The Society for Vascular Surgeons and the Society for Thoracic Surgeons are seeking comments on draft Reporting Standards for Type-B Aortic Dissection. Reports focusing on type-B aortic dissection have become increasingly common in recent years, but there is currently no guidance for investigators on reporting. Submit your comments here and direct questions to Kristin Hitchcock, the SVS senior manager for guidelines & quality.

The Society for Vascular Surgeons and the Society for Thoracic Surgeons are seeking comments on draft Reporting Standards for Type-B Aortic Dissection. Reports focusing on type-B aortic dissection have become increasingly common in recent years, but there is currently no guidance for investigators on reporting. Submit your comments here and direct questions to Kristin Hitchcock, the SVS senior manager for guidelines & quality.

The Society for Vascular Surgeons and the Society for Thoracic Surgeons are seeking comments on draft Reporting Standards for Type-B Aortic Dissection. Reports focusing on type-B aortic dissection have become increasingly common in recent years, but there is currently no guidance for investigators on reporting. Submit your comments here and direct questions to Kristin Hitchcock, the SVS senior manager for guidelines & quality.

Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.

The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.

Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.

Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.

In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.

Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).

“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”

They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.

The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.

However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.

The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.

“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.

Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
 

The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.

COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.

SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
 

Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.

The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.

Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.

Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.

In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.

Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).

“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”

They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.

The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.

However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.

The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.

“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.

Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
 

The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.

COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.

SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
 

Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.

The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.

Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.

Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.

In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.

Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).

“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”

They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.

The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.

However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.

The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.

“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.

Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
 

The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.

COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.

SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
 

For medical inpatients, the advent of virtual care began decades ago with telephones and the ability of physicians to give “verbal orders” while outside the hospital. It evolved into widespread adoption of pagers and is now ubiquitous through smart phones, texting, and HIPPA-compliant applications. In the past few years, inpatient telemedicine programs have been developed and studied including tele-ICU, telestroke, and now the telehospitalist.

Telemedicine is not new and has seen rapid adoption in the outpatient setting over the past decade,¹ especially since the passing of telemedicine parity laws in 35 states to support equal reimbursement with face-to-face visits.² In addition, 24 states have joined the Interstate Medical Licensure Compact (IMLC).³ This voluntary program provides an expedited pathway to licensure for qualified physicians who practice in multiple states. The goal is to increase access to care for patients in underserved and rural areas and to allow easier consultation through telemedicine. Combined, these two federal initiatives have lowered two major barriers to entry for telemedicine: reimbursement and credentialing.

Only a handful of papers have been published on the telehospitalist model with one of the first in 2007 in The Hospitalist reporting on the intersection between tele-ICU and telehospitalist care.⁴ More recent work describes the implementation of a telehospitalist program between a large university hospitalist program and a rural, critical access hospital.⁵ A key goal of this program, developed by Dr. Ethan Kuperman and colleagues at the University of Iowa, was to keep patients at the critical access hospital that previously would have been transferred. This has obvious benefits for patients, the critical access hospital, and the local community. It also benefited the tertiary care referral center, which was dealing with high occupancy rates. Keeping lower acuity patients at the critical access hospital helps maintain access for more complex patients at the referral center. This same principle has applied to the use of the tele-ICU where lower acuity ICU patients could remain in the small, rural ICU, and only those patients who the intensivist believes would benefit from a higher level of care in a tertiary center would be transferred.

As this study and others have shown, telemedicine is ripe for adoption by hospitalists. The bigger question is how should it fit into the current model of hospital medicine? There are several different applications we are familiar with and each has unique considerations. The first model, as applied in the Kuperman paper, is for a larger hospitalist program to provide a telehospitalist service to a smaller, unaffiliated hospital (for example, critical access hospitals) that employs nurse practitioners or physician assistants on site but can’t recruit or retain full-time hospitalist coverage. In this collaborative model of care, the local provider performs the physical exam but provides care under the guidance and supervision of a hospital medicine specialist. This is expected to improve outcomes and bring the benefits of hospital medicine, including improved outcomes and decreased hospital spending, to smaller communities.⁶ In this model, the critical access hospital pays a fee for the service and retains the billing to third party payers.

A variation on that model would provide telehospitalist services to other hospitals within an existing health care network (such as Kaiser Permanente, Intermountain Healthcare, government hospitals) that have different financial models with incentives to collaborate. The Veterans Health Administration is embarking on a pilot through the VA Office of Rural Health to provide a telehospitalist service to small rural VA hospitals using the consultative model during the day with a nurse practitioner at the local site and physician backup from the emergency department. Although existing night cross-coverage will be maintained by a physician on call, this telehospitalist service may also evolve into providing cross-coverage on nights and weekends.

A third would be like a locum tenens model in which telehospitalist services are contracted for short periods of time when coverage is needed for vacations or staff shortages. A fourth model of telehospitalist care would be to international areas in need of hospitalist expertise, like a medical mission model but without the expense or time required to travel. Other models will likely evolve based on the demand for services, supply of hospitalists, changes in regulations, and reimbursement.

Another important consideration is how this will evolve for the practicing hospitalist. Will we have dedicated virtual hospitalists, akin to the “nocturnist” who covers nights and weekends? Or will working on the telehospitalist service be in the rotation of duties like many programs have with teaching and “nonteaching” services, medical consultation, and even transition clinics and emergency department triage responsibilities? It could serve as a lower-intensity service that can be staffed during office-based time that would include scholarly work, quality improvement, and administrative duties. If financially viable, it could be mutually beneficial for both the provider and recipient sides of telehospitalist care.

For any of these models to work, technical aspects must be ironed-out. It is indispensable for the provider to have remote access to the electronic health record for data review, documentation, and placing orders if needed. Adequate broadband for effective video connection, accompanied by the appropriate HIPPA-compliant software and hardware must be in place. Although highly specialized hardware has been developed, including remote stethoscopes and otoscopes, the key component is a good camera and video screen on each end of the interaction. Based upon prior experience with telemedicine programs, establishment of trusting relationships with the receiving hospital staff, physicians, and nurse practitioners is also critical. Optimally, the telehospitalist would have an opportunity to travel to the remote site to meet with the local care team and learn about the local resources and community. Many other operational and logistical issues need to be considered and will be supported by the Society of Hospital Medicine through publications, online resources, and national and regional meeting educational content on telehospitalist programs.

As hospital medicine adopts the telehospitalist model, it brings with it important considerations. First, is how we embrace the concept of the medical virtualist, a term used to describe physicians who spend the majority or all of their time caring for patients using a virtual medium.⁷ We find it difficult to imagine spending all or the majority of our time as a virtual hospitalist, but years ago many could not imagine someone being a full-time hospitalist or nocturnist. Some individuals will see this as a career opportunity that allows them to work as a hospitalist regardless of where they live or where the hospital is located. That has obvious advantages for both career choice and the provision of hospital medicine expertise to low-resourced or low-volume settings, such as rural or international locations and nights and weekends.

Second, the telehospitalist model will require professional standards, training, reimbursement and coding adjustments, hardware and software development, and managing patient expectations for care.

Lastly, hospitals, health care systems, hospitalist groups, and even individual hospitalists will have to determine how best to take advantage of this innovative model of care to provide the highest possible quality, in a cost-efficient manner, that supports professional satisfaction and development.
 

Dr. Kaboli and Dr. Gutierrez are based at the Center for Access and Delivery Research and Evaluation (CADRE) at the Iowa City VA Healthcare System, the Veterans Rural Health Resource Center-Iowa City, VA Office of Rural Health, and the department of internal medicine, University of Iowa, both in Iowa City.

References

1. Barnett ML et al. Trends in telemedicine use in a large commercially insured population, 2005-2017. JAMA. 2018;320(20):2147-9.

2. American Telemedicine Association State Policy Resource Center. 2018; http://www.americantelemed.org/main/policy-page/state-policy-resource-center. Accessed 2018 Dec 14.

3. Interstate Medical Licensure Compact 2018; https://imlcc.org/. Accessed 2018 Dec 14.

4. Hengehold D. The telehospitalist. The Hospitalist. 2007;7(July). https://www.the-hospitalist.org/hospitalist/article/123381/telehospitalist. Accessed 2018 Dec 14.

5. Kuperman EF et al. The virtual hospitalist: A single-site implementation bringing hospitalist coverage to critical access hospitals. J Hosp Med. 2018;13(11):759-63.

6. Peterson MC. A systematic review of outcomes and quality measures in adult patients cared for by hospitalists vs nonhospitalists. Mayo Clinic proceedings. 2009;84(3):248-54.

7. Nochomovitz M, Sharma R. Is it time for a new medical specialty?: The medical virtualist. JAMA. 2018;319(5):437-8.

For medical inpatients, the advent of virtual care began decades ago with telephones and the ability of physicians to give “verbal orders” while outside the hospital. It evolved into widespread adoption of pagers and is now ubiquitous through smart phones, texting, and HIPPA-compliant applications. In the past few years, inpatient telemedicine programs have been developed and studied including tele-ICU, telestroke, and now the telehospitalist.

Telemedicine is not new and has seen rapid adoption in the outpatient setting over the past decade,¹ especially since the passing of telemedicine parity laws in 35 states to support equal reimbursement with face-to-face visits.² In addition, 24 states have joined the Interstate Medical Licensure Compact (IMLC).³ This voluntary program provides an expedited pathway to licensure for qualified physicians who practice in multiple states. The goal is to increase access to care for patients in underserved and rural areas and to allow easier consultation through telemedicine. Combined, these two federal initiatives have lowered two major barriers to entry for telemedicine: reimbursement and credentialing.

Only a handful of papers have been published on the telehospitalist model with one of the first in 2007 in The Hospitalist reporting on the intersection between tele-ICU and telehospitalist care.⁴ More recent work describes the implementation of a telehospitalist program between a large university hospitalist program and a rural, critical access hospital.⁵ A key goal of this program, developed by Dr. Ethan Kuperman and colleagues at the University of Iowa, was to keep patients at the critical access hospital that previously would have been transferred. This has obvious benefits for patients, the critical access hospital, and the local community. It also benefited the tertiary care referral center, which was dealing with high occupancy rates. Keeping lower acuity patients at the critical access hospital helps maintain access for more complex patients at the referral center. This same principle has applied to the use of the tele-ICU where lower acuity ICU patients could remain in the small, rural ICU, and only those patients who the intensivist believes would benefit from a higher level of care in a tertiary center would be transferred.

As this study and others have shown, telemedicine is ripe for adoption by hospitalists. The bigger question is how should it fit into the current model of hospital medicine? There are several different applications we are familiar with and each has unique considerations. The first model, as applied in the Kuperman paper, is for a larger hospitalist program to provide a telehospitalist service to a smaller, unaffiliated hospital (for example, critical access hospitals) that employs nurse practitioners or physician assistants on site but can’t recruit or retain full-time hospitalist coverage. In this collaborative model of care, the local provider performs the physical exam but provides care under the guidance and supervision of a hospital medicine specialist. This is expected to improve outcomes and bring the benefits of hospital medicine, including improved outcomes and decreased hospital spending, to smaller communities.⁶ In this model, the critical access hospital pays a fee for the service and retains the billing to third party payers.

A variation on that model would provide telehospitalist services to other hospitals within an existing health care network (such as Kaiser Permanente, Intermountain Healthcare, government hospitals) that have different financial models with incentives to collaborate. The Veterans Health Administration is embarking on a pilot through the VA Office of Rural Health to provide a telehospitalist service to small rural VA hospitals using the consultative model during the day with a nurse practitioner at the local site and physician backup from the emergency department. Although existing night cross-coverage will be maintained by a physician on call, this telehospitalist service may also evolve into providing cross-coverage on nights and weekends.

A third would be like a locum tenens model in which telehospitalist services are contracted for short periods of time when coverage is needed for vacations or staff shortages. A fourth model of telehospitalist care would be to international areas in need of hospitalist expertise, like a medical mission model but without the expense or time required to travel. Other models will likely evolve based on the demand for services, supply of hospitalists, changes in regulations, and reimbursement.

Another important consideration is how this will evolve for the practicing hospitalist. Will we have dedicated virtual hospitalists, akin to the “nocturnist” who covers nights and weekends? Or will working on the telehospitalist service be in the rotation of duties like many programs have with teaching and “nonteaching” services, medical consultation, and even transition clinics and emergency department triage responsibilities? It could serve as a lower-intensity service that can be staffed during office-based time that would include scholarly work, quality improvement, and administrative duties. If financially viable, it could be mutually beneficial for both the provider and recipient sides of telehospitalist care.

For any of these models to work, technical aspects must be ironed-out. It is indispensable for the provider to have remote access to the electronic health record for data review, documentation, and placing orders if needed. Adequate broadband for effective video connection, accompanied by the appropriate HIPPA-compliant software and hardware must be in place. Although highly specialized hardware has been developed, including remote stethoscopes and otoscopes, the key component is a good camera and video screen on each end of the interaction. Based upon prior experience with telemedicine programs, establishment of trusting relationships with the receiving hospital staff, physicians, and nurse practitioners is also critical. Optimally, the telehospitalist would have an opportunity to travel to the remote site to meet with the local care team and learn about the local resources and community. Many other operational and logistical issues need to be considered and will be supported by the Society of Hospital Medicine through publications, online resources, and national and regional meeting educational content on telehospitalist programs.

As hospital medicine adopts the telehospitalist model, it brings with it important considerations. First, is how we embrace the concept of the medical virtualist, a term used to describe physicians who spend the majority or all of their time caring for patients using a virtual medium.⁷ We find it difficult to imagine spending all or the majority of our time as a virtual hospitalist, but years ago many could not imagine someone being a full-time hospitalist or nocturnist. Some individuals will see this as a career opportunity that allows them to work as a hospitalist regardless of where they live or where the hospital is located. That has obvious advantages for both career choice and the provision of hospital medicine expertise to low-resourced or low-volume settings, such as rural or international locations and nights and weekends.

Second, the telehospitalist model will require professional standards, training, reimbursement and coding adjustments, hardware and software development, and managing patient expectations for care.

Lastly, hospitals, health care systems, hospitalist groups, and even individual hospitalists will have to determine how best to take advantage of this innovative model of care to provide the highest possible quality, in a cost-efficient manner, that supports professional satisfaction and development.
 

Dr. Kaboli and Dr. Gutierrez are based at the Center for Access and Delivery Research and Evaluation (CADRE) at the Iowa City VA Healthcare System, the Veterans Rural Health Resource Center-Iowa City, VA Office of Rural Health, and the department of internal medicine, University of Iowa, both in Iowa City.

References

1. Barnett ML et al. Trends in telemedicine use in a large commercially insured population, 2005-2017. JAMA. 2018;320(20):2147-9.

2. American Telemedicine Association State Policy Resource Center. 2018; http://www.americantelemed.org/main/policy-page/state-policy-resource-center. Accessed 2018 Dec 14.

3. Interstate Medical Licensure Compact 2018; https://imlcc.org/. Accessed 2018 Dec 14.

4. Hengehold D. The telehospitalist. The Hospitalist. 2007;7(July). https://www.the-hospitalist.org/hospitalist/article/123381/telehospitalist. Accessed 2018 Dec 14.

5. Kuperman EF et al. The virtual hospitalist: A single-site implementation bringing hospitalist coverage to critical access hospitals. J Hosp Med. 2018;13(11):759-63.

6. Peterson MC. A systematic review of outcomes and quality measures in adult patients cared for by hospitalists vs nonhospitalists. Mayo Clinic proceedings. 2009;84(3):248-54.

7. Nochomovitz M, Sharma R. Is it time for a new medical specialty?: The medical virtualist. JAMA. 2018;319(5):437-8.

For medical inpatients, the advent of virtual care began decades ago with telephones and the ability of physicians to give “verbal orders” while outside the hospital. It evolved into widespread adoption of pagers and is now ubiquitous through smart phones, texting, and HIPPA-compliant applications. In the past few years, inpatient telemedicine programs have been developed and studied including tele-ICU, telestroke, and now the telehospitalist.

Telemedicine is not new and has seen rapid adoption in the outpatient setting over the past decade,¹ especially since the passing of telemedicine parity laws in 35 states to support equal reimbursement with face-to-face visits.² In addition, 24 states have joined the Interstate Medical Licensure Compact (IMLC).³ This voluntary program provides an expedited pathway to licensure for qualified physicians who practice in multiple states. The goal is to increase access to care for patients in underserved and rural areas and to allow easier consultation through telemedicine. Combined, these two federal initiatives have lowered two major barriers to entry for telemedicine: reimbursement and credentialing.

Only a handful of papers have been published on the telehospitalist model with one of the first in 2007 in The Hospitalist reporting on the intersection between tele-ICU and telehospitalist care.⁴ More recent work describes the implementation of a telehospitalist program between a large university hospitalist program and a rural, critical access hospital.⁵ A key goal of this program, developed by Dr. Ethan Kuperman and colleagues at the University of Iowa, was to keep patients at the critical access hospital that previously would have been transferred. This has obvious benefits for patients, the critical access hospital, and the local community. It also benefited the tertiary care referral center, which was dealing with high occupancy rates. Keeping lower acuity patients at the critical access hospital helps maintain access for more complex patients at the referral center. This same principle has applied to the use of the tele-ICU where lower acuity ICU patients could remain in the small, rural ICU, and only those patients who the intensivist believes would benefit from a higher level of care in a tertiary center would be transferred.

As this study and others have shown, telemedicine is ripe for adoption by hospitalists. The bigger question is how should it fit into the current model of hospital medicine? There are several different applications we are familiar with and each has unique considerations. The first model, as applied in the Kuperman paper, is for a larger hospitalist program to provide a telehospitalist service to a smaller, unaffiliated hospital (for example, critical access hospitals) that employs nurse practitioners or physician assistants on site but can’t recruit or retain full-time hospitalist coverage. In this collaborative model of care, the local provider performs the physical exam but provides care under the guidance and supervision of a hospital medicine specialist. This is expected to improve outcomes and bring the benefits of hospital medicine, including improved outcomes and decreased hospital spending, to smaller communities.⁶ In this model, the critical access hospital pays a fee for the service and retains the billing to third party payers.

A variation on that model would provide telehospitalist services to other hospitals within an existing health care network (such as Kaiser Permanente, Intermountain Healthcare, government hospitals) that have different financial models with incentives to collaborate. The Veterans Health Administration is embarking on a pilot through the VA Office of Rural Health to provide a telehospitalist service to small rural VA hospitals using the consultative model during the day with a nurse practitioner at the local site and physician backup from the emergency department. Although existing night cross-coverage will be maintained by a physician on call, this telehospitalist service may also evolve into providing cross-coverage on nights and weekends.

A third would be like a locum tenens model in which telehospitalist services are contracted for short periods of time when coverage is needed for vacations or staff shortages. A fourth model of telehospitalist care would be to international areas in need of hospitalist expertise, like a medical mission model but without the expense or time required to travel. Other models will likely evolve based on the demand for services, supply of hospitalists, changes in regulations, and reimbursement.

Another important consideration is how this will evolve for the practicing hospitalist. Will we have dedicated virtual hospitalists, akin to the “nocturnist” who covers nights and weekends? Or will working on the telehospitalist service be in the rotation of duties like many programs have with teaching and “nonteaching” services, medical consultation, and even transition clinics and emergency department triage responsibilities? It could serve as a lower-intensity service that can be staffed during office-based time that would include scholarly work, quality improvement, and administrative duties. If financially viable, it could be mutually beneficial for both the provider and recipient sides of telehospitalist care.

For any of these models to work, technical aspects must be ironed-out. It is indispensable for the provider to have remote access to the electronic health record for data review, documentation, and placing orders if needed. Adequate broadband for effective video connection, accompanied by the appropriate HIPPA-compliant software and hardware must be in place. Although highly specialized hardware has been developed, including remote stethoscopes and otoscopes, the key component is a good camera and video screen on each end of the interaction. Based upon prior experience with telemedicine programs, establishment of trusting relationships with the receiving hospital staff, physicians, and nurse practitioners is also critical. Optimally, the telehospitalist would have an opportunity to travel to the remote site to meet with the local care team and learn about the local resources and community. Many other operational and logistical issues need to be considered and will be supported by the Society of Hospital Medicine through publications, online resources, and national and regional meeting educational content on telehospitalist programs.

As hospital medicine adopts the telehospitalist model, it brings with it important considerations. First, is how we embrace the concept of the medical virtualist, a term used to describe physicians who spend the majority or all of their time caring for patients using a virtual medium.⁷ We find it difficult to imagine spending all or the majority of our time as a virtual hospitalist, but years ago many could not imagine someone being a full-time hospitalist or nocturnist. Some individuals will see this as a career opportunity that allows them to work as a hospitalist regardless of where they live or where the hospital is located. That has obvious advantages for both career choice and the provision of hospital medicine expertise to low-resourced or low-volume settings, such as rural or international locations and nights and weekends.

Second, the telehospitalist model will require professional standards, training, reimbursement and coding adjustments, hardware and software development, and managing patient expectations for care.

Lastly, hospitals, health care systems, hospitalist groups, and even individual hospitalists will have to determine how best to take advantage of this innovative model of care to provide the highest possible quality, in a cost-efficient manner, that supports professional satisfaction and development.
 

Dr. Kaboli and Dr. Gutierrez are based at the Center for Access and Delivery Research and Evaluation (CADRE) at the Iowa City VA Healthcare System, the Veterans Rural Health Resource Center-Iowa City, VA Office of Rural Health, and the department of internal medicine, University of Iowa, both in Iowa City.

References

1. Barnett ML et al. Trends in telemedicine use in a large commercially insured population, 2005-2017. JAMA. 2018;320(20):2147-9.

2. American Telemedicine Association State Policy Resource Center. 2018; http://www.americantelemed.org/main/policy-page/state-policy-resource-center. Accessed 2018 Dec 14.

3. Interstate Medical Licensure Compact 2018; https://imlcc.org/. Accessed 2018 Dec 14.

4. Hengehold D. The telehospitalist. The Hospitalist. 2007;7(July). https://www.the-hospitalist.org/hospitalist/article/123381/telehospitalist. Accessed 2018 Dec 14.

5. Kuperman EF et al. The virtual hospitalist: A single-site implementation bringing hospitalist coverage to critical access hospitals. J Hosp Med. 2018;13(11):759-63.

6. Peterson MC. A systematic review of outcomes and quality measures in adult patients cared for by hospitalists vs nonhospitalists. Mayo Clinic proceedings. 2009;84(3):248-54.

7. Nochomovitz M, Sharma R. Is it time for a new medical specialty?: The medical virtualist. JAMA. 2018;319(5):437-8.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

HONOLULU – Women with BRCA1/2 mutations who undergo risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing salpingectomy followed by delayed risk-reducing oophorectomy (RRS/RRO) experience reduced cancer-related worry after surgery and low levels of decision regret, according to preliminary findings from the Dutch multicenter TUBA trial.

Bruce Jancin/MDedge News

Of 384 women included to date in the ongoing trial, 51% carried a BRCA1 mutation and 49% carried a BRCA2 mutation; 72% chose RRS/RRO. A total of 289 completed the 3-month follow-up and 197 completed 1-year follow-up. At 3 and 12 months the decline on the Cancer Worry Scale was similar in the groups after adjusting for age and other baseline characteristics, with 1.9- and 1.4-point declines from baseline scores of 14.4 and 14.0 at 3 months, and 2.2- and 1.0-point declines at 12 months in the RRSO and RRS/RRO groups, respectively, Miranda P. Steenbeek, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The mean scores on the 100-point Decision Regret Scale at 1-year follow-up were low at 13.4 and 13.0 after RRSO and RRS, respectively.

“But it is interesting that there is one group of women who underwent standard salpingo-oophorectomy, but weren’t using hormone replacement therapy [HRT], as these women had a higher level of decision regret [mean score, 18.8],” said Dr. Steenbeek of Radboud University Nijmegen, the Netherlands. “It is interesting to see how these results will develop over time.”

Current recommendations for preventive surgery in woman at increased risk because of BRCA1/2 mutations call for RRSO around age 40 years. However, an innovative approach using RRS followed by RRO has emerged as recent data indicate the fallopian tube, rather than the ovary, as the origin of high-grade serous ovarian cancer, she explained.


The TUBA trial was launched at 13 Dutch oncology centers in 2015, and plans to enroll 510 BRCA1/2 mutation carriers. Participants choose either standard RRSO within current guidelines (at age 35-40 years for BRCA1 carriers, age 40-45 years for BRCA2 carriers) or the innovative RRS approach followed by RRO at up to 5 years after the current guideline age (at age 40-45 years for BRCA1 carriers, age 45-50 years for BRCA2 carriers), she said.

These early findings show that baseline levels of cancer worry are higher among women choosing RRSO, which might explain the slightly larger postsurgery decline in worry in the RRSO group, Dr. Steenbeek said, noting that the higher level of regret with RRSO without HRT might be related to more severe menopausal complaints in that subset of patients.

“Based on these results we cannot conclude whether or not salpingectomy is a safe alternative to for salpingo-oophorectomy, and therefore it is very important to not perform salpingectomy with delayed oophorectomy outside the safety of a clinical and control of a clinical trial,” she said, adding that a report on the quality of life data from the study is expected in 2020.

Dr. Steenbeek reported having no disclosures.

[email protected]

SOURCE: Steenbeek MP et al. SGO 2019, Abstract LB2.

HONOLULU – Women with BRCA1/2 mutations who undergo risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing salpingectomy followed by delayed risk-reducing oophorectomy (RRS/RRO) experience reduced cancer-related worry after surgery and low levels of decision regret, according to preliminary findings from the Dutch multicenter TUBA trial.

Bruce Jancin/MDedge News

Of 384 women included to date in the ongoing trial, 51% carried a BRCA1 mutation and 49% carried a BRCA2 mutation; 72% chose RRS/RRO. A total of 289 completed the 3-month follow-up and 197 completed 1-year follow-up. At 3 and 12 months the decline on the Cancer Worry Scale was similar in the groups after adjusting for age and other baseline characteristics, with 1.9- and 1.4-point declines from baseline scores of 14.4 and 14.0 at 3 months, and 2.2- and 1.0-point declines at 12 months in the RRSO and RRS/RRO groups, respectively, Miranda P. Steenbeek, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The mean scores on the 100-point Decision Regret Scale at 1-year follow-up were low at 13.4 and 13.0 after RRSO and RRS, respectively.

“But it is interesting that there is one group of women who underwent standard salpingo-oophorectomy, but weren’t using hormone replacement therapy [HRT], as these women had a higher level of decision regret [mean score, 18.8],” said Dr. Steenbeek of Radboud University Nijmegen, the Netherlands. “It is interesting to see how these results will develop over time.”

Current recommendations for preventive surgery in woman at increased risk because of BRCA1/2 mutations call for RRSO around age 40 years. However, an innovative approach using RRS followed by RRO has emerged as recent data indicate the fallopian tube, rather than the ovary, as the origin of high-grade serous ovarian cancer, she explained.


The TUBA trial was launched at 13 Dutch oncology centers in 2015, and plans to enroll 510 BRCA1/2 mutation carriers. Participants choose either standard RRSO within current guidelines (at age 35-40 years for BRCA1 carriers, age 40-45 years for BRCA2 carriers) or the innovative RRS approach followed by RRO at up to 5 years after the current guideline age (at age 40-45 years for BRCA1 carriers, age 45-50 years for BRCA2 carriers), she said.

These early findings show that baseline levels of cancer worry are higher among women choosing RRSO, which might explain the slightly larger postsurgery decline in worry in the RRSO group, Dr. Steenbeek said, noting that the higher level of regret with RRSO without HRT might be related to more severe menopausal complaints in that subset of patients.

“Based on these results we cannot conclude whether or not salpingectomy is a safe alternative to for salpingo-oophorectomy, and therefore it is very important to not perform salpingectomy with delayed oophorectomy outside the safety of a clinical and control of a clinical trial,” she said, adding that a report on the quality of life data from the study is expected in 2020.

Dr. Steenbeek reported having no disclosures.

[email protected]

SOURCE: Steenbeek MP et al. SGO 2019, Abstract LB2.

HONOLULU – Women with BRCA1/2 mutations who undergo risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing salpingectomy followed by delayed risk-reducing oophorectomy (RRS/RRO) experience reduced cancer-related worry after surgery and low levels of decision regret, according to preliminary findings from the Dutch multicenter TUBA trial.

Bruce Jancin/MDedge News

Of 384 women included to date in the ongoing trial, 51% carried a BRCA1 mutation and 49% carried a BRCA2 mutation; 72% chose RRS/RRO. A total of 289 completed the 3-month follow-up and 197 completed 1-year follow-up. At 3 and 12 months the decline on the Cancer Worry Scale was similar in the groups after adjusting for age and other baseline characteristics, with 1.9- and 1.4-point declines from baseline scores of 14.4 and 14.0 at 3 months, and 2.2- and 1.0-point declines at 12 months in the RRSO and RRS/RRO groups, respectively, Miranda P. Steenbeek, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The mean scores on the 100-point Decision Regret Scale at 1-year follow-up were low at 13.4 and 13.0 after RRSO and RRS, respectively.

“But it is interesting that there is one group of women who underwent standard salpingo-oophorectomy, but weren’t using hormone replacement therapy [HRT], as these women had a higher level of decision regret [mean score, 18.8],” said Dr. Steenbeek of Radboud University Nijmegen, the Netherlands. “It is interesting to see how these results will develop over time.”

Current recommendations for preventive surgery in woman at increased risk because of BRCA1/2 mutations call for RRSO around age 40 years. However, an innovative approach using RRS followed by RRO has emerged as recent data indicate the fallopian tube, rather than the ovary, as the origin of high-grade serous ovarian cancer, she explained.


The TUBA trial was launched at 13 Dutch oncology centers in 2015, and plans to enroll 510 BRCA1/2 mutation carriers. Participants choose either standard RRSO within current guidelines (at age 35-40 years for BRCA1 carriers, age 40-45 years for BRCA2 carriers) or the innovative RRS approach followed by RRO at up to 5 years after the current guideline age (at age 40-45 years for BRCA1 carriers, age 45-50 years for BRCA2 carriers), she said.

These early findings show that baseline levels of cancer worry are higher among women choosing RRSO, which might explain the slightly larger postsurgery decline in worry in the RRSO group, Dr. Steenbeek said, noting that the higher level of regret with RRSO without HRT might be related to more severe menopausal complaints in that subset of patients.

“Based on these results we cannot conclude whether or not salpingectomy is a safe alternative to for salpingo-oophorectomy, and therefore it is very important to not perform salpingectomy with delayed oophorectomy outside the safety of a clinical and control of a clinical trial,” she said, adding that a report on the quality of life data from the study is expected in 2020.

Dr. Steenbeek reported having no disclosures.

[email protected]

SOURCE: Steenbeek MP et al. SGO 2019, Abstract LB2.

For neurology, the 2019 Match marked the fourth consecutive year of double-digit increases in the number of first-year residency positions, according to the National Resident Matching Program (NRMP).

This year, 617 first-year (PGY-1) neurology slots were offered, an increase of 11.8% over the 552 offered in 2018 and well above the 6.5% gain recorded for the Match as whole. The 114 neurology programs participating this year filled 96.3% of those PGY-1 positions, compared with 94.7% for the 52 programs that offered PGY-2 positions, the NRMP reported.

“The results of the Match are closely watched because they can be predictors of future physician workforce supply. There also is significant interest in the competitiveness of specialties, as measured by the percentage of positions filled overall and the percentage filled by senior students in U.S. allopathic medical schools,” the NRMP said.


The proportion of PGY-1 neurology positions filled by U.S. seniors dropped to 46.0% from 50.7% last year, although the number of U.S. seniors filling spots actually went up from 280 in 2018 to 284. The PGY-2 positions saw declines in both cases: The 175 U.S. seniors represented 62.3% of the 2019 spots, compared with the 190 U.S. seniors who filled 66.2% of slots in 2018, the NRMP data show.

The total numbers of applicants (38,376) and positions offered (35,185) were both record highs for the Match, although they were affected, in part, by “increased numbers of osteopathic programs that joined the Main Residency Match as a result of the ongoing transition to a single accreditation system for graduate medical education programs,” the NRMP noted.

[email protected]

For neurology, the 2019 Match marked the fourth consecutive year of double-digit increases in the number of first-year residency positions, according to the National Resident Matching Program (NRMP).

This year, 617 first-year (PGY-1) neurology slots were offered, an increase of 11.8% over the 552 offered in 2018 and well above the 6.5% gain recorded for the Match as whole. The 114 neurology programs participating this year filled 96.3% of those PGY-1 positions, compared with 94.7% for the 52 programs that offered PGY-2 positions, the NRMP reported.

“The results of the Match are closely watched because they can be predictors of future physician workforce supply. There also is significant interest in the competitiveness of specialties, as measured by the percentage of positions filled overall and the percentage filled by senior students in U.S. allopathic medical schools,” the NRMP said.


The proportion of PGY-1 neurology positions filled by U.S. seniors dropped to 46.0% from 50.7% last year, although the number of U.S. seniors filling spots actually went up from 280 in 2018 to 284. The PGY-2 positions saw declines in both cases: The 175 U.S. seniors represented 62.3% of the 2019 spots, compared with the 190 U.S. seniors who filled 66.2% of slots in 2018, the NRMP data show.

The total numbers of applicants (38,376) and positions offered (35,185) were both record highs for the Match, although they were affected, in part, by “increased numbers of osteopathic programs that joined the Main Residency Match as a result of the ongoing transition to a single accreditation system for graduate medical education programs,” the NRMP noted.

[email protected]

For neurology, the 2019 Match marked the fourth consecutive year of double-digit increases in the number of first-year residency positions, according to the National Resident Matching Program (NRMP).

This year, 617 first-year (PGY-1) neurology slots were offered, an increase of 11.8% over the 552 offered in 2018 and well above the 6.5% gain recorded for the Match as whole. The 114 neurology programs participating this year filled 96.3% of those PGY-1 positions, compared with 94.7% for the 52 programs that offered PGY-2 positions, the NRMP reported.

“The results of the Match are closely watched because they can be predictors of future physician workforce supply. There also is significant interest in the competitiveness of specialties, as measured by the percentage of positions filled overall and the percentage filled by senior students in U.S. allopathic medical schools,” the NRMP said.


The proportion of PGY-1 neurology positions filled by U.S. seniors dropped to 46.0% from 50.7% last year, although the number of U.S. seniors filling spots actually went up from 280 in 2018 to 284. The PGY-2 positions saw declines in both cases: The 175 U.S. seniors represented 62.3% of the 2019 spots, compared with the 190 U.S. seniors who filled 66.2% of slots in 2018, the NRMP data show.

The total numbers of applicants (38,376) and positions offered (35,185) were both record highs for the Match, although they were affected, in part, by “increased numbers of osteopathic programs that joined the Main Residency Match as a result of the ongoing transition to a single accreditation system for graduate medical education programs,” the NRMP noted.

[email protected]

WASHINGTON – Many patients with vitiligo are interested in treating their condition with vitamins, supplements, or a modified diet, but research on whether these measures have an impact remains limited, Nada Elbuluk, MD, said at the annual meeting of the American Academy of Dermatology.

While the literature suggests that supplements with antioxidant properties benefit patients who are receiving phototherapy for vitiligo, “we need more well designed, controlled studies in the future to know where this belongs in our treatment armamentarium,” said Dr. Elbuluk of the department of dermatology at the University of Southern California, Los Angeles.

During a session at the AAD meeting, Dr. Elbuluk, who is also director of the pigmentary disorders clinic at USC, reviewed the evidence for the use of these adjunctive therapies in patients with vitiligo.
 

Vitamins

The pathogenesis of vitiligo includes the overproduction of reactive oxygen species and oxidative stress, factors that contribute to melanocyte damage and death. In addition, many patients with vitiligo are deficient in certain vitamins and minerals, the basis of the hypothesis that supplementation could be beneficial, according to Dr. Elbuluk.

Vitamin B₁₂ and folic acid contribute to DNA repair, synthesis, and methylation, and researchers have hypothesized that these vitamins also play a role in melanin synthesis. In a review of the literature, Dr. Elbuluk and her colleagues found four studies that evaluated vitamin B₁₂ and folic acid in vitiligo. In one study, a controlled trial in which patients took B₁₂ and folic acid with and without phototherapy, the investigators observed no significant difference in repigmentation between groups. The other three studies were uncontrolled and thus provide an insufficient understanding of the effect of B₁₂ and folic acid, said Dr. Elbuluk.

Vitamin D is involved in melanocyte and keratinocyte growth and differentiation, and inhibits T cell activation. Data indicate that low vitamin D levels are common in patients with vitiligo and comorbid autoimmune diseases. In one study, patients who received narrow-band UVB had an increase in vitamin D levels that could contribute to photo-induced melanogenesis, and an open-label study indicated that patients who took vitamin D daily (without phototherapy) for 6 months had an increase of repigmentation over time. “Topical vitamin D analogs have also been used in vitiligo treatment with varying success,” Dr. Elbuluk noted.

“I check vitamin D levels on my patients and make sure that they are within normal range. But I think the degree of supplementation and its role in vitiligo needs to be further elucidated,” she said. And because vitamin D is fat soluble, there is a risk of toxicity if a patient takes too much.

Vitamin C, vitamin E, and alpha-lipoic acid have antioxidant properties. In a double-blind, randomized, controlled trial, one group of patients took vitamins C and E and alpha-lipoic acid for 2 months before and during treatment with narrow-band UVB twice per week (Clin Exp Dermatol. 2007 Nov;32[6]:631-6). Another group underwent phototherapy without supplementation. A significantly greater proportion of patients who received the antioxidants obtained more than 75% repigmentation compared with those who did not. In another study, 73% of patients who received oral vitamin E and narrow band UVB phototherapy had marked to excellent repigmentation, compared with 55.6% of those who had phototherapy only (J Clin Pharmacol. 2009 Jul;49[7]:852-5).

The results of these studies support the idea that antioxidants can stabilize disease, reduce oxidative stress, and improve the effect of phototherapy, Dr. Elbuluk said.
 

Herbal supplements

Several research teams have examined Ginkgo biloba as a possible treatment for vitiligo. This plant is native to China and has antioxidant and anti-inflammatory properties; its most common side effect is gastrointestinal distress. Because it entails a risk of coagulopathy, it may not be appropriate for patients receiving anticoagulant treatment, Dr. Elbuluk pointed out. In a double-blinded, randomized, controlled trial comparing ginkgo biloba alone with placebo in patients with vitiligo, treatment was associated with cessation of active disease in most patients, and more than 40% of patients receiving ginkgo biloba had 75% repigmentation or more.

Polypodium leucotomos, a fern native to Central and South America, protects against UV radiation damage, modulates the immune system, and has anti-inflammatory and antioxidant effects. It has a good safety profile and is well tolerated at a dose of 240 mg/day, she said. It sometimes causes gastrointestinal discomfort or pruritus. Several randomized, controlled trials in patients with vitiligo showed that supplementation with polypodium leucotomos improves repigmentation, particularly in photo-exposed areas, she noted.

Khellin is an extract from the Mediterranean khella plant that is thought to stimulate melanocyte proliferation and melanogenesis. Several studies have examined khellin supplementation in combination with phototherapy. Khellin can be administered orally or topically and appears to be more beneficial than sunlight or phototherapy alone in stabilizing disease or inducing repigmentation. Oral khellin can cause many side effects, including nausea, transaminitis, and hypotension, so researchers have been more interested in using topical khellin as a liposomal vehicle to improve drug delivery, Dr. Elbuluk said.
 

Minerals

Some patients with vitiligo have deficiencies in zinc and copper. Zinc is an antioxidant that aids wound healing, protects against free radicals, supports melanogenesis, and possibly prevents melanocyte death, but can cause gastrointestinal irritation. Copper, too, is an antioxidant and coenzyme involved in melanogenesis. One study compared topical steroid treatment with and without oral zinc supplementation. Dual treatment was associated with greater repigmentation, but the difference was not statistically significant. No studies have examined copper supplementation, she said.

L-phenylalanine, diet, and green tea

Investigators have proposed that the amino acid L-phenylalanine, a precursor to tyrosine in the pathway of melanin synthesis, might interfere with antibody production against melanocytes. This supplement is administered orally by weight, typically in conjunction with phototherapy or sunlight. Various studies have observed positive outcomes of L-phenylalanine combined with phototherapy or sunlight. L-phenylalanine tends to be safe and has been administered to children with vitiligo.

Many patients with vitiligo “have already tried diets by the time they come to me,” said Dr. Elbuluk. No controlled studies have analyzed the role of diet in the prevention or treatment of vitiligo, but case reports describe gluten-free diets in this population, including one report of a patient with celiac disease whose vitiligo improved after adoption of such a diet. Another case report described a patient without celiac disease who had refractory acrofacial vitiligo, which improved after the adoption of a gluten-free diet. Evidence supports a gluten-free diet for patients with celiac disease, but does not support this challenging diet for people without celiac disease, she pointed out.

Green tea includes catechins, which have antioxidant and anti-inflammatory properties. Its main component is epigallocatechin gallate (EGCG), which is thought to modulate T cell mediated responses. In one animal study, administration of EGCG delayed the onset of vitiligo and decreased the area of depigmentation in a mouse model. Although these findings are promising, clinical trials are needed to determine whether EGCG is beneficial in humans with vitiligo, said Dr. Elbuluk.

The literature on diets and supplementation as treatments for vitiligo has several shortcomings, with studies that used heterogeneous methodologies, and many that used nonstandard outcome measures that have not been validated. Sample sizes often are small, and many trials are uncontrolled. “These limitations make it harder to make sense of the data and have take-home conclusions,” Dr. Elbuluk said.

She had no disclosures.

[email protected]

SOURCE: Elbuluk N. AAD 19, Session S002.

WASHINGTON – Many patients with vitiligo are interested in treating their condition with vitamins, supplements, or a modified diet, but research on whether these measures have an impact remains limited, Nada Elbuluk, MD, said at the annual meeting of the American Academy of Dermatology.

While the literature suggests that supplements with antioxidant properties benefit patients who are receiving phototherapy for vitiligo, “we need more well designed, controlled studies in the future to know where this belongs in our treatment armamentarium,” said Dr. Elbuluk of the department of dermatology at the University of Southern California, Los Angeles.

During a session at the AAD meeting, Dr. Elbuluk, who is also director of the pigmentary disorders clinic at USC, reviewed the evidence for the use of these adjunctive therapies in patients with vitiligo.
 

Vitamins

The pathogenesis of vitiligo includes the overproduction of reactive oxygen species and oxidative stress, factors that contribute to melanocyte damage and death. In addition, many patients with vitiligo are deficient in certain vitamins and minerals, the basis of the hypothesis that supplementation could be beneficial, according to Dr. Elbuluk.

Vitamin B₁₂ and folic acid contribute to DNA repair, synthesis, and methylation, and researchers have hypothesized that these vitamins also play a role in melanin synthesis. In a review of the literature, Dr. Elbuluk and her colleagues found four studies that evaluated vitamin B₁₂ and folic acid in vitiligo. In one study, a controlled trial in which patients took B₁₂ and folic acid with and without phototherapy, the investigators observed no significant difference in repigmentation between groups. The other three studies were uncontrolled and thus provide an insufficient understanding of the effect of B₁₂ and folic acid, said Dr. Elbuluk.

Vitamin D is involved in melanocyte and keratinocyte growth and differentiation, and inhibits T cell activation. Data indicate that low vitamin D levels are common in patients with vitiligo and comorbid autoimmune diseases. In one study, patients who received narrow-band UVB had an increase in vitamin D levels that could contribute to photo-induced melanogenesis, and an open-label study indicated that patients who took vitamin D daily (without phototherapy) for 6 months had an increase of repigmentation over time. “Topical vitamin D analogs have also been used in vitiligo treatment with varying success,” Dr. Elbuluk noted.

“I check vitamin D levels on my patients and make sure that they are within normal range. But I think the degree of supplementation and its role in vitiligo needs to be further elucidated,” she said. And because vitamin D is fat soluble, there is a risk of toxicity if a patient takes too much.

Vitamin C, vitamin E, and alpha-lipoic acid have antioxidant properties. In a double-blind, randomized, controlled trial, one group of patients took vitamins C and E and alpha-lipoic acid for 2 months before and during treatment with narrow-band UVB twice per week (Clin Exp Dermatol. 2007 Nov;32[6]:631-6). Another group underwent phototherapy without supplementation. A significantly greater proportion of patients who received the antioxidants obtained more than 75% repigmentation compared with those who did not. In another study, 73% of patients who received oral vitamin E and narrow band UVB phototherapy had marked to excellent repigmentation, compared with 55.6% of those who had phototherapy only (J Clin Pharmacol. 2009 Jul;49[7]:852-5).

The results of these studies support the idea that antioxidants can stabilize disease, reduce oxidative stress, and improve the effect of phototherapy, Dr. Elbuluk said.
 

Herbal supplements

Several research teams have examined Ginkgo biloba as a possible treatment for vitiligo. This plant is native to China and has antioxidant and anti-inflammatory properties; its most common side effect is gastrointestinal distress. Because it entails a risk of coagulopathy, it may not be appropriate for patients receiving anticoagulant treatment, Dr. Elbuluk pointed out. In a double-blinded, randomized, controlled trial comparing ginkgo biloba alone with placebo in patients with vitiligo, treatment was associated with cessation of active disease in most patients, and more than 40% of patients receiving ginkgo biloba had 75% repigmentation or more.

Polypodium leucotomos, a fern native to Central and South America, protects against UV radiation damage, modulates the immune system, and has anti-inflammatory and antioxidant effects. It has a good safety profile and is well tolerated at a dose of 240 mg/day, she said. It sometimes causes gastrointestinal discomfort or pruritus. Several randomized, controlled trials in patients with vitiligo showed that supplementation with polypodium leucotomos improves repigmentation, particularly in photo-exposed areas, she noted.

Khellin is an extract from the Mediterranean khella plant that is thought to stimulate melanocyte proliferation and melanogenesis. Several studies have examined khellin supplementation in combination with phototherapy. Khellin can be administered orally or topically and appears to be more beneficial than sunlight or phototherapy alone in stabilizing disease or inducing repigmentation. Oral khellin can cause many side effects, including nausea, transaminitis, and hypotension, so researchers have been more interested in using topical khellin as a liposomal vehicle to improve drug delivery, Dr. Elbuluk said.
 

Minerals

Some patients with vitiligo have deficiencies in zinc and copper. Zinc is an antioxidant that aids wound healing, protects against free radicals, supports melanogenesis, and possibly prevents melanocyte death, but can cause gastrointestinal irritation. Copper, too, is an antioxidant and coenzyme involved in melanogenesis. One study compared topical steroid treatment with and without oral zinc supplementation. Dual treatment was associated with greater repigmentation, but the difference was not statistically significant. No studies have examined copper supplementation, she said.

L-phenylalanine, diet, and green tea

Investigators have proposed that the amino acid L-phenylalanine, a precursor to tyrosine in the pathway of melanin synthesis, might interfere with antibody production against melanocytes. This supplement is administered orally by weight, typically in conjunction with phototherapy or sunlight. Various studies have observed positive outcomes of L-phenylalanine combined with phototherapy or sunlight. L-phenylalanine tends to be safe and has been administered to children with vitiligo.

Many patients with vitiligo “have already tried diets by the time they come to me,” said Dr. Elbuluk. No controlled studies have analyzed the role of diet in the prevention or treatment of vitiligo, but case reports describe gluten-free diets in this population, including one report of a patient with celiac disease whose vitiligo improved after adoption of such a diet. Another case report described a patient without celiac disease who had refractory acrofacial vitiligo, which improved after the adoption of a gluten-free diet. Evidence supports a gluten-free diet for patients with celiac disease, but does not support this challenging diet for people without celiac disease, she pointed out.

Green tea includes catechins, which have antioxidant and anti-inflammatory properties. Its main component is epigallocatechin gallate (EGCG), which is thought to modulate T cell mediated responses. In one animal study, administration of EGCG delayed the onset of vitiligo and decreased the area of depigmentation in a mouse model. Although these findings are promising, clinical trials are needed to determine whether EGCG is beneficial in humans with vitiligo, said Dr. Elbuluk.

The literature on diets and supplementation as treatments for vitiligo has several shortcomings, with studies that used heterogeneous methodologies, and many that used nonstandard outcome measures that have not been validated. Sample sizes often are small, and many trials are uncontrolled. “These limitations make it harder to make sense of the data and have take-home conclusions,” Dr. Elbuluk said.

She had no disclosures.

[email protected]

SOURCE: Elbuluk N. AAD 19, Session S002.

WASHINGTON – Many patients with vitiligo are interested in treating their condition with vitamins, supplements, or a modified diet, but research on whether these measures have an impact remains limited, Nada Elbuluk, MD, said at the annual meeting of the American Academy of Dermatology.

While the literature suggests that supplements with antioxidant properties benefit patients who are receiving phototherapy for vitiligo, “we need more well designed, controlled studies in the future to know where this belongs in our treatment armamentarium,” said Dr. Elbuluk of the department of dermatology at the University of Southern California, Los Angeles.

During a session at the AAD meeting, Dr. Elbuluk, who is also director of the pigmentary disorders clinic at USC, reviewed the evidence for the use of these adjunctive therapies in patients with vitiligo.
 

Vitamins

The pathogenesis of vitiligo includes the overproduction of reactive oxygen species and oxidative stress, factors that contribute to melanocyte damage and death. In addition, many patients with vitiligo are deficient in certain vitamins and minerals, the basis of the hypothesis that supplementation could be beneficial, according to Dr. Elbuluk.

Vitamin B₁₂ and folic acid contribute to DNA repair, synthesis, and methylation, and researchers have hypothesized that these vitamins also play a role in melanin synthesis. In a review of the literature, Dr. Elbuluk and her colleagues found four studies that evaluated vitamin B₁₂ and folic acid in vitiligo. In one study, a controlled trial in which patients took B₁₂ and folic acid with and without phototherapy, the investigators observed no significant difference in repigmentation between groups. The other three studies were uncontrolled and thus provide an insufficient understanding of the effect of B₁₂ and folic acid, said Dr. Elbuluk.

Vitamin D is involved in melanocyte and keratinocyte growth and differentiation, and inhibits T cell activation. Data indicate that low vitamin D levels are common in patients with vitiligo and comorbid autoimmune diseases. In one study, patients who received narrow-band UVB had an increase in vitamin D levels that could contribute to photo-induced melanogenesis, and an open-label study indicated that patients who took vitamin D daily (without phototherapy) for 6 months had an increase of repigmentation over time. “Topical vitamin D analogs have also been used in vitiligo treatment with varying success,” Dr. Elbuluk noted.

“I check vitamin D levels on my patients and make sure that they are within normal range. But I think the degree of supplementation and its role in vitiligo needs to be further elucidated,” she said. And because vitamin D is fat soluble, there is a risk of toxicity if a patient takes too much.

Vitamin C, vitamin E, and alpha-lipoic acid have antioxidant properties. In a double-blind, randomized, controlled trial, one group of patients took vitamins C and E and alpha-lipoic acid for 2 months before and during treatment with narrow-band UVB twice per week (Clin Exp Dermatol. 2007 Nov;32[6]:631-6). Another group underwent phototherapy without supplementation. A significantly greater proportion of patients who received the antioxidants obtained more than 75% repigmentation compared with those who did not. In another study, 73% of patients who received oral vitamin E and narrow band UVB phototherapy had marked to excellent repigmentation, compared with 55.6% of those who had phototherapy only (J Clin Pharmacol. 2009 Jul;49[7]:852-5).

The results of these studies support the idea that antioxidants can stabilize disease, reduce oxidative stress, and improve the effect of phototherapy, Dr. Elbuluk said.
 

Herbal supplements

Several research teams have examined Ginkgo biloba as a possible treatment for vitiligo. This plant is native to China and has antioxidant and anti-inflammatory properties; its most common side effect is gastrointestinal distress. Because it entails a risk of coagulopathy, it may not be appropriate for patients receiving anticoagulant treatment, Dr. Elbuluk pointed out. In a double-blinded, randomized, controlled trial comparing ginkgo biloba alone with placebo in patients with vitiligo, treatment was associated with cessation of active disease in most patients, and more than 40% of patients receiving ginkgo biloba had 75% repigmentation or more.

Polypodium leucotomos, a fern native to Central and South America, protects against UV radiation damage, modulates the immune system, and has anti-inflammatory and antioxidant effects. It has a good safety profile and is well tolerated at a dose of 240 mg/day, she said. It sometimes causes gastrointestinal discomfort or pruritus. Several randomized, controlled trials in patients with vitiligo showed that supplementation with polypodium leucotomos improves repigmentation, particularly in photo-exposed areas, she noted.

Khellin is an extract from the Mediterranean khella plant that is thought to stimulate melanocyte proliferation and melanogenesis. Several studies have examined khellin supplementation in combination with phototherapy. Khellin can be administered orally or topically and appears to be more beneficial than sunlight or phototherapy alone in stabilizing disease or inducing repigmentation. Oral khellin can cause many side effects, including nausea, transaminitis, and hypotension, so researchers have been more interested in using topical khellin as a liposomal vehicle to improve drug delivery, Dr. Elbuluk said.
 

Minerals

Some patients with vitiligo have deficiencies in zinc and copper. Zinc is an antioxidant that aids wound healing, protects against free radicals, supports melanogenesis, and possibly prevents melanocyte death, but can cause gastrointestinal irritation. Copper, too, is an antioxidant and coenzyme involved in melanogenesis. One study compared topical steroid treatment with and without oral zinc supplementation. Dual treatment was associated with greater repigmentation, but the difference was not statistically significant. No studies have examined copper supplementation, she said.

L-phenylalanine, diet, and green tea

Investigators have proposed that the amino acid L-phenylalanine, a precursor to tyrosine in the pathway of melanin synthesis, might interfere with antibody production against melanocytes. This supplement is administered orally by weight, typically in conjunction with phototherapy or sunlight. Various studies have observed positive outcomes of L-phenylalanine combined with phototherapy or sunlight. L-phenylalanine tends to be safe and has been administered to children with vitiligo.

Many patients with vitiligo “have already tried diets by the time they come to me,” said Dr. Elbuluk. No controlled studies have analyzed the role of diet in the prevention or treatment of vitiligo, but case reports describe gluten-free diets in this population, including one report of a patient with celiac disease whose vitiligo improved after adoption of such a diet. Another case report described a patient without celiac disease who had refractory acrofacial vitiligo, which improved after the adoption of a gluten-free diet. Evidence supports a gluten-free diet for patients with celiac disease, but does not support this challenging diet for people without celiac disease, she pointed out.

Green tea includes catechins, which have antioxidant and anti-inflammatory properties. Its main component is epigallocatechin gallate (EGCG), which is thought to modulate T cell mediated responses. In one animal study, administration of EGCG delayed the onset of vitiligo and decreased the area of depigmentation in a mouse model. Although these findings are promising, clinical trials are needed to determine whether EGCG is beneficial in humans with vitiligo, said Dr. Elbuluk.

The literature on diets and supplementation as treatments for vitiligo has several shortcomings, with studies that used heterogeneous methodologies, and many that used nonstandard outcome measures that have not been validated. Sample sizes often are small, and many trials are uncontrolled. “These limitations make it harder to make sense of the data and have take-home conclusions,” Dr. Elbuluk said.

She had no disclosures.

[email protected]

SOURCE: Elbuluk N. AAD 19, Session S002.

Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.

The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?

TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.

FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).

HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.

The primary measure of the study was the time to platelet count response of greater than 150 x 10⁹/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.

The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.

In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.

End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.

While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.

The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.

Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.

Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.

As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.

Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.

Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.

The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?

TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.

FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).

HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.

The primary measure of the study was the time to platelet count response of greater than 150 x 10⁹/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.

The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.

In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.

End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.

While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.

The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.

Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.

Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.

As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.

Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.

Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.

The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?

TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.

FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).

HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.

The primary measure of the study was the time to platelet count response of greater than 150 x 10⁹/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.

The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.

In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.

End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.

While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.

The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.

Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.

Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.

As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.

Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.

On Match 15, 2019, tens of thousands of U.S. medical students matched into residency. For the seventh consecutive year overall match numbers are up, some specialties are concerned about post-residency workforce numbers, and social media offers congratulations and support.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

On Match 15, 2019, tens of thousands of U.S. medical students matched into residency. For the seventh consecutive year overall match numbers are up, some specialties are concerned about post-residency workforce numbers, and social media offers congratulations and support.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

On Match 15, 2019, tens of thousands of U.S. medical students matched into residency. For the seventh consecutive year overall match numbers are up, some specialties are concerned about post-residency workforce numbers, and social media offers congratulations and support.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.

“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.

The study was published simultaneously in the New England Journal of Medicine.

Ingram Publishing/ThinkStock

In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.

Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).

The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.

The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
 

SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.

Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.

“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.

The study was published simultaneously in the New England Journal of Medicine.

Ingram Publishing/ThinkStock

In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.

Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).

The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.

The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
 

SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.

Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.

“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.

The study was published simultaneously in the New England Journal of Medicine.

Ingram Publishing/ThinkStock

In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.

Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).

The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.

The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
 

SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.