Photo by Neil Osterweil

BOSTON—If donors can’t get to the apheresis center, bring the apheresis center to the donors.

Researchers have found that apheresis platelet collection in the field is practical with proper planning and support.

A team at the University of California at Los Angeles (UCLA) Blood and Platelet Center explored adding mobile apheresis units to their existing community blood drives.

They found that, with careful planning and coordination, they could augment their supply of blood products and introduce potential new donors to the idea of apheresis donations at the hospital.

The researchers reported these findings in a poster presentation at AABB 2018 (poster BBC 135).

It all started with a needs drive for an oncology patient at UCLA, explained David Anthony, manager of the UCLA Blood and Platelet Center.

“She wanted to bring in donors and had her whole community behind her,” Anthony said. “And we thought, well, she’s an oncology patient, and she uses platelets, and we had talked about doing platelets out in the field rather than just at fixed sites, and we thought that this would be a good chance to try it.”

Until the mobile unit was established, apheresis platelet collections for the hospital-based donor center were limited to two fixed collection sites, with mobile units used only for collection of whole blood.

To see whether concurrent whole blood and platelet community drives were practical, the center’s blood donor field recruiter requested to schedule a community drive in a region of the county where potential donors had expressed a high level of interest in apheresis platelet donations.

Operations staff visited the site to assess its suitability, including appropriate space for donor registration and history taking, separate areas for whole blood and apheresis donations, and a donor recovery area. The assessment included ensuring there were suitable electrical outlets, space, and support for apheresis machines.

“Over about 2 weeks, we discussed with our medical directors, [infusion technicians], and our mobile people what we would need to do it,” Anthony said. “The recruiter out in the field was able to go to a high school drive out in that area, recruit donors, and get [platelet] precounts from them so that we could find out who was a good candidate.”

Once they had platelet counts from potential apheresis donors, 10 donors were prescreened based on their eligibility to donate multiple products, history of donations and red blood cell loss, and, for women who had previously had more than one pregnancy, favorable human leukocyte antigen test results.

Four of the prescreened donors were scheduled to donate platelets, and the time slot also included two backup donors, one of whom ultimately donated platelets.

The first drive resulted in the collection of seven platelet products, including three double products and one single product.

The donated products resulted in about a $3,000 cost savings by obviating the need for purchasing products from an outside supplier and bolstered the blood bank’s inventory on a normally low collection day, the researchers reported.

“We’ve had two more apheresis drives since then, and we’ll have another one in 3 weeks,” Anthony said.

He acknowledged that it is more challenging to recruit, educate, and retain donors in the field than in the brick-and-mortar hospital setting.

“We have to make sure that they’re going to show up if we’re going to make the effort to take a machine out there, whereas, at our centers, we have regular donors who come in every 2 weeks,” Anthony said. “It’s easy for them to make an appointment, and they know where we are.”

The center plans to continue concurrent monthly whole blood and platelet collection drives, he added.

This pilot program was internally funded. The researchers reported having no relevant conflicts of interest.

Photo by Neil Osterweil

BOSTON—If donors can’t get to the apheresis center, bring the apheresis center to the donors.

Researchers have found that apheresis platelet collection in the field is practical with proper planning and support.

A team at the University of California at Los Angeles (UCLA) Blood and Platelet Center explored adding mobile apheresis units to their existing community blood drives.

They found that, with careful planning and coordination, they could augment their supply of blood products and introduce potential new donors to the idea of apheresis donations at the hospital.

The researchers reported these findings in a poster presentation at AABB 2018 (poster BBC 135).

It all started with a needs drive for an oncology patient at UCLA, explained David Anthony, manager of the UCLA Blood and Platelet Center.

“She wanted to bring in donors and had her whole community behind her,” Anthony said. “And we thought, well, she’s an oncology patient, and she uses platelets, and we had talked about doing platelets out in the field rather than just at fixed sites, and we thought that this would be a good chance to try it.”

Until the mobile unit was established, apheresis platelet collections for the hospital-based donor center were limited to two fixed collection sites, with mobile units used only for collection of whole blood.

To see whether concurrent whole blood and platelet community drives were practical, the center’s blood donor field recruiter requested to schedule a community drive in a region of the county where potential donors had expressed a high level of interest in apheresis platelet donations.

Operations staff visited the site to assess its suitability, including appropriate space for donor registration and history taking, separate areas for whole blood and apheresis donations, and a donor recovery area. The assessment included ensuring there were suitable electrical outlets, space, and support for apheresis machines.

“Over about 2 weeks, we discussed with our medical directors, [infusion technicians], and our mobile people what we would need to do it,” Anthony said. “The recruiter out in the field was able to go to a high school drive out in that area, recruit donors, and get [platelet] precounts from them so that we could find out who was a good candidate.”

Once they had platelet counts from potential apheresis donors, 10 donors were prescreened based on their eligibility to donate multiple products, history of donations and red blood cell loss, and, for women who had previously had more than one pregnancy, favorable human leukocyte antigen test results.

Four of the prescreened donors were scheduled to donate platelets, and the time slot also included two backup donors, one of whom ultimately donated platelets.

The first drive resulted in the collection of seven platelet products, including three double products and one single product.

The donated products resulted in about a $3,000 cost savings by obviating the need for purchasing products from an outside supplier and bolstered the blood bank’s inventory on a normally low collection day, the researchers reported.

“We’ve had two more apheresis drives since then, and we’ll have another one in 3 weeks,” Anthony said.

He acknowledged that it is more challenging to recruit, educate, and retain donors in the field than in the brick-and-mortar hospital setting.

“We have to make sure that they’re going to show up if we’re going to make the effort to take a machine out there, whereas, at our centers, we have regular donors who come in every 2 weeks,” Anthony said. “It’s easy for them to make an appointment, and they know where we are.”

The center plans to continue concurrent monthly whole blood and platelet collection drives, he added.

This pilot program was internally funded. The researchers reported having no relevant conflicts of interest.

Photo by Neil Osterweil

BOSTON—If donors can’t get to the apheresis center, bring the apheresis center to the donors.

Researchers have found that apheresis platelet collection in the field is practical with proper planning and support.

A team at the University of California at Los Angeles (UCLA) Blood and Platelet Center explored adding mobile apheresis units to their existing community blood drives.

They found that, with careful planning and coordination, they could augment their supply of blood products and introduce potential new donors to the idea of apheresis donations at the hospital.

The researchers reported these findings in a poster presentation at AABB 2018 (poster BBC 135).

It all started with a needs drive for an oncology patient at UCLA, explained David Anthony, manager of the UCLA Blood and Platelet Center.

“She wanted to bring in donors and had her whole community behind her,” Anthony said. “And we thought, well, she’s an oncology patient, and she uses platelets, and we had talked about doing platelets out in the field rather than just at fixed sites, and we thought that this would be a good chance to try it.”

Until the mobile unit was established, apheresis platelet collections for the hospital-based donor center were limited to two fixed collection sites, with mobile units used only for collection of whole blood.

To see whether concurrent whole blood and platelet community drives were practical, the center’s blood donor field recruiter requested to schedule a community drive in a region of the county where potential donors had expressed a high level of interest in apheresis platelet donations.

Operations staff visited the site to assess its suitability, including appropriate space for donor registration and history taking, separate areas for whole blood and apheresis donations, and a donor recovery area. The assessment included ensuring there were suitable electrical outlets, space, and support for apheresis machines.

“Over about 2 weeks, we discussed with our medical directors, [infusion technicians], and our mobile people what we would need to do it,” Anthony said. “The recruiter out in the field was able to go to a high school drive out in that area, recruit donors, and get [platelet] precounts from them so that we could find out who was a good candidate.”

Once they had platelet counts from potential apheresis donors, 10 donors were prescreened based on their eligibility to donate multiple products, history of donations and red blood cell loss, and, for women who had previously had more than one pregnancy, favorable human leukocyte antigen test results.

Four of the prescreened donors were scheduled to donate platelets, and the time slot also included two backup donors, one of whom ultimately donated platelets.

The first drive resulted in the collection of seven platelet products, including three double products and one single product.

The donated products resulted in about a $3,000 cost savings by obviating the need for purchasing products from an outside supplier and bolstered the blood bank’s inventory on a normally low collection day, the researchers reported.

“We’ve had two more apheresis drives since then, and we’ll have another one in 3 weeks,” Anthony said.

He acknowledged that it is more challenging to recruit, educate, and retain donors in the field than in the brick-and-mortar hospital setting.

“We have to make sure that they’re going to show up if we’re going to make the effort to take a machine out there, whereas, at our centers, we have regular donors who come in every 2 weeks,” Anthony said. “It’s easy for them to make an appointment, and they know where we are.”

The center plans to continue concurrent monthly whole blood and platelet collection drives, he added.

This pilot program was internally funded. The researchers reported having no relevant conflicts of interest.

Photo by Darren Baker

The U.S. Food and Drug Administration (FDA) has issued a draft guidance on the use of minimal residual disease (MRD) assessment in trials of patients with hematologic malignancies.

The FDA said it developed this guidance to assist sponsors who are planning to use MRD as a biomarker in clinical trials conducted under an investigational new drug application or to support FDA approval of products intended to treat hematologic malignancies.

“As a result of important workshops where we’ve heard from stakeholders and an analysis of marketing applications showing inconsistent quality of MRD data, the FDA identified a need to provide sponsors with guidance on the use of MRD as a biomarker in regulatory submissions,” said FDA Commissioner Scott Gottlieb, MD.

The guidance explains how MRD might be used in clinical trials, highlights considerations for MRD assessment that are specific to certain hematologic malignancies, and lists requirements for regulatory submissions that utilize MRD.

The full document, “Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment,” is available for download from the FDA website.

How MRD can be used

The guidance notes that MRD could potentially be used as a biomarker in clinical trials, specifically, as a diagnostic, prognostic, predictive, efficacy-response, or monitoring biomarker.

MRD could also be used as a surrogate endpoint, and there are two mechanisms for obtaining FDA feedback on the use of a novel surrogate endpoint to support approval of a product:

1. The drug development tool qualification process
2. Discussions with the specific Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research review division.

Furthermore, a sponsor can use MRD “to select patients at high risk or to enrich the trial population,” according to the guidance.

Disease specifics

The guidance also details specific considerations for MRD assessment in individual hematologic malignancies. For example:

• In acute lymphoblastic leukemia, a patient with an MRD level of 0.1% or more in first or second complete remission has a high risk of relapse.
• In trials of acute myeloid leukemia, the sponsor should provide data showing that the marker selected to assess MRD “reflects the leukemia and not underlying clonal hematopoiesis.”
• Patients with low-risk acute promyelocytic leukemia who achieve MRD negativity after arsenic/tretinoin-based therapy are generally considered cured.
• In chronic lymphocytic leukemia, MRD can be assessed in the peripheral blood or bone marrow, but the sample source should remain the same throughout a trial.
• In chronic myeloid leukemia, MRD can be used to select and monitor patients who are eligible to discontinue treatment with tyrosine kinase inhibitors.
• In multiple myeloma, imaging techniques may be combined with MRD assessment of the bone marrow to assess patient response to treatment.

Types of technology

The guidance lists the four general technologies used for MRD assessment in hematologic malignancies:

• Multiparametric flow cytometry
• Next-generation sequencing
• Quantitative reverse transcription polymerase chain reaction of specific gene fusions
• Allele-specific oligonucleotide polymerase chain reaction.

The FDA said it does not have a preference as to which technology is used in a trial. However, the sponsor must pre-specify the technology used and should utilize the same technology throughout a trial.

The FDA also said it “does not foresee the need for co-development of an MRD assay with a drug product.” However, the assay must be analytically valid for results important to the trial, and MRD assessment must be a clinically valid biomarker in the context in which it’s used.

If the MRD assay used is not FDA-cleared or -approved, additional information about the assay must be provided to the FDA.

Photo by Darren Baker

The U.S. Food and Drug Administration (FDA) has issued a draft guidance on the use of minimal residual disease (MRD) assessment in trials of patients with hematologic malignancies.

The FDA said it developed this guidance to assist sponsors who are planning to use MRD as a biomarker in clinical trials conducted under an investigational new drug application or to support FDA approval of products intended to treat hematologic malignancies.

“As a result of important workshops where we’ve heard from stakeholders and an analysis of marketing applications showing inconsistent quality of MRD data, the FDA identified a need to provide sponsors with guidance on the use of MRD as a biomarker in regulatory submissions,” said FDA Commissioner Scott Gottlieb, MD.

The guidance explains how MRD might be used in clinical trials, highlights considerations for MRD assessment that are specific to certain hematologic malignancies, and lists requirements for regulatory submissions that utilize MRD.

The full document, “Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment,” is available for download from the FDA website.

How MRD can be used

The guidance notes that MRD could potentially be used as a biomarker in clinical trials, specifically, as a diagnostic, prognostic, predictive, efficacy-response, or monitoring biomarker.

MRD could also be used as a surrogate endpoint, and there are two mechanisms for obtaining FDA feedback on the use of a novel surrogate endpoint to support approval of a product:

1. The drug development tool qualification process
2. Discussions with the specific Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research review division.

Furthermore, a sponsor can use MRD “to select patients at high risk or to enrich the trial population,” according to the guidance.

Disease specifics

The guidance also details specific considerations for MRD assessment in individual hematologic malignancies. For example:

• In acute lymphoblastic leukemia, a patient with an MRD level of 0.1% or more in first or second complete remission has a high risk of relapse.
• In trials of acute myeloid leukemia, the sponsor should provide data showing that the marker selected to assess MRD “reflects the leukemia and not underlying clonal hematopoiesis.”
• Patients with low-risk acute promyelocytic leukemia who achieve MRD negativity after arsenic/tretinoin-based therapy are generally considered cured.
• In chronic lymphocytic leukemia, MRD can be assessed in the peripheral blood or bone marrow, but the sample source should remain the same throughout a trial.
• In chronic myeloid leukemia, MRD can be used to select and monitor patients who are eligible to discontinue treatment with tyrosine kinase inhibitors.
• In multiple myeloma, imaging techniques may be combined with MRD assessment of the bone marrow to assess patient response to treatment.

Types of technology

The guidance lists the four general technologies used for MRD assessment in hematologic malignancies:

• Multiparametric flow cytometry
• Next-generation sequencing
• Quantitative reverse transcription polymerase chain reaction of specific gene fusions
• Allele-specific oligonucleotide polymerase chain reaction.

The FDA said it does not have a preference as to which technology is used in a trial. However, the sponsor must pre-specify the technology used and should utilize the same technology throughout a trial.

The FDA also said it “does not foresee the need for co-development of an MRD assay with a drug product.” However, the assay must be analytically valid for results important to the trial, and MRD assessment must be a clinically valid biomarker in the context in which it’s used.

If the MRD assay used is not FDA-cleared or -approved, additional information about the assay must be provided to the FDA.

Photo by Darren Baker

The U.S. Food and Drug Administration (FDA) has issued a draft guidance on the use of minimal residual disease (MRD) assessment in trials of patients with hematologic malignancies.

The FDA said it developed this guidance to assist sponsors who are planning to use MRD as a biomarker in clinical trials conducted under an investigational new drug application or to support FDA approval of products intended to treat hematologic malignancies.

“As a result of important workshops where we’ve heard from stakeholders and an analysis of marketing applications showing inconsistent quality of MRD data, the FDA identified a need to provide sponsors with guidance on the use of MRD as a biomarker in regulatory submissions,” said FDA Commissioner Scott Gottlieb, MD.

The guidance explains how MRD might be used in clinical trials, highlights considerations for MRD assessment that are specific to certain hematologic malignancies, and lists requirements for regulatory submissions that utilize MRD.

The full document, “Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment,” is available for download from the FDA website.

How MRD can be used

The guidance notes that MRD could potentially be used as a biomarker in clinical trials, specifically, as a diagnostic, prognostic, predictive, efficacy-response, or monitoring biomarker.

MRD could also be used as a surrogate endpoint, and there are two mechanisms for obtaining FDA feedback on the use of a novel surrogate endpoint to support approval of a product:

1. The drug development tool qualification process
2. Discussions with the specific Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research review division.

Furthermore, a sponsor can use MRD “to select patients at high risk or to enrich the trial population,” according to the guidance.

Disease specifics

The guidance also details specific considerations for MRD assessment in individual hematologic malignancies. For example:

• In acute lymphoblastic leukemia, a patient with an MRD level of 0.1% or more in first or second complete remission has a high risk of relapse.
• In trials of acute myeloid leukemia, the sponsor should provide data showing that the marker selected to assess MRD “reflects the leukemia and not underlying clonal hematopoiesis.”
• Patients with low-risk acute promyelocytic leukemia who achieve MRD negativity after arsenic/tretinoin-based therapy are generally considered cured.
• In chronic lymphocytic leukemia, MRD can be assessed in the peripheral blood or bone marrow, but the sample source should remain the same throughout a trial.
• In chronic myeloid leukemia, MRD can be used to select and monitor patients who are eligible to discontinue treatment with tyrosine kinase inhibitors.
• In multiple myeloma, imaging techniques may be combined with MRD assessment of the bone marrow to assess patient response to treatment.

Types of technology

The guidance lists the four general technologies used for MRD assessment in hematologic malignancies:

• Multiparametric flow cytometry
• Next-generation sequencing
• Quantitative reverse transcription polymerase chain reaction of specific gene fusions
• Allele-specific oligonucleotide polymerase chain reaction.

The FDA said it does not have a preference as to which technology is used in a trial. However, the sponsor must pre-specify the technology used and should utilize the same technology throughout a trial.

The FDA also said it “does not foresee the need for co-development of an MRD assay with a drug product.” However, the assay must be analytically valid for results important to the trial, and MRD assessment must be a clinically valid biomarker in the context in which it’s used.

If the MRD assay used is not FDA-cleared or -approved, additional information about the assay must be provided to the FDA.

Toni Valković, MD, PhD

DUBROVNIK, CROATIA—Clinical trials are needed to answer the many questions related to minimal residual disease (MRD) assessment in multiple myeloma (MM), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

MM patients are increasingly assessed for MRD, which is a strong prognostic factor and surrogate for overall survival, according to Toni Valković, MD, PhD, of University Hospital Center Rijeka in Croatia.

However, Dr. Valković said MRD assessment has not become a part of routine clinical practice, perhaps because we haven’t determined the best way to utilize MRD assessment in MM patients.

The optimal sensitivity threshold, technique, and timing of MRD assessment are not known, and it isn’t clear how MRD should be used to guide treatment.

What we know

Dr. Valković cited studies showing that MRD negativity is associated with superior survival in MM¹, and, when MRD negativity is achieved, high-risk cytogenetics, age, and previous treatment regimens appear to have no further impact on prognosis.²

Dr. Valković went on to explain the benefits and detriments of multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment.³

NGS requires a baseline patient sample, but MFC does not. More cells are required with MFC than with NGS (>5 million vs. <1 million).

With MFC, samples must be processed within 24 to 48 hours, whereas, with NGS, fresh or stored samples can be used. MFC can be done in a few hours, while NGS can take several days.

Despite these differences, both methods provide similar levels of sensitivity for detecting MRD (≥1 in 10⁵).

Dr. Valković also noted that MRD should be evaluated outside the bone marrow as well, which can be done with positron emission tomography-computed tomography (PET-CT).

Research has shown that patients who are MRD-negative according to both MFC and PET-CT have better outcomes than patients who are MRD-positive by MFC, PET-CT, or both.⁴

What we don’t know

Though he compared MFC and NGS, Dr. Valković said we don’t know the optimal technique for assessing MRD in the bone marrow.

Another uncertainty is the optimal sensitivity threshold. In the POLLUX study⁵, researchers found that a threshold of 10^-4 resulted in lots of patients with MRD negativity, but some of these were false-negatives.

So although 10^-4 proved inaccurate, it isn’t clear if the optimal threshold is 10^-5 or 10^-6, Dr. Valković said.

Likewise, it isn’t clear if PET-CT is the optimal method for evaluating MRD outside the bone marrow.

In a study published in 2017, PET produced false-negatives in MM patients.⁶ In 11% of patients (26/227), there was evidence of disease with diffusion-weighted magnetic resonance imaging with background signal suppression, but there was no apparent disease with PET. The researchers said low expression of hexokinase-2 was associated with a false-negative PET result.

Finally, Dr. Valković said we don’t know how best to use MRD to tailor therapy in MM patients. He posed the following questions:

• If patients don’t achieve MRD negativity, should they continue on the therapy?
• If MRD-negative patients become MRD-positive, should they begin therapy immediately, or should treatment be put off until a biochemical or clinical relapse?
• Should MRD status be used to determine the number of treatment cycles a patient receives, the timing of transplant, or when to begin and end maintenance therapy?

“There are a lot of issues and unanswered questions related to the optimal techniques for the evaluation of MRD and their sensitivity, the timing for MRD assessment during and after therapy, and its role in the treatment decisions, which should be answered in future clinical studies,” Dr. Valković concluded.

He did not declare any conflicts of interest.

1. Munshi NC et al. JAMA Oncol. 2017;3(1):28-35. doi:10.1001/jamaoncol.2016.3160

2. Paiva B et al. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319

3. Kumar S et al. Lancet Oncol. 2016; 17 (8):e328-46 doi: https://doi.org/10.1016/S1470-2045(16)30206-6

4. Fernandez RA et al. Blood. 2017; 130:3098

5. Dimopoulos MA et al. Haematologica. 2018 Sep 20. pii: haematol.2018.194282. doi: 10.3324/haematol.2018.194282

6. Rasche L et al. Blood. 2017 Jul 6;130(1):30-34. doi: 10.1182/blood-2017-03-774422

Toni Valković, MD, PhD

DUBROVNIK, CROATIA—Clinical trials are needed to answer the many questions related to minimal residual disease (MRD) assessment in multiple myeloma (MM), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

MM patients are increasingly assessed for MRD, which is a strong prognostic factor and surrogate for overall survival, according to Toni Valković, MD, PhD, of University Hospital Center Rijeka in Croatia.

However, Dr. Valković said MRD assessment has not become a part of routine clinical practice, perhaps because we haven’t determined the best way to utilize MRD assessment in MM patients.

The optimal sensitivity threshold, technique, and timing of MRD assessment are not known, and it isn’t clear how MRD should be used to guide treatment.

What we know

Dr. Valković cited studies showing that MRD negativity is associated with superior survival in MM¹, and, when MRD negativity is achieved, high-risk cytogenetics, age, and previous treatment regimens appear to have no further impact on prognosis.²

Dr. Valković went on to explain the benefits and detriments of multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment.³

NGS requires a baseline patient sample, but MFC does not. More cells are required with MFC than with NGS (>5 million vs. <1 million).

With MFC, samples must be processed within 24 to 48 hours, whereas, with NGS, fresh or stored samples can be used. MFC can be done in a few hours, while NGS can take several days.

Despite these differences, both methods provide similar levels of sensitivity for detecting MRD (≥1 in 10⁵).

Dr. Valković also noted that MRD should be evaluated outside the bone marrow as well, which can be done with positron emission tomography-computed tomography (PET-CT).

Research has shown that patients who are MRD-negative according to both MFC and PET-CT have better outcomes than patients who are MRD-positive by MFC, PET-CT, or both.⁴

What we don’t know

Though he compared MFC and NGS, Dr. Valković said we don’t know the optimal technique for assessing MRD in the bone marrow.

Another uncertainty is the optimal sensitivity threshold. In the POLLUX study⁵, researchers found that a threshold of 10^-4 resulted in lots of patients with MRD negativity, but some of these were false-negatives.

So although 10^-4 proved inaccurate, it isn’t clear if the optimal threshold is 10^-5 or 10^-6, Dr. Valković said.

Likewise, it isn’t clear if PET-CT is the optimal method for evaluating MRD outside the bone marrow.

In a study published in 2017, PET produced false-negatives in MM patients.⁶ In 11% of patients (26/227), there was evidence of disease with diffusion-weighted magnetic resonance imaging with background signal suppression, but there was no apparent disease with PET. The researchers said low expression of hexokinase-2 was associated with a false-negative PET result.

Finally, Dr. Valković said we don’t know how best to use MRD to tailor therapy in MM patients. He posed the following questions:

• If patients don’t achieve MRD negativity, should they continue on the therapy?
• If MRD-negative patients become MRD-positive, should they begin therapy immediately, or should treatment be put off until a biochemical or clinical relapse?
• Should MRD status be used to determine the number of treatment cycles a patient receives, the timing of transplant, or when to begin and end maintenance therapy?

“There are a lot of issues and unanswered questions related to the optimal techniques for the evaluation of MRD and their sensitivity, the timing for MRD assessment during and after therapy, and its role in the treatment decisions, which should be answered in future clinical studies,” Dr. Valković concluded.

He did not declare any conflicts of interest.

1. Munshi NC et al. JAMA Oncol. 2017;3(1):28-35. doi:10.1001/jamaoncol.2016.3160

2. Paiva B et al. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319

3. Kumar S et al. Lancet Oncol. 2016; 17 (8):e328-46 doi: https://doi.org/10.1016/S1470-2045(16)30206-6

4. Fernandez RA et al. Blood. 2017; 130:3098

5. Dimopoulos MA et al. Haematologica. 2018 Sep 20. pii: haematol.2018.194282. doi: 10.3324/haematol.2018.194282

6. Rasche L et al. Blood. 2017 Jul 6;130(1):30-34. doi: 10.1182/blood-2017-03-774422

Toni Valković, MD, PhD

DUBROVNIK, CROATIA—Clinical trials are needed to answer the many questions related to minimal residual disease (MRD) assessment in multiple myeloma (MM), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

MM patients are increasingly assessed for MRD, which is a strong prognostic factor and surrogate for overall survival, according to Toni Valković, MD, PhD, of University Hospital Center Rijeka in Croatia.

However, Dr. Valković said MRD assessment has not become a part of routine clinical practice, perhaps because we haven’t determined the best way to utilize MRD assessment in MM patients.

The optimal sensitivity threshold, technique, and timing of MRD assessment are not known, and it isn’t clear how MRD should be used to guide treatment.

What we know

Dr. Valković cited studies showing that MRD negativity is associated with superior survival in MM¹, and, when MRD negativity is achieved, high-risk cytogenetics, age, and previous treatment regimens appear to have no further impact on prognosis.²

Dr. Valković went on to explain the benefits and detriments of multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment.³

NGS requires a baseline patient sample, but MFC does not. More cells are required with MFC than with NGS (>5 million vs. <1 million).

With MFC, samples must be processed within 24 to 48 hours, whereas, with NGS, fresh or stored samples can be used. MFC can be done in a few hours, while NGS can take several days.

Despite these differences, both methods provide similar levels of sensitivity for detecting MRD (≥1 in 10⁵).

Dr. Valković also noted that MRD should be evaluated outside the bone marrow as well, which can be done with positron emission tomography-computed tomography (PET-CT).

Research has shown that patients who are MRD-negative according to both MFC and PET-CT have better outcomes than patients who are MRD-positive by MFC, PET-CT, or both.⁴

What we don’t know

Though he compared MFC and NGS, Dr. Valković said we don’t know the optimal technique for assessing MRD in the bone marrow.

Another uncertainty is the optimal sensitivity threshold. In the POLLUX study⁵, researchers found that a threshold of 10^-4 resulted in lots of patients with MRD negativity, but some of these were false-negatives.

So although 10^-4 proved inaccurate, it isn’t clear if the optimal threshold is 10^-5 or 10^-6, Dr. Valković said.

Likewise, it isn’t clear if PET-CT is the optimal method for evaluating MRD outside the bone marrow.

In a study published in 2017, PET produced false-negatives in MM patients.⁶ In 11% of patients (26/227), there was evidence of disease with diffusion-weighted magnetic resonance imaging with background signal suppression, but there was no apparent disease with PET. The researchers said low expression of hexokinase-2 was associated with a false-negative PET result.

Finally, Dr. Valković said we don’t know how best to use MRD to tailor therapy in MM patients. He posed the following questions:

• If patients don’t achieve MRD negativity, should they continue on the therapy?
• If MRD-negative patients become MRD-positive, should they begin therapy immediately, or should treatment be put off until a biochemical or clinical relapse?
• Should MRD status be used to determine the number of treatment cycles a patient receives, the timing of transplant, or when to begin and end maintenance therapy?

“There are a lot of issues and unanswered questions related to the optimal techniques for the evaluation of MRD and their sensitivity, the timing for MRD assessment during and after therapy, and its role in the treatment decisions, which should be answered in future clinical studies,” Dr. Valković concluded.

He did not declare any conflicts of interest.

1. Munshi NC et al. JAMA Oncol. 2017;3(1):28-35. doi:10.1001/jamaoncol.2016.3160

2. Paiva B et al. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319

3. Kumar S et al. Lancet Oncol. 2016; 17 (8):e328-46 doi: https://doi.org/10.1016/S1470-2045(16)30206-6

4. Fernandez RA et al. Blood. 2017; 130:3098

5. Dimopoulos MA et al. Haematologica. 2018 Sep 20. pii: haematol.2018.194282. doi: 10.3324/haematol.2018.194282

6. Rasche L et al. Blood. 2017 Jul 6;130(1):30-34. doi: 10.1182/blood-2017-03-774422

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

 

 

TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

 

 

TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

IN THIS ARTICLE

• Prostate cancer screening tools
• Ethic disparities
• Screening guidance

Prostate cancer, the second most common cancer to affect American men, is a slow-growing cancer that is curable when detected early. While the overall incidence has declined in the past 20 years (see Figure 1), prostate cancer remains a major concern among black men due to disproportionate incidence and mortality rates.^1-3 A general understanding of the prostate and of prostate cancer lays the groundwork to acknowledge and address this divide.

ANATOMY OF THE PROSTATE

Although most men know where the prostate gland is located, many do not understand how it functions.⁴ The largest accessory gland of the male reproductive system, the prostate is located below the bladder and in front of the rectum (see Figure 2).⁵ The urethra passes through this gland; therefore, enlargement of the prostate can cause constriction of the urethra, which can affect the ability to eliminate urine from the body.⁵

The prostate is broken down into four distinct regions (see Figure 3). Certain types of inflammation may occur more often in some regions of the prostate than others; as such, 75% of prostate cancer occurs in the peripheral zone (the region located closest to the rectal wall).^5,6

DIAGNOSING PROSTATE CANCER

Signs and symptoms

According to the CDC, the signs and symptoms of prostate cancer include

• Difficulty starting urination
• Weak or interrupted flow of urine
• Frequent urination (especially at night)
• Difficulty emptying the bladder
• Pain or burning during urination
• Blood in the urine or semen
• Pain in the back, hips, or pelvis
• Painful ejaculation.

However, none of these signs and symptoms are unique to prostate cancer.⁷ For instance, difficulty starting urination, weak or interrupted flow of urine, and frequent urination can also be attributed to benign prostatic hyperplasia. Further, in its early stages, prostate cancer may not exhibit any signs or symptoms, making accurate screening essential for detection and treatment.⁷

Screening tools

There are two primary tools for detection of prostate cancer: the prostate-specific antigen (PSA) test and the digital rectal exam (DRE).⁸ The blood test for PSA is routinely used as a screening tool and is therefore considered a standard test for prostate cancer.⁹ A PSA level above 4.0 ng/mL is considered abnormal.¹⁰ Although measuring the PSA level can improve the odds of early prostate cancer detection, there is considerable debate over its dependability in this regard, as PSA can be elevated for benign reasons.

Sociocultural and genetic risk factors

While both black and white men are at an increased risk for prostate cancer if a first-degree relative (ie, father, brother, son) had the disease, one in five black men will develop prostate cancer in their lifetimes, compared with one in seven white men.³ And despite a five-year survival rate of nearly 100% for regional prostate cancer, black men are more than two times as likely as white men to die of the disease (1 in 23 and 1 in 38, respectively).^8,11 From 2011 to 2015, the age-adjusted mortality rate of prostate cancer among black men was 40.8, versus 18.2 for non-Hispanic white men (per 100,000 population).¹²

Continue to: The disparity in prostate cancer mortality...

The disparity in prostate cancer mortality among black men has been attributed to multiple variables. Cultural differences can play a role in whether patients choose to undergo prostate cancer screening. Black men are, for example, less likely than other men to participate in preventive health care practices.¹³ Although an in-depth discussion is outside the scope of this article, researchers have identified some plausible factors for this, including economic limitations, lack of access to health care, distrust of the health care system, and an indifference to pain or discomfort.^13,14 Decisions surrounding prostate screening can also be affected by a patient’s perceived risk for prostate cancer, the impact of a cancer diagnosis, and the availability of treatment.

Other factors that contribute to the higher incidence and mortality rate among black men include genetic predisposition, health beliefs, and knowledge about the prostate and cancer screenings.¹⁵ While most researchers have focused on men ages 40 and older, Ogunsanya et al suggested that educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.¹⁵

PRACTICE POINTS

• Prostate cancer remains a major concern among black men due to disproportionate incidence and mortality.
• Developing prostate cancer screening recommendations for black men would help reduce mortality and morbidity in this population.
• Educating black men about screening for prostate cancer at an earlier age may help them to make informed decisions later in life.

IMPLICATIONS FOR PRACTICE

The age at which men should begin screening for prostate cancer has been a source of controversy due to the lack of consensus between the American Cancer Society, the American Urological Association, and the United States Preventive Services Task Force (USPSTF) guidelines (see Table).^16-18 The current USPSTF recommendations for prostate cancer screening do not take into account ethnic differences, despite the identified racial disparity.¹⁹ Ambiguity in public health policy creates a quandary in the decision-making process regarding testing and treatment.^9,19,20

Early screening and intervention is necessary to help mitigate prostate cancer morbidity and mortality.²¹The authors support the use of the American Cancer Society guidelines, which are comprehensive and clearly define who is considered to be at risk. The guidelines suggest screening black men and men with known family histories (considered to be at high risk) at age 45, and screening men with a strong family history (multiple first-degree relatives who developed prostate cancer at a young age) beginning at age 40.

In addition, these guidelines recommend the use of both the DRE and PSA screening tests. Screening should be performed every two years for men who have a PSA level < 2.5 ng/mL, and every year for men who have a level > 2.5 ng/mL.

Continue to: TREATMENT

 

 

TREATMENT

Fortunately, there are several treatment options for men who are diagnosed with prostate cancer.²² These include watchful waiting, surgery, radiation, cryotherapy, hormone therapy, and chemotherapy. The type of treatment chosen depends on many factors, such as the tumor grade or cancer stage, the implications for quality of life, and the shared provider/patient decision-making process. Indeed, choosing the right treatment is a specialized approach that varies according to case and circumstance.²²

CONCLUSION

There has been an increase in prostate cancer screening in recent years. However, black men still lag behind when it comes to having DRE and PSA tests. Many factors, including cultural perceptions of medical care among black men, often cause delays in seeking evaluation and treatment. Developing consistent and uniform prostate cancer screening recommendations for black men would be an important step in reducing mortality and morbidity in this population.

Nationwide bans on corporal punishment of children in the home and school seem to have had a positive impact on fighting among adolescents, with males in those countries about 30% less likely to engage in fighting and females almost 60% less likely to do so, according to a study of school-based health surveys completed by 403,604 adolescents in 88 different countries published in BMJ Open.

“These findings add to a growing body of evidence on links between corporal punishment and adolescent health and safety. A growing number of countries have banned corporal punishment as an acceptable means of child discipline, and this is an important step that should be encouraged,” said Frank J. Elgar, PhD, of McGill University in Montreal and his colleagues. “Health providers are well positioned to offer practical and effective tools that support such approaches to child discipline. Cultural shifts from punitive to positive discipline happen slowly.”

The researchers placed countries into three categories: those that have banned corporate punishment in the home and at school; those that have banned it in school only (which include the United States, Canada, and the United Kingdom); and those that have not banned corporal punishment in either setting.

Frequent fighting rates varied widely, Dr. Elgar and his colleagues noted, ranging from a low of less than 1% among females in Costa Rica, which bans all forms of corporal punishment, to a high of 35% among males in Samoa, which allows corporal punishment in both settings.

The 30 countries with full bans had rates of fighting 31% lower in males and 58% lower in females than the 20 countries with no ban. Thirty-eight countries with bans in schools but not in the home reported less fighting in females only – 44% lower than countries without bans.

The reasons for the gender difference in fighting rates among countries with partial bans is unclear, the authors said. “It could be that males, compared with females, experience more physical violence outside school settings or are affected differently by corporal punishment by teachers,” Dr. Elgar and his coauthors said. “Further investigation is needed.”

The study analyzed findings of two well-established surveys used internationally to measure fighting among adolescents: the World Health Organization Health Behavior in School-aged Children (HBSC) study and the Global School-based Health Survey (GSHS). The former is conducted among children ages 11, 13, and 15 in Canada, the United States, and most European countries every 4 years. The GSHS measures fighting among children aged 13-17 years in 55 low- and middle-income countries.

Among the limitations the study authors acknowledged was the inability to account for when the surveys were completed and when the bans were implemented, enforced, or modified, but they also pointed out the large and diverse sample of countries as a strength of the study.

Dr. Elgar and coauthors reported having no financial relationships. The work was supported by grants from the Canadian Institutes for Health Research, the Social Sciences and Humanities Research Council, and the Canada Research Chairs programme.

SOURCE: Elgar FJ et al. BMJ Open. 2018;8:e021616.

Nationwide bans on corporal punishment of children in the home and school seem to have had a positive impact on fighting among adolescents, with males in those countries about 30% less likely to engage in fighting and females almost 60% less likely to do so, according to a study of school-based health surveys completed by 403,604 adolescents in 88 different countries published in BMJ Open.

“These findings add to a growing body of evidence on links between corporal punishment and adolescent health and safety. A growing number of countries have banned corporal punishment as an acceptable means of child discipline, and this is an important step that should be encouraged,” said Frank J. Elgar, PhD, of McGill University in Montreal and his colleagues. “Health providers are well positioned to offer practical and effective tools that support such approaches to child discipline. Cultural shifts from punitive to positive discipline happen slowly.”

The researchers placed countries into three categories: those that have banned corporate punishment in the home and at school; those that have banned it in school only (which include the United States, Canada, and the United Kingdom); and those that have not banned corporal punishment in either setting.

Frequent fighting rates varied widely, Dr. Elgar and his colleagues noted, ranging from a low of less than 1% among females in Costa Rica, which bans all forms of corporal punishment, to a high of 35% among males in Samoa, which allows corporal punishment in both settings.

The 30 countries with full bans had rates of fighting 31% lower in males and 58% lower in females than the 20 countries with no ban. Thirty-eight countries with bans in schools but not in the home reported less fighting in females only – 44% lower than countries without bans.

The reasons for the gender difference in fighting rates among countries with partial bans is unclear, the authors said. “It could be that males, compared with females, experience more physical violence outside school settings or are affected differently by corporal punishment by teachers,” Dr. Elgar and his coauthors said. “Further investigation is needed.”

The study analyzed findings of two well-established surveys used internationally to measure fighting among adolescents: the World Health Organization Health Behavior in School-aged Children (HBSC) study and the Global School-based Health Survey (GSHS). The former is conducted among children ages 11, 13, and 15 in Canada, the United States, and most European countries every 4 years. The GSHS measures fighting among children aged 13-17 years in 55 low- and middle-income countries.

Among the limitations the study authors acknowledged was the inability to account for when the surveys were completed and when the bans were implemented, enforced, or modified, but they also pointed out the large and diverse sample of countries as a strength of the study.

Dr. Elgar and coauthors reported having no financial relationships. The work was supported by grants from the Canadian Institutes for Health Research, the Social Sciences and Humanities Research Council, and the Canada Research Chairs programme.

SOURCE: Elgar FJ et al. BMJ Open. 2018;8:e021616.

Nationwide bans on corporal punishment of children in the home and school seem to have had a positive impact on fighting among adolescents, with males in those countries about 30% less likely to engage in fighting and females almost 60% less likely to do so, according to a study of school-based health surveys completed by 403,604 adolescents in 88 different countries published in BMJ Open.

“These findings add to a growing body of evidence on links between corporal punishment and adolescent health and safety. A growing number of countries have banned corporal punishment as an acceptable means of child discipline, and this is an important step that should be encouraged,” said Frank J. Elgar, PhD, of McGill University in Montreal and his colleagues. “Health providers are well positioned to offer practical and effective tools that support such approaches to child discipline. Cultural shifts from punitive to positive discipline happen slowly.”

The researchers placed countries into three categories: those that have banned corporate punishment in the home and at school; those that have banned it in school only (which include the United States, Canada, and the United Kingdom); and those that have not banned corporal punishment in either setting.

Frequent fighting rates varied widely, Dr. Elgar and his colleagues noted, ranging from a low of less than 1% among females in Costa Rica, which bans all forms of corporal punishment, to a high of 35% among males in Samoa, which allows corporal punishment in both settings.

The 30 countries with full bans had rates of fighting 31% lower in males and 58% lower in females than the 20 countries with no ban. Thirty-eight countries with bans in schools but not in the home reported less fighting in females only – 44% lower than countries without bans.

The reasons for the gender difference in fighting rates among countries with partial bans is unclear, the authors said. “It could be that males, compared with females, experience more physical violence outside school settings or are affected differently by corporal punishment by teachers,” Dr. Elgar and his coauthors said. “Further investigation is needed.”

The study analyzed findings of two well-established surveys used internationally to measure fighting among adolescents: the World Health Organization Health Behavior in School-aged Children (HBSC) study and the Global School-based Health Survey (GSHS). The former is conducted among children ages 11, 13, and 15 in Canada, the United States, and most European countries every 4 years. The GSHS measures fighting among children aged 13-17 years in 55 low- and middle-income countries.

Among the limitations the study authors acknowledged was the inability to account for when the surveys were completed and when the bans were implemented, enforced, or modified, but they also pointed out the large and diverse sample of countries as a strength of the study.

Dr. Elgar and coauthors reported having no financial relationships. The work was supported by grants from the Canadian Institutes for Health Research, the Social Sciences and Humanities Research Council, and the Canada Research Chairs programme.

SOURCE: Elgar FJ et al. BMJ Open. 2018;8:e021616.

Adults aged 65 years and older with a self-harm history are more likely to die from unnatural causes – specifically suicide – than are those who do not self-harm, according to what researchers called the first study of self-harm that exclusively focused on older adults from the perspective of primary care.

giocalde/Thinkstock

“This work should alert policy makers and primary health care professionals to progress towards implementing preventive measures among older adults who consult with a GP,” lead author Catharine Morgan, PhD, and her coauthors, wrote in the Lancet Psychiatry.

The study, which reviewed the primary care records of 4,124 older adults in the United Kingdom with incidents of self-harm, found that older adults were infrequently referred to mental health specialists while being prescribed potentially toxic tricyclic antidepressants at a high proportion, said Dr. Morgan, of the National Institute for Health Research (NIHR) Greater Manchester (England) Patient Safety Translational Research Centre at the University of Manchester, and her coauthors. They also noted that, “compared with their peers who had not harmed themselves, adults in the self-harm cohort were an estimated 20 times more likely to die unnaturally during the first year after a self-harm episode and three or four times more likely to die unnaturally in subsequent years.”

The coauthors also found that, compared with a comparison cohort, the prevalence of a previous mental illness was twice as high among older adults who had engaged in self-harm (hazard ratio, 2.10; 95% confidence interval, 2.03-2.17). Older adults with a self-harm history also had a 20% higher prevalence of a physical illness (HR, 1.20; 95% CI, 1.17-1.23), compared with those without such a history.

Dr. Morgan and her coauthors also uncovered differing likelihoods of referral to specialists, depending on socioeconomic status of the surrounding area. Older patients in “more socially deprived localities” were less likely to be referred to mental health services. Women also were more likely than men were to be referred, highlighting “an important target for improvement across the health care system.” They also recommended avoiding tricyclics for older patients and encouraged maintaining “frequent medication reviews after self-harm.”

The coauthors noted potential limitations in their study, including reliance on clinicians who entered the primary care records and reluctance of coroners to report suicide as the cause of death in certain scenarios. However, they strongly encouraged general practitioners to intervene early and consider alternative medications when treating older patients who exhibit risk factors.

“Health care professionals should take the opportunity to consider the risk of self-harm when an older person consults with other health problems, especially when major physical illnesses and psychopathology are both present, to reduce the risk of an escalation in self-harming behaviour and associated mortality,” they wrote.

The NIHR Greater Manchester Patient Safety Translational Research Centre funded the study. Dr. Morgan and three of her coauthors declared no conflicts of interest. Two authors reported grants from the NIHR, and one author reported grants from the Department of Health and Social Care and the Healthcare Quality Improvement Partnership.

SOURCE: Morgan C et al. Lancet Psychiatry. 2018 Oct 15. doi: 10.1016/S2215-0366(18)30348-1.

Adults aged 65 years and older with a self-harm history are more likely to die from unnatural causes – specifically suicide – than are those who do not self-harm, according to what researchers called the first study of self-harm that exclusively focused on older adults from the perspective of primary care.

giocalde/Thinkstock

“This work should alert policy makers and primary health care professionals to progress towards implementing preventive measures among older adults who consult with a GP,” lead author Catharine Morgan, PhD, and her coauthors, wrote in the Lancet Psychiatry.

The study, which reviewed the primary care records of 4,124 older adults in the United Kingdom with incidents of self-harm, found that older adults were infrequently referred to mental health specialists while being prescribed potentially toxic tricyclic antidepressants at a high proportion, said Dr. Morgan, of the National Institute for Health Research (NIHR) Greater Manchester (England) Patient Safety Translational Research Centre at the University of Manchester, and her coauthors. They also noted that, “compared with their peers who had not harmed themselves, adults in the self-harm cohort were an estimated 20 times more likely to die unnaturally during the first year after a self-harm episode and three or four times more likely to die unnaturally in subsequent years.”

The coauthors also found that, compared with a comparison cohort, the prevalence of a previous mental illness was twice as high among older adults who had engaged in self-harm (hazard ratio, 2.10; 95% confidence interval, 2.03-2.17). Older adults with a self-harm history also had a 20% higher prevalence of a physical illness (HR, 1.20; 95% CI, 1.17-1.23), compared with those without such a history.

Dr. Morgan and her coauthors also uncovered differing likelihoods of referral to specialists, depending on socioeconomic status of the surrounding area. Older patients in “more socially deprived localities” were less likely to be referred to mental health services. Women also were more likely than men were to be referred, highlighting “an important target for improvement across the health care system.” They also recommended avoiding tricyclics for older patients and encouraged maintaining “frequent medication reviews after self-harm.”

The coauthors noted potential limitations in their study, including reliance on clinicians who entered the primary care records and reluctance of coroners to report suicide as the cause of death in certain scenarios. However, they strongly encouraged general practitioners to intervene early and consider alternative medications when treating older patients who exhibit risk factors.

“Health care professionals should take the opportunity to consider the risk of self-harm when an older person consults with other health problems, especially when major physical illnesses and psychopathology are both present, to reduce the risk of an escalation in self-harming behaviour and associated mortality,” they wrote.

The NIHR Greater Manchester Patient Safety Translational Research Centre funded the study. Dr. Morgan and three of her coauthors declared no conflicts of interest. Two authors reported grants from the NIHR, and one author reported grants from the Department of Health and Social Care and the Healthcare Quality Improvement Partnership.

SOURCE: Morgan C et al. Lancet Psychiatry. 2018 Oct 15. doi: 10.1016/S2215-0366(18)30348-1.

Adults aged 65 years and older with a self-harm history are more likely to die from unnatural causes – specifically suicide – than are those who do not self-harm, according to what researchers called the first study of self-harm that exclusively focused on older adults from the perspective of primary care.

giocalde/Thinkstock

“This work should alert policy makers and primary health care professionals to progress towards implementing preventive measures among older adults who consult with a GP,” lead author Catharine Morgan, PhD, and her coauthors, wrote in the Lancet Psychiatry.

The study, which reviewed the primary care records of 4,124 older adults in the United Kingdom with incidents of self-harm, found that older adults were infrequently referred to mental health specialists while being prescribed potentially toxic tricyclic antidepressants at a high proportion, said Dr. Morgan, of the National Institute for Health Research (NIHR) Greater Manchester (England) Patient Safety Translational Research Centre at the University of Manchester, and her coauthors. They also noted that, “compared with their peers who had not harmed themselves, adults in the self-harm cohort were an estimated 20 times more likely to die unnaturally during the first year after a self-harm episode and three or four times more likely to die unnaturally in subsequent years.”

The coauthors also found that, compared with a comparison cohort, the prevalence of a previous mental illness was twice as high among older adults who had engaged in self-harm (hazard ratio, 2.10; 95% confidence interval, 2.03-2.17). Older adults with a self-harm history also had a 20% higher prevalence of a physical illness (HR, 1.20; 95% CI, 1.17-1.23), compared with those without such a history.

Dr. Morgan and her coauthors also uncovered differing likelihoods of referral to specialists, depending on socioeconomic status of the surrounding area. Older patients in “more socially deprived localities” were less likely to be referred to mental health services. Women also were more likely than men were to be referred, highlighting “an important target for improvement across the health care system.” They also recommended avoiding tricyclics for older patients and encouraged maintaining “frequent medication reviews after self-harm.”

The coauthors noted potential limitations in their study, including reliance on clinicians who entered the primary care records and reluctance of coroners to report suicide as the cause of death in certain scenarios. However, they strongly encouraged general practitioners to intervene early and consider alternative medications when treating older patients who exhibit risk factors.

“Health care professionals should take the opportunity to consider the risk of self-harm when an older person consults with other health problems, especially when major physical illnesses and psychopathology are both present, to reduce the risk of an escalation in self-harming behaviour and associated mortality,” they wrote.

The NIHR Greater Manchester Patient Safety Translational Research Centre funded the study. Dr. Morgan and three of her coauthors declared no conflicts of interest. Two authors reported grants from the NIHR, and one author reported grants from the Department of Health and Social Care and the Healthcare Quality Improvement Partnership.

SOURCE: Morgan C et al. Lancet Psychiatry. 2018 Oct 15. doi: 10.1016/S2215-0366(18)30348-1.

MUNICH – A formula for scoring diet quality that during its development phase significantly correlated with overall survival received validation when tested using three independent, large data sets that together included almost 80,000 people.

Vidyard Video

With these new findings the PURE Healthy Diet Score had now shown consistent, significant correlations with overall survival and the incidence of MI and stroke in a total of about 218,000 people from 50 countries who had been followed in any of four separate studies. This new validation is especially notable because the optimal diet identified by the scoring system diverged from current American diet recommendations in two important ways: Optimal food consumption included three daily servings of full-fat dairy and 1.5 servings daily of unprocessed red meat Andrew Mente, PhD, reported at the annual congress of the European Society of Cardiology. He explained this finding as possibly related to the global scope of the study, which included many people from low- or middle-income countries where average diets are usually low in important nutrients.

The PURE Healthy Diet Score should now be “considered for broad, global dietary recommendations,” Dr. Mente said in a video interview. Testing a diet profile in a large, randomized trial would be ideal, but also difficult to run. Until then, the only alternative for defining an evidence-based optimal diet is observational data, as in the current study. The PURE Healthy Diet Score “is ready for routine use,” said Dr. Mente, a clinical epidemiologist at McMaster University in Hamilton, Canada.

In a model that adjusted for all measured confounders the people in PURE with the best-outcome diet had a statistically significant, 25% reduced all-cause mortality, compared with people in the quintile with the worst diet.

To validate the formula the researchers used data collected from three other trials run by their group at McMaster University:

• The ONTARGET and TRANSCEND studies (N Engl J Med. 2008 Apr 10;358[15]:1547-58), which together included diet and outcomes data for 31,546 patients with vascular disease. Diet analysis and scoring showed that enrolled people in the quintile with the highest score had a statistically significant 24% relative reduction in mortality, compared with the quintile with the worst score after adjusting for measured confounders.
• The INTERHEART study (Lancet. 2004 Sep 11;364[9438]:937-52), which had data for 27,098 people and showed that the primary outcome of incident MI was a statistically significant 22% lower after adjustment in the quintile with the best diet score, compared with the quintile with the worst score.
• The INTERSTROKE study (Lancet. 2016 Aug 20;388[10046]:761-75), with data for 20,834 people, showed that the rate of stroke was a statistically significant 25% lower after adjustment in the quintile with the highest diet score, compared with those with the lowest score.

Dr. Mente had no financial disclosures.

[email protected]

MUNICH – A formula for scoring diet quality that during its development phase significantly correlated with overall survival received validation when tested using three independent, large data sets that together included almost 80,000 people.

Vidyard Video

With these new findings the PURE Healthy Diet Score had now shown consistent, significant correlations with overall survival and the incidence of MI and stroke in a total of about 218,000 people from 50 countries who had been followed in any of four separate studies. This new validation is especially notable because the optimal diet identified by the scoring system diverged from current American diet recommendations in two important ways: Optimal food consumption included three daily servings of full-fat dairy and 1.5 servings daily of unprocessed red meat Andrew Mente, PhD, reported at the annual congress of the European Society of Cardiology. He explained this finding as possibly related to the global scope of the study, which included many people from low- or middle-income countries where average diets are usually low in important nutrients.

The PURE Healthy Diet Score should now be “considered for broad, global dietary recommendations,” Dr. Mente said in a video interview. Testing a diet profile in a large, randomized trial would be ideal, but also difficult to run. Until then, the only alternative for defining an evidence-based optimal diet is observational data, as in the current study. The PURE Healthy Diet Score “is ready for routine use,” said Dr. Mente, a clinical epidemiologist at McMaster University in Hamilton, Canada.

In a model that adjusted for all measured confounders the people in PURE with the best-outcome diet had a statistically significant, 25% reduced all-cause mortality, compared with people in the quintile with the worst diet.

To validate the formula the researchers used data collected from three other trials run by their group at McMaster University:

• The ONTARGET and TRANSCEND studies (N Engl J Med. 2008 Apr 10;358[15]:1547-58), which together included diet and outcomes data for 31,546 patients with vascular disease. Diet analysis and scoring showed that enrolled people in the quintile with the highest score had a statistically significant 24% relative reduction in mortality, compared with the quintile with the worst score after adjusting for measured confounders.
• The INTERHEART study (Lancet. 2004 Sep 11;364[9438]:937-52), which had data for 27,098 people and showed that the primary outcome of incident MI was a statistically significant 22% lower after adjustment in the quintile with the best diet score, compared with the quintile with the worst score.
• The INTERSTROKE study (Lancet. 2016 Aug 20;388[10046]:761-75), with data for 20,834 people, showed that the rate of stroke was a statistically significant 25% lower after adjustment in the quintile with the highest diet score, compared with those with the lowest score.

Dr. Mente had no financial disclosures.

[email protected]

MUNICH – A formula for scoring diet quality that during its development phase significantly correlated with overall survival received validation when tested using three independent, large data sets that together included almost 80,000 people.

Vidyard Video

With these new findings the PURE Healthy Diet Score had now shown consistent, significant correlations with overall survival and the incidence of MI and stroke in a total of about 218,000 people from 50 countries who had been followed in any of four separate studies. This new validation is especially notable because the optimal diet identified by the scoring system diverged from current American diet recommendations in two important ways: Optimal food consumption included three daily servings of full-fat dairy and 1.5 servings daily of unprocessed red meat Andrew Mente, PhD, reported at the annual congress of the European Society of Cardiology. He explained this finding as possibly related to the global scope of the study, which included many people from low- or middle-income countries where average diets are usually low in important nutrients.

The PURE Healthy Diet Score should now be “considered for broad, global dietary recommendations,” Dr. Mente said in a video interview. Testing a diet profile in a large, randomized trial would be ideal, but also difficult to run. Until then, the only alternative for defining an evidence-based optimal diet is observational data, as in the current study. The PURE Healthy Diet Score “is ready for routine use,” said Dr. Mente, a clinical epidemiologist at McMaster University in Hamilton, Canada.

In a model that adjusted for all measured confounders the people in PURE with the best-outcome diet had a statistically significant, 25% reduced all-cause mortality, compared with people in the quintile with the worst diet.

To validate the formula the researchers used data collected from three other trials run by their group at McMaster University:

• The ONTARGET and TRANSCEND studies (N Engl J Med. 2008 Apr 10;358[15]:1547-58), which together included diet and outcomes data for 31,546 patients with vascular disease. Diet analysis and scoring showed that enrolled people in the quintile with the highest score had a statistically significant 24% relative reduction in mortality, compared with the quintile with the worst score after adjusting for measured confounders.
• The INTERHEART study (Lancet. 2004 Sep 11;364[9438]:937-52), which had data for 27,098 people and showed that the primary outcome of incident MI was a statistically significant 22% lower after adjustment in the quintile with the best diet score, compared with the quintile with the worst score.
• The INTERSTROKE study (Lancet. 2016 Aug 20;388[10046]:761-75), with data for 20,834 people, showed that the rate of stroke was a statistically significant 25% lower after adjustment in the quintile with the highest diet score, compared with those with the lowest score.

Dr. Mente had no financial disclosures.

[email protected]

DUBROVNIK, CROATIA – Long-term efficacy and toxicity should inform decisions about tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), according to one expert.

Studies have indicated that long-term survival rates are similar whether CML patients receive frontline treatment with imatinib or second-generation TKIs. But the newer TKIs pose a higher risk of uncommon toxicities, Hagop M. Kantarjian, MD, said during the keynote presentation at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Dr. Kantarjian, a professor at MD Anderson Cancer Center in Houston, said most CML patients should receive daily treatment with TKIs – even if they are in complete cytogenetic response or 100% Philadelphia chromosome positive – because they will live longer.

Frontline treatment options for CML that are approved by the Food and Drug Administration include imatinib, dasatinib, nilotinib, and bosutinib.

Dr. Kantarjian noted that dasatinib and nilotinib bested imatinib in early analyses from clinical trials, but all three TKIs produced similar rates of overall survival (OS) and progression-free survival (PFS) at extended follow-up.

Dasatinib and imatinib produced similar rates of 5-year OS and PFS in the DASISION trial (J Clin Oncol. 2016 Jul 10;34[20]:2333-40).

In ENESTnd, 5-year OS and PFS rates were similar with nilotinib and imatinib (Leukemia. 2016 May;30[5]:1044-54).

However, the higher incidence of uncommon toxicities with the newer TKIs must be taken into account, Dr. Kantarjian said.
 

Choosing a TKI

Dr. Kantarjian recommends frontline imatinib for older patients (aged 65-70) and those who are low risk based on their Sokal score.

Second-generation TKIs should be given up front to patients who are at higher risk by Sokal and for “very young patients in whom early treatment discontinuation is important,” he said.

“In accelerated or blast phase, I always use the second-generation TKIs,” he said. “If there’s no binding mutation, I prefer dasatinib. I think it’s the most potent of them. If there are toxicities with dasatinib, bosutinib is equivalent in efficacy, so they are interchangeable.”

A TKI should not be discarded unless there is loss of complete cytogenetic response – not major molecular response – at the maximum tolerated adjusted dose that does not cause grade 3-4 toxicities or chronic grade 2 toxicities, Dr. Kantarjian added.

“We have to remember that we can go down on the dosages of, for example, imatinib, down to 200 mg a day, dasatinib as low as 20 mg a day, nilotinib as low as 150 mg twice a day or even 200 mg daily, and bosutinib down to 200 mg daily,” he said. “So if we have a patient who’s responding with side effects, we should not abandon the particular TKI, we should try to manipulate the dose schedule if they are having a good response.”

Dr. Kantarjian noted that pleural effusion is a toxicity of particular concern with dasatinib, but lowering the dose to 50 mg daily results in similar efficacy and significantly less toxicity than 100 mg daily. For patients over the age of 70, a 20-mg dose can be used.

Vaso-occlusive and vasospastic reactions are increasingly observed in patients treated with nilotinib. For that reason, Dr. Kantarjian said he prefers to forgo up-front nilotinib, particularly in patients who have cardiovascular or neurotoxic problems.

“The incidence of vaso-occlusive and vasospastic reactions is now close to 10%-15% at about 10 years with nilotinib,” Dr. Kantarjian said. “So it is not a trivial toxicity.”

For patients with vaso-occlusive/vasospastic reactions, “bosutinib is probably the safest drug,” Dr. Kantarjian said.

For second- or third-line therapy, patients can receive ponatinib or a second-generation TKI (dasatinib, nilotinib, or bosutinib), as well as omacetaxine or allogeneic stem cell transplant.

“If you disregard toxicities, I think ponatinib is the most powerful TKI, and I think that’s because we are using it at a higher dose that produces so many toxicities,” Dr. Kantarjian said.

Ponatinib is not used up front because of these toxicities, particularly pancreatitis, skin rashes, vaso-occlusive disorders, and hypertension, he added.

Dr. Kantarjian suggests giving ponatinib at 30 mg daily in patients with T315I mutation and those without guiding mutations who are resistant to second-generation TKIs.
 

Discontinuing a TKI

Dr. Kantarjian said patients can discontinue TKI therapy if they:

• Are low- or intermediate-risk by Sokal.
• Have quantifiable BCR-ABL transcripts.
• Are in chronic phase.
• Achieved an optimal response to their first TKI.
• Have been on TKI therapy for more than 8 years.
• Achieved a complete molecular response.
• Have had a molecular response for more than 2-3 years.
• Are available for monitoring every other month for the first 2 years.

Dr. Kantarjian did not report any conflicts of interest at the meeting. However, he has previously reported relationships with Novartis, Bristol-Myers Squibb, Pfizer, and Ariad Pharmaceuticals.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.

[email protected]

DUBROVNIK, CROATIA – Long-term efficacy and toxicity should inform decisions about tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), according to one expert.

Studies have indicated that long-term survival rates are similar whether CML patients receive frontline treatment with imatinib or second-generation TKIs. But the newer TKIs pose a higher risk of uncommon toxicities, Hagop M. Kantarjian, MD, said during the keynote presentation at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Dr. Kantarjian, a professor at MD Anderson Cancer Center in Houston, said most CML patients should receive daily treatment with TKIs – even if they are in complete cytogenetic response or 100% Philadelphia chromosome positive – because they will live longer.

Frontline treatment options for CML that are approved by the Food and Drug Administration include imatinib, dasatinib, nilotinib, and bosutinib.

Dr. Kantarjian noted that dasatinib and nilotinib bested imatinib in early analyses from clinical trials, but all three TKIs produced similar rates of overall survival (OS) and progression-free survival (PFS) at extended follow-up.

Dasatinib and imatinib produced similar rates of 5-year OS and PFS in the DASISION trial (J Clin Oncol. 2016 Jul 10;34[20]:2333-40).

In ENESTnd, 5-year OS and PFS rates were similar with nilotinib and imatinib (Leukemia. 2016 May;30[5]:1044-54).

However, the higher incidence of uncommon toxicities with the newer TKIs must be taken into account, Dr. Kantarjian said.
 

Choosing a TKI

Dr. Kantarjian recommends frontline imatinib for older patients (aged 65-70) and those who are low risk based on their Sokal score.

Second-generation TKIs should be given up front to patients who are at higher risk by Sokal and for “very young patients in whom early treatment discontinuation is important,” he said.

“In accelerated or blast phase, I always use the second-generation TKIs,” he said. “If there’s no binding mutation, I prefer dasatinib. I think it’s the most potent of them. If there are toxicities with dasatinib, bosutinib is equivalent in efficacy, so they are interchangeable.”

A TKI should not be discarded unless there is loss of complete cytogenetic response – not major molecular response – at the maximum tolerated adjusted dose that does not cause grade 3-4 toxicities or chronic grade 2 toxicities, Dr. Kantarjian added.

“We have to remember that we can go down on the dosages of, for example, imatinib, down to 200 mg a day, dasatinib as low as 20 mg a day, nilotinib as low as 150 mg twice a day or even 200 mg daily, and bosutinib down to 200 mg daily,” he said. “So if we have a patient who’s responding with side effects, we should not abandon the particular TKI, we should try to manipulate the dose schedule if they are having a good response.”

Dr. Kantarjian noted that pleural effusion is a toxicity of particular concern with dasatinib, but lowering the dose to 50 mg daily results in similar efficacy and significantly less toxicity than 100 mg daily. For patients over the age of 70, a 20-mg dose can be used.

Vaso-occlusive and vasospastic reactions are increasingly observed in patients treated with nilotinib. For that reason, Dr. Kantarjian said he prefers to forgo up-front nilotinib, particularly in patients who have cardiovascular or neurotoxic problems.

“The incidence of vaso-occlusive and vasospastic reactions is now close to 10%-15% at about 10 years with nilotinib,” Dr. Kantarjian said. “So it is not a trivial toxicity.”

For patients with vaso-occlusive/vasospastic reactions, “bosutinib is probably the safest drug,” Dr. Kantarjian said.

For second- or third-line therapy, patients can receive ponatinib or a second-generation TKI (dasatinib, nilotinib, or bosutinib), as well as omacetaxine or allogeneic stem cell transplant.

“If you disregard toxicities, I think ponatinib is the most powerful TKI, and I think that’s because we are using it at a higher dose that produces so many toxicities,” Dr. Kantarjian said.

Ponatinib is not used up front because of these toxicities, particularly pancreatitis, skin rashes, vaso-occlusive disorders, and hypertension, he added.

Dr. Kantarjian suggests giving ponatinib at 30 mg daily in patients with T315I mutation and those without guiding mutations who are resistant to second-generation TKIs.
 

Discontinuing a TKI

Dr. Kantarjian said patients can discontinue TKI therapy if they:

• Are low- or intermediate-risk by Sokal.
• Have quantifiable BCR-ABL transcripts.
• Are in chronic phase.
• Achieved an optimal response to their first TKI.
• Have been on TKI therapy for more than 8 years.
• Achieved a complete molecular response.
• Have had a molecular response for more than 2-3 years.
• Are available for monitoring every other month for the first 2 years.

Dr. Kantarjian did not report any conflicts of interest at the meeting. However, he has previously reported relationships with Novartis, Bristol-Myers Squibb, Pfizer, and Ariad Pharmaceuticals.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.

[email protected]

DUBROVNIK, CROATIA – Long-term efficacy and toxicity should inform decisions about tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), according to one expert.

Studies have indicated that long-term survival rates are similar whether CML patients receive frontline treatment with imatinib or second-generation TKIs. But the newer TKIs pose a higher risk of uncommon toxicities, Hagop M. Kantarjian, MD, said during the keynote presentation at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Dr. Kantarjian, a professor at MD Anderson Cancer Center in Houston, said most CML patients should receive daily treatment with TKIs – even if they are in complete cytogenetic response or 100% Philadelphia chromosome positive – because they will live longer.

Frontline treatment options for CML that are approved by the Food and Drug Administration include imatinib, dasatinib, nilotinib, and bosutinib.

Dr. Kantarjian noted that dasatinib and nilotinib bested imatinib in early analyses from clinical trials, but all three TKIs produced similar rates of overall survival (OS) and progression-free survival (PFS) at extended follow-up.

Dasatinib and imatinib produced similar rates of 5-year OS and PFS in the DASISION trial (J Clin Oncol. 2016 Jul 10;34[20]:2333-40).

In ENESTnd, 5-year OS and PFS rates were similar with nilotinib and imatinib (Leukemia. 2016 May;30[5]:1044-54).

However, the higher incidence of uncommon toxicities with the newer TKIs must be taken into account, Dr. Kantarjian said.
 

Choosing a TKI

Dr. Kantarjian recommends frontline imatinib for older patients (aged 65-70) and those who are low risk based on their Sokal score.

Second-generation TKIs should be given up front to patients who are at higher risk by Sokal and for “very young patients in whom early treatment discontinuation is important,” he said.

“In accelerated or blast phase, I always use the second-generation TKIs,” he said. “If there’s no binding mutation, I prefer dasatinib. I think it’s the most potent of them. If there are toxicities with dasatinib, bosutinib is equivalent in efficacy, so they are interchangeable.”

A TKI should not be discarded unless there is loss of complete cytogenetic response – not major molecular response – at the maximum tolerated adjusted dose that does not cause grade 3-4 toxicities or chronic grade 2 toxicities, Dr. Kantarjian added.

“We have to remember that we can go down on the dosages of, for example, imatinib, down to 200 mg a day, dasatinib as low as 20 mg a day, nilotinib as low as 150 mg twice a day or even 200 mg daily, and bosutinib down to 200 mg daily,” he said. “So if we have a patient who’s responding with side effects, we should not abandon the particular TKI, we should try to manipulate the dose schedule if they are having a good response.”

Dr. Kantarjian noted that pleural effusion is a toxicity of particular concern with dasatinib, but lowering the dose to 50 mg daily results in similar efficacy and significantly less toxicity than 100 mg daily. For patients over the age of 70, a 20-mg dose can be used.

Vaso-occlusive and vasospastic reactions are increasingly observed in patients treated with nilotinib. For that reason, Dr. Kantarjian said he prefers to forgo up-front nilotinib, particularly in patients who have cardiovascular or neurotoxic problems.

“The incidence of vaso-occlusive and vasospastic reactions is now close to 10%-15% at about 10 years with nilotinib,” Dr. Kantarjian said. “So it is not a trivial toxicity.”

For patients with vaso-occlusive/vasospastic reactions, “bosutinib is probably the safest drug,” Dr. Kantarjian said.

For second- or third-line therapy, patients can receive ponatinib or a second-generation TKI (dasatinib, nilotinib, or bosutinib), as well as omacetaxine or allogeneic stem cell transplant.

“If you disregard toxicities, I think ponatinib is the most powerful TKI, and I think that’s because we are using it at a higher dose that produces so many toxicities,” Dr. Kantarjian said.

Ponatinib is not used up front because of these toxicities, particularly pancreatitis, skin rashes, vaso-occlusive disorders, and hypertension, he added.

Dr. Kantarjian suggests giving ponatinib at 30 mg daily in patients with T315I mutation and those without guiding mutations who are resistant to second-generation TKIs.
 

Discontinuing a TKI

Dr. Kantarjian said patients can discontinue TKI therapy if they:

• Are low- or intermediate-risk by Sokal.
• Have quantifiable BCR-ABL transcripts.
• Are in chronic phase.
• Achieved an optimal response to their first TKI.
• Have been on TKI therapy for more than 8 years.
• Achieved a complete molecular response.
• Have had a molecular response for more than 2-3 years.
• Are available for monitoring every other month for the first 2 years.

Dr. Kantarjian did not report any conflicts of interest at the meeting. However, he has previously reported relationships with Novartis, Bristol-Myers Squibb, Pfizer, and Ariad Pharmaceuticals.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.

[email protected]

As we relentlessly enter information into our EHRs, we typically perceive that we are just recording information about our patients to provide continuity of care and have an accurate representation of what was done. While that is true, the information we record is now increasingly being examined for many additional purposes. A whole new area of study has emerged over the last few years known as “real-world data,” and innovators are beginning to explore how machine learning (currently employed in other areas by such companies as Amazon and Google) may be used to improve the care of patients. The information we are putting into our EHRs is being translated into discrete data and is then combined with data from labs, pharmacies, and claims databases to examine how medications actually work when used in the wide and wild world of practice.

Let’s first talk about why real-world data are important. Traditionally, the evidence we rely upon in medicine has come from randomized trials to give us an unbiased assessment about the safety and the efficacy of the medications that we use. The Achilles’ heel of randomized trials is that, by their nature, they employ a carefully defined group of patients – with specific inclusion and exclusion criteria – who may not be like the patients in our practices. Randomized trials are also conducted in sites that are different than most of our offices. The clinics where randomized trials are conducted have dedicated personnel to follow up on patients, to make sure that patients take their medications, and ensure that patients remember their follow up visits. What this means is that the results in of those studies might not reflect the results seen in the real world.

A nice example of this was reported recently in the area of diabetes management. Randomized trials have shown that the glucagonlike peptide–1 (GLP-1) class of medications have about twice the effectiveness in lowering hemoglobin A_1c as do the dipeptidyl peptidase–4 (DPP-4) inhibitor class of medications, but that difference in efficacy is not seen in practice. When looked at in real-world studies, the two classes of medications have about the same glucose-lowering efficacy. Why might that be? In reality, it might be that compliance with GLP-1s is less than that of DPP-4s because of the side effects of nausea and GI intolerance. When patients miss more doses of their GLP-1, they do not achieve the HbA_1c lowering seen in trials in which compliance is far better.¹

This exploration of real-world outcomes is just a first step in using the information documented in our charts. The exciting next step will be machine learning, also called deep learning.² In this process, computers look at an enormous number of data points and find relationships that would otherwise not be detected. Imagine a supercomputer analyzing every blood pressure after any medication is changed across thousands, or even millions, of patients, and linking the outcome of that medication choice with the next blood pressure.³ Then imagine the computer meshing millions of data points that include all patients’ weights, ages, sexes, family histories of cardiovascular disease, renal function, etc. and matching those parameters with the specific medication and follow-up blood pressures. While much has been discussed about using genetics to advance personalized medicine, one can imagine these machine-based algorithms discovering connections about which medications work best for individuals with specific characteristics – without the need for additional testing. When the final loop of this cascade is connected, the computer could present recommendations to the clinician about which medication is optimal for the patient and then refine these recommendations, based on outcomes, to optimize safety and efficacy.

Some have argued that there is no way a computer will be able to perform as well as an experienced clinician who utilizes a combination of data and intuition to choose the best medication for his or her patient. This argument is similar to the controversy over autonomous driving cars. Many have asked how you can be assured that the cars will never have an accident. That is, of course, the wrong question. The correct question, as articulated very nicely by one of the innovators in that field, George Holtz, is how we can make a car that is safer than the way that cars are currently being driven (which means fewer deaths than the 15,000 that occur annually with humans behind the wheel).⁴

Our current method of providing care often leaves patients without appropriate guideline-recommended medications, and many don’t reach their HbA_1c, blood pressure, cholesterol, and asthma-control goals. The era of machine learning with machine-generated algorithms may be much closer than we think, which will allow us to spend more time talking with patients, educating them about their disease, and supporting them in their efforts to remain healthy – an attractive future for both us and our patients.
 

References

1. Carls GS et al. Understanding the gap between efficacy in randomized controlled trials and effectiveness in real-world use of GLP-1RA and DPP-4 therapies in patients with type 2 diabetes. Diabetes Care. 2017 Nov;40(11):1469-78.

2. Naylor CD. On the prospects for a (deep) learning health care system. JAMA. 2018 Sep 18;320(11):1099-100.

3. Wang YR et al. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch Intern Med. 2007 Jan 22;167(2):141-7.

4. Super Hacker George Hotz: “I can make your car drive itself for under $1,000.”

As we relentlessly enter information into our EHRs, we typically perceive that we are just recording information about our patients to provide continuity of care and have an accurate representation of what was done. While that is true, the information we record is now increasingly being examined for many additional purposes. A whole new area of study has emerged over the last few years known as “real-world data,” and innovators are beginning to explore how machine learning (currently employed in other areas by such companies as Amazon and Google) may be used to improve the care of patients. The information we are putting into our EHRs is being translated into discrete data and is then combined with data from labs, pharmacies, and claims databases to examine how medications actually work when used in the wide and wild world of practice.

Let’s first talk about why real-world data are important. Traditionally, the evidence we rely upon in medicine has come from randomized trials to give us an unbiased assessment about the safety and the efficacy of the medications that we use. The Achilles’ heel of randomized trials is that, by their nature, they employ a carefully defined group of patients – with specific inclusion and exclusion criteria – who may not be like the patients in our practices. Randomized trials are also conducted in sites that are different than most of our offices. The clinics where randomized trials are conducted have dedicated personnel to follow up on patients, to make sure that patients take their medications, and ensure that patients remember their follow up visits. What this means is that the results in of those studies might not reflect the results seen in the real world.

A nice example of this was reported recently in the area of diabetes management. Randomized trials have shown that the glucagonlike peptide–1 (GLP-1) class of medications have about twice the effectiveness in lowering hemoglobin A_1c as do the dipeptidyl peptidase–4 (DPP-4) inhibitor class of medications, but that difference in efficacy is not seen in practice. When looked at in real-world studies, the two classes of medications have about the same glucose-lowering efficacy. Why might that be? In reality, it might be that compliance with GLP-1s is less than that of DPP-4s because of the side effects of nausea and GI intolerance. When patients miss more doses of their GLP-1, they do not achieve the HbA_1c lowering seen in trials in which compliance is far better.¹

This exploration of real-world outcomes is just a first step in using the information documented in our charts. The exciting next step will be machine learning, also called deep learning.² In this process, computers look at an enormous number of data points and find relationships that would otherwise not be detected. Imagine a supercomputer analyzing every blood pressure after any medication is changed across thousands, or even millions, of patients, and linking the outcome of that medication choice with the next blood pressure.³ Then imagine the computer meshing millions of data points that include all patients’ weights, ages, sexes, family histories of cardiovascular disease, renal function, etc. and matching those parameters with the specific medication and follow-up blood pressures. While much has been discussed about using genetics to advance personalized medicine, one can imagine these machine-based algorithms discovering connections about which medications work best for individuals with specific characteristics – without the need for additional testing. When the final loop of this cascade is connected, the computer could present recommendations to the clinician about which medication is optimal for the patient and then refine these recommendations, based on outcomes, to optimize safety and efficacy.

Some have argued that there is no way a computer will be able to perform as well as an experienced clinician who utilizes a combination of data and intuition to choose the best medication for his or her patient. This argument is similar to the controversy over autonomous driving cars. Many have asked how you can be assured that the cars will never have an accident. That is, of course, the wrong question. The correct question, as articulated very nicely by one of the innovators in that field, George Holtz, is how we can make a car that is safer than the way that cars are currently being driven (which means fewer deaths than the 15,000 that occur annually with humans behind the wheel).⁴

Our current method of providing care often leaves patients without appropriate guideline-recommended medications, and many don’t reach their HbA_1c, blood pressure, cholesterol, and asthma-control goals. The era of machine learning with machine-generated algorithms may be much closer than we think, which will allow us to spend more time talking with patients, educating them about their disease, and supporting them in their efforts to remain healthy – an attractive future for both us and our patients.
 

References

1. Carls GS et al. Understanding the gap between efficacy in randomized controlled trials and effectiveness in real-world use of GLP-1RA and DPP-4 therapies in patients with type 2 diabetes. Diabetes Care. 2017 Nov;40(11):1469-78.

2. Naylor CD. On the prospects for a (deep) learning health care system. JAMA. 2018 Sep 18;320(11):1099-100.

3. Wang YR et al. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch Intern Med. 2007 Jan 22;167(2):141-7.

4. Super Hacker George Hotz: “I can make your car drive itself for under $1,000.”

As we relentlessly enter information into our EHRs, we typically perceive that we are just recording information about our patients to provide continuity of care and have an accurate representation of what was done. While that is true, the information we record is now increasingly being examined for many additional purposes. A whole new area of study has emerged over the last few years known as “real-world data,” and innovators are beginning to explore how machine learning (currently employed in other areas by such companies as Amazon and Google) may be used to improve the care of patients. The information we are putting into our EHRs is being translated into discrete data and is then combined with data from labs, pharmacies, and claims databases to examine how medications actually work when used in the wide and wild world of practice.

Let’s first talk about why real-world data are important. Traditionally, the evidence we rely upon in medicine has come from randomized trials to give us an unbiased assessment about the safety and the efficacy of the medications that we use. The Achilles’ heel of randomized trials is that, by their nature, they employ a carefully defined group of patients – with specific inclusion and exclusion criteria – who may not be like the patients in our practices. Randomized trials are also conducted in sites that are different than most of our offices. The clinics where randomized trials are conducted have dedicated personnel to follow up on patients, to make sure that patients take their medications, and ensure that patients remember their follow up visits. What this means is that the results in of those studies might not reflect the results seen in the real world.

A nice example of this was reported recently in the area of diabetes management. Randomized trials have shown that the glucagonlike peptide–1 (GLP-1) class of medications have about twice the effectiveness in lowering hemoglobin A_1c as do the dipeptidyl peptidase–4 (DPP-4) inhibitor class of medications, but that difference in efficacy is not seen in practice. When looked at in real-world studies, the two classes of medications have about the same glucose-lowering efficacy. Why might that be? In reality, it might be that compliance with GLP-1s is less than that of DPP-4s because of the side effects of nausea and GI intolerance. When patients miss more doses of their GLP-1, they do not achieve the HbA_1c lowering seen in trials in which compliance is far better.¹

This exploration of real-world outcomes is just a first step in using the information documented in our charts. The exciting next step will be machine learning, also called deep learning.² In this process, computers look at an enormous number of data points and find relationships that would otherwise not be detected. Imagine a supercomputer analyzing every blood pressure after any medication is changed across thousands, or even millions, of patients, and linking the outcome of that medication choice with the next blood pressure.³ Then imagine the computer meshing millions of data points that include all patients’ weights, ages, sexes, family histories of cardiovascular disease, renal function, etc. and matching those parameters with the specific medication and follow-up blood pressures. While much has been discussed about using genetics to advance personalized medicine, one can imagine these machine-based algorithms discovering connections about which medications work best for individuals with specific characteristics – without the need for additional testing. When the final loop of this cascade is connected, the computer could present recommendations to the clinician about which medication is optimal for the patient and then refine these recommendations, based on outcomes, to optimize safety and efficacy.

Some have argued that there is no way a computer will be able to perform as well as an experienced clinician who utilizes a combination of data and intuition to choose the best medication for his or her patient. This argument is similar to the controversy over autonomous driving cars. Many have asked how you can be assured that the cars will never have an accident. That is, of course, the wrong question. The correct question, as articulated very nicely by one of the innovators in that field, George Holtz, is how we can make a car that is safer than the way that cars are currently being driven (which means fewer deaths than the 15,000 that occur annually with humans behind the wheel).⁴

Our current method of providing care often leaves patients without appropriate guideline-recommended medications, and many don’t reach their HbA_1c, blood pressure, cholesterol, and asthma-control goals. The era of machine learning with machine-generated algorithms may be much closer than we think, which will allow us to spend more time talking with patients, educating them about their disease, and supporting them in their efforts to remain healthy – an attractive future for both us and our patients.
 

References

1. Carls GS et al. Understanding the gap between efficacy in randomized controlled trials and effectiveness in real-world use of GLP-1RA and DPP-4 therapies in patients with type 2 diabetes. Diabetes Care. 2017 Nov;40(11):1469-78.

2. Naylor CD. On the prospects for a (deep) learning health care system. JAMA. 2018 Sep 18;320(11):1099-100.

3. Wang YR et al. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch Intern Med. 2007 Jan 22;167(2):141-7.

4. Super Hacker George Hotz: “I can make your car drive itself for under $1,000.”