NEW ORLEANS – Treatment with fingolimod improved gait impairment in treatment-naive multiple sclerosis (MS) patients and those on a previous first-line therapy in a small, single-center study.

“Fingolimod [Gilenya] is the first disease-modifying treatment shown to improve gait impairment in MS,” commented Dr. Soledad Pérez-Sánchez of Virgen Macarena University Hospital, Seville, Spain, who presented the study as a poster at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©solitude72/iStockphoto

The investigators also found that patients who were unsuccessfully treated with natalizumab (Tysabri) prior to fingolimod did not improve their gait during the course of the 6-month study. Natalizumab is a second-line drug in Spain, and fingolimod is a second-line therapy there as well, except in cases of aggressive onset of disease, according to the investigators.

Of 36 patients in the study, 24 were treatment-naïve/first-line patients (17 females and 7 males; mean age, 38.25 years), with the remaining 12 (9 females, 3 males; mean age, 44.25 years) having been treated with natalizumab. The mean duration of MS was 11.2 years in the naïve/first-line group and 17.9 years in patients on natalizumab prior to fingolimod. The mean Extended Disability Status Scale score in the two groups was similar at 3.79 and 3.38, respectively.

The investigators measured gait profile changes during fingolimod treatment with the Gaitrite Electronic System, which comprises an electronic pathway equipped with sensors designed to measure the timing and position of walking. The measurement parameters included velocity, ambulation time, and functional ambulation profile (FAP), the time to move unassisted through five common environmental terrains.

All patients completed the walking test prior to treatment and 3 months after treatment. At 6 months, 20 naïve/first-line patients and 11 patients previously on natalizumab completed the test. For each group of patients, the results prior to treatment and 3 months after were statistically similar. But significant differences were evident for naïve/first-line patients between the 3- and 6-month measures of velocity (89.10±31.03 to 100.70±23.75 cm/s; P = .01) and FAP (82.81±16.93 to 91.95±9.02 seconds; P = .01). These measurements trended toward significance when the values prior to treatment and 6 months after treatment were compared (P = .096, .077, and .065, in the same respective order).

Patients who had been treated with natalizumab did not display appreciable changes in velocity, ambulation time, and FAP.

“Our study shows that fingolimod improves gait impairment in naïve patients and those switched from first-line therapy. Our data are consistent with other clinical measures published so far which have pointed to better outcomes with fingolimod in naïve/first-line patients than in natalizumab-switched patients,” Dr. Pérez-Sánchez and her colleagues said.

The single-center study design and small number of patients limit any conclusions on the use of fingolimod as a gait-improving therapy in MS until further studies are completed, according to the researchers.

Funding was provided by Novartis. Dr. Pérez-Sánchez had no disclosures.

NEW ORLEANS – Treatment with fingolimod improved gait impairment in treatment-naive multiple sclerosis (MS) patients and those on a previous first-line therapy in a small, single-center study.

“Fingolimod [Gilenya] is the first disease-modifying treatment shown to improve gait impairment in MS,” commented Dr. Soledad Pérez-Sánchez of Virgen Macarena University Hospital, Seville, Spain, who presented the study as a poster at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©solitude72/iStockphoto

The investigators also found that patients who were unsuccessfully treated with natalizumab (Tysabri) prior to fingolimod did not improve their gait during the course of the 6-month study. Natalizumab is a second-line drug in Spain, and fingolimod is a second-line therapy there as well, except in cases of aggressive onset of disease, according to the investigators.

Of 36 patients in the study, 24 were treatment-naïve/first-line patients (17 females and 7 males; mean age, 38.25 years), with the remaining 12 (9 females, 3 males; mean age, 44.25 years) having been treated with natalizumab. The mean duration of MS was 11.2 years in the naïve/first-line group and 17.9 years in patients on natalizumab prior to fingolimod. The mean Extended Disability Status Scale score in the two groups was similar at 3.79 and 3.38, respectively.

The investigators measured gait profile changes during fingolimod treatment with the Gaitrite Electronic System, which comprises an electronic pathway equipped with sensors designed to measure the timing and position of walking. The measurement parameters included velocity, ambulation time, and functional ambulation profile (FAP), the time to move unassisted through five common environmental terrains.

All patients completed the walking test prior to treatment and 3 months after treatment. At 6 months, 20 naïve/first-line patients and 11 patients previously on natalizumab completed the test. For each group of patients, the results prior to treatment and 3 months after were statistically similar. But significant differences were evident for naïve/first-line patients between the 3- and 6-month measures of velocity (89.10±31.03 to 100.70±23.75 cm/s; P = .01) and FAP (82.81±16.93 to 91.95±9.02 seconds; P = .01). These measurements trended toward significance when the values prior to treatment and 6 months after treatment were compared (P = .096, .077, and .065, in the same respective order).

Patients who had been treated with natalizumab did not display appreciable changes in velocity, ambulation time, and FAP.

“Our study shows that fingolimod improves gait impairment in naïve patients and those switched from first-line therapy. Our data are consistent with other clinical measures published so far which have pointed to better outcomes with fingolimod in naïve/first-line patients than in natalizumab-switched patients,” Dr. Pérez-Sánchez and her colleagues said.

The single-center study design and small number of patients limit any conclusions on the use of fingolimod as a gait-improving therapy in MS until further studies are completed, according to the researchers.

Funding was provided by Novartis. Dr. Pérez-Sánchez had no disclosures.

NEW ORLEANS – Treatment with fingolimod improved gait impairment in treatment-naive multiple sclerosis (MS) patients and those on a previous first-line therapy in a small, single-center study.

“Fingolimod [Gilenya] is the first disease-modifying treatment shown to improve gait impairment in MS,” commented Dr. Soledad Pérez-Sánchez of Virgen Macarena University Hospital, Seville, Spain, who presented the study as a poster at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

©solitude72/iStockphoto

The investigators also found that patients who were unsuccessfully treated with natalizumab (Tysabri) prior to fingolimod did not improve their gait during the course of the 6-month study. Natalizumab is a second-line drug in Spain, and fingolimod is a second-line therapy there as well, except in cases of aggressive onset of disease, according to the investigators.

Of 36 patients in the study, 24 were treatment-naïve/first-line patients (17 females and 7 males; mean age, 38.25 years), with the remaining 12 (9 females, 3 males; mean age, 44.25 years) having been treated with natalizumab. The mean duration of MS was 11.2 years in the naïve/first-line group and 17.9 years in patients on natalizumab prior to fingolimod. The mean Extended Disability Status Scale score in the two groups was similar at 3.79 and 3.38, respectively.

The investigators measured gait profile changes during fingolimod treatment with the Gaitrite Electronic System, which comprises an electronic pathway equipped with sensors designed to measure the timing and position of walking. The measurement parameters included velocity, ambulation time, and functional ambulation profile (FAP), the time to move unassisted through five common environmental terrains.

All patients completed the walking test prior to treatment and 3 months after treatment. At 6 months, 20 naïve/first-line patients and 11 patients previously on natalizumab completed the test. For each group of patients, the results prior to treatment and 3 months after were statistically similar. But significant differences were evident for naïve/first-line patients between the 3- and 6-month measures of velocity (89.10±31.03 to 100.70±23.75 cm/s; P = .01) and FAP (82.81±16.93 to 91.95±9.02 seconds; P = .01). These measurements trended toward significance when the values prior to treatment and 6 months after treatment were compared (P = .096, .077, and .065, in the same respective order).

Patients who had been treated with natalizumab did not display appreciable changes in velocity, ambulation time, and FAP.

“Our study shows that fingolimod improves gait impairment in naïve patients and those switched from first-line therapy. Our data are consistent with other clinical measures published so far which have pointed to better outcomes with fingolimod in naïve/first-line patients than in natalizumab-switched patients,” Dr. Pérez-Sánchez and her colleagues said.

The single-center study design and small number of patients limit any conclusions on the use of fingolimod as a gait-improving therapy in MS until further studies are completed, according to the researchers.

Funding was provided by Novartis. Dr. Pérez-Sánchez had no disclosures.

Drug release in a cancer cell

Image courtesy of PNAS

DNA origami nanostructures may be used to overcome drug resistance in acute myeloid leukemia (AML), according to preclinical research published in the journal Small.

Researchers found they could create these nanostructures in 10 minutes and load them with the anthracycline daunorubicin.

When the team introduced the structures to daunorubicin-resistant AML cells, the drug delivery vehicles entered the cells via endocytosis.

This allowed the drug to bypass defenses in the cell membrane that are effective against the free drug.

Once the nanostructures broke down, daunorubicin flooded the cells and killed them off.

Other research groups have used this delivery technique to overcome drug resistance in solid tumors, but this is the first time researchers have shown the same technique works on drug-resistant leukemia cells.

To create the DNA origami nanostructures, the researchers used the genome of a common bacteriophage and synthetic strands that were designed to fold up the bacteriophage DNA.

Although the folded-up shape performs a function, the DNA itself does not, explained Patrick Halley, a graduate student at The Ohio State University in Columbus.

“[T]he DNA capsule doesn’t do anything except hold a shape,” Halley said. “It’s just a static, rigid structure that carries things. It doesn’t encode any proteins or do anything else that we normally think of DNA as doing.”

The researchers tested the DNA origami nanostructures in AML cell lines that had developed resistance to daunorubicin. When molecules of daunorubicin enter these cells, the cells recognize the drug molecules and eject them through openings in the cell wall.

“Cancer cells have novel ways of resisting drugs, like these ‘pumps,’ and the exciting part of packaging the drug this way is that we can circumvent those defenses so that the drug accumulates in the cancer cell and causes it to die,” said John Byrd, MD, of The Ohio State University.

“Potentially, we can also tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects.”

In tests, the resistant AML cells effectively absorbed molecules of daunorubicin when they were hidden inside the rod-shaped nanostructures.

The researchers tracked the nanostructures inside the cells using fluorescent tags. Each structure measures about 15 nanometers wide and 100 nanometers long, and each has 4 hollow, open-ended interior compartments.

Study author Christopher Lucas, PhD, of The Ohio State University, said the design of the nanostructures maximizes the surface area available to carry the drug.

“The way daunorubicin works is it tucks into the cancer cell’s DNA and prevents it from replicating,” Dr Lucas said. “So we designed a capsule structure that would have lots of accessible DNA base-pairs for it to tuck into. When the capsule breaks down, the drug molecules are freed to flood the cell.”

The researchers said they designed the nanostructures to be strong and stable so they wouldn’t fully disintegrate and release the bulk of the drug until it was too late for the cells to eject them.

And that’s what the team observed with a fluorescence microscope. The cells drew the nanostructures into the organelles that would normally digest them (if they were food).

When the nanostructures broke down, the drug flooded the cells and caused them to disintegrate. Most cells died within the first 15 hours after consuming the nanostructures.

“DNA origami nanostructures have a lot of potential for drug delivery, not just for making effective drug delivery vehicles, but enabling new ways to study drug delivery,” said Carlos Castro, PhD, of The Ohio State University.

“For instance, we can vary the shape or mechanical stiffness of a structure very precisely and see how that affects entry into cells.”

Dr Castro said he hopes to create a streamlined and economically viable process for building DNA origami nanostructures as part of a modular drug delivery system.

Dr Byrd said the technique should work on most any form of drug-resistant cancer if further research shows it can be translated to animal models.

Drug release in a cancer cell

Image courtesy of PNAS

DNA origami nanostructures may be used to overcome drug resistance in acute myeloid leukemia (AML), according to preclinical research published in the journal Small.

Researchers found they could create these nanostructures in 10 minutes and load them with the anthracycline daunorubicin.

When the team introduced the structures to daunorubicin-resistant AML cells, the drug delivery vehicles entered the cells via endocytosis.

This allowed the drug to bypass defenses in the cell membrane that are effective against the free drug.

Once the nanostructures broke down, daunorubicin flooded the cells and killed them off.

Other research groups have used this delivery technique to overcome drug resistance in solid tumors, but this is the first time researchers have shown the same technique works on drug-resistant leukemia cells.

To create the DNA origami nanostructures, the researchers used the genome of a common bacteriophage and synthetic strands that were designed to fold up the bacteriophage DNA.

Although the folded-up shape performs a function, the DNA itself does not, explained Patrick Halley, a graduate student at The Ohio State University in Columbus.

“[T]he DNA capsule doesn’t do anything except hold a shape,” Halley said. “It’s just a static, rigid structure that carries things. It doesn’t encode any proteins or do anything else that we normally think of DNA as doing.”

The researchers tested the DNA origami nanostructures in AML cell lines that had developed resistance to daunorubicin. When molecules of daunorubicin enter these cells, the cells recognize the drug molecules and eject them through openings in the cell wall.

“Cancer cells have novel ways of resisting drugs, like these ‘pumps,’ and the exciting part of packaging the drug this way is that we can circumvent those defenses so that the drug accumulates in the cancer cell and causes it to die,” said John Byrd, MD, of The Ohio State University.

“Potentially, we can also tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects.”

In tests, the resistant AML cells effectively absorbed molecules of daunorubicin when they were hidden inside the rod-shaped nanostructures.

The researchers tracked the nanostructures inside the cells using fluorescent tags. Each structure measures about 15 nanometers wide and 100 nanometers long, and each has 4 hollow, open-ended interior compartments.

Study author Christopher Lucas, PhD, of The Ohio State University, said the design of the nanostructures maximizes the surface area available to carry the drug.

“The way daunorubicin works is it tucks into the cancer cell’s DNA and prevents it from replicating,” Dr Lucas said. “So we designed a capsule structure that would have lots of accessible DNA base-pairs for it to tuck into. When the capsule breaks down, the drug molecules are freed to flood the cell.”

The researchers said they designed the nanostructures to be strong and stable so they wouldn’t fully disintegrate and release the bulk of the drug until it was too late for the cells to eject them.

And that’s what the team observed with a fluorescence microscope. The cells drew the nanostructures into the organelles that would normally digest them (if they were food).

When the nanostructures broke down, the drug flooded the cells and caused them to disintegrate. Most cells died within the first 15 hours after consuming the nanostructures.

“DNA origami nanostructures have a lot of potential for drug delivery, not just for making effective drug delivery vehicles, but enabling new ways to study drug delivery,” said Carlos Castro, PhD, of The Ohio State University.

“For instance, we can vary the shape or mechanical stiffness of a structure very precisely and see how that affects entry into cells.”

Dr Castro said he hopes to create a streamlined and economically viable process for building DNA origami nanostructures as part of a modular drug delivery system.

Dr Byrd said the technique should work on most any form of drug-resistant cancer if further research shows it can be translated to animal models.

Drug release in a cancer cell

Image courtesy of PNAS

DNA origami nanostructures may be used to overcome drug resistance in acute myeloid leukemia (AML), according to preclinical research published in the journal Small.

Researchers found they could create these nanostructures in 10 minutes and load them with the anthracycline daunorubicin.

When the team introduced the structures to daunorubicin-resistant AML cells, the drug delivery vehicles entered the cells via endocytosis.

This allowed the drug to bypass defenses in the cell membrane that are effective against the free drug.

Once the nanostructures broke down, daunorubicin flooded the cells and killed them off.

Other research groups have used this delivery technique to overcome drug resistance in solid tumors, but this is the first time researchers have shown the same technique works on drug-resistant leukemia cells.

To create the DNA origami nanostructures, the researchers used the genome of a common bacteriophage and synthetic strands that were designed to fold up the bacteriophage DNA.

Although the folded-up shape performs a function, the DNA itself does not, explained Patrick Halley, a graduate student at The Ohio State University in Columbus.

“[T]he DNA capsule doesn’t do anything except hold a shape,” Halley said. “It’s just a static, rigid structure that carries things. It doesn’t encode any proteins or do anything else that we normally think of DNA as doing.”

The researchers tested the DNA origami nanostructures in AML cell lines that had developed resistance to daunorubicin. When molecules of daunorubicin enter these cells, the cells recognize the drug molecules and eject them through openings in the cell wall.

“Cancer cells have novel ways of resisting drugs, like these ‘pumps,’ and the exciting part of packaging the drug this way is that we can circumvent those defenses so that the drug accumulates in the cancer cell and causes it to die,” said John Byrd, MD, of The Ohio State University.

“Potentially, we can also tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects.”

In tests, the resistant AML cells effectively absorbed molecules of daunorubicin when they were hidden inside the rod-shaped nanostructures.

The researchers tracked the nanostructures inside the cells using fluorescent tags. Each structure measures about 15 nanometers wide and 100 nanometers long, and each has 4 hollow, open-ended interior compartments.

Study author Christopher Lucas, PhD, of The Ohio State University, said the design of the nanostructures maximizes the surface area available to carry the drug.

“The way daunorubicin works is it tucks into the cancer cell’s DNA and prevents it from replicating,” Dr Lucas said. “So we designed a capsule structure that would have lots of accessible DNA base-pairs for it to tuck into. When the capsule breaks down, the drug molecules are freed to flood the cell.”

The researchers said they designed the nanostructures to be strong and stable so they wouldn’t fully disintegrate and release the bulk of the drug until it was too late for the cells to eject them.

And that’s what the team observed with a fluorescence microscope. The cells drew the nanostructures into the organelles that would normally digest them (if they were food).

When the nanostructures broke down, the drug flooded the cells and caused them to disintegrate. Most cells died within the first 15 hours after consuming the nanostructures.

“DNA origami nanostructures have a lot of potential for drug delivery, not just for making effective drug delivery vehicles, but enabling new ways to study drug delivery,” said Carlos Castro, PhD, of The Ohio State University.

“For instance, we can vary the shape or mechanical stiffness of a structure very precisely and see how that affects entry into cells.”

Dr Castro said he hopes to create a streamlined and economically viable process for building DNA origami nanostructures as part of a modular drug delivery system.

Dr Byrd said the technique should work on most any form of drug-resistant cancer if further research shows it can be translated to animal models.

Cancer patient

receiving treatment

Photo by Rhoda Baer

A new report suggests African Americans (AAs) have significantly lower rates of most hematologic malignancies than non-Hispanic white (NHW) individuals in the US.

AAs of both sexes had significantly lower rates of leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) than NHWs, but the rate of myeloma was significantly higher among AAs.

The death rates for these malignancies followed the same patterns, with the exception of HL. There was no significant difference in HL mortality between AAs and NHWs of either sex.

These findings can be found in the report, “Cancer Statistics for African Americans, 2016,” appearing in CA: A Cancer Journal for Clinicians.

To compile this report, the researchers used data from the Surveillance, Epidemiology, and End Results program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries.

Incidence

For part of the report, the researchers compared the incidence of cancers between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

Among females, the incidence of leukemia was 8.6 per 100,000 in AAs and 10.7 per 100,000 in NHWs (P<0.05). Among males, the incidence was 13.2 per 100,000 in AAs and 17.7 per 100,000 in NHWs (P<0.05).

The incidence of HL in females was 2.4 per 100,000 in AAs and 2.7 per 100,000 in NHWs (P<0.05). The incidence of HL in males was 3.2 per 100,000 in AAs and 3.4 per 100,000 in NHWs (P<0.05).

The incidence of NHL in females was 12.0 per 100,000 in AAs and 16.6 per 100,000 in NHWs (P<0.05). The incidence of NHL in males was 17.2 per 100,000 in AAs and 24.1 per 100,000 in NHWs (P<0.05).

The incidence of myeloma in females was 11.1 per 100,000 in AAs and 4.3 per 100,000 in NHWs (P<0.05). The incidence of myeloma in males was 14.8 per 100,000 in AAs and 7.0 per 100,000 in NHWs (P<0.05).

Mortality

The researchers also compared cancer mortality between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

The death rate for female leukemia patients was 4.8 per 100,000 in AAs and 5.4 per 100,000 in NHWs (P<0.05). The death rate for male leukemia patients was 8.1 per 100,000 in AAs and 9.9 per 100,000 in NHWs (P<0.05).

The death rate for female HL patients was 0.3 per 100,000 for both AAs and NHWs. The death rate for male HL patients was 0.4 per 100,000 for AAs and 0.5 per 100,000 in NHWs (not significant).

The death rate for female NHL patients was 3.6 per 100,000 in AAs and 5.0 per 100,000 in NHWs (P<0.05). The death rate for male NHL patients was 5.9 per 100,000 in AAs and 8.3 per 100,000 in NHWs (P<0.05).

The death rate for female myeloma patients was 5.4 per 100,000 in AAs and 2.4 per 100,000 in NHWs (P<0.05). The death rate for male myeloma patients was 7.8 per 100,000 in AAs and 4.0 per 100,000 in NHWs (P<0.05).

The researchers noted that the reasons for the higher rates of myeloma and myeloma death among AAs are, at present, unknown.

Cancer patient

receiving treatment

Photo by Rhoda Baer

A new report suggests African Americans (AAs) have significantly lower rates of most hematologic malignancies than non-Hispanic white (NHW) individuals in the US.

AAs of both sexes had significantly lower rates of leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) than NHWs, but the rate of myeloma was significantly higher among AAs.

The death rates for these malignancies followed the same patterns, with the exception of HL. There was no significant difference in HL mortality between AAs and NHWs of either sex.

These findings can be found in the report, “Cancer Statistics for African Americans, 2016,” appearing in CA: A Cancer Journal for Clinicians.

To compile this report, the researchers used data from the Surveillance, Epidemiology, and End Results program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries.

Incidence

For part of the report, the researchers compared the incidence of cancers between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

Among females, the incidence of leukemia was 8.6 per 100,000 in AAs and 10.7 per 100,000 in NHWs (P<0.05). Among males, the incidence was 13.2 per 100,000 in AAs and 17.7 per 100,000 in NHWs (P<0.05).

The incidence of HL in females was 2.4 per 100,000 in AAs and 2.7 per 100,000 in NHWs (P<0.05). The incidence of HL in males was 3.2 per 100,000 in AAs and 3.4 per 100,000 in NHWs (P<0.05).

The incidence of NHL in females was 12.0 per 100,000 in AAs and 16.6 per 100,000 in NHWs (P<0.05). The incidence of NHL in males was 17.2 per 100,000 in AAs and 24.1 per 100,000 in NHWs (P<0.05).

The incidence of myeloma in females was 11.1 per 100,000 in AAs and 4.3 per 100,000 in NHWs (P<0.05). The incidence of myeloma in males was 14.8 per 100,000 in AAs and 7.0 per 100,000 in NHWs (P<0.05).

Mortality

The researchers also compared cancer mortality between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

The death rate for female leukemia patients was 4.8 per 100,000 in AAs and 5.4 per 100,000 in NHWs (P<0.05). The death rate for male leukemia patients was 8.1 per 100,000 in AAs and 9.9 per 100,000 in NHWs (P<0.05).

The death rate for female HL patients was 0.3 per 100,000 for both AAs and NHWs. The death rate for male HL patients was 0.4 per 100,000 for AAs and 0.5 per 100,000 in NHWs (not significant).

The death rate for female NHL patients was 3.6 per 100,000 in AAs and 5.0 per 100,000 in NHWs (P<0.05). The death rate for male NHL patients was 5.9 per 100,000 in AAs and 8.3 per 100,000 in NHWs (P<0.05).

The death rate for female myeloma patients was 5.4 per 100,000 in AAs and 2.4 per 100,000 in NHWs (P<0.05). The death rate for male myeloma patients was 7.8 per 100,000 in AAs and 4.0 per 100,000 in NHWs (P<0.05).

The researchers noted that the reasons for the higher rates of myeloma and myeloma death among AAs are, at present, unknown.

Cancer patient

receiving treatment

Photo by Rhoda Baer

A new report suggests African Americans (AAs) have significantly lower rates of most hematologic malignancies than non-Hispanic white (NHW) individuals in the US.

AAs of both sexes had significantly lower rates of leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) than NHWs, but the rate of myeloma was significantly higher among AAs.

The death rates for these malignancies followed the same patterns, with the exception of HL. There was no significant difference in HL mortality between AAs and NHWs of either sex.

These findings can be found in the report, “Cancer Statistics for African Americans, 2016,” appearing in CA: A Cancer Journal for Clinicians.

To compile this report, the researchers used data from the Surveillance, Epidemiology, and End Results program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries.

Incidence

For part of the report, the researchers compared the incidence of cancers between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

Among females, the incidence of leukemia was 8.6 per 100,000 in AAs and 10.7 per 100,000 in NHWs (P<0.05). Among males, the incidence was 13.2 per 100,000 in AAs and 17.7 per 100,000 in NHWs (P<0.05).

The incidence of HL in females was 2.4 per 100,000 in AAs and 2.7 per 100,000 in NHWs (P<0.05). The incidence of HL in males was 3.2 per 100,000 in AAs and 3.4 per 100,000 in NHWs (P<0.05).

The incidence of NHL in females was 12.0 per 100,000 in AAs and 16.6 per 100,000 in NHWs (P<0.05). The incidence of NHL in males was 17.2 per 100,000 in AAs and 24.1 per 100,000 in NHWs (P<0.05).

The incidence of myeloma in females was 11.1 per 100,000 in AAs and 4.3 per 100,000 in NHWs (P<0.05). The incidence of myeloma in males was 14.8 per 100,000 in AAs and 7.0 per 100,000 in NHWs (P<0.05).

Mortality

The researchers also compared cancer mortality between AAs and NHWs (divided by gender) for the period from 2008 to 2012.

The death rate for female leukemia patients was 4.8 per 100,000 in AAs and 5.4 per 100,000 in NHWs (P<0.05). The death rate for male leukemia patients was 8.1 per 100,000 in AAs and 9.9 per 100,000 in NHWs (P<0.05).

The death rate for female HL patients was 0.3 per 100,000 for both AAs and NHWs. The death rate for male HL patients was 0.4 per 100,000 for AAs and 0.5 per 100,000 in NHWs (not significant).

The death rate for female NHL patients was 3.6 per 100,000 in AAs and 5.0 per 100,000 in NHWs (P<0.05). The death rate for male NHL patients was 5.9 per 100,000 in AAs and 8.3 per 100,000 in NHWs (P<0.05).

The death rate for female myeloma patients was 5.4 per 100,000 in AAs and 2.4 per 100,000 in NHWs (P<0.05). The death rate for male myeloma patients was 7.8 per 100,000 in AAs and 4.0 per 100,000 in NHWs (P<0.05).

The researchers noted that the reasons for the higher rates of myeloma and myeloma death among AAs are, at present, unknown.

Excellent communication between physicians and patients is a crucial element of hospital quality, but it’s also an ongoing challenge for many institutions. One physician wondered whether letting patients read their physicians’ notes could help.

“I wanted to find new methods to improve patient understanding of their medical care plan,” says Craig Weinert, MD, MPH, medical director for adult inpatient services at the University of Minnesota Medical Center and author of “Giving Doctors’ Daily Progress Notes to Hospitalized Patients and Families to Improve Patient Experience” in the American Journal of Medical Quality. “It seemed logical to me that giving patients access to the same information that all the other members of the healthcare team were reading would improve communication. This is the overall hypothesis of the Open Notes movement.”

Another reason Dr. Weinert pursued the study: In his clinical job as an intensivist, he encounters frequent disagreements with patients’ families regarding prognosis and goals of care.

“No one has figured out how to increase the alignment of prognosis between the family and the medical team,” Dr. Weinert says. “I think having the families read the doctors’ notes, where the issues with poor-prognosis multi-organ failure are repeatedly spelled out, might help families more quickly grasp the futility of continuing care.”

During the study, hospitalized patients or family members on six wards of a university hospital received a printed copy of their medical team’s daily progress notes. Surveys afterward showed 74% to 86% of patients and family members responded favorably. Physicians were mostly satisfied, too.

“Most doctors, at the end of the study, thought that Open Notes went better than they had predicted,” Dr. Weinert says.

Complete transparency of medical records is the future of medicine, he says. It’s what patients want, “especially the younger generation.”

“Over the next 10 years,” he says, “I predict ... all [electronic medical record] vendors will have electronic portals that allow clinic and hospitalized patients access to almost everything in the EMR.”

Reference

1. Weinert C. Giving doctors’ daily progress notes to hospitalized patients and families to improve patient experience. Am J Med Qual. 2015. doi:10.1177/1062860615610424.

Excellent communication between physicians and patients is a crucial element of hospital quality, but it’s also an ongoing challenge for many institutions. One physician wondered whether letting patients read their physicians’ notes could help.

“I wanted to find new methods to improve patient understanding of their medical care plan,” says Craig Weinert, MD, MPH, medical director for adult inpatient services at the University of Minnesota Medical Center and author of “Giving Doctors’ Daily Progress Notes to Hospitalized Patients and Families to Improve Patient Experience” in the American Journal of Medical Quality. “It seemed logical to me that giving patients access to the same information that all the other members of the healthcare team were reading would improve communication. This is the overall hypothesis of the Open Notes movement.”

Another reason Dr. Weinert pursued the study: In his clinical job as an intensivist, he encounters frequent disagreements with patients’ families regarding prognosis and goals of care.

“No one has figured out how to increase the alignment of prognosis between the family and the medical team,” Dr. Weinert says. “I think having the families read the doctors’ notes, where the issues with poor-prognosis multi-organ failure are repeatedly spelled out, might help families more quickly grasp the futility of continuing care.”

During the study, hospitalized patients or family members on six wards of a university hospital received a printed copy of their medical team’s daily progress notes. Surveys afterward showed 74% to 86% of patients and family members responded favorably. Physicians were mostly satisfied, too.

“Most doctors, at the end of the study, thought that Open Notes went better than they had predicted,” Dr. Weinert says.

Complete transparency of medical records is the future of medicine, he says. It’s what patients want, “especially the younger generation.”

“Over the next 10 years,” he says, “I predict ... all [electronic medical record] vendors will have electronic portals that allow clinic and hospitalized patients access to almost everything in the EMR.”

Reference

1. Weinert C. Giving doctors’ daily progress notes to hospitalized patients and families to improve patient experience. Am J Med Qual. 2015. doi:10.1177/1062860615610424.

Excellent communication between physicians and patients is a crucial element of hospital quality, but it’s also an ongoing challenge for many institutions. One physician wondered whether letting patients read their physicians’ notes could help.

“I wanted to find new methods to improve patient understanding of their medical care plan,” says Craig Weinert, MD, MPH, medical director for adult inpatient services at the University of Minnesota Medical Center and author of “Giving Doctors’ Daily Progress Notes to Hospitalized Patients and Families to Improve Patient Experience” in the American Journal of Medical Quality. “It seemed logical to me that giving patients access to the same information that all the other members of the healthcare team were reading would improve communication. This is the overall hypothesis of the Open Notes movement.”

Another reason Dr. Weinert pursued the study: In his clinical job as an intensivist, he encounters frequent disagreements with patients’ families regarding prognosis and goals of care.

“No one has figured out how to increase the alignment of prognosis between the family and the medical team,” Dr. Weinert says. “I think having the families read the doctors’ notes, where the issues with poor-prognosis multi-organ failure are repeatedly spelled out, might help families more quickly grasp the futility of continuing care.”

During the study, hospitalized patients or family members on six wards of a university hospital received a printed copy of their medical team’s daily progress notes. Surveys afterward showed 74% to 86% of patients and family members responded favorably. Physicians were mostly satisfied, too.

“Most doctors, at the end of the study, thought that Open Notes went better than they had predicted,” Dr. Weinert says.

Complete transparency of medical records is the future of medicine, he says. It’s what patients want, “especially the younger generation.”

“Over the next 10 years,” he says, “I predict ... all [electronic medical record] vendors will have electronic portals that allow clinic and hospitalized patients access to almost everything in the EMR.”

Reference

1. Weinert C. Giving doctors’ daily progress notes to hospitalized patients and families to improve patient experience. Am J Med Qual. 2015. doi:10.1177/1062860615610424.

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

Genetically modified zebrafish

New research suggests T-cell acute lymphoblastic leukemia (T-ALL) cells use the tricarboxylic acid (TCA) cycle to support their growth and survival.

Investigators say the findings could aid the development of therapeutics that can kill T-ALL cells by targeting an enzyme that exists in the TCA cycle—dihydrolipoamide S-succinyltransferase (DLST).

The team described this research in the journal Leukemia.

“Researchers have wrongly assumed that cancer cells do not use the TCA cycle to support their growth,” said study author Hui Feng, MD, PhD, of Boston University Medical Center in Massachusetts.

“Our new findings provide solid evidence that these cancer cells depend on the TCA cycle for their survival. Additionally, we demonstrated the importance of DLST in T-cell leukemia development and have identified a targetable enzyme for T-cell leukemia treatment.”

For this study, the investigators set out to examine the mechanisms underlying MYC-mediated tumorigenesis in T-ALL.

They used a zebrafish model of MYC-induced T-ALL to screen for genes that contribute to disease onset. The results suggested the TCA-cycle enzyme DLST is an important contributor to T-ALL development.

And experiments showed that heterozygous inactivation of DLST significantly delayed disease onset in the zebrafish, apparently without affecting the development of the fish.

Further analysis revealed that inhibiting the activity of DLST could effectively kill human T-ALL cells. Specifically, RNAi knockdown of DLST decreased cell viability and induced apoptosis in human T-ALL cell

lines.

The investigators found that knockdown of DLST disrupted the TCA cycle in the human T-ALL cells. But adding succinate, the downstream TCA-cycle intermediate, to the cells rescued defects in cell viability caused by DLST knockdown.

The investigators said the therapeutic benefit of DLST inhibition may extend to cancers other than T-ALL as well.

Genetically modified zebrafish

New research suggests T-cell acute lymphoblastic leukemia (T-ALL) cells use the tricarboxylic acid (TCA) cycle to support their growth and survival.

Investigators say the findings could aid the development of therapeutics that can kill T-ALL cells by targeting an enzyme that exists in the TCA cycle—dihydrolipoamide S-succinyltransferase (DLST).

The team described this research in the journal Leukemia.

“Researchers have wrongly assumed that cancer cells do not use the TCA cycle to support their growth,” said study author Hui Feng, MD, PhD, of Boston University Medical Center in Massachusetts.

“Our new findings provide solid evidence that these cancer cells depend on the TCA cycle for their survival. Additionally, we demonstrated the importance of DLST in T-cell leukemia development and have identified a targetable enzyme for T-cell leukemia treatment.”

For this study, the investigators set out to examine the mechanisms underlying MYC-mediated tumorigenesis in T-ALL.

They used a zebrafish model of MYC-induced T-ALL to screen for genes that contribute to disease onset. The results suggested the TCA-cycle enzyme DLST is an important contributor to T-ALL development.

And experiments showed that heterozygous inactivation of DLST significantly delayed disease onset in the zebrafish, apparently without affecting the development of the fish.

Further analysis revealed that inhibiting the activity of DLST could effectively kill human T-ALL cells. Specifically, RNAi knockdown of DLST decreased cell viability and induced apoptosis in human T-ALL cell

lines.

The investigators found that knockdown of DLST disrupted the TCA cycle in the human T-ALL cells. But adding succinate, the downstream TCA-cycle intermediate, to the cells rescued defects in cell viability caused by DLST knockdown.

The investigators said the therapeutic benefit of DLST inhibition may extend to cancers other than T-ALL as well.

Genetically modified zebrafish

New research suggests T-cell acute lymphoblastic leukemia (T-ALL) cells use the tricarboxylic acid (TCA) cycle to support their growth and survival.

Investigators say the findings could aid the development of therapeutics that can kill T-ALL cells by targeting an enzyme that exists in the TCA cycle—dihydrolipoamide S-succinyltransferase (DLST).

The team described this research in the journal Leukemia.

“Researchers have wrongly assumed that cancer cells do not use the TCA cycle to support their growth,” said study author Hui Feng, MD, PhD, of Boston University Medical Center in Massachusetts.

“Our new findings provide solid evidence that these cancer cells depend on the TCA cycle for their survival. Additionally, we demonstrated the importance of DLST in T-cell leukemia development and have identified a targetable enzyme for T-cell leukemia treatment.”

For this study, the investigators set out to examine the mechanisms underlying MYC-mediated tumorigenesis in T-ALL.

They used a zebrafish model of MYC-induced T-ALL to screen for genes that contribute to disease onset. The results suggested the TCA-cycle enzyme DLST is an important contributor to T-ALL development.

And experiments showed that heterozygous inactivation of DLST significantly delayed disease onset in the zebrafish, apparently without affecting the development of the fish.

Further analysis revealed that inhibiting the activity of DLST could effectively kill human T-ALL cells. Specifically, RNAi knockdown of DLST decreased cell viability and induced apoptosis in human T-ALL cell

lines.

The investigators found that knockdown of DLST disrupted the TCA cycle in the human T-ALL cells. But adding succinate, the downstream TCA-cycle intermediate, to the cells rescued defects in cell viability caused by DLST knockdown.

The investigators said the therapeutic benefit of DLST inhibition may extend to cancers other than T-ALL as well.

Micrograph showing CLL

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.

The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.

The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.

To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.

Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.

About acalabrutinib

Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.

Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.

The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).

Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.

At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.

The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).

Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).

The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.

The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.

Micrograph showing CLL

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.

The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.

The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.

To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.

Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.

About acalabrutinib

Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.

Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.

The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).

Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.

At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.

The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).

Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).

The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.

The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.

Micrograph showing CLL

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.

The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.

The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.

To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.

Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.

About acalabrutinib

Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.

Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.

The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).

Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.

At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.

The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).

Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).

The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.

The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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; [email protected].

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; [email protected].

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; [email protected].

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).

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“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.