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Physicians and EHR time
Clinical question: How much time do ambulatory-care physicians spend on electronic health records (EHRs)?
Background: There is growing concern about physicians’ increased time and effort allocated to the EHR and decreased clinical face time and meaningful interaction with patients. Prior studies have shown that increased physician EHR task load is associated with increased physician stress and dissatisfaction.
Setting: Ambulatory-care practices.
Synopsis: Fifty-seven physicians from 16 practices in four U.S. states participated and were observed for more than 430 office hours. Additionally, 21 physicians completed a self-reported after-hours diary. During office hours, physicians spent 49.2% of their total time on the EHR and desk work and only 27% on face time with patients. While in the exam room, physicians spent 52.9% of the time on direct clinical face time and 37% on the EHR and desk work. Self-reported diaries showed an additional 1-2 hours of follow-up work on the EHR. These observations might not be generalizable to other practices. No formal statistical comparisons by physicians, practice, or EHR characteristics were done.
Bottom line: Ambulatory-care physicians appear to spend more time with EHR tasks and desk work than clinical face time with patients.
Citation: Sinsky C, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion studies in 4 specialties [published online ahead of print Sept. 6, 2016]. Ann Intern Med. 165(11):753-760.
Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.
Clinical question: How much time do ambulatory-care physicians spend on electronic health records (EHRs)?
Background: There is growing concern about physicians’ increased time and effort allocated to the EHR and decreased clinical face time and meaningful interaction with patients. Prior studies have shown that increased physician EHR task load is associated with increased physician stress and dissatisfaction.
Setting: Ambulatory-care practices.
Synopsis: Fifty-seven physicians from 16 practices in four U.S. states participated and were observed for more than 430 office hours. Additionally, 21 physicians completed a self-reported after-hours diary. During office hours, physicians spent 49.2% of their total time on the EHR and desk work and only 27% on face time with patients. While in the exam room, physicians spent 52.9% of the time on direct clinical face time and 37% on the EHR and desk work. Self-reported diaries showed an additional 1-2 hours of follow-up work on the EHR. These observations might not be generalizable to other practices. No formal statistical comparisons by physicians, practice, or EHR characteristics were done.
Bottom line: Ambulatory-care physicians appear to spend more time with EHR tasks and desk work than clinical face time with patients.
Citation: Sinsky C, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion studies in 4 specialties [published online ahead of print Sept. 6, 2016]. Ann Intern Med. 165(11):753-760.
Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.
Clinical question: How much time do ambulatory-care physicians spend on electronic health records (EHRs)?
Background: There is growing concern about physicians’ increased time and effort allocated to the EHR and decreased clinical face time and meaningful interaction with patients. Prior studies have shown that increased physician EHR task load is associated with increased physician stress and dissatisfaction.
Setting: Ambulatory-care practices.
Synopsis: Fifty-seven physicians from 16 practices in four U.S. states participated and were observed for more than 430 office hours. Additionally, 21 physicians completed a self-reported after-hours diary. During office hours, physicians spent 49.2% of their total time on the EHR and desk work and only 27% on face time with patients. While in the exam room, physicians spent 52.9% of the time on direct clinical face time and 37% on the EHR and desk work. Self-reported diaries showed an additional 1-2 hours of follow-up work on the EHR. These observations might not be generalizable to other practices. No formal statistical comparisons by physicians, practice, or EHR characteristics were done.
Bottom line: Ambulatory-care physicians appear to spend more time with EHR tasks and desk work than clinical face time with patients.
Citation: Sinsky C, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion studies in 4 specialties [published online ahead of print Sept. 6, 2016]. Ann Intern Med. 165(11):753-760.
Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.
Machine learning beats clinical prediction of temporal lobe epilepsy surgery outcomes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Models built with machine learning techniques using resting state fMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%.
Data source: A prospective study of 56 patients with temporal lobe epilepsy.
Disclosures: Dr. He reported no conflicts of interest.
USPSTF nixes routine genital herpes screening
Asymptomatic adolescents and adults, including pregnant women, should not undergo routine serologic screening for genital herpes because the harms of this approach outweigh the benefits, according to an updated US Preventive Services Task Force (USPSTF) Recommendation Statement published online in JAMA.
The USPSTF last addressed screening for herpes simplex virus (HSV) in a 2005 Recommendation Statement, which advised against routine screening of asymptomatic patients at that time. “A small number” of clinical trials examined the issue since then, so the group commissioned a review of the literature through October 2016 to incorporate any new findings into the update, said Kirsten Bibbins-Domingo, MD, PhD, chair of the USPSTF and lead author of the update, and her associates.
Dr. Feltner and her colleagues concluded that current serologic screening tests produce a high rate of false-positive results – as much as 50% – and that those in turn lead to psychosocial harms such as distress and disruption of personal relationships, as well as increased costs and potential medical harm associated with confirmatory testing and unnecessary treatment.
Given the false-positive rates of the most widely used screening tests and the 15% prevalence of genital herpes in the general population, “screening 10,000 persons would result in approximately 1,485 true-positive and 1,445 false-positive results.” Moreover, confirmatory testing is offered only at a single research laboratory, said Dr. Bibbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates on the Task Force.
Based on these findings and given the natural history and epidemiology of genital herpes, they characterized the potential benefits of routine screening as “no greater than small,” and the harms as “at least moderate” (JAMA. 2016 Dec 20;316[23]:2525-30. doi: 10.1001/jama.2016.16776).
The American Academy of Family Physicians, the American College of Obstetrics and Gynecology, and the Centers for Disease Control and Prevention also recommend against routine HSV screening of adolescents and adults, including pregnant women, the investigators noted.
The USPSTF is an independent, voluntary group that evaluates preventive health care services and is funded by the Agency for Healthcare Research and Quality by mandate of the U.S. Congress. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.
[email protected]
On Twitter @idpractitioner
It’s disappointing that the performance of screening tests hasn’t improved during the 10 years since the last USPSTF Recommendation Statement.
These findings should serve as a call to action for federal health agencies and their partners in industry to prioritize the development of better tests and stem the continuing epidemic of genital herpes.
Another important step would be to work vigorously to reduce the pervasive stigma of this disease, which also hinders management and control efforts. The public continues to harbor misperceptions about the severity of genital herpes and the availability of effective treatment, which adds to disproportionate stigmatization of those infected.
Edward W. Hook III, MD, is in the department of microbiology at the University of Alabama at Birmingham. He reported ties to Hologic, Roche Molecular, Becton Dickinson, and Cepheid. Dr. Hook made these remarks in an editorial accompanying the USPSTF Recommendation Statement (JAMA. 2016 Dec 20;316[23]:2493-4).
It’s disappointing that the performance of screening tests hasn’t improved during the 10 years since the last USPSTF Recommendation Statement.
These findings should serve as a call to action for federal health agencies and their partners in industry to prioritize the development of better tests and stem the continuing epidemic of genital herpes.
Another important step would be to work vigorously to reduce the pervasive stigma of this disease, which also hinders management and control efforts. The public continues to harbor misperceptions about the severity of genital herpes and the availability of effective treatment, which adds to disproportionate stigmatization of those infected.
Edward W. Hook III, MD, is in the department of microbiology at the University of Alabama at Birmingham. He reported ties to Hologic, Roche Molecular, Becton Dickinson, and Cepheid. Dr. Hook made these remarks in an editorial accompanying the USPSTF Recommendation Statement (JAMA. 2016 Dec 20;316[23]:2493-4).
It’s disappointing that the performance of screening tests hasn’t improved during the 10 years since the last USPSTF Recommendation Statement.
These findings should serve as a call to action for federal health agencies and their partners in industry to prioritize the development of better tests and stem the continuing epidemic of genital herpes.
Another important step would be to work vigorously to reduce the pervasive stigma of this disease, which also hinders management and control efforts. The public continues to harbor misperceptions about the severity of genital herpes and the availability of effective treatment, which adds to disproportionate stigmatization of those infected.
Edward W. Hook III, MD, is in the department of microbiology at the University of Alabama at Birmingham. He reported ties to Hologic, Roche Molecular, Becton Dickinson, and Cepheid. Dr. Hook made these remarks in an editorial accompanying the USPSTF Recommendation Statement (JAMA. 2016 Dec 20;316[23]:2493-4).
Asymptomatic adolescents and adults, including pregnant women, should not undergo routine serologic screening for genital herpes because the harms of this approach outweigh the benefits, according to an updated US Preventive Services Task Force (USPSTF) Recommendation Statement published online in JAMA.
The USPSTF last addressed screening for herpes simplex virus (HSV) in a 2005 Recommendation Statement, which advised against routine screening of asymptomatic patients at that time. “A small number” of clinical trials examined the issue since then, so the group commissioned a review of the literature through October 2016 to incorporate any new findings into the update, said Kirsten Bibbins-Domingo, MD, PhD, chair of the USPSTF and lead author of the update, and her associates.
Dr. Feltner and her colleagues concluded that current serologic screening tests produce a high rate of false-positive results – as much as 50% – and that those in turn lead to psychosocial harms such as distress and disruption of personal relationships, as well as increased costs and potential medical harm associated with confirmatory testing and unnecessary treatment.
Given the false-positive rates of the most widely used screening tests and the 15% prevalence of genital herpes in the general population, “screening 10,000 persons would result in approximately 1,485 true-positive and 1,445 false-positive results.” Moreover, confirmatory testing is offered only at a single research laboratory, said Dr. Bibbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates on the Task Force.
Based on these findings and given the natural history and epidemiology of genital herpes, they characterized the potential benefits of routine screening as “no greater than small,” and the harms as “at least moderate” (JAMA. 2016 Dec 20;316[23]:2525-30. doi: 10.1001/jama.2016.16776).
The American Academy of Family Physicians, the American College of Obstetrics and Gynecology, and the Centers for Disease Control and Prevention also recommend against routine HSV screening of adolescents and adults, including pregnant women, the investigators noted.
The USPSTF is an independent, voluntary group that evaluates preventive health care services and is funded by the Agency for Healthcare Research and Quality by mandate of the U.S. Congress. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.
[email protected]
On Twitter @idpractitioner
Asymptomatic adolescents and adults, including pregnant women, should not undergo routine serologic screening for genital herpes because the harms of this approach outweigh the benefits, according to an updated US Preventive Services Task Force (USPSTF) Recommendation Statement published online in JAMA.
The USPSTF last addressed screening for herpes simplex virus (HSV) in a 2005 Recommendation Statement, which advised against routine screening of asymptomatic patients at that time. “A small number” of clinical trials examined the issue since then, so the group commissioned a review of the literature through October 2016 to incorporate any new findings into the update, said Kirsten Bibbins-Domingo, MD, PhD, chair of the USPSTF and lead author of the update, and her associates.
Dr. Feltner and her colleagues concluded that current serologic screening tests produce a high rate of false-positive results – as much as 50% – and that those in turn lead to psychosocial harms such as distress and disruption of personal relationships, as well as increased costs and potential medical harm associated with confirmatory testing and unnecessary treatment.
Given the false-positive rates of the most widely used screening tests and the 15% prevalence of genital herpes in the general population, “screening 10,000 persons would result in approximately 1,485 true-positive and 1,445 false-positive results.” Moreover, confirmatory testing is offered only at a single research laboratory, said Dr. Bibbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates on the Task Force.
Based on these findings and given the natural history and epidemiology of genital herpes, they characterized the potential benefits of routine screening as “no greater than small,” and the harms as “at least moderate” (JAMA. 2016 Dec 20;316[23]:2525-30. doi: 10.1001/jama.2016.16776).
The American Academy of Family Physicians, the American College of Obstetrics and Gynecology, and the Centers for Disease Control and Prevention also recommend against routine HSV screening of adolescents and adults, including pregnant women, the investigators noted.
The USPSTF is an independent, voluntary group that evaluates preventive health care services and is funded by the Agency for Healthcare Research and Quality by mandate of the U.S. Congress. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.
[email protected]
On Twitter @idpractitioner
FROM JAMA
Key clinical point: Asymptomatic adults and adolescents should not undergo routine serologic screening for genital herpes because the harms outweigh the benefits, according to an updated USPSTF recommendation statement.
Major finding: Given the nearly 50% false-positive rate of current screening tests, screening 10,000 members of the general population would result in approximately 1,485 true-positive and 1,445 false-positive results.
Data source: A systematic review of 17 studies involving 9,736 participants regarding the accuracy, benefits, and harms of HSV screening.
Disclosures: The USPSTF is an independent, voluntary group that evaluates preventive health care services and is funded by the Agency for Healthcare Research and Quality by mandate of the U.S. Congress. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.
Pritelivir beats valacyclovir at suppressing genital HSV-2 infection
A 1-month course of pritelivir reduced genital HSV-2 shedding more than valacyclovir did in a small phase II clinical trial, according to a report published online in JAMA.
Previous phase I studies suggested that oral daily pritelivir was safe and tolerable in the patient population under evaluation (healthy adults with four to nine annual genital HSV-2 recurrences). Researchers performed this randomized, double-blind, crossover trial to assess the drug’s efficacy in 91 adults (mean age 48 years) who had frequent recurrences of genital symptoms and lesions. Study participants at four U.S. clinical research centers received pritelivir or valacyclovir for 28 days, followed by a washout period, then a 28-day course of the other drug, said lead investigator Anna Wald, MD, of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, and her associates.
The primary endpoint – the number of swabs that tested positive for HSV-2 relative to the total number of swabs collected – was 2.4% during pritelivir treatment and 5.3% during valacyclovir treatment, a significant difference (relative risk, 0.42). Genital lesions were reported on 1.9% of days during pritelivir treatment, compared with 3.9% of days during valacyclovir treatment (RR, 0.40). In addition, the frequency of subclinical shedding also was significantly lower with pritelivir (1.8% vs. 4.1%), while the percentage of episodes resolving within 24 hours was significantly higher (87% vs. 69%).
The rate and severity of adverse events were similar between the two study groups. There were no serious adverse events or deaths. Compared with valacyclovir, pritelivir was associated with more statistically significant but clinically irrelevant changes in lymphocyte counts and creatinine levels. One patient in each study group developed mild allergic reactions thought to be possibly related to treatment, which resolved upon discontinuation of the study drugs.
AiCuris, maker of pritelivir, supported the study. Dr. Wald reported ties to AiCuris, Amgen, GlaxoSmithKline, Merck, Gilead, Vical, Genocea, and Admedus; her associates reported ties to numerous industry sources.
[email protected]
On Twitter @idpractitioner
A 1-month course of pritelivir reduced genital HSV-2 shedding more than valacyclovir did in a small phase II clinical trial, according to a report published online in JAMA.
Previous phase I studies suggested that oral daily pritelivir was safe and tolerable in the patient population under evaluation (healthy adults with four to nine annual genital HSV-2 recurrences). Researchers performed this randomized, double-blind, crossover trial to assess the drug’s efficacy in 91 adults (mean age 48 years) who had frequent recurrences of genital symptoms and lesions. Study participants at four U.S. clinical research centers received pritelivir or valacyclovir for 28 days, followed by a washout period, then a 28-day course of the other drug, said lead investigator Anna Wald, MD, of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, and her associates.
The primary endpoint – the number of swabs that tested positive for HSV-2 relative to the total number of swabs collected – was 2.4% during pritelivir treatment and 5.3% during valacyclovir treatment, a significant difference (relative risk, 0.42). Genital lesions were reported on 1.9% of days during pritelivir treatment, compared with 3.9% of days during valacyclovir treatment (RR, 0.40). In addition, the frequency of subclinical shedding also was significantly lower with pritelivir (1.8% vs. 4.1%), while the percentage of episodes resolving within 24 hours was significantly higher (87% vs. 69%).
The rate and severity of adverse events were similar between the two study groups. There were no serious adverse events or deaths. Compared with valacyclovir, pritelivir was associated with more statistically significant but clinically irrelevant changes in lymphocyte counts and creatinine levels. One patient in each study group developed mild allergic reactions thought to be possibly related to treatment, which resolved upon discontinuation of the study drugs.
AiCuris, maker of pritelivir, supported the study. Dr. Wald reported ties to AiCuris, Amgen, GlaxoSmithKline, Merck, Gilead, Vical, Genocea, and Admedus; her associates reported ties to numerous industry sources.
[email protected]
On Twitter @idpractitioner
A 1-month course of pritelivir reduced genital HSV-2 shedding more than valacyclovir did in a small phase II clinical trial, according to a report published online in JAMA.
Previous phase I studies suggested that oral daily pritelivir was safe and tolerable in the patient population under evaluation (healthy adults with four to nine annual genital HSV-2 recurrences). Researchers performed this randomized, double-blind, crossover trial to assess the drug’s efficacy in 91 adults (mean age 48 years) who had frequent recurrences of genital symptoms and lesions. Study participants at four U.S. clinical research centers received pritelivir or valacyclovir for 28 days, followed by a washout period, then a 28-day course of the other drug, said lead investigator Anna Wald, MD, of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, and her associates.
The primary endpoint – the number of swabs that tested positive for HSV-2 relative to the total number of swabs collected – was 2.4% during pritelivir treatment and 5.3% during valacyclovir treatment, a significant difference (relative risk, 0.42). Genital lesions were reported on 1.9% of days during pritelivir treatment, compared with 3.9% of days during valacyclovir treatment (RR, 0.40). In addition, the frequency of subclinical shedding also was significantly lower with pritelivir (1.8% vs. 4.1%), while the percentage of episodes resolving within 24 hours was significantly higher (87% vs. 69%).
The rate and severity of adverse events were similar between the two study groups. There were no serious adverse events or deaths. Compared with valacyclovir, pritelivir was associated with more statistically significant but clinically irrelevant changes in lymphocyte counts and creatinine levels. One patient in each study group developed mild allergic reactions thought to be possibly related to treatment, which resolved upon discontinuation of the study drugs.
AiCuris, maker of pritelivir, supported the study. Dr. Wald reported ties to AiCuris, Amgen, GlaxoSmithKline, Merck, Gilead, Vical, Genocea, and Admedus; her associates reported ties to numerous industry sources.
[email protected]
On Twitter @idpractitioner
Key clinical point:
Major finding: Among genital swabs, 2.4% tested positive for HSV-2 during pritelivir treatment and 5.3% did during valacyclovir treatment (relative risk, 0.42).
Data source: A randomized, double-blind, crossover trial involving 91 adults with frequently recurring genital HSV-2.
Disclosures: AiCuris, maker of pritelivir, supported the study. Dr. Wald reported ties to AiCuris, Amgen, GlaxoSmithKline, Merck, Gilead, Vical, Genocea, and Admedus; her associates reported ties to numerous industry sources.
University of Minnesota producing more than its fair share of FPs
, according to the American Academy of Family Physicians.
Data from the AAFP’s annual survey of family medicine residency programs showed that, over a 3-year period from 2013 to 2015, 19% of the University of Minnesota’s medical school graduates entered a family medicine residency, reported Stanley M. Kozakowski, MD, and his associates (Fam Med. 2016;48[9]:688-95).
In 2015, the University of Minnesota produced 42 graduates who became FP residents, the highest number for any of the 134 U.S. medical schools granting MD degrees in family medicine. Among schools granting DO degrees, however, the leader for 2015 was Des Moines University, which had 68 students (32.7%) enter family medicine, the investigators said. Of the 2,463 individuals who were first-year family medicine residents in 2015, 1,640 graduated from MD-granting schools and 823 graduated from DO-granting schools.
, according to the American Academy of Family Physicians.
Data from the AAFP’s annual survey of family medicine residency programs showed that, over a 3-year period from 2013 to 2015, 19% of the University of Minnesota’s medical school graduates entered a family medicine residency, reported Stanley M. Kozakowski, MD, and his associates (Fam Med. 2016;48[9]:688-95).
In 2015, the University of Minnesota produced 42 graduates who became FP residents, the highest number for any of the 134 U.S. medical schools granting MD degrees in family medicine. Among schools granting DO degrees, however, the leader for 2015 was Des Moines University, which had 68 students (32.7%) enter family medicine, the investigators said. Of the 2,463 individuals who were first-year family medicine residents in 2015, 1,640 graduated from MD-granting schools and 823 graduated from DO-granting schools.
, according to the American Academy of Family Physicians.
Data from the AAFP’s annual survey of family medicine residency programs showed that, over a 3-year period from 2013 to 2015, 19% of the University of Minnesota’s medical school graduates entered a family medicine residency, reported Stanley M. Kozakowski, MD, and his associates (Fam Med. 2016;48[9]:688-95).
In 2015, the University of Minnesota produced 42 graduates who became FP residents, the highest number for any of the 134 U.S. medical schools granting MD degrees in family medicine. Among schools granting DO degrees, however, the leader for 2015 was Des Moines University, which had 68 students (32.7%) enter family medicine, the investigators said. Of the 2,463 individuals who were first-year family medicine residents in 2015, 1,640 graduated from MD-granting schools and 823 graduated from DO-granting schools.
FROM FAMILY MEDICINE
Flu Vaccine Provides Substantial Benefits for Patients With Diabetes
Is it safe to give flu vaccinations to patients with an impaired immune response, such as those with diabetes? The evidence was both sparse and inconclusive, say researchers from Imperial College London. But their 7-year study of 124,503 patients with type 2 diabetes suggests “substantial benefits.”
The study covered 4 periods in each cohort year: preinfluenza, influenza season, postinfluenza, and summer. The outcome measures were hospital admissions for acute myocardial infarction (MI), stroke, pneumonia, influenza, and heart failure as well as all-cause death.
During the study, there were 5,142 admissions for acute MI; 4,515 for stroke; 14,154 for pneumonia or influenza; 12,915 for heart failure; and 21,070 deaths.
Vaccine recipients were older and generally more ill; they had more coexisting conditions and were taking more medications than nonrecipients. However, vaccination was associated with significant reductions in all the outcomes during the flu season. After adjusting for residual confounding, the researchers found 19% lower rates of admissions for acute MI, 30% for stroke, 22% for heart failure, and 15% for pneumonia or influenza. The mortality rate for patients was 24% lower than that of nonrecipients.
That was during flu season, but vaccination also was associated with significantly fewer events during the pre- and postinfluenza seasons for all outcomes except for acute MI and pneumonia/influenza in the preinfluenza period.
Concerns about the benefits of influenza vaccination in older adults and patients with chronic illnesses affect the acceptance and uptake of vaccination, the researchers note. But their findings, they add, “underline the importance of influenza vaccination as part of comprehensive secondary prevention in this high-risk population.”
Source:
Vamos EP, Pape UJ, Curcin V, et al. CMAJ. 2016;188(14):E342-E351.
Is it safe to give flu vaccinations to patients with an impaired immune response, such as those with diabetes? The evidence was both sparse and inconclusive, say researchers from Imperial College London. But their 7-year study of 124,503 patients with type 2 diabetes suggests “substantial benefits.”
The study covered 4 periods in each cohort year: preinfluenza, influenza season, postinfluenza, and summer. The outcome measures were hospital admissions for acute myocardial infarction (MI), stroke, pneumonia, influenza, and heart failure as well as all-cause death.
During the study, there were 5,142 admissions for acute MI; 4,515 for stroke; 14,154 for pneumonia or influenza; 12,915 for heart failure; and 21,070 deaths.
Vaccine recipients were older and generally more ill; they had more coexisting conditions and were taking more medications than nonrecipients. However, vaccination was associated with significant reductions in all the outcomes during the flu season. After adjusting for residual confounding, the researchers found 19% lower rates of admissions for acute MI, 30% for stroke, 22% for heart failure, and 15% for pneumonia or influenza. The mortality rate for patients was 24% lower than that of nonrecipients.
That was during flu season, but vaccination also was associated with significantly fewer events during the pre- and postinfluenza seasons for all outcomes except for acute MI and pneumonia/influenza in the preinfluenza period.
Concerns about the benefits of influenza vaccination in older adults and patients with chronic illnesses affect the acceptance and uptake of vaccination, the researchers note. But their findings, they add, “underline the importance of influenza vaccination as part of comprehensive secondary prevention in this high-risk population.”
Source:
Vamos EP, Pape UJ, Curcin V, et al. CMAJ. 2016;188(14):E342-E351.
Is it safe to give flu vaccinations to patients with an impaired immune response, such as those with diabetes? The evidence was both sparse and inconclusive, say researchers from Imperial College London. But their 7-year study of 124,503 patients with type 2 diabetes suggests “substantial benefits.”
The study covered 4 periods in each cohort year: preinfluenza, influenza season, postinfluenza, and summer. The outcome measures were hospital admissions for acute myocardial infarction (MI), stroke, pneumonia, influenza, and heart failure as well as all-cause death.
During the study, there were 5,142 admissions for acute MI; 4,515 for stroke; 14,154 for pneumonia or influenza; 12,915 for heart failure; and 21,070 deaths.
Vaccine recipients were older and generally more ill; they had more coexisting conditions and were taking more medications than nonrecipients. However, vaccination was associated with significant reductions in all the outcomes during the flu season. After adjusting for residual confounding, the researchers found 19% lower rates of admissions for acute MI, 30% for stroke, 22% for heart failure, and 15% for pneumonia or influenza. The mortality rate for patients was 24% lower than that of nonrecipients.
That was during flu season, but vaccination also was associated with significantly fewer events during the pre- and postinfluenza seasons for all outcomes except for acute MI and pneumonia/influenza in the preinfluenza period.
Concerns about the benefits of influenza vaccination in older adults and patients with chronic illnesses affect the acceptance and uptake of vaccination, the researchers note. But their findings, they add, “underline the importance of influenza vaccination as part of comprehensive secondary prevention in this high-risk population.”
Source:
Vamos EP, Pape UJ, Curcin V, et al. CMAJ. 2016;188(14):E342-E351.
Ruxolitinib may prevent CRS after CAR T-cell therapy
Photo courtesy of NCI
SAN DIEGO—A novel xenograft model of acute myeloid leukemia (AML) demonstrated that the JAK/STAT inhibitor ruxolitinib can prevent severe cytokine release syndrome (CRS) without impairing the anti-tumor effect of chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASH Annual Meeting.
Almost all patients responding to CART-cell therapy develop CRS, and up to 60% develop severe CRS.
The research team believes the mouse model and findings with ruxolitinib will provide an important platform for studying CRS prevention and treatment.
At ASH, Saad Kenderian, MD, of the Mayo Clinic in Rochester, Minnesota, explained that CRS produces very high levels of the inflammatory protein IL-6.
Treatment with ruxolitinib in clinical studies has reduced human inflammatory cytokines. Therefore, it made sense to the investigators to study ruxolitinib as a means to prevent CRS after CAR T-cell therapy.
Tocilizumab has been used to treat grade 3 and 4 CRS, but physicians are concerned that earlier introduction during the course of CRS may impair CAR T-cell function.
At present, no relevant preclinical model for CRS after CAR T-cell therapy exists, “which is limiting the development of CRS preventative modalities that could, in turn, enhance the feasibility of CAR T-cell therapy,” Dr Kenderian said.
And so the investigators decided to create an animal model.
Dr Kenderian described the work at the meeting as abstract 652.
Mouse model for human CRS
Using NSG-S mice (non-obese diabetic, SCID ɣ -/- mice additionally transgenic for human stem cell factor, IL-3, and GM-CSF), investigators injected them with blasts from AML patients. After 3 to 4 weeks, investigators treated the mice with 1 x 106 CD123-directed CAR T cells.
Dr Kenderian noted this dose of CART123 was 10 times higher than doses previously used in primary AML xenograft models.
The mice became weak, emaciated, developed hunched bodies, became withdrawn, had poor motor responses, and died in 7 to 10 days. The illness started within 1 week of CAR T-cell injection and correlated with significant expansion of T cells in the peripheral blood of these mice.
The team studied the serum from these mice 7 days after CART123 injection. They found extreme elevation of human IL-6, interferon-γ, tumor necrosis factor-α, and other inflammatory cytokines. This response resembled human CRS after CAR T-cell therapy.
Ruxolitinib treatment
The investigators first studied ruxolitinib activity in vitro with CART123 cells and found that ruxolitinib did not impair CAR T-cell effector functions.
“And also, ruxolitinib was not directly toxic to CAR T cells,” Dr Kenderian added.
But ruxolitinib did slow CAR T-cell proliferation in vitro.
They next tested ruxolitinib and CART123 in the mouse model.
Once the mice experienced high-burden disease, investigators treated them with CART123. That same day, investigators began treating the mice with ruxolitinib for 1 week. The mice were randomized to 30, 60, 90 mg/kg, or vehicle twice a day.
Twenty-nine days after AML injection, the mice treated with CART123 plus 90 mg or 60 mg of ruxolitinib experienced less weight loss than those treated with CART123 plus 30 mg of ruxolitinib or CART123-only.
“And more importantly, all mice had eradication of their disease,” Dr Kenderian said.
Mice treated with CART123 plus 90 mg, 60 mg, or 30 mg of ruxolitinib or CART123 alone had fewer AML blasts at day 28 than mice treated with 60 mg of ruxolitinib alone.
The investigators then analyzed the effect of ruxolitinib on the anti-tumor effect of CART123 and found that ruxolitinib did not impair it.
The attenuation of inflammatory cytokines translated to a survival advantage for mice treated with CART123 and ruxolitinib.
The investigators believe the addition of ruxolitinib to CAR T-cell therapy is a modality that should be investigated in patients at high-risk of developing CRS.
Dr Kenderian disclosed patents, royalties, and research funding from Novartis. 
Photo courtesy of NCI
SAN DIEGO—A novel xenograft model of acute myeloid leukemia (AML) demonstrated that the JAK/STAT inhibitor ruxolitinib can prevent severe cytokine release syndrome (CRS) without impairing the anti-tumor effect of chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASH Annual Meeting.
Almost all patients responding to CART-cell therapy develop CRS, and up to 60% develop severe CRS.
The research team believes the mouse model and findings with ruxolitinib will provide an important platform for studying CRS prevention and treatment.
At ASH, Saad Kenderian, MD, of the Mayo Clinic in Rochester, Minnesota, explained that CRS produces very high levels of the inflammatory protein IL-6.
Treatment with ruxolitinib in clinical studies has reduced human inflammatory cytokines. Therefore, it made sense to the investigators to study ruxolitinib as a means to prevent CRS after CAR T-cell therapy.
Tocilizumab has been used to treat grade 3 and 4 CRS, but physicians are concerned that earlier introduction during the course of CRS may impair CAR T-cell function.
At present, no relevant preclinical model for CRS after CAR T-cell therapy exists, “which is limiting the development of CRS preventative modalities that could, in turn, enhance the feasibility of CAR T-cell therapy,” Dr Kenderian said.
And so the investigators decided to create an animal model.
Dr Kenderian described the work at the meeting as abstract 652.
Mouse model for human CRS
Using NSG-S mice (non-obese diabetic, SCID ɣ -/- mice additionally transgenic for human stem cell factor, IL-3, and GM-CSF), investigators injected them with blasts from AML patients. After 3 to 4 weeks, investigators treated the mice with 1 x 106 CD123-directed CAR T cells.
Dr Kenderian noted this dose of CART123 was 10 times higher than doses previously used in primary AML xenograft models.
The mice became weak, emaciated, developed hunched bodies, became withdrawn, had poor motor responses, and died in 7 to 10 days. The illness started within 1 week of CAR T-cell injection and correlated with significant expansion of T cells in the peripheral blood of these mice.
The team studied the serum from these mice 7 days after CART123 injection. They found extreme elevation of human IL-6, interferon-γ, tumor necrosis factor-α, and other inflammatory cytokines. This response resembled human CRS after CAR T-cell therapy.
Ruxolitinib treatment
The investigators first studied ruxolitinib activity in vitro with CART123 cells and found that ruxolitinib did not impair CAR T-cell effector functions.
“And also, ruxolitinib was not directly toxic to CAR T cells,” Dr Kenderian added.
But ruxolitinib did slow CAR T-cell proliferation in vitro.
They next tested ruxolitinib and CART123 in the mouse model.
Once the mice experienced high-burden disease, investigators treated them with CART123. That same day, investigators began treating the mice with ruxolitinib for 1 week. The mice were randomized to 30, 60, 90 mg/kg, or vehicle twice a day.
Twenty-nine days after AML injection, the mice treated with CART123 plus 90 mg or 60 mg of ruxolitinib experienced less weight loss than those treated with CART123 plus 30 mg of ruxolitinib or CART123-only.
“And more importantly, all mice had eradication of their disease,” Dr Kenderian said.
Mice treated with CART123 plus 90 mg, 60 mg, or 30 mg of ruxolitinib or CART123 alone had fewer AML blasts at day 28 than mice treated with 60 mg of ruxolitinib alone.
The investigators then analyzed the effect of ruxolitinib on the anti-tumor effect of CART123 and found that ruxolitinib did not impair it.
The attenuation of inflammatory cytokines translated to a survival advantage for mice treated with CART123 and ruxolitinib.
The investigators believe the addition of ruxolitinib to CAR T-cell therapy is a modality that should be investigated in patients at high-risk of developing CRS.
Dr Kenderian disclosed patents, royalties, and research funding from Novartis.
Photo courtesy of NCI
SAN DIEGO—A novel xenograft model of acute myeloid leukemia (AML) demonstrated that the JAK/STAT inhibitor ruxolitinib can prevent severe cytokine release syndrome (CRS) without impairing the anti-tumor effect of chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASH Annual Meeting.
Almost all patients responding to CART-cell therapy develop CRS, and up to 60% develop severe CRS.
The research team believes the mouse model and findings with ruxolitinib will provide an important platform for studying CRS prevention and treatment.
At ASH, Saad Kenderian, MD, of the Mayo Clinic in Rochester, Minnesota, explained that CRS produces very high levels of the inflammatory protein IL-6.
Treatment with ruxolitinib in clinical studies has reduced human inflammatory cytokines. Therefore, it made sense to the investigators to study ruxolitinib as a means to prevent CRS after CAR T-cell therapy.
Tocilizumab has been used to treat grade 3 and 4 CRS, but physicians are concerned that earlier introduction during the course of CRS may impair CAR T-cell function.
At present, no relevant preclinical model for CRS after CAR T-cell therapy exists, “which is limiting the development of CRS preventative modalities that could, in turn, enhance the feasibility of CAR T-cell therapy,” Dr Kenderian said.
And so the investigators decided to create an animal model.
Dr Kenderian described the work at the meeting as abstract 652.
Mouse model for human CRS
Using NSG-S mice (non-obese diabetic, SCID ɣ -/- mice additionally transgenic for human stem cell factor, IL-3, and GM-CSF), investigators injected them with blasts from AML patients. After 3 to 4 weeks, investigators treated the mice with 1 x 106 CD123-directed CAR T cells.
Dr Kenderian noted this dose of CART123 was 10 times higher than doses previously used in primary AML xenograft models.
The mice became weak, emaciated, developed hunched bodies, became withdrawn, had poor motor responses, and died in 7 to 10 days. The illness started within 1 week of CAR T-cell injection and correlated with significant expansion of T cells in the peripheral blood of these mice.
The team studied the serum from these mice 7 days after CART123 injection. They found extreme elevation of human IL-6, interferon-γ, tumor necrosis factor-α, and other inflammatory cytokines. This response resembled human CRS after CAR T-cell therapy.
Ruxolitinib treatment
The investigators first studied ruxolitinib activity in vitro with CART123 cells and found that ruxolitinib did not impair CAR T-cell effector functions.
“And also, ruxolitinib was not directly toxic to CAR T cells,” Dr Kenderian added.
But ruxolitinib did slow CAR T-cell proliferation in vitro.
They next tested ruxolitinib and CART123 in the mouse model.
Once the mice experienced high-burden disease, investigators treated them with CART123. That same day, investigators began treating the mice with ruxolitinib for 1 week. The mice were randomized to 30, 60, 90 mg/kg, or vehicle twice a day.
Twenty-nine days after AML injection, the mice treated with CART123 plus 90 mg or 60 mg of ruxolitinib experienced less weight loss than those treated with CART123 plus 30 mg of ruxolitinib or CART123-only.
“And more importantly, all mice had eradication of their disease,” Dr Kenderian said.
Mice treated with CART123 plus 90 mg, 60 mg, or 30 mg of ruxolitinib or CART123 alone had fewer AML blasts at day 28 than mice treated with 60 mg of ruxolitinib alone.
The investigators then analyzed the effect of ruxolitinib on the anti-tumor effect of CART123 and found that ruxolitinib did not impair it.
The attenuation of inflammatory cytokines translated to a survival advantage for mice treated with CART123 and ruxolitinib.
The investigators believe the addition of ruxolitinib to CAR T-cell therapy is a modality that should be investigated in patients at high-risk of developing CRS.
Dr Kenderian disclosed patents, royalties, and research funding from Novartis.
Trial supports early treatment of lower-risk ET
Photo courtesy of CDC
SAN DIEGO—Results from the ARETA trial suggest patients with essential thrombocythemia (ET) can benefit from early treatment even if they are not considered high-risk.
In this phase 3 trial, non-high-risk patients were less likely to experience ET-related cardiovascular events or disease progression if they received extended-release anagrelide rather than placebo.
Patients who received extended-release anagrelide were also less likely to become high-risk over time.
And extended-release anagrelide had a safety profile consistent with conventional anagrelide formulations, according to investigator Heinz Gisslinger, MD, of the Medical University of Vienna in Austria.
Dr Gisslinger reported final results of the ARETA trial at the 2016 ASH Annual Meeting (abstract 476).
The trial was sponsored by AOP Orphan Pharmaceuticals AG, the company developing the extended-release formulation of anagrelide, known as anagrelide retard (AR).
Dr Gisslinger noted that the goals of developing AR are to achieve lower peak plasma concentration of anagrelide, reduce the frequency and intensity of peak concentration related to adverse events (AEs), allow for an easier dosing scheme (once daily vs 2 to 3 times daily), and improve patient compliance.
He also pointed out that results of the phase 3 TEAM-ET trial suggest AR is non-inferior to the standard formulation of anagrelide (Thromboreductin, also a product of AOP Orphan Pharmaceuticals).
So with the ARETA trial, Dr Gisslinger and his colleagues set out to determine if AR would be beneficial as an early intervention in patients with non-high-risk ET.
Patients
The trial enrolled 146 patients who had platelet counts below 1000 G/L and met at least 1 of the following criteria:
- Age 40 to 60 years
- ET duration of more than 3 years
- Any risk factor for thrombotic complications (JAK2 mutation, protein C and/or S deficiency, antithrombin III deficiency, factor V Leiden or prothrombin mutation, or cardiovascular risk factors).
Seventy-seven patients were randomized to AR, and 69 were randomized to placebo. In both treatment arms, 100% of patients were Caucasian, and about 74% were female.
The mean age was 40.9 (range, 20-60) in the AR arm and 45.2 (range, 19-59) in the placebo arm. The median disease duration was 75.0 days (range, 1-2502) and 78.0 days (range, 1-2195), respectively. The mean platelet count was 748.6 G/L and 745.3 G/L, respectively.
A majority of patients in both arms had JAK2 mutations (62.7% in the AR arm and 63.8% in the placebo arm). Fewer had CALR mutations (22.7% and 13.6%, respectively) and MPL mutations (16.7% and 12.5%).
Treatment
Patients were stratified by JAK2 status and randomized to receive AR at 2 to 8 mg/day or placebo.
The dosing of AR started at 1 tablet (2 mg) per day during week 1 and was titrated up according to platelet response to 2 tablets in week 2. Dosing was further increased or decreased according to platelet response in weeks 3 and 4.
The maximum dose was 4 tablets (8 mg) per day. After week 4, the maximum dose to achieve optimal platelet counts (<450 G/L) was maintained, and patients continued with weekly visits through week 6.
After that, patients had visits every 3 months in both the main phase of this study and the extension phase. The main phase lasted 1 year, and the extension phase lasted up to 3 years.
Sixty patients (77.9%) in the AR arm and 52 (75.4%) in the placebo arm completed the main phase of the study.
Fifty-seven patients in the AR arm entered the extension phase, and 44 (57.1%) completed it. Thirty-four patients in the placebo arm entered the extension phase, and 21 (30.4%) completed it.
Efficacy
The primary endpoint was time to ET-related cardiovascular events (as confirmed by a blinded expert panel) or disease progression/worsening (platelet increase >1000 G/L).
The 1-year event-free rate (patients who did not meet criteria for the primary endpoint) was 87% in the AR arm and 69% in the placebo arm (hazard ratio=0.356, P=0.0008).
According to the expert panel, there were 12 ET-related events in 11 patients in the AR arm, as well as 17 such events in 14 patients in the placebo arm. This included major and minor arterial, venous, and bleeding events.
In total, there were 13 patients who had ET-related events or met platelet criteria in the AR arm (13 events) and 26 patients who had ET-related events or met platelet criteria in the placebo arm (30 events).
Nine patients in the AR arm (11.7%) and 18 in the placebo arm (26.1%) changed to high-risk status at some point during the trial (odds ratio=2.67, P=0.033).
Safety
The overall incidence of AEs was 88.3% in the AR arm and 69.6% in the placebo arm. The incidence of treatment-related AEs was 76.6% and 27.5%, respectively.
The incidence of treatment-related serious AEs was 1.3% and 0%, respectively. And the incidence of treatment-related AEs leading to withdrawal was 9.1% and 7.2%, respectively.
Treatment-related AEs occurring in more than 10% of patients in either arm (the AR and placebo arms, respectively) included headache (41.6% and 15.9%), dizziness (35.1% and 14.5%), palpitations (28.6% and 1.4%), and tachycardia (10.4% and 1.4%).
In closing, Dr Gisslinger noted that the primary endpoint of this study was met, and AR allowed for platelet count normalization and delayed progression to high-risk status.
Furthermore, the safety profile of AR is consistent with conventional anagrelide formulations, but AR allows for a more convenient dosing schedule.
Dr Gisslinger concluded, “[T]hese data from the ARETA study support an early treatment concept for all ET patients where platelet count or symptom reduction is a goal and those patients who can be attributed as intermediate-risk patients.”
Photo courtesy of CDC
SAN DIEGO—Results from the ARETA trial suggest patients with essential thrombocythemia (ET) can benefit from early treatment even if they are not considered high-risk.
In this phase 3 trial, non-high-risk patients were less likely to experience ET-related cardiovascular events or disease progression if they received extended-release anagrelide rather than placebo.
Patients who received extended-release anagrelide were also less likely to become high-risk over time.
And extended-release anagrelide had a safety profile consistent with conventional anagrelide formulations, according to investigator Heinz Gisslinger, MD, of the Medical University of Vienna in Austria.
Dr Gisslinger reported final results of the ARETA trial at the 2016 ASH Annual Meeting (abstract 476).
The trial was sponsored by AOP Orphan Pharmaceuticals AG, the company developing the extended-release formulation of anagrelide, known as anagrelide retard (AR).
Dr Gisslinger noted that the goals of developing AR are to achieve lower peak plasma concentration of anagrelide, reduce the frequency and intensity of peak concentration related to adverse events (AEs), allow for an easier dosing scheme (once daily vs 2 to 3 times daily), and improve patient compliance.
He also pointed out that results of the phase 3 TEAM-ET trial suggest AR is non-inferior to the standard formulation of anagrelide (Thromboreductin, also a product of AOP Orphan Pharmaceuticals).
So with the ARETA trial, Dr Gisslinger and his colleagues set out to determine if AR would be beneficial as an early intervention in patients with non-high-risk ET.
Patients
The trial enrolled 146 patients who had platelet counts below 1000 G/L and met at least 1 of the following criteria:
- Age 40 to 60 years
- ET duration of more than 3 years
- Any risk factor for thrombotic complications (JAK2 mutation, protein C and/or S deficiency, antithrombin III deficiency, factor V Leiden or prothrombin mutation, or cardiovascular risk factors).
Seventy-seven patients were randomized to AR, and 69 were randomized to placebo. In both treatment arms, 100% of patients were Caucasian, and about 74% were female.
The mean age was 40.9 (range, 20-60) in the AR arm and 45.2 (range, 19-59) in the placebo arm. The median disease duration was 75.0 days (range, 1-2502) and 78.0 days (range, 1-2195), respectively. The mean platelet count was 748.6 G/L and 745.3 G/L, respectively.
A majority of patients in both arms had JAK2 mutations (62.7% in the AR arm and 63.8% in the placebo arm). Fewer had CALR mutations (22.7% and 13.6%, respectively) and MPL mutations (16.7% and 12.5%).
Treatment
Patients were stratified by JAK2 status and randomized to receive AR at 2 to 8 mg/day or placebo.
The dosing of AR started at 1 tablet (2 mg) per day during week 1 and was titrated up according to platelet response to 2 tablets in week 2. Dosing was further increased or decreased according to platelet response in weeks 3 and 4.
The maximum dose was 4 tablets (8 mg) per day. After week 4, the maximum dose to achieve optimal platelet counts (<450 G/L) was maintained, and patients continued with weekly visits through week 6.
After that, patients had visits every 3 months in both the main phase of this study and the extension phase. The main phase lasted 1 year, and the extension phase lasted up to 3 years.
Sixty patients (77.9%) in the AR arm and 52 (75.4%) in the placebo arm completed the main phase of the study.
Fifty-seven patients in the AR arm entered the extension phase, and 44 (57.1%) completed it. Thirty-four patients in the placebo arm entered the extension phase, and 21 (30.4%) completed it.
Efficacy
The primary endpoint was time to ET-related cardiovascular events (as confirmed by a blinded expert panel) or disease progression/worsening (platelet increase >1000 G/L).
The 1-year event-free rate (patients who did not meet criteria for the primary endpoint) was 87% in the AR arm and 69% in the placebo arm (hazard ratio=0.356, P=0.0008).
According to the expert panel, there were 12 ET-related events in 11 patients in the AR arm, as well as 17 such events in 14 patients in the placebo arm. This included major and minor arterial, venous, and bleeding events.
In total, there were 13 patients who had ET-related events or met platelet criteria in the AR arm (13 events) and 26 patients who had ET-related events or met platelet criteria in the placebo arm (30 events).
Nine patients in the AR arm (11.7%) and 18 in the placebo arm (26.1%) changed to high-risk status at some point during the trial (odds ratio=2.67, P=0.033).
Safety
The overall incidence of AEs was 88.3% in the AR arm and 69.6% in the placebo arm. The incidence of treatment-related AEs was 76.6% and 27.5%, respectively.
The incidence of treatment-related serious AEs was 1.3% and 0%, respectively. And the incidence of treatment-related AEs leading to withdrawal was 9.1% and 7.2%, respectively.
Treatment-related AEs occurring in more than 10% of patients in either arm (the AR and placebo arms, respectively) included headache (41.6% and 15.9%), dizziness (35.1% and 14.5%), palpitations (28.6% and 1.4%), and tachycardia (10.4% and 1.4%).
In closing, Dr Gisslinger noted that the primary endpoint of this study was met, and AR allowed for platelet count normalization and delayed progression to high-risk status.
Furthermore, the safety profile of AR is consistent with conventional anagrelide formulations, but AR allows for a more convenient dosing schedule.
Dr Gisslinger concluded, “[T]hese data from the ARETA study support an early treatment concept for all ET patients where platelet count or symptom reduction is a goal and those patients who can be attributed as intermediate-risk patients.”
Photo courtesy of CDC
SAN DIEGO—Results from the ARETA trial suggest patients with essential thrombocythemia (ET) can benefit from early treatment even if they are not considered high-risk.
In this phase 3 trial, non-high-risk patients were less likely to experience ET-related cardiovascular events or disease progression if they received extended-release anagrelide rather than placebo.
Patients who received extended-release anagrelide were also less likely to become high-risk over time.
And extended-release anagrelide had a safety profile consistent with conventional anagrelide formulations, according to investigator Heinz Gisslinger, MD, of the Medical University of Vienna in Austria.
Dr Gisslinger reported final results of the ARETA trial at the 2016 ASH Annual Meeting (abstract 476).
The trial was sponsored by AOP Orphan Pharmaceuticals AG, the company developing the extended-release formulation of anagrelide, known as anagrelide retard (AR).
Dr Gisslinger noted that the goals of developing AR are to achieve lower peak plasma concentration of anagrelide, reduce the frequency and intensity of peak concentration related to adverse events (AEs), allow for an easier dosing scheme (once daily vs 2 to 3 times daily), and improve patient compliance.
He also pointed out that results of the phase 3 TEAM-ET trial suggest AR is non-inferior to the standard formulation of anagrelide (Thromboreductin, also a product of AOP Orphan Pharmaceuticals).
So with the ARETA trial, Dr Gisslinger and his colleagues set out to determine if AR would be beneficial as an early intervention in patients with non-high-risk ET.
Patients
The trial enrolled 146 patients who had platelet counts below 1000 G/L and met at least 1 of the following criteria:
- Age 40 to 60 years
- ET duration of more than 3 years
- Any risk factor for thrombotic complications (JAK2 mutation, protein C and/or S deficiency, antithrombin III deficiency, factor V Leiden or prothrombin mutation, or cardiovascular risk factors).
Seventy-seven patients were randomized to AR, and 69 were randomized to placebo. In both treatment arms, 100% of patients were Caucasian, and about 74% were female.
The mean age was 40.9 (range, 20-60) in the AR arm and 45.2 (range, 19-59) in the placebo arm. The median disease duration was 75.0 days (range, 1-2502) and 78.0 days (range, 1-2195), respectively. The mean platelet count was 748.6 G/L and 745.3 G/L, respectively.
A majority of patients in both arms had JAK2 mutations (62.7% in the AR arm and 63.8% in the placebo arm). Fewer had CALR mutations (22.7% and 13.6%, respectively) and MPL mutations (16.7% and 12.5%).
Treatment
Patients were stratified by JAK2 status and randomized to receive AR at 2 to 8 mg/day or placebo.
The dosing of AR started at 1 tablet (2 mg) per day during week 1 and was titrated up according to platelet response to 2 tablets in week 2. Dosing was further increased or decreased according to platelet response in weeks 3 and 4.
The maximum dose was 4 tablets (8 mg) per day. After week 4, the maximum dose to achieve optimal platelet counts (<450 G/L) was maintained, and patients continued with weekly visits through week 6.
After that, patients had visits every 3 months in both the main phase of this study and the extension phase. The main phase lasted 1 year, and the extension phase lasted up to 3 years.
Sixty patients (77.9%) in the AR arm and 52 (75.4%) in the placebo arm completed the main phase of the study.
Fifty-seven patients in the AR arm entered the extension phase, and 44 (57.1%) completed it. Thirty-four patients in the placebo arm entered the extension phase, and 21 (30.4%) completed it.
Efficacy
The primary endpoint was time to ET-related cardiovascular events (as confirmed by a blinded expert panel) or disease progression/worsening (platelet increase >1000 G/L).
The 1-year event-free rate (patients who did not meet criteria for the primary endpoint) was 87% in the AR arm and 69% in the placebo arm (hazard ratio=0.356, P=0.0008).
According to the expert panel, there were 12 ET-related events in 11 patients in the AR arm, as well as 17 such events in 14 patients in the placebo arm. This included major and minor arterial, venous, and bleeding events.
In total, there were 13 patients who had ET-related events or met platelet criteria in the AR arm (13 events) and 26 patients who had ET-related events or met platelet criteria in the placebo arm (30 events).
Nine patients in the AR arm (11.7%) and 18 in the placebo arm (26.1%) changed to high-risk status at some point during the trial (odds ratio=2.67, P=0.033).
Safety
The overall incidence of AEs was 88.3% in the AR arm and 69.6% in the placebo arm. The incidence of treatment-related AEs was 76.6% and 27.5%, respectively.
The incidence of treatment-related serious AEs was 1.3% and 0%, respectively. And the incidence of treatment-related AEs leading to withdrawal was 9.1% and 7.2%, respectively.
Treatment-related AEs occurring in more than 10% of patients in either arm (the AR and placebo arms, respectively) included headache (41.6% and 15.9%), dizziness (35.1% and 14.5%), palpitations (28.6% and 1.4%), and tachycardia (10.4% and 1.4%).
In closing, Dr Gisslinger noted that the primary endpoint of this study was met, and AR allowed for platelet count normalization and delayed progression to high-risk status.
Furthermore, the safety profile of AR is consistent with conventional anagrelide formulations, but AR allows for a more convenient dosing schedule.
Dr Gisslinger concluded, “[T]hese data from the ARETA study support an early treatment concept for all ET patients where platelet count or symptom reduction is a goal and those patients who can be attributed as intermediate-risk patients.”
Agios stops developing drug for PK deficiency
Agios Pharmaceuticals, Inc. is no longer developing one of its pyruvate kinase-R (PKR) activators, AG-519, for the treatment of pyruvate kinase (PK) deficiency.
The company withdrew its investigational new drug application for AG-519 following a verbal notification of a clinical hold from the US Food and Drug Administration (FDA).
The hold resulted from an adverse event—cholestatic hepatitis—observed in a phase 1 trial of healthy volunteers.
“[W]e received feedback from the FDA that AG-519 no longer has an appropriate risk-benefit ratio to move forward in clinical development and was placed on clinical hold due to that case of cholestatic hepatitis,” said David Schenkein, MD, chief executive officer at Agios.
“We made the decision to withdraw the IND [investigational new drug application] and discontinue development of AG-519 and advance AG-348, our first-in-class and lead pyruvate kinase activator into pivotal development. We share the FDA’s commitment to patient safety and believe this is the right decision to ultimately help people with PK deficiency.”
About AG-519
Agios has described AG-519 as a potent, highly selective, and orally bioavailable PKR activator devoid of the aromatase inhibitory effects that were observed with the company’s other PKR activator, AG-348.
AG-519 was evaluated in a phase 1 study of healthy volunteers in the UK. The goal of this study was to assess the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and bioavailability.
A case of drug-induced cholestatic hepatitis occurred in the bioavailability portion of the study. This volunteer continues to be monitored and is showing improvement, according to Dr Schenkein.
Agios said other adverse events observed in this trial were largely mild or moderate (grade 1/2). The most common of these was headache.
The company did note a case of grade 2 thrombocytopenia that resolved spontaneously within 7 days after the last dose of AG-519.
Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 1264).
AG-519 was also under investigation in a palatability study of volunteers in the US. The goal of this study was to develop a formulation of the drug for potential future development.
In total, 98 volunteers have received AG-519. No volunteers or patients are currently receiving the drug.
About AG-348
Agios’s decision to stop developing AG-519 does not affect the company’s ongoing phase 2 study (DRIVE PK) of AG-348, an activator of both wild-type and mutated PKR enzymes.
“AG-348 and AG-519 are different molecules with different structures,” Dr Schenkein noted.
Agios is advancing AG-348 into development as the first potential disease-modifying treatment for PK deficiency.
Results from a pair of phase 1 studies of AG-348 were presented at the 2014 ASH Annual Meeting (abstract 4007).
About PK deficiency
PK deficiency is a rare inherited disease that presents as hemolytic anemia. The inherited mutations in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate levels, and a build-up of upstream metabolites, including 2,3-DPG.
The current standard of care for PK deficiency is supportive care, including blood transfusions, splenectomy, chelation therapy to address iron overload, and/or interventions for other treatment- and disease-related morbidities.
There is, at present, no approved therapy to treat the underlying cause of PK deficiency.
Agios Pharmaceuticals, Inc. is no longer developing one of its pyruvate kinase-R (PKR) activators, AG-519, for the treatment of pyruvate kinase (PK) deficiency.
The company withdrew its investigational new drug application for AG-519 following a verbal notification of a clinical hold from the US Food and Drug Administration (FDA).
The hold resulted from an adverse event—cholestatic hepatitis—observed in a phase 1 trial of healthy volunteers.
“[W]e received feedback from the FDA that AG-519 no longer has an appropriate risk-benefit ratio to move forward in clinical development and was placed on clinical hold due to that case of cholestatic hepatitis,” said David Schenkein, MD, chief executive officer at Agios.
“We made the decision to withdraw the IND [investigational new drug application] and discontinue development of AG-519 and advance AG-348, our first-in-class and lead pyruvate kinase activator into pivotal development. We share the FDA’s commitment to patient safety and believe this is the right decision to ultimately help people with PK deficiency.”
About AG-519
Agios has described AG-519 as a potent, highly selective, and orally bioavailable PKR activator devoid of the aromatase inhibitory effects that were observed with the company’s other PKR activator, AG-348.
AG-519 was evaluated in a phase 1 study of healthy volunteers in the UK. The goal of this study was to assess the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and bioavailability.
A case of drug-induced cholestatic hepatitis occurred in the bioavailability portion of the study. This volunteer continues to be monitored and is showing improvement, according to Dr Schenkein.
Agios said other adverse events observed in this trial were largely mild or moderate (grade 1/2). The most common of these was headache.
The company did note a case of grade 2 thrombocytopenia that resolved spontaneously within 7 days after the last dose of AG-519.
Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 1264).
AG-519 was also under investigation in a palatability study of volunteers in the US. The goal of this study was to develop a formulation of the drug for potential future development.
In total, 98 volunteers have received AG-519. No volunteers or patients are currently receiving the drug.
About AG-348
Agios’s decision to stop developing AG-519 does not affect the company’s ongoing phase 2 study (DRIVE PK) of AG-348, an activator of both wild-type and mutated PKR enzymes.
“AG-348 and AG-519 are different molecules with different structures,” Dr Schenkein noted.
Agios is advancing AG-348 into development as the first potential disease-modifying treatment for PK deficiency.
Results from a pair of phase 1 studies of AG-348 were presented at the 2014 ASH Annual Meeting (abstract 4007).
About PK deficiency
PK deficiency is a rare inherited disease that presents as hemolytic anemia. The inherited mutations in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate levels, and a build-up of upstream metabolites, including 2,3-DPG.
The current standard of care for PK deficiency is supportive care, including blood transfusions, splenectomy, chelation therapy to address iron overload, and/or interventions for other treatment- and disease-related morbidities.
There is, at present, no approved therapy to treat the underlying cause of PK deficiency.
Agios Pharmaceuticals, Inc. is no longer developing one of its pyruvate kinase-R (PKR) activators, AG-519, for the treatment of pyruvate kinase (PK) deficiency.
The company withdrew its investigational new drug application for AG-519 following a verbal notification of a clinical hold from the US Food and Drug Administration (FDA).
The hold resulted from an adverse event—cholestatic hepatitis—observed in a phase 1 trial of healthy volunteers.
“[W]e received feedback from the FDA that AG-519 no longer has an appropriate risk-benefit ratio to move forward in clinical development and was placed on clinical hold due to that case of cholestatic hepatitis,” said David Schenkein, MD, chief executive officer at Agios.
“We made the decision to withdraw the IND [investigational new drug application] and discontinue development of AG-519 and advance AG-348, our first-in-class and lead pyruvate kinase activator into pivotal development. We share the FDA’s commitment to patient safety and believe this is the right decision to ultimately help people with PK deficiency.”
About AG-519
Agios has described AG-519 as a potent, highly selective, and orally bioavailable PKR activator devoid of the aromatase inhibitory effects that were observed with the company’s other PKR activator, AG-348.
AG-519 was evaluated in a phase 1 study of healthy volunteers in the UK. The goal of this study was to assess the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and bioavailability.
A case of drug-induced cholestatic hepatitis occurred in the bioavailability portion of the study. This volunteer continues to be monitored and is showing improvement, according to Dr Schenkein.
Agios said other adverse events observed in this trial were largely mild or moderate (grade 1/2). The most common of these was headache.
The company did note a case of grade 2 thrombocytopenia that resolved spontaneously within 7 days after the last dose of AG-519.
Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 1264).
AG-519 was also under investigation in a palatability study of volunteers in the US. The goal of this study was to develop a formulation of the drug for potential future development.
In total, 98 volunteers have received AG-519. No volunteers or patients are currently receiving the drug.
About AG-348
Agios’s decision to stop developing AG-519 does not affect the company’s ongoing phase 2 study (DRIVE PK) of AG-348, an activator of both wild-type and mutated PKR enzymes.
“AG-348 and AG-519 are different molecules with different structures,” Dr Schenkein noted.
Agios is advancing AG-348 into development as the first potential disease-modifying treatment for PK deficiency.
Results from a pair of phase 1 studies of AG-348 were presented at the 2014 ASH Annual Meeting (abstract 4007).
About PK deficiency
PK deficiency is a rare inherited disease that presents as hemolytic anemia. The inherited mutations in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate levels, and a build-up of upstream metabolites, including 2,3-DPG.
The current standard of care for PK deficiency is supportive care, including blood transfusions, splenectomy, chelation therapy to address iron overload, and/or interventions for other treatment- and disease-related morbidities.
There is, at present, no approved therapy to treat the underlying cause of PK deficiency.
Hospitalized patients may fare better with female doctors
Photo courtesy of CDC
New research suggests that hospitalized patients on Medicare may fare better when treated by female internists.
Researchers analyzed data on more than 1.5 million hospitalizations of Medicare beneficiaries and found that patients treated by female physicians had lower rates of 30-day mortality and hospital readmission than those treated by male physicians.
The results were published in JAMA Internal Medicine alongside a related editorial.
“There’s a lot of evidence out there that male and female physicians practice medicine differently,” noted study author Ashish K. Jha, MD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Female physicians are more likely to adhere to clinical practice guidelines. They’re more likely to practice evidence-based medicine. And while that data has been out there, we don’t really know to what extent that actually matters for patient outcomes.”
So with this study, Dr Jha and his colleagues set out to determine if differences in practice patterns translate into differences in patient outcomes.
The researchers analyzed data on 1,583,028 hospitalizations to assess 30-day mortality rates and 1,540,797 hospitalizations to assess readmissions. The hospitalizations occurred from January 1, 2011, to December 31, 2014.
In the 30-day mortality analysis, the patients’ mean age was 80.2 years, 621,412 patients were male, and 961,616 were female.
In the hospital readmission analysis, the mean patient age was 80.1 years, 602,115 patients were male, and 938,682 were female.
Physician characteristics
During the study period, 58,344 internists treated at least 1 hospitalized Medicare beneficiary. Among those physicians, 18,751 were women (32.1%).
Female physicians tended to be younger than males, with mean ages of 42.8 and 47.8, respectively. Females were also more likely than males to have had osteopathic training—8.4% and 7.0%, respectively.
Females were more likely than males to work in large hospitals (41.9% vs 35.7%), nonprofit hospitals (78.2% vs 75.6%), major teaching hospitals (29.0% vs 21.1%), and hospitals located in the Northeast (26.8% vs 22.7%).
Female physicians tended to treat fewer patients than males—131.9 and 180.5 hospitalizations per year, respectively.
Patient characteristics were largely similar between male and female physicians. However, female physicians treated a higher proportion of female patients than male physicians did—62.1% and 60.2%, respectively.
Results
An adjusted analysis showed that patients treated by female physicians had lower 30-day mortality rates than those treated by males—11.07% and 11.49%, respectively (risk difference, –0.43%; 95% confidence interval, –0.57% to –0.28%; P<0.001; number needed to treat to prevent 1 death, 233).
An adjusted analysis for 30-day hospital readmission rates showed a lower rate for patients treated by females than those treated by males—15.02% and 15.57%, respectively (risk difference, –0.55%; 95% confidence interval, –0.71% to –0.39%; P<0.001; number needed to treat to prevent 1 readmission, 182).
These analyses were adjusted for patient characteristics, hospital-fixed effects, and physician characteristics.
The researchers noted that patients treated by female physicians had lower 30-day mortality and readmission rates regardless of their medical condition or the severity of their illness.
“Across a wide range of conditions, we see a very consistent pattern—that patients who are treated by female physicians had modest but consistently better outcomes than patients treated by male physicians,” Dr Jha said.
“That was true across conditions. It was also true across severity of illness. In fact, among the patients who were the sickest, that’s where we saw some of the largest gaps between female and male physicians.”
The researchers also adjusted their analyses for patients’ length of stay, use of care, discharge location, patient volume, and physicians’ years of practice. But this did not affect the results.
Dr Jha and his colleagues said the results of this study suggest differences in practice patterns between male and female physicians may have important clinical implications for patients. And understanding why these differences exist may provide valuable insights into improving the quality of patient care.
Photo courtesy of CDC
New research suggests that hospitalized patients on Medicare may fare better when treated by female internists.
Researchers analyzed data on more than 1.5 million hospitalizations of Medicare beneficiaries and found that patients treated by female physicians had lower rates of 30-day mortality and hospital readmission than those treated by male physicians.
The results were published in JAMA Internal Medicine alongside a related editorial.
“There’s a lot of evidence out there that male and female physicians practice medicine differently,” noted study author Ashish K. Jha, MD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Female physicians are more likely to adhere to clinical practice guidelines. They’re more likely to practice evidence-based medicine. And while that data has been out there, we don’t really know to what extent that actually matters for patient outcomes.”
So with this study, Dr Jha and his colleagues set out to determine if differences in practice patterns translate into differences in patient outcomes.
The researchers analyzed data on 1,583,028 hospitalizations to assess 30-day mortality rates and 1,540,797 hospitalizations to assess readmissions. The hospitalizations occurred from January 1, 2011, to December 31, 2014.
In the 30-day mortality analysis, the patients’ mean age was 80.2 years, 621,412 patients were male, and 961,616 were female.
In the hospital readmission analysis, the mean patient age was 80.1 years, 602,115 patients were male, and 938,682 were female.
Physician characteristics
During the study period, 58,344 internists treated at least 1 hospitalized Medicare beneficiary. Among those physicians, 18,751 were women (32.1%).
Female physicians tended to be younger than males, with mean ages of 42.8 and 47.8, respectively. Females were also more likely than males to have had osteopathic training—8.4% and 7.0%, respectively.
Females were more likely than males to work in large hospitals (41.9% vs 35.7%), nonprofit hospitals (78.2% vs 75.6%), major teaching hospitals (29.0% vs 21.1%), and hospitals located in the Northeast (26.8% vs 22.7%).
Female physicians tended to treat fewer patients than males—131.9 and 180.5 hospitalizations per year, respectively.
Patient characteristics were largely similar between male and female physicians. However, female physicians treated a higher proportion of female patients than male physicians did—62.1% and 60.2%, respectively.
Results
An adjusted analysis showed that patients treated by female physicians had lower 30-day mortality rates than those treated by males—11.07% and 11.49%, respectively (risk difference, –0.43%; 95% confidence interval, –0.57% to –0.28%; P<0.001; number needed to treat to prevent 1 death, 233).
An adjusted analysis for 30-day hospital readmission rates showed a lower rate for patients treated by females than those treated by males—15.02% and 15.57%, respectively (risk difference, –0.55%; 95% confidence interval, –0.71% to –0.39%; P<0.001; number needed to treat to prevent 1 readmission, 182).
These analyses were adjusted for patient characteristics, hospital-fixed effects, and physician characteristics.
The researchers noted that patients treated by female physicians had lower 30-day mortality and readmission rates regardless of their medical condition or the severity of their illness.
“Across a wide range of conditions, we see a very consistent pattern—that patients who are treated by female physicians had modest but consistently better outcomes than patients treated by male physicians,” Dr Jha said.
“That was true across conditions. It was also true across severity of illness. In fact, among the patients who were the sickest, that’s where we saw some of the largest gaps between female and male physicians.”
The researchers also adjusted their analyses for patients’ length of stay, use of care, discharge location, patient volume, and physicians’ years of practice. But this did not affect the results.
Dr Jha and his colleagues said the results of this study suggest differences in practice patterns between male and female physicians may have important clinical implications for patients. And understanding why these differences exist may provide valuable insights into improving the quality of patient care.
Photo courtesy of CDC
New research suggests that hospitalized patients on Medicare may fare better when treated by female internists.
Researchers analyzed data on more than 1.5 million hospitalizations of Medicare beneficiaries and found that patients treated by female physicians had lower rates of 30-day mortality and hospital readmission than those treated by male physicians.
The results were published in JAMA Internal Medicine alongside a related editorial.
“There’s a lot of evidence out there that male and female physicians practice medicine differently,” noted study author Ashish K. Jha, MD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Female physicians are more likely to adhere to clinical practice guidelines. They’re more likely to practice evidence-based medicine. And while that data has been out there, we don’t really know to what extent that actually matters for patient outcomes.”
So with this study, Dr Jha and his colleagues set out to determine if differences in practice patterns translate into differences in patient outcomes.
The researchers analyzed data on 1,583,028 hospitalizations to assess 30-day mortality rates and 1,540,797 hospitalizations to assess readmissions. The hospitalizations occurred from January 1, 2011, to December 31, 2014.
In the 30-day mortality analysis, the patients’ mean age was 80.2 years, 621,412 patients were male, and 961,616 were female.
In the hospital readmission analysis, the mean patient age was 80.1 years, 602,115 patients were male, and 938,682 were female.
Physician characteristics
During the study period, 58,344 internists treated at least 1 hospitalized Medicare beneficiary. Among those physicians, 18,751 were women (32.1%).
Female physicians tended to be younger than males, with mean ages of 42.8 and 47.8, respectively. Females were also more likely than males to have had osteopathic training—8.4% and 7.0%, respectively.
Females were more likely than males to work in large hospitals (41.9% vs 35.7%), nonprofit hospitals (78.2% vs 75.6%), major teaching hospitals (29.0% vs 21.1%), and hospitals located in the Northeast (26.8% vs 22.7%).
Female physicians tended to treat fewer patients than males—131.9 and 180.5 hospitalizations per year, respectively.
Patient characteristics were largely similar between male and female physicians. However, female physicians treated a higher proportion of female patients than male physicians did—62.1% and 60.2%, respectively.
Results
An adjusted analysis showed that patients treated by female physicians had lower 30-day mortality rates than those treated by males—11.07% and 11.49%, respectively (risk difference, –0.43%; 95% confidence interval, –0.57% to –0.28%; P<0.001; number needed to treat to prevent 1 death, 233).
An adjusted analysis for 30-day hospital readmission rates showed a lower rate for patients treated by females than those treated by males—15.02% and 15.57%, respectively (risk difference, –0.55%; 95% confidence interval, –0.71% to –0.39%; P<0.001; number needed to treat to prevent 1 readmission, 182).
These analyses were adjusted for patient characteristics, hospital-fixed effects, and physician characteristics.
The researchers noted that patients treated by female physicians had lower 30-day mortality and readmission rates regardless of their medical condition or the severity of their illness.
“Across a wide range of conditions, we see a very consistent pattern—that patients who are treated by female physicians had modest but consistently better outcomes than patients treated by male physicians,” Dr Jha said.
“That was true across conditions. It was also true across severity of illness. In fact, among the patients who were the sickest, that’s where we saw some of the largest gaps between female and male physicians.”
The researchers also adjusted their analyses for patients’ length of stay, use of care, discharge location, patient volume, and physicians’ years of practice. But this did not affect the results.
Dr Jha and his colleagues said the results of this study suggest differences in practice patterns between male and female physicians may have important clinical implications for patients. And understanding why these differences exist may provide valuable insights into improving the quality of patient care.