Clinical question: Does an initial stable international normalized ratio (INR) predict long-term stability?

Background: Warfarin decreases stroke risk among patients with atrial fibrillation; however, it interacts with food and drugs and requires monitoring to achieve a therapeutic INR. It is unclear if patients on warfarin with an initial stable INR value remain stable over time. Additionally, it is controversial whether patients on warfarin with previously stable INRs should benefit from switching to a non–vitamin K oral anticoagulant.

Study design: Retrospective study.

Setting: Outpatient clinics.

Only 26% of patients taking warfarin had a stable INR during the first 6 months, and only 34% continued to have a stable INR in the subsequent year.

Bottom line: Initial stable INR within the first 6 months among patients taking warfarin does not predict long-term INR stability in the subsequent year.

Citation: Pokorney SD, Simon DN, Thomas L, et al. Stability of international normalized ratios in patients taking long-term warfarin therapy. JAMA.2016;316(6):661-663

Dr. Florindez is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

Clinical question: Does an initial stable international normalized ratio (INR) predict long-term stability?

Background: Warfarin decreases stroke risk among patients with atrial fibrillation; however, it interacts with food and drugs and requires monitoring to achieve a therapeutic INR. It is unclear if patients on warfarin with an initial stable INR value remain stable over time. Additionally, it is controversial whether patients on warfarin with previously stable INRs should benefit from switching to a non–vitamin K oral anticoagulant.

Study design: Retrospective study.

Setting: Outpatient clinics.

Only 26% of patients taking warfarin had a stable INR during the first 6 months, and only 34% continued to have a stable INR in the subsequent year.

Bottom line: Initial stable INR within the first 6 months among patients taking warfarin does not predict long-term INR stability in the subsequent year.

Citation: Pokorney SD, Simon DN, Thomas L, et al. Stability of international normalized ratios in patients taking long-term warfarin therapy. JAMA.2016;316(6):661-663

Dr. Florindez is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

Clinical question: Does an initial stable international normalized ratio (INR) predict long-term stability?

Background: Warfarin decreases stroke risk among patients with atrial fibrillation; however, it interacts with food and drugs and requires monitoring to achieve a therapeutic INR. It is unclear if patients on warfarin with an initial stable INR value remain stable over time. Additionally, it is controversial whether patients on warfarin with previously stable INRs should benefit from switching to a non–vitamin K oral anticoagulant.

Study design: Retrospective study.

Setting: Outpatient clinics.

Only 26% of patients taking warfarin had a stable INR during the first 6 months, and only 34% continued to have a stable INR in the subsequent year.

Bottom line: Initial stable INR within the first 6 months among patients taking warfarin does not predict long-term INR stability in the subsequent year.

Citation: Pokorney SD, Simon DN, Thomas L, et al. Stability of international normalized ratios in patients taking long-term warfarin therapy. JAMA.2016;316(6):661-663

Dr. Florindez is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

Recently, researchers have been challenged to design methods that ensure that key constituents are partners in research, and not simply participants. Here we describe some innovative approaches we used to engage stakeholders. The approaches are drawn from a patient-centered outcomes research project, focusing on the graphic display of patient-reported outcomes (PROs) data. PROs represent patients’ perspectives on the impact of health, disease, and treatment, without interpretation by a clinician or anyone else. PROs include, among other things, patients’ assessments of their symptoms, their level of physical and psychosocial functioning, and health-related quality-of-life.¹

As a first example of the key role of stakeholders in this project, input from cancer patients and clinicians, drawn from previous research, motivated us to ask whether there might be a “better way” to display PRO data when used to inform clinical practice. Specifically, even though cancer patients and clinicians endorse the importance of PRO data to promote patient-centered care, both groups report challenges using PROs in practice because of difficulty understanding what the PRO scores mean (eg, what is a good score or a bad score?; for individual patients, which scores should clinicians be concerned about?; for clinical trial PROs, what differences in PRO scores between treatments are clinically important?). The challenges in interpreting PRO data result in part from a large number of PRO measures (eg, one database includes more than 1,000 instruments)² and no standards across PRO measures regarding how they are scored and scaled, or in how the data are presented.³ For example, on some PRO measures, higher scores represent better outcomes; on some PRO measures, lower scores represent better outcomes; and on some PRO measures, whether higher or lower scores represent better outcomes depends on the domain being measured. Further, some measures are scaled 0-100, with the extremes representing the best/worst scores possible, whereas others are normed to, for example, a population average of 50. Because of this variation, a score of 70 can have a completely different meaning depending on the PRO measure (or domain within a measure). As noted above, previous research has documented that this variation limits patients’ and clinicians’ understanding of the PRO scores, creating an important barrier to their use in practice.^4-5

To address this stakeholder-driven research question, we undertook a three-part study to identify approaches for PRO data display that can be easily interpreted, regardless of scoring or scaling conventions, with the overall goal of improving patient and clinician understanding and use of PROs in oncology clinical practice. Part 1 of the study identified attributes of graphic displays of PRO data that are helpful and confusing.⁶ Part 2 involved developing improved PRO data presentation approaches.⁷ Part 3 evaluated the accuracy-of-interpretation and clarity of the developed approaches.^8-10 The methods and findings of the three-part study are reported elsewhere;^6-10 here, we describe the various approaches employed to engage stakeholders throughout the project.

As described above, the first reflection of stakeholder input was in the research question we asked. We then sought to identify the key stakeholder groups and ensure that they participated in each stage of the project. The relevant stakeholder groups we identified were: patients and their caregivers; health care providers (eg, oncologists, oncology nurses) who need to understand PRO data for their own consideration and for discussion with patients; and PRO researchers who develop, validate, and apply PRO measures.

Having identified these three key stakeholder groups, we sought to obtain broad representation of their perspectives. For example, we ensured that our investigative team included a cancer survivor, a cancer care provider, and PRO researchers. To supplement the stakeholder input from the investigative team, we formed a nine-member Stakeholder Advisory Board, with multiple representatives from each key constituency. We also aimed to be as broad as possible in the populations sampled for data collection. For example, we extended beyond the Johns Hopkins cancer center to include the Johns Hopkins Clinical Research Network, a consortium of academic and community health systems across the mid-Atlantic United States. Beyond the in-person data collection across the region, our study also included an internet survey of cancer patients/survivors, cancer care providers, and PRO researchers from across the United States and internationally. Taken together, these approaches improve the diversity of our sample and, thereby, the generalizability of our findings.

In addition to obtaining broad perspectives across stakeholder groups, we created genuine partnerships with the stakeholders to inform every aspect of the project. As described above, the study itself was motivated by feedback from cancer patients and clinicians regarding the challenges they experienced when trying to interpret PRO scores, and we therefore ensured that each stakeholder group contributed to the study’s design. Stakeholders also played a critical role in the conduct of the study. For example, in the first part of the study, we conducted one-on-one interviews with 50 cancer patients and 20 cancer clinicians to obtain their insights regarding attributes of current approaches for presenting PRO data that are helpful and confusing.⁶ At the completion of each interview, we asked participants whether they would be interested in partnering with the researchers in developing improved presentation formats in the next phase of the project. These volunteers were organized into work groups that reviewed the findings from the initial round of interviews with the investigative team, provided suggestions regarding candidate formats that could be used to improve presentation approaches, and helped pilot the internet survey.⁷ In this way, research participants had the opportunity to evolve into research partners, providing critically important input throughout the process.

The implementation and dissemination of findings is another area in which stakeholder partnership is particularly valuable. For example, several of our stakeholder partners have an advocacy background, which can be quite useful for conveying the project’s results in a compelling way. Other stakeholders, such as journal editors, are in a position to act directly to implement the study findings by, for example, adding best practices for presenting PRO data to their journal’s author instructions. Notably, some of the skills stakeholders bring come in addition to their role as stakeholders. For example, one of our patient stakeholders has a background in marketing, and this marketing expertise (completely separate from his patient experience) has helped the research team think about how to present data to broad audiences in a meaningful way.

In summary, this project has implemented stakeholder-driven approaches to address an important barrier to patient-centered cancer care. Several key lessons in stakeholder engagement have emerged from this experience. It is important to identify the key constituencies early on in the process. Involving stakeholders from the start enables them to play important roles in every aspect of the study, starting with study design conception. There are also innovative ways to integrate stakeholders in study conduct, such as our work groups of research participants who volunteered to partner with the research team to develop improved data presentation approaches. Implementation and dissemination is another area where stakeholders, based on their background and connections, can play a critical role. Throughout the process, it is valuable to challenge the project to obtain perspectives from as broad a range of stakeholders as possible. Finally, stakeholders have expertise beyond their stakeholder roles, and these skills can be quite valuable to the overall research agenda. In this project, our partnership with stakeholders has helped improve the presentation of PRO data to patients and providers, thereby improving the patient-centeredness of cancer care.

Acknowledgments

The PRO Data Presentation Stakeholder Advisory Board includes Neil K Aaronson, PhD (Netherlands Cancer Institute, Amsterdam); Patricia A Ganz, MD (University of California-Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, CA); Ravin Garg, MD (Anne Arundel Medical Center, Annapolis, MD); Michael Fisch, MD (MD Anderson Cancer Center, Houston, TX); Vanessa Hoffman, MPH (Bladder Cancer Advocacy Network, Washington, DC); Bryce B Reeve, PhD (University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center, Chapel Hill, NC); Eden Stotsky-Himelfarb (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD); Ellen Stovall (National Coalition for Cancer Survivorship, Washington, DC [posthumous]); Matthew Zachary (Stupid Cancer, New York, NY).

The authors thank The Johns Hopkins Clinical Research Network site investigators and staff and, in particular, the patients and clinicians who participated in this project.

Supported by a Patient-Centered Outcomes Research Institute (PCORI) Award (R-1410-24904). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of PCORI, its board of governors or methodology committee. Drs Snyder and Smith are members of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (P30 CA 006973). The funders had no role in the study design; data collection, analysis, or interpretation; writing; or decision to submit.

Recently, researchers have been challenged to design methods that ensure that key constituents are partners in research, and not simply participants. Here we describe some innovative approaches we used to engage stakeholders. The approaches are drawn from a patient-centered outcomes research project, focusing on the graphic display of patient-reported outcomes (PROs) data. PROs represent patients’ perspectives on the impact of health, disease, and treatment, without interpretation by a clinician or anyone else. PROs include, among other things, patients’ assessments of their symptoms, their level of physical and psychosocial functioning, and health-related quality-of-life.¹

As a first example of the key role of stakeholders in this project, input from cancer patients and clinicians, drawn from previous research, motivated us to ask whether there might be a “better way” to display PRO data when used to inform clinical practice. Specifically, even though cancer patients and clinicians endorse the importance of PRO data to promote patient-centered care, both groups report challenges using PROs in practice because of difficulty understanding what the PRO scores mean (eg, what is a good score or a bad score?; for individual patients, which scores should clinicians be concerned about?; for clinical trial PROs, what differences in PRO scores between treatments are clinically important?). The challenges in interpreting PRO data result in part from a large number of PRO measures (eg, one database includes more than 1,000 instruments)² and no standards across PRO measures regarding how they are scored and scaled, or in how the data are presented.³ For example, on some PRO measures, higher scores represent better outcomes; on some PRO measures, lower scores represent better outcomes; and on some PRO measures, whether higher or lower scores represent better outcomes depends on the domain being measured. Further, some measures are scaled 0-100, with the extremes representing the best/worst scores possible, whereas others are normed to, for example, a population average of 50. Because of this variation, a score of 70 can have a completely different meaning depending on the PRO measure (or domain within a measure). As noted above, previous research has documented that this variation limits patients’ and clinicians’ understanding of the PRO scores, creating an important barrier to their use in practice.^4-5

To address this stakeholder-driven research question, we undertook a three-part study to identify approaches for PRO data display that can be easily interpreted, regardless of scoring or scaling conventions, with the overall goal of improving patient and clinician understanding and use of PROs in oncology clinical practice. Part 1 of the study identified attributes of graphic displays of PRO data that are helpful and confusing.⁶ Part 2 involved developing improved PRO data presentation approaches.⁷ Part 3 evaluated the accuracy-of-interpretation and clarity of the developed approaches.^8-10 The methods and findings of the three-part study are reported elsewhere;^6-10 here, we describe the various approaches employed to engage stakeholders throughout the project.

As described above, the first reflection of stakeholder input was in the research question we asked. We then sought to identify the key stakeholder groups and ensure that they participated in each stage of the project. The relevant stakeholder groups we identified were: patients and their caregivers; health care providers (eg, oncologists, oncology nurses) who need to understand PRO data for their own consideration and for discussion with patients; and PRO researchers who develop, validate, and apply PRO measures.

Having identified these three key stakeholder groups, we sought to obtain broad representation of their perspectives. For example, we ensured that our investigative team included a cancer survivor, a cancer care provider, and PRO researchers. To supplement the stakeholder input from the investigative team, we formed a nine-member Stakeholder Advisory Board, with multiple representatives from each key constituency. We also aimed to be as broad as possible in the populations sampled for data collection. For example, we extended beyond the Johns Hopkins cancer center to include the Johns Hopkins Clinical Research Network, a consortium of academic and community health systems across the mid-Atlantic United States. Beyond the in-person data collection across the region, our study also included an internet survey of cancer patients/survivors, cancer care providers, and PRO researchers from across the United States and internationally. Taken together, these approaches improve the diversity of our sample and, thereby, the generalizability of our findings.

In addition to obtaining broad perspectives across stakeholder groups, we created genuine partnerships with the stakeholders to inform every aspect of the project. As described above, the study itself was motivated by feedback from cancer patients and clinicians regarding the challenges they experienced when trying to interpret PRO scores, and we therefore ensured that each stakeholder group contributed to the study’s design. Stakeholders also played a critical role in the conduct of the study. For example, in the first part of the study, we conducted one-on-one interviews with 50 cancer patients and 20 cancer clinicians to obtain their insights regarding attributes of current approaches for presenting PRO data that are helpful and confusing.⁶ At the completion of each interview, we asked participants whether they would be interested in partnering with the researchers in developing improved presentation formats in the next phase of the project. These volunteers were organized into work groups that reviewed the findings from the initial round of interviews with the investigative team, provided suggestions regarding candidate formats that could be used to improve presentation approaches, and helped pilot the internet survey.⁷ In this way, research participants had the opportunity to evolve into research partners, providing critically important input throughout the process.

The implementation and dissemination of findings is another area in which stakeholder partnership is particularly valuable. For example, several of our stakeholder partners have an advocacy background, which can be quite useful for conveying the project’s results in a compelling way. Other stakeholders, such as journal editors, are in a position to act directly to implement the study findings by, for example, adding best practices for presenting PRO data to their journal’s author instructions. Notably, some of the skills stakeholders bring come in addition to their role as stakeholders. For example, one of our patient stakeholders has a background in marketing, and this marketing expertise (completely separate from his patient experience) has helped the research team think about how to present data to broad audiences in a meaningful way.

In summary, this project has implemented stakeholder-driven approaches to address an important barrier to patient-centered cancer care. Several key lessons in stakeholder engagement have emerged from this experience. It is important to identify the key constituencies early on in the process. Involving stakeholders from the start enables them to play important roles in every aspect of the study, starting with study design conception. There are also innovative ways to integrate stakeholders in study conduct, such as our work groups of research participants who volunteered to partner with the research team to develop improved data presentation approaches. Implementation and dissemination is another area where stakeholders, based on their background and connections, can play a critical role. Throughout the process, it is valuable to challenge the project to obtain perspectives from as broad a range of stakeholders as possible. Finally, stakeholders have expertise beyond their stakeholder roles, and these skills can be quite valuable to the overall research agenda. In this project, our partnership with stakeholders has helped improve the presentation of PRO data to patients and providers, thereby improving the patient-centeredness of cancer care.

Acknowledgments

The PRO Data Presentation Stakeholder Advisory Board includes Neil K Aaronson, PhD (Netherlands Cancer Institute, Amsterdam); Patricia A Ganz, MD (University of California-Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, CA); Ravin Garg, MD (Anne Arundel Medical Center, Annapolis, MD); Michael Fisch, MD (MD Anderson Cancer Center, Houston, TX); Vanessa Hoffman, MPH (Bladder Cancer Advocacy Network, Washington, DC); Bryce B Reeve, PhD (University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center, Chapel Hill, NC); Eden Stotsky-Himelfarb (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD); Ellen Stovall (National Coalition for Cancer Survivorship, Washington, DC [posthumous]); Matthew Zachary (Stupid Cancer, New York, NY).

The authors thank The Johns Hopkins Clinical Research Network site investigators and staff and, in particular, the patients and clinicians who participated in this project.

Supported by a Patient-Centered Outcomes Research Institute (PCORI) Award (R-1410-24904). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of PCORI, its board of governors or methodology committee. Drs Snyder and Smith are members of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (P30 CA 006973). The funders had no role in the study design; data collection, analysis, or interpretation; writing; or decision to submit.

Recently, researchers have been challenged to design methods that ensure that key constituents are partners in research, and not simply participants. Here we describe some innovative approaches we used to engage stakeholders. The approaches are drawn from a patient-centered outcomes research project, focusing on the graphic display of patient-reported outcomes (PROs) data. PROs represent patients’ perspectives on the impact of health, disease, and treatment, without interpretation by a clinician or anyone else. PROs include, among other things, patients’ assessments of their symptoms, their level of physical and psychosocial functioning, and health-related quality-of-life.¹

As a first example of the key role of stakeholders in this project, input from cancer patients and clinicians, drawn from previous research, motivated us to ask whether there might be a “better way” to display PRO data when used to inform clinical practice. Specifically, even though cancer patients and clinicians endorse the importance of PRO data to promote patient-centered care, both groups report challenges using PROs in practice because of difficulty understanding what the PRO scores mean (eg, what is a good score or a bad score?; for individual patients, which scores should clinicians be concerned about?; for clinical trial PROs, what differences in PRO scores between treatments are clinically important?). The challenges in interpreting PRO data result in part from a large number of PRO measures (eg, one database includes more than 1,000 instruments)² and no standards across PRO measures regarding how they are scored and scaled, or in how the data are presented.³ For example, on some PRO measures, higher scores represent better outcomes; on some PRO measures, lower scores represent better outcomes; and on some PRO measures, whether higher or lower scores represent better outcomes depends on the domain being measured. Further, some measures are scaled 0-100, with the extremes representing the best/worst scores possible, whereas others are normed to, for example, a population average of 50. Because of this variation, a score of 70 can have a completely different meaning depending on the PRO measure (or domain within a measure). As noted above, previous research has documented that this variation limits patients’ and clinicians’ understanding of the PRO scores, creating an important barrier to their use in practice.^4-5

To address this stakeholder-driven research question, we undertook a three-part study to identify approaches for PRO data display that can be easily interpreted, regardless of scoring or scaling conventions, with the overall goal of improving patient and clinician understanding and use of PROs in oncology clinical practice. Part 1 of the study identified attributes of graphic displays of PRO data that are helpful and confusing.⁶ Part 2 involved developing improved PRO data presentation approaches.⁷ Part 3 evaluated the accuracy-of-interpretation and clarity of the developed approaches.^8-10 The methods and findings of the three-part study are reported elsewhere;^6-10 here, we describe the various approaches employed to engage stakeholders throughout the project.

As described above, the first reflection of stakeholder input was in the research question we asked. We then sought to identify the key stakeholder groups and ensure that they participated in each stage of the project. The relevant stakeholder groups we identified were: patients and their caregivers; health care providers (eg, oncologists, oncology nurses) who need to understand PRO data for their own consideration and for discussion with patients; and PRO researchers who develop, validate, and apply PRO measures.

Having identified these three key stakeholder groups, we sought to obtain broad representation of their perspectives. For example, we ensured that our investigative team included a cancer survivor, a cancer care provider, and PRO researchers. To supplement the stakeholder input from the investigative team, we formed a nine-member Stakeholder Advisory Board, with multiple representatives from each key constituency. We also aimed to be as broad as possible in the populations sampled for data collection. For example, we extended beyond the Johns Hopkins cancer center to include the Johns Hopkins Clinical Research Network, a consortium of academic and community health systems across the mid-Atlantic United States. Beyond the in-person data collection across the region, our study also included an internet survey of cancer patients/survivors, cancer care providers, and PRO researchers from across the United States and internationally. Taken together, these approaches improve the diversity of our sample and, thereby, the generalizability of our findings.

In addition to obtaining broad perspectives across stakeholder groups, we created genuine partnerships with the stakeholders to inform every aspect of the project. As described above, the study itself was motivated by feedback from cancer patients and clinicians regarding the challenges they experienced when trying to interpret PRO scores, and we therefore ensured that each stakeholder group contributed to the study’s design. Stakeholders also played a critical role in the conduct of the study. For example, in the first part of the study, we conducted one-on-one interviews with 50 cancer patients and 20 cancer clinicians to obtain their insights regarding attributes of current approaches for presenting PRO data that are helpful and confusing.⁶ At the completion of each interview, we asked participants whether they would be interested in partnering with the researchers in developing improved presentation formats in the next phase of the project. These volunteers were organized into work groups that reviewed the findings from the initial round of interviews with the investigative team, provided suggestions regarding candidate formats that could be used to improve presentation approaches, and helped pilot the internet survey.⁷ In this way, research participants had the opportunity to evolve into research partners, providing critically important input throughout the process.

The implementation and dissemination of findings is another area in which stakeholder partnership is particularly valuable. For example, several of our stakeholder partners have an advocacy background, which can be quite useful for conveying the project’s results in a compelling way. Other stakeholders, such as journal editors, are in a position to act directly to implement the study findings by, for example, adding best practices for presenting PRO data to their journal’s author instructions. Notably, some of the skills stakeholders bring come in addition to their role as stakeholders. For example, one of our patient stakeholders has a background in marketing, and this marketing expertise (completely separate from his patient experience) has helped the research team think about how to present data to broad audiences in a meaningful way.

In summary, this project has implemented stakeholder-driven approaches to address an important barrier to patient-centered cancer care. Several key lessons in stakeholder engagement have emerged from this experience. It is important to identify the key constituencies early on in the process. Involving stakeholders from the start enables them to play important roles in every aspect of the study, starting with study design conception. There are also innovative ways to integrate stakeholders in study conduct, such as our work groups of research participants who volunteered to partner with the research team to develop improved data presentation approaches. Implementation and dissemination is another area where stakeholders, based on their background and connections, can play a critical role. Throughout the process, it is valuable to challenge the project to obtain perspectives from as broad a range of stakeholders as possible. Finally, stakeholders have expertise beyond their stakeholder roles, and these skills can be quite valuable to the overall research agenda. In this project, our partnership with stakeholders has helped improve the presentation of PRO data to patients and providers, thereby improving the patient-centeredness of cancer care.

Acknowledgments

The PRO Data Presentation Stakeholder Advisory Board includes Neil K Aaronson, PhD (Netherlands Cancer Institute, Amsterdam); Patricia A Ganz, MD (University of California-Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, CA); Ravin Garg, MD (Anne Arundel Medical Center, Annapolis, MD); Michael Fisch, MD (MD Anderson Cancer Center, Houston, TX); Vanessa Hoffman, MPH (Bladder Cancer Advocacy Network, Washington, DC); Bryce B Reeve, PhD (University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center, Chapel Hill, NC); Eden Stotsky-Himelfarb (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD); Ellen Stovall (National Coalition for Cancer Survivorship, Washington, DC [posthumous]); Matthew Zachary (Stupid Cancer, New York, NY).

The authors thank The Johns Hopkins Clinical Research Network site investigators and staff and, in particular, the patients and clinicians who participated in this project.

Supported by a Patient-Centered Outcomes Research Institute (PCORI) Award (R-1410-24904). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of PCORI, its board of governors or methodology committee. Drs Snyder and Smith are members of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (P30 CA 006973). The funders had no role in the study design; data collection, analysis, or interpretation; writing; or decision to submit.

With loss of deep fat pad compartments and bony resorption with normal aging, soft tissue fillers have become a mainstay in minimally invasive aesthetic treatments. Preference of injecting with a needle versus a cannula is often user and training dependent. Blunt-tipped cannulas may provide a lower risk of bruising, as well as potentially devastating complications such as intravascular occlusion that can lead to skin necrosis and blindness. Even for advanced injectors, however, cannula use may portend a learning curve if the clinicians are used to injecting with needles.

A recently published observational study using cadaver heads looked at precision in supraperiosteal placement with a sharp needle compared with a blunt tipped cannula.¹ The investigators injected dye material with soft-tissue fillers at different aesthetic facial sites on the supraperiosteum, then observed the placement of dye and filler after dissection. In this study, the placement of product was more precise with the cannulas. The filler was injected on the periosteum with a needle. Some of the filler then migrated along the trajectory of the needle path back toward the epidermis, ending up in multiple tissue layers. So there was more extrusion of the filler in the superficial layers with a needle without a retrograde injection technique. Even with the needle tip on the periosteum and no movement of the needle, the needle technique showed a higher risk of intra-arterial injections. This study is limited by the fact that in vivo circumstances could potentially alter the outcome, as could user injection technique.

References

1. Aesthet Surg J. 2016 Dec 16. pii: sjw220.

2. Aesthetic Plast Surg. 2016 Dec 28. doi: 10.1007/s00266-016-0756-0.

3. Aesthetic Plast Surg. 2016 Dec 23. doi: 10.1007/s00266-016-0725-7.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

With loss of deep fat pad compartments and bony resorption with normal aging, soft tissue fillers have become a mainstay in minimally invasive aesthetic treatments. Preference of injecting with a needle versus a cannula is often user and training dependent. Blunt-tipped cannulas may provide a lower risk of bruising, as well as potentially devastating complications such as intravascular occlusion that can lead to skin necrosis and blindness. Even for advanced injectors, however, cannula use may portend a learning curve if the clinicians are used to injecting with needles.

A recently published observational study using cadaver heads looked at precision in supraperiosteal placement with a sharp needle compared with a blunt tipped cannula.¹ The investigators injected dye material with soft-tissue fillers at different aesthetic facial sites on the supraperiosteum, then observed the placement of dye and filler after dissection. In this study, the placement of product was more precise with the cannulas. The filler was injected on the periosteum with a needle. Some of the filler then migrated along the trajectory of the needle path back toward the epidermis, ending up in multiple tissue layers. So there was more extrusion of the filler in the superficial layers with a needle without a retrograde injection technique. Even with the needle tip on the periosteum and no movement of the needle, the needle technique showed a higher risk of intra-arterial injections. This study is limited by the fact that in vivo circumstances could potentially alter the outcome, as could user injection technique.

References

1. Aesthet Surg J. 2016 Dec 16. pii: sjw220.

2. Aesthetic Plast Surg. 2016 Dec 28. doi: 10.1007/s00266-016-0756-0.

3. Aesthetic Plast Surg. 2016 Dec 23. doi: 10.1007/s00266-016-0725-7.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

With loss of deep fat pad compartments and bony resorption with normal aging, soft tissue fillers have become a mainstay in minimally invasive aesthetic treatments. Preference of injecting with a needle versus a cannula is often user and training dependent. Blunt-tipped cannulas may provide a lower risk of bruising, as well as potentially devastating complications such as intravascular occlusion that can lead to skin necrosis and blindness. Even for advanced injectors, however, cannula use may portend a learning curve if the clinicians are used to injecting with needles.

A recently published observational study using cadaver heads looked at precision in supraperiosteal placement with a sharp needle compared with a blunt tipped cannula.¹ The investigators injected dye material with soft-tissue fillers at different aesthetic facial sites on the supraperiosteum, then observed the placement of dye and filler after dissection. In this study, the placement of product was more precise with the cannulas. The filler was injected on the periosteum with a needle. Some of the filler then migrated along the trajectory of the needle path back toward the epidermis, ending up in multiple tissue layers. So there was more extrusion of the filler in the superficial layers with a needle without a retrograde injection technique. Even with the needle tip on the periosteum and no movement of the needle, the needle technique showed a higher risk of intra-arterial injections. This study is limited by the fact that in vivo circumstances could potentially alter the outcome, as could user injection technique.

References

1. Aesthet Surg J. 2016 Dec 16. pii: sjw220.

2. Aesthetic Plast Surg. 2016 Dec 28. doi: 10.1007/s00266-016-0756-0.

3. Aesthetic Plast Surg. 2016 Dec 23. doi: 10.1007/s00266-016-0725-7.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Men experiencing sarcopenia who also have been diagnosed with chronic obstructive pulmonary disease (COPD) are at a significantly higher risk of developing osteopenia and osteoporosis than are men who do not suffer from COPD, according to a new study published in Chest.

“Muscle depletion has been considered a risk factor for low [bone mineral density (BMD)] in the healthy general population [but] data on the association between sarcopenia and osteopenia/osteoporosis in COPD patients are lacking,” wrote the investigators of the study, coauthored by Moo Suk Park, MD, of Yonsei University in Seoul, South Korea (Chest. 2017 Jan. doi: 10.1016/j.chest.2016.12.006).

“Although previous studies showed that loss of fat-free mass (FFM) was related to BMD loss in COPD patients, it is difficult to know the genuine relationship between skeletal muscle mass and BMD because whole body FFM contains a large proportion of water-retaining organs and nonmuscle soft tissue,” the authors continued.

The investigators examined data from the Korean National Health and Nutritional Examination Survey (KNHANES), looking for men at least 20 years of age with COPD who had both pulmonary function test and the dual-energy x-ray absorptiometry (DXA) performed on them during the years 2008-2011. A total of 864 men were deemed eligible for inclusion, and were scored for sarcopenia and osteopenia/osteoporosis; the former was assessed via the appendicular skeletal mass index (ASMI), with the latter done via T-score.

“Sarcopenia and presarcopenia were defined according to the presence of ASMI values that were less than two standard deviations (SDs) and between 2SDs and 1SD, respectively, below the mean value of a young male reference group aged 20-39 years,” according to the investigators. “Osteoporosis, osteopenia, and normal BMD were identified according to the lowest T-score of the three measured locations and were defined according to the World Health Organization criteria.”

*This article was updated on 1/20/17 at 1:30 p.m. It misstated the affiliation for Vera Palo, MD, FCCP.  

[email protected]

Men experiencing sarcopenia who also have been diagnosed with chronic obstructive pulmonary disease (COPD) are at a significantly higher risk of developing osteopenia and osteoporosis than are men who do not suffer from COPD, according to a new study published in Chest.

“Muscle depletion has been considered a risk factor for low [bone mineral density (BMD)] in the healthy general population [but] data on the association between sarcopenia and osteopenia/osteoporosis in COPD patients are lacking,” wrote the investigators of the study, coauthored by Moo Suk Park, MD, of Yonsei University in Seoul, South Korea (Chest. 2017 Jan. doi: 10.1016/j.chest.2016.12.006).

“Although previous studies showed that loss of fat-free mass (FFM) was related to BMD loss in COPD patients, it is difficult to know the genuine relationship between skeletal muscle mass and BMD because whole body FFM contains a large proportion of water-retaining organs and nonmuscle soft tissue,” the authors continued.

The investigators examined data from the Korean National Health and Nutritional Examination Survey (KNHANES), looking for men at least 20 years of age with COPD who had both pulmonary function test and the dual-energy x-ray absorptiometry (DXA) performed on them during the years 2008-2011. A total of 864 men were deemed eligible for inclusion, and were scored for sarcopenia and osteopenia/osteoporosis; the former was assessed via the appendicular skeletal mass index (ASMI), with the latter done via T-score.

“Sarcopenia and presarcopenia were defined according to the presence of ASMI values that were less than two standard deviations (SDs) and between 2SDs and 1SD, respectively, below the mean value of a young male reference group aged 20-39 years,” according to the investigators. “Osteoporosis, osteopenia, and normal BMD were identified according to the lowest T-score of the three measured locations and were defined according to the World Health Organization criteria.”

*This article was updated on 1/20/17 at 1:30 p.m. It misstated the affiliation for Vera Palo, MD, FCCP.  

[email protected]

Men experiencing sarcopenia who also have been diagnosed with chronic obstructive pulmonary disease (COPD) are at a significantly higher risk of developing osteopenia and osteoporosis than are men who do not suffer from COPD, according to a new study published in Chest.

“Muscle depletion has been considered a risk factor for low [bone mineral density (BMD)] in the healthy general population [but] data on the association between sarcopenia and osteopenia/osteoporosis in COPD patients are lacking,” wrote the investigators of the study, coauthored by Moo Suk Park, MD, of Yonsei University in Seoul, South Korea (Chest. 2017 Jan. doi: 10.1016/j.chest.2016.12.006).

“Although previous studies showed that loss of fat-free mass (FFM) was related to BMD loss in COPD patients, it is difficult to know the genuine relationship between skeletal muscle mass and BMD because whole body FFM contains a large proportion of water-retaining organs and nonmuscle soft tissue,” the authors continued.

The investigators examined data from the Korean National Health and Nutritional Examination Survey (KNHANES), looking for men at least 20 years of age with COPD who had both pulmonary function test and the dual-energy x-ray absorptiometry (DXA) performed on them during the years 2008-2011. A total of 864 men were deemed eligible for inclusion, and were scored for sarcopenia and osteopenia/osteoporosis; the former was assessed via the appendicular skeletal mass index (ASMI), with the latter done via T-score.

“Sarcopenia and presarcopenia were defined according to the presence of ASMI values that were less than two standard deviations (SDs) and between 2SDs and 1SD, respectively, below the mean value of a young male reference group aged 20-39 years,” according to the investigators. “Osteoporosis, osteopenia, and normal BMD were identified according to the lowest T-score of the three measured locations and were defined according to the World Health Organization criteria.”

*This article was updated on 1/20/17 at 1:30 p.m. It misstated the affiliation for Vera Palo, MD, FCCP.  

[email protected]

The number of pregnant women with laboratory evidence of Zika infection jumped up a bit at the end of 2016, and the United States approached 40,000 Zika cases among all Americans at the beginning of the new year, according to reports from the Centers for Disease Control and Prevention.

There were 187 additional pregnant women with Zika virus infection reported in the 2 weeks ending Dec. 27, compared with the 136 new reports of infected women in each of the two previous comparable periods (Dec. 1-13 and Nov. 18-30). Most of the 187 new cases were reported in the U.S. territories, while 46 were reported in the 50 states and the District of Columbia. There have been delays in reporting, the CDC noted, so these cannot be considered real-time estimates.

copyright jarun011/Thinkstock

[email protected]

The number of pregnant women with laboratory evidence of Zika infection jumped up a bit at the end of 2016, and the United States approached 40,000 Zika cases among all Americans at the beginning of the new year, according to reports from the Centers for Disease Control and Prevention.

There were 187 additional pregnant women with Zika virus infection reported in the 2 weeks ending Dec. 27, compared with the 136 new reports of infected women in each of the two previous comparable periods (Dec. 1-13 and Nov. 18-30). Most of the 187 new cases were reported in the U.S. territories, while 46 were reported in the 50 states and the District of Columbia. There have been delays in reporting, the CDC noted, so these cannot be considered real-time estimates.

copyright jarun011/Thinkstock

[email protected]

The number of pregnant women with laboratory evidence of Zika infection jumped up a bit at the end of 2016, and the United States approached 40,000 Zika cases among all Americans at the beginning of the new year, according to reports from the Centers for Disease Control and Prevention.

There were 187 additional pregnant women with Zika virus infection reported in the 2 weeks ending Dec. 27, compared with the 136 new reports of infected women in each of the two previous comparable periods (Dec. 1-13 and Nov. 18-30). Most of the 187 new cases were reported in the U.S. territories, while 46 were reported in the 50 states and the District of Columbia. There have been delays in reporting, the CDC noted, so these cannot be considered real-time estimates.

copyright jarun011/Thinkstock

[email protected]

Clinical question: How has inpatient antibiotic use changed in the United States in recent years?

Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.

Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.

Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.

Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

Clinical question: How has inpatient antibiotic use changed in the United States in recent years?

Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.

Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.

Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.

Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

Clinical question: How has inpatient antibiotic use changed in the United States in recent years?

Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.

Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.

Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.

Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.

About one-third of people with psoriatic arthritis have clinical enthesitis, according to results from a prospective cohort study of more than 800 patients.

Enthesitis, or soreness and inflammation at sites where soft tissue attaches to bone, is considered to be common in psoriatic arthritis (PsA), but its true prevalence has been difficult to define in this population, according to a group of researchers led by Ari Polachek, MD, of the University of Toronto.

Previous studies attempting to quantify enthesitis prevalence in PsA populations have found it to be as low as 8% to more than 50% of patients affected, Dr. Polachek and his colleagues noted, but such disparities can likely be attributed to the use of different enthesitis measures. To define enthesitis in the current study, the investigators used the SPondyloArthritis Research Consortium Canada (SPARCC) enthesitis index, which they called “valid and reliable, particularly for patients with PsA.”

Dr. Polachek and his colleagues detected enthesitis in 281 (35%) of 803 patents who had been recruited during 2008-2014 at a single clinic dedicated to PsA. The enthesitis diagnoses were established for at least one site on an initial visit (n = 128) or during a mean 3 years’ follow-up (n = 192).

The investigators reported that the annual incidence of enthesitis in this population was 0.9% (Arthritis Care Res. 2016 Dec 20. doi: 10.1002/acr.23174). About half of the patients in the cohort had only one site affected, and one-third had two sites affected. The most common of these sites were the Achilles tendon, plantar fascia, and the lateral epicondyle, Dr. Polachek and colleagues reported. They also found several factors associated with enthesitis: higher inflamed joint count (odds ratio, 1.06; P = .0002), less clinical damage (OR, 0.9; P = .04), more pain (OR, 1.15; P = .01), and presence of tenosynovitis (OR, 5.3; P less than .0001) or dactylitis (OR, 2.5; P = .02).

Significant risk factors for enthesitis included higher body mass index (hazard ratio, 1.04; P = .02), more actively inflamed joints (HR, 1.04; P = .0004), and younger age (HR, 0.98; P = .02). Among the patients in the cohort, 57% were male, the mean age was 50.8 years, and mean PsA disease duration was 12.3 years. Median time to resolution of enthesitis was 7.5 months, with 70% of patients improving without changes to their treatment.

The University of Toronto PsA research program receives funding from Krembil Foundation. Dr. Polachek disclosed grant funding from Janssen Canada. No other authors reported conflicts of interest.

About one-third of people with psoriatic arthritis have clinical enthesitis, according to results from a prospective cohort study of more than 800 patients.

Enthesitis, or soreness and inflammation at sites where soft tissue attaches to bone, is considered to be common in psoriatic arthritis (PsA), but its true prevalence has been difficult to define in this population, according to a group of researchers led by Ari Polachek, MD, of the University of Toronto.

Previous studies attempting to quantify enthesitis prevalence in PsA populations have found it to be as low as 8% to more than 50% of patients affected, Dr. Polachek and his colleagues noted, but such disparities can likely be attributed to the use of different enthesitis measures. To define enthesitis in the current study, the investigators used the SPondyloArthritis Research Consortium Canada (SPARCC) enthesitis index, which they called “valid and reliable, particularly for patients with PsA.”

Dr. Polachek and his colleagues detected enthesitis in 281 (35%) of 803 patents who had been recruited during 2008-2014 at a single clinic dedicated to PsA. The enthesitis diagnoses were established for at least one site on an initial visit (n = 128) or during a mean 3 years’ follow-up (n = 192).

The investigators reported that the annual incidence of enthesitis in this population was 0.9% (Arthritis Care Res. 2016 Dec 20. doi: 10.1002/acr.23174). About half of the patients in the cohort had only one site affected, and one-third had two sites affected. The most common of these sites were the Achilles tendon, plantar fascia, and the lateral epicondyle, Dr. Polachek and colleagues reported. They also found several factors associated with enthesitis: higher inflamed joint count (odds ratio, 1.06; P = .0002), less clinical damage (OR, 0.9; P = .04), more pain (OR, 1.15; P = .01), and presence of tenosynovitis (OR, 5.3; P less than .0001) or dactylitis (OR, 2.5; P = .02).

Significant risk factors for enthesitis included higher body mass index (hazard ratio, 1.04; P = .02), more actively inflamed joints (HR, 1.04; P = .0004), and younger age (HR, 0.98; P = .02). Among the patients in the cohort, 57% were male, the mean age was 50.8 years, and mean PsA disease duration was 12.3 years. Median time to resolution of enthesitis was 7.5 months, with 70% of patients improving without changes to their treatment.

The University of Toronto PsA research program receives funding from Krembil Foundation. Dr. Polachek disclosed grant funding from Janssen Canada. No other authors reported conflicts of interest.

About one-third of people with psoriatic arthritis have clinical enthesitis, according to results from a prospective cohort study of more than 800 patients.

Enthesitis, or soreness and inflammation at sites where soft tissue attaches to bone, is considered to be common in psoriatic arthritis (PsA), but its true prevalence has been difficult to define in this population, according to a group of researchers led by Ari Polachek, MD, of the University of Toronto.

Previous studies attempting to quantify enthesitis prevalence in PsA populations have found it to be as low as 8% to more than 50% of patients affected, Dr. Polachek and his colleagues noted, but such disparities can likely be attributed to the use of different enthesitis measures. To define enthesitis in the current study, the investigators used the SPondyloArthritis Research Consortium Canada (SPARCC) enthesitis index, which they called “valid and reliable, particularly for patients with PsA.”

Dr. Polachek and his colleagues detected enthesitis in 281 (35%) of 803 patents who had been recruited during 2008-2014 at a single clinic dedicated to PsA. The enthesitis diagnoses were established for at least one site on an initial visit (n = 128) or during a mean 3 years’ follow-up (n = 192).

The investigators reported that the annual incidence of enthesitis in this population was 0.9% (Arthritis Care Res. 2016 Dec 20. doi: 10.1002/acr.23174). About half of the patients in the cohort had only one site affected, and one-third had two sites affected. The most common of these sites were the Achilles tendon, plantar fascia, and the lateral epicondyle, Dr. Polachek and colleagues reported. They also found several factors associated with enthesitis: higher inflamed joint count (odds ratio, 1.06; P = .0002), less clinical damage (OR, 0.9; P = .04), more pain (OR, 1.15; P = .01), and presence of tenosynovitis (OR, 5.3; P less than .0001) or dactylitis (OR, 2.5; P = .02).

Significant risk factors for enthesitis included higher body mass index (hazard ratio, 1.04; P = .02), more actively inflamed joints (HR, 1.04; P = .0004), and younger age (HR, 0.98; P = .02). Among the patients in the cohort, 57% were male, the mean age was 50.8 years, and mean PsA disease duration was 12.3 years. Median time to resolution of enthesitis was 7.5 months, with 70% of patients improving without changes to their treatment.

The University of Toronto PsA research program receives funding from Krembil Foundation. Dr. Polachek disclosed grant funding from Janssen Canada. No other authors reported conflicts of interest.

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

Adjuvant chemotherapy prolonged survival after radical nephroureterectomy by nearly a year, compared with observation alone, among patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma, researchers reported.

After a median follow-up period of 49 months, median overall survival was 47 months with adjuvant chemotherapy and 36 months with observation alone (P less than .001), reported Thomas Seisen, MD, of Harvard Medical School, Boston, and his associates.

This analysis included 3,253 patients with pT3/T4 and/or pN+ upper tract urothelial carcinoma from the National Cancer Database. A total of 762 (23%) patients received adjuvant chemotherapy within 90 days after surgery, while 2,491 (77%) patients underwent observation only (J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.414).

Kaplan Meier analyses yielded 5-year adjusted overall survival rates of 44% and 36%, respectively. Adjuvant chemotherapy conferred a significant overall survival benefit in a Cox proportional hazards regression analysis (hazard ratio, 0.77; 95% confidence interval, 0.68 to 0.88), and the effect held up in tests designed to minimize selection bias – including propensity score adjustment (HR, 0.82; 0.73 to 0.93), stratification (HR, 0.84; 0.74 to 0.95), and matching (HR, 0.84; 0.75 to 0.95).

The effect persisted across subgroups stratified by age, gender, comorbidity burden, pathologic stage, and surgical margin status, and there was no significant variability in treatment effects, the researchers said. The findings are subject to “the usual biases related to the observational study design,” but pending level 1 evidence, they inform the management of patients with advanced upper tract urothelial carcinoma who undergo radical nephroureterectomy, the researchers concluded.

The work was supported by the Vattikuti Urology Institute, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the Prostate Cancer Foundation. Dr. Seisen had no relevant financial disclosures.

[email protected]

How many calories are there in a cheeseburger? (Yes, I too am looking forward to a svelter 2017). The answer, according to my new assistant, is 300 calories. She knows the dose of acetaminophen for a 10-year-old, 65-pound child is 325 mg every 4-6 hours. She also plays George Michael, reorders my Dentyne Ice gum, and turns off the lights. She is Alexa of Amazon’s Echo, the intelligent personal assistant.

Echo and Google Home are popular voice-assisted home appliances. Amazon has built a natural language processing system, so to use it, you simply say, “Alexa,” pause, then ask your question (What’s the weather in New York?) or deliver your command (Play Spotify). It’s hands free, so you can interface while typing, reading, or cooking dinner.

1. Physicians can ask for real-time help such as: What are treatment options for juvenile dermatomyositis? Order doxycycline 100 mg by mouth, twice daily, quantity sufficient 10 days.

2. Physicians might also use it to dictate notes intelligently, and even extract patient instructions directly from the notes to be emailed to the patient.

3. Surgeons could command an MRI to be viewed without having to scrub out.

4. Bedridden or chronically ill patients could use it to refill medications, make doctor appointments, or contact a caregiver in an emergency.

5. Patients could receive customized instructions, such as the answer to “How often do I change my surgical bandage?”

For all its potential, voice-assisted personal assistants have a long way to go. It would be a mistake to think these won’t be integrated into the entire health care chain from care to wellness, but it will be awhile before we get there.

Interestingly, when I asked my Apple Siri how many calories are in a cheeseburger, she reported 500, which is much more than Alexa’s 300. Which is why, for now, devices like Alexa are ideal for ordering a pizza hands free from your recliner. Just don’t ask how many calories are in it.
 

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]. He has no disclosures related to this column.

How many calories are there in a cheeseburger? (Yes, I too am looking forward to a svelter 2017). The answer, according to my new assistant, is 300 calories. She knows the dose of acetaminophen for a 10-year-old, 65-pound child is 325 mg every 4-6 hours. She also plays George Michael, reorders my Dentyne Ice gum, and turns off the lights. She is Alexa of Amazon’s Echo, the intelligent personal assistant.

Echo and Google Home are popular voice-assisted home appliances. Amazon has built a natural language processing system, so to use it, you simply say, “Alexa,” pause, then ask your question (What’s the weather in New York?) or deliver your command (Play Spotify). It’s hands free, so you can interface while typing, reading, or cooking dinner.

1. Physicians can ask for real-time help such as: What are treatment options for juvenile dermatomyositis? Order doxycycline 100 mg by mouth, twice daily, quantity sufficient 10 days.

2. Physicians might also use it to dictate notes intelligently, and even extract patient instructions directly from the notes to be emailed to the patient.

3. Surgeons could command an MRI to be viewed without having to scrub out.

4. Bedridden or chronically ill patients could use it to refill medications, make doctor appointments, or contact a caregiver in an emergency.

5. Patients could receive customized instructions, such as the answer to “How often do I change my surgical bandage?”

For all its potential, voice-assisted personal assistants have a long way to go. It would be a mistake to think these won’t be integrated into the entire health care chain from care to wellness, but it will be awhile before we get there.

Interestingly, when I asked my Apple Siri how many calories are in a cheeseburger, she reported 500, which is much more than Alexa’s 300. Which is why, for now, devices like Alexa are ideal for ordering a pizza hands free from your recliner. Just don’t ask how many calories are in it.
 

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]. He has no disclosures related to this column.

How many calories are there in a cheeseburger? (Yes, I too am looking forward to a svelter 2017). The answer, according to my new assistant, is 300 calories. She knows the dose of acetaminophen for a 10-year-old, 65-pound child is 325 mg every 4-6 hours. She also plays George Michael, reorders my Dentyne Ice gum, and turns off the lights. She is Alexa of Amazon’s Echo, the intelligent personal assistant.

Echo and Google Home are popular voice-assisted home appliances. Amazon has built a natural language processing system, so to use it, you simply say, “Alexa,” pause, then ask your question (What’s the weather in New York?) or deliver your command (Play Spotify). It’s hands free, so you can interface while typing, reading, or cooking dinner.

1. Physicians can ask for real-time help such as: What are treatment options for juvenile dermatomyositis? Order doxycycline 100 mg by mouth, twice daily, quantity sufficient 10 days.

2. Physicians might also use it to dictate notes intelligently, and even extract patient instructions directly from the notes to be emailed to the patient.

3. Surgeons could command an MRI to be viewed without having to scrub out.

4. Bedridden or chronically ill patients could use it to refill medications, make doctor appointments, or contact a caregiver in an emergency.

5. Patients could receive customized instructions, such as the answer to “How often do I change my surgical bandage?”

For all its potential, voice-assisted personal assistants have a long way to go. It would be a mistake to think these won’t be integrated into the entire health care chain from care to wellness, but it will be awhile before we get there.

Interestingly, when I asked my Apple Siri how many calories are in a cheeseburger, she reported 500, which is much more than Alexa’s 300. Which is why, for now, devices like Alexa are ideal for ordering a pizza hands free from your recliner. Just don’t ask how many calories are in it.
 

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]. He has no disclosures related to this column.