more rigorous sustained decline, in which the decline is maintained for the course of the study. The disease phenotypes can also be important in trial design when it comes to screening patients. For example, one recognized MS phenotype is an active form that features clinical relapses and/or gadolinium-enhancing lesions on MRI, but which does not progress. Inclusion of this phenotype in a study can dilute the power of the study to detect a treatment effect if the progressive disease is in a nonprogressive phase during the study period.

Subgroup analysis of a trial with a failed primary outcome may reveal some patients who respond better to treatment, as in the OLYMPUS randomized, placebo-controlled trial. While the difference to confirmed disease progression in PPMS between rituximab and placebo was not significant overall, disease progression was significantly delayed in older patients.

Informative negative trials

With a solid trial design, a failed outcome can be informative, as it is likely because of a biological reason rather than a faulty trial design. The randomized, double-blind, phase III INFORMS trial of fingolimod versus placebo in PPMS is an example. While the primary and secondary outcomes involving delay to 3-month confirmed disease progression were not met, fingolimod treatment was associated with significantly fewer T2 and gadolinium-enhanced T1 lesions. Scrutiny of the study results could inform future trials.

A second example is the ASCEND trial of natalizumab in patients with secondary progressive MS. The trial’s failure likely reflected the very rigorous primary endpoint of a delay of confirmed disease progression at 3 months that was sustained up to 6 months or longer.

The MS-SPI randomized, multicenter, double-blind, placebo-controlled study that evaluated oral biotin in patients with PPMS or secondary progressive MS was especially noteworthy for its primary endpoint of improvement in disease at 1 year. The endpoint was met by 13% of those in the treatment arm versus 0% in the placebo arm (P = .0051).

“I wish I had more breaking news to report. But we are making progress with progressive disease. We learn from each study, and we are developing a clearer understanding of how to more effectively approach progression,” Dr. Lublin said.

Dr. Lublin reported receiving research support and/or serving as a consultant for many companies marketing MS drugs, including Biogen, Genentech, and Novartis.