Study Overview

Objective. To compare rates of asthma action plan use in limited English proficiency (LEP) caregivers compared with English proficient (EP) caregivers.

Design. Cross-sectional survey.

Participants and setting. A convenience sample of 107 Latino caregivers of children with asthma at an urban academic emergency department (ED). Surveys in the preferred language of the patient (English or Spanish, with the translated version previously validated) were distributed at the time of the ED visit. Interpreters were utilized when requested.

Main outcome measure. Caregiver use of an asthma action plan.

Main results. 51 LEP caregivers and 56 EP caregivers completed the survey. Mothers completed the surveys 87% of the time and the average age of patients was 4 years.  Among the EP caregivers, 64% reported using an asthma action plan, while only 39% of the LEP caregivers reported using one. The difference was statistally significant (P = 0.01). Through both correlations and regressions, English proficiency was the only variable (others included health insurance status and level of caregiver education) that showed a significant effect on asthma action plan use.

Conclusions. Children whose caregiver had LEP were significantly less likely to have and use an asthma action plan. Asthma education in the language of choice of the patient may help improve asthma care.

Commentary

With 20% of US households now speaking a language other than English at home [1], language barriers between providers and patients present multiple challenges to health services delivery and can significantly contribute to immigrant health disparities. Despite US laws and multiple federal agency policies requiring the use of interpreters during health care encounters, organizations continue to fall short of providing interpreter services and often lack adequate or equivalent materials for patient education. Too often, providers overestimate their language skills [2,3], use colleagues as ad hoc interpreters out of convenience [4], or rely on family members for interpretation [4]—a practice that is universally discouraged.

Recent research does suggest that the timing of interpreter use is critical. In planned encounters such as primary care visits, interpreters can and should be scheduled for visits when a language-concordant provider is not available. During hospitalizations, including ED visits, interpreters are most effective when used on admission, during patient teaching, and upon discharge, and the timing of these visits has been shown to affect length of stay and readmission rates [5,6].

This study magnifies the consequences of failing to provide language-concordant services to patients and their caregivers. It also helps to identify one of the sources of pediatric asthma health disparities in Latino populations. The emphasis on the role of the caregiver in action plan utilization is a unique aspect of this study and it is one of the first to examine the issue in this way. It highlights the importance of caregivers in health system transitions and illustrates how a language barrier can potentially impact transitions.

The authors’ explicit use of a power analysis to calculate their sample size is a strength of the study. Furthermore, the authors differentiated their respondents by country of origin, something that rarely occurs in studies of Latinos [7], and allows the reader to differentiate the impact of the intervention at a micro level within this population. The presentation of Spanish language quotes with their translations within the manuscript provides transparency for bilingual readers to verify the accuracy of the authors’ translation.

There are, however, a number of methodological issues that should be noted. The authors acknowledge that they did not account for asthma severity in the survey nor control for it in the analysis, did not assess health literacy, and did not differentiate their results based on country of origin. The latter point is important because the immigration experience and demographic profiles of Latinos differs significantly by country of origin and could factor in to action plan use. The translation process used for survey instrument translation also did not illustrate how it accounted for the well-established linguistic variation that occurs in the Spanish language. Additionally, US census data shows that the main countries of origin of Latinos in the service area of the study are Puerto Rico, Ecuador, and Mexico [1]. The survey itself had Ecuador as a write in and Dominican as a response option. The combination presented in the survey reflects the Latino demographic composition in the nearest large urban area. Thus, when collecting country of origin data on immigrant patients, country choices should reflect local demographics and not national trends for maximum precision.

Another concern is that Spanish language literacy was not assessed. Many Latino immigrants may have limited reading ability in Spanish. For Mexican immigrants in particular, Spanish may be a second language after their indigenous language. This is also true for some South American Latino immigrants from the Andean region. Many Latino immigrants come to the United States with less than an 8th grade education and likely come from educational systems of poor quality, which subsequently affects their Spanish language reading and writing skills [8]. Assessing education level based on US equivalents is not an accurate way to gauge literacy. Thus, assessing reading literacy in Spanish before surveying patients would have been a useful step that could have further refined the results. These factors will have implications for action plan utilization and implementation for any chronic disease.

Providers often think that language barriers are an obvious factor in health disparities and service delivery, but few studies have actually captured or quantified the effects of language barriers on health outcomes. Most studies only identify language barriers as an access issue. This study provides a good illustration of the impact of a language barrier on a known and effective intervention for pediatric asthma management. Practitioners can take the consequences illustrated in this study and easily extrapolate the contribution to health disparities on a broader scale.

Applications for Clinical Practice

Practitioners caring for patients in EDs where the patient or caregiver has a language barrier should make every effort to use appropriate interpreter services when patient teaching occurs. Assessing not only for health literacy but reading ability in the LEP patient or caregiver is also important, since it will affect dyad’s ability to implement self-care measures recommended in patient teaching sessions or action plan implementation. Asking the patient what their country of origin is, regardless of their legal status, will help practitioners refine patient teaching and the language they (and the interpreter when appropriate) use to illustrate what needs to be done to manage their condition.

—Allison Squires, PhD, RN

Study Overview

Objective. To compare rates of asthma action plan use in limited English proficiency (LEP) caregivers compared with English proficient (EP) caregivers.

Design. Cross-sectional survey.

Participants and setting. A convenience sample of 107 Latino caregivers of children with asthma at an urban academic emergency department (ED). Surveys in the preferred language of the patient (English or Spanish, with the translated version previously validated) were distributed at the time of the ED visit. Interpreters were utilized when requested.

Main outcome measure. Caregiver use of an asthma action plan.

Main results. 51 LEP caregivers and 56 EP caregivers completed the survey. Mothers completed the surveys 87% of the time and the average age of patients was 4 years.  Among the EP caregivers, 64% reported using an asthma action plan, while only 39% of the LEP caregivers reported using one. The difference was statistally significant (P = 0.01). Through both correlations and regressions, English proficiency was the only variable (others included health insurance status and level of caregiver education) that showed a significant effect on asthma action plan use.

Conclusions. Children whose caregiver had LEP were significantly less likely to have and use an asthma action plan. Asthma education in the language of choice of the patient may help improve asthma care.

Commentary

With 20% of US households now speaking a language other than English at home [1], language barriers between providers and patients present multiple challenges to health services delivery and can significantly contribute to immigrant health disparities. Despite US laws and multiple federal agency policies requiring the use of interpreters during health care encounters, organizations continue to fall short of providing interpreter services and often lack adequate or equivalent materials for patient education. Too often, providers overestimate their language skills [2,3], use colleagues as ad hoc interpreters out of convenience [4], or rely on family members for interpretation [4]—a practice that is universally discouraged.

Recent research does suggest that the timing of interpreter use is critical. In planned encounters such as primary care visits, interpreters can and should be scheduled for visits when a language-concordant provider is not available. During hospitalizations, including ED visits, interpreters are most effective when used on admission, during patient teaching, and upon discharge, and the timing of these visits has been shown to affect length of stay and readmission rates [5,6].

This study magnifies the consequences of failing to provide language-concordant services to patients and their caregivers. It also helps to identify one of the sources of pediatric asthma health disparities in Latino populations. The emphasis on the role of the caregiver in action plan utilization is a unique aspect of this study and it is one of the first to examine the issue in this way. It highlights the importance of caregivers in health system transitions and illustrates how a language barrier can potentially impact transitions.

The authors’ explicit use of a power analysis to calculate their sample size is a strength of the study. Furthermore, the authors differentiated their respondents by country of origin, something that rarely occurs in studies of Latinos [7], and allows the reader to differentiate the impact of the intervention at a micro level within this population. The presentation of Spanish language quotes with their translations within the manuscript provides transparency for bilingual readers to verify the accuracy of the authors’ translation.

There are, however, a number of methodological issues that should be noted. The authors acknowledge that they did not account for asthma severity in the survey nor control for it in the analysis, did not assess health literacy, and did not differentiate their results based on country of origin. The latter point is important because the immigration experience and demographic profiles of Latinos differs significantly by country of origin and could factor in to action plan use. The translation process used for survey instrument translation also did not illustrate how it accounted for the well-established linguistic variation that occurs in the Spanish language. Additionally, US census data shows that the main countries of origin of Latinos in the service area of the study are Puerto Rico, Ecuador, and Mexico [1]. The survey itself had Ecuador as a write in and Dominican as a response option. The combination presented in the survey reflects the Latino demographic composition in the nearest large urban area. Thus, when collecting country of origin data on immigrant patients, country choices should reflect local demographics and not national trends for maximum precision.

Another concern is that Spanish language literacy was not assessed. Many Latino immigrants may have limited reading ability in Spanish. For Mexican immigrants in particular, Spanish may be a second language after their indigenous language. This is also true for some South American Latino immigrants from the Andean region. Many Latino immigrants come to the United States with less than an 8th grade education and likely come from educational systems of poor quality, which subsequently affects their Spanish language reading and writing skills [8]. Assessing education level based on US equivalents is not an accurate way to gauge literacy. Thus, assessing reading literacy in Spanish before surveying patients would have been a useful step that could have further refined the results. These factors will have implications for action plan utilization and implementation for any chronic disease.

Providers often think that language barriers are an obvious factor in health disparities and service delivery, but few studies have actually captured or quantified the effects of language barriers on health outcomes. Most studies only identify language barriers as an access issue. This study provides a good illustration of the impact of a language barrier on a known and effective intervention for pediatric asthma management. Practitioners can take the consequences illustrated in this study and easily extrapolate the contribution to health disparities on a broader scale.

Applications for Clinical Practice

Practitioners caring for patients in EDs where the patient or caregiver has a language barrier should make every effort to use appropriate interpreter services when patient teaching occurs. Assessing not only for health literacy but reading ability in the LEP patient or caregiver is also important, since it will affect dyad’s ability to implement self-care measures recommended in patient teaching sessions or action plan implementation. Asking the patient what their country of origin is, regardless of their legal status, will help practitioners refine patient teaching and the language they (and the interpreter when appropriate) use to illustrate what needs to be done to manage their condition.

—Allison Squires, PhD, RN

Study Overview

Objective. To compare rates of asthma action plan use in limited English proficiency (LEP) caregivers compared with English proficient (EP) caregivers.

Design. Cross-sectional survey.

Participants and setting. A convenience sample of 107 Latino caregivers of children with asthma at an urban academic emergency department (ED). Surveys in the preferred language of the patient (English or Spanish, with the translated version previously validated) were distributed at the time of the ED visit. Interpreters were utilized when requested.

Main outcome measure. Caregiver use of an asthma action plan.

Main results. 51 LEP caregivers and 56 EP caregivers completed the survey. Mothers completed the surveys 87% of the time and the average age of patients was 4 years.  Among the EP caregivers, 64% reported using an asthma action plan, while only 39% of the LEP caregivers reported using one. The difference was statistally significant (P = 0.01). Through both correlations and regressions, English proficiency was the only variable (others included health insurance status and level of caregiver education) that showed a significant effect on asthma action plan use.

Conclusions. Children whose caregiver had LEP were significantly less likely to have and use an asthma action plan. Asthma education in the language of choice of the patient may help improve asthma care.

Commentary

With 20% of US households now speaking a language other than English at home [1], language barriers between providers and patients present multiple challenges to health services delivery and can significantly contribute to immigrant health disparities. Despite US laws and multiple federal agency policies requiring the use of interpreters during health care encounters, organizations continue to fall short of providing interpreter services and often lack adequate or equivalent materials for patient education. Too often, providers overestimate their language skills [2,3], use colleagues as ad hoc interpreters out of convenience [4], or rely on family members for interpretation [4]—a practice that is universally discouraged.

Recent research does suggest that the timing of interpreter use is critical. In planned encounters such as primary care visits, interpreters can and should be scheduled for visits when a language-concordant provider is not available. During hospitalizations, including ED visits, interpreters are most effective when used on admission, during patient teaching, and upon discharge, and the timing of these visits has been shown to affect length of stay and readmission rates [5,6].

This study magnifies the consequences of failing to provide language-concordant services to patients and their caregivers. It also helps to identify one of the sources of pediatric asthma health disparities in Latino populations. The emphasis on the role of the caregiver in action plan utilization is a unique aspect of this study and it is one of the first to examine the issue in this way. It highlights the importance of caregivers in health system transitions and illustrates how a language barrier can potentially impact transitions.

The authors’ explicit use of a power analysis to calculate their sample size is a strength of the study. Furthermore, the authors differentiated their respondents by country of origin, something that rarely occurs in studies of Latinos [7], and allows the reader to differentiate the impact of the intervention at a micro level within this population. The presentation of Spanish language quotes with their translations within the manuscript provides transparency for bilingual readers to verify the accuracy of the authors’ translation.

There are, however, a number of methodological issues that should be noted. The authors acknowledge that they did not account for asthma severity in the survey nor control for it in the analysis, did not assess health literacy, and did not differentiate their results based on country of origin. The latter point is important because the immigration experience and demographic profiles of Latinos differs significantly by country of origin and could factor in to action plan use. The translation process used for survey instrument translation also did not illustrate how it accounted for the well-established linguistic variation that occurs in the Spanish language. Additionally, US census data shows that the main countries of origin of Latinos in the service area of the study are Puerto Rico, Ecuador, and Mexico [1]. The survey itself had Ecuador as a write in and Dominican as a response option. The combination presented in the survey reflects the Latino demographic composition in the nearest large urban area. Thus, when collecting country of origin data on immigrant patients, country choices should reflect local demographics and not national trends for maximum precision.

Another concern is that Spanish language literacy was not assessed. Many Latino immigrants may have limited reading ability in Spanish. For Mexican immigrants in particular, Spanish may be a second language after their indigenous language. This is also true for some South American Latino immigrants from the Andean region. Many Latino immigrants come to the United States with less than an 8th grade education and likely come from educational systems of poor quality, which subsequently affects their Spanish language reading and writing skills [8]. Assessing education level based on US equivalents is not an accurate way to gauge literacy. Thus, assessing reading literacy in Spanish before surveying patients would have been a useful step that could have further refined the results. These factors will have implications for action plan utilization and implementation for any chronic disease.

Providers often think that language barriers are an obvious factor in health disparities and service delivery, but few studies have actually captured or quantified the effects of language barriers on health outcomes. Most studies only identify language barriers as an access issue. This study provides a good illustration of the impact of a language barrier on a known and effective intervention for pediatric asthma management. Practitioners can take the consequences illustrated in this study and easily extrapolate the contribution to health disparities on a broader scale.

Applications for Clinical Practice

Practitioners caring for patients in EDs where the patient or caregiver has a language barrier should make every effort to use appropriate interpreter services when patient teaching occurs. Assessing not only for health literacy but reading ability in the LEP patient or caregiver is also important, since it will affect dyad’s ability to implement self-care measures recommended in patient teaching sessions or action plan implementation. Asking the patient what their country of origin is, regardless of their legal status, will help practitioners refine patient teaching and the language they (and the interpreter when appropriate) use to illustrate what needs to be done to manage their condition.

—Allison Squires, PhD, RN

Platelets in a blood smear

Some processes used to sterilize blood for transfusion are harmful to platelet function and could cause serious health issues in transfusion recipients, researchers say.

They found that some pathogen-reduction treatments impact platelets to the extent that they may be the cause of hemorrhages in recipients. 

The pathogen reduction treatments “were developed more than 20 years ago, before we understood the importance of the genetic material contained in platelets,” explained study author Patrick Provost, PhD, of Université Laval and the CHU de Québec Research Center in Canada. 

Platelets contain up to a third of the human genome in the form of ribonucleic acid (RNA), which enables them to synthesize over 1,000 proteins essential to the normal functioning of the human body.

The researchers studied the effects of 3 pathogen-reduction strategies—irradiation, riboflavin plus UVB light (Mirasol), and amotosalen plus UVA light (Intercept)—on platelet microRNAs, messenger RNAs (mRNAs), activation, and function. 

They reported their findings in the journal Platelets. 

The investigators collected 50 single-donor (apheresis) platelet concentrates (PCs) and subjected them to 5 treatments.

The control platelets were stored in donor plasma; additive solution platelets were stored in 65% storage solution and 35% donor plasma; the irradiation platelets were treated with 30Gy gamma irradiation and stored in donor plasma; the platelets treated with Mirasol were stored in donor plasma; and the platelets treated with Intercept were stored in the same solution as the additive solution group.

All treatments followed standard procedures or the manufacturer’s instructions.

After platelet isolation and RNA extraction, the investigators analyzed the levels of microRNA and mRNA levels of the platelets and assessed the impact of those levels on platelet activation and function.

MicroRNA profiles

They learned that platelets stored with additive solution or irradiation had significantly (P<0.05) reduced levels of one microRNA each, and only on day 7 of storage. Additive solution reduced the level of miR-223 and irradiation reduced the level of let-73. 

Mirasol did not significantly reduce the level of any of the 11 tested micro RNAs. 

And Intercept significantly reduced the level of 6 microRNAs on day 1, 1 microRNA on day 4, and 2 microRNAs on day 7. By day 7, let-7e was reduced by up to 70%.

The microRNA levels remained stable in the control sample for the entire 7-day storage period.

Platelet activation and function

Platelet counts in the Mirasol- and Intercept-treated platelets were significantly lower (P<0.001) on storage days 1, 4, and 7 compared with control platelets.

Pathogen-reduction treatments did not affect platelet microRNA synthesis, platelet microRNA function, nor did they induce the formation of cross-linked RNA adducts.

However, pathogen reduction caused platelet activation, which correlates with the observed reduction in platelet microRNAs. 

The investigators measured CD62P expression, a marker of platelet activation, on the platelet surface. The additive solution platelets and Intercept-treated platelets, and to a lesser degree the irradiation group, had greater CD62P surface expression than the control group (P<0.05) on day 1. 

The Mirasol group had similar activation to that of the control group.

On day 4, all treatment groups showed more activation than the control group (P<0.05). And on day 7, all groups had about the same activation level as the control group.

Pathogen reduction also impacted the aggregation response of platelets. Mirasol-treated platelets, which had the same aggregation response as that of controls on day 1, had no response on days 4 and 7. 

And the aggregation response for Intercept-treated and additive solution platelets was already absent on day 1 and remained so on days 4 and 7.

Additive solution and Intercept also reduced platelet volume on day 1, which the investigators say could be explained by the platelet activation and release of microparticles induced by the treatments.

MicroRNA release

The investigators hypothesized that activated stored platelets could release microRNAs through microparticles in the supernatant. So they collected supernatant from each of the 5 groups and analyzed their total content of miR-223, which is one of the most abundant platelet microRNAs. 

They discovered that the total amount of miR-223 was increased 30% to 86% in the microparticles released from additive solution and Intercept-treated platelets. They did not observe this increase in irradiation- or Mirasol-treated platelets compared to controls. 

"The platelets end up depleted of RNA so, once transfused, they're unable to do what they normally would," Dr Provost said. Nevertheless, the clinical implications of the reduction in platelet activation and impaired platelet aggregation after Intercept treatment remain to be established.

The  pathogen-reduction treatments are already marketed in some European countries, notably Switzerland, France, and Germany, and are under consideration in other countries, including Canada and the United States. 

"In light of what we have demonstrated, the potentially harmful effects of these treatments should be carefully evaluated in the countries where they are not yet approved. It should also be re-evaluated in those countries where they are," Dr Provost said.

Platelets in a blood smear

Some processes used to sterilize blood for transfusion are harmful to platelet function and could cause serious health issues in transfusion recipients, researchers say.

They found that some pathogen-reduction treatments impact platelets to the extent that they may be the cause of hemorrhages in recipients. 

The pathogen reduction treatments “were developed more than 20 years ago, before we understood the importance of the genetic material contained in platelets,” explained study author Patrick Provost, PhD, of Université Laval and the CHU de Québec Research Center in Canada. 

Platelets contain up to a third of the human genome in the form of ribonucleic acid (RNA), which enables them to synthesize over 1,000 proteins essential to the normal functioning of the human body.

The researchers studied the effects of 3 pathogen-reduction strategies—irradiation, riboflavin plus UVB light (Mirasol), and amotosalen plus UVA light (Intercept)—on platelet microRNAs, messenger RNAs (mRNAs), activation, and function. 

They reported their findings in the journal Platelets. 

The investigators collected 50 single-donor (apheresis) platelet concentrates (PCs) and subjected them to 5 treatments.

The control platelets were stored in donor plasma; additive solution platelets were stored in 65% storage solution and 35% donor plasma; the irradiation platelets were treated with 30Gy gamma irradiation and stored in donor plasma; the platelets treated with Mirasol were stored in donor plasma; and the platelets treated with Intercept were stored in the same solution as the additive solution group.

All treatments followed standard procedures or the manufacturer’s instructions.

After platelet isolation and RNA extraction, the investigators analyzed the levels of microRNA and mRNA levels of the platelets and assessed the impact of those levels on platelet activation and function.

MicroRNA profiles

They learned that platelets stored with additive solution or irradiation had significantly (P<0.05) reduced levels of one microRNA each, and only on day 7 of storage. Additive solution reduced the level of miR-223 and irradiation reduced the level of let-73. 

Mirasol did not significantly reduce the level of any of the 11 tested micro RNAs. 

And Intercept significantly reduced the level of 6 microRNAs on day 1, 1 microRNA on day 4, and 2 microRNAs on day 7. By day 7, let-7e was reduced by up to 70%.

The microRNA levels remained stable in the control sample for the entire 7-day storage period.

Platelet activation and function

Platelet counts in the Mirasol- and Intercept-treated platelets were significantly lower (P<0.001) on storage days 1, 4, and 7 compared with control platelets.

Pathogen-reduction treatments did not affect platelet microRNA synthesis, platelet microRNA function, nor did they induce the formation of cross-linked RNA adducts.

However, pathogen reduction caused platelet activation, which correlates with the observed reduction in platelet microRNAs. 

The investigators measured CD62P expression, a marker of platelet activation, on the platelet surface. The additive solution platelets and Intercept-treated platelets, and to a lesser degree the irradiation group, had greater CD62P surface expression than the control group (P<0.05) on day 1. 

The Mirasol group had similar activation to that of the control group.

On day 4, all treatment groups showed more activation than the control group (P<0.05). And on day 7, all groups had about the same activation level as the control group.

Pathogen reduction also impacted the aggregation response of platelets. Mirasol-treated platelets, which had the same aggregation response as that of controls on day 1, had no response on days 4 and 7. 

And the aggregation response for Intercept-treated and additive solution platelets was already absent on day 1 and remained so on days 4 and 7.

Additive solution and Intercept also reduced platelet volume on day 1, which the investigators say could be explained by the platelet activation and release of microparticles induced by the treatments.

MicroRNA release

The investigators hypothesized that activated stored platelets could release microRNAs through microparticles in the supernatant. So they collected supernatant from each of the 5 groups and analyzed their total content of miR-223, which is one of the most abundant platelet microRNAs. 

They discovered that the total amount of miR-223 was increased 30% to 86% in the microparticles released from additive solution and Intercept-treated platelets. They did not observe this increase in irradiation- or Mirasol-treated platelets compared to controls. 

"The platelets end up depleted of RNA so, once transfused, they're unable to do what they normally would," Dr Provost said. Nevertheless, the clinical implications of the reduction in platelet activation and impaired platelet aggregation after Intercept treatment remain to be established.

The  pathogen-reduction treatments are already marketed in some European countries, notably Switzerland, France, and Germany, and are under consideration in other countries, including Canada and the United States. 

"In light of what we have demonstrated, the potentially harmful effects of these treatments should be carefully evaluated in the countries where they are not yet approved. It should also be re-evaluated in those countries where they are," Dr Provost said.

Platelets in a blood smear

Some processes used to sterilize blood for transfusion are harmful to platelet function and could cause serious health issues in transfusion recipients, researchers say.

They found that some pathogen-reduction treatments impact platelets to the extent that they may be the cause of hemorrhages in recipients. 

The pathogen reduction treatments “were developed more than 20 years ago, before we understood the importance of the genetic material contained in platelets,” explained study author Patrick Provost, PhD, of Université Laval and the CHU de Québec Research Center in Canada. 

Platelets contain up to a third of the human genome in the form of ribonucleic acid (RNA), which enables them to synthesize over 1,000 proteins essential to the normal functioning of the human body.

The researchers studied the effects of 3 pathogen-reduction strategies—irradiation, riboflavin plus UVB light (Mirasol), and amotosalen plus UVA light (Intercept)—on platelet microRNAs, messenger RNAs (mRNAs), activation, and function. 

They reported their findings in the journal Platelets. 

The investigators collected 50 single-donor (apheresis) platelet concentrates (PCs) and subjected them to 5 treatments.

The control platelets were stored in donor plasma; additive solution platelets were stored in 65% storage solution and 35% donor plasma; the irradiation platelets were treated with 30Gy gamma irradiation and stored in donor plasma; the platelets treated with Mirasol were stored in donor plasma; and the platelets treated with Intercept were stored in the same solution as the additive solution group.

All treatments followed standard procedures or the manufacturer’s instructions.

After platelet isolation and RNA extraction, the investigators analyzed the levels of microRNA and mRNA levels of the platelets and assessed the impact of those levels on platelet activation and function.

MicroRNA profiles

They learned that platelets stored with additive solution or irradiation had significantly (P<0.05) reduced levels of one microRNA each, and only on day 7 of storage. Additive solution reduced the level of miR-223 and irradiation reduced the level of let-73. 

Mirasol did not significantly reduce the level of any of the 11 tested micro RNAs. 

And Intercept significantly reduced the level of 6 microRNAs on day 1, 1 microRNA on day 4, and 2 microRNAs on day 7. By day 7, let-7e was reduced by up to 70%.

The microRNA levels remained stable in the control sample for the entire 7-day storage period.

Platelet activation and function

Platelet counts in the Mirasol- and Intercept-treated platelets were significantly lower (P<0.001) on storage days 1, 4, and 7 compared with control platelets.

Pathogen-reduction treatments did not affect platelet microRNA synthesis, platelet microRNA function, nor did they induce the formation of cross-linked RNA adducts.

However, pathogen reduction caused platelet activation, which correlates with the observed reduction in platelet microRNAs. 

The investigators measured CD62P expression, a marker of platelet activation, on the platelet surface. The additive solution platelets and Intercept-treated platelets, and to a lesser degree the irradiation group, had greater CD62P surface expression than the control group (P<0.05) on day 1. 

The Mirasol group had similar activation to that of the control group.

On day 4, all treatment groups showed more activation than the control group (P<0.05). And on day 7, all groups had about the same activation level as the control group.

Pathogen reduction also impacted the aggregation response of platelets. Mirasol-treated platelets, which had the same aggregation response as that of controls on day 1, had no response on days 4 and 7. 

And the aggregation response for Intercept-treated and additive solution platelets was already absent on day 1 and remained so on days 4 and 7.

Additive solution and Intercept also reduced platelet volume on day 1, which the investigators say could be explained by the platelet activation and release of microparticles induced by the treatments.

MicroRNA release

The investigators hypothesized that activated stored platelets could release microRNAs through microparticles in the supernatant. So they collected supernatant from each of the 5 groups and analyzed their total content of miR-223, which is one of the most abundant platelet microRNAs. 

They discovered that the total amount of miR-223 was increased 30% to 86% in the microparticles released from additive solution and Intercept-treated platelets. They did not observe this increase in irradiation- or Mirasol-treated platelets compared to controls. 

"The platelets end up depleted of RNA so, once transfused, they're unable to do what they normally would," Dr Provost said. Nevertheless, the clinical implications of the reduction in platelet activation and impaired platelet aggregation after Intercept treatment remain to be established.

The  pathogen-reduction treatments are already marketed in some European countries, notably Switzerland, France, and Germany, and are under consideration in other countries, including Canada and the United States. 

"In light of what we have demonstrated, the potentially harmful effects of these treatments should be carefully evaluated in the countries where they are not yet approved. It should also be re-evaluated in those countries where they are," Dr Provost said.

SAN FRANCISCO – Those looking for guidance from the American Diabetes Association regarding the guidelines released last fall from the American College of Cardiology and the American Heart Association dropping cholesterol treatment goals will have to wait until next year.

That’s when the ADA’s Clinical Practice Recommendations, released each year in January, will incorporate the Professional Practice Committee’s review of the ACC/AHA guidelines and the evidence behind it. The new recommendations caused some controversy and raised some questions about treatment of certain patient groups, most notably those with diabetes.

The ADA hasn’t recommended any changes to its current guidelines, which still incorporate treatment to target. But it has been reviewing the guidelines to see if it would recommend any changes for its 2015 guidelines.

Dr. Robert E. Ratner, chief scientific and medical officer for the American Diabetes Association, further explained the organization’s position on treatment of lipids in patients with diabetes in a video interview at the annual scientific sessions of the ADA.

The association is also holding a debate at this year’s meeting to discuss the pros and cons of the new lipid guidelines for patients with diabetes.

In a press conference, Dr. Robert Eckel, professor of medicine and Charles A. Boettcher chair in atherosclerosis at University of Colorado, Anschutz Medical Campus, Aurora, said he was in support of the ACC/AHA guidelines, having served on the Task Force on Practice Guidelines, and that he believed that almost all patients with diabetes should be on a statin. He stressed that the new guidelines are evidence based.

But Dr. Henry Ginsberg, Irving Professor of Medicine and Director of the Irving Institute for Clinical and Translational Research at Columbia University, New York, argued that the guidelines’ evidence-based construct was too narrow.

In a video interview, Dr. Ginsberg further discussed his position and his practice tips for physicians.

Both physicians agreed that patients should be treated on an individual basis. For instance, patients who are statin intolerant won’t meet the guidelines’ criteria and "we’ll have to go beyond the guidelines," said Dr. Eckel.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

SAN FRANCISCO – Those looking for guidance from the American Diabetes Association regarding the guidelines released last fall from the American College of Cardiology and the American Heart Association dropping cholesterol treatment goals will have to wait until next year.

That’s when the ADA’s Clinical Practice Recommendations, released each year in January, will incorporate the Professional Practice Committee’s review of the ACC/AHA guidelines and the evidence behind it. The new recommendations caused some controversy and raised some questions about treatment of certain patient groups, most notably those with diabetes.

The ADA hasn’t recommended any changes to its current guidelines, which still incorporate treatment to target. But it has been reviewing the guidelines to see if it would recommend any changes for its 2015 guidelines.

Dr. Robert E. Ratner, chief scientific and medical officer for the American Diabetes Association, further explained the organization’s position on treatment of lipids in patients with diabetes in a video interview at the annual scientific sessions of the ADA.

The association is also holding a debate at this year’s meeting to discuss the pros and cons of the new lipid guidelines for patients with diabetes.

In a press conference, Dr. Robert Eckel, professor of medicine and Charles A. Boettcher chair in atherosclerosis at University of Colorado, Anschutz Medical Campus, Aurora, said he was in support of the ACC/AHA guidelines, having served on the Task Force on Practice Guidelines, and that he believed that almost all patients with diabetes should be on a statin. He stressed that the new guidelines are evidence based.

But Dr. Henry Ginsberg, Irving Professor of Medicine and Director of the Irving Institute for Clinical and Translational Research at Columbia University, New York, argued that the guidelines’ evidence-based construct was too narrow.

In a video interview, Dr. Ginsberg further discussed his position and his practice tips for physicians.

Both physicians agreed that patients should be treated on an individual basis. For instance, patients who are statin intolerant won’t meet the guidelines’ criteria and "we’ll have to go beyond the guidelines," said Dr. Eckel.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

SAN FRANCISCO – Those looking for guidance from the American Diabetes Association regarding the guidelines released last fall from the American College of Cardiology and the American Heart Association dropping cholesterol treatment goals will have to wait until next year.

That’s when the ADA’s Clinical Practice Recommendations, released each year in January, will incorporate the Professional Practice Committee’s review of the ACC/AHA guidelines and the evidence behind it. The new recommendations caused some controversy and raised some questions about treatment of certain patient groups, most notably those with diabetes.

The ADA hasn’t recommended any changes to its current guidelines, which still incorporate treatment to target. But it has been reviewing the guidelines to see if it would recommend any changes for its 2015 guidelines.

Dr. Robert E. Ratner, chief scientific and medical officer for the American Diabetes Association, further explained the organization’s position on treatment of lipids in patients with diabetes in a video interview at the annual scientific sessions of the ADA.

The association is also holding a debate at this year’s meeting to discuss the pros and cons of the new lipid guidelines for patients with diabetes.

In a press conference, Dr. Robert Eckel, professor of medicine and Charles A. Boettcher chair in atherosclerosis at University of Colorado, Anschutz Medical Campus, Aurora, said he was in support of the ACC/AHA guidelines, having served on the Task Force on Practice Guidelines, and that he believed that almost all patients with diabetes should be on a statin. He stressed that the new guidelines are evidence based.

But Dr. Henry Ginsberg, Irving Professor of Medicine and Director of the Irving Institute for Clinical and Translational Research at Columbia University, New York, argued that the guidelines’ evidence-based construct was too narrow.

In a video interview, Dr. Ginsberg further discussed his position and his practice tips for physicians.

Both physicians agreed that patients should be treated on an individual basis. For instance, patients who are statin intolerant won’t meet the guidelines’ criteria and "we’ll have to go beyond the guidelines," said Dr. Eckel.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Eighty percent of physicians are now using electronic health records in their offices. We have been impressed that the younger physicians to whom we have spoken often view their experience with EHRs very differently from older physicians. Is such a difference inevitable, perhaps, not just because change is more difficult for many people as they get older but also because expectations are influenced by experience. Noticing these different thoughts and feelings, we’ve asked two physicians more than 55 years old and two younger physicians to share some thoughts on their experiences with electronic records.

Mathew Clark (family physician)

I’ve been in practice for 31 years and using an EHR system for just under 5. I’m not thrilled with it, but I accept that it’s an unavoidable part of my practice now, and so I don’t waste energy being upset about it. I’ve learned to function efficiently with an EHR, doing the best I can. I remember physicians, before the days of SOAP notes, who would write pithy, useful notes such as "probable strep, Pen VK 500 bid for 10 days" on 3x5 index cards. Such notes lacked detail, and it’s not hard to imagine the problems this lack of detail might create, but they were readable at a glance, and told you what you needed to know. On the other hand, the massively detailed, bloated notes we see with our EHRs, obscured by "copy-forward" text and fictional (in other words, never really asked or examined) information, present very significant practical and legal issues of their own, and take hours of physician time to complete. Given a choice, I’d probably go for the index cards.

Natalie McGann (family physician)

I have been a family physician in practice for 4 years since graduating from residency. The advent of the EHR hasn’t been an overwhelming transition for those of us in the early stages of our careers. Much of our schooling to date has included laptops and other electronic devices that for many prove an easier means of communication. Despite that fact that EHRs require a host of extraneous clicks and check boxes, it is still less cumbersome than documenting encounters on paper. For the generation of young physicians accustomed to having answers at their fingertips, the idea of flipping through paper charts to collate a patient’s medical record seems far more complicated than clicking a few tabs without ever leaving your chair. I, and most colleagues in my peer group to whom I’ve spoken, agree that we would not be likely to a join a practice that doesn’t utilize an EHR or have a current plan to adopt one. Anything less would feel like a step back at this point.

Danielle Carcia (intern, family medicine residency)

Overall, I enjoy using electronic medical records. I feel that it places all pertinent information about the patient in an easy-to-follow and concise manner. The ability to read through past providers and even at times specialists visits with a patient can be very helpful when navigating an appointment with a new patient. As a young physician, electronics have been an extension of myself for my entire adult life, so a computer in front of me during an office visit is comforting. I do not feel it distracts from my interaction with patients, or takes away from their experience at all, just the opposite, it allows me to more confidently care for them with up to date, and organized information at my fingertips.

Dave Depietro (family physician)

I have been a family physician for 25 years and feel that the EHRs have affected my office in a number of ways. It has definitely improved the efficacy of office tasks such as doing prescription refills, interoffice communication, and scheduling. Also before EHRs, the turnaround time for a dictated note was about a week, and now most notes are completed by the end of the day. This makes it easier if I am taking care of one of my partner’s patients or dealing with a patient I recently saw. Also in this day of pay for performance we can now gather data much easier. This would be almost impossible to do if we still had paper charts.

EHRs unfortunately also have their downsides. The main problem I see is that they add a significant amount of time for providers to complete tasks. When I dictated a note, I could have completed a note within 1-2 minutes where now with EHRs, it can take maybe 3-5 minutes/patient. Also to approve labs, x-rays, etc. it just takes longer. I feel that EHRs have added about 1½ hr to my day. I feel most of my colleagues have the same complaint. They routinely take work home at night and spend 1-2 hours at home completing notes. Many of my peers seem stressed and frustrated. Even though EHRs make the office more efficient, I feel that the provider pays the price. My other complaint is the cost of IT support to keep the EHRs running smoothly. The promise of EHRs is that they would save physicians’ money and reduce staffing, however I have not seen that happen.

I ask myself, at the end of the day, would I go back to paper charts? The answer is no. Despite their downsides, I feel that the positives of EHRs outweigh the negatives. Older doctors just need to adapt to this new way of practicing medicine.

The Bottom Line

Clearly there is a range of opinion about the effect of electronic health records on our practices and our lives, with those opinions at least partly segregated by age. We are interested in your thoughts and plan to publish some of those thoughts in future columns, so please let us know at info@ehrpc.com. Thanks.

Dr. Notte is a family physician and clinical informaticist for Abington Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. He is editor in chief of Redi-Reference Inc., a software company that creates mobile apps.

Eighty percent of physicians are now using electronic health records in their offices. We have been impressed that the younger physicians to whom we have spoken often view their experience with EHRs very differently from older physicians. Is such a difference inevitable, perhaps, not just because change is more difficult for many people as they get older but also because expectations are influenced by experience. Noticing these different thoughts and feelings, we’ve asked two physicians more than 55 years old and two younger physicians to share some thoughts on their experiences with electronic records.

Mathew Clark (family physician)

I’ve been in practice for 31 years and using an EHR system for just under 5. I’m not thrilled with it, but I accept that it’s an unavoidable part of my practice now, and so I don’t waste energy being upset about it. I’ve learned to function efficiently with an EHR, doing the best I can. I remember physicians, before the days of SOAP notes, who would write pithy, useful notes such as "probable strep, Pen VK 500 bid for 10 days" on 3x5 index cards. Such notes lacked detail, and it’s not hard to imagine the problems this lack of detail might create, but they were readable at a glance, and told you what you needed to know. On the other hand, the massively detailed, bloated notes we see with our EHRs, obscured by "copy-forward" text and fictional (in other words, never really asked or examined) information, present very significant practical and legal issues of their own, and take hours of physician time to complete. Given a choice, I’d probably go for the index cards.

Natalie McGann (family physician)

I have been a family physician in practice for 4 years since graduating from residency. The advent of the EHR hasn’t been an overwhelming transition for those of us in the early stages of our careers. Much of our schooling to date has included laptops and other electronic devices that for many prove an easier means of communication. Despite that fact that EHRs require a host of extraneous clicks and check boxes, it is still less cumbersome than documenting encounters on paper. For the generation of young physicians accustomed to having answers at their fingertips, the idea of flipping through paper charts to collate a patient’s medical record seems far more complicated than clicking a few tabs without ever leaving your chair. I, and most colleagues in my peer group to whom I’ve spoken, agree that we would not be likely to a join a practice that doesn’t utilize an EHR or have a current plan to adopt one. Anything less would feel like a step back at this point.

Danielle Carcia (intern, family medicine residency)

Overall, I enjoy using electronic medical records. I feel that it places all pertinent information about the patient in an easy-to-follow and concise manner. The ability to read through past providers and even at times specialists visits with a patient can be very helpful when navigating an appointment with a new patient. As a young physician, electronics have been an extension of myself for my entire adult life, so a computer in front of me during an office visit is comforting. I do not feel it distracts from my interaction with patients, or takes away from their experience at all, just the opposite, it allows me to more confidently care for them with up to date, and organized information at my fingertips.

Dave Depietro (family physician)

I have been a family physician for 25 years and feel that the EHRs have affected my office in a number of ways. It has definitely improved the efficacy of office tasks such as doing prescription refills, interoffice communication, and scheduling. Also before EHRs, the turnaround time for a dictated note was about a week, and now most notes are completed by the end of the day. This makes it easier if I am taking care of one of my partner’s patients or dealing with a patient I recently saw. Also in this day of pay for performance we can now gather data much easier. This would be almost impossible to do if we still had paper charts.

EHRs unfortunately also have their downsides. The main problem I see is that they add a significant amount of time for providers to complete tasks. When I dictated a note, I could have completed a note within 1-2 minutes where now with EHRs, it can take maybe 3-5 minutes/patient. Also to approve labs, x-rays, etc. it just takes longer. I feel that EHRs have added about 1½ hr to my day. I feel most of my colleagues have the same complaint. They routinely take work home at night and spend 1-2 hours at home completing notes. Many of my peers seem stressed and frustrated. Even though EHRs make the office more efficient, I feel that the provider pays the price. My other complaint is the cost of IT support to keep the EHRs running smoothly. The promise of EHRs is that they would save physicians’ money and reduce staffing, however I have not seen that happen.

I ask myself, at the end of the day, would I go back to paper charts? The answer is no. Despite their downsides, I feel that the positives of EHRs outweigh the negatives. Older doctors just need to adapt to this new way of practicing medicine.

The Bottom Line

Clearly there is a range of opinion about the effect of electronic health records on our practices and our lives, with those opinions at least partly segregated by age. We are interested in your thoughts and plan to publish some of those thoughts in future columns, so please let us know at info@ehrpc.com. Thanks.

Dr. Notte is a family physician and clinical informaticist for Abington Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. He is editor in chief of Redi-Reference Inc., a software company that creates mobile apps.

Eighty percent of physicians are now using electronic health records in their offices. We have been impressed that the younger physicians to whom we have spoken often view their experience with EHRs very differently from older physicians. Is such a difference inevitable, perhaps, not just because change is more difficult for many people as they get older but also because expectations are influenced by experience. Noticing these different thoughts and feelings, we’ve asked two physicians more than 55 years old and two younger physicians to share some thoughts on their experiences with electronic records.

Mathew Clark (family physician)

I’ve been in practice for 31 years and using an EHR system for just under 5. I’m not thrilled with it, but I accept that it’s an unavoidable part of my practice now, and so I don’t waste energy being upset about it. I’ve learned to function efficiently with an EHR, doing the best I can. I remember physicians, before the days of SOAP notes, who would write pithy, useful notes such as "probable strep, Pen VK 500 bid for 10 days" on 3x5 index cards. Such notes lacked detail, and it’s not hard to imagine the problems this lack of detail might create, but they were readable at a glance, and told you what you needed to know. On the other hand, the massively detailed, bloated notes we see with our EHRs, obscured by "copy-forward" text and fictional (in other words, never really asked or examined) information, present very significant practical and legal issues of their own, and take hours of physician time to complete. Given a choice, I’d probably go for the index cards.

Natalie McGann (family physician)

I have been a family physician in practice for 4 years since graduating from residency. The advent of the EHR hasn’t been an overwhelming transition for those of us in the early stages of our careers. Much of our schooling to date has included laptops and other electronic devices that for many prove an easier means of communication. Despite that fact that EHRs require a host of extraneous clicks and check boxes, it is still less cumbersome than documenting encounters on paper. For the generation of young physicians accustomed to having answers at their fingertips, the idea of flipping through paper charts to collate a patient’s medical record seems far more complicated than clicking a few tabs without ever leaving your chair. I, and most colleagues in my peer group to whom I’ve spoken, agree that we would not be likely to a join a practice that doesn’t utilize an EHR or have a current plan to adopt one. Anything less would feel like a step back at this point.

Danielle Carcia (intern, family medicine residency)

Overall, I enjoy using electronic medical records. I feel that it places all pertinent information about the patient in an easy-to-follow and concise manner. The ability to read through past providers and even at times specialists visits with a patient can be very helpful when navigating an appointment with a new patient. As a young physician, electronics have been an extension of myself for my entire adult life, so a computer in front of me during an office visit is comforting. I do not feel it distracts from my interaction with patients, or takes away from their experience at all, just the opposite, it allows me to more confidently care for them with up to date, and organized information at my fingertips.

Dave Depietro (family physician)

I have been a family physician for 25 years and feel that the EHRs have affected my office in a number of ways. It has definitely improved the efficacy of office tasks such as doing prescription refills, interoffice communication, and scheduling. Also before EHRs, the turnaround time for a dictated note was about a week, and now most notes are completed by the end of the day. This makes it easier if I am taking care of one of my partner’s patients or dealing with a patient I recently saw. Also in this day of pay for performance we can now gather data much easier. This would be almost impossible to do if we still had paper charts.

EHRs unfortunately also have their downsides. The main problem I see is that they add a significant amount of time for providers to complete tasks. When I dictated a note, I could have completed a note within 1-2 minutes where now with EHRs, it can take maybe 3-5 minutes/patient. Also to approve labs, x-rays, etc. it just takes longer. I feel that EHRs have added about 1½ hr to my day. I feel most of my colleagues have the same complaint. They routinely take work home at night and spend 1-2 hours at home completing notes. Many of my peers seem stressed and frustrated. Even though EHRs make the office more efficient, I feel that the provider pays the price. My other complaint is the cost of IT support to keep the EHRs running smoothly. The promise of EHRs is that they would save physicians’ money and reduce staffing, however I have not seen that happen.

I ask myself, at the end of the day, would I go back to paper charts? The answer is no. Despite their downsides, I feel that the positives of EHRs outweigh the negatives. Older doctors just need to adapt to this new way of practicing medicine.

The Bottom Line

Clearly there is a range of opinion about the effect of electronic health records on our practices and our lives, with those opinions at least partly segregated by age. We are interested in your thoughts and plan to publish some of those thoughts in future columns, so please let us know at info@ehrpc.com. Thanks.

Dr. Notte is a family physician and clinical informaticist for Abington Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. He is editor in chief of Redi-Reference Inc., a software company that creates mobile apps.

The US Food and Drug Administration (FDA) has removed the partial clinical hold on the investigator-sponsored trial of imetelstat in myelofibrosis, which the agency imposed in March.

The partial hold was placed because of a safety signal of liver toxicity in myelofibrosis patients receiving the drug.

The principal investigator of the trial, Ayalew Tefferi, MD, of Mayo Clinic in Rochester, Minnesota, provided follow-up information to the FDA regarding the reversibility of the hepatotoxicity.

Upon review of the additional data, the FDA allowed the myelofibrosis trial to proceed.

Imetelstat is a lipid-conjugated oligonucleotide that binds with high affinity to the RNA template of telomerase, thereby inhibiting telomerase activity.

Most cancers are characterized by short telomeres and a high level of telomerase activity, which makes telomerase a rational target for the treatment of cancer.

Imetelstat is also being investigated in essential thrombocythemia and other myeloid hematologic malignancies.

The trial in myelofibrosis enrolled 33 high-risk or intermediate-2 risk patients with either primary or secondary myelofibrosis. Dr Teferi presented the data at the annual meeting of the American Society of Hematology in 2013 as abstract 662.

At the time of the meeting, myelosuppression appeared to be the major dose-limiting toxicity.

Geron’s Investigational New Drug application to the FDA for imetelstat remains on full clinical hold. This affects clinical trials in essential thrombocythemia, polycythemia vera, and multiple myeloma.

The US Food and Drug Administration (FDA) has removed the partial clinical hold on the investigator-sponsored trial of imetelstat in myelofibrosis, which the agency imposed in March.

The partial hold was placed because of a safety signal of liver toxicity in myelofibrosis patients receiving the drug.

The principal investigator of the trial, Ayalew Tefferi, MD, of Mayo Clinic in Rochester, Minnesota, provided follow-up information to the FDA regarding the reversibility of the hepatotoxicity.

Upon review of the additional data, the FDA allowed the myelofibrosis trial to proceed.

Imetelstat is a lipid-conjugated oligonucleotide that binds with high affinity to the RNA template of telomerase, thereby inhibiting telomerase activity.

Most cancers are characterized by short telomeres and a high level of telomerase activity, which makes telomerase a rational target for the treatment of cancer.

Imetelstat is also being investigated in essential thrombocythemia and other myeloid hematologic malignancies.

The trial in myelofibrosis enrolled 33 high-risk or intermediate-2 risk patients with either primary or secondary myelofibrosis. Dr Teferi presented the data at the annual meeting of the American Society of Hematology in 2013 as abstract 662.

At the time of the meeting, myelosuppression appeared to be the major dose-limiting toxicity.

Geron’s Investigational New Drug application to the FDA for imetelstat remains on full clinical hold. This affects clinical trials in essential thrombocythemia, polycythemia vera, and multiple myeloma.

The US Food and Drug Administration (FDA) has removed the partial clinical hold on the investigator-sponsored trial of imetelstat in myelofibrosis, which the agency imposed in March.

The partial hold was placed because of a safety signal of liver toxicity in myelofibrosis patients receiving the drug.

The principal investigator of the trial, Ayalew Tefferi, MD, of Mayo Clinic in Rochester, Minnesota, provided follow-up information to the FDA regarding the reversibility of the hepatotoxicity.

Upon review of the additional data, the FDA allowed the myelofibrosis trial to proceed.

Imetelstat is a lipid-conjugated oligonucleotide that binds with high affinity to the RNA template of telomerase, thereby inhibiting telomerase activity.

Most cancers are characterized by short telomeres and a high level of telomerase activity, which makes telomerase a rational target for the treatment of cancer.

Imetelstat is also being investigated in essential thrombocythemia and other myeloid hematologic malignancies.

The trial in myelofibrosis enrolled 33 high-risk or intermediate-2 risk patients with either primary or secondary myelofibrosis. Dr Teferi presented the data at the annual meeting of the American Society of Hematology in 2013 as abstract 662.

At the time of the meeting, myelosuppression appeared to be the major dose-limiting toxicity.

Geron’s Investigational New Drug application to the FDA for imetelstat remains on full clinical hold. This affects clinical trials in essential thrombocythemia, polycythemia vera, and multiple myeloma.

Poster hall at ASCO 2014

©ASCO/Todd Buchanan

CHICAGO—Infusion of autologous CD19-targeted chimeric antigen receptor (CAR)-modified T cells appears to have promising anti-tumor activity and be well-tolerated as a consolidation to frontline chemotherapy in patients with high-risk chronic lymphocytic leukemia (CLL), researchers report.

In a phase 1 trial, the modified T cells benefitted 43% of patients, including 1 who achieved a complete response and 2 who achieved marrow responses only.

Jae Park, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported the findings at the 2014 ASCO Annual Meeting as abstract 7020.

Dr Park and colleagues enrolled 7 CLL patients who had detectable minimal residual disease after achieving either a partial or complete response following 6 cycles of pentostatin, cyclophosphamide, and rituximab.

Patients then received cyclophosphamide conditioning therapy, followed by 3 escalating doses of CAR T cells in 3 dose cohorts.

Six patients had unmutated IgHV, and 2 patients had del 11q. Four patients had palpable lymphadenopathy, including 1 patient with bulky lymph nodes, prior to T-cell infusion.

After a median follow-up of 11 months, 1 patient achieved a complete response, and 2 patients achieved complete responses in the bone marrow but had progressive disease in the lymph nodes.

Three patients achieved a partial response, and 1 patient had progressive disease, but this patient had rapidly rising absolute lymphocyte count at the time of T-cell infusion, Dr Park noted.

The investigators observed no dose-limiting toxicity. Mild and self-limiting cytokine release syndrome occurred in 3 patients.

“There was a positive correlation between the development of cytokine release syndrome and the CAR T-cell persistence,” Dr Park said.

“Our findings suggest that the CD19-targeted CAR T cells are more effective in eradicating disease in the marrow versus lymph nodes,” he added. “And further studies are being conducted to better understand the mechanism of resistance.”

ASCO discussant Veronika Bachanova, MD, of the University of Minnesota, noted that all previous studies of CAR T-cell therapy in CLL were conducted with relapsed/refractory patients.

“The novelty of this study,” she commented, “is the use of CAR T cells upfront.”

She noted that it can take as long as 8 months to develop the CAR T cells for therapy, adding that “the vector design is of critical importance, since inhibitory signals influence therapy.”

Poster hall at ASCO 2014

©ASCO/Todd Buchanan

CHICAGO—Infusion of autologous CD19-targeted chimeric antigen receptor (CAR)-modified T cells appears to have promising anti-tumor activity and be well-tolerated as a consolidation to frontline chemotherapy in patients with high-risk chronic lymphocytic leukemia (CLL), researchers report.

In a phase 1 trial, the modified T cells benefitted 43% of patients, including 1 who achieved a complete response and 2 who achieved marrow responses only.

Jae Park, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported the findings at the 2014 ASCO Annual Meeting as abstract 7020.

Dr Park and colleagues enrolled 7 CLL patients who had detectable minimal residual disease after achieving either a partial or complete response following 6 cycles of pentostatin, cyclophosphamide, and rituximab.

Patients then received cyclophosphamide conditioning therapy, followed by 3 escalating doses of CAR T cells in 3 dose cohorts.

Six patients had unmutated IgHV, and 2 patients had del 11q. Four patients had palpable lymphadenopathy, including 1 patient with bulky lymph nodes, prior to T-cell infusion.

After a median follow-up of 11 months, 1 patient achieved a complete response, and 2 patients achieved complete responses in the bone marrow but had progressive disease in the lymph nodes.

Three patients achieved a partial response, and 1 patient had progressive disease, but this patient had rapidly rising absolute lymphocyte count at the time of T-cell infusion, Dr Park noted.

The investigators observed no dose-limiting toxicity. Mild and self-limiting cytokine release syndrome occurred in 3 patients.

“There was a positive correlation between the development of cytokine release syndrome and the CAR T-cell persistence,” Dr Park said.

“Our findings suggest that the CD19-targeted CAR T cells are more effective in eradicating disease in the marrow versus lymph nodes,” he added. “And further studies are being conducted to better understand the mechanism of resistance.”

ASCO discussant Veronika Bachanova, MD, of the University of Minnesota, noted that all previous studies of CAR T-cell therapy in CLL were conducted with relapsed/refractory patients.

“The novelty of this study,” she commented, “is the use of CAR T cells upfront.”

She noted that it can take as long as 8 months to develop the CAR T cells for therapy, adding that “the vector design is of critical importance, since inhibitory signals influence therapy.”

Poster hall at ASCO 2014

©ASCO/Todd Buchanan

CHICAGO—Infusion of autologous CD19-targeted chimeric antigen receptor (CAR)-modified T cells appears to have promising anti-tumor activity and be well-tolerated as a consolidation to frontline chemotherapy in patients with high-risk chronic lymphocytic leukemia (CLL), researchers report.

In a phase 1 trial, the modified T cells benefitted 43% of patients, including 1 who achieved a complete response and 2 who achieved marrow responses only.

Jae Park, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported the findings at the 2014 ASCO Annual Meeting as abstract 7020.

Dr Park and colleagues enrolled 7 CLL patients who had detectable minimal residual disease after achieving either a partial or complete response following 6 cycles of pentostatin, cyclophosphamide, and rituximab.

Patients then received cyclophosphamide conditioning therapy, followed by 3 escalating doses of CAR T cells in 3 dose cohorts.

Six patients had unmutated IgHV, and 2 patients had del 11q. Four patients had palpable lymphadenopathy, including 1 patient with bulky lymph nodes, prior to T-cell infusion.

After a median follow-up of 11 months, 1 patient achieved a complete response, and 2 patients achieved complete responses in the bone marrow but had progressive disease in the lymph nodes.

Three patients achieved a partial response, and 1 patient had progressive disease, but this patient had rapidly rising absolute lymphocyte count at the time of T-cell infusion, Dr Park noted.

The investigators observed no dose-limiting toxicity. Mild and self-limiting cytokine release syndrome occurred in 3 patients.

“There was a positive correlation between the development of cytokine release syndrome and the CAR T-cell persistence,” Dr Park said.

“Our findings suggest that the CD19-targeted CAR T cells are more effective in eradicating disease in the marrow versus lymph nodes,” he added. “And further studies are being conducted to better understand the mechanism of resistance.”

ASCO discussant Veronika Bachanova, MD, of the University of Minnesota, noted that all previous studies of CAR T-cell therapy in CLL were conducted with relapsed/refractory patients.

“The novelty of this study,” she commented, “is the use of CAR T cells upfront.”

She noted that it can take as long as 8 months to develop the CAR T cells for therapy, adding that “the vector design is of critical importance, since inhibitory signals influence therapy.”

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

Info booth at ASCO 2014

©ASCO/Scott Morgan

CHICAGO—Substituting lenalidomide for thalidomide in the standard treatment of newly diagnosed multiple myeloma (MM) improves quality of life and

lowers toxicity without significant loss of response, results of a phase 3 study suggest.

Combination melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment option for transplant ineligible, newly diagnosed MM.

Early phase 1/2 studies suggested substituting lenalidomide for thalidomide might result in similar efficacy and less toxicity.

“However, neither feature can be confidently predicted, since long-term follow-up of the melphalan, prednisone, and lenalidomide (MPR) regimen is lacking, and myelosuppression may prove limiting, compromising drug dose and efficacy,” said A. Keith Stewart, MD, from the Mayo Clinic in Scottsdale, Arizona.

So Dr Stewart and his colleagues conducted a randomized, multicenter, phase 3 trial comparing MPT to MPR in untreated, symptomatic, transplant-ineligible MM patients. Dr Stewart presented the results at the 2014 ASCO Annual Meeting as abstract 8511.

The study included 306 patients with a median age of 76 years. The primary objective was to evaluate the  difference in progression-free survival (PFS) between patients receiving MPT and those treated with MPR.

Patients received melphalan at 9 mg/m² and prednisone at 100 mg orally on days 1-4, with thalidomide at 100 mg daily. Or they received melphalan at 5 mg/m² and prednisone at 100 mg orally on days 1-4, with lenalidomide at 10 mg orally on days 1-21.

MPT or MPR therapy was continued for twelve 28-day cycles, followed by thalidomide at 100 mg or lenalidomide at 10 mg daily until relapse. Patients were required to have aspirin prophylaxis.

Secondary study objectives included overall survival, toxicities, response rates, depth of response, and quality of life change. Treatment arms were balanced for age, ISS stage, and other major prognostic factors.

The median follow-up was 40.7 months. The median time on therapy was 12 months overall and 23 months for the 46% of patients on maintenance therapy, with no differences by arm. Some 7% of patients remained on treatment through cycle 60.

The results showed similar response rates between the 2 arms. The partial response rate was 64% for the MPT group, compared with 60% for the MPR group, with no difference in very good partial response/complete response rates (18.8% vs 23%).

The median PFS was 21 months for patients receiving MPT and 18.7 months for those receiving MPR. The median overall survival was not significantly different between the arms—52.6% for the MPT arm and 47.7% for the MPR arm.

Toxicities of grade 3 or higher were significantly more likely in the MPT arm (73%) than in the MPR arm (58%), as was non-hematologic toxicity (59% and 40%, respectively).

The incidence of second primary malignancies was higher with MPT (3.47/100 person years) than with MPR (2.01/100 person years). And deep vein thrombosis or pulmonary embolism occurred in 8.8% of MPT patients and 6.7% MPR patients.

“The quality of life analysis favored MPR by induction end,” Dr Stewart said. “Response rates, PFS, and overall survival were similar between the 2 arms. However, there was significantly better quality of life at 12 months and lower toxicity with MPR.”

Dr Stewart noted, however, that in the US, “melphalan-based regimens are now seldom utilized due to availability of lenalidomide and bortezomib in newly diagnosed patients.”

PARIS – New international guidelines for polymyalgia rheumatica will focus on standardizing treatment practice across specialties.

When adopted, the proposed guidelines will succeed those published by the British Society of Rheumatology in 2009, according to Dr. Bhaskar Dasgupta, a primary author of the new guidelines and leader of the study group.

"This is the first transatlantic EULAR-ACR [European League against Rheumatism-American College of Rheumatology] guideline in rheumatology," he said at the annual European Congress of Rheumatology. "It is very patient-centered and was developed with patient input."

There has been a great need for a document such as this, he said. Primary care physicians are almost always on the front line of diagnosing polymyalgia rheumatica and often [the first] to treat these patients – with variable success, said Dr. Dasgupta, head of the Southend Hospital rheumatology department, Essex, England.

"This disorder is as common as – or more common than – rheumatoid arthritis, with a very high prevalence and incidence," he said. "It’s often diagnosed by general practitioners, with patients referred to nonrheumatologists. Yet there is a very wide variation in practice and a lot of uncertainty in the diagnosis. We are concerned that we have handed this over to primary care physicians when it needs so much clinical acumen to tease this out from other conditions.

The guidelines were developed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and involving appraisal of 445 relevant publications in polymyalgia rheumatica (PMR), published since 1970. The document was reviewed on several occasions by an international panel that included 51 investigators from the United States and represented countries in Western and Eastern Europe, as well as Australia, New Zealand, Brazil, South America, Japan, and India. All recommendations were adopted unanimously without the need to vote, according to Dr. Dasgupta.

According to the proposed document, most patients are diagnosed and treated in primary care settings, but there are no well-elucidated referral algorithms for referral to specialty care. This can contribute to variability in treatment.

For instance, "a proportion of PMR patients do not adequately respond to glucocorticoid therapy and suffer frequent relapses and dependency on long-term high doses," according to the guidelines. "Prolonged glucocorticoid therapy is associated with considerable side effects especially when high doses are employed." Dr. Dasgupta said the proposed guidelines address groups that are at especially high risk for these problems. "While effective, steroids have the potential to cause serious side effects," he said. "It is important to know how to use them [steroids] correctly in PMR. The subgroups that are vulnerable to side effects – such as patients with diabetes, hypertension, osteoporosis, and glaucoma, and high disease activity should be recognized – female sex and those with peripheral arthritis or high inflammatory markers."

The guidelines are structured as a treatment algorithm, which begins with accurate diagnosis and patient assessment. They recommend that most patients be started on oral prednisone at the equivalent of 12.5-25 mg/day, or if the patient is at high risk of steroid-related side effects, to begin with intramuscular glucocorticoids.

If there is inadequate response, the guidelines recommend an increase in glucocorticoid dose or methotrexate for those at high risk of side effects, relapse, or prolonged therapy.

If there is improvement within 4 weeks, consider a gradual tapering of steroids. If not, a confirmation of the diagnosis is in order, the guidelines note. Patients who respond well to the taper will likely go into remission and may continue the taper. Patients who relapse should have a diagnostic confirmation and/or specialist referral.

"Ultimately, in order to be accepted, the guidelines will require confirmation of their usefulness in clinical practice. PMR recommendations endorsed by both the ACR and EULAR would have a significant impact on clinical decision making, would reduce practice variation, and would stimulate further research in areas where there is currently lack of adequate evidence."

In addition, he said, the role for early methotrexate in treatment of the condition is now emerging and will be included in the guidelines for consideration in special subgroups.

The guidelines must still be ratified by both the ACR and EULAR. Once that happens, they will be simultaneously published in both associations’ journals – no later than mid-2015, Dr. Dasgupta said.

Dr. Dasgupta disclosed that he has helped design clinical trials for a number of drug companies and has received remuneration for educational symposia from others.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PARIS – New international guidelines for polymyalgia rheumatica will focus on standardizing treatment practice across specialties.

When adopted, the proposed guidelines will succeed those published by the British Society of Rheumatology in 2009, according to Dr. Bhaskar Dasgupta, a primary author of the new guidelines and leader of the study group.

"This is the first transatlantic EULAR-ACR [European League against Rheumatism-American College of Rheumatology] guideline in rheumatology," he said at the annual European Congress of Rheumatology. "It is very patient-centered and was developed with patient input."

There has been a great need for a document such as this, he said. Primary care physicians are almost always on the front line of diagnosing polymyalgia rheumatica and often [the first] to treat these patients – with variable success, said Dr. Dasgupta, head of the Southend Hospital rheumatology department, Essex, England.

"This disorder is as common as – or more common than – rheumatoid arthritis, with a very high prevalence and incidence," he said. "It’s often diagnosed by general practitioners, with patients referred to nonrheumatologists. Yet there is a very wide variation in practice and a lot of uncertainty in the diagnosis. We are concerned that we have handed this over to primary care physicians when it needs so much clinical acumen to tease this out from other conditions.

The guidelines were developed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and involving appraisal of 445 relevant publications in polymyalgia rheumatica (PMR), published since 1970. The document was reviewed on several occasions by an international panel that included 51 investigators from the United States and represented countries in Western and Eastern Europe, as well as Australia, New Zealand, Brazil, South America, Japan, and India. All recommendations were adopted unanimously without the need to vote, according to Dr. Dasgupta.

According to the proposed document, most patients are diagnosed and treated in primary care settings, but there are no well-elucidated referral algorithms for referral to specialty care. This can contribute to variability in treatment.

For instance, "a proportion of PMR patients do not adequately respond to glucocorticoid therapy and suffer frequent relapses and dependency on long-term high doses," according to the guidelines. "Prolonged glucocorticoid therapy is associated with considerable side effects especially when high doses are employed." Dr. Dasgupta said the proposed guidelines address groups that are at especially high risk for these problems. "While effective, steroids have the potential to cause serious side effects," he said. "It is important to know how to use them [steroids] correctly in PMR. The subgroups that are vulnerable to side effects – such as patients with diabetes, hypertension, osteoporosis, and glaucoma, and high disease activity should be recognized – female sex and those with peripheral arthritis or high inflammatory markers."

The guidelines are structured as a treatment algorithm, which begins with accurate diagnosis and patient assessment. They recommend that most patients be started on oral prednisone at the equivalent of 12.5-25 mg/day, or if the patient is at high risk of steroid-related side effects, to begin with intramuscular glucocorticoids.

If there is inadequate response, the guidelines recommend an increase in glucocorticoid dose or methotrexate for those at high risk of side effects, relapse, or prolonged therapy.

If there is improvement within 4 weeks, consider a gradual tapering of steroids. If not, a confirmation of the diagnosis is in order, the guidelines note. Patients who respond well to the taper will likely go into remission and may continue the taper. Patients who relapse should have a diagnostic confirmation and/or specialist referral.

"Ultimately, in order to be accepted, the guidelines will require confirmation of their usefulness in clinical practice. PMR recommendations endorsed by both the ACR and EULAR would have a significant impact on clinical decision making, would reduce practice variation, and would stimulate further research in areas where there is currently lack of adequate evidence."

In addition, he said, the role for early methotrexate in treatment of the condition is now emerging and will be included in the guidelines for consideration in special subgroups.

The guidelines must still be ratified by both the ACR and EULAR. Once that happens, they will be simultaneously published in both associations’ journals – no later than mid-2015, Dr. Dasgupta said.

Dr. Dasgupta disclosed that he has helped design clinical trials for a number of drug companies and has received remuneration for educational symposia from others.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PARIS – New international guidelines for polymyalgia rheumatica will focus on standardizing treatment practice across specialties.

When adopted, the proposed guidelines will succeed those published by the British Society of Rheumatology in 2009, according to Dr. Bhaskar Dasgupta, a primary author of the new guidelines and leader of the study group.

"This is the first transatlantic EULAR-ACR [European League against Rheumatism-American College of Rheumatology] guideline in rheumatology," he said at the annual European Congress of Rheumatology. "It is very patient-centered and was developed with patient input."

There has been a great need for a document such as this, he said. Primary care physicians are almost always on the front line of diagnosing polymyalgia rheumatica and often [the first] to treat these patients – with variable success, said Dr. Dasgupta, head of the Southend Hospital rheumatology department, Essex, England.

"This disorder is as common as – or more common than – rheumatoid arthritis, with a very high prevalence and incidence," he said. "It’s often diagnosed by general practitioners, with patients referred to nonrheumatologists. Yet there is a very wide variation in practice and a lot of uncertainty in the diagnosis. We are concerned that we have handed this over to primary care physicians when it needs so much clinical acumen to tease this out from other conditions.

The guidelines were developed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and involving appraisal of 445 relevant publications in polymyalgia rheumatica (PMR), published since 1970. The document was reviewed on several occasions by an international panel that included 51 investigators from the United States and represented countries in Western and Eastern Europe, as well as Australia, New Zealand, Brazil, South America, Japan, and India. All recommendations were adopted unanimously without the need to vote, according to Dr. Dasgupta.

According to the proposed document, most patients are diagnosed and treated in primary care settings, but there are no well-elucidated referral algorithms for referral to specialty care. This can contribute to variability in treatment.

For instance, "a proportion of PMR patients do not adequately respond to glucocorticoid therapy and suffer frequent relapses and dependency on long-term high doses," according to the guidelines. "Prolonged glucocorticoid therapy is associated with considerable side effects especially when high doses are employed." Dr. Dasgupta said the proposed guidelines address groups that are at especially high risk for these problems. "While effective, steroids have the potential to cause serious side effects," he said. "It is important to know how to use them [steroids] correctly in PMR. The subgroups that are vulnerable to side effects – such as patients with diabetes, hypertension, osteoporosis, and glaucoma, and high disease activity should be recognized – female sex and those with peripheral arthritis or high inflammatory markers."

The guidelines are structured as a treatment algorithm, which begins with accurate diagnosis and patient assessment. They recommend that most patients be started on oral prednisone at the equivalent of 12.5-25 mg/day, or if the patient is at high risk of steroid-related side effects, to begin with intramuscular glucocorticoids.

If there is inadequate response, the guidelines recommend an increase in glucocorticoid dose or methotrexate for those at high risk of side effects, relapse, or prolonged therapy.

If there is improvement within 4 weeks, consider a gradual tapering of steroids. If not, a confirmation of the diagnosis is in order, the guidelines note. Patients who respond well to the taper will likely go into remission and may continue the taper. Patients who relapse should have a diagnostic confirmation and/or specialist referral.

"Ultimately, in order to be accepted, the guidelines will require confirmation of their usefulness in clinical practice. PMR recommendations endorsed by both the ACR and EULAR would have a significant impact on clinical decision making, would reduce practice variation, and would stimulate further research in areas where there is currently lack of adequate evidence."

In addition, he said, the role for early methotrexate in treatment of the condition is now emerging and will be included in the guidelines for consideration in special subgroups.

The guidelines must still be ratified by both the ACR and EULAR. Once that happens, they will be simultaneously published in both associations’ journals – no later than mid-2015, Dr. Dasgupta said.

Dr. Dasgupta disclosed that he has helped design clinical trials for a number of drug companies and has received remuneration for educational symposia from others.

msullivan@frontlinemedcom.com

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