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Adding docetaxel to hormone therapy for advanced prostate cancer nets QOL benefit
SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.
Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.
The new analysis focused on health economic and quality of life outcomes. Results of a model based largely on STAMPEDE data showed that adding docetaxel to first-line hormone therapy yielded an increase of about 0.4 quality-adjusted life-years among men with nonmetastatic disease and about 0.5 quality-adjusted life-years among men with metastatic disease.
Adding docetaxel actually led to a small reduction in total lifetime costs, on the order of several hundred pounds sterling, for patients with nonmetastatic disease, because the drug costs were more than offset by reductions in costs associated with adverse outcomes. On the other hand, adding docetaxel increased total costs by a fairly modest amount, roughly 3,000 pounds sterling, for patients with metastatic disease, but that increase was due in large part to costs associated with prolonged survival.
“Upfront docetaxel gives you a gain in quality-adjusted life-years in all subgroups,” Dr. James said. “Analysis suggests a high degree of certainty relating to the quality-adjusted life-year gain associated with docetaxel.”
“The results therefore support the existing health care policy in the U.K. and elsewhere across the world in newly diagnosed metastatic patients. You’ve got a pretty modest cost for a survival gain and a quality gain,” he maintained. “But very importantly, we think these results extend the applicability to nonmetastatic patients because at the patient level there is very clear evidence of a quality-adjusted life-year gain, and the modeling also predicts an eventual survival gain. And at the provider level, it’s a very cost-effective use of resources. For a very modest upfront docetaxel cost, it actually is cost saving in the nonmetastatic patient because of the subsequent downstream [averted events], things like spinal cord compression.”
Full results of the analysis, including model-predicted overall survival, will be reported at the symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Clinical implications
“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”
Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”
“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
Study details
The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.
Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.
Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.
“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.
“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”
In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group
Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).
Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.
When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.
Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.
SOURCE: James ND et al. GUCS Abstract 162.
SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.
Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.
The new analysis focused on health economic and quality of life outcomes. Results of a model based largely on STAMPEDE data showed that adding docetaxel to first-line hormone therapy yielded an increase of about 0.4 quality-adjusted life-years among men with nonmetastatic disease and about 0.5 quality-adjusted life-years among men with metastatic disease.
Adding docetaxel actually led to a small reduction in total lifetime costs, on the order of several hundred pounds sterling, for patients with nonmetastatic disease, because the drug costs were more than offset by reductions in costs associated with adverse outcomes. On the other hand, adding docetaxel increased total costs by a fairly modest amount, roughly 3,000 pounds sterling, for patients with metastatic disease, but that increase was due in large part to costs associated with prolonged survival.
“Upfront docetaxel gives you a gain in quality-adjusted life-years in all subgroups,” Dr. James said. “Analysis suggests a high degree of certainty relating to the quality-adjusted life-year gain associated with docetaxel.”
“The results therefore support the existing health care policy in the U.K. and elsewhere across the world in newly diagnosed metastatic patients. You’ve got a pretty modest cost for a survival gain and a quality gain,” he maintained. “But very importantly, we think these results extend the applicability to nonmetastatic patients because at the patient level there is very clear evidence of a quality-adjusted life-year gain, and the modeling also predicts an eventual survival gain. And at the provider level, it’s a very cost-effective use of resources. For a very modest upfront docetaxel cost, it actually is cost saving in the nonmetastatic patient because of the subsequent downstream [averted events], things like spinal cord compression.”
Full results of the analysis, including model-predicted overall survival, will be reported at the symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Clinical implications
“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”
Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”
“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
Study details
The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.
Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.
Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.
“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.
“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”
In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group
Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).
Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.
When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.
Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.
SOURCE: James ND et al. GUCS Abstract 162.
SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.
Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.
The new analysis focused on health economic and quality of life outcomes. Results of a model based largely on STAMPEDE data showed that adding docetaxel to first-line hormone therapy yielded an increase of about 0.4 quality-adjusted life-years among men with nonmetastatic disease and about 0.5 quality-adjusted life-years among men with metastatic disease.
Adding docetaxel actually led to a small reduction in total lifetime costs, on the order of several hundred pounds sterling, for patients with nonmetastatic disease, because the drug costs were more than offset by reductions in costs associated with adverse outcomes. On the other hand, adding docetaxel increased total costs by a fairly modest amount, roughly 3,000 pounds sterling, for patients with metastatic disease, but that increase was due in large part to costs associated with prolonged survival.
“Upfront docetaxel gives you a gain in quality-adjusted life-years in all subgroups,” Dr. James said. “Analysis suggests a high degree of certainty relating to the quality-adjusted life-year gain associated with docetaxel.”
“The results therefore support the existing health care policy in the U.K. and elsewhere across the world in newly diagnosed metastatic patients. You’ve got a pretty modest cost for a survival gain and a quality gain,” he maintained. “But very importantly, we think these results extend the applicability to nonmetastatic patients because at the patient level there is very clear evidence of a quality-adjusted life-year gain, and the modeling also predicts an eventual survival gain. And at the provider level, it’s a very cost-effective use of resources. For a very modest upfront docetaxel cost, it actually is cost saving in the nonmetastatic patient because of the subsequent downstream [averted events], things like spinal cord compression.”
Full results of the analysis, including model-predicted overall survival, will be reported at the symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Clinical implications
“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”
Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”
“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
Study details
The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.
Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.
Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.
“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.
“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”
In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group
Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).
Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.
When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.
Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.
SOURCE: James ND et al. GUCS Abstract 162.
REPORTING FROM GUCS 2018
Key clinical point:
Major finding: Compared with hormone therapy alone, adding docetaxel increased quality-adjusted life-years by about 0.4 among men with nonmetastatic disease and 0.5 among men with metastatic disease.
Data source: A health economic and quality of life analysis of data from a randomized controlled trial among 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer starting first-line hormone therapy (STAMPEDE trial).
Disclosures: Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, UK.
Source: James ND et al. GUCS Abstract 162.
Singing Praises, Naming Names
Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.
Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.
New EAA Members
Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.
Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series
Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.
Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.
William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.
Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the
Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.
Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.
Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.
New EAA Members
Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.
Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series
Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.
Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.
William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.
Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the
Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.
Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.
Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.
New EAA Members
Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.
Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series
Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.
Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.
William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.
Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the
Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.
FDA approves abiraterone acetate for metastatic high-risk CSPC
The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).
The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.
The most common adverse reactions in LATITUDE for patients in the abiraterone acetate arm included hypertension, hot flush, hypokalemia, increased alanine aminotransferase or aspartate aminotransferase, headache, urinary tract infection, upper respiratory tract infection, and cough.
The recommended dose for abiraterone acetate for metastatic CSPC is 1,000 mg orally once daily with prednisone 5 mg orally once daily. Patients receiving the drug should also receive a gonadotropin-releasing hormone analogue concurrently or should have had bilateral orchiectomy, the FDA said.
Abiraterone acetate is marketed as Zytiga by Janssen Biotech.
The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).
The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.
The most common adverse reactions in LATITUDE for patients in the abiraterone acetate arm included hypertension, hot flush, hypokalemia, increased alanine aminotransferase or aspartate aminotransferase, headache, urinary tract infection, upper respiratory tract infection, and cough.
The recommended dose for abiraterone acetate for metastatic CSPC is 1,000 mg orally once daily with prednisone 5 mg orally once daily. Patients receiving the drug should also receive a gonadotropin-releasing hormone analogue concurrently or should have had bilateral orchiectomy, the FDA said.
Abiraterone acetate is marketed as Zytiga by Janssen Biotech.
The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).
The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.
The most common adverse reactions in LATITUDE for patients in the abiraterone acetate arm included hypertension, hot flush, hypokalemia, increased alanine aminotransferase or aspartate aminotransferase, headache, urinary tract infection, upper respiratory tract infection, and cough.
The recommended dose for abiraterone acetate for metastatic CSPC is 1,000 mg orally once daily with prednisone 5 mg orally once daily. Patients receiving the drug should also receive a gonadotropin-releasing hormone analogue concurrently or should have had bilateral orchiectomy, the FDA said.
Abiraterone acetate is marketed as Zytiga by Janssen Biotech.
Mother has severe pain — uterine rupture: $9M settlement
Mother has severe pain — uterine rupture: $9M settlement
At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous
She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00
The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.
The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.
PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.
VERDICT: A $9 million Michigan settlement was reached during mediation.
Baby dies at birth: $1.3M settlement
A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.
PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.
PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.
VERDICT: A $1.3 million Virginia settlement was reached.
Was tachycardic FHR ignored? $3M settlement
A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.
After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.
DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.
VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Mother has severe pain — uterine rupture: $9M settlement
At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous
She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00
The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.
The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.
PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.
VERDICT: A $9 million Michigan settlement was reached during mediation.
Baby dies at birth: $1.3M settlement
A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.
PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.
PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.
VERDICT: A $1.3 million Virginia settlement was reached.
Was tachycardic FHR ignored? $3M settlement
A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.
After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.
DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.
VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Mother has severe pain — uterine rupture: $9M settlement
At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous
She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00
The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.
The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.
PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.
VERDICT: A $9 million Michigan settlement was reached during mediation.
Baby dies at birth: $1.3M settlement
A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.
PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.
PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.
VERDICT: A $1.3 million Virginia settlement was reached.
Was tachycardic FHR ignored? $3M settlement
A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.
After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.
PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.
DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.
VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
National Early Warning Score discriminates deterioration of inpatients with liver disease
, within 24 hours in hospitalized patients, according to a study published in the journal Clinical Gastroenterology and Hepatology.
Although existing predictive models estimate medium- and long-term prognosis in patients with liver disease, none are validated for short-term outcomes in inpatient settings. Despite the potential concern that patients with liver disease present with chronic physiological derangements affecting National Early Warning Score (NEWS) parameters, the score accurately discriminated patients at risk of death, admission to the ICU, or cardiac arrest within a 24-hour period for a range of liver-related diagnoses achieving an area under receiver operating characteristics (AUROC) curve of 0.894 (95% confidence intervals, 0.887-0.902), 0.857 (95% CI, 0.847-0.868), and 0.722 (95% CI, 0.685-0.759), respectively.
NEWS was launched in 2012 to reduce variations among existing early warning scores by the Royal College of Physicians for use in all adults except pregnant women. Theresa J. Hydes MD, PhD, and her colleagues at the department of gastroenterology & hepatology, Portsmouth (England) Hospitals NHS Trust, sought to validate NEWS in 35,585 unselected medical patients.
The NEWS allocates weighted points, based on derangement of vital signs from defined normal ranges including pulse, respiratory rate, systolic blood pressure, an alert-verbal-painful-unresponsive scale, temperature, peripheral oxygen saturations, and use of supplemental oxygen. The summation of allocated points to directs changes in the level of care, for example, more frequent monitoring, involving senior staff, or calling a rapid response team.
The study was performed in a large, acute care hospital in southern England and analyzed a database of electronically captured vital signs recorded in real time from completed consecutive admissions of patients aged 16 years or older, during 2010-2014. International Classification of Diseases-10 codes were used to categorize patients for any finished consultant episode. The categories included patients with primary diagnosis of liver disease, those with nonprimary liver diagnosis (comorbidity), and patients not allocated any liver disease codes (controls). The NEWS performance was examined according to whether liver disease was acute or chronic, alcohol induced, or associated with portal hypertension, with four clinical subgroups: acute alcohol-induced liver injury, other acute injury, chronic liver disease without cirrhosis, or cirrhosis. The final dataset comprised 722 patients (1,112 episodes) with a primary liver diagnosis, and 2,339 patients (3,658 episodes) with a nonprimary liver diagnosis.
The primary study endpoint was any of the following events occurring within 24 hours of an observation set: in-hospital mortality, unanticipated ICU admission, or cardiac arrest. “The NEWS identified patients with primary, nonprimary, and no diagnoses of liver disease with AUROC values of 0.873 (95% CI, 0.860-0.886), 0.898 (95% CI, 0.891-0.905), and 0.879 (95% CI, 0.877-0.881), respectively. High AUROC values also were obtained for all clinical subgroups; the NEWS identified patients with alcohol-related liver disease with an AUROC value of 0.927 (95% CI, 0.912-0.941). The NEWS identified patients with liver diseases with higher AUROC values than [did] other early warning scoring systems,” according to Dr. Hydes and her colleagues.
“Because of its widespread use, the NEWS serves a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings or escalation criteria,” wrote the authors.
The study was supported by VitalPAC, a collaborative development of the Learning Clinic and Portsmouth Hospitals NHS Trust. Dr. Schmidt, Dr. Aspinall, and Dr. Meredith are employed by PHT. Dr. Hydes had no conflicts of interest.
SOURCE: Hydes TJ et al. Clin Gastroenterol Hepatol. 2017 Dec 22. doi: 10.1016/j.cgh.2017.12.035.
, within 24 hours in hospitalized patients, according to a study published in the journal Clinical Gastroenterology and Hepatology.
Although existing predictive models estimate medium- and long-term prognosis in patients with liver disease, none are validated for short-term outcomes in inpatient settings. Despite the potential concern that patients with liver disease present with chronic physiological derangements affecting National Early Warning Score (NEWS) parameters, the score accurately discriminated patients at risk of death, admission to the ICU, or cardiac arrest within a 24-hour period for a range of liver-related diagnoses achieving an area under receiver operating characteristics (AUROC) curve of 0.894 (95% confidence intervals, 0.887-0.902), 0.857 (95% CI, 0.847-0.868), and 0.722 (95% CI, 0.685-0.759), respectively.
NEWS was launched in 2012 to reduce variations among existing early warning scores by the Royal College of Physicians for use in all adults except pregnant women. Theresa J. Hydes MD, PhD, and her colleagues at the department of gastroenterology & hepatology, Portsmouth (England) Hospitals NHS Trust, sought to validate NEWS in 35,585 unselected medical patients.
The NEWS allocates weighted points, based on derangement of vital signs from defined normal ranges including pulse, respiratory rate, systolic blood pressure, an alert-verbal-painful-unresponsive scale, temperature, peripheral oxygen saturations, and use of supplemental oxygen. The summation of allocated points to directs changes in the level of care, for example, more frequent monitoring, involving senior staff, or calling a rapid response team.
The study was performed in a large, acute care hospital in southern England and analyzed a database of electronically captured vital signs recorded in real time from completed consecutive admissions of patients aged 16 years or older, during 2010-2014. International Classification of Diseases-10 codes were used to categorize patients for any finished consultant episode. The categories included patients with primary diagnosis of liver disease, those with nonprimary liver diagnosis (comorbidity), and patients not allocated any liver disease codes (controls). The NEWS performance was examined according to whether liver disease was acute or chronic, alcohol induced, or associated with portal hypertension, with four clinical subgroups: acute alcohol-induced liver injury, other acute injury, chronic liver disease without cirrhosis, or cirrhosis. The final dataset comprised 722 patients (1,112 episodes) with a primary liver diagnosis, and 2,339 patients (3,658 episodes) with a nonprimary liver diagnosis.
The primary study endpoint was any of the following events occurring within 24 hours of an observation set: in-hospital mortality, unanticipated ICU admission, or cardiac arrest. “The NEWS identified patients with primary, nonprimary, and no diagnoses of liver disease with AUROC values of 0.873 (95% CI, 0.860-0.886), 0.898 (95% CI, 0.891-0.905), and 0.879 (95% CI, 0.877-0.881), respectively. High AUROC values also were obtained for all clinical subgroups; the NEWS identified patients with alcohol-related liver disease with an AUROC value of 0.927 (95% CI, 0.912-0.941). The NEWS identified patients with liver diseases with higher AUROC values than [did] other early warning scoring systems,” according to Dr. Hydes and her colleagues.
“Because of its widespread use, the NEWS serves a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings or escalation criteria,” wrote the authors.
The study was supported by VitalPAC, a collaborative development of the Learning Clinic and Portsmouth Hospitals NHS Trust. Dr. Schmidt, Dr. Aspinall, and Dr. Meredith are employed by PHT. Dr. Hydes had no conflicts of interest.
SOURCE: Hydes TJ et al. Clin Gastroenterol Hepatol. 2017 Dec 22. doi: 10.1016/j.cgh.2017.12.035.
, within 24 hours in hospitalized patients, according to a study published in the journal Clinical Gastroenterology and Hepatology.
Although existing predictive models estimate medium- and long-term prognosis in patients with liver disease, none are validated for short-term outcomes in inpatient settings. Despite the potential concern that patients with liver disease present with chronic physiological derangements affecting National Early Warning Score (NEWS) parameters, the score accurately discriminated patients at risk of death, admission to the ICU, or cardiac arrest within a 24-hour period for a range of liver-related diagnoses achieving an area under receiver operating characteristics (AUROC) curve of 0.894 (95% confidence intervals, 0.887-0.902), 0.857 (95% CI, 0.847-0.868), and 0.722 (95% CI, 0.685-0.759), respectively.
NEWS was launched in 2012 to reduce variations among existing early warning scores by the Royal College of Physicians for use in all adults except pregnant women. Theresa J. Hydes MD, PhD, and her colleagues at the department of gastroenterology & hepatology, Portsmouth (England) Hospitals NHS Trust, sought to validate NEWS in 35,585 unselected medical patients.
The NEWS allocates weighted points, based on derangement of vital signs from defined normal ranges including pulse, respiratory rate, systolic blood pressure, an alert-verbal-painful-unresponsive scale, temperature, peripheral oxygen saturations, and use of supplemental oxygen. The summation of allocated points to directs changes in the level of care, for example, more frequent monitoring, involving senior staff, or calling a rapid response team.
The study was performed in a large, acute care hospital in southern England and analyzed a database of electronically captured vital signs recorded in real time from completed consecutive admissions of patients aged 16 years or older, during 2010-2014. International Classification of Diseases-10 codes were used to categorize patients for any finished consultant episode. The categories included patients with primary diagnosis of liver disease, those with nonprimary liver diagnosis (comorbidity), and patients not allocated any liver disease codes (controls). The NEWS performance was examined according to whether liver disease was acute or chronic, alcohol induced, or associated with portal hypertension, with four clinical subgroups: acute alcohol-induced liver injury, other acute injury, chronic liver disease without cirrhosis, or cirrhosis. The final dataset comprised 722 patients (1,112 episodes) with a primary liver diagnosis, and 2,339 patients (3,658 episodes) with a nonprimary liver diagnosis.
The primary study endpoint was any of the following events occurring within 24 hours of an observation set: in-hospital mortality, unanticipated ICU admission, or cardiac arrest. “The NEWS identified patients with primary, nonprimary, and no diagnoses of liver disease with AUROC values of 0.873 (95% CI, 0.860-0.886), 0.898 (95% CI, 0.891-0.905), and 0.879 (95% CI, 0.877-0.881), respectively. High AUROC values also were obtained for all clinical subgroups; the NEWS identified patients with alcohol-related liver disease with an AUROC value of 0.927 (95% CI, 0.912-0.941). The NEWS identified patients with liver diseases with higher AUROC values than [did] other early warning scoring systems,” according to Dr. Hydes and her colleagues.
“Because of its widespread use, the NEWS serves a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings or escalation criteria,” wrote the authors.
The study was supported by VitalPAC, a collaborative development of the Learning Clinic and Portsmouth Hospitals NHS Trust. Dr. Schmidt, Dr. Aspinall, and Dr. Meredith are employed by PHT. Dr. Hydes had no conflicts of interest.
SOURCE: Hydes TJ et al. Clin Gastroenterol Hepatol. 2017 Dec 22. doi: 10.1016/j.cgh.2017.12.035.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The performance of the National Early Warning Score, used to identify deteriorating adult hospital inpatients with acute and chronic liver diseases within 24 hours of admission, was assessed.
Major finding: NEWS accurately discriminates risk of death, ICU admission, or cardiac arrest within 24 hours in patients with liver-related diagnoses.
Study details: A database of electronically captured vital signs recorded in real-time from completed consecutive admissions (episodes) of patients aged at least 16 years between Jan. 1, 2010, and Oct. 31, 2014. Nurses recorded data at the bedside using electronic devices running VitalPAC software.
Disclosures: The study was supported by VitalPAC, a collaborative development of the Learning Clinic and Portsmouth Hospitals NHS Trust (PHT). Dr. Schmidt, Dr. Aspinall, and Dr. Meredith are employed by PHT. Dr. Hydes had no conflicts of interest.
Source: Hydes TJ et al. Clin Gastroenterol Hepatol. 2017 Dec 22. doi: 10.1016/j.cgh.2017.12.035
Tune in to cardiovascular risk in psoriasis
Stay attentive to cardiovascular disease risk in patients with psoriasis because effective treatment of psoriasis could improve their vascular risk as well, said Jeffrey M. Sobell, MD, of Tufts University in Boston.
he said at the Caribbean Dermatology Symposium.
The metabolic syndrome and its associated cardiovascular risk of myocardial infarction and stroke is significantly more prevalent in psoriasis patients, compared with controls, Dr. Sobell said at the meeting, provided by Global Academy for Medical Education.
A possible reason for this link may be that the chronic inflammation associated with psoriasis leads to atherosclerosis, Dr. Sobell noted. The inflammation is evident on PET imaging with a radiolabeled glucose known as fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET/CT) The technology, first used in cancer and neuroimaging, can detect early subclinical inflammation and allows for exact measurements of inflammatory activity, and measuring inflammation of the aorta can serve as a surrogate marker for treatment, he said.
Treating skin disease appears to impact vascular disease, Dr. Sobell said. In a study published in JAMA Cardiology, researchers followed 115 patients for 1 year using FDG-PET/CT (JAMA Cardiol. 2017. doi: 10.1001/jamacardio.2017.1213)
Overall, when psoriasis improved, so did signs of vascular inflammation. “When the skin is more severe and treated more aggressively with anti-TNF therapy, the reduction in vascular disease is stronger,” Dr. Sobell said.
Data from another large study presented as a late-breaker at the American Academy of Dermatology in 2017 showed that treatment of psoriasis with tumor necrosis factor–alpha inhibitor therapy significantly reduced all-cause mortality in patients with psoriasis or psoriatic arthritis, he noted.
Psoriasis patients often are underscreened for cardiac risk factors, but identifying them can help guide treatment, Dr. Sobell said.
“Dermatologists should at minimum direct patients to primary care physicians for appropriate screening and assessment,” he emphasized.
Dr. Sobell disclosed relationships with Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, and Sun Pharma.
Global Academy and this news organization are owned by the same parent company.
Stay attentive to cardiovascular disease risk in patients with psoriasis because effective treatment of psoriasis could improve their vascular risk as well, said Jeffrey M. Sobell, MD, of Tufts University in Boston.
he said at the Caribbean Dermatology Symposium.
The metabolic syndrome and its associated cardiovascular risk of myocardial infarction and stroke is significantly more prevalent in psoriasis patients, compared with controls, Dr. Sobell said at the meeting, provided by Global Academy for Medical Education.
A possible reason for this link may be that the chronic inflammation associated with psoriasis leads to atherosclerosis, Dr. Sobell noted. The inflammation is evident on PET imaging with a radiolabeled glucose known as fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET/CT) The technology, first used in cancer and neuroimaging, can detect early subclinical inflammation and allows for exact measurements of inflammatory activity, and measuring inflammation of the aorta can serve as a surrogate marker for treatment, he said.
Treating skin disease appears to impact vascular disease, Dr. Sobell said. In a study published in JAMA Cardiology, researchers followed 115 patients for 1 year using FDG-PET/CT (JAMA Cardiol. 2017. doi: 10.1001/jamacardio.2017.1213)
Overall, when psoriasis improved, so did signs of vascular inflammation. “When the skin is more severe and treated more aggressively with anti-TNF therapy, the reduction in vascular disease is stronger,” Dr. Sobell said.
Data from another large study presented as a late-breaker at the American Academy of Dermatology in 2017 showed that treatment of psoriasis with tumor necrosis factor–alpha inhibitor therapy significantly reduced all-cause mortality in patients with psoriasis or psoriatic arthritis, he noted.
Psoriasis patients often are underscreened for cardiac risk factors, but identifying them can help guide treatment, Dr. Sobell said.
“Dermatologists should at minimum direct patients to primary care physicians for appropriate screening and assessment,” he emphasized.
Dr. Sobell disclosed relationships with Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, and Sun Pharma.
Global Academy and this news organization are owned by the same parent company.
Stay attentive to cardiovascular disease risk in patients with psoriasis because effective treatment of psoriasis could improve their vascular risk as well, said Jeffrey M. Sobell, MD, of Tufts University in Boston.
he said at the Caribbean Dermatology Symposium.
The metabolic syndrome and its associated cardiovascular risk of myocardial infarction and stroke is significantly more prevalent in psoriasis patients, compared with controls, Dr. Sobell said at the meeting, provided by Global Academy for Medical Education.
A possible reason for this link may be that the chronic inflammation associated with psoriasis leads to atherosclerosis, Dr. Sobell noted. The inflammation is evident on PET imaging with a radiolabeled glucose known as fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET/CT) The technology, first used in cancer and neuroimaging, can detect early subclinical inflammation and allows for exact measurements of inflammatory activity, and measuring inflammation of the aorta can serve as a surrogate marker for treatment, he said.
Treating skin disease appears to impact vascular disease, Dr. Sobell said. In a study published in JAMA Cardiology, researchers followed 115 patients for 1 year using FDG-PET/CT (JAMA Cardiol. 2017. doi: 10.1001/jamacardio.2017.1213)
Overall, when psoriasis improved, so did signs of vascular inflammation. “When the skin is more severe and treated more aggressively with anti-TNF therapy, the reduction in vascular disease is stronger,” Dr. Sobell said.
Data from another large study presented as a late-breaker at the American Academy of Dermatology in 2017 showed that treatment of psoriasis with tumor necrosis factor–alpha inhibitor therapy significantly reduced all-cause mortality in patients with psoriasis or psoriatic arthritis, he noted.
Psoriasis patients often are underscreened for cardiac risk factors, but identifying them can help guide treatment, Dr. Sobell said.
“Dermatologists should at minimum direct patients to primary care physicians for appropriate screening and assessment,” he emphasized.
Dr. Sobell disclosed relationships with Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, and Sun Pharma.
Global Academy and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE CARIBBEAN DERMATOLOGY SYMPOSIUM
PAM50-based score identifies low-risk subset with node-positive early-stage breast cancer
The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.
This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.
The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.
Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.
The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.
“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.
The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.
Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.
Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.
The study by Laenkholm et al. provides encouraging data for the clinical utility of molecular assays to aid decision making for node-positive disease.
The investigators were able to select a subset of patients with node-positive disease with an estimated 10-year distant recurrence risk of less than or equal to 5%, based on the PAM50 risk of recurrence score. It could be argued that the data do not address the issue of whether chemotherapy would offer some benefit (predictive) in a node-positive population; however, a counterargument is that whatever small added benefit may be derived from adjuvant chemotherapy would be offset by adverse effects, resulting in a net gain of zero. The collective data from evaluation of other assays in this population suggest that patients with ER-positive disease, one to three positive nodes, and a low recurrence score can safely avoid adjuvant chemotherapy and receive endocrine therapy alone. This supports the current NCCN guidelines, which indicate the recurrence score assay can be considered in patients with one to three positive nodes. The more definitive answer on whether adjuvant chemotherapy adds benefit to endocrine therapy will be determined from the RxPONDER study, in which patients with ER+ disease, one to three positive nodes, and a recurrence score less than or equal to 25 will be randomly assigned to chemotherapy or not.
Ricardo L. B. Costa, MD, MS, is with the H. Lee Moffitt Cancer Center, Tampa. William J. Gradishar, MD, is with Northwestern University, Chicago. Dr. Costa disclosed ties with Bristol-Myers Squibb. Dr. Gradishar reported having no relevant financial disclosures. Their comments were adapted from an editorial (J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.76.9802).
The study by Laenkholm et al. provides encouraging data for the clinical utility of molecular assays to aid decision making for node-positive disease.
The investigators were able to select a subset of patients with node-positive disease with an estimated 10-year distant recurrence risk of less than or equal to 5%, based on the PAM50 risk of recurrence score. It could be argued that the data do not address the issue of whether chemotherapy would offer some benefit (predictive) in a node-positive population; however, a counterargument is that whatever small added benefit may be derived from adjuvant chemotherapy would be offset by adverse effects, resulting in a net gain of zero. The collective data from evaluation of other assays in this population suggest that patients with ER-positive disease, one to three positive nodes, and a low recurrence score can safely avoid adjuvant chemotherapy and receive endocrine therapy alone. This supports the current NCCN guidelines, which indicate the recurrence score assay can be considered in patients with one to three positive nodes. The more definitive answer on whether adjuvant chemotherapy adds benefit to endocrine therapy will be determined from the RxPONDER study, in which patients with ER+ disease, one to three positive nodes, and a recurrence score less than or equal to 25 will be randomly assigned to chemotherapy or not.
Ricardo L. B. Costa, MD, MS, is with the H. Lee Moffitt Cancer Center, Tampa. William J. Gradishar, MD, is with Northwestern University, Chicago. Dr. Costa disclosed ties with Bristol-Myers Squibb. Dr. Gradishar reported having no relevant financial disclosures. Their comments were adapted from an editorial (J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.76.9802).
The study by Laenkholm et al. provides encouraging data for the clinical utility of molecular assays to aid decision making for node-positive disease.
The investigators were able to select a subset of patients with node-positive disease with an estimated 10-year distant recurrence risk of less than or equal to 5%, based on the PAM50 risk of recurrence score. It could be argued that the data do not address the issue of whether chemotherapy would offer some benefit (predictive) in a node-positive population; however, a counterargument is that whatever small added benefit may be derived from adjuvant chemotherapy would be offset by adverse effects, resulting in a net gain of zero. The collective data from evaluation of other assays in this population suggest that patients with ER-positive disease, one to three positive nodes, and a low recurrence score can safely avoid adjuvant chemotherapy and receive endocrine therapy alone. This supports the current NCCN guidelines, which indicate the recurrence score assay can be considered in patients with one to three positive nodes. The more definitive answer on whether adjuvant chemotherapy adds benefit to endocrine therapy will be determined from the RxPONDER study, in which patients with ER+ disease, one to three positive nodes, and a recurrence score less than or equal to 25 will be randomly assigned to chemotherapy or not.
Ricardo L. B. Costa, MD, MS, is with the H. Lee Moffitt Cancer Center, Tampa. William J. Gradishar, MD, is with Northwestern University, Chicago. Dr. Costa disclosed ties with Bristol-Myers Squibb. Dr. Gradishar reported having no relevant financial disclosures. Their comments were adapted from an editorial (J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.76.9802).
The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.
This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.
The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.
Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.
The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.
“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.
The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.
Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.
Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.
The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.
This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.
The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.
Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.
The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.
“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.
The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.
Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.
Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The score enabled selection of a subset of patients with node-positive or node-negative disease with an estimated 10-year DR absolute risk of less than 5%.
Major finding: About 37% of patients with a single positive lymph node and 15% of patients with two positive nodes were identified as low risk by Prosigna, with very favorable outcomes when treated with adjuvant endocrine therapy alone.
Study details: Danish Breast Cancer Cooperative Group database including postmenopausal patients in Denmark diagnosed with ER-positive invasive breast cancer from 2000 through 2003 and treated with endocrine therapy for 5 years.
Disclosures: Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
Source: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.
Get ready for certolizumab for psoriasis
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Reported penicillin allergies hike inpatient costs
Total inpatient costs for patients who report being allergic to penicillin are much higher than for those who don’t report an allergy, according to a recent systematic review and meta-analysis.
The review, which eventually included 30 articles, found that total inpatient costs ranged from an average $1,145-$4,254 higher per patient with a reported penicillin allergy compared to nonallergic patients, said T. Joseph Mattingly, PharmD, and his associates. Outpatient prescription costs were also estimated to be steeper, running $14-$93 higher per patient who reported a penicillin allergy.
Although 10%-20% of patients report a penicillin allergy, “[a] majority of patients who report PCN [penicillin] allergy are not truly allergic upon confirmatory testing,” Dr. Mattingly and his colleagues wrote.
This overreporting of penicillin allergies is a problem for the patient and the health care system because “reported antibiotic allergies have been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased length of stay, increased antibiotic-related adverse events, increased rates of C. difficile infection, intensive care unit (ICU) admission, death, as well as increased treatment cost,” said Dr. Mattingly and his coauthors.
Health care providers often “tend to take reported allergies at face value,” said coauthor Anne Fulton, suggesting that primary care practices can help by considering skin testing for those patients who carry a label of penicillin allergy, but don’t have a documented confirmatory test. The cost for a commonly used skin test for penicillin allergy runs about $200, said Ms. Fulton, a doctoral candidate at the University of Maryland, Baltimore, in an interview.
When conducting the meta-analysis, Dr. Mattingly and his coauthors converted all figures to 2017 U.S. dollars, using Consumer Price Index figures to adjust for inflation. This yields conservative estimates for cost, as drug and health care prices have far outstripped the general rate of inflation during the period in which the studies occurred, Ms. Fulton acknowledged.
The investigators highlighted the need for ongoing study in this area. “To our knowledge, there are no evaluations of long-term outpatient outcomes related to the effects of PCN allergy and the potential impact of delabeling patients who do not have a true allergy,” they wrote.
Ms. Fulton agreed, noting that the studies covered in the meta-analysis were primarily focused on short-term outcomes, though there are many potential long-term benefits to delabeling patients who are not truly penicillin allergic.
For the patient, this includes the opportunity to receive optimal antimicrobial therapy, as well as potential savings in copays and other out-of-pocket expenses for outpatient medications, she said.
As antimicrobial resistance becomes an ever more pressing problem, there are more opportunities for targeted therapy if inappropriate allergy labeling is addressed, Ms. Fulton added.
Further study should use “cost-effectiveness analysis methods that include societal and health sector perspectives capturing immediate and future outcomes and costs to evaluate the use of skin-testing procedures in either inpatient or outpatient settings,” the investigators wrote.
The study was supported by ALK, the manufacturer of Pre-Pen, a commercially available penicillin allergy skin test.
SOURCE: Mattingly TJ et al. J Allergy Clin Immunol Pract. 2018 Jan 31. doi: 10.1016/j.jaip.2017.12.033.
Total inpatient costs for patients who report being allergic to penicillin are much higher than for those who don’t report an allergy, according to a recent systematic review and meta-analysis.
The review, which eventually included 30 articles, found that total inpatient costs ranged from an average $1,145-$4,254 higher per patient with a reported penicillin allergy compared to nonallergic patients, said T. Joseph Mattingly, PharmD, and his associates. Outpatient prescription costs were also estimated to be steeper, running $14-$93 higher per patient who reported a penicillin allergy.
Although 10%-20% of patients report a penicillin allergy, “[a] majority of patients who report PCN [penicillin] allergy are not truly allergic upon confirmatory testing,” Dr. Mattingly and his colleagues wrote.
This overreporting of penicillin allergies is a problem for the patient and the health care system because “reported antibiotic allergies have been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased length of stay, increased antibiotic-related adverse events, increased rates of C. difficile infection, intensive care unit (ICU) admission, death, as well as increased treatment cost,” said Dr. Mattingly and his coauthors.
Health care providers often “tend to take reported allergies at face value,” said coauthor Anne Fulton, suggesting that primary care practices can help by considering skin testing for those patients who carry a label of penicillin allergy, but don’t have a documented confirmatory test. The cost for a commonly used skin test for penicillin allergy runs about $200, said Ms. Fulton, a doctoral candidate at the University of Maryland, Baltimore, in an interview.
When conducting the meta-analysis, Dr. Mattingly and his coauthors converted all figures to 2017 U.S. dollars, using Consumer Price Index figures to adjust for inflation. This yields conservative estimates for cost, as drug and health care prices have far outstripped the general rate of inflation during the period in which the studies occurred, Ms. Fulton acknowledged.
The investigators highlighted the need for ongoing study in this area. “To our knowledge, there are no evaluations of long-term outpatient outcomes related to the effects of PCN allergy and the potential impact of delabeling patients who do not have a true allergy,” they wrote.
Ms. Fulton agreed, noting that the studies covered in the meta-analysis were primarily focused on short-term outcomes, though there are many potential long-term benefits to delabeling patients who are not truly penicillin allergic.
For the patient, this includes the opportunity to receive optimal antimicrobial therapy, as well as potential savings in copays and other out-of-pocket expenses for outpatient medications, she said.
As antimicrobial resistance becomes an ever more pressing problem, there are more opportunities for targeted therapy if inappropriate allergy labeling is addressed, Ms. Fulton added.
Further study should use “cost-effectiveness analysis methods that include societal and health sector perspectives capturing immediate and future outcomes and costs to evaluate the use of skin-testing procedures in either inpatient or outpatient settings,” the investigators wrote.
The study was supported by ALK, the manufacturer of Pre-Pen, a commercially available penicillin allergy skin test.
SOURCE: Mattingly TJ et al. J Allergy Clin Immunol Pract. 2018 Jan 31. doi: 10.1016/j.jaip.2017.12.033.
Total inpatient costs for patients who report being allergic to penicillin are much higher than for those who don’t report an allergy, according to a recent systematic review and meta-analysis.
The review, which eventually included 30 articles, found that total inpatient costs ranged from an average $1,145-$4,254 higher per patient with a reported penicillin allergy compared to nonallergic patients, said T. Joseph Mattingly, PharmD, and his associates. Outpatient prescription costs were also estimated to be steeper, running $14-$93 higher per patient who reported a penicillin allergy.
Although 10%-20% of patients report a penicillin allergy, “[a] majority of patients who report PCN [penicillin] allergy are not truly allergic upon confirmatory testing,” Dr. Mattingly and his colleagues wrote.
This overreporting of penicillin allergies is a problem for the patient and the health care system because “reported antibiotic allergies have been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased length of stay, increased antibiotic-related adverse events, increased rates of C. difficile infection, intensive care unit (ICU) admission, death, as well as increased treatment cost,” said Dr. Mattingly and his coauthors.
Health care providers often “tend to take reported allergies at face value,” said coauthor Anne Fulton, suggesting that primary care practices can help by considering skin testing for those patients who carry a label of penicillin allergy, but don’t have a documented confirmatory test. The cost for a commonly used skin test for penicillin allergy runs about $200, said Ms. Fulton, a doctoral candidate at the University of Maryland, Baltimore, in an interview.
When conducting the meta-analysis, Dr. Mattingly and his coauthors converted all figures to 2017 U.S. dollars, using Consumer Price Index figures to adjust for inflation. This yields conservative estimates for cost, as drug and health care prices have far outstripped the general rate of inflation during the period in which the studies occurred, Ms. Fulton acknowledged.
The investigators highlighted the need for ongoing study in this area. “To our knowledge, there are no evaluations of long-term outpatient outcomes related to the effects of PCN allergy and the potential impact of delabeling patients who do not have a true allergy,” they wrote.
Ms. Fulton agreed, noting that the studies covered in the meta-analysis were primarily focused on short-term outcomes, though there are many potential long-term benefits to delabeling patients who are not truly penicillin allergic.
For the patient, this includes the opportunity to receive optimal antimicrobial therapy, as well as potential savings in copays and other out-of-pocket expenses for outpatient medications, she said.
As antimicrobial resistance becomes an ever more pressing problem, there are more opportunities for targeted therapy if inappropriate allergy labeling is addressed, Ms. Fulton added.
Further study should use “cost-effectiveness analysis methods that include societal and health sector perspectives capturing immediate and future outcomes and costs to evaluate the use of skin-testing procedures in either inpatient or outpatient settings,” the investigators wrote.
The study was supported by ALK, the manufacturer of Pre-Pen, a commercially available penicillin allergy skin test.
SOURCE: Mattingly TJ et al. J Allergy Clin Immunol Pract. 2018 Jan 31. doi: 10.1016/j.jaip.2017.12.033.
FROM JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY: IN PRACTICE
Key clinical point: Inpatient costs were $1,145 – $4,254 higher for those reporting penicillin allergy.
Major finding: Though most studies addressed inpatient admissions, outpatient costs were also significantly higher.
Study details: Systematic review and meta-analysis of 30 articles addressing reported penicillin allergy.
Disclosures: The study was sponsored by ALK.
Source: Mattingly TJ et al. J Allergy Clin Immunol Pract. 2018 Jan 31. doi: 10.1016/j.jaip.2017.12.033.
FDA approves new combination drug for HIV patients
The Food and Drug Administration has approved a combination drug intended to treat HIV-1 infections – bictegravir, emtricitabine, tenofovir alafenamide – in virologically suppressed (HIV-1 RNA less than 50 copies/mL) adults who have no history of antiretroviral treatment or as a replacement for their current antiretroviral regimen.
The approval of the new combination drug (Biktarvy) was based on four active, randomized, controlled trials comprising three double-blind studies and one open label study. After 48 weeks of treatment in all trials, CD4+ cell count was evaluated to determine the efficacy of bictegravir, emtricitabine, tenofovir alafenamide, compared with other antiretroviral therapies.
In trial 1489, patients were randomized 1:1 to receive Biktarvy (n = 314) or ABC/DTG/3TC (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg) (n = 315). Trial 1490 was similar to trial 1489, with patients randomized 1:1 to receive either Biktarvy (n = 320) or DTG + FTC/TAF (dolutegravir + 50 mg, emtricitabine 200 mg/tenofovir alafenamide fumarate 25 mg) (n = 325). In trial 1489, the mean increase in CD4+ count after 48 weeks was 233 cells per mm3 and 229/mm3 in the Biktarvy and ABC/DTG/3TC groups, respectively. Similarly, counts in trial 1490 CD4+ after 48 weeks were 180/mm3 and 201/mm3 in the Biktarvy and DTG + FTC/TAF groups, respectively.
Trial 1844, another randomized trial, was composed of patients who switched to Biktarvy from their older treatment. Patients were randomized 1:1 to the new treatment (n = 282) or their previous antiretroviral regimen (n = 281).
Over 48 weeks, the mean change in CD4+ cell count was –31 cells per mm3 in subjects who switched to Biktarvy and 4/mm3 in subjects who stayed on ABC/DTG/3TC.
The open-label portion of the study, trial 1878, evaluated the safety and efficacy of switching from other retroviral treatments (n = 287) to Biktarvy (n = 290). The average change in CD4+ count after 48 weeks was 25 cells per mm3 who switched to Biktarvy and 0/mm3 who stayed on their previous regimens.
The new combination has received a boxed warning regarding the risk of severe acute exacerbations of hepatitis B that have been reported in patients coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of Biktarvy. Such patients should be closely monitored for hepatic function with both clinical and laboratory follow-up for at least several months in patients if they discontinue Biktarvy. If appropriate, antihepatitis B therapy may be warranted.
The approved recommended dosage for bictegravir, emtricitabine, tenofovir alafenamide combination drug is one tablet daily with or without food. More information is available on the FDA website.
The Food and Drug Administration has approved a combination drug intended to treat HIV-1 infections – bictegravir, emtricitabine, tenofovir alafenamide – in virologically suppressed (HIV-1 RNA less than 50 copies/mL) adults who have no history of antiretroviral treatment or as a replacement for their current antiretroviral regimen.
The approval of the new combination drug (Biktarvy) was based on four active, randomized, controlled trials comprising three double-blind studies and one open label study. After 48 weeks of treatment in all trials, CD4+ cell count was evaluated to determine the efficacy of bictegravir, emtricitabine, tenofovir alafenamide, compared with other antiretroviral therapies.
In trial 1489, patients were randomized 1:1 to receive Biktarvy (n = 314) or ABC/DTG/3TC (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg) (n = 315). Trial 1490 was similar to trial 1489, with patients randomized 1:1 to receive either Biktarvy (n = 320) or DTG + FTC/TAF (dolutegravir + 50 mg, emtricitabine 200 mg/tenofovir alafenamide fumarate 25 mg) (n = 325). In trial 1489, the mean increase in CD4+ count after 48 weeks was 233 cells per mm3 and 229/mm3 in the Biktarvy and ABC/DTG/3TC groups, respectively. Similarly, counts in trial 1490 CD4+ after 48 weeks were 180/mm3 and 201/mm3 in the Biktarvy and DTG + FTC/TAF groups, respectively.
Trial 1844, another randomized trial, was composed of patients who switched to Biktarvy from their older treatment. Patients were randomized 1:1 to the new treatment (n = 282) or their previous antiretroviral regimen (n = 281).
Over 48 weeks, the mean change in CD4+ cell count was –31 cells per mm3 in subjects who switched to Biktarvy and 4/mm3 in subjects who stayed on ABC/DTG/3TC.
The open-label portion of the study, trial 1878, evaluated the safety and efficacy of switching from other retroviral treatments (n = 287) to Biktarvy (n = 290). The average change in CD4+ count after 48 weeks was 25 cells per mm3 who switched to Biktarvy and 0/mm3 who stayed on their previous regimens.
The new combination has received a boxed warning regarding the risk of severe acute exacerbations of hepatitis B that have been reported in patients coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of Biktarvy. Such patients should be closely monitored for hepatic function with both clinical and laboratory follow-up for at least several months in patients if they discontinue Biktarvy. If appropriate, antihepatitis B therapy may be warranted.
The approved recommended dosage for bictegravir, emtricitabine, tenofovir alafenamide combination drug is one tablet daily with or without food. More information is available on the FDA website.
The Food and Drug Administration has approved a combination drug intended to treat HIV-1 infections – bictegravir, emtricitabine, tenofovir alafenamide – in virologically suppressed (HIV-1 RNA less than 50 copies/mL) adults who have no history of antiretroviral treatment or as a replacement for their current antiretroviral regimen.
The approval of the new combination drug (Biktarvy) was based on four active, randomized, controlled trials comprising three double-blind studies and one open label study. After 48 weeks of treatment in all trials, CD4+ cell count was evaluated to determine the efficacy of bictegravir, emtricitabine, tenofovir alafenamide, compared with other antiretroviral therapies.
In trial 1489, patients were randomized 1:1 to receive Biktarvy (n = 314) or ABC/DTG/3TC (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg) (n = 315). Trial 1490 was similar to trial 1489, with patients randomized 1:1 to receive either Biktarvy (n = 320) or DTG + FTC/TAF (dolutegravir + 50 mg, emtricitabine 200 mg/tenofovir alafenamide fumarate 25 mg) (n = 325). In trial 1489, the mean increase in CD4+ count after 48 weeks was 233 cells per mm3 and 229/mm3 in the Biktarvy and ABC/DTG/3TC groups, respectively. Similarly, counts in trial 1490 CD4+ after 48 weeks were 180/mm3 and 201/mm3 in the Biktarvy and DTG + FTC/TAF groups, respectively.
Trial 1844, another randomized trial, was composed of patients who switched to Biktarvy from their older treatment. Patients were randomized 1:1 to the new treatment (n = 282) or their previous antiretroviral regimen (n = 281).
Over 48 weeks, the mean change in CD4+ cell count was –31 cells per mm3 in subjects who switched to Biktarvy and 4/mm3 in subjects who stayed on ABC/DTG/3TC.
The open-label portion of the study, trial 1878, evaluated the safety and efficacy of switching from other retroviral treatments (n = 287) to Biktarvy (n = 290). The average change in CD4+ count after 48 weeks was 25 cells per mm3 who switched to Biktarvy and 0/mm3 who stayed on their previous regimens.
The new combination has received a boxed warning regarding the risk of severe acute exacerbations of hepatitis B that have been reported in patients coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of Biktarvy. Such patients should be closely monitored for hepatic function with both clinical and laboratory follow-up for at least several months in patients if they discontinue Biktarvy. If appropriate, antihepatitis B therapy may be warranted.
The approved recommended dosage for bictegravir, emtricitabine, tenofovir alafenamide combination drug is one tablet daily with or without food. More information is available on the FDA website.